Cox Anatabine Report

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Live Long and Prosper NutraceuticallyBy Patrick Cox

Continued on Next Pa

Inside This Issue

The Market Potential for a SafeAnti-Inflammaging Compound

Secondhand Smoke Signals

The Anatabine Discovery

Portfolio Positions

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As Ive said many times, the best way to get rich is simply to live longer and let themathematics of exponential portfolio growth do its work. This month, I have a companthat has a synthesized form of a natural alkaloid I believe will allow you to do just thatI also believe that equity in this company will yield truly transformational returns.

However and I admit this is a big however this technology is in the very earlystages. This company is so disruptive, I wouldnt be surprised if some of the industries itwill disrupt will try to discredit or stop the product. Moreover, we dont yet have long-termdouble-blind human studies on the use of this substance.

On the other hand, we dont yet have blinded human data for quite a few of ourcompanies drug candidates. This isnt unique. There is, however, something about thisproduct that inspired in me a particular degree of skepticism and caution. I assume,therefore, that it may provoke the same skepticism in you. Specifically, this companysproduct is a nutraceutical.

Nutraceuticals Vs. Drugs

Nutraceuticals, as you know, are foods or food-derived products meant to providehealth benefits. They may function exactly like substances considered drugs legally, butthey are not categorized as drugs.

For example, you may take or sell the extract of willow bark for use as an anti-inflammatory, anti-clotting agent or painkiller without getting government permission.You cant make medical claims about willow bark extract, or the active ingredient, salicylacid, however. Current government policy in the U.S. and some other countries reservesthat right for products that have passed extremely lengthy and expensive procedures.

If you synthesize a very similar compound, acetylsalicylic acid or aspirin, you have adrug. With regulatory approval, you can, therefore, make certain kinds of claims regardinits efficacy in the prevention of heart attacks or strokes. There is very little difference in th

actual function of the two products, though.

One other difference is in the realm of patent law. Drugs can be patented, period.Nutraceuticals can be patented for specific uses only.

Because nutraceuticals are not subject to testing requirements and regulations, theyare much easier to bring to market. In some instances, impure and even dangerous nutraceuticals have been widely sold. The FDA can force a product off the market if it is foundto be harmful, but the agency does not have legal authority to require clinical testing.

As a result, there have been some major problems in this area. You undoubtedly reca

April 2011 Vol. 5 Issu


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when beta-carotene, derived from plants such as tomatoes, was widely heralded a panacea.Books were written claiming it would cure cancer and extend life spans. Despite the lackof blinded studies, untold millions were spent on beta-carotene supplements. Finally, whenbeta-carotene supplementation was tested clinically, the claims were discredited. Someclinical results showed that the nutraceutical actually increased cancer risk.

So supplement makers went back to the drawing board. We know there are clear

benefits from eating lots of tomato products, particularly in the area of cancer prevention.Some reasoned that another nutrient, which is always found in conjunction with beta-caro-tene, was responsible for the solanaceous fruits health benefits. They settled on lycopene.In effect, they decided that beta-carotene is a marker for lycopene and they had mistakenthe marker for the active ingredient. Thus far, theres little evidence that lycopene lowerscancer risks, either.

Another nutraceutical that has proven disappointing is resveratrol, the anti-fungalphenol found in red grapes and other plants. You may have noticed that Ive never wavedthe resveratrol flag. There has never, in fact, been any real evidence that it conveys beneficiaeffects to mammals.

At the height of the resveratrol craze, I tried the product for a while to see if I could

detect benefits others swore they were experiencing. I noticed nothing and stopped. Recently,a concentrated drug form of resveratrol actually produced harmful effects in humans.

Millions of words, though, have been written by people who claim incredible benefitsfrom resveratrol supplementation. Lacking any real evidence, I have to conclude this may bea sort of group placebo effect. Supplement fads arrive and legions of seekers arise to praisesome fresh nutraceuticals wondrous effects.

Weve seen this cycle play out so many times. Fans of a product swear it is improvingtheir health, but eventually stop taking it... often just as another supplement fad arrives.The people who claim medical benefits are absolutely sincere, however. This makes it verydifficult to judge anecdotal testimonials regarding nutraceuticals.

On the other hand, there are incredibly important and effective nutraceuticals. Omega-3fatty acids, in both the fish oil extract and the purified synthesized form, are linked by realdata to improved health. The nutraceutical form of vitamin D is also an important supplementwith clinically verified health benefits. If your circulating levels of 25-hydroxyvitamin D arebelow 45 ng/ml, I would strongly recommend that you speak with a doctor who keeps upwith the scientific literature.

Im telling you all this for a reason. Im recommending a company that has nutraceuticalproducts, so I want you to go in with your eyes open. I also want you to know why I wasso skeptical and why Ive gone to extra lengths to verify the story and the people involved.

Im convinced that this is one of the most important breakthrough technologies of ourtime. I wont pretend, however, that were not in the Wild Wild West of investing when we

venture into nutraceutical territory.

That isnt necessarily a bad thing, though.

2

Im convinced

that this is one

of the most

important

breakthrough

technologies

of our time.

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The same dynamics that make this area volatile and unpredictable can also lead toenormous profits.

(Incidentally, the Wild Wild West was never as dangerous as the urban east, past andpresent. My friends Dr. Terry Anderson and Dr. P.J. Hill of Montana State University demon-strate this in a wonderfully entertaining academic journal article that you can read at this link.)

Given all these caveats, Im nevertheless convinced that the company were addingto the portfolio this month has a product that actually does what other supplements onlywished they could do. As I said earlier, I believe that most people who take the anatabine

citrate supplement made by Star Scientific Inc. (NASDAQ: CIGX) will see significantlyimproved quality and length of life.

Yes, I realize how radical that statement really is. If I heard this from someone else,I would almost certainly dismiss the claim as ignorant or dishonest. In fact, I did. For thatreason, Ive wrestled with the best way to present the science behind this product.

Having spent more than a month researching this biochemical technology, Ive come tothe conclusion that there is no way to completely convey the scientific and financial storybehind this company in one issue. It took me weeks to overcome my initial skepticismregarding this technology. Ive spoken at length to extremely important respected scientistsand have hours of taped interviews. Ive read tens of thousands of words on the sciencebehind this breakthrough. Ive visited one of the worlds top biotech research laboratories andhave met researchers whom Ive known about for over a decade, but never expected to meet.

Ive never wanted you, my readers, to blindly take my opinion about anything. Im paidto give you disruptive technology companies... but obviously, they cannot all be equal. Thisis why I lay out the evidence and science with source materials included. I do this so youcan come to your conclusions and make decisions based on your own situation.

Given my own initial rejection of this biotechnology, I have to believe that intelligentreaders will be as skeptical as I was when it first came to me. You should be, in fact.I doubted even though I was already familiar with much of the science and many of theresearchers whom Ive encountered in the past month. Nevertheless, it was difficult for

me to accept the importance and magnitude of this discovery. For many of you who donot follow medical research obsessively, as I do, this story will sound more like sciencefiction than science.

Therefore, this issue is going to serve only as an introduction to this nutraceuticalbiotechnology. A single comprehensive article on the core science would be too long andtechnical for almost anybody but doctors and scientists. Therefore, this will have to serveas an initial overview. More detail will be provided in forthcoming issues. That said, I warnyou that it is also one of my longest. I beseech you, though, to read this issue entirely.

This technology is going to have a far bigger impact on a wider variety of companiesthan you might initially think.

Moreover, telling the story in even more depth would require that I get the approval ofnumerous scientists Ive interviewed. I never quote any of my sources without approval, andusually only after they have seen the quotation in writing. Because this month has beenso unusual, I didnt have time to do that. I will, though, have verified quotations regardingthis biotechnology in future updates. More data, including real human clinical data, will beavailable within the next few months. Ill keep you up-to-date as evidence appears.

I believe that Star Scientifics anatabine supplement will not only make you healthierand wealthier, it will have an impact on the U.S. and world economies. I dont know howsoon the biggest impacts will arrive, but its going to happen unless something completelyunexpected prevents it.

This technologyis going to have

a far bigger

impact on awider variety

of companies

than you might

initially think.
http://mises.org/journals/jls/3_1/3_1_2.pdfhttp://mises.org/journals/jls/3_1/3_1_2.pdf


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There is no one among all my readers, by the way, who has not already taken anatabinein some form. It is, after all, basically, food. You were not, however, taking it at the currentlyachievable level of purity or in optimal quantities. It is, in fact, found in members of theSolanaceae family of plants. These include tomatoes, red peppers and, most importantfrom the perspective of this story, tobacco.

The Star Scientific StoryYou may know that I have been extremely fortunate to have had a number of articlesabout biotechnologies published by John Mauldin. With his 1.5 million readers, includingmany extremely influential thinkers, Mauldins network is formidable.

Through Mauldin, I have gained access to biotech scientists whom I might not haveencountered until they achieved a much higher level of visibility. Word of BreakthroughTechnology Alert, because of his generous help, has penetrated much further into theworld of emerging biotechnologies. These days, Im regularly approached by people whobelieve they have important technologies. This is an enviable position to be in.

Some of these companies dont measure up. Usually, it is because theyre unaware ofprogress in related fields that will make their platforms prematurely obsolete. Generally,

however, people dont approach me unless they believe their science is solid and theirpotential is transformational.

One such person is now a reader of this newsletter. He sent me, though Mauldin,information about a company that claims to have a nutraceutical that significantly reduceschronic low-level inflammation.

This is such a big claim. I assumed I was seeing the same old beta-carotene resveratrolhealth food fad cycle playing out once again. Such a compound would be a world-changingbreakthrough, even if it were a regulated drug. A safe nutraceutical that controls chroniclow-level inflammation, outside the bureaucrats regulatory reach, is just too good to betrue. I didnt believe it for a second. I didnt even consider it. Let me explain why.

The Inflammaging StoryThe name of the neural circuit that regulates the immune response to injury and invasion is

the inflammatory reflex. Inflammation is an extremely complex mechanism that involvesthe destruction through apoptosis of damaged cells, the healing of salvageable cells andthe growth of entirely new cells.

In the last decade or so, it has become increasingly clear that inflammation plays amajor complicating role in almost all diseases. When we are young, the primary role ofthis important biological response is to heal injury or infection. In the last century or so,the inflammatory reflex has begun to play a role that it almost never did in the past.

For the vast majority of human history, life was hard and life spans were short. ForGreeks during the Classical period of the 5th and 4th centuries B.C., the average person

lived only about 28 years. It was nearly the same for ancient Romans. Life spans rose toabout 30 years in medieval Britain and reached, in the developed world, about 45 in theearly 20th century.

I think people tend to underestimate just how rough life was until very recently. Beforeit was possible to mass-produce penicillin, during the Second World War, a broken bonethat protruded through the skin resulted in death at least 50% of the time. Being thrownfrom a horse, kicked by a cow or bitten by any kind of animal was a serious, potentiallylife-ending matter. Early automobile accidents were far more dangerous because of the riskof secondary infection. Lacking safer modern technologies, industrial and household accidentswere more common and far more lethal.

4

Such a compound

would be a

world-changing

breakthrough,

even if it were

a regulated drug.


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In the olden days, the only way to survive a nearly inevitable sequence of injuries wasa strong inflammatory immune response. If individuals didnt have the ability to mount apowerful inflammatory response, they were unlikely to live long enough to pass on their DNA.

Today, however, life expectancies are pushing 80 years in North America. Despite theinane delusions of green fantasists, modern life is altogether safer and better. Medicaltechnologies allow us to survive injuries and infections that would have quickly killed our

grandparents.

Herein lies the rub, however. We still have an inflammatory reflex that was tuned inancient Greece and medieval Europe.

It is now understood that inflammation plays a role in virtually all diseases. In fact,inflammation increases the rate of aging itself and leads to various pathologies. This is whyyour dentist lectures you about flossing. Inflammation from unhealthy gums increases theodds of getting heart disease and even Alzheimers.

Even with perfect gums, however, chronic inflammation increases as you age.Eventually, it creates a problem serious enough to trigger a cascade effect. Uncontrolledinflammation causes the simultaneous healing and destruction of cells. This can lead tocancers, heart attacks, lupus, IBS, macular degeneration, stroke, obesity, ED, allergies,

psoriasis, Crohns disease, endometriosis, rheumatoid arthritis, hair loss, diseases of theorgans such as the thyroid and liver as well as... well, you name it.

The general public learned about this for the first time in a 2004 Time magazine coverstory titled The Fire Within.

Today, scientists have advanced the science much further. Many are now using theterm inflammaging, coined by Claudio Franceschi, professor of immunology at theUniversity of Bologna.

It appears, in fact, that our immune systems react to the normal effects of aging asif they were injuries. This initiates inflammation, an immune response. This inflammationcauses cellular stress, which increases the degree of chronic inflammation which causes

even more damage. It is, by definition, an autoimmune disorder. Some scientists call itauto[innate]immunity subclinical syndrome.

It is a vicious circle, a chronic cycle that spins faster and faster until the organismitself eventually fails. Aging, we now know, is not linear. Like so many other things, it isan exponential process that accelerates over time.

If there were a way to stop chronic low-level inflammation, however, we could putthe brakes on the autoimmune inflammation cycle. If we could stop chronic low-levelinflammation, our bodies could heal naturally, just as they did before inflammaging kickedin. We would even see cells damaged by past inflammation-related diseases heal normally.

Were not talking about regenerative medicine, of course. Our cells eventually reachtheir Hayflick limit even if we halt the inflammaging cycle. We will eventually run out of

the telomeres used every time a cell replaces itself through chromosome replication.

Cells that are running out of telomeres stop functioning properly and eventually fail.Regenerative medicine promises to replace aged cells and tissue with young telomere-restored cells and tissue. An alternative route is the activation of the telomerase gene,which we know can restore telomeres to youthful lengths.

In the meantime, however, we need to slow the process of telomere loss. For sometime, scientists have known that inflammation is the primary accelerator of telomere loss.This is why so few of us reach our theoretical maximum life spans, which could be 120years or more.

Today, scientists

have advanced

the science much

further.
http://www.time.com/time/magazine/article/0,9171,993419,00.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/17116321http://www.immunityageing.com/content/3/1/12http://en.wikipedia.org/wiki/Hayflick_limithttp://en.wikipedia.org/wiki/Hayflick_limithttp://www.immunityageing.com/content/3/1/12http://www.ncbi.nlm.nih.gov/pubmed/17116321http://www.time.com/time/magazine/article/0,9171,993419,00.html


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We would be much, much more likely to reach that theoretical upper limit if we agedas we did when we were young. Its often said that time speeds up as get older. Nowwe know there is a great deal of truth to that adage, though not in the sense it is usuallyintended. A drug that actually controlled inflammaging would restore the aging process toa more linear progression, as it was when we were young.

For this reason, many scientists are looking for the means to reduce or stop inflam-

maging. Not infrequently, this hypothetical drug has been referred to as the holy grailof drug discovery.

The Market Potential for a Safe Anti-Inflammaging CompoundThe market for such a compound would be so big it is nearly incomprehensible. It

is instructive, though, to consider one relatively weak anti-inflammation drug. Lipitor,technically atorvastatin, does lower indicators of inflammation. The most well-known,because doctors can test for it easily, is C-reactive protein (CRP). CRP levels rise withinflammation and their reduction demonstrates lowered inflammation. As a result, Lipitoris known to reduce the danger of cardiovascular and other diseases for many people.

Measured by sales, Lipitor is the most successful drug in history. Last year, Pfizer sold

over $5 billion of Lipitor. This is despite a broad range of adverse effects and competinganti-inflammatory statins. At its peak in 2006, Pfizer was earning almost $13 billion annuallyfrom Lipitor. The patents expire this year, by the way, and Lipitor represents about 15% ofPfizers total revenues.

The reason I didnt take Star Scientific seriously was that the company was saying,essentially, that it had found a compound that is far more effective than Lipitor or the otherstatins while being safer and cheaper. That, my friends, is the holy grail of modern medicineso many scientists are seeking.

More unbelievable still, theyre saying it isnt even a drug in the legal sense. The holygrail is an extremely safe nutraceutical a food that all of us consume in small quantitiesregularly. This, I believed, was simply way too good to be true. I never read past the first

few paragraphs of their materials. I didnt like the name of the company, Star Scientific.I didnt like its ticker, CIGX.

Nothing more would have come of it if I had not accepted an invitation from JohnMauldin to a dinner in Palm Beach. My associate Ray Blanco and I drove across the state

and found ourselves in a bar with John. Shortly thereafter, the Breakthrough TechnologyAlertreader who had originally sent me the information about Star Scientific joined us.With him was the CEO of Star Scientific, Jonnie Williams.

The Jonnie Williams StoryI didnt initially recognize the name, but as soon as he began talking about himself, it

all came together. I remember when Jonnie Williams invented the tobacco curing technology

that dramatically reduces carcinogenic toxins. He financed that research, by the way, with asmall part of the fortune he had made as a major investor or co-founder in several successfubiotechs, including VISX.

Williams improved tobacco technology is universally used today. This technologyhas extended millions of lives around the world. I remember also when Williams enteredinto Americas largest patent lawsuit, by size of damages requested, with R.J. ReynoldsTobacco Co.

An associate of Williams, a world-renowned scientist, has since described him to me asa force of nature. Its a good description. Without his drive and particular combination of

6

This technology

has extended

millions of lives

around the world.
http://www.dailyfinance.com/story/investing/top-selling-drugs-are-about-to-lose-patent-protection-ready/19830027/http://www.dailyfinance.com/story/investing/top-selling-drugs-are-about-to-lose-patent-protection-ready/19830027/


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curiosity, optimism, skills and character, this discovery might never have been made.

Williams has absolutely no doubt about the nutraceutical he has discovered. Ifyoure accustomed to speaking with extremely careful scientists, as I am, hes nothinglike that. Nothing.

That evening in Palm Beach, he repeated to me the basic claims his friend had sent me.He said, though not in these words, that he had discovered a safe nutraceutical that controlsthe vicious cycle of inflammaging. At that point, I was smiling politely and listening. I stilldidnt believe him, but he convinced me he was sincere. He wasnt lying, I figured. He was

just wrong.

I was curious enough, however, to take Williams up on his offer to meet with scientistsworking with his technology in Sarasota, Fla., where hes based. I had asked him questionsthat he didnt have answers to, so he encouraged me to come up and see the lab andtalk to the scientists.

Road Trip to SarasotaRay Blanco and I programmed the GPS locator and drove to Sarasota with the windows

open. Florida is beautiful this time of year, and we have similar tastes in music. I was preparedto waste a day.

We arrived at Williams office at the airstrip where he keeps his plane. On the way tothe lab, he gave us the backstory to the discovery of anatabine. Im going to give you avery abbreviated version, because the whole saga could and ought to fill a book. Its atruly fascinating scientific and entrepreneurial detective story.

Williams Virginia family had been associated with the tobacco industry for generationsand he had seen cigarettes prematurely kill many friends and family. Wealthy from his bio-tech investments, he retired. Nearly by accident, however, he found himself the owner of atobacco processing plant.

With the raw materials at hand and an insatiable curiosity, he started wondering if he

might be able to make tobacco less dangerous. This was based on the fact that the tobaccoplant itself contains no carcinogens. Only when its cured do the toxins form.

Eventually, he invented a superior processing technology using microwaves to speedthe drying process, reducing carcinogenic toxin creation significantly. It wasnt enough forhim, though. He then set out to find a way to help people quit smoking entirely.

The standard smoking-cessation aid at the time, and today, is nicotine chewing gum.Unfortunately, the success rate for nicotine gum is barely higher than for normal chewinggum. You would probably be better off using a xylitol gum, a clinically validated nutraceutical.

Williams reasoned that there must be something in tobacco other than nicotine thatdraws people back to the whole tobacco plant product. He was not the only person to

reach this conclusion, though he was the first person to methodically and earnestly lookfor the answer.

The Crow ConnectionOn a personal note, Ive been fascinated with the medical properties of tobacco

my whole life. Because my great-grandfather was honored by the Crow, or Apsalooke,tribe for some technology-related things he did for them following the Battle of theLittle Big Horn, Ive always had family among the Crow. As a child, I lived in CrowAgency, Montana, and saw traditional Crow rituals and dances. Many dealt with themedicinal properties of tobacco.

He invented a

superior process-

ing technology

using microwave

to speed the dryin

process, reducing

carcinogenic

toxin creation

significantly.
http://en.wikipedia.org/wiki/Xylitolhttp://en.wikipedia.org/wiki/Xylitol


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8

No evidence has

been found of

any increase in

cancer rates,

including mouth

and stomach.

The tobacco medicine pipe is common to many tribes in North America. For the

Crow, however, the sacred tobacco bundle is the central religious icon. The legend of

the creation of the Crow tribe begins, in fact, with the gift of tobacco to the Apsalooke

patriarch by his star-faring father. The medicine pipe is on the tribes modern emblem and

the sacred tobacco bundle is at its center.

The Mesolithic Crow, however, were not chain-smoking cigarettes. Tobacco cultivation

was rigidly ritualized and forbidden to all but a few. The medicine pipes use was limited tocertain important occasions and locations, such as the sweat lodge. Used with that sort of

moderation, tobacco seems to have very few ill effects. Beyond its pleasant antidepressant

monoamine oxidase (MAO) inhibiting effect, there are well-documented medical benefits.

For example, its long been known that smokers are much less likely to get Parkinsons

disease. This applies even to very moderate smokers, such as people who only occasionally

sneak a cigarette. I suspect that the Mesolithic Crow smoked about as much tobacco as

was needed to get the benefits of tobacco without most of the ill effects.

(Personally, when I smoked, I was never able to achieve that level of moderation. It

would require, I think, a strict social and religious structure such as the Crow had.)

Secondhand Smoke SignalsIronically, there are even some benefits from secondhand smoke. I remember when

the flight attendants organization funded a study to determine just how bad cabin smoke

is on thyroid health. The study was performed by prominent Johns Hopkins endocrinologist

Dr. Paul Ladenson and others. When the study was completed, the data actually showed

a reduction in Hashimotos thyroiditis, commonly called thyroid disease, among those

exposed to secondhand smoke and smokers. Subsequently, other studies have verified

those results.

Today, incidentally, Dr. Ladenson advises Star Scientific. He is the John Eager Howard

Professor of Endocrinology and Metabolism at Johns Hopkins as well as the director of the

Division of Endocrinology and Metabolism Medicine. I was given access to him for purposesof clarifying and verifying my conclusions. Ill have more on that when I get the time for

him to approve quotes.

We can see other benefits of tobacco by looking at population studies of smokeless

tobacco (ST) users. Decades of data have been collected on the Scandinavian form of ST,

called snus. No evidence has been found of any increase in cancer rates, including mouth

and stomach.

ST users exhibit a number of health benefits, including an approximate 10-year delay

in the onset of Alzheimers disease. This benefit is not found in smokers. Apparently,

inhaling large quantities of smoke is so damaging to the brain, it counteracts tobaccos

AD-delaying benefits.

No health benefits accrue to users of nicotine gum, however. So theres plenty of evidence

to conclude that people are drawn to something else in tobacco than nicotine, apparently as a

form of self-medication. If the active ingredients that satisfied those urges could be included

in a chewing gum, Williams believed that he would have a smoking-cessation aid that could

put big tobacco out of business.

The company started with hard dissolvable ST lozenges made from Virginia tobaccos.

Star Scientific believes it has the lowest level of the tobacco-specific nitrosamines (TSNAs) of

any tobacco product in the world. TSNAs are the source of cured tobaccos toxicity.
http://www.crowtribe.com/emblem.htmhttp://www.crowtribe.com/emblem.htmhttp://www.biopsychiatry.com/maoi-smoke.htmhttp://www.sciencedaily.com/releases/2000/03/000329081250.htmhttp://www.sciencedaily.com/releases/2000/03/000329081250.htmhttp://jcem.endojournals.org/cgi/content/full/jcem;89/12/6077http://www.tobaccoprogram.org/pdf/TC12349.pdfhttp://www.tobaccoprogram.org/pdf/TC12349.pdfhttp://jcem.endojournals.org/cgi/content/full/jcem;89/12/6077http://www.sciencedaily.com/releases/2000/03/000329081250.htmhttp://www.sciencedaily.com/releases/2000/03/000329081250.htmhttp://www.biopsychiatry.com/maoi-smoke.htmhttp://www.crowtribe.com/emblem.htmhttp://www.crowtribe.com/emblem.htm


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People began

talking about

unexpected

improvements

in a range of

inflammation-

related conditions

The Anatabine DiscoveryJonnie Williams also gave top scientists the resources they needed to find out whats

in tobacco that people actually crave. Eventually, he discovered the active ingredient hewas seeking. It is an alkaloid called anatabine found in many other solanaceous plants,including tomatoes.

He then had to learn to synthesize this food-derived nutraceutical so that it was safe forhuman consumption. A nonfood form of anatabine, available through chemical suppliers, ishighly toxic.

When he had accomplished this, the nutraceutical was subjected to extensive toxicitytests by a team of world-class scientists. Williams has attracted truly extraordinary people tohis cause, including Dr. Curtis Wright, his current medical director and senior vice presidentof the wholly owned subsidiary that will develop a drug form of anatabine using the isomerthey have isolated, Rock Creek Pharmaceuticals. Formerly the acting director of the FDAsdivision that covered analgesics, anesthetics and addictive substances, Wright is a leadingexpert on toxicity and regulatory issues.

Even at massive doses, anatabine proved remarkably safe in multiple animal tests. SoStar Scientific then created CiGRX, pronounced cig-ar-ex. CiGRX contains anatabine and

yerba mate, another nutraceutical MAO inhibitor. It is widely available in supplement sectionsof stores today as a natural smoking-cessation aid. People began to use the product, whichlooks and tastes like mint tic tacs.

Soon, users began reporting more-than-successful efforts to quit smoking. People begantalking about unexpected improvements in a range of inflammation-related conditions.Though anecdotal, evidence began to mount.

A different sort of turning point took place when Williams wife developed severethyroid disease. Famously devoted to her, Williams arranged for his wife to be treated byone of the top thyroid specialists in the world, Dr. Patrizio Caturegli. Caturegli studied withinternationally known Italian endocrinologist professor Aldo Pinchera of the University ofPisa. Today, Caturegli is associate professor of pathology, endocrinology and immunology

at Johns Hopkins.

Williams wife had already developed thyroid nodules. At that point, surgery was nec-essary and scheduled 30 days out. Williams told Caturegli about the anatabine supplement.Caturegli suggested that there would be no harm in her trying the product. She did. Thefibrosis reversed and the surgery was canceled. Her condition has continued to improve,and Williams reports that she is completely free of the symptoms of thyroid disease.

Dr. Caturegli told me he is currently arranging human clinic trials of anatabine forthyroid disease with professor Pinchera and the University of Pisa. Italys regulations areless onerous than Americas, so FDA-compliant results will be produced rapidly.

Roskamp InstituteWhen Williams suggested that I see the lab, I had no idea. In fact, we went to theRoskamp Institute, founded by philanthropist Robert Roskamp. Roskamps life itself isinspiring, as is the work of his institute.

When Robert Roskamps emotionally troubled brothers life ended prematurely, he quithis teaching post and set out to design and provide better facilities for emotionally disabledadults. His efforts were extremely successful, resulting in many facilities across America. Inthe process, he became very familiar with the tragedy of Alzheimers disease.

Upon retiring, he sold his holdings and found himself very wealthy. He and his wife


10/12

10

They are renowned

for discovering an

amyloid link to

AD as well as the

so-called Swedish

mutation.

founded the Roskamp Foundation. In 2003, they opened the Roskamp Institute to tacklethe problems of Alzheimers and other disorders of the brain. Based in Sarasota, thisworld-class research facility has laboratories equipped for biochemistry, genomics, proteomicsmass spectrometry, in silico simulations with their own supercomputer and more.

Running the Institute with a staff of more than 50 researchers are two of the worldsleading Alzheimers scientists, Dr. Michael Mullan and Dr. Fiona Crawford. They are renowned

for discovering an amyloid link to AD as well as the so-called Swedish mutation. Thatbreakthrough led to the creation of genetically engineered mice that are critical to theentire field of Alzheimers research.

I personally find the synchronicity involved in the Williams/Roskamp alliance startling.I assumed that Williams had located in Sarasota because of the Roskamp Institute. In fact,hes there because his son and daughter are at the Bollettieri tennis school in Bradenton,near Sarasota. Williams wife heard about Roskamp Institute through a local magazinearticle and suggested to him that he talk to the scientists there about anatabine.

Today, anatabine is a major research focus at Roskamp. Given what I told you earlierabout smokeless tobaccos ability to delay onset of AD, you shouldnt be surprised to learnthat animal studies are extremely promising.

Moreover, Mullan and Crawford have learned a great deal about anatabines mechanismof action. I always feel somewhat guilty for taking time from scientists as important asCrawford and Mullan, but they have been extremely generous in helping me understandwhat theyve learned about anatabine. So finally, were getting to the really good part.Fasten, as they say, your safety belt.

NF-KB (Nuclear Factor Kappa-Light-Chain-Enhancer ofActivated B Cells)

In recent months, Ive written to you often about gene transcription factors. As youknow, transcription factors are the biological command codes that activate the incrediblycomplex genetic program that is our DNA. Transcription is the process by which DNA is

read. This reading of DNA sequences happens faster than the rotation speed of a jetengine and results in a kind of mirror image protein called RNA. RNA is the language thatDNA uses to communicate with the rest of the body. This animation of transcription is helpful

At the molecular level, transcription is so complex that nothing else compares. Thesophistication of our genome is simply indescribable; the most advanced electronics arelaughably primitive in comparison. Transcription factors trigger additional transcriptionfactors. Sequences of DNA are turned on or off, depending on the sequence of the program,leading to precise changes in the cell. The result can be as simple as a response to a changein temperature or one cell changing into an entirely different type of cell.

One transcription factor has particularly interested scientists. It is NF-KB. PronouncedN F kappa B, it is shorthand for nuclear factor kappa-light-chain-enhancer of activated

B cells. You dont have to know that. What you should know, however, is that NF-KB is asort of primary master transcription factor for the immune response system.

Unlike most gene transcription factors, it doesnt have to be synthesized. NF-KB exists inalmost all human and animal cell types. It acts as a first responder, always on call and readyto mount an immune response if needed. Unfortunately, it can also mount that responsewhen its not needed.

Remember, almost none of those who contributed to your genetic makeup, yourancestors, lived past the age of 30. Survival past that age was not selected for genetically.Its possible to live a lot longer now, but this new longevity has existed for only the last few
http://www.rfdn.org/index.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/1302033?dopt=Abstracthttp://www.youtube.com/watch?v=ztPkv7wc3yUhttp://www.youtube.com/watch?v=ztPkv7wc3yUhttp://www.ncbi.nlm.nih.gov/pubmed/1302033?dopt=Abstracthttp://www.rfdn.org/index.html


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Thanks to

Roskamp labs,

that anatabine

moderates these

excess NF-KBs.

This is nearly

miraculous.

hundred years or so. Thats a blip on the clock of human existence. Being old is an aberration,historically and biologically. As a result, were not very good at it.

Its now clear that inflammaging is an autoimmune disorder caused when the immuneregulatory system interprets the effects of aging as injury. Therefore, the very condition ofbeing old provokes NF-KB activation, initiating an immune response to injury.

Injuries and disease require immediate response, and thats what NF-KB facilitates. Ifyou dont have an actual injury or disease, however, the NF-KB creates all manner of havocon the cellular level. For more on this, you might read the Finnish study titled Activationof Innate Immunity System During Aging: NF-KB Signaling Is the Molecular Culprit ofInflamm-Aging. The abstract and outline arehere.

So when inflammaging occurs due to wrongly deployed NF-KB, we see importantindicators of inflammation. These includes CRPs, tumor necrosis factors and Interleukin-1betas (IL-1).

Now we know, thanks to Roskamp labs, that anatabine moderates these excess NF-KBs.This is nearly miraculous. This is as far upstream in the inflammation regulatory system asyou can go. Scientists have been going after things downstream like CRPs, IL-1s and MAOs,but this is always hazardous. It creates unexpected problems and can throw the entire regu-

latory axis out of balance. Anatabine doesnt work like that. It simply calms NF-KB activity sothe inflammation doesnt lead to increased CRP, IL-1and other inflammatory actors.

Look closely at the following chart published by Roskamp. It shows the impact ofanatabine and Lipitor on mice given an inflammation-inducing substance, LPS-1. This is alipopolysaccharide that is found in bacterial cell walls and provokes a strong inflammatoryimmune response in animals.

The chart shows IL-1 levels, which are a more important indicator of inflammationthan CRPs. This chart clearly shows that anatabine, labeled by its laboratory designationRCP, is far more effective than Lipitor. At the right dose, anatabine appears to shut downinflammation completely:

3500

3000

2500

2000

1500

1000

500

0

CTRL1

LPS10ug/ml-1

RCP200ug-1

RCP200ug+LPS-1

RCP400ug-1

RCP400ug+LPS-1

RCP600ug-1

RCP600ug+LPS-1

RCP1000ug-1

CP10000ug+LPS-1

lipitor-10um-1

lipitor-10um+lps-1

IL1beta pg/ml+/-SD whole blood
http://www.sciencedirect.com/science?_ob=ArticleURL_udi=B6X1H-4PPMXJW-1_user=10_coverDate=04%2F30%2F2008_rdoc=1_fmt=high_orig=gateway_origin=gateway_sort=d_docanchor==c_acct=C000050221_version=1_urlVersion=0_userid=10=df2264d08b72a7b1d36e0501c216dc5a=ahttp://www.sciencedirect.com/science?_ob=ArticleURL_udi=B6X1H-4PPMXJW-1_user=10_coverDate=04%2F30%2F2008_rdoc=1_fmt=high_orig=gateway_origin=gateway_sort=d_docanchor==c_acct=C000050221_version=1_urlVersion=0_userid=10=df2264d08b72a7b1d36e0501c216dc5a=a


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Because this is a nutraceutical, many people are already taking it. Both Ray Blanco andI are using it, as is everybody I know who has anything to do with Star Scientific. Anecdotalevidence is not double-blind science, but the sheer volume and consistency of personalreports is overwhelming. The fact that so much is coming from scientists is also significant.Im not going to give you specifics at this time, but I will say that I cannot imagine doingwithout this nutraceutical after having taken it for only six weeks.

Moreover, I spoke with Dr. Dale Wilson of the McLaren Regional Medical Center,who is organizing a major blinded study to take place in Flint, Mich. CRP data from thisstudy will be available in a few months. Roskamp is also in the process of organizing anAlzheimers test.

Dr. Wilson also pointed out to me that NF-KBs are involved in apoptosis, programmedcell death. This means that, theoretically, anatabine may increase the life of healthy cellsand prevent the cell immortality that occurs in cancer cells.

One of the most exciting things about anatabine is its potential role as a telomereprotector. Studies are under way right now, and Ill go back to Roskamp to view theresults soon.

I am struck, incidentally, by the timing of this technologys emergence only monthsafter BioTimes launch of a subsidiary to provide truly rejuvenative therapy for the cardio-vascular and immune systems. For many who might not live to acquire those upgrades,I believe this simple, inexpensive nutraceutical could buy you the time you need. I alsobelieve stock in this company could provide the funds to pay for the procedure.

Incidentally, the U.S. Patent Office has just confirmed Williams safer tobacco curingpatents, now owned by Star Scientific. His application has been confirmed a year earlierthan Reynolds. This clears the way for the company to go after billions in past royaltiesfrom the many tobacco companies that currently use Williams technology. I so wish I wereallowed to buy the stocks I recommend.

Williams legal victory in the patent arena highlights another important point about Star

Scientific. Having taken on big tobacco, he may be the most lawyered up man in America.His legal team is as good as they get, and hes patented every conceivable nutraceutical useof anatabine. One of the most interesting is use in conjunction with spinal cord injuries. Itsbeen known for some time that suppressing NF-KB activity after an injury promotes neuralhealing. Moreover, there are significant trade secrets and patents regarding the process of

making the food grade that belong to Star Scientific.

Its not yet clear to me how disruptive this technology will be to the existing pharma-ceutical industry. Reducing inflammation will certainly delay onset of many serious illnesses.Its not obvious, though, that it will actually prevent those illnesses from re-emerging whenwere much, much older and closer to our Hayflick limits. This is one of the many questions

Im going to try to answer in the months to come.
http://phx.corporate-ir.net/phoenix.zhtml?c=105863&p=irol-newsArticle&ID=1538610&highlight=http://phx.corporate-ir.net/phoenix.zhtml?c=105863&p=irol-newsArticle&ID=1538610&highlight=http://phx.corporate-ir.net/phoenix.zhtml?c=105863&p=irol-newsArticle&ID=1538610&highlight=http://phx.corporate-ir.net/phoenix.zhtml?c=105863&p=irol-newsArticle&ID=1538610&highlight=

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