AUTM BWR 07 · 2020. 7. 3. · Preface 11 Biotechnology Chapter 1 17 BIOX Technology Makes Biodiesel Faster and Cheaper A University of Toronto chemistry professor's research that

THE BETTER WORLD REPORT PART ONE

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The Better World ProjectThe Association of University Technology Managers launched the

Better World Project in 2005 to promote public understanding of

how academic research and technology transfer have changed

our way of life and made the world a better place. The project

draws from more than a decade’s worth of case studies and news

from AUTM members — the professionals who make academic

technology transfer happen.

This second edition of the project focuses on startup companies

spun off from U.S. and Canadian academic research.

Future reports will include stories and perspectives from around

the globe that convey the benefits of academic research in

human terms.

Materials and SupportThe Better World Project includes:

• The Better World Report Part One: In-depth articles about

25 successful startup companies; spin-offs from academic

research that have changed the world

• The Better World Report Part Two: Technology transfer

success stories, innovations that have gone from academic

research to realization in the market

• Better World Project Online: A searchable database to help

you find stories of interest to you and your community

The Better World Project materials are available in print and

electronic forms. Visit The Better World Project Web site or

contact AUTM headquarters for details.

AUTM Better World Project

60 Revere Drive, Suite 500

Northbrook, IL 60062

USA

847/559-0846

[email protected]

www.betterworldproject.net

The Association of University Technology ManagersAUTM is a nonprofit professional association with membership of

more than 3,500 intellectual property managers and business

executives from nearly 50 countries. The association’s mission is

to advance the field of technology transfer, and enhance the

ability to bring academic and nonprofit research to people

around the world. AUTM members represent more than 350

universities, research institutions, teaching hospitals and

government agencies as well as hundreds of companies involved

with managing and licensing innovations derived from academic

and nonprofit research.

The Better World Project is supported in part by a generous grant

from the Ewing Marion Kauffman Foundation.

Copyright © 2007 by the Association of

University Technology Managers®

All rights reserved. Reproduction in whole or in part without the

written consent of AUTM® is prohibited. This publication does

not imply endorsement by AUTM of any product or service.

Association of University Technology Managers®, AUTM®

and are registered trademarks of the Association of

University Technology Managers.

Printed in the USA.

ISBN 0-9778444-3-9

®

AUTM extends its thanks to Nikki Borman for spearheading the 2007 Edition of the

Better World Project; all members of the AUTM Board of Trustees for their ideas, feedback

and participation; the National Venture Capital Association; National Business Incubation

Association; National Association of Seed and Venture Funds; and the Licensing Executives

Society – USA & Canada for their support of this project; Dr. Lee Elliot Major and the

Universities UK project team (Alex Bols, Sam Hall and Simon Wright) for allowing AUTM

to include innovations and ideas presented in June 2006 edition of EurekaUK, and all of

the institutions and companies who told their stories.

The Better World Report is a testament to the efforts of institutions’ technology transfer

offices, their directors and staffs, who gathered and submitted these stories and more.

These contributions tell the story of how institutions are doing their part to improve the

world we live in not only through education but through innovation. And it is the Return

on Innovation that we bring to light in this report.

Editors and Staff: The stories in the Better World Report were researched and written by

The Blue Waters Group, a communications consultancy serving the knowledge industry.

The Better World Report was produced by The Sherwood Group Inc., a nonprofit

association management firm serving science, technology and health care specialty fields.

AUTM’s management staff and the communications department at The Sherwood Group

provide strategic, editorial and design support for The Better World Project.

THE BETTER WORLD REPORT PART ONE 3

Acknowledgements

Forward 9Preface 11

BiotechnologyChapter 1 17BIOX Technology Makes Biodiesel Faster and CheaperA University of Toronto chemistry professor's research that began with sewage sludge oils has led to breakthroughs in producing biodiesel — a cleaner form of fuel for diesel engines.

Chapter 2 23Berkeley Lab and Symyx Technologies: A Winning CombinationWith its unique approach to materials identification and analysis, Symyx Technologies is helping powerhouse companies worldwide blaze new trails in the realm of research and development.

Computer SciencesChapter 3 27Farecast: The First and Only Airfare Prediction Web SiteA University of Washington professor developed Farecast.com, a Web site that helps travelers save money by forecasting the best time to buy airline tickets for the best prices.

Chapter 4 33Intelligent Micro Patterning, LLC: Unique and Imaginative Thin Film Solutions Help Move Other Innovations ForwardA University of South Florida marine scientist invents a novel approach to using direct optical projection for micro patterning that today impacts major industrial companies around the world.

EducationChapter 5 37ALEKS Tutors Students in Learning to Succeed The groundbreaking intelligent tutoring system developed at the University of California, Irvine, equalizes educational opportunities by knowing exactly what the student knows and what the student is ready to learn.

Chapter 6 43Taking the Science of Measurement to a Higher Level By designing analytical equipment that’s easy to use, inexpensive and more precise, Queen’s University and Qubit Systems are changing the way universities teach and conduct research.


Contents

THE BETTER WORLD REPORT PART ONE6

ElectronicsChapter 7 49Making Light the Messenger: How Wavefront CodingTM

Is Revolutionizing the World of OpticsBy deliberately distorting the light rays that strike an object and processing the intercepts with a special algorithm, the University of Colorado at Boulder andCDM Optics create perfectly focused images with an astounding depth of field.

Chapter 8 53Phiar Adding New High-Speed Waves to ElectronicsQuantum tunneling technology from the University of Colorado at Boulder and Phiar Corp. is adding a new, high speed wave to a variety of electronic industries.

EnvironmentalChapter 9 59Enval Offers Breakthrough RecyclingThe University of Cambridge, with Enval Ltd., hopes it has a technology that can do something useful with the aluminum from juice cartons, much of which ends up in landfills around the world.

Chapter 10 63Carrier Aeroseal: Sealing Heating and Air Conditioning Leaks from the Inside OutAeroseal and Berkeley Lab revolutionized the process of searching for, and sealing, hidden leaks in heating and air ducts.

Chapter 11 69CEA Systems Offers More Efficient Ways to Bring Food to the Table and the Lab CEA Systems, and its partner, Cornell University, have developed an agricultural technology that could save energy, provide better food security and control, and lead to the creation of products for pharmaceuticals and other high-value plant-based compounds.

Chapter 12 75Green Power for the Planet’s Biggest Polluters Westport Innovations, with a jumpstart from the University of British Columbia,is driving a change in the way the world powers its buses and trucks, which area major source of urban air pollution and greenhouse gases in industrialized areas around the globe.

Contents

Health ServicesChapter 13 79New Technology Holds the Promise of Earlier and More Accurate Detection of Alzheimer’s DiseaseDiagnostic Potentials Ltd., a spin-off from the University of Glasgow, has completed a pivotal clinical trial demonstrating that the ADEPT System can detect Alzheimer’s at an early stage. Coupling dense array EEG with a computer program designed to test patient’s cognitive skills, this technology may revolutionize the way clinicians diagnose a degenerative and highly debilitating disease.

Chapter 14 83DNA Testing: Changing Lives with a Billion-in-One PrecisionUsing technology developed at the University of Glasgow, Crucial Genetics provides the DNA testing that can “make or break” a case in the courtroom.

MedicalChapter 15 89KineMed Offers Kinetic View of the BodyThe University of California, Berkeley and KineMed, a drug development company, have built a new way of seeing the inner workings of the human body and predicting clinical outcomes.

Chapter 16 95Syntermed Software Advances Nuclear Medicine With a ToolboxBreakthroughs by researchers, led by Professor Ernest Garcia of Emory University, help physicians interpret images and improve patients’ lives.

Chapter 17 101TomoTherapy’s Revolutionary Cancer Treatment Zeroes in on Tumors with PrecisionHelical TomoTherapy®, developed by University of Wisconsin-Madison researchers, combined with built-in computerized tomography imaging, targets only the cancerous mass, sparing surrounding tissue and nearby organs from damaging radiation.

Chapter 18 105Groundbreaking Cell-Binding Technology Helps Patients Grow New BoneCeraPedics, LLC, a Lakewood, Colo., company is developing and commercializing bonegraft products based on milestone technology developed at the University of California, San Francisco.

Chapter 19 109Concentric Medical, Inc.: Saving Stroke VictimsDue to a pair of University of California, Los Angeles physicians’ innovation and determination, the removal of potentially fatal blood clots in the brain may one day become standard procedure in hospitals around the world.


Contents


PharmaceuticalsChapter 20 115AtheroGenics Devises New Treatment for Heart PatientsEmory University and AtheroGenics, a small pharmaceutical company, are changing the way doctors treat heart disease — the leading cause of death in the United States.

PharmaceuticalsChapter 21 119DUSA Pharmaceuticals Sheds Light on Cancer With an initial grant of $8,000 and a long-held interest in light-based therapies, two researchers from Queen’s University and the Royal Military College of Canada, both in Kingston, Ontario, develop a uniquely effective method to treat cancer, licensed by DUSA Pharmaceuticals.

Chapter 22 123Revolutionary Cell Technology Helps Fight Deadly DiseasesIt was a first for science when research at Leiden University in The Netherlands led to the development of PER.C6® technology, which uses human cells to produce vaccines for combating infectious diseases like the flu, AIDS, and the West Nile and Ebola viruses.

Chapter 23 129XenoTech: A Metabolism Research LeaderAndrew Parkinson doesn’t consider himself to be an entrepreneur, but he and his staff at XenoTech, LLC, have built a leader in the field of drug metabolism research, after years of work at the University of Kansas Medical Center.

SafetyChapter 24 135BullEx Digital Safety Makes Hot Product Out of Fire Extinguisher TrainingRensselaer Polytechnic Institute undergraduates produce new technology in school’s Inventor’s Studio.

Chapter 25 141Groundbreaking Technology “Sees” Sound in Three Dimensions Acoustic holography technology, developed at Wayne State University, accurately visualizes sound as it flows through space and time, helping product design engineers “plug” leaks in products and machinery.

Contents

SWelcome to a Better World

Stories are like doorways. They open before us and we step into someplace new,

someplace we haven’t been before, and we are the better for it. And so it is with the

stories in the AUTM Better World Report™. That’s why the Association of University

Technology Managers is so proud to bring them to you.

This 2007 edition of the Better World Report tells the story of how the translation

of academic research into products and services is contributing to a better world.

These are stories about the outcome — the benefits — of moving academic discovery

from the lab to the daily lives of people.

We began this communication program in 2006 with the publication of our first

Better World Report and its companion piece, Reports from the Field. These two

reports put a human face to the complexities of technology transfer by focusing on

the social and economic benefits of the process.

This year our two-volume edition of the Better World Reports expands on last year’s

effort. It is a direct response to the overwhelmingly positive feedback we’ve received

from AUTM’s members, as well as from leaders in government, business, finance,

public policy and the media, for providing these real-life vignettes.

Part One, “Building a Stronger Economy: Profiles of 25 Companies Rooted in

Academic Research” focuses on examples of the phenomenon of new business

spin-offs from university research in the United States, Canada, the United Kingdom

and the Netherlands.

Volume Two of the 2007 Better World Report is called ”Technology Transfer Works:

100 Innovations from Academic Research to Real-World Application” and presents a

collection of 100 vignettes of academic research-based products that are playing a

role in a healthier, safer and more convenient world today. From Coumadin blood

thinners to QUIKCLOT® blood clotting agents, new flower hybrids to a redder cran-

berry, university researchers solve problems and, more importantly, create opportuni-

ties. All of our stories reflect the fact that the transfer of knowledge knows no bound-

aries in today’s global economy.


Forward


The underlying message of all these stories is the importance of support for

academic research, as the very foundation of our own work at AUTM to connect

research discoveries with the world around us, save lives, improve the quality of life,

and increase competitiveness and productivity.

Elected officials and policy makers increasingly recognize the many ways in which

academic research can be tied to economic performance, as well as to the health and

safety of people everywhere. AUTM is recognized as a reliable source of objective

information about the relationship of research to the marketplace. In addition to our

new communications initiative in the Better World Report, we publish the widely-rec-

ognized AUTM Licensing Survey™, containing a depth of information and statistical

data underscoring the impact of our work.

How the process of technology transfer works — the patents borne, the licensing

and royalties granted — can vary from university to university, but it is always

carefully and expertly managed by people who are passionate about the science,

research, law, finance, regulatory policies, and, in the end, the marketplace.

These are the members of AUTM, who over its 30-year history have become

recognized as some of the most reliable sources of information about — and some of

the prime movers in — today’s global, knowledge-based economy.

The stories in the Better World Report are just one way we have of offering an

insight into the researchers, the investors, and the owners of new businesses who are

creating a new world. In the end, these are stories about ROI — whether it’s Return

on Investment, or Return on Imagination — and like all good stories, we will let you

interpret them as you wish.

On behalf of all the people who make up the Association of University Technology

Managers, thank you for sharing our enthusiasm for a better world.

Forward

TWelcoming the ChallengeBy G. Steven Burrill

The Better World Project shares a remarkable collection of human-interest stories

that truly convey the importance of research and technology transfer in our world

today. This report will continue to be well-read and referenced among those who

have an interest not only in the development of academic research but by those who

strive to understand its financial and social impact. The impact this book demonstrates

is not one of licenses and royalties, but of problems solved, cures advanced and new

companies formed.

While I will be referring to my own particular passion of biotechnology, the

successes and impact that we have seen involving taking an idea, nurtured in the lab

through to the marketing of a new medicine follows a similar pattern — involving

commitment, dedication, and risk-taking — that ties all these exciting stories together.

If biotechnology’s umbilical cord is venture financing, then innovation is its life’s

blood. Biotechnology, which started out as a hope, a dream and a promise some

36 years ago has evolved into a viable and stable global industry with more than

5,000 companies in existence today. This remarkable growth would not have been

possible without the technology transfer and research achievements that took place

in academic institutions across the nation and around the world.

However, to continue my analogy, the idea represents the embryonic form; it

requires many steps from birth as a commercial enterprise through to coming of age

where a medicine finally receives approval and can go on to make a contribution to

society by saving lives and improving the quality of life.

The evolution of the underlying science, which underpins everything that is done

in biotech will become even faster paced as we move along the continuum to find

faster and less expensive methods to bring drugs to market. We also need to find

better and better ways to process the massive amounts of data we are getting

from the remarkable technologies that we have today and transform them into

preventative cures for our health care problems.


Preface


For years it has been recognized that using genetics to target the right medicines

to the right patients at the right time could improve health care. However, it is only

since the completion of the Human Genome Project that new genetic information and

technologies have begun to make an impact on medical practice. This project is often

thought of as the pinnacle in technology transfer. It was made possible through the

discoveries of Herb Boyer and Stanley Cohen, who provided the turning point in

DNA research and founded the biotech industry through the creation of one of the

most successful startup companies born of academic research and venture capital,

Genentech.

The promise is compelling for the future of health care — personalized medicine

offering earlier and more precise diagnoses, treatments tailored to the individual,

reduction of side affects and adverse reactions to drugs, breakthroughs in treatment,

and ultimately prevention of major diseases such as cancer, diabetes and Alzheimer’s.

However, it is challenging pharmaceutical and biotechnology companies alike to

adapt. Until recently, their focus has been on the discovery of blockbuster drugs.

With the convergence of IT and genomics, smarter drug delivery and “labs on a chip”

we are progressing down an inevitable path towards targeted medicines — and spot-

ting “early warning” signs of impending health problems. Factor in the emergence of

molecular diagnostics and the re-emergence of genomics and proteomics companies

and you have a new environment of personalized, predictive and preventive medicine

(the three “Ps”) that will revolutionalize the health care system, as we know it today.

The technologies and discoveries embodied in the three Ps can come none too soon

because we are already witnessing major drivers threatening to disrupt the present

system: drug safety concerns, new medicine reimbursement issues, escalating costs of

health care where 75 cents of every dollar is consumed for the management of chron-

ic care and the increasing health demands of an aging population. The current cost of

chronic diseases in the U.S. alone is approaching $1.5 trillion. By 2030, 20% of the

U.S. population will be over 65 years of age and seniors consume about five times as

many drugs per person as their working-age counterparts. In addition, it is estimated

that 125 million Americans have one or more chronic conditions (e.g. congestive heart

failure, diabetes).

Preface

Personalized medicine is the use of new methods of molecular analysis to better

manage a patient’s disease or predisposition toward a disease. It aims to achieve

optimal medical outcomes by helping physicians and patients choose the disease

management approaches likely to work best in the context of the patient’s unique

genetic and environmental profile. Such approaches may include genetic screening

programs that more precisely diagnose diseases and their sub-types, or help physicians

select the type and dose of medication best suited to a certain group of patients.

Advances have already been incorporated into the clinical setting, most notably by

individualizing treatment decisions in oncology, in particular for leukemia, and for

breast, colon and pancreatic cancers. Scientific revolution is unparalleled in our history

and we have more than 800 potential biotech treatments in clinical trials.

However, the cost of biotech innovation is huge — a daunting $1.2 – $1.8 billion to

bring a new drug to market. It also involves high risk, as only a fraction of the drug

candidates that start their journey towards market ever make it. Small wonder that

investing in biotech is not for the faint of heart.

Thus, as investors, we are taking a chance, it’s true, but we view this as a very

necessary investment in the future of mankind — and that gives us courage. There is

also an opportunity for moving the science forward into commercialization and for

creating value. This, of course, requires a tremendous amount of due diligence and

dogged research, but those of us who have stayed with this industry for decades

know that the effort is well worth it. The collaboration between researcher,

technology transfer professional and investor will continue to take on the challenge

of delivering science into the public’s hands, because it is their sole purpose to do so.

There is no higher priority than making human lives better.

2006 was biotech’s second active year in a row in terms of buyouts, as large

biotechnology and pharmaceutical companies went beyond licensing agreements to

fill out development and product pipelines. We haven’t seen this many deals in any

year between pharma/biotech and biotech/biotech in the industry’s history. The huge

premiums that big pharma is willing to pay for biotech innovation reflects their

pipeline problems. Compared to the daunting costs that are needed to bring a new

drug to market and the long 10- to 15-year development cycle, paying big premiums,


Preface


even for drugs that are not yet in the clinic, is both a cheap and efficient way of

reducing development costs and shortening commercialization timelines for the

pharma acquirers. Demonstrating the desire to move life-enhancing products into

human hands faster and with greater effectiveness.

There will be no slow down in partnering deals and a significant portion of the

$20 billion that is projected to be raised in 2007 will be directed at gaining access to

technology at an earlier stage in its development as companies strengthen their

product indication franchises.

Since the mid-1990s, the life sciences have undergone a major revolution.

The systematic sequencing of the human and other genomes has triggered major

changes in biological research, which was previously based on the traditional

bottom-up philosophy of individual investigators contributing knowledge piecemeal.

But technological advances and large-scale approaches to knowledge production

require new ways to plan, fund and conduct research. These developments have also

raised enormous interest not only from industry but also from politicians who count

on the life sciences to create new jobs and economic developments.

I applaud AUTM for producing this second edition of the Better World Reports.

It truly demonstrates the efforts of academic technology transfer professional and

their industry counterparts working together to meet the ever growing needs of the

public. Whether it be medicines, green technologies, improved methods of food

production or safer transportation, startup companies are yet another way we achieve

this goal. This publication provides just a snapshot of the impact technology transfer

has, both financial and social, around the world.

The ongoing challenge for all of us is not only to continue to discover fabulous new

technologies but ensure that they are effectively transferred into the exciting new

products of the 21st century.

Preface

G. Steven Burrill, one of the original architects of the biotechnology industry, has

been involved in the growth of the industry for more than 40 years. He is founder

and CEO of Burrill & Company, a life sciences merchant bank focused exclusively on

companies involved in biotechnology, pharmaceuticals, diagnostics, devices and

related medical technologies. Burrill’s technical and venture investing competence

spans the entire spectrum of life sciences.


Preface

Chapter

BIOXTechnologyMakesBiodieselFaster andCheaper

A University of Toronto chemistry professor’s

research that began with sewage sludge oils

has led to breakthroughs in producing biodiesel —

a cleaner form of fuel for diesel engines.

17

1


The BIOX plant in Hamilton, Ontario, Canada, is capable of producing 60 million liters (18 million gallons) of biodiesel a year.

O


1

University ofToronto

BIOX Corp.

Oil and water don’t mix, as any elementary school science teacher will tell you.

That basic concept is the foundation of a University of Toronto chemistry professor’s

discovery that has significantly cut the time and cost for creating biodiesel —

a renewable fuel for diesel engines derived from natural oils like soybean oil and a

variety of other feedstocks such as animal fats, greases and used cooking oils.

It also led to the creation of an Ontario firm called BIOX Corp., which has 33

employees and is headed by Chief Executive Officer Tim Haig. BIOX recently built a

$24 million plant in the steel-making city of Hamilton.

The facility is capable of producing 60 million liters (18 million gallons) of biodiesel

a year and shipped its first batch of fuel to the United States in late 2006. Over time,

the company hopes to build plants throughout North America and Europe.

BIOX’s Beginnings

The BIOX story goes back more than a decade to when David Boocock, Ph.D., then

head of the University of Toronto chemical engineering department, was looking into

the oils that were produced when sewage sludge was heated. He is now a professor

emeritus at the school.

“I was investigating the technology of using pyrolysis to turn the sludge into a

liquid fuel,” he recalls. Pyrolysis is the use of heat to break down complex chemical

substances into simpler substances.

“I identified that there were good oils and bad oils,” he explains. “The bad came

from the proteins and the good came from the lipids.” Lipids are also known as fats.

That led Boocock — an organic chemist by training — to biodiesel that was being

manufactured in Germany.

“I knew that it was lipid-like, so I looked at the literature and came to the

conclusion that most of what was being published was wrong,” he notes.

The people making biodiesel believed that methanol and vegetable oils and animal

fats, plus a catalyst, would mix, he said.

“They don’t,” says Boocock. “Chemical engineers call this a mass transfer problem.

They were trying to measure the rates of reactions, but it was based on a faulty

premise.”


1

Biotechnology

To cut to the quick, Boocock came up with an inert co-solvent to add to the oil and

methanol. The three melded and became one.

“It was clear and you could see through it,” he comments. “And when it was

mixed, the reactions speed up and go a lot further.”

That, in a nutshell, was the technology that launched BIOX. Boocock continued to

refine his discovery, and in 1999, it began to look like the technology had a business

application. The Natural Sciences and Engineering Research Council of Canada

provided funding for Boocock’s research underlying BIOX.

Biodiesel’s Growing Importance

Cyril Gibbons is the commercialization director for physical sciences and engineering

for Innovations at University of Toronto (IUT), a group of professionals charged with

commercializing innovations developed by University of Toronto researchers and its

health care partners. He commented that there was not a lot of interest in the tech-

nology until the cost of fuel began its upward swing.

Boocock said the discovery of mad cow disease in Canadian cattle several years ago

also made producing biodiesel cheaper.

“It is the cost of the feedstocks that largely control what it costs to make biodiesel,”

he says. “And when mad cow disease appeared, this resulted in a dramatic falling in

prices of ‘refurbished’ waste fats and oils (from animals).”

Regulations cut off transfer of those materials between countries, essentially

wiping out the foreign market, so the BIOX process also helps solve a waste problem,

he said.

Gibbons adds: “From the

environmental side, there are

many reasons to use biodiesel

because it is significantly clean-

er, emitting 80 percent fewer

hydrocarbons, 60 percent less

carbon dioxide and 50 percent

less particulate matter than

petroleum diesel.”


1

University ofToronto

BIOX Corp.

He says that Innovations helped Boocock patent his discovery and retains a small

interest in BIOX.

Moreover, scientists say high quality biodiesel blends easily with petroleum diesel in

any proportion, requires no engine modification, and is actually good for the engine.

“Before 1999, biodiesel was considered too expensive too produce,” he says. “But

the cost of oil is now about double what it was back then, so the economics shifted

strongly in our favor.”

Growth Opportunities for BIOX

In 2000, Innovations found a Toronto investor willing to put up the money to build

a prototype plant. The company, Madison Ventures Ltd., introduced Haig to

Innovations, and BIOX was off and running.

Haig, an engineer who had worked with wind farms and other renewable energy

sources, said he was fascinated by the simplicity of Dr. Boocock’s discovery. Instead of

applying more heat or pressure to the process — what Haig called the “sledgeham-

mer” approach — Boocock went back to the first principles.

“David is a finesse guy,” says Haig. “Rather than using brute force, he found a way

to make the liquids — oil and alcohol — go together by adding a co-solvent that

made the two want to stay in one phase until the reaction was complete.”

Haig worked with Scott and Joe Monteith, the principals behind Madison Ventures,

who also happened to make grease traps for restaurants.

“It was a lot for what was then just an idea,” says Haig. “But Joe Monteith was a

chemist, too, and he saw elegance in the technology.”

Haig also got about $500,000 in grant money from the Canadian government to

help build the pilot plant.

“Prior to that, we had no idea if it would be scalable,” explains Haig, adding that

the pilot was finished in April of 2001.

“We ran that for some time and found out there was a fine line between making

soap and biodiesel,” he recalls. “As you would expect, we had some issues. But our

first plant, in Oakville, ultimately proved the chemistry.”

Haig then “beat the pavement” to find more high net worth investors so the com-

pany could buy the University of Toronto biodiesel intellectual property outright and

build another plant in Boston.

“The second plant proved efficient separation,” he says. “In the first, you had a

concoction of a whole batch of carbon chains. In the second, we proved we could

separate carbon chains into the right bucket at the right price.”

With that hurdle passed, they scaled up to build the big new plant in Hamilton.

“We finished it this summer and it is working well,” Haig says confidently. “We

raised another $48 million this summer and we intend to build three, four or five

more plants in the next few years, selling to companies that want to mix what we are

producing with regular diesel — probably at blends of 2 to 5 percent.

“And you know the ironic thing about all this?” Haig asks. “Rudolph Diesel

invented the diesel engine to run on vegetable oil.”

Pierre Schuurmans, chief operating officer of Birch Hill Equity Partners

Management, Inc., said his company put up $48 million so BIOX can continue

to grow.

“We think they have a low-cost technology in process that puts them in a good

position to meet the growing demand,” Schuurmans explains. “With mandates and

subsidies in some places, BIOX is very competitive.”

— By Brian E. Clark


1

Biotechnology

Chapter

Berkeley Laband SymyxTechnologies:A WinningCombination

With its unique approach to materials identification and

analysis, Symyx Technologies is helping

powerhouse companies worldwide blaze new trails

in the realm of research and development.

23

2


Symyx scientist using Symyx Software and Tools for a research collaboration program.

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2 Take one brilliant idea, a supportive national laboratory and a savvy technology

transfer office, and occasionally the combination will hit the jackpot. It’s all quite

fitting given that the essence of this story is a technology based on the concept of

combinations. The key elements, when brought together, resulted in the company

Symyx Technologies, Inc., which today generates over $100 million in sales annually.

Symyx was sparked by the innovative research of renowned scientist Peter G.

Schultz, Ph.D., who began his career studying DNA, catalytic antibodies and other

biological molecules. Professor Schultz was intrigued by the concept that manipulating

antibodies in different combinations yielded an exponentially higher number of

biological products, thereby opening the door to broader testing for immune-related

drugs. As a chemistry professor and principal investigator at the Lawrence Berkeley

National Laboratory in Berkeley, Calif., back in the 1990s, he applied the same

approach to the growing field of materials sciences.

While conventional materials development involved creating new materials one at

a time, and then painstakingly testing each one for desired qualities, analyzing

combinations of materials promised to revolutionize the process. Professor Schultz and

his colleagues at Berkeley Lab invented and reduced to practice a highly efficient and

automated process, called high throughput, for simultaneously analyzing 10,000

different materials, or “combinatorial libraries.” Using the techniques of miniaturizing

and simultaneous parallel processing, they designed a technology that allowed them

to identify new materials with specific and desirable physical and chemical properties.

These lead compounds were then analyzed and characterized to determine

their structure.

The scientists achieved their goal of applying the concept of high throughput

research to combinatorial chemistry, and applied it to the discovery of new materials –

from magnets and super conductors, to catalysts and polymers. When they published

this milestone in 1995, it warranted the cover story of the journal Science. That very

same year Symyx was founded.

“It was a very broad concept with high risk that needed to be developed and

commercialized within an entrepreneurial venture,” says Symyx President and CEO

Isy Goldwasser. “That’s why Symyx was quickly founded to advance this technology.”

Lawrence BerkeleyNationalLaboratory

SymyxTechnologies

New Strategies for Successful Technology Transfer

The partnership between Symyx and the Berkeley Lab Technology Transfer

Department was somewhat unusual, but proved to be beneficial to both parties.

According to Viviana Wolinsky, licensing manager at the Berkeley Lab, the Symyx-

Berkeley license transaction is believed to be the first of its kind whereby a national

lab accepted partial payment in the form of equity. This arrangement allowed the

startup company, based on the core intellectual property created at the Berkeley Lab,

to devote more of its initial capital to developing the promising technology.

“As a Department of Energy lab, we’re always keen to make appropriate choices

with licensing,” says Wolinksy. “We realized that Symyx had a great plan from the

start — it made the right choices and has really gone far beyond initial plans.”

The original funding for the work was an $80,000 grant to Professor Schultz for his

research from Berkeley Lab’s Laboratory Directed Research and Development (LDRD)

Program. The LDRD program is a source of discretionary funding that awards grants

through a scientific and management peer review process for early-stage projects that

are directed to the advanced study of hypotheses, concepts, or innovative approaches

to scientific problems.

By 1998, Symyx had raised $38.7 million from a variety of private and ven-

ture sources, including Alejandro Zaffaroni, Bayer INNOVATION, Chemical and

Materials Enterprise Associates, Institutional Venture Partners (which is now

Versant Ventures) and Venrock Associates. The company, headquartered in

Santa Clara, Calif., went public in 1999 and is listed on NASDAQ.

Today Symyx is an impressive example of a federally funded technology that

resulted in a vibrant and profitable startup, creating hundreds of high-value

jobs. Symyx has more than 375 employees, the majority of whom are high-

level scientists and technical staff.

“We’re proud of this job creation, as well as other direct and indirect effects on

economic development,” says Wolinsky. “Symyx has become a research powerhouse

for other businesses both nationally and abroad.”

Symyx’s performance continues to shine. Last year the company reached over $108

million in revenue. Goldwasser says that as the first company worldwide to offer this

technology, it has built a leadership role and therefore gains the most business and


2

Biotechnology

Chemist using Symyx Software to design and executeexperiments. Photo courtesy of Symyx Technologies, Inc.


2the most investments. Currently its equity is worth approximately $750 million, a

value that has benefited both the Berkeley Lab and other Symyx shareholders.

Impacting the Big Industries

The list of materials and technologies that have emerged from the company’s

founding technology continues to grow, as does the list of pharmaceutical, chemical,

energy and electronics companies that have benefited from Symyx Tools, Software

and research services. Two of the company’s more prestigious clients are ExxonMobil

and Dow Chemical, and each has made a long-term commitment to change its

organization to conduct research and development the way Symyx does,

according to Goldwasser.

“Industry-leading companies like these don’t usually seek help from outsiders, so it’s

been a big shift for them,” he says. “This exemplifies how Symyx has changed an

industry that is normally very resistant to change.”

The materials that have been developed in the years since Symyx introduced its

broad methodology include new polymers, chemical catalysts and specialty formula-

tions. With over 320 issued patents, Symyx has the largest portfolio of any company

devoted to high throughput materials discovery.

“Most technologies out of universities and national labs are very early stage tech-

nologies that need further nurturing and are not ready to jump out of the lab and into

the marketplace,” says Wolinksy. “But Symyx was able to take a very early stage

technology, and a great concept, and exploit it to its fullest so that it’s now providing

huge value across an entire panoply of industrial sectors. It’s very rewarding to see a

licensee that has devoted its resources and creative energies so well.”

Goldwasser, who began his involvement with Symyx as a summer student with

Schultz, is perhaps most proud of the way in which Symyx is changing the field of

materials sciences.

“We have been very profitable and very fast growing for a small company,”

he says. “What’s most impressive for everyone is that we have really achieved what

we initially defined as our overall vision — to change the way that research and

development is conducted, by making it faster, better and more efficient.”

— By Nicole Resnick


SymyxTechnologies

Chapter

Farecast: The First andOnly AirfarePrediction Web Site

A University of Washington professor developed

Farecast.com, a Web site that helps travelers

save money by forecasting the best time to buy

airline tickets for the best prices.

27

3


O


3 Oren Etzioni doesn’t believe in getting mad. But making sure he doesn’t get burned

twice, well, that’s another thing.

So a few years back, after the University of Washington (UW) computer science

and engineering professor learned that the passenger in the seat beside him paid

approximately $70 less for the same flight — and had purchased it later — his brain

started to spin.

“My family and I were on our way to my brother’s wedding,” he recalls. “Because

there were four of us, it wasn’t an insignificant amount of money that we’d spent on

our airfares.”

That set him thinking how he could use data-mining technology to figure out the

best time to buy a ticket for the best price.

It wasn’t too long before his annoying experience, and the ensuing research,

sparked a company first dubbed Hamlet, as in “To Buy Or Not To Buy.” Since then,

the name has changed to Farecast, to better reflect its mission.

It has attracted more than $8.5 million in venture capital funding, made 150 billion

price observations and spawned a workforce of more than 20 employees in Seattle.

And by late 2006, it was covering 75 airports and 2,000 market combinations.

Since its June 2006 launch, Farecast.com has also become popular with users,

logging more than 1.5 million unique visitors in its initial beta phase.

Moreover, the Web site has earned accolades right and left, including honors from

Time magazine, Popular Science, Business Week, Kiplinger.com and Frommers.com.

And after initial skepticism from the airline industry, it has now been accepted and

even endorsed by some key players.

In a statement, American Airlines says: “We support Farecast because they

provide useful information that helps consumers make smarter and more confident

purchase decisions.”

Etzioni first worked with colleagues at the University of Southern California on the

project because they had an infrastructure to gather the necessary flight and pricing

data to anticipate price fluctuations. For a start, they studied Seattle and Boston.

“That was how it began,” he says.

University ofWashington

Farecast

They then wrote a paper and presented it at the 2003 Conference on Knowledge,

Discovery and Data Mining. The University of Washington followed up with a brief

press release on the academic study.

What came next shocked Etzioni.

“I never thought anybody read those press releases,” he says. “But this one

triggered a huge amount of interest.”

Media outlets that covered the story at the outset included Wired, MSNBC, “NBC

Nightly News,” The Seattle Times and Business Week. Since then, it has received

much more coverage.

“I got hundreds of e-mails from people saying ‘Hey, I want this,’” says Etzioni.

“In addition, people in the travel industry contacted me and said ‘When can we have

it?’ At that point, I realized I’d struck a raw nerve.

“I thought what we’d done was kind of neat,” he allows. “But before that flurry of

interest, I never thought it would be the basis for a company.”

Etzioni was also motivated by a somewhat indignant student, who accused the

professor of being unhelpful.

“This fellow was sitting in back of my class. He proceeded to tell me how expen-

sive fares were and said he was going to fly home to see his mother,” Etzioni says.

“He asked if I could tell him the best time to buy a ticket. When I said I couldn’t

because what I’d done was a limited study, he accused me of holding back on him.”

That, and the growing public interest in his project, spurred

Etzioni on.

The Washington Research Foundation (WRF), which helps

Washington state research institutions derive and enhance value

from their emerging technologies, contributed $30,000 for

additional research after the initial results were established,

Etzioni says. Even though all he had was a speculative concept

and a research prototype, Seattle’s Madrona Venture Group and

WRF Capital (which manages the Washington Research

Foundation’s seed venture fund) ponied up $1.5 million in

October 2004 to get the company off the ground.


3

Computer Sciences


3About a year after the first round of funding, Greylock Partners joined Madrona

and WRF in a second round that raised another $7 million.

“Madrona agreed to take a chance on us in part because I serve as an advisor for

them and because they have a long relationship with our department and have fund-

ed many startups coming out of it,” he says.

The University of Washington’s Technology Transfer Office then stepped in to help

with the licensing deal, which included an inter-institutional agreement with the

University of Southern California.

“Everyone said ‘We have some great early-stage stuff here,’” says Chuck Williams

of the UW. “All the parties wanted to jump on Oren’s idea.”

Hugh Crean, Farecast’s president and CEO, joined the company in November 2004.

He says consumers typically save about $40 on a ticket using the service and that

Farecast is accurate nearly 75 percent of the time.

Because Farecast sends customers directly to the airlines Web sites, once they have

decided on a flight, they do not have to pay a service fee, like online travel agencies

often charge.

“Essentially, we’re like the weatherman,” Crean says. “We make forecasts so

people can avoid experiences like Oren’s. It really isn’t any fun to sit on a plane and

find out you bought your ticket earlier than someone next to you did, but you

paid more.”

Farecast’s patented airfare prediction shows whether the lowest fares for trips

are rising or dropping over the next seven days. The company also shows

anticipated price movements, confidence levels and buying tips when consumers

search for flights.

“With many airfares running around $300, these tickets aren’t an inconsequential

purchase,” says Crean. “We want to be like a ‘Consumer Reports’ and help online

travel shoppers save money and buy with confidence.”

To create its proprietary airfare predictions, Crean says Farecast systematically

aggregates large amounts of airfare data on a daily basis, and tracks and measures

price fluctuations.

University ofWashington

Farecast

Along with each flight search, Farecast.com provides an airfare history graph.

The airfare history graph shows online travel shoppers what the lowest available price

for their trip has been each day, up to 90 days in the past.

To back up its fare predictions, Farecast in mid-December started testing a new

product called “Fare Guard,” which gives users an option to lock in low fares for one

week without buying the ticket. The cost during the initial test period was a mere $1.

It is scheduled to go up to $9.95 when the product officially launches in 2007.

“We offer Fare Guard when we predict that fares are dropping, so we’re putting

our money where our mouth is,” says Crean.



3

Computer Sciences

Chapter

IntelligentMicroPatterning, LLC: Unique andImaginativeThin FilmSolutions HelpMove OtherInnovationsForward

A University of South Florida marine scientist invents

a novel approach to using direct optical projection

for micro patterning helped launch a thriving spin-off

company, and today helps bring research to a new level.

33

4


An SF-100 maskless lithography system configuredwith the 1/3 reduction option

M


4 Marine scientist David Fries describes the scene: there he was, watching the sunset

from the back deck of a sailing vessel off the coast of Florida and collecting data for

an experiment designed to test an underwater device he had invented. Then, during

a lull in the work, Fries let his mind wander, and that is when the idea for a new

technology — one that had eluded him for the previous two years — suddenly came

to him.

This particular scientific concept involved the use of spatial light modulators, or tiny

mirrors, to make patterns — a process also known as lithography. Much like a printing

press transfers words or images onto paper, Fries’ new direct optical projection

lithography uses light to create patterns, such as that of a circuit board, onto a wide

variety of surfaces and materials. Fries, a researcher at the University of San Francisco

(USF) College of Marine Sciences, designed a successful prototype and joined with

Jay Sasserath, Ph.D., a local scientist-turned-businessman to develop a marketable

product and start a thriving spin-off company.

Today, Intelligent Micro Patterning (IMP), LLC, headquartered in St. Petersburg,

Fla., influences manufacturing and scientific discovery all around the globe. The com-

pany provides unique and critical tools, in the formation of thin film solutions, needed

by researchers and manufacturers across a wide range of sectors such as biotechnolo-

gy, nanotech devices and microwave devices. Intelligent Micro Patterning’s patented

Smart Filter 100 technology produces microdevices like mini-circuit boards and sensors

and can pattern onto various surfaces from glass microscope slides and intravenous

needles to the inside of a ping pong ball. The ability to pattern onto copper tape,

for instance, has been a key step in the development of radio frequency identification

chips, such as those used in tollway fee transmitters and dog ID implants. Other

applications include the patterning of metal conductor lines onto traditionally non-

conductive materials such as ceramic.

Help From Family and Humble Beginnings

Going from the “eureka” moment to a profitable business did require some help.

Fries refined his initial idea, assembled a prototype patterning device in his laboratory

at USF and assigned his nine-year-old son the task of first-time user of the prototype.

University of South Florida

Intelligent MicroPatterning, LLC

When they demonstrated success, Fries knew that it was time to approach the

Division of Patents and Licensing at USF. The technology transfer experts encouraged

Fries to partner with an experienced businessperson, and he did so with Sasserath —

no stranger to the microelectronics industry in the St. Petersburg area.

Sasserath has served as CEO since the company was founded in 2001. At that time,

the Smart Filter technology had just been licensed from USF, while the company was

granted the exclusive global rights to the technology. Fries continues to serve as chief

technical officer of Intelligent Micro Patterning.

“The original research for the development of the technology was funded through

a project that David Fries had with the Office of Naval Research,” says Sasserath.

“This was used to develop the technology in the late ‘90s.”

From the perspective of the Division of Patents and Licensing at USF, the founding

and steady progress of IMP has been an ideal experience. Director Valerie McDevitt

points out that a key component of the formula has been the experienced and

aggressive managers who “knew how to take a product and run with it.” Add to the

mix a savvy researcher who has remained a USF faculty member and maintains many

beneficial university connections, and finally, a smart and sound technology for which

there was a niche.

“Altogether, we had all the pieces to the puzzle,” says McDevitt, “so the company

hit the ground running and got to a profitable point very quickly.”

McDevitt says that Intelligent Micro Patterning is a very good example of her divi-

sion’s key mission of economic development. The company provides an added bonus

by hiring university students and faculty.

Ever since Fries first obtained initial development funding for demonstrating the

prototype at the university, the two have succeeded in gaining enough private fund-

ing to allow the company to remain financially independent. As the principal owners

of the company, they have yet to tap into venture capital or other primary outside

funding sources.

Impacting the Local and Global Markets

Now with four full-time and 10 part-time employees, Intelligent Micro Patterning is

expanding at an encouraging rate. The company proudly announced record financial


4

Computer Sciences


4results for the year 2005, according to Sasserath, earning more than $1 million in annual

revenue. Its success was driven by the introduction of the SF-100 Auto Stage — an

automated version of the SF-100 maskless lithography system. The year also marked

the move of the company to significantly larger facilities in the St. Petersburg area.

The presence of Intelligent Micro Patterning within the St. Petersburg business

community has been especially fulfilling for Fries, whose civic-mindedness is evident.

“I have always felt that this area could use some balance in its economic picture,

with a more diverse portfolio,” he says, “As an entrepreneurial seat, it needs to grow

its reputation, [and there’s] something I can do to make it happen. Our company and

others can begin to feed off each other and create an industrial ecosystem over the

long term.”

Looking beyond the local economy, Intelligent Micro Patterning established a

worldwide sales and service effort with offices throughout North America, Europe and

Asia. Sixteen sales representatives are now employed by the company and the list of

industrial giants who are using the Smart Filter technology include Hewlett Packard

and two other Fortune 100 companies.

“Our company partners with technologists that seek new, unique, and innovative

technologies to accomplish their goals,” says Sasserath.

Half the sales of the Smart Filter system are in the biotechnology sector and include

researchers who need to manipulate cells and DNA, produce biochips or design

state-of-the-art biotech devices. While many of Intelligent Micro Patterning’s clients

are major universities such as Purdue, Arizona State and the University of North

Carolina, half the company’s business is with private companies, and information

about the use of IMP’s technology is proprietary.

Fries is pleased with the growth that Intelligent Micro Patterning has achieved in its

brief lifespan as a university spin-off. Probably most rewarding for him is what the

technology represents with respect to those who use it.

“Our company allows people to have access to a technology that can accelerate

innovation,” says Fries. “Through its ability to help people develop other technologies

and test their products more quickly, it is helping to shape society by allowing the

cycle of innovation to move faster.”


University of South Florida

Intelligent MicroPatterning, LLC

Chapter

ALEKS Tutors Studentsin Learning toSucceed

The groundbreaking intelligent tutoring system

developed at the University of California, Irvine,

equalizes educational opportunities because

it knows exactly what the student knows and

what the student is ready to learn.

37

5


Gary Oakland, a seventhgrade teacher in Chula

Vista, Calif., uses ALEKS toteach math to his students. Ph

oto

cour

tesy

of

Ron

Bec

ijos

A


5 “Alan,” a student at Hilltop Middle School in Chula Vista, Calif., knows firsthand

that when it comes to learning, one size doesn’t fit all.

He was getting Ds and Fs on his seventh-grade report card when his father called

Gary Oakland, a teacher at his school, saying he didn’t know how to help his son.

Over the past five years, Oakland has had great success with ALEKS (Assessment

and LEarning in Knowledge Spaces), a groundbreaking technology developed at the

University of California, Irvine (UCI) in the mid-1990s. The revolutionary artificial

intelligence technology, now used by hundreds of thousands of students in more than

1,000 schools, was developed by Jean Claude Falmagne, Ph.D., chairman and founder

of ALEKS and emeritus professor of cognitive science at the University of California,

Irvine, along with and a team of researchers.

Oakland suggested Alan try working with ALEKS. Using his home computer, Alan

started getting excited about learning. Pretty soon he finished 100 percent of the

state’s standard Grade 7 math requirements. Oakland, who has trained all of the math

teachers and math department heads in his school district on ALEKS, says, “Over this

past summer, Alan, who is now in eighth grade, completed 85 percent of an algebra

course all on his own without ever spending a day in an algebra class.”

ALEKS has revolutionized learning because it interacts with students at a highly indi-

vidual level of readiness instead of teaching to the “fat part of the curve.” Subjects

such as math, chemistry and accounting, have been traditionally taught in a linear

method — in a start-to-finish sequence.

“But the reality is not everyone learns at the same pace, and not everyone can

afford a tutor,” Oakland says. “You should be able to achieve success by teaching in a

logical, sequential manner, but it doesn’t work that way. Everyone learns differently.”

Anyone who has worked with ALEKS knows it is all about outcomes. Students are

taken on a fantastic voyage of learning, and in the process, ALEKS helps them achieve

academic success, often for the first time in their lives.

ALEKS Unveiled

In 1993, Falmagne says researchers at UCI received a “lucky break.”

“We received a $2.4 million grant from the National Science Foundation to develop

University ofCalifornia, Irvine

ALEKS

the software that would become ALEKS,” he explains.

The technology is based on Knowledge Space Theory, a milestone in cognitive

psychology and applied mathematics. Its origin goes back to the early 1980s when

Falmagne, along with Dr. Jean-Paul Doignon of the Free University of Brussels in

Belgium, and scientists at New York University and other universities, began to

develop Knowledge Space Theory.

“Knowledge Space Theory is not only about finding out what someone knows,

but that knowledge acquisition takes place in a ‘learning space,’” says Falmagne

who notes the extremely complex software took 10 years and millions of lines of

code to create.

In 1997, the UCI Office of Technology Alliances licensed the technology to

ALEKS Corp. Two years later, McGraw-Hill became the distributor of ALEKS in

higher education.

“In 1999, our first commercial products of Basic Math and Beginning Algebra for

two-year colleges got off the ground,” notes Falmagne. “Our partnership with

McGraw-Hill has also allowed us to develop many other products.”

Classroom Dynamics

From the moment the computer screen lights up, ALEKS takes students on a

rewarding journey. The technology can be used for independent learning — students

can get ahead on their own by accessing ALEKS from any computer or the software

can be used for specific courses as well as in school computer labs.

In November 2006, Oakland made a presentation to the California Math Council

showing how ALEKS can help students with varying scholastic aptitudes succeed

beyond their wildest dreams.

Oakland’s school, located about 15 miles from Mexico, has a student population

that is about 75 percent Hispanic.

ALEKS is fully bilingual in Spanish and English for math through Grade 9, with

instantaneous “one click” translation.

In 2001, when the school received a flyer about ALEKS, Oakland was teaching an

after-school algebra recovery program to seventh- and eighth-grade students (to help

them “recover” their grades from failing the class the year before).


5

Education


5“The students have to make up 60 hours to repeat or ‘recover’ a class,” Oakland

says. “Some of our students weren’t even coming to school.”

On top of failing grades, he says behavioral issues created a nightmare atmosphere

for both students and teachers. But there was hope in the form of ALEKS.

“The more they use ALEKS, the more apt they are to get good grades,” Oakland

comments. “When they get their first ‘A’ it’s a heady experience — there’s no

stopping them.”

“First off, ALEKS does an assessment to determine precisely which topics the

student has already mastered,” says R.G. Wilmot Lampros, president of ALEKS Corp.,

Tustin, Calif. “ALEKS avoids multiple choice questions. There are no lucky guesses —

it’s not geared to finding out how good a test taker a person is. The student has to

know how to solve a problem.”

Oakland’s school didn’t have a computer lab, but he was determined to build one

so his students could use ALEKS. Oakland, along with an information technology

staffer from the school, brought in 60 old computers that didn’t work.

“Together we repaired and rebuilt the computers, bought inexpensive keyboards,

and repaired tables and chairs,” he recalls. “In the end we had our computer lab

complete with 34 computers.”

Oakland saw positive results from ALEKS from the start. He willingly made the long

drive from the mountains where he lives to teach the algebra recovery classes on

weekends and during the summer in addition to after school classes, which are now

math support classes.

Lampros notes that ALEKS was not developed around the idea of using technology

to maximize high-end graphics.

“That’s one of the reasons why ALEKS’ success is so fascinating,” he says. “We use

graphics where they are pedagogically useful. Students fall in love with ALEKS not

because of its visuals, but because using it enables them to learn and excel.”

They also see an immediate assessment of what they know and how to do a

problem right.

“They tell me they love ‘seeing’ what they know,” says Oakland, referring to the

program’s popular pie chart feature. “When students click on it, ALEKS shows them

University ofCalifornia, Irvine

ALEKS

not only what they can do but, what they are ready to do next. They love seeing

where their knowledge is growing.”

Learning Comes Alive

Harold Baker, Ph.D., director of customer support, has been with ALEKS since

before it became a commercial product. From early on, he recalls a vivid image of

how ALEKS makes math come alive.

“A student with developmental disabilities was sitting at her computer at a commu-

nity college unable to type like other students, but she was so caught up in learning

math from ALEKS, that she used her pencil’s eraser to enter numbers and letters from

her keyboard,” he says.

What ALEKS is not, he says, is a program that just gives more homework online.

“There are possibilities for deep customization with ALEKS — it has many features to

make sure teachers are successful as well as students,” he says.

“Studies have shown that early failure in math, particularly in Algebra 1 and 2 is

often a predictor of failures in other disciplines,” say Baker. “If a student has failed

before, he will likely fail again. ALEKS breaks the cycle of repeated failure.”

ALEKS offers another classroom benefit. It frees up teacher time and allows teachers

to spend more time with individual students (or small groups) and do more creative

things. “Instead of just teaching math and other subjects, teachers can have fun

teaching students the applications of math such as how math is used in building

bridges,” notes Baker.

What’s next for ALEKS? The company will launch an elementary chemistry program

in early 2007. Recently, a study by researchers at the University of Memphis, showing

how an ALEKS statistics program can eliminate racial disparities, was accepted by the

American Educational Research Association for presentation at its annual meeting.

Summing up why students like ALEKS, Falmagne says, “It talks directly to them,

and it always rewards their time and effort.”

While ALEKS has made a difference in many students’ lives, more will benefit in the

future. “The potential for success for students throughout the world is unlimited,”

says Baker. “ALEKS is an intelligent tutoring system that really works.”

— By Sharyn Alden


5

Education

Chapter

Taking theScience ofMeasurementto a HigherLevel

By designing analytical equipment that’s

easy to use, inexpensive and more precise,

Qubit Systems is changing the way

universities teach and conduct research.

43

6


Natural physiological measurements are made easy by Qubit Systems portable instruments, as shown by this researcher measuring soil respiration parameters of an alfalfa field.

F


6 Founded in 1995 as a spin-off company from Queen’s University in Kingston,

Ontario, Qubit Systems Inc. is indeed a technology transfer success story. The

Canadian company designs and manufactures state-of-the-art analytical instruments

for teaching and research in the biological sciences. Today Qubit Systems provides

standard and customized research and instrumentation systems for more than 500

educational and research institutes around the world.

Professors David Layzell, Stephen Hunt and Nicholas Dowling of Queen’s University

recognized the need for durable, inexpensive laboratory equipment for their students.

“When using research equipment in teaching labs, the costs and availability of such

equipment often means that students merely gather around expensive pieces of

research equipment for demos of physiological processes,” says Hunt, president and

CEO of Qubit. “We wanted to change all that. Since Qubit equipment is sometimes

only one-tenth the cost of typical research equipment, labs can purchase several

Qubit packages for the price of one research instrument. This allows small groups of

students to do hands-on experiments themselves, which is really the only way to

teach, instead of just gaping at a black box spitting numbers.”

Several of Qubit’s products are the first of their kind, such as a patented differential

oxygen analyzer that allows researchers to conduct experiments in plant and

insect metabolic analysis that were previously impossible.

“Nobody else was able to make an O2 analyzer with the required

resolution,” says Hunt. “We have also come up with innovative ways to

measure nitrogen fixation from legumes, which is greatly expanding our

knowledge of this very important process.”

These new methods have shown that previous studies greatly under-

estimated N2 fixation rates. Research based on improved techniques will

hopefully lead toward new farming methods that result in healthier plants

and higher yields.

PARTEQ Innovations is the not-for-profit technology transfer office of

Queen’s University and has supported Qubit from its inception. In the early

days the company worked out of an incubator facility that was jointly funded

Queen’s University Kingston, Ontario

Qubit Systems Inc.

The Human Respirometry package allows investigations into respiratory and cardiovascularphysiology by measuring heart rate and breathingfrequency and comparing the CO2 and O2 concentrations in inhaled vs. exhaled breath.

by Queen’s University and the City of Kingston. PARTEQ also financed Qubit’s initial

work with a loan of $24,000 and helped secure a larger $150,000 loan through the

Business Development Bank of Canada. Additionally, PARTEQ assisted Qubit with its

business plan and intellectual property protection. To date, Qubit has six patents in

the U.S., Canada, Europe and Australia.

Easier for Students

Qubit’s technology and innovative designs have resulted in simplified, inexpensive,

highly accurate instruments that work well for both research and teaching. The

analyzers are integrated into complete software-controlled systems for measuring

processes such as photosynthesis and respiration in living organisms.

“The simplicity of Qubit’s designs allows students to understand the processes they

are measuring better than our more elegant, expensive, portable photosynthesis

machine does,” indicates Professor Judy Parrish, Ph.D., of Milliken University in

Decatur, Ill.

Because they are developed by university professors with actual teaching experi-

ence, Qubit’s educational packages are designed to fit perfectly into curriculum lab

work. Several packages are one-of-a-kind products that make it possible to explore

subjects such as fish respirometry, nitrogen fixation, and soil respiration — all of which

are key indicators of the health of our waters and soils.

“Another excellent feature is that the students can assemble the unit, get it

working, and then handle the data,” adds Warwick Silvester, Ph.D., of the University

of Waikato in Hamilton, New Zealand. “This is great from a teaching point of view in

that students feel they are in control and they learn the real pitfalls in setup and

data handling.”

Because Qubit’s gear is low-cost, universities can afford to furnish entire laboratories

with multiple Qubit teaching packages, an attractive option for higher-education

institutions in poorer nations.

“In addition to their teaching value, many of our educational packages have the

resolution and accuracy suitable for research applications, allowing scientists in

developing countries with low R&D budgets to carry out top-level research at a very

affordable price,” comments Hunt.


6

Education


6The high resolution and durability of Qubit equipment makes it ideal for use in both

the laboratory and in a wide variety of field situations. Researchers on an icebreaker in

the Canadian arctic, and others in the tropical rainforests of Costa Rica, use Qubit

equipment to monitor respiration in samples as diverse as crustaceans and the eggs of

sea turtles. In fact, an increasing number of articles in notable research journals are

based on research conducted with Qubit instrumentation.

Qubit is also tackling problems associated with global warming by providing

analyzers to measure fluctuations in greenhouse gases in a variety of environments.

In addition, Qubit equipment is being used in a unique study to determine if the

accumulation of greenhouse gases may have resulted in past global catastrophes.

Scientists at the University of Washington are using Qubit technology to recreate

the atmosphere from the Permian period — the last period of the Paleozoic Era —

to study how an ancient period of global warming may have resulted in an extinction

of plant and animal species.

In the Near Future

Qubit Systems now derives more than 60 percent of its revenues from products

designed for scientific research. Recent partnerships with companies in the United

Kingdom, Denmark and the Czech Republic have led to exciting new projects in

pharmaceutical development, fish biology and plant science. Qubit also builds

customized instruments for private-sector companies, such as a system for the food

industry that determines the freshness of salads prior to packaging, and equipment

for the pharmaceutical industry that creates the low-oxygen environment required for

keeping extremely expensive chemicals (reagents) from breaking down during storage.

The company is also hard at work developing new products in the field of human

exercise physiology. These devices, which can be used in private practice, research and

teaching, will analyze breath gases to better evaluate cardiovascular health and

fitness. Medical students will be able to determine their own metabolic rates through

breath analysis, which provides much more accurate assessment of fitness than

other methods.

“Many breath-analysis systems available now cost $40,000-$50,000, and only

large health care centers can afford them,” says Hunt. “Ours will be half that cost,

Queen’s University Kingston, Ontario

Qubit Systems Inc.

making it much easier for individual physicians to afford them. This means patients

won’t have to be sent to hospitals for testing, which should help lower overall health

care costs. Other products derived from our fitness-testing equipment will be ideal

for personal fitness assessment in health clubs, and for use by individuals who must

monitor their diets and metabolism very closely, such as people who are obese or

have cardiovascular problems.”

— By Mark Crawford


6

Education

Chapter

Making Light theMessenger: How WavefrontCodingTM isRevolutionizingthe World ofOptics

By deliberately distorting the light rays that strike

an object and processing the intercepts with

a special algorithm, CDM Optics creates perfectly

focused images with an astounding depth of field.

49

7


Image taken with a commercial 3 megapixel auto focus camera

Image taken with an OmniVision 3 megapixel camera with Wavefront CodingTM

I


7 If you look at the blurry image that CDM Optics’ high-tech equipment produces,

you might think, “Even I can take a better picture than this.” But keep in mind that’s

only the first step. With a little electronic finessing the image is transformed into a

sharply focused photograph with remarkable depth of focus — up to ten times

greater than any top-ranked camera can produce.

Using innovative optics and algorithms, CDM Optics technology enhances the

performance of camera systems by increasing the depth of field and correcting optical

aberrations that typically occur with standard cameras. It also drastically reduces the

size, weight and cost of an optical system.

Today nearly every field that relies on optics and lenses, such as astronomy,

transportation, life sciences, manufacturing, shipping and distribution, security and

military operations, could benefit from CDM Optics technology.

The company was founded by Thomas Cathey, a professor of electrical engineering

at University of Colorado at Boulder (CU), Edward Dowski, one of Cathey’s Ph.D.

students, and R.C. “Merc” Mercure, a successful entrepreneur with a doctorate in

physics from CU.

The initial research and development work was conducted at CU’s imaging systems

laboratory in the department of electrical and computer engineering. Funding for the

initial research at the University of Colorado leading to the invention of Wavefront

Coding™ was provided by the National Science Foundation. startup funding leading

to the commercialization of the technology at CDM Optics, Inc., was provided by

Small Business Innovation Research Grants, grants from the State of Colorado and

from the Department of Energy’s Rocky Flats Initiative. In 2005 CDM Optics was

purchased by OmniVision Technologies, Inc., a California-based company that

produces image sensors for markets around the world. As its subsidiary, CDM Optics

develops imaging equipment for cell phones, infrared sensors, night vision surveillance

systems, iris identification systems, and biological and medical research.

How the Technology Works

Wavefront technology basically codes a stream of light by passing it through a

special lens and then decodes it by signal processing, with a computer.

University ofColorado atBoulder

CDM Optics

“We came up with the idea of deliberately distorting the light rays by passing them

through a lens that’s shaped like a saddle — relatively flat in the middle, but with

scalloped edges,” says Cathey. “The result is a specific optical aberration, which looks

like a blurry image.”

Although it doesn’t look like it’s worth 1,000 words, the picture is packed with data

that can be decoded by the computer. The image is blurry because the light rays are

spread out, which keeps them from being focused in a single plane. Each point of

light, wherever it strikes the object, becomes a fixed point in space and a data point.

Image processing then removes the blur point-by-point using an algorithm in the

computer. The result is a perfectly focused image with a much greater depth of field.

“If you took a picture of a picket fence with a regular camera,” says Mercure, “the

first picket is in focus, the second picket is slightly out of focus, the third is blurry, etc.

If you took the same picture with our equipment, those three pickets, as well as the

next six or seven, will all be in focus.”

There are big advantages to CDM Wavefront CodingTM.

• Cameras that use Wavefront CodingTM won’t need the extra, built-in mechanisms

that correct for standard lens aberrations, or curvature changes due to changes in

temperature, which means fewer lens elements, smaller size and lower manufac-

turing costs.

• For scientists, CDM Optics systems in microscopes will allow them to focus over

a wider and deeper area. For example, researchers at the National Cancer

Institute can focus on a single living cell with one image, rather than relying on

multiple images that represent different cross sections through the cell.

This makes it easier to track rapid changes in the cell structure and speeds up the

rate of research.

• Photographers will be able to take better-quality, more detailed photos because

they won’t have to worry about focusing precisely on a specific plane. “When

people take a picture with an auto-focus camera, there is a one- or two-second

delay as they wait for the camera to focus,” says Mercure. “Our technology

eliminates that delay and makes the camera truly a ‘point and shoot.’”

Future Is Clear

Although CDM Optics is now a subsidiary of OmniVision, it continues to


7

Electronics


7be part of the Boulder community and contributes to the local economy. CDM Optics’

close working relationship with researchers at the University of Colorado at Boulder

have resulted in the licensing of newer and value-added technologies that are being

developed by the company.

OmniVision recently released a digital camera chip for back-up and parking-assist

cameras in cars and trucks — a natural application for Wavefront CodingTM.

OmniVision and CDM Optics are also developing the next generation of machine-

vision devices, such as scanners.

“Because of the increased depth of field, barcode scanners using wavefront

technology will be able to read labels on curved and slanted surfaces,” says Dowski.

These scanners can also be used for light assembly and inspecting electronic circuits.

Iris recognition is rapidly becoming the biometric application of choice in areas

where security is a top concern, such as airports, border crossings, and high-level

public and private office buildings. Although it’s the most accurate way to recognize

an individual, the process can be very slow. People often have to wait in long lines to

position their eye within a small area of restricted focus. Wavefront CodingTM can sig-

nificantly enlarge that area of focus, which makes it easier to position people for iris

identification.

“Federal agencies such as Homeland Security and the Department of Defense are

looking at Wavefront CodingTM as a way to capture iris images at much greater

distances than current technology can,” says Mercure. “People may simply be able to

pass through this ‘space’ as they walk by from five or six feet away.”

Other research projects involve medical/biotech applications. Olympus Optical of

Tokyo is studying CDM Optics’ technology as a way to create extended-depth-of-

field endoscopes — instruments used for close examination inside patients’ bodies.

It may even be possible in the future to restore vision in the elderly using Wavefront

technology.

“In this case, Wavefront CodingTM optics would be built into contact lenses or even

surgically attached to corneal tissue,” says Mercure. “This would not make everyday

scenes more recognizable, but it could provide patterns of light that the brain could

learn to decipher.”


University ofColorado atBoulder

CDM Optics

Chapter

Phiar Adding NewHigh-SpeedWaves toElectronics

Phiar Corp.’s quantum tunneling technology

is centered around the idea of

electrons as “waves” rather than “particles.”

53

8


Phiar tests its diodes using high frequency probes to determine the efficiency of its products at 60 GHz.

G


8 Garret Moddel considers an unfinished tuna salad in California one of the best

lunches of his life.

“It was at a presentation to the investors of Menlo Ventures on our technology,”

says Moddel, the co-founder, chairman and CTO of Phiar Corp. in Boulder, Colo.

“I told them we might have a whole new platform technology. In a way, just as

vacuum tubes gave way to semiconductors about 50 years ago, now perhaps we

have the potential for semiconductors to give way to something that is newer, faster,

more easily integrated and cheaper.

“I remember I ordered tuna salad. I couldn’t eat it because I was talking. After I was

done with the presentation, Mark Siegel, one of the managing directors, says, ‘We’ll

get back to you’ and told me I could go into the next conference room to finish

lunch. I sat down to eat my tuna salad and about halfway through it, Mark came into

the room and says, ‘We’re going to fund you.’ So I never did finish the tuna salad.”

That led to $9.3 million in venture funding for Phiar, which officially opened on

July 2, 2001. Today, the company employs 16 people. The company has a partnership

with Motorola, which could become a major purchaser of the technology. It recently

moved to a 10,000-square-foot facility that includes a clean room, testing and

development labs, as well as office space.

Phiar’s Technology: Less Costly, Much Faster

Phiar is developing components for what the company describes as “true monolithic

integration of high-frequency electronic and electromagnetic-wave functions onto sili-

con chips and other substrates.” Phiar’s metal-insulator technology replaces costly

hybrid semiconductors and extends the functions to higher frequencies.

The company is implementing this concept as practical components — diodes,

detectors, transistors, varactors, modulators — to provide a full suite of low cost,

ultra-fast, integrated components for building high-frequency electronic and terahertz

(THz) wave circuits and systems.

Quantum tunneling is the basis of Phiar’s technology. At the heart of the

phenomenon is the quantum mechanical notion that electrons are “waves” rather

than “particles.”

University ofColorado at Boulder

Phiar Corp.

Phiar remains focused on research and development. At the time of publication, the

company did not have commercialized products for sale. Diodes and detectors will be

the first Phiar products to market, followed by transistors and other devices,

culminating in transceivers. The company expects to have its diodes and detectors in

production in 2007. The company targets 2008 for production-ready transistors for

transceivers.

Growth Opportunities

Potential applications for the technology seem almost unlimited. “The term

‘platform technology’ has been abused,” says Adam Rentschler, director of business

development. “But Phiar’s is truly a platform technology. Metal-insulator electronics

will impact everything from aircraft landing assistance and improved airport security

screening to wireless consumer electronics and adaptive cruise control for cars.

“The radar and imaging applications for our technology are very exciting.

An example is aircraft landing assistance imaging that sees through clouds, fog or

smoke. There are applications for security screening. The idea here is you can shoot

safe, non-tissue damaging waves at people. The screening will reveal things missed

by metal detectors like ceramic knives or plastic explosives.

“On the automotive radar front, we are not doing anything that can’t be done

today with other solutions, but we can reduce the costs of these systems by about a

factor of 10. If auto makers can get their costs down from about $1,000 to let’s say

$100, all of a sudden you’re going to see these systems — today found only in luxury

vehicles — popping up on KIAs and Hyundais.”

Wireless data transfer is another potential application. “The promise is putting five

DVDs of data on an iPod in two seconds,” Rentschler says. “When the supporting

technology in hard drives and flash memory catches up with us, this will be a reality.

We’ll also be able to stream 50 channels of uncompressed high def TV simultaneously.”

The technology has potential applications in medical imaging and other fields.

The Birth of a Startup

Moddel, who is on the faculty at the University of Colorado at Boulder (CU), has

been interested in startup companies since the early years of his career, when he was

part of a solar cell startup in California.


8

Electronics


8“When I first graduated from grad school, I went to a little Silicon Valley startup

company,” Moddel says. “We wanted to make solar cells and paint the world with

solar technology and reduce the power of the oil companies. It was very idealistic.

It was fascinating, and we developed a lot of technology, but we really had no

markets. I learned a lot about what to do and what not to do with startups.

I probably got the bug then.”

Moddel remained interested in solar cells and in the potential of metal-insulators

while at CU. He and a grad student, Blake Eliasson, who now is director of engineer-

ing for Phiar, worked long and hard on the technology.

The team ran into a challenge: single-insulator diodes were not efficient enough.

Eliasson had a novel solution: Two insulators (rather than one), can be engineered to

form a quantum well in the middle of the device, greatly enhancing performance.

Attorney Steve Shear, Moddel and Eliasson decided to start a company to

explore the breakthrough. That led Moddel to that memorable “non-lunch” at

Menlo Ventures.

After many months of negotiations with the CU, Moddel simultaneously inked deals

with Menlo Ventures and CU’s Technology Transfer Office.

Moddel served as Phiar’s CEO for four years. During his tenure, Phiar grew from

three to 10 employees and raised the $9.3 million in venture capital.

In May 2005, Moddel stepped aside as CEO and Goodman was hired. To date,

Goodman has successfully negotiated the Joint Development Agreement and

Intellectual Property Agreement with Motorola, moved the company to the

10,000-square-foot fabrication and testing facility and continues to strengthen the

team with top talent.

Partnerships between startups and universities have become keys for technology

development. “Tech transfer has come a long way at the university,” Moddel says.

“They have been very helpful. Now if you want to do breakthrough technology, it’s at

universities and startups. It’s a different culture and the economy has changed.”

Tom Smerdon of the Office of Technology Transfer at CU, says Phiar was one of

several startups that began with ties to the university. “It’s been making fine progress

on development,” Smerdon says.

University ofColorado at Boulder

Phiar Corp.

Partnerships like Phiar’s with Motorola are another key. “That sort of makes us

real,” Moddel says.

“We view the metal-insulator technology from Phiar, combined with Motorola’s

technology and expertise, as being an innovative approach to potentially providing

the device speeds that will be required in future generations of wireless, radar and

imaging solutions provided by Motorola,” says Vida Ilderem, vice president and direc-

tor of the center of excellence for embedded systems and physical sciences research,

Motorola Labs, in a press release when the partnership between Phiar and Motorola

was first announced.

And, of course, the venture capital from Menlo Ventures was another key —

even if Moddel never did finish that tuna salad.

— By Gregg Hoffmann


8

Electronics

Chapter

Enval OffersBreakthroughRecycling

The University of Cambridge, with Enval Ltd.,

hopes it has a technology that

can do something useful with the aluminum

from juice cartons, much of which ends up

in landfills around the world.

59

9


Carlos Ludlow-Palafox operating the machine and overview of the equipment: (from front toback of image) condensation/collection system; reactor; feeding and purge system.En

val p

hoto

s co

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sy o

f Em

man

uel C

olle

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Ben

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(ph

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I


9 In Western Europe, more than 30,000 tons of aluminum are used annually in the

lining of drink cartons. The statistics are similar for North America.

Enval Ltd. hopes its technology can recover the aluminum, much of which ends up

in landfills.

Using technology developed at the University of Cambridge in the United Kingdom,

Enval uses the process of pyrolysis — applying heat to create a chemical change in a

substance, in the absence of oxygen — to separate the aluminum from plastic that

also is a by-product from the partial paper recycling of cartons. That aluminum then

can be sold for reuse.

Enval also hopes to add energy efficiency to the process by manufacturing a

portable pyrolysis machine, rather than having to haul the aluminum and plastic to a

central processing location.

“The paper content of cartons has been recycled for quite some time and reused

as pulp paper by paper companies, but the residue from the depulping process,

containing valuable aluminum, is often sent to a landfill,” says Carlos Ludlow-Palafox,

Ph.D., co-founder and chief technical officer of Enval.

“After treatment with the new technology, the metal has a ready market and the

oils, generated from the plastic layer, can be used to power the recycling machine.

The rubbish sites save money, by avoiding paying landfill taxes. The metal industry

saves money and a lot of energy, by purchasing ready-to-use secondary aluminum.

And, as consumers, we no longer feel guilty about throwing away yet another drink

container that cannot be completely recycled. The planet wins.”

Similar processes have been used in Brazil and Finland, and experimented with in

other parts of the world. But, Enval has technology that can be portable.

“It is not energy efficient to haul aluminum liners and plastic to a treatment site,”

Ludlow-Palafox says. “It is a relatively light, fluffy material that takes up space, but

does not have much weight. So, the portability of our pyrolysis machine has great

potential.”

University ofCambridge, UK

Enval Ltd.

Startup Support

Enval is building a pilot plant pyrolysis machine, thanks in part to startup money

from the University of Cambridge and an angel group of investors headed by CREATE

Partners. That group has made an initial seed investment of £200,000 with a view to

investing further amounts over the next three years.

The investment will allow Enval to build a first-class execution team, to develop a

pilot plant for industrial demonstration and to secure initial contracts with industry

partners around the world.

Tetra Pak, a leading maker of drink cartons, and others have expressed interest in

the technology.

“We are delighted to support a promising technology that, if successful on a large

scale, will substantially increase recycling in the UK,” says Richard Hands, environ-

mental manager for Tetra Pak UK & Ireland, in a Nov. 8, 2006, press release.

The process used by Enval started more than eight years ago as Ludlow-Palafox’s

Ph.D. project at Cambridge. He worked with Howard Chase,

professor of biochemical and environmental engineering and former

head of the department of chemical engineering at the University

of Cambridge.

“I had been interested in the process of pyrolysis, so we did the

scientific research and developed a lab prototype of a device,”

Ludlow-Palafox says. “I was looking at it from the viewpoint of a

scientist at that time. I could see it had commercial applications poten-

tial, but I did not think at that time I would be the one to do it.”

But, in 2003, Ludlow-Palafox found himself getting involved in the

business process. Cambridge Enterprise, which works with technolo-

gy transfer at the university, began working with the researchers,

clarifying the route to market the technology, patenting the inven-

tion and using a Proof of Concept grant from the Higher Education

Innovation fund to build the first continuous prototype of the

process. The University Challenge Fund supported market research

that identified a number of paper companies interested in the process.


9

Environmental

Top of the reactor showing the feeding pipe, stirring systemand the waveguides which feed the microwaves to the reactor.

Enval photos courtesy of Emmanuel College and Ben Johnson (photographer)


9Ludlow-Palafox and Chase, together with Alexander Domin, Ph.D., entered the

2005 Cambridge University Entrepreneurs Business Plan Competition and won.

That led to incorporation and the additional funding from CREATE.

Groundbreaking Opportunity

“Enval is a groundbreaking opportunity,” says Boyd Mulvey, chief executive of

CREATE, in a Nov. 8, 2006, press release. “The new process offers industry a simple

and cost-effective solution to solving a serious environmental problem. Enval has a

robust, patented technology and now, with venture capital and Angel investor back-

ing, the company has the financial resources to deliver that solution.

“CREATE has worked successfully with GEIF Ventures, Cambridge Angels,

Cambridge Capital Group and the University of Cambridge Challenge Fund to provide

the investment into this compelling business plan.”

Ludlow-Palafox spent much of the latter part of 2006 traveling throughout Europe

talking to paper companies and other potential partners for Enval.

“Again, I started at this from the approach of a scientist,” Ludlow-Palafox says.

“I now love what I am doing (the combined role of a scientist and entrepreneur).

It was difficult going through the period of seeking funding — wondering whether

you were going to get any or enough — but now it is rewarding to see the potential

in the marketplace.”

Enval initially stood for “Environmental Aluminum.” But, the technology could be

used in other recycling possibilities for tires, oil and other waste materials. So, Enval

could evolve into “Environmental Value.”

“The research has potential for the marketplace,” says Ludlow-Palafox, who still

works with Chase on advising some of the Cambridge researchers. “What better way

to bring it to the marketplace than through a company that already is working on it.”


University ofCambridge, UK

Enval Ltd.

Chapter

CarrierAeroseal:SealingHeating andAirConditioningLeaks from theInside Out

Aeroseal, now a division of Carrier Corp.,

revolutionized the process of searching for,

and sealing, hidden leaks in heating and air ducts.

63

10


Aeroseal equipment being prepared to inject sealant into anexhaust duct system on the UC-Davis campus in February 2006.

Photo courtesy of Carrier Aeroseal

M


10 Move over duct tape, a new competitor on the market is getting the job done

faster and with more energy savings.

Long thought to be the right solution for stopping leaks around hot or cold air

ducts, fabric-backed duct tape fails to seal leaks in ducts and pipes, according to

Lawrence Berkeley National Laboratory in Berkeley, Calif.

Instead, Aeroseal duct-sealing technology, invented and developed by the Energy

Performance of Buildings Group at Lawrence Berkeley National Laboratory, is making

waves for its ability to seal more leakage because of its unconventional method of

getting at inaccessible leaks.

Each year about $5 billion of energy escapes into thin air due to leaky ducts in

American homes. The new technology stops the leaks from the inside of the ducts by

coating the leaks with tiny sealant particles. The discovery can benefit virtually anyone

with a heating and cooling system by offering increased energy savings and comfort.

Mark Modera, Ph.D., inventor and principal investigator for the research group that

developed the technology, is also the principal engineer with Carrier Aeroseal. He

points out why it’s challenging to maintain a comfortable environment if there are

duct leaks.

“You won’t have the same degree of comfort in a two-story home that you’re

trying to cool in summer when you have duct leaks,” he explains. “But the Carrier

Aeroseal technology allows more air and cooling upstairs and ultimately provides

more comfort.”

Addressing Energy Costs

Viviana Wolinsky, licensing manager at Berkeley Lab says, “Even in the very early

stages of the development, we could see that the duct-sealing technology had

far-reaching benefits for everyone interested in decreasing energy costs.”

Wolinsky points out that no one wants to pay more for their energy bills than they

have to, but when leaky ducts mean you’re paying to heat or cool the air outside

your home or office, it’s doubly frustrating.


Carrier Corp.

“The prospect of being able to make homes and commercial buildings more energy

efficient by sealing ducts from the inside, and at the same time making interior envi-

ronments more comfortable, was exciting from a technology standpoint,” she says.

Idea Comes to Life

The first concept for the technology came to Modera in 1987 when it was apparent

that the current methods for sealing leaks weren’t effective.

“It’s difficult, often impossible, to seal duct leaks from the outside when the ducts

are in inaccessible locations,” says Modera. “When exploring technologies to seal

leaks from the inside, I found that sealing leaks in straight pipes is one thing, but too

often there are bends and junctions in the ducts and that’s where the problem lies.”

Modera used his skills as a research scientist to gain information about duct sealing.

When he saw a newspaper advertisement touting a company’s ability to seal duct

leaks, he set up a duct system and invited the company to take a look at it.

“I discovered their method didn‘t seal the system I showed them,” he recalls.

“That‘s when I decided that maybe I could design a technology that would seal ducts

from the inside.”

Invention Driven by Marketplace Needs

In 1990, the original funding came as part of a multi-year, multi-million dollar

Department of Energy (DOE)-sponsored Cooperative Research & Development

Agreement between Berkeley Lab and the California Institute for Energy and the

Environment, $50,000 of which was for developing duct technology. Subsequent

funding of more than $1 million was provided by the Environmental Protection

Agency, DOE and the Electric Power Research Institute.

For three years, Modera and a graduate student worked on developing the

technology, and in 1993, Modera says, “We figured it out.”

Modera explains how the technology works using the analogy of a car driven at

high speeds.

“If a car is driven at 90 miles per hour in the city, it will skid out and crash going

around the first sharp turn. Similarly, our technology works by using airborne

adhesive particles injected into the ducts so that, when they speed up trying to go

through a leak, they ‘pile up’ or ‘crash’ into the sides of the leak and seal it.”


10

Environmental


10Carrier Seals the Deal

In 1997, the technology was licensed for use in the residential market as well as for

small commercial buildings. The logical next step was to create a business so the

technology could reach customers who needed it. By 1997, Dr. Modera began spend-

ing about half of his time in the lab so that he could devote enough time to starting

the company.

The marketing of Aeroseal, which is the name of the company as well as the prod-

uct, was initially done through franchises primarily sold to heating and cooling dealers.

In 2001, the business was sold to Carrier Corp., which in turn created the

subsidiary, Carrier Aeroseal. Two years later the company obtained a license from

Lawrence Berkeley National Laboratory for improved nozzles and was able to offer

the same product and service to the non-residential market.

Hospital Sees Benefits from Duct Sealing

When Cleveland’s MetroHealth Medical Center hired Karpinski Engineering as a

consultant to improve the heating, ventilation and air conditioning systems in its

Central Sterilization Department, the firm specified that the Carrier Aeroseal method

of duct sealing should be utilized for a portion of existing ductwork on the project.

A previous balance report had shown significant leakage in the hospital’s ductwork

in this part of the facility.

“We felt that the Carrier Aeroseal technology would be ideal for this project,” says

Nathan Anderson, a project engineer with Karpinski. “The hospital has an exhaust fan

on the roof and ductwork that was originally installed in the 1970s. When originally

constructed, this ductwork was enclosed in a shaft and after the leakage was

revealed, the duct was inaccessible for sealing.”

The first steps involved Modera taking measurements and sealing off the existing

exhaust grills, and a sealant was injected from the inside of the ducts.

The technology can block off existing exhaust openings that range from a quarter

inch to a half inch in size. The time varies from a few hours to a few days depending

on the characteristics of individual heating and cooling systems.


Carrier Corp.

“With Carrier Aeroseal, it’s a computerized, high-tech process,” says Anderson.

“Once the openings were blocked off, sealing ducts from the inside took just about

30 minutes.”

The “after sealing” report at the time the project was completed in April 2006,

showed about 85 percent of the leakage had been plugged — 1,570 cubic feet per

minute (cfm) leakage prior to sealing, 230 cfm leakage after sealing.

“By specifying Carrier Aeroseal, we accomplished our goal, which was to improve

the exhaust airflow rates,” says Anderson. “If we had not sealed off the ducts from

the inside, there would have been significant demolition work involved to accomplish

sealing from the outside because of the inaccessibility to the ductwork.”

Meeting the goals of the hospital was paramount for the engineering firm.

“By using this new technology, which has a 10-year warranty, we saved the

hospital time and money,” says Anderson.

The engineering firm is so satisfied with the technology, it has specified Carrier

Aeroseal to seal 21 ducts in another significant Cleveland building.

“The technology is simple, easy and relevant to today’s world,” says Wolinsky.

“Customers realize a demonstrable payback. When they see how much air is escaping

in the before-test when compared to after the ducts are sealed, it’s a powerful visual.”

Between 2003 and 2006 Carrier Aeroseal sealed 20 large buildings ranging from

offices to hospitals. The company intends to focus on promoting the technology via a

larger launch into commercial markets during 2007 and 2008.

“The driving forces are energy savings and building/system performance improve-

ment,” Modera points out. “During the past four years of accelerated testing, the

technology has never failed.”

— By Sharyn Alden


10

Environmental

Chapter

CEA SystemsOffers MoreEfficient Waysto Bring Foodto the Tableand the Lab

CEA Systems, and its partner, Cornell University,

have developed an agricultural technology that could save

energy, provide better food security and control, and lead

to the creation of products for pharmaceuticals and

other high-value plant-based compounds.

69

11


Hydroponically-grown baby spinach, free from grit and dirt, three days before harvest.

A


11 A vast majority of people in the world live within 10 miles of their major food

sources, but in the United States much of our food travels as far as 2,000 miles from

the farm to the table.

CEA Systems, and its partner, Cornell University in Ithaca, N.Y., think they have the

technology that could change that, thus saving energy while providing better food

security and control, as well as developing products for pharmaceuticals and other

high-value plant-based compounds.

CEA, which stands for Controlled Environment Agriculture, is an advanced and

intensive form of hydroponically based agriculture. Plants are grown within a

controlled environment so that horticultural practices can be optimized. Cornell has

long been a leader in this research.

Techniques are not simpler than older systems for growing plants. Indeed, they

demand sound knowledge of chemistry, horticulture, engineering, plant physiology,

plant pathology, computers and entomology.

“We basically use the control of light, and an optimized solution of nutrients, in our

agriculture,” says Louis Albright, Ph.D., one of the founders of the CEA program at

Cornell and current director of the program.

The plants are grown in a high-tech greenhouse, where the environmental

variables — total amount of daily light, carbon dioxide concentration and

temperature — are controlled by a computer. The environmental variables monitored

include relative humidity, temperature, carbon dioxide and light intensity.

“By using the computer, we can predict temperatures, light and other factors and

adjust the process through shades and supplemental light,” Professor Albright

explains.

The hydroponic system used is called the deep trough system. In this system, the

tank is filled with a nutrient solution and the plants are grown on Styrofoam with

holes, which floats on the surface.

In a deep trough system, aeration is necessary since the water surface is completely

covered by Styrofoam, which minimizes evaporation and discourages algae growth.

Pure oxygen is injected into the system to ensure that enough oxygen is supplied to

the roots. Acid and base injections also are made to maintain pH.

Cornell University

CEA Systems

A dedicated computer is used to control and monitor variables in the nutrient

solution, which include temperature, electrical conductivity, pH, dissolved oxygen,

nitrate concentration and nutrient solution volume.

All Grown Up and No Place to Go

Cornell originally had a commercial partner, Agway, in its greenhouse research,

but that Northeast-based cooperative pulled out because of their own financial

concerns. Cornell was left with a CEA operation with market possibilities, but no

commercial partner.

Mike Hall, a retired Air Force pilot and Cornell graduate, was interested in the

Cornell CEA work and stepped in.

“I was raised on a small farm in upstate New York and remained interested in

agriculture,” says Hall, who is now with CEA Systems, a business and commercial

development firm. “I also worked with cutting edge technology while in the

Air Force and was aware of what was being done at Cornell. So, these things sort of

came together.”

CEA Systems, which grew out of Hall’s efforts, is a privately held corporation based

in Ithaca, N.Y. CEA Systems is in partnership with the Cornell Center for Technology,

Enterprise and Commercialization, which manages Cornell University’s intellectual

property. It is charged with the development and deployment of CEA technology and

know-how for the profit of the partners. The exclusive license for the CEA technology

was granted to CEA Systems in 2002.

“Our mission is to identify and develop commercial applications for the intellectual

property and technology flowing from the Cornell University CEA research program,”

Hall said.

John Brenner, senior technology manager of the Cornell Center for Technology,

Enterprise and Commercialization, says, “CEA represents the enormous potential, the

complexity and the unexpected outcomes related to university-based technology

transfer. From the standpoint of potential, CEA is a platform to launch a completely

new paradigm in plant-based science research and education. All of production agri-

culture has been focused on the plant’s survivability in field-grown batch agriculture.


11

Environmental


11“CEA offers the ability to optimize a plant’s growing environment such that it con-

centrates its energy on productivity, not simply survival, while at the same time offer-

ing continuous production in place of batch production. The simple shift from

survivability to productivity offers wide scientific research opportunities to learn

exactly what are the optimal conditions for various plants and then how to breed or

otherwise modify the plants for even greater productivity once you can control the

plant’s environmental parameters.

“The potential extends to other plant-based products that are currently impossible

to produce reliably such as pharmaceuticals and other industrial products. In each case

the potential represents decades of research, education and economic opportunity.”

Potential Growth Opportunities

CEA Systems continues to seek commercial partners for joint venture opportunities

in high quality, nutritionally-enhanced crops; environmental systems; energy-efficient

food production and distribution and pharmaceutical production.

The latter in that list might come first, according to Hall.

“When I was in the Air Force, the move to jets in commercial airlines might not

have happened if the military had not worked in that area first,” Hall says.

“There is somewhat of an analogy to CEA. There is resistance to change in the

produce and food industry. We have regionalized it, with much of our leafy

vegetables raised in California and other western areas and trucked to the population

centers in the Northeast and elsewhere. We believe that will change eventually

because of escalating petroleum costs and other factors.”

“At this point, however, we also can provide pharmaceuticals from the nutrients in

the produce we grow. We can control that effectively because of the controlled

environment. So that might develop first, with a trickle down into the food industry

over time.”

Hall and Professor Albright emphasized that 70 percent of the light in the CEA

system comes from natural, outside sources, even in the somewhat cloudy region of

the Northeast. Supplemental light from electricity can be produced cheaper than

petroleum for transport if the latter continues to go up in price.

Cornell University

CEA Systems

Contaminants from pesticides, manure and other additives used in conventional

agriculture, and even organic agriculture, can be eliminated through hydroponic agri-

culture. “We like to think we are doing organic farming, only better,” Albright says.

Hall said that incidents like the e. coli outbreak in spinach and onions in 2006 only

spark more interest in CEA.

The CEA research has attracted funding from the New York State Energy Research

and Development Authority, the Empire State Electric Energy Research Corporation,

Agway, Inc., Country Products Group, the New York State Electric and Gas

Corporation, the Niagara Mohawk Power Corporation, the Electric Power Research

Institute, NASA and Westbrook Greenhouses.

CEA at Cornell has published research on dry bean growth for a NASA mission to

Mars, a host of work on hydroponic lettuce and spinach production, supplemental

lighting in indoor agriculture and a variety of related topics.

Various related courses are offered through Cornell’s departments. Handbooks for

growers of hydroponic lettuce, spinach and bok choy are available.

CEA Systems also has instituted a sub-licensing program to provide the system to

local sheltered workshop organizations for client employment in a cash flow business

model so that such agencies are able to deliver a product to the marketplace. The first

example is Finger Lakes Fresh Lettuce, produced by Challenge Industries in Ithaca, N.Y.

“People who might not get a chance to work in a high-tech agriculture

environment are getting practical experience and do a wonderful job in packaging

and a variety of other areas,” Hall says.

Hall and Professor Albright feel strongly that the day is approaching when we will

want to move our food production closer to where people live. “I don’t know exactly

when it will happen, but I believe it is coming within the next 10 years,” Hall said.

Professor Albright adds, “We want to be ready.”



11

Environmental

Chapter

Green Powerfor the Planet’sBiggestPolluters

Westport Innovations, a small company in

Vancouver, British Columbia, is driving a change in the

way the world powers its buses and trucks, which are a

major source of urban air pollution and greenhouse gases

in industrialized areas around the globe.

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A Westport engineer upfits a Cummins ISX engine with

Westport HPDI fuel injectors. © 2

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12 Air pollution casts an ugly cloud over the world’s largest cities, hanging over

crowded highways in places like Sao Paolo and Mexico City. Trucks and buses alone

contribute more than 20 percent of total particulate air pollution around the globe.

These heavy-duty vehicles are usually powered by diesel engines, long a favorite of

manufacturers and suppliers of commercial vehicles because of their characteristics,

which combine robust performance with energy-efficiency. Unfortunately, the engines

also are a major source of urban air pollution.

For the air quality regulation authority in Los Angeles, the “last remaining

beachhead” to cleaning up air pollution in the area were the ports of Los Angeles and

Long Beach. Together, the two ports contribute 9 percent of the smog; 12 percent of

the particulate matter pollution, or soot; and 45 percent of the sulfur oxides, or acid

rain air in Greater Los Angeles, according to the ports’ Clean Air Action Plan.

Westport Innovations is working with the South Coast Air Quality Management

District in Los Angeles to reduce particulate air pollution from diesel engines in

the trucks that transport container cargo from the ports. The Vancouver,

British Columbia-based company is helping government agencies and suppliers

of vehicles around the world switch to a cleaner natural gas power while retain-

ing the positive traits of diesel.

Westport’s engines are developed around a technology called high-pressure

direct injection (HPDI), invented by Philip Hill, an emeritus professor of mechani-

cal engineering at the University of British Columbia in Vancouver. Hill wanted

to preserve the characteristics of the diesel engine that made it popular, while

reducing its harmful by-products.

“Diesel has amazing fuel flexibility and energy efficiency, but, unfortunately,

these engines also produce disproportionate amounts of air pollution,” says David

Demers, founder and chief executive of Westport. “If we could start with a cleaner

fuel, inevitably we would get few problems coming out of the tailpipe.”

Hill explains: “There was a serious defect in the diesel engine, and that was the

emission of particulates and nitrous oxide, and that demanded a solution.”

Hill dedicated his career to working out a solution, starting in the early 1980s, with

funding from the Canadian Science and Engineering Research Council and the Science

University ofBritish Columbia

WestportInnovations

A Norcal Waste Systems (California) driver refuels his Westport HPDI LNG truck.

© 2006 Westport Power Inc.

Council of British Columbia. Most common engines are spark-ignited, and most gaso-

line-powered cars today use a three-way catalyst that reduces dangerous emissions,

but these catalysts are not useful for diesel engines.

HPDI was the answer. It allows diesel engines to use a cleaner fuel without

sacrificing performance. Injecting a small amount of diesel pilot fuel into the

combustion chamber before a main injection of natural gas starts combustion,

preserving performance, but with much lower emissions.

Hill knew his discovery could greatly improve the quality of the very air that we

breathe. Originally, his goal was to repower the bus fleets in North America.

Eventually, this was expanded to potentially include all heavy-duty transport engines

around the world.

In 1995, the University of British Columbia introduced Hill to David Demers, a

successful entrepreneur, and Westport Innovations was born, built around the core

technology of HPDI. It now owns more than 200 patents. Demers says the original

plan was to further develop and demonstrate the benefits of the technology, and

license it to diesel engine companies around the world. But it turned out to be more

complicated than that.

“It’s the classic story of a new technology company that discovers there is no

market for their fantastic new idea,” he says. “Most people didn’t understand how

this innovation could be important to their future.”

Facing the market realities, the company targeted a few of the leading engine

companies active in the California transit bus market. Demers says the management

team knew it would need a complete solution for vehicle fleets, including new fueling

infrastructure and gas suppliers, in order to create a market that could use

its technology.

“We could’ve set up as a new engine company and compete with the existing

industry, but we would need a new plant, new vehicles, new support channels —

a tremendous investment and a lot of risk involved,” Demers says. “It made more

sense for us to try to partner with companies that already had that expertise and

those support channels in place.”

The industry at the time was experiencing excess capacity around the world and

competition was fierce, according to Demers. So it made sense for major diesel


12

Environmental


12companies to work with Westport on a niche market like natural gas, enabling them

to focus on their core business. Companies that used the Westport technology had a

competitive advantage. The Westport engines burned cleaner but they still had the

workhorse properties of old-fashioned diesel.

To solve the infrastructure problem, Westport partnered with the natural gas com-

pany BCGas (now Terasen) in British Columbia to build the infrastructure necessary to

meet the needs of commercial fleets around the world. This included new natural gas

fueling stations in Southern California and elsewhere. This venture, now called Clean

Energy Fuels, is the largest supplier of natural gas vehicle fuel in North America.

Today, Westport is developing technology with Cummins, Ford, BMW, Isuzu and

many others. Uncertainty about access to secure oil supplies, combined with more

stringent air quality standards, has created a demand for Westport technologies.

Stricter regulations pose tough challenges for city governments, making natural gas

attractive because it costs less and produces fewer emissions. Demers notes that most

pollution comes from transportation, and most fuel consumption, in general, is by

heavy vehicles. China and India, the world’s two fastest growing economies, must

build transportation infrastructure to meet their economic goals, and yet are chal-

lenged by environmental regulations. Westport helps suppliers of heavy vehicles meet

the regulations and at the same time keep a check on soaring oil prices.

Westport has partnered with Cummins to become Cummins-Westport, in order to

leverage Cummins’ global manufacturing, distribution and support network. Cummins

does the manufacturing at plants around the world; Cummins-Westport does the

engineering and marketing. Demers says Westport will try to replicate that model with

other companies in other parts of the world.

Demers has seen a change in attitudes from global vehicle manufacturers and

energy suppliers, and their customers, regarding global climate change. He says they

are convinced that something needs to be done about greenhouse gas emissions.

And he feels a certain pride in the contributions of Westport.

“I think we are already changing the world,” he says. “We’ve seen material

improvements in air quality in every place we’ve shipped — and we’ve shipped more

than 14,000 engines to heavily populated areas around the world.”

— By Jill Ladwig

University ofBritish Columbia

WestportInnovations

Chapter

NewTechnologyHolds thePromise ofEarlier andMore AccurateDetection ofAlzheimer’sDisease

Diagnostic Potentials Ltd., a spin-off from the University

of Glasgow, has completed a pivotal clinical trial demon-

strating that the ADEPT System can detect Alzheimer’s at

an early stage. Coupling dense array EEG with a computer

program designed to test patient’s cognitive skills, this

technology may revolutionize the way clinicians diagnose

a degenerative and highly debilitating disease.

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Real-time functional imaging of brain electrical activity is one of the key tools used by Diagnostic Potentials Ltd., shown here by chief scientist Kerry Kilborn, Ph.D.

I


13 It looks like an elaborate hairnet, or a strange wig of wires, and those who place

it on their heads work at a computer terminal. While it sounds like the setup for

some kind of virtual reality game, in fact it is not. Rather, this describes a

cutting-edge technology that may hold the key to the early and accurate diagnosis

of a dreaded disease.

Alzheimer’s, a progressive and degenerative disease, continues to stymie clinicians,

drain nations’ economies and shatter many lives. Currently, the diagnosis of early

stage Alzheimer’s dementia is difficult because affected individuals display symptoms

that appear to be part of the normal aging process. Yet it is during the early phase in

the disease’s development that an accurate diagnosis would be most beneficial and

allow for more effective intervention.

Diagnostic Potentials, located in Glasgow, Scotland, is on track to develop the

missing diagnostic tool. A spin-off from the University of Glasgow’s department of

psychology, the company has gotten off the ground with the help of funding from

United Kingdom government research trust funds. With the completion of the first

clinical trial to evaluate its leading technology — the ADEPT system — the founders

of Diagnostic Potentials are optimistic.

ADEPT uses EEG (electroencephalogram) to measure the electrical activity

of the brain while an individual performs a set of computerized cognitive

tasks designed to assess intellectual function. The goal of the technology is

to identify differences in the electrical signals in individuals with fully func-

tioning brain activity, and individuals exhibiting early stages of Alzheimer’s.

In the latter case, memory function becomes impaired and can be measured

through changes in EEG patterns.

Chief scientific officer and co-founder of Diagnostic Potentials, Kerry

Kilborn, Ph.D., says this technology is less invasive and claustrophobic than

other forms of brain scans presently used to probe for signs of Alzheimer’s.

The EEG array sensor net is designed like a spongy hairnet and patients

undergoing the test simply place it on their heads. The critical difference

between the sensor net used with ADEPT and conventional EEG nets is the

number of sensors used to measure brain activity — 128 rather than 12.

University ofGlasgow

DiagnosticPotentials Ltd.

Diagnostic Potentials Ltd. develops tools to aid in thedetection and diagnosis of Alzheimer's disease usinghigh resolution EEG provided by the Geodesic SensorNet. Image courtesy of EGI, Inc.

This provides a tremendous advantage because by covering most of the upper brain,

the dense array produces higher resolution maps of electrical fields on the scalp and

can better capture brain function.

A Clinician’s Dream

Alan Hughes, M.D., geriatric psychiatrist and honorary senior clinical lecturer at

Inverclyde Royal Hospital in Greenock, Scotland, was involved in the first clinical trial

of ADEPT. As a clinician who treats elderly patients, he understands the present

limitations of diagnosing Alzheimer’s and realizes how essential it is to make the

proper diagnosis early in the disease when treatment is more effective.

“The most useful time of diagnosis, from the patients’ point of view, is when they

can do the most about their illness — when they can participate in decisions about

their treatment, make their wishes known, and discuss them with family members,”

says Dr. Hughes.

Technically speaking, Dr. Hughes says the development of this technology is

significant because current tools for Alzheimer’s dementia such as computerized axial

tomography (CAT) scans simply provide a picture of what the brain looks like at a

specific time. An early stage Alzheimer’s brain often looks the same as the brains of

individuals affected with other diseases.

“This approach, looking at brain function, allows us to be more accurate and gives

us more valuable information,” he says.

Generous Help from the Public and Private Sectors

The transfer of the ADEPT technology from a psychology laboratory at the

University of Glasgow initially presented some intellectual and financial challenges

according to Professor Kilborn. Commercialization support from the Scottish

Biomedical Research Trust and the Department of Trade and Industry for commercial,

legal and intellectual property work were the critical components in the 1999 launch

of Diagnostic Potentials. The Scottish Technology Fund, along with private investors,

helped the founders to raise £384,000 (approximately $618,000 U.S.) to commence

the development phase of the company and support three full-time employees.

The fledgling company devoted the next two years to achieving the ADEPT

technology’s proof of concept while occupying a small space in the Scottish Enterprise

research incubator. They reached their goal and filed for a patent by 2001. THE BETTER WORLD REPORT PART ONE 81

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Health Services


13Although buoyed by this breakthrough, the company faced an uphill battle over the

next few years.

“We had used most of the funding that was raised by that time,” recalls Professor

Kilborn, “so we had to write a new business plan and attract more potential investors

for a second round of funding.”

Despite a real turndown in the market at that time, the company persevered and

eventually found support from several sources — the Wellcome Trust Fund charity,

Scottish Executive, and Scottish Enterprise — totaling over £800,000 (more than $1.3

million U.S.).

Kevin Cullen, Ph.D., director of research and enterprise for the University of

Glasgow, points out that Diagnostic Potentials is an excellent example of how long it

takes to move good university science out of the lab and into the marketplace.

“The story of Diagnostic Potentials demonstrates the process of university commer-

cialization and how necessary it is to find those little pots of money to keep a project

alive at times when the academics are under pressure,” he says. “The process requires

a highly motivated, enthusiastic and determined academic in a supportive academic

environment to make it work.”

With a second round of funding secured, Professor Kilborn and his colleagues

focused on designing a full-scale clinical trial — one that necessitated rebuilding the

ADEPT technology and software from the ground up. In the last several years they

launched and completed the first multi-site clinical trial involving 148 patients at four

different centers across the United Kingdom. Publication of the results is pending, and

Professor Kilborn hints that they are promising.

The trials are demonstrating that the ADEPT technology can identify Alzheimer’s

disease in cases where it might not be easily diagnosed. Cullen is focusing on

the trial’s implications beyond the primary findings and expresses hope that the

technology will be capable of mass applications — especially given our society’s

aging population.

“The ADEPT approach is creative, and from the commercial perspective, we hope

to convince those in the company to look into other markets and explore other

applications,” he says.



DiagnosticPotentials Ltd.

Chapter

DNA Testing:Changing Liveswith a Billion-in-OnePrecision

Using the latest technology, Crucial Genetics

provides the DNA testing that can

“make or break” a case in the courtroom.

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Crucial Genetics can create DNA profiles of individuals based on the analysis of swabsamples taken from inside a subject’s cheek.Ph

oto

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14 Identity has become a powerful driver in today’s world, especially as identity theft

breaks new records every year. Verifying identities through DNA testing has become

a part of daily life as well, leading to richly rewarding experiences that include

reuniting family members and bringing people closer together. Identification through

DNA testing can also bring long-needed closure to traumatic events and start the

process of healing. In short, identity can be the one thing that matters most when

lives are being rebuilt.

This is exactly what Crucial Genetics, a Scotland-based DNA testing company, does

for clients around the world. Using the most modern technology available, Crucial

Genetics delivers the genetic data that is often the difference in “making or breaking”

a case in the courtroom.

“The work we do could be the deciding factor in a murder trial, or it could help

someone confirm the identity of his or her biological father,” says Jacqueline Perry,

Crucial Genetics’ laboratory manager.

Headquartered at Southern General Hospital in Glasgow, Crucial Genetics is

part-owned by the University of Glasgow, an institution with an international

reputation for genetic and forensic research. This close association provides Crucial

Genetics scientists with access to top university researchers who have a remarkable

range of knowledge and expertise in the biosciences.

In the early 1990s, Dr. John Gow, a molecular geneticist who is also director of the

Centre for Forensic Investigation at Glasgow Caledonian University and a leader in

field of DNA research, recognized the commercial need for DNA testing in Scotland.

“The world was showing an ever-increasing need for, and greater reliance on,

DNA testing,” says Gow. “The technology was also rapidly evolving, which made

commercial applications more feasible and affordable.”

In 2003 Gow and his team pioneered several new techniques that enabled the

university to distinguish between family members in disputed paternity cases.

Encouraged by these results, Crucial Genetics was formed in 2004 as a

spin-off company.


Crucial Genetics

“University of Glasgow supported the venture through business model develop-

ment, full marketing support, and securing funding from investors such as Fifty-Six

Ltd., a venture capital firm,” says Kevin Cullen, Ph.D., director of research and enter-

prise for the University of Glasgow.

Over the last two years Crucial Genetics has grown rapidly, tripling in size and

quickly becoming the laboratory of choice in Scotland for DNA testing.

A Unique Technology

Crucial Genetics uses the most advanced automated fluorescent DNA laser scanning

equipment available for STR/PCR DNA profiling — that is, the short tandem repeat

(STR) polymerase chain reaction (PCR) method. This procedure compares 16 genes

and is so sensitive that it can identify someone’s entire DNA profile from one

individual cell. Results are available within 48 hours of testing. The accuracy is

astounding — results are 99.9999 percent reliable, meaning the odds of two people

having the same DNA are more than one-billion-to-one.

Most of Crucial Genetics’ work is directed toward paternity testing, forensic testing,

genetically modified foodstuff testing and the pedigree analysis for animals.

The procedure of preparation and analysis is actually a three-laboratory process.

A swab sample is taken from inside the subject’s cheek. The head of the swab is

injected into a test tube, where the cheek cells are immersed in a concentrated

alkaline salt solution. This solution rapidly enters the cells, expanding the cell and

rupturing the cell walls. The freed DNA molecules, which carry a negative charge,

collect on positively charged magnetic beads within the test tube.

The beads are washed and the pure DNA is released from the beads. The DNA is

then prepared for analysis in a second laboratory, where each of the 16 genes that

will be identified during testing is tagged with a chemical dye.

In the third laboratory the pieces of DNA are separated by size in a genetic analyzer.

An argon laser excites the dyes, which then fluoresce. The fluorescence data is collect-

ed and analyzed by a computer, which converts the numbers into a DNA profile.


14

Health Services


14Results that Matter

Whether it’s the somber identification of human remains, or the joyous reunion of

long-lost family members, Crucial Genetics makes it possible using state-of-the-art

laboratory techniques. The company works closely with police departments,

immigration offices, insurance companies and health care organizations, often

providing critical evidence for police cases and courtroom trials. Crucial Genetics

scientists have helped identify casualties from natural disasters and the war in Iraq.

This type of closure allows grieving families to hold funeral services and begin the

long process of healing.

In 2005 Crucial Genetics became the only private DNA profiling firm in Scotland to

be approved by the United Kingdom Accreditation Service to carry out human

genetic profiling.

“This is a business where you simply cannot afford to make mistakes,” says Gow.

“Having this accreditation illustrates that we operate at the highest level,

both in terms of scientific expertise and capability, as well as professional and

ethical standards.”

Crucial Genetics has also launched the United Kingdom’s first secure DNA storage

and profiling facility — 80 meters underground. Individuals can have samples of their

DNA stored for future use in this highly secure facility, especially those working in

high-risk fields such as construction, security, transportation and the military. Knowing

a loved one can be identified in the event of a tragedy creates peace of mind for the

entire family.

“Storing DNA can be very useful to individuals, as well as organizations,” says Gow.

“Genetic pre-disposition testing will allow families to trace a range of diseases to

which they are susceptible. But if one piece of the family’s DNA is unavailable,

no preventative action can be taken.”

Crucial Genetics also provides markers for genealogical studies and confirming

paternal lineage and common ancestry along the male line. The company is creating

an expansive database of DNA profiles that can connect Scottish individuals to their

ancestral clans.


Crucial Genetics

Thousands of children were orphaned after the devastating tsunami that struck Sri

Lanka, Indonesia and Thailand in December 2005. A baby found alive floating in the

ocean — later named Baby 81 — was claimed by over ten distraught women who

had lost infants during the flood. With assistance from Crucial Genetics, the baby was

reunited with its true biological mother.

“We’ve helped put criminals behind bars and, in some cases, have saved people

who were innocent,” says Max Hamilton, business development manager for Crucial

Genetics. “Our paternity work stabilizes the lives of mothers and children by proving

who the natural fathers are, who often then provide support. Ultimately we impact

people’s lives on a daily basis by simply helping them find the truth.”



14

Health Services

Chapter

KineMedOffers KineticView of theBody

KineMed is a drug development company built upon a

new way of seeing the inner workings of the human body

and thus predicting clinical outcomes.

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1) Animals or patients are given a small amount of heavy water or other stable isotope labeled tracer.

2) The heavy water or other label becomes evenly distributed throughout the body pool.3) All biomolecules made while the tracer is present are labeled as "new."

The cell or biomolecule of interest is then isolated from blood, tissue, saliva or urine.4) The new "heavier" molecule can then be measured by ultra-sensitive mass spectrometry

and rates of synthesis or turnover are determined.

K


15 KineMed intends to change the way the world sees health and disease. The

biotechnology company, based in Emeryville, Calif., has developed a technology that

allows researchers to monitor and measure the myriad dynamics taking place at the

cellular and molecular levels in the human body. The unique vantage point offered by

KineMed’s technology enables researchers to understand the full landscape of dynam-

ic pathways of disease and thus predict the onset and monitor the course of

an illness. These tools also enable researchers to discover new uses for drugs and

expedite the drug development process.

David Fineman, co-founder of KineMed, explains: “To understand biological

systems, you have to understand the dynamics of those systems. You have to

understand the functional relationships that drive important clinical outcomes.

KineMed enables seeing the multiplicity of drug effects in the biochemical and

physiological pathways in the body.”

Measuring exactly what drugs do in living systems leads to a more comprehensive

understanding of a drug as it acts within the complexity of a human being.

Most importantly, the KineMed technology accomplishes this with no effect on the

system itself.

“It’s like having a ghost observer in the body – something that can observe every-

thing that’s taking place but have no impact on the process,” says Fineman.

Using non-radioactive, or stable, isotopic labeling, a scientist can measure the rates

of flux, or change, as the label is incorporated into molecules in the body.

“The label is a biochemical tag,” says Marc Hellerstein, M.D., Ph.D., the inventor of

the technology. “It is an atom that is part of one molecule, and is transferred to

another molecule when some biochemical event occurs.”

The tag provides researchers with a record of that event.

One way that KineMed achieves this is by administering to a patient a small dose of

deuterium in a glass of water. Deuterium, a “heavy” form of hydrogen, is naturally

occurring in nature and harmless at low levels. Deuterium has an extra neutron in the

nucleus that does not change its chemical behavior in the body, but allows its fate to

be monitored. The additional weight of the neutron makes it distinguishable by mass

University ofCalifornia, Berkeley

KineMed

spectrometry, providing scientists with a way to “light up” pathways so they can see

exactly what effects their drug is having on target cells, where the drug acted, and

what the consequences are within the whole body system.

“For drug discovery, this is a ‘systems biology’ approach, which provides authentic

biomarkers of the actual processes involved in disease or health,” says Fineman.

Hellerstein, who is a professor of nutrition at the University of California, Berkeley,

professor of medicine at University of California, San Francisco, and a physician

specializing in diabetes treatment at San Francisco General Hospital, had long been

interested in metabolism. He also has a lifelong interest in translational medicine,

which, loosely defined, is the process of bringing new tests and therapies out of the

laboratory and into the clinic.

Hellerstein was struck by the differences he encountered between standard medical

care and biological laboratory research.

“I couldn’t understand why we were not measuring the same cellular and molecular

processes in a human being that we could do routinely with cells in the lab,” he says.

Hellerstein’s uncle, a cardiologist in Cleveland, had told his nephew the story of a

researcher who had catheterized his own heart and injected himself with dye — and

discovered that he could visualize the entire circulatory system of the heart. Today

that’s known as angiography. For years, the discovery was only used as a laboratory

research tool, until its value for diagnosing coronary heart disease was recognized.

“A mindset exists that prevents us from translating research tools to the clinic,”

Hellerstein says. “But I was convinced that the type of tools I had been working on

to answer questions in human metabolism could be used in medical diagnostics and

drug discovery.”

Hellerstein patented his first invention through University of California, Berkeley.

The first patent was on a method for non-invasively measuring the synthesis of

polymers, such as proteins, cholesterol and glycogen, in the body. Prior to the

invention, these measurements had some fundamental limitations.

“We could give a label to a person, but how could we figure out how much of the

label really made it into the cells?” he explains. “You never knew how much label

got into the biosynthetic machinery that generated a polymer, because it was

non-accessible.”


15

Medical


15He solved the problem by developing a combined mathematical and mass spectro-

metric approach to calculate definitively how much of the label was being delivered

into the cells.

While his research was largely funded by National Institutes of Health (NIH) grants

at the time of his discovery, the research into kinetic measurements was “sort of

between the cracks,” while he was involved in AIDS research.

Today, there are more than 100 patents in the portfolio, the core technology having

been licensed to KineMed. Hellerstein and Fineman, who are longtime friends,

co-founded the company. The technology works by measuring the flow of molecules

through pathways, like a motion picture capturing the dynamics of a good billiards

break.

“It’s like being able to see the entire table, and watch all the balls go in different

directions, seeing where they hit each other and what path they travel across the

table, all at the same time,” says Fineman.

“The molecules in the body don’t just sit there,” says Hellerstein, “yet most

diagnostic tests today are static measurements. You can see an X-ray or CT-scan of a

structure, or measure the level of messenger RNA in a cell, but these types of

measurements do not show movement, and in truth, everything is dynamic.

So it was clear that there was a huge gap in the tool kit.”

Applying new strategies for tagging key processes in the body with non-radioactive

tracers, combined with new mass spectrometric and mathematical analyses of these

dynamic processes, enabled Hellerstein to see the kinetics of various biological

pathways and processes. He characterizes most diseases as disorders of kinetics and

the control of kinetics.

“Cancer is related to the production rate of cancer cells,” he says. “Liver cirrhosis is

about the production and breakdown rates of collagen; AIDS is about the production

and death rates of T-cells. Biochemistry is regulated through rate control,” that is,

kinetics.

KineMed is now investigating the dynamic basis of various diseases by isolating

specific molecules and looking at them through a kinetic lens. The company has

hired dozens of researchers with various specialties to develop its own drugs and

University ofCalifornia, Berkeley

KineMed

has relationships with more than 20 drug companies that are using KineMed’s plat-

form in combination with other methods of drug discovery and testing.

“Kinetic medicine adds a new dimension in biology by including the measurement

of time, the element that’s been missing in the area of drug development and molecu-

lar biology,” says Hellerstein.

KineMed is already making a difference in research, having developed assays for

several major disease states, including cholesterol metabolism, insulin resistance, neu-

ronal dysfunction, fibrosis and inflammation. That’s powerful technology that can lead

to more powerful medicine.

— By Jill Ladwig


15

Medical

Chapter

SyntermedSoftwareAdvancesNuclearMedicine Witha Toolbox

Breakthroughs by researchers, led by

Professor Ernest Garcia of Emory University,

help physicians interpret images and

improve patients’ lives.

95THE BETTER WORLD REPORT PART ONE

16

The screen above demonstrates the Emory Cardiac Toolbox™ display screen. This screen is automaticaly generated and presented to the physician for interpretation.

B


16 But for a massive layoff of astrophysicists at NASA in 1971, Ernie Garcia and the

company he founded, Syntermed, might never have become leaders in the field of

nuclear medicine.

That’s because Garcia, a native of Cuba who was then in graduate school at the

University of Miami, had his heart set on modeling galaxies. With the cutbacks at

NASA, Garcia was forced to shift gears.

“All of the sudden, it seemed like half the astrophysicists in the world were

unemployed,” recalls Garcia. He is now a professor in the radiology department at the

Emory University School of Medicine in Atlanta and a former president of the

American Society of Nuclear Cardiology.

Garcia is also the originator of what has come to be known as the Emory Cardiac

Toolbox™, which is part of an extensive set of software tools created over the past

20 years by a team of clinicians and scientists he heads at Emory.

Much of this technology was developed in collaboration with other institutions,

especially the Georgia Institute of Technology, with which Emory shares one of the

nation’s top-ranked biomedical engineering programs. Research funding for the

technology that led to the Emory Cardiac Toolbox and the company Syntermed

came from several sources, including the health care industry and the Georgia

Research Alliance.

When Garcia was in graduate school, he fortuitously received software

development training from Florida Power & Light.

“Computers and software were very different back then,” he says. “I was very

lucky that they taught me something that the scientific community was not trained in

at that time.”

“It turned out to be more fulfilling work than predicting what galaxies would do,”

he notes. “In medicine, you get to know your results a lot faster — and save lives.”

So Garcia earned his Ph.D. in physics with a focus on nuclear medicine. Luckily for

him, the University of Miami had one of the best programs anywhere, he recalls.

“There were a lot of top scientists there, but I was the only one with software

expertise, so I got to do a lot, even as a graduate student,” he says.

Emory UniversityandGeorgia Instituteof Technology

Syntermed

Garcia quickly grasped the power of meshing computers with clinical applications.

“That’s how the whole thing got started,” he muses.

Now, when physicians look at multicolored, rotating and pulsing hearts on comput-

er screens, the chances are good many of them are using software created by Garcia

and his team.

To date, Syntermed has issued more than 10,000 licenses to doctors, clinics and

hospitals around the globe. The company’s software is used in nearly 40 percent of all

nuclear imaging labs in the United States.

Syntermed’s Beginnings: Fulfilling a Need

When the first heart images appeared in the early 1970s, they showed previously

invisible anomalies. But without good software, they were difficult to interpret. That’s

where Garcia stepped in. His first efforts focused on measuring hypoperfusion, or lack

of blood flow to the heart.

Though it may seem hard to imagine, Garcia and other scientists gave away their

early software. “It went into ‘users’ libraries,’ and yes, it was free,” he says.

In the early 1980s, after he had begun working at the Cedars-Sinai Medical Center

in Los Angeles, Garcia says he found himself spending too much of his time answer-

ing questions about the software.

“It was very evident to me that this was actually hurting the field,” he says. “I was

supporting the programs that I was giving away. I realized that if people would pay

for it, we could do a much better job.”

Not long after that epiphany, a nuclear pharmaceutical company contacted Garcia

and his colleagues to help create a user-friendly software program that would both

quantify and interpret the results of heart muscle perfusion studies for the average cli-

nician.

The company — New England Medical — made a low-dose radioactive agent that

made the flow of blood through the vessels and heart visible in the digital images.

“Because they funded it, they wanted the rights to the program,” Garcia says.

“That led to a lot of legal discussions, but ultimately we worked out a compromise.”

The deal permitted the researchers to keep ownership of the intellectual property

while allowing the drug company exclusive use of the software for the first year, in


16

Medical


15recognition of the funding it had provided. After that year was over, Garcia and

Cedars-Sinai were allowed to add and license additional software applications that

would benefit products from other companies.

A Continuing Success Story

When Garcia moved to Emory in 1985, he continued to collaborate with former

colleagues at Cedars-Sinai and began to do work with researchers at Georgia Tech.

For a decade or so, Emory was content to license the growing catalog of software to

drug and medical device companies, which included GE, Siemens, Philips, Toshiba and

others.

Things had become a bit more complicated in the late 1980s, however, when the

U.S. Food and Drug Administration (FDA) began regulating medical software as a

medical device. To meet FDA’s strict guidelines and requirements, Emory became a

medical device company, a status it kept until Syntermed was spun off in 1999.

Mary Severson, the chief technology officer in the Office of Technology Transfer at

Emory, says licensing the Emory Cardiac Toolbox™, including transferring the 501(k)

registration and existing original equipment manufacturer (OEM) licenses to

Syntermed, relieved the university of liability exposure.

“It also meant we didn’t have to meet FDA requirements as a medical device

maker,” she says. “It made sense because universities are not set up to be companies.

In addition, starting Syntermed provided a position from which the technology could

expand.”

Because the technology was a proven money maker, Syntermed hit the ground run-

ning and required no outside financing.

Emory and Georgia Tech remain shareholders in the privately held firm, at which

Garcia serves as the chief scientific advisor. Garcia recruited Michael Lee, a serial

entrepreneur and former manager of intellectual property and marketing at Georgia

Tech, to be the company’s CEO.

“I give Garcia and Severson a great deal of credit,” says Lee. “They took a chance

with Syntermed, but they saw the benefits of moving the IP out of Emory and into a

for-profit environment. They worked as true partners and allowed us to maintain a

portion of the licensing fee to cover our operating expenses. That is what we used to

Emory UniversityandGeorgia Instituteof Technology

Syntermed

start the company. Other than that, we pretty much boot-strapped it.”

Since its incorporation in 1999, the company has continued to grow and innovate.

Recent Syntermed innovations allow physicians to review, interpret, and generate a

report for their patients’ myocardial perfusion studies using an Intranet or an Internet

connection.

In addition, Syntermed Inc.’s research and products have moved beyond the heart.

NeuroQ™, developed by Dr. Daniel Silverman at University of California, Los Angeles,

is a powerful tool to assist in the interpretation of positron emission tomography

scans — imaging scans that measure brain activity.

Garcia says the name Syntermed was chosen because it stands for “Synergistic

Internet Medicine.”

“Part of our idea is to sell software services and to provide them through the

Internet,” he says. One of those services, called Syntermed Life, was recently intro-

duced at an American Society of Nuclear Cardiology conference.

Garcia says the pieces are “falling together” to allow clinical laboratories to use the

software and computer services they need on a pay-per-use or monthly-fee basis

directly from the Internet.

New modes of delivery, he predicts, will lead to additional improvements from his

and other labs, and ultimately, better patient care.



16

Medical

Chapter

TomoTherapy’sRevolutionaryCancerTreatmentZeroes in onTumors withPrecision

Helical TomoTherapy® brand radiotherapy,

combined with built-in computerized tomography

imaging, targets only the cancerous mass,

sparing surrounding tissue and

nearby organs from damaging radiation.

101

17


A therapist prepares a patient for radiation treatment on the TomoTherapy® Hi-Art System®.

U


17 University of Wisconsin-Madison professors Thomas Mackie and Paul Reckwerdt

wanted to solve a big problem in cancer treatment therapy — the serious damage to

normal tissues and organs created by standard radiation therapy. They were intrigued

with the idea of building a machine that could deliver a tightly controlled pattern of

radiation that preferentially strikes cancer tumors, sparing the surrounding tissue

from harm.

That was just a thought in the early 1990s. Today, TomoTherapy Inc.’s Hi-Art ®

System is the most advanced radiation therapy device in the world. Physicians in more

than a dozen countries use this remarkable technology to customize a treatment plan

that delivers a precisely configured field of radiation to the tumor that is essentially

the same shape and volume as the tumor itself. With annual revenues of about $130

million, and a workforce of 500 with 300 more jobs on the way, it’s safe to say

TomoTherapy Inc., headquartered in Madison, Wis., is a success.

The breakthrough that Reckwerdt and Mackie discovered is called helical

TomoTherapy-brand radiotherapy, which creates a helical pattern of radiation around

the patient. This allows rotating beamlets of radiation to be directed into the patient’s

body from any angle, a far better approach than the two or three angles of penetra-

tion that traditional radiation therapy has provided.

The second key part of the Hi-Art System is a built-in computerized tomography

(CT) scanner. For helical TomoTherapy-brand radiotherapy to be effective, it must be

guided with utmost accuracy.

“The CT imaging allows physicians to exactly locate the patient’s tumor, see if the

shape has changed, and place the patient in perfect position for each session of

radiation,” says Mackie, an M.D. and UW-Madison professor of medical physics and

human oncology, as well as chairman of the board at TomoTherapy Inc.

The initial R&D was undertaken at the University of Wisconsin with a $250,000

federal grant from the National Cancer Institute. The Technology Transfer Office at

the Wisconsin Alumni Research Foundation (WARF) filed its first patent applications

on the technology in 1992. WARF also contributed more than $1 million to help fund

continuing research. TomoTherapy Inc. was established in 1997 and five years later its

University ofWisconsin-Madison

TomoTherapy Inc.

Hi-Art System prototype was approved by the U.S. Food and Drug Administration.

Today more than 100 Hi-Art Systems are in operation around the world. Currently the

company holds 70 patents, with at least a dozen others pending.

“Moving to this unique platform is a quantum leap for radiation therapy,” says

Richard Hudes, M.D., and chief of the division of radiation oncology at St. Agnes

Cancer Center in Baltimore, Md. “Referring doctors need to know that TomoTherapy

provides a significantly improved radiation delivery method of unparalleled accuracy.”

A Precise Weapon Against Cancer

Doctors use the CT scanner to map the contours of the tumor, as well as define

areas of risk (such as organs) that need to be protected from the radiation. The CT

data is logged into the Hi-Art System, which calculates the parameters of the radiation

and where it will be focused inside the patient’s body. Because cancer tumors can

change shape and location on almost a daily basis, regular CT scanning is a great way

to fine-tune the treatment for maximum effectiveness.

Because the radiation beam can be configured so exactly, it is the ideal treatment

for patients with “untreatable” cancers.

“One of our patients had a tumor growing around the orbital area of his eye,”

says John Koenig, director of Froedtert Hospital’s Radiation Oncology Center in

Milwaukee, Wis., which began using the machine in 2004. “Standard radiation

treatment would have caused the patient to lose sight in that eye, but we were able

to treat the cancer successfully with TomoTherapy equipment. Tumors on the spine

are also difficult treatment areas, but the Hi-Art System can design a plan where the

field of radiation actually wraps around the spinal column to deliver radiation to the

tumors, without damaging the spinal cord.”

After being scanned, the patient is placed on a table within a tunnel-like device

called a gantry ring. Photon radiation in the ring travels in multiple circles around

patient, through the gantry ring. The table is moved slowly through the gantry ring as

it rotates. Each time the radiation comes full circle, it penetrates the tumor along a

slightly different plane. The shape of the radiation beam changes with each slice of

treatment, according to the shape of the tumor in that plane. Treatment proceeds for

about 15 to 20 minutes until the entire tumor has been radiated.


17

Medical


17Not only does the Hi-Art System treat patients who were not treatable before, it

can also safely deliver second courses of radiation therapy.

“If a patient’s tumor returns after radiotherapy, it is usually not possible to retreat

the same area with conventional radiation treatment because the normal tissues have

reached their toleration level,” says Koenig. “But TomoTherapy equipment delivers

such a finely tuned dose that even previously irradiated areas can be treated, giving

new hope to patients with recurrent disease.”

Moving Ahead

TomoTherapy Inc.’s 80 percent growth rate shows how quickly the health care

industry has taken notice of its Hi-Art System. Not only have the medical outcomes

been eye-opening, but the price tag of $3.5 million is actually very competitive with

the less-functional systems that most hospitals use. And there’s still plenty of room to

grow — TomoTherapy Inc. has only 10 percent of the radiation therapy market.

The company isn’t resting on its laurels — 20 percent of its revenues are reinvested

in research and development. Because of its rapid growth, TomoTherapy Inc. recently

opened a new operations center in Madison. The $8.2 million, 66,000-square-foot

facility will allow the company to quadruple its current testing and production capacity.

“We use TomoTherapy equipment for almost all our patients,” says Koenig.

“Patients know they are getting a more precise treatment that lessens the side effects

of radiation. Their quality of life during treatment is much higher, with less nausea,

diarrhea, fatigue or hair loss. If TomoTherapy equipment is used in the first course of

treatment, it can reduce or eliminate the need for surgery or chemotherapy, which

means lower health care costs.”

“Any time we can avoid a complication, we avoid extra cost to the health care

system,” adds Mackie. “Our technology may lower the cost of drug care

tremendously, which is the most costly part of cancer therapy. For a typical cancer

center, the yearly cost of drugs alone would pay for all its radiation equipment.”

“Cancer rates are increasing around the world,” says Mackie. “Cancer is a

frightening disease and standard treatment can be painful and debilitating.

TomoTherapy has a better way to treat most cancers and our mission is to bring

this technology to the global market.”


University ofWisconsin-Madison

TomoTherapy Inc.

Chapter

GroundbreakingCell-BindingTechnologyHelps PatientsGrow New Bone

CeraPedics, LLC, a Lakewood, Colo.,

company is developing and commercializing

bone graft products based on milestone

technology developed at the

University of California, San Francisco.

105

18


The mixing process takes place using specially designed equipment within an ISO Class 8 clean room.

I


18 It’s been the dream of medical researchers for decades: to step beyond

Mother Nature’s limitations and grow new bone.

Now, the prospect of growing new bone at the site of spine fusions, trauma and

joint reconstruction has become a reality. CeraPedics, based in Lakewood, Colo., is

developing and commercializing products that are expected to treat a large and

growing segment of the population requiring bone replacement surgery.

The Holy Grail in bone grafting has long been autogenous bone — one’s own

bone. Now through the development of a bone-growing technology called P-15,

CeraPedics’ bone growth products can imitate autogenous bone. This is proving to be

a safe and effective alternative to the current method of performing surgeries involving

the removal of bone from a hip to repair or replace bone lost to disease or trauma.

P-15 originally was developed by Professor Emeritus Rajendra Bhatnagar at the

University of California, San Francisco (UCSF), whose research was funded by grants

from the National Institutes of Health.

Andrew Tofe, Ph.D., a nuclear scientist, licensed the technology from UCSF in 2001,

and founded CeraPedics. Interestingly, the proving ground for CeraPedics was in the

dental market. Tofe’s former company, CeraMed Dental, used the technology to

develop P-15 dental products which helped fill in defects in the bone of the oral

cavity. CeraMed Dental was sold to DENTSPLY International Inc. in 2001. According

to Tofe, CeraPedics was founded on a simple concept.

“We had success growing bone in the oral cavity, which is a cesspool of bacteria

and other contaminants,” he explains. “Imagine what you can do in orthopedics,

where you have a mostly cellular, sterile environment.”

Championing the Future

Transforming human cells into new tissues such as bone more than 40 years of

research by Bhatnagar who led UCSF’s bioengineering group. The breakthrough, first

commercialized in 1999, was extraordinary for another reason. Bhatnagar’s discovery

focused on using fibroblasts found in the central layers of human skin to transform

the cells into bone.

The creative spirit at UCSF was alive and well when Bhatnagar reasoned that since

University ofCalifornia, San Francisco

CeraPedics, LLC

skin is the largest organ of the human body, and therefore easily accessible, it would

be possible to take fibroblasts from living skin and gum cells to grow bone cells for

filling in space between broken bones. His discovery led to the development of tech-

nology such as P-15, which facilitates the successful promotion of new bone growth.

“Dr. Bhatnagar’s discovery was phenomenal,” says Don Freeman, CeraPedics’

director of clinical research and marketing.

While bone grafts aren’t new, P-15 is changing the way bone substitutes are being used.

“The beauty of P-15,” says Freeman, “is that it accelerates the body’s natural

rejuvenation process, and at the same time, the technology is safe, cost-effective,

and less painful for patients.”

While autogenous bone or bone taken from another region in your body is

considered the “gold standard” of bone grafts, Freeman says, “It involves a second

surgical procedure, usually from the hip, and usually involves a significant amount of

postoperative pain as well as the increased cost of operating room and surgeon’s

time to harvest the graft.”

The small peptide combined with the calcium phosphate uses a “cell

attachment mechanism” that makes human bone cells grow new bone cells.

“Peptide is defined as a chain of amino acids — building blocks of

protein,” says Freeman. “In the case of P-15, it is a peptide that is

15 amino acids in length, which is a relatively small peptide.”

In describing the role of calcium phosphate, Freeman points out this is the

inorganic or mineral portion of the bone which provides the hard

structure needed to support the body.

The organic part of bone is mainly type 1 collagen, a primary protein of

connective tissue, which the bone cells attach to, beginning the process of

bone formation.

“Think of a key fitting in a lock,” Freeman explains. “When a bone cell attaches to

the calcium phosphate matrix via P-15, it changes the environment. This ‘attachment’

factor then starts the process of new bone formation in the body.”

The P-15 technology offers an affordable alternative to current growth factor tech-

nology and is expected to be kept within typical insurance reimbursement coverage.

“P-15 is a synthetic peptide, which means it can be produced at a significantly


18

Medical

Pre-filled syringe of P-15 Bone Graft Substitute is carefully placed in a pouch prior to sterilization and final packaging.


18lower cost than other technologies such as growth factors,” explains Tofe.

A Growing Need for Bone Graft Products

The market for bone graft substitutes is moving forward at record speed. In 2005,

“U.S. Markets for Spinal Fusion Products,” published by Windhover

Information/Medtech Insight reported that the U.S. market for such bone growth fac-

tors was expected to grow from $303 million in 2005 to $1.4 billion in 2009. The rea-

sons are many, including an aging baby boomer population and the body’s natural

deterioration of the muscular and skeletal system, as well as the increased cost of new

bone growth factor technologies.

One of the fastest growing segments of this market is in spinal fusion procedures,

where bone graft substitutes such as P-15 are used. The number of procedures in

spinal surgery is expected to grow from approximately 581,000 in 2004 to about

763,000 in 2009. CeraPedics anticipates having a large share of this growing market

with a product that will be more affordable than current growth factor products.

The company began clinical trials in spinal fusion surgery in the second half of 2006.

Reports from the Field

Michael Janssen, D.O., orthopedic spine surgeon and chairman of the Spine

Education and Research Institute, a medical educational and research facility in

Thornton, Colo., says, “Because of the attachment factor of P-15, which positively

changes the environment, we anticipate that it will have enormous impact in advanc-

ing surgical techniques and patient outcomes.”

Janssen, also is the principal investigator in the current U.S. Food and Drug

Administration investigational studies of P-15.

“We’re very excited about the possibilities it offers toward promoting the health

and welfare of patients,” he says.

When Professor Bhatnagar successfully developed the technology that facilitates the

formation of new bone, he expressed hope that someday the research would help

people with degenerative diseases and injuries.

That time has come. CeraPedics’ bone graft products not only are expected to help

millions of people with ongoing pain, they are also positioned to alleviate the cost and

inconvenience of numerous surgeries.

— By Sharyn Alden

University ofCalifornia, San Francisco

CeraPedics, LLC

Chapter

ConcentricMedical, Inc.:Saving StrokeVictims

Due to a pair of physicians’ innovation and determination,

the removal of potentially fatal blood clots in the brain

may one day become standard procedure in hospitals

around the world. Concentric Medical, Inc., is doing its

part to make the Merci® Retriever more effective and more

available to stroke victims with no time to spare.

109

19


Merci® Retriever is designed to restore blood flow in ischemic stroke patients by retrieving and removing clots. Im

age

cour

tesy

of

Con

cent

ric

Med

ical

E


19 Eighteen-year-old Melissa Welch of California serves as a poster child for the

medical intervention that saved her life two years ago. Twenty-year-old Marissa

Arnold of Connecticut made national television last year because of the dramatic

result achieved by the same clinical device. These young women are just two

examples of the thousands who can count themselves lucky.

The enemy in these situations is stroke. The savior is Concentric Medical, Inc.’s

Merci® Retriever.

The rate of strokes is rising, and according to the American Stroke Association,

it is the leading cause of serious, long-term disability in the United States. Stroke is the

third largest cause of death, ranking behind heart disease and all forms of cancer,

but it is quickly gaining ground as the number two killer.

Close to 80 percent of the 750,000 strokes that occur each year nationwide are

ischemic strokes — that is, caused by the blockage of a blood vessel, usually by a clot

that forms elsewhere then travels to and lodges in a blood vessel in the brain.

It would seem that the clot-busting drug, tissue plasminogen activator (t-PA), can

occasionally work miracles. However, it is effective only if administered within a critical

three-hour window of time following the onset of a stroke. Also controversial is

t-PA’s increased risk of a brain hemorrhage.

While a frustrating situation for clinicians who treat ischemic stroke patients,

it inspired a dedicated pair of neuroradiologists to invent a tool that offers patients a

greater shot at recovery. Just over 10 years ago, University of California, Los Angeles

(UCLA) physicians Pierre Gobin, M.D., and J.P. Wensel, M.D., began designing a

device that could travel to the site of a blood clot in the brain and actually remove

the clot.

Great strides in this concept had already been achieved with coronary arteries.

But there are dramatic differences between the heart and the brain, as Gobin attests.

“A blocked coronary artery is caused by plaques that form there and narrow the

vessel,” he explains. “In the brain it’s completely different where in most cases the

blockage forms from a clot that travels there from somewhere else in the body. Our

idea was that if a clot arrives and lodges in a brain vessel, it could be extracted.”

University ofCalifornia, Los Angeles

ConcentricMedical, Inc.

Melissa Welch was 16 when she had a stroke and was airlifted to a centerwhere they utilized the Merci® RetrievalSystem to remove a blocked artery in herbrain. She is now functionally normal. Images courtesy of Concentric Medical

An Idea Becomes Reality

From concept to successful product, today the Merci Retrieval System is comprised

of three key components. After a blood clot in the brain is located by angiography, a

clinician inserts the Merci balloon guide catheter through a small incision in the

patient’s groin. Under X-ray guidance, the catheter is then maneuvered up to the

carotid artery in the patient’s neck, and a guidewire, along with the Merci micro-

catheter, are deployed through the catheter and into the brain where they are placed

just beyond the clot. The third component, the Merci Retriever — a corkscrew-shaped

platinum wire — is then deployed to grab and ensnare the clot. After capturing the

clot, the clinician inflates the balloon guide catheter to temporarily stop the forward

flow of blood while the clot is withdrawn and gently pulled into the catheter and out

of the body. Once the balloon is deflated, blood flow is restored through the now

open vessel.

The development of the Merci Retrieval System relied on critical support from the

UCLA Office of Intellectual Property where Drs. Gobin and Wensel filed a patent on

their invention. UCLA invested in the domestic rights and Dr. Gobin, believing

strongly enough in the device to share the financial risk inherent in patenting such

early stage technology, took over the foreign rights. While searching for the right

partners to create a spin-off company, Dr. Gobin remained committed to his mission

and succeeded in finding interested investors and obtaining venture capital. In 1999

he launched the company Concentric Medical.

“This was a good example whereby the inventor’s dedication and persistence on

the commercial front paid off,” says UCLA Office of Intellectual Property’s Director of

Licensing Emily Loughran. “While we maintain an active network of potential industry

licensees there is no substitute for having a motivated and involved inventor teaming

with our efforts. Inventors are often the best source of industry contacts and are the

most appropriate individuals to serve as the catalyst for the formation of a startup

around the technology, as was the case here.”

Concentric Medical spent its infancy in a San Francisco Bay Area incubator called

the Foundry. According to Gobin, the Foundry was an excellent place to start a com-

pany, as it provided engineering expertise and funding. As the company gained finan-


19

Medical


19cial support, the design of the Merci Retriever continued to improve. A preliminary

safety trial of the device was underway within a few years, and the results paved the

way for the launch of a pivotal clinical trial.

A veteran business mind with expertise in developing new medical device compa-

nies, Gary Curtis came on board as president and CEO of Concentric Medical in 2002.

At this critical time the company needed additional venture capital to fund a clinical

trial and move forward with commercialization of the Merci Retriever. With more than

35 years of experience in the startup medical device arena, Curtis has played a valu-

able role in the commercialization of numerous major medical tools including total hip

replacement and interventional cardiovascular devices.

FDA Approval Spurs Concentric’s Momentum

Now headquartered in Mountain View, Calif., Concentric Medical is still privately

held and benefits from an impressive number of major investors, including New

Enterprise Associates, ProQuest Investments, Oxford Bioscience Partners, and

Schroder Ventures Life Sciences. Curtis says the company has achieved a revenue rate

of approximately $1 million a month; he expects to be doubling that and approaching

profitability by the end of this year. “We focused on the U.S. marketplace for my first

four years, and we’re just starting to explore international markets and opportunities,”

he says. “We have many hopes and expectations.”

The 65 employees of Concentric Medical feel fortunate to be part of a company

that is truly saving lives. A major milestone occurred in 2004 when the Merci Retrieval

System was cleared by the U.S. Food and Drug Administration, making it the first ever

FDA-approved medical device for removing blood clots from the brains of ischemic

stroke patients.

“With the approval of our product and the development of such interventions, we

now help about 250 patients per month,” says Curtis. “It’s a very rewarding way to

come to work each day.”

Since the approval of the Merci Retrieval System, there are now close to 250 hospi-

tals in North America that have the product on their shelves, as well as trained clini-

cians able to use it for treating patients. Curtis estimates that since the device has

been available, it has treated about 4,000 patients through clinical trials and interven-

University ofCalifornia, Los Angeles

ConcentricMedical, Inc.

tions. Studies of the Merci Retriever have shown that if blood flow is restored to

stroke victims within an eight-hour window of time, then half those patients will

regain functional independence within 90 days. Without the means of such an inter-

vention, only one out of 32 people suffering a stroke achieve that independence.

“We really consider Concentric Medical to be one of our big success stories,” says

Loughran. “For very early stage technologies such as the Merci Retriever, the number

of products that not only make it through FDA approval but are then actually widely

used are few. We’re excited to see this become one that is so valuable for the man-

agement and treatment of stroke.”

Thankful Patients

Unlike the majority of stroke victims who either die or suffer permanent disability,

Melissa Welch and Marissa Arnold were fortunate to enjoy a full recovery. Welch was

home from the hospital a week after her stroke just in time to spend Christmas with

her family. Arnold was back to her full course load and playing varsity soccer as a jun-

ior at Mt. Holyoke College in South Hadley, Mass., just two weeks after her frighten-

ing episode. The design, development and commercialization of the Merci Retriever

serves as a stellar example of how successful technology transfer to the marketplace is

making our world a better place.



19

Medical

Chapter

AtheroGenicsDevises NewTreatment forHeart Patients

AtheroGenics is a small pharmaceutical company

that is changing the way doctors treat heart disease —

the leading cause of death in the United States.

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20


H


20 Heart disease is the number one killer of people in the United States. But one

company, AtheroGenics, offers promising results in the war on heart disease.

Atherosclerosis, the dangerous buildup of plaque in the arteries that often leads to

coronary artery disease, affects nearly 14 million Americans. AtheroGenics was

founded in Atlanta in 1993 to advance research that would shed light on the

process of atherosclerosis. The drugs commonly used at the time did not treat

inflammation, one of the deadliest aspects of the disease, but one that escaped most

researchers’ attention.

According to the American Heart Association, new research suggests that

“inflammation in the circulating blood may play an important role in triggering heart

attacks and strokes.” The American Heart Association adds that inflammation is the

body’s natural response to injury, and blood clotting is frequently a part of that

response. Further, blood clots may slow or even stop blood flow. But the relationship

between inflammation and these other diseases was not always evident.

“We were the first to see these as inflammatory diseases,” says inventor Russell

Medford, M.D., Ph.D., who is now the chief executive of AtheroGenics.

Medford explains that heart disease is caused by an increase in white blood cells in

the coronary artery, which causes the main circulation route for blood traveling to the

heart to become chronically inflamed. When he began his research into the area,

Medford’s hypothesis was that inflammation is a major common pathway to risk

factors associated with heart disease.

In 1993, Medford and his colleague at Emory University, R. Wayne Alexander, M.D.,

Ph.D., working with a grant from the Georgia Research Alliance, discovered a mecha-

nism inside the blood vessel walls of the arteries that could control the excess accumu-

lation of white blood cells, without affecting the body’s ability to fight off infection.

They figured out that endothelial cells, the cells that line the wall of the blood vessels,

are responsible for recruiting white blood cells to the site of inflammation.

Medford and Alexander developed a tool called a vascular protectant, or

V-Protectant® technology, to block the endothelial cells’ signals from reaching the

white blood cells. The endothelial cells’ signals are called oxidant signals, and they

activate genes that produce a protein that attracts the white blood cells. Their first

Emory University

AtheroGenics

patents from Emory University were on the mechanism and pathways for chronic

inflammation. Medford and Alexander realized that an excess of these proteins consti-

tutes a disease state, and that this state might look similar in patients suffering from

other chronic inflammatory diseases, such as rheumatoid arthritis and asthma. Millions

of people who suffered from these diseases were receiving only partial treatment with

commonly prescribed drugs.

A molecular cardiologist, Medford has spent his career developing small molecules

as candidates to interrupt the pathways that lead to inflammation. Many of the drugs

administered for heart disease, for example, are targeted at a known symptom, such

as low-density lipoprotein (LDL), also known as “bad” cholesterol. But Medford says

that LDL is only one of several factors that induce inflammation. The two scientist-

physicians formed AtheroGenics to develop small molecules that could serve as

candidates to intervene in those critical pathways that lead to chronic inflammation.

“While there have been great advances in treating heart disease, even with the best

treatment available, today’s heart disease drugs only reduce the risk by about 30 per-

cent,” Medford says. “AtheroGenics sought to find a drug that would go above and

beyond the 30 percent success rate. He says adding the AtheroGenics’ anti-inflamma-

tory drug candidate to the standard regimen for atherosclerosis may increase the suc-

cess rate in treating the disease.

Medford successfully proved the concept at the molecular level and is now seeking

to prove efficacy and safety in humans. AtheroGenics is currently finishing a Phase III

clinical trial for the drug compound called AGI-1067 to treat atherosclerosis. The study

included 6,000 patients in four countries, all of whom have heart disease. According

to Medford, all 6,000 received the most aggressive drug therapy, which will include

LDL-lowering drugs called statins. Half of the patients are also getting the

AtheroGenics compound; half are receiving a placebo.

“I’m anxious to see if we can reduce the probability of patients having subsequent

stroke or surgery or death — what we call major adverse cardiac events,” Medford says.

The company expects the results in early 2007. If all goes well, they will then file a

New Drug Application with the U.S. Food and Drug Administration.

“We built a company that is capable of taking drugs from discovery through clinical

testing,” says Medford.


20

Pharmaceuticals


20This is not an easy feat for fledgling companies, when it costs as much as $800

million and ten years to get a new drug to market, by some estimates.

AtheroGenics began partnering with pharmaceutical company AstraZeneca in 2005

to co-promote its products and, in 2006, received an award from Scrip World

Pharmaceutical News, the global news publication for the pharmaceutical and

biotechnology industries, for the Best Alliance of the Year. The company went public

in 2000 and has raised more than $450 million to date, according to Medford.

Part of the company’s long-term business strategy, according to its Web site, is to

extend the V-Protectant® platform to create new therapies to address unmet medical

needs, such as chronic organ transplant rejection, rheumatoid arthritis, asthma and

other diseases. It also plans to collaborate with large pharmaceutical companies to

commercialize its products.

If AGI-1067 proves successful, AtheroGenics also plans for a sales force of more

than 100 in the United States, which Medford hopes will allow the company to begin

to penetrate the commercial drug infrastructure in this country. He says the deal with

AstraZeneca ensures worldwide market coverage to make the broadest possible

impact: something a small company simply cannot achieve alone.

“It is an excellent feeling, to take an idea we developed at Emory, and translate that

idea into a drug candidate, into a clinical event trial that may change the way we

treat heart disease,” Medford says. “It is a real privilege because it could change how

people are treated, and this is a major cause of death and suffering.”

— By Jill Ladwig

Emory University

AtheroGenics

Chapter

DUSAPharmaceuticalsSheds Light on Cancer

With an initial grant of $8,000 and a long-held interest

in light-based therapies, two researchers in

Kingston, Ontario, develop a uniquely effective method to

treat cancer, licensed by DUSA Pharmaceuticals.

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O


21 On a shoestring budget and little else but a burning curiosity about light-based

medicine, Jim Kennedy developed a simple and effective cure for actinic keratoses

(AKs), the most common precursor of skin cancer. As researchers at Queen’s

University and the Royal Military College of Canada, both located in Kingston,

Ontario, Kennedy and colleague Roy Pottier invented an unusually effective method

for treating AKs and other skin cancers by combining two completely natural and

harmless products: visible light and aminolevulinic acid (ALA), a small molecule

synthesized by almost every nucleated cell in the human body.

Their research suggested the possibility that the administration of ALA to a cancer

patient, when combined with an appropriate dose of visible light, might destroy at

least certain types of cancerous and precancerous cells. Their hypothesis turned out

to be correct. Subsequent studies showed that ALA could be effective when

administered in an appropriate vehicle by topical application, ingestion or through

intradermal, subcutaneous or intravenous injection.

Kennedy has dedicated his professional life to the treatment of cancer. He began his

academic career studying cancer immunology in the department of pathology at

Queen’s University. But he switched his research focus when he learned about

photodynamic therapy, that is, the use of light, together with a photosensitizing

agent, to treat disease. Also instrumental in his career change was meeting

Dr. Tom Dougherty of Roswell Park Cancer Institute in Buffalo, N.Y.

Dougherty was using photodynamic therapy as a way to destroy tumors in rats.

Kennedy became fascinated by the potential of this new technique for treating cancer.

His new focus required a change in grant-funding agencies and in professional

affiliation, so he could have access to cancer patients.

“It was a risk,” Kennedy says, “at that time, photodynamic therapy was almost

completely unknown to the medical community, and grants for research in such an

obscure field were difficult to obtain.”

Kennedy’s research in the area began with an $8,000 grant from the Ontario

Cancer Treatment and Research Foundation to study photosensitizing compounds,

also known as photosensitizers.

Queen’s Universityand the Royal MilitaryCollege of Canada

DUSAPharmaceuticals

“These are compounds that absorb the energy of light and then transfer it to mole-

cules of oxygen, which in turn become activated in such a way that they tend to react

chemically with adjacent materials,” Kennedy explains.

In the case of cancer treatment, photosensitizers can be combined with light to

destroy cancerous cells. After many years of work, Kennedy and Pottier discovered that

administering large amounts of ALA to patients could induce the accumulation of intra-

cellular protoporphyrin IX (PpIX) in cells — especially in potentially cancerous cells.

PpIX can serve as a sort of marker in malignant or pre-cancerous cells.

Administering ALA causes cells to accumulate higher levels of PpIX, thereby increasing

the ability to detect malignant or pre-malignant cells, if the right equipment is used.

“It turns out that malignant, pre-malignant, and certain other abnormal cells

accumulate significantly more PpIX than do normal cells,” Kennedy explains.

“This allows us to use ALA-photodynamic therapy to kill such cells preferentially —

the normal cells experience only minor damage that is easily repaired, while the

abnormal cells are severely damaged.”

Because ALA is a small molecule, it passes easily through skin, unlike the other

compounds they had tried, which had to be injected. Kennedy immediately tried

ALA to treat tumors in mice, with mixed results. Then Kennedy, the quintessential

scientist, tried it on himself — the skin of his arm, a patch of whiskers, a healing

scratch on his skin.

“I wanted to see if it was like radiation therapy and I would lose my hair or cause

depigmentation or a scar,” he says, but there were no such side effects.

In 1987, Kennedy decided to try topical ALA on a patient he’d been treating who

had cancerous tumors on her forehead, and he activated the process using a slide

projector with a red filter. The experiment worked, and worked well. That success was

followed by another: a man with a number of serious medical problems and large,

painful ulcers of basal cell carcinomas at multiple sites on his skin. Because of his

medical condition, his doctors did not want to operate to remove these cancers and

asked Kennedy to see if his new therapy might get rid of the ulcers. Again, the

treatment helped.

In 1991, Geoff Shulman, a dermatologist and businessman, heard a lecture by

Kennedy about the use of photodynamic therapy to treat skin cancer. He too


21

Pharmaceuticals


21became intrigued and just happened to be in the perfect spot to bring the idea to

commercialization.

A few years earlier, Shulman had helped his father launch a pharmaceutical compa-

ny in Canada. Suffering from Parkinson’s disease, his father, who was also a doctor,

found his most effective treatment was a drug called Deprenyl, which was not

available at that time in Canada or the United States. The younger Shulman helped

his father found a company called Deprenyl to bring that drug to Canada.

“The commercial potential of this light therapy for cancers and precancers appeared

to be very large,” says Shulman, “and the risks appeared to be relatively low, since

Dr. Kennedy had already shown it worked in hundreds of patients.”

Most drugs fail in clinical trials before ever getting to market, according to Shulman;

this one was already curing people. With that kind of clinical success in place,

Shulman knew the odds of getting the drug approved were good. He also knew that

in order to ensure success, they had to get it approved in the United States.

“If it was approved only in Canada, it wouldn’t be worth it,” Shulman says.

So he set up DUSA Pharmaceuticals as a U.S. company. But the road to market

for DUSA turned out to be a much longer journey than the one he’d been on

with Deprenyl.

Kennedy and Pottier began treating patients with the experimental compound in

1987 and published their first paper in 1990. The first patent was issued one year

later, held by Queen’s University. When Shulman learned of it that year, he met with

Kennedy and soon afterwards, Pottier. Deprenyl spun off Deprenyl USA, which later

became DUSA Pharmaceuticals and licensed the invention. It wasn’t until 1999 that

the company won the first approval from the U.S. Food and Drug Administration,

and in 2000, launched Levulan® PDT for the treatment of AKs.

Today, DUSA has 90 employees, including its own 40-person dermatology sales

force, and, after many years in the “development stage,” it is growing. Sales have

jumped from $1 million in 2003, to $11 million in 2005, to a projected $25 million in

2006. The company has used ALA-photodynamic therapy as a platform technology

for applications such as aging skin and acne. In 2004, DUSA also entered into an

agreement with the National Cancer Institute to test Levulan PDT in patients with oral

and esophageal cancer. — By Jill Ladwig

Queen’s Universityand the Royal MilitaryCollege of Canada

DUSAPharmaceuticals

Chapter

RevolutionaryCellTechnologyHelps FightDeadlyDiseases

It was a first for science when research in The Netherlands

led to the development of PER.C6® technology,

which uses human cells to produce vaccines

for combating infectious diseases like the flu, AIDS,

and the West Nile and Ebola viruses.

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Sample analysis. © 2006, Crucell N.V.

I


22 In late 2006, the United Nations and the World Health Organization released a

report stating that AIDS had claimed 2.9 million lives during the year, and that since

1981, more than 25 million people have died of the disease.

AIDS and other life-threatening illnesses are now being targeted by companies who

have licensed the groundbreaking PERC.6® technology, first developed in the early

1990s at Leiden University, in Leiden, The Netherlands. Subsequently, Crucell, the

company founded by the technology’s co-inventor, is now a sizable worldwide player

in developing and producing vaccines.

The combination of scientist, inventor, business leader and company founder is not

common. But those familiar with Domenico (Dinko) Valerio, Ph.D., previously a gene

therapy professor and biomedical scientist at Leiden University, as well as Crucell’s

former president and CEO, know he’s a world apart when it comes to thinking

outside the box.

While the world’s biopharmaceuticals labs were producing vaccines from animal

cells, Valerio was working at Leiden University on a revolutionary technology that

would change the way vaccines are made.

During the 1980s, when it was less common to combine disciplines, Valerio found

a way to combine his drive to be a good scientist with a drive to be a good

business leader.

Invention Makes Waves

Valerio, whose work as the co-inventor of PER.C6® technology, a human cell

platform, is credited with making the unique production process of vaccine products

available to industry. PER.C6®, which uses a human cell line, forever changed the face

of antibody and vaccine products.

Up until the development of PER.C6®, animal cells, like fertilized chicken eggs used

to produce flu vaccine, and hamster cells used in rheumatoid arthritis medicine, were

the only types of cells used to make vaccines. The driving force behind Valerio’s work

was his interest in responding to the need for vaccines for all people.

“Not only was animal cell vaccine production limiting, it also didn’t address the

need for new vaccine types that can only be produced on human cells,” he explains.

Leiden University

Crucell

In 1993, Valerio had started a biotechnology company called IntroGene. As an

entrepreneur and scientist, he set out to do what no one had done before — to

develop an alternative vaccine-manufacturing technology using human cells.

While scientists had considered the development of a technology using human cells,

the obstacles against commercializing it were huge.

“Human cells had never been used because of the difficulty growing a large enough

number for commercial purposes,” says Valerio. “PER.C6® technology is very differ-

ent. It uses healthy cells in a controlled environment that allows the cells to divide and

multiply in indefinite numbers.”

In 1994, Valerio worked together with scientists in the lab of Alex van der Eb, a

professor of tumor virology, who had pioneered the concept of gene transfer into

mammalian cells.

“He created one of the first human cell lines,” says Valerio, who views his former

professor also as a mentor. “I was interested in this work because I wanted to make

products that required human cell lines. There was nothing appropriate for manufac-

ture at the time in terms of safety, scalability and availability.”

Once the scientists saw that viruses propagated well on PerC.6®, their

work took a new direction.

Three years later, IntroGene had successfully launched PER.C6®. By 1999,

IntroGene was positioned to move into new fields, developing vaccines and

producing antibodies from its human cell line.

Building Crucell

In 2000, IntroGene’s purchase of the company U-Bisys led to the creation

of Crucell, and Valerio became its president and CEO. The company’s goal

was to develop and market a range of vaccines and antibodies for use in

fighting infectious diseases.

Valerio points out the successful building of Crucell, a NASDAQ and

Euronext-listed company, came about in part because Leiden is ideally suited for col-

laborative biomedical research.

“They have a reputation of being a world-class research institution, and there was

then a willingness to take advantage of commercial opportunities,” says Valerio.


22

Pharmaceuticals

Filling ampules with vaccine. © 2006, Crucell N.V.


22“It’s one thing to have superb technology at academic centers; it’s another thing to

put that technology to commercial use.”

It was a decisive moment in 2000 when a team of Crucell researchers and scientists

recruited by Valerio recognized that the base ingredient of the gene therapy they

were working on could be used to make a vaccine that would prevent an infection

with viruses.

“We moved from gene therapy to developing PerC.6® into a vaccine manufacturing

platform,” says Valerio, who also notes it was the same year that he took the

company public.

Merck & Co. recognized that the cell line that Valerio had developed had a critical

component needed for the AIDS vaccine. Valerio also was interested in using the cell

line to develop his own company’s products.

“The cell line is broadly applicable,” he says.

Of the many products that today are being generated on PER.C6® several are now

being tested in humans. These include vaccines for influenza, West Nile and Ebola

viruses and tuberculosis.

The Right Team in Place

Paul van Grevenstein, formerly a managing director at Leiden University Medical

Center (LUMC) and responsible for all technology transfer at LUMC, agrees that

Leiden has an outstanding biomedical research base. Van Grevenstein, who now

heads an international tech transfer consulting firm, handled the negotiations with

IntroGene/Crucell.

“We negotiated two main agreements,” he explains. “One, which was called the

master agreement, dealt with the spinning out from the university, and another, a few

years later, dealt with the ultimate assignment of Leiden’s share in the then still early

stage PERC.6® technology.”

When discussing the factors that helped the creation of Crucell, van Grevenstein

notes that the management of Leiden University in those days was supportive of the

technology transfer possibility of Valerio’s discoveries. One other important factor, he

notes, is that founder Valerio is also adept at surrounding himself with exceptional

people and that he dares taking calculated risks.

Leiden University

Crucell

“One of the elements of this tech transfer story is that at some stage, Dinko

changed the company’s emphasis from a gene therapy track to a business model

using the PERC.6® technology,” he says. “That took foresight and courage.

“Valerio was very clear about the steps he wanted to take to grow the company,”

van Grevenstein continues. “Tech transfer is at its best when it is done for the creation

of value, taking the technology to the next step through collaborative research.”

Crucell has grown quickly over the last decade and is now the largest independent

vaccine company in the world. In 2004 Valerio stepped down as CEO and founded a

new company together with international venture capital veteran Michiel de Haan,

called Aescap Venture Management in Amsterdam. In this venture capital company

Valerio has what he calls a “second career” by selecting, investing and coaching

companies to become the Crucell of the future.

Meanwhile, Crucell’s development of vaccines continues, and the success story that

put the company on the world stage over a decade ago continues to make great

strides in developing vaccines that eradicate infectious diseases worldwide.

— By Sharyn Alden


22

Pharmaceuticals

Chapter

XenoTech:A MetabolismResearchLeader

Andrew Parkinson doesn’t consider himself

to be an entrepreneur, but he and his staff at

XenoTech, LLC, have built a leader in

the field of drug metabolism research.

129

23


Jeff Holsapple and Jason Barricklow discuss analytical results from one of XenoTech's many LC/MS/MS units.

A


23 Andrew Parkinson, Ph.D., doesn’t consider himself to be a typical entrepreneur.

“I’m actually not much of a risk-taker when it comes to science and business,”

says the founder and owner of XenoTech, LLC, a leader in drug metabolism research,

based in Lenexa, Kan. “It was with a lot of trepidation that I entered into this business

and started this company.”

But once Parkinson did enter the business, he and his company were on their way

to becoming leaders in the field. Today, XenoTech employs more than 80 people.

The scientific staff is divided into focused departments: Drug Metabolism, Drug

Inhibition and Enzyme Induction and Products.

XenoTech’s products are used to support drug metabolism-related research and

include liver, intestinal, renal and pulmonary microsomes and a wide variety of in vitro

research products and materials.

The company’s products and services deliver information recommended

by the U.S. Food and Drug Administration (FDA) to predict inter-individual

variation in drug safety and drug ability to perform as expected, and to

explain adverse drug-to-drug interactions.

Customers include pharmaceutical laboratories, food companies, chemical

industry firms, academic institutions and regulatory organizations through-

out the world. They primarily come from throughout North America, Europe

and Japan.

In addition to providing research products for use by these organizations,

XenoTech also offers research services to its clients. XenoTech’s in vitro

services are designed to provide the type of information encouraged in the

FDA’s April 1997 Guidance for Industry.

The company’s services include enzyme inhibition, which predicts the

potential for compounds to inhibit the metabolism of other drugs and hence risk

adverse reactions. It also specializes in reaction phenotyping (enzyme mapping), which

is used to determine the metabolic pathways involved in biotransformation of com-

pounds. Another specialized research service involves species comparisons, which

University ofKansas MedicalCenter

XenoTech, LLC

Jason Neat inspects primary human hepatocytes usedto help predict potential drug-drug interactions.

identify the non-human species whose metabolic profiles for specific compounds most

closely resemble that of human.

Filling a Need in the Research Market

XenoTech scientists have made presentations, taught courses and consulted on

metabolism-related issues for the FDA and numerous organizations worldwide.

XenoTech also has significant experience preparing customized reports for sponsors

from around the world.

Parkinson first started to realize the need for such services while a professor at the

University of Kansas Medical Center (KUMC) in 1983, doing research on Cytochrome

P450 (CYP) enzymes — major enzymes in the liver.

“We would get requests from pharmaceutical companies and other private sector

groups to do research or provide reagents and products to them,” Parkinson says.

The research funding for such work became attractive to Parkinson and the Medical

Center. The university became a 20 percent owner of what became XenoTech, and

the company started in an incubator space provided by the university. Eventually,

it occupied all 6,000 to 7,000 square feet of that space.

“XenoTech, as a success story, is a great example to other KUMC faculty

researchers regarding how commercialization is a valid way to transfer research

information into the public domain for the public good,” said Richard Huston, director

of Technology Transfer Office and associate director of the Research Institute at

Kansas University Medical Center. “It also was also one of the first tenants in the

Kansas City Biotechnology Development Center during the mid-1990s, which is

located on the north edge of the KUMC campus. Today [the Center] has about

6,600 square feet of modernized wet lab space that was updated after XenoTech’s

departure. Two client firms have occupied the space over the past year, one with

$19 million of recently acquired venture capital and possibilities for other clients are

on the horizon. XenoTech’s success is an inspiration to other KUMC researchers who

have great technologies that can be developed for commercialization.”

“It has changed a great deal,” Parkinson says of university technology transfer.

“At that time, you didn’t really have the vehicles for tech transfer and royalties from

startups to universities that you have today.”


23

Pharmaceuticals


23Parkinson raised capital separately from the university. Some of it came by putting

his home and property up as collateral.

Making the Leap to the Business World

The company grew slowly but consistently through the late 1980s and early 1990s,

until the formal establishment of XenoTech in 1994. Then, around 1999-2000, after

what Parkinson admits was some “long agonizing,” he decided to leave his tenured

position at the university and devote himself full-time to XenoTech.

“It had come to either selling the company, letting it whither or leaving the

university,” Dr. Parkinson says. “I chose the latter.”

Parkinson also bought out the university’s 20 percent ownership.

XenoTech’s company tagline reads, “Uncommon Science, Uncommon Service.”

The company offers services based on Good Laboratory Practices (GLP) when desired,

and a variety of products for in vitro drug metabolism research.

XenoTech offers drug inhibition, enzyme induction and drug metabolism studies as

either non-GLP studies or as studies in compliance with GLP regulations in the U.S.,

Japan and Europe.

“Some of the studies we do are required to comply with the FDA GLP standards,

but not follow them strictly,” Parkinson says. “Others are required to comply. We

believe it is good to offer both.”

XenoTech has twice been selected as one of the five finalists for the 2006 Kansas

Governor’s Exporter of the Year Award. With sales and services to companies in 19

countries, XenoTech has thought big and globally, while using many Kansas vendors

for needs from organs for the research to office supplies and legal and professional

consulting. The company also is very involved in state and local community initiatives

and charities.

XenoTech maintains strict confidentiality with its clients, but the company did pro-

vide the following excerpt from a client’s letter:

“XenoTech staff proved to be exceptionally helpful when it came down

to design a study protocol in a timely fashion. They also showed flexibility

and understanding when we needed to include strict timelines for delivery

of critical study milestones. In addition, XenoTech’s CEO, Dr. Andrew

University ofKansas MedicalCenter

XenoTech, LLC

Parkinson, offered to function as an expert consultant by helping to

respond to the FDA drafting a Position Paper on the status quo of in vitro

CYP induction and its relevance to in vivo drug-drug interactions.

“The study was completed ahead of schedule. It was the combined

effort of all people involved at XenoTech that allowed us to address all

questions raised to the FDA’s full satisfaction.”

Parkinson admits this type of input is rewarding for somebody who doesn’t consider

himself an entrepreneur.

“I feel very uncomfortable with that entrepreneur description,” Parkinson says.

“We have wonderful people who have helped build XenoTech. They deserve much of

the credit.”



23

Pharmaceuticals

Chapter

BullEx DigitalSafety MakesHot ProductOut of FireExtinguisherTraining

Rensselaer Polytechnic Institute undergraduates

produce new technology

in school’s Inventor’s Studio.

135

24


The BullEx Intelligent Training System™ (I.T.S.), employs patented sensor technology to simulate the use of a fire extinguisher.

N


24 Not all technology breakthroughs spring from the brains and laboratories of those

with a Ph.D. Sometimes undergraduates have pretty darn good ideas, too.

That’s the whole point of the Inventor’s Studio at Rensselaer Polytechnic Institute

(RPI) in Troy, N.Y., where students came up with a live fire extinguisher training

simulator that ultimately led to the founding of BullEx Digital Safety.

“The goal of the course is to define problems that most people don’t even know

exist,” says Burt Swersey, an RPI faculty member who runs the Inventor’s Studio.

“And then invent and patent solutions.”

But the students in Swersey’s class didn’t start out seeking to create what has come

to be known as the Intelligent Training System™, a safe and relatively inexpensive

technology that can detect the accuracy of trainees’ sweeps of compressed air and

water from its SmartExtnguishers™ onto what looks like an oversized camping stove.

Company officials say the system that evolved is an ideal teaching tool, thanks to

an onboard control system that realistically and automatically varies the propane-fed

flames to simulate a variety of fire types. The system also allows the trainer to control

the flame range, score and rate trainees, and vary the degree of difficulty.

Experts note that fires account for more than $9 billion in property loss in the

U.S. each year. Yet the majority of these fires can be stopped before growing too

large with a single extinguisher, operated by a trained user.

Better training in the use of fire extinguishers is greatly needed, they say, because

most homeowners — if they have them at all — don’t know how to use them.

In addition, federal law requires industries to train workers how to use their fire

extinguishers.

Students as Inventors

Swersey, who has been teaching in the Inventor’s Studio for the past eight years in

the department of mechanical, aerospace and nuclear engineering, gives most of the

credit for the Intelligent Training System to two former students — Paul Darois and

Steve Galonska — who began working on a related project when they were sopho-

mores at RPI several years ago. Swersey is also listed as a co-inventor on the patent

application, as are former RPI students John Blackburn and Travis Bashaw.

RensselaerPolytechnicInstitute

BullEx DigitalSafety

“I believe this product will save lives and prevent property damage. That’s a pretty

great thing,” says Swersey, who has started and run several medical device companies

in New York. A Cornell University graduate, he began his career at Polaroid and is a

devotee of Edwin Land, who pushed employees to find unrecognized needs and

create products to solve them.

Swersey says Darois and Galonska first designed a cook stove that would turn itself

off if a fire erupted. But many other inventors had worked on that problem and

obtained patents. So they toyed with making race cars and airplanes safer from fires.

Eventually, they looked at fire extinguishers and found that the system for training

users could be improved significantly.

“Basically, the state of the art was to ignite kerosene in a container in a parking lot

and have trainees use a fire extinguisher to put out the fire. It’s expensive, $20 plus to

recharge the extinguisher, makes a mess and provides no metrics of the test,” he says.

“And that’s how it’s still done around much of the world.”

Swersey says it was important that Darois and Galonska did not “fall in love” with

their first idea.

“Iteration is the key,” he states. “Rarely is the first idea the winner. You need

successive iterations and they kept working until they created a design that was far

better than what exists.”

Swersey says he distinctly remembers the day a few years back when Galonska

came into his class and proudly showed him a sensor he had purchased for about $7.

“He said ‘Hey, look at this’ and proceeded to demonstrate it,” he recalls.

Galonska stood 15 feet from his partner Darois and ignited a cigarette lighter. When

Galonska pointed the sensor at the flame, “low and behold” the simple little circuit he

had built went off, Swersey says.

“The sensor could see the cigarette lighter 15 feet away,” he says. “That was a key

moment. And it resulted from their attitude — constantly striving for improvement and

taking initiative, rather than waiting to be told what to do. They attacked problems

with optimism and confidence that they could learn any new technology on their own

and would do whatever was needed to succeed. That is the most important lesson.”

They continued improving the mechanical and electronic design and running a suc-

cession of tests. And rather quickly, the training system, which uses advanced sensors


24

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24embedded in the burner in combination with the control system to determine the stu-

dents’ technique, was ready to be shown to users.

BullEx: “An Inspiration”

Other key players in the BullEx story are volunteer firefighter Ryan O’Donnell, who

is now the company’s CEO, and John Blackburn, electrical engineer and head of tech-

nology. O’Donnell and Blackburn took over the company, when Galonska and Darois

chose to pursue other careers after they graduated. O’Donnell and Blackburn were

also in Swersey’s class and overlapped with the original inventors.

Phil Weilerstein also played an important role. He is the executive director of the

National Collegiate Inventors and Innovators Alliance (NCIIA), which gave out grants

worth nearly $30,000 to the fledgling company. NCIIA is supported by the Lemelson

Foundation. Its namesake, Jerome Lemelson, was a prolific inventor.

“BullEx is an inspiration that we have broadcast widely in our network to make it

clear to other faculty that they need to do the kinds of things that were done for this

team and to look for students who can be nurtured the way these students have,”

Weilerstein says.

“They killed a lot of birds with one stone and went from the classroom to a compa-

ny,” he says. “O’Donnell pulled together a team, took a great idea and made this

happen with determination and know-how. But it wouldn’t have happened without

the RPI environment.

“Their story exemplifies the opportunities that are there for students in higher

education for locally funded and developed innovations that can have a positive

impact on the local economy without any large federal grants or venture capital

funding,” he says.

Charles Rancourt, who heads Rensselaer’s Office of Technology and

Commercialization, says he, too, is inspired by the success of BullEx and its student

entrepreneurs. Rancourt’s office helped the inventors with the patenting process and

coordinated the licensing of the technology to BullEx.

“They were very successful at winning business plan competitions to help launch

the company,” he says. “But the thing I would emphasize is that this was a student

RensselaerPolytechnicInstitute

BullEx DigitalSafety

project. They took an invention that had commercial potential and then had the initia-

tive to start a company that is the ‘real deal’ with customers all over the country.”

O’Donnell, who remains a volunteer fireman, said the company earned about

$150,000 in grants and awards from the NCIIA and a number of state and local

business plan competitions. It also took out a “significant” loan to get off the ground

in 2005.

BullEx, which is based in Albany, N.Y., has 30 employees and is making a profit, he

says. It now has customers in virtually every market and industry group, including the

U.S. Army, General Electric, Harvard University and the state of Alaska.

“We’re making a difference in a lot of positive ways,” says O’Donnell, who earned

his degree from RPI in engineering. “From here, our aim is to keep growing, capitalize

on new innovations and offer systems similar to the fire extinguisher training technol-

ogy that can provide a real and cost-effective benefit to customers.”



24

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Chapter

GroundbreakingTechnology“Sees” Soundin ThreeDimensions

Acoustic holography technology, developed at

Wayne State University, accurately visualizes sound as it

flows through space and time, helping product design

engineers “plug” leaks in products and machinery.

141

25


SenSound system being used to create a 3-D acoustic map the top surfaces of an engine.

I


25 Imagine airplane designers being able to “see” where unwanted noise is coming

from in a plane’s fuselage or engine. Or what if automotive engineers could “see” the

rattling noise coming from a car door’s panel on a computer screen.

These marvels of technology may sound like science fiction, but they’re actually

the invention and by-product of years of research by Sean Wu, Ph.D., distinguished

professor of engineering at Wayne State University in Detroit.

Until now, noise diagnostics has been primarily a process of elimination.

“You might get lucky, you might not,” says Ravi Beniwal, senior applications

engineer with SenSound, LLC, the company formed to commercialize the technology

invented at Wayne State.

“Most of the time people just guestimate where the noise is coming from, but our

technology pinpoints exactly where noise is ‘leaking,’” Beniwal says.

The technology, licensed to SenSound in 2004, is making waves because of the

innovative way it “sees” the origin of noise in cars, boats, airplanes and other

machines and products. The benefits are significant because the technology helps

engineers design quieter products and achieve better noise-related quality control.

“There’s a lot of need for this technology in industry,” says Beniwal, “because we

can help engineers make everything quieter.”

Inventing the “Sound Camera”

Manmohan Moondra, senior product development engineer with SenSound,

knows firsthand the excitement behind developing a groundbreaking sound

analysis system. In 2002, when he was a research assistant at Wayne State, he

worked on some of the software with Professor Wu and also validated the

software between 2002 and 2004.

“We developed software that uses a microphone array sound camera to

‘photograph’ sound and convert the analog signals from the microphones to

digital pictures of sound,” says Moondra. “The really exciting part is when we

connect the software to the computer and can see the images of what the

microphones pick up.”

Wayne StateUniversity

SenSound, LLC

SenSound founders (L to R), Sergio Mazza, Prof. Sean F. Wu and Gary Kendra

Before the development of this technology, sound diagnostics with acoustic

holography was limited to a two-dimensional plane, but SenSound has taken it a step

further by showing sound in three dimensions. More than $800,000 in grants from

the National Science Foundation, along with additional financial support from the

Ford Motor Co., DaimlerChrysler Challenge Fund, Cadillac Products Automotive Co.

and L&L Products, contributed to the development of Wayne State University

Technologies licensed by SenSound.

From Discovery to Startup

The next step for Professor Wu and Wayne State was to find the right partners for

establishing a startup company.

Judy Johncox, director of venture development at Wayne State University, says

once the sound diagnostics technology was developed at the university, the next

question was whether it would be sustainable for a startup company.

“We brought together Gary Kendra, a lawyer with Kendra Law Firm in Detroit

whose practice area focuses on technology and commercialization and Sergio Mazza,

who had approached the university as a private investor,” says Johncox. “Their

synergy and common goals were apparent from the beginning. It took about three

months to complete the licensing agreement in December 2003.”

“The result was SenSound, the first company that uses 3-D holography to take

measurements in the field, and then trace the noise to a source,” says Moondra.

SenSound has had a strong showing since it was launched in 2004 with more than

$800,000 in revenue in 2005. The company already has 10 employees, many of

whom are graduates of Wayne State.

“This company is exceptional in many ways,” says Johncox. “With startup

companies, it usually takes two to three years to have a revenue stream, but they

went from sales to revenue in the first year.”

Kendra points out SenSound’s strong leadership from the CEO has helped the

company succeed.

“Sergio has a strong international presence, which has helped us make a lot of

headway,” he notes.


25

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25Infinite Applications

When Beniwal, who designs the diagnostic tests for SenSound, makes presentations

to potential customers, the common reaction when shown how the technology works

is, “Wow!”

“People are not used to seeing sound in diagnostic tests,” says Beniwal. “When

they see what we can do, it usually amazes them.”

The sound detectives look for unwanted sound in numerous locations. To locate

noise in an airplane, Moondra and Beniwal took sound measurements while flying at

30,000 feet. Next, they brought the 3-D sound photos back to their computers, and

then crunched the numbers based on the new diagnostics technology.

“On a model of the plane, you can ‘see’ the entire sound field inside the fuselage,”

says Moondra. “The beauty of this technology is that when airplane designers have

this information, they can make intelligent decisions about where to place various

components, like where to put insulation or install seats on the plane.”

In another example, Beniwal tested several variations and operating conditions of a

car’s noisy door panel. The motor that operated the window was quiet, and the door

was quiet, but when put together, they produced noise. By creating a model of the

sound field, SenSound shows the customer where the unwanted sound is streaming in.

“Noise is interesting,” says Beniwal. “You can put several silent components

together and build a noisy system. There’s also the combination of vibration and

sound which are interrelated, but even though all sound is produced by vibrations,

not all vibrations can produce sound. Our value is saving companies time and money

by getting to the root of the problem faster. If you can hear the noise above the

background, we can visualize and detect it,” says Beniwal.

There is no end in sight for applications of SenSound services and products.

“The capabilities for industry and consumer products are just tremendous,” says

Johncox.

New Horizons

Consumers and employees will soon benefit from SenSound’s innovative

problem-solving technology as the company moves forward and targets workplace

environments and consumer products.

Wayne StateUniversity

SenSound, LLC

“The possibilities for SenSound’s technology are endless,” says Kendra, who points

out the next great horizon of regulatory activity is noise control.

“Noise is going to become an even bigger social and aesthetic issue in the future,”

Kendra says. “For example, Europe has started to become very aggressive about

noise. If you’re going to send equipment like snow blowers or lawn movers to Europe,

you need to know how to respond to controlling and reducing noise.”

Kendra recognizes that educating the marketplace about the value of manufactur-

ing noise-free products in a work environment with less noise, is part of the compa-

ny’s challenge in the future.

Kendra expects SenSound’s patented technology of noise diagnostics will continue

indefinitely to make great strides in unraveling the mysteries of unwanted sound.

“We can identify unwanted sound wherever it affects quality control,” he says.

“Our approach is more scientific, more mathematic, and more accurate. The trade-off

is a quicker turnaround of identifying problems for designers, and better products in

the long run.”

— By Sharyn Alden


25

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ISBN 0-9778444-3-9

®

Read more about academic innovation and technology transfer at

www.betterworldproject.net.

Cheaper and cleaner

biodiesel, deeper medical

screening, revolutionary

DNA testing technology,

green power, accurate

airfare prediction tools,

and discoveries that enable

and transform even more

discoveries – just a few

examples of the

25 companies profiled

here and the products that

may never have material-

ized if not for academic

research and the transfer

of these discoveries to

the marketplace.

The phenomenon of new business spin-offs from university research

knows no bounds.• High-tech semiconductor technology from Florida

• Tutoring programs from California

• Optical breakthroughs from Colorado

• Recycling initiatives from the UK

• Food security from New York

This is an economics book of different kind. It is not about theories,

calculations, or principles of business. This book contains real-world

examples of how new businesses are developed, jobs created,

income generated, and problems solved, and how university

research served as the catalyst. You’ll read about professors turned

entrepreneurs, risk takers who experimented with vaccines on them-

selves first, and ideas generated when they were least expected.

It’s about ROI — Return on Innovation.

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