Biotechnology and Biomedicine: Global Perspective

Gundu H. R. Rao, Emeritus ProfessorLaboratory Medicine and Pathology, Anesthesiology,

Lillehei Heart Institute, Institute For Engineering Medicine, University of Minnesota, Minneapolis,

Minnesota USA. gundurao9@gmail.com

Biotechnology and Biomedicine: Global PerspectiveBiotechnology is vast discipline, where integrated technology derived

from biological sources is applied for the development of various useful consumer products.

Biotechnology applications include, to name a few, agriculture, food and beverage processing, forestry, environment, animal science, and medicine.

Some biotechnologies have been in use for thousands of years: For example, every living organism is a biotechnology factory.

Selected breeding of crops and animals. Foods and beverages using microorganisms in nature: yogurt, bread, wine, beer etc.

Some of the later BT developments include: Fermentations-antibiotics, enzymes, amino acids, vitamins, poly-saccharides, gums, high fructose syrups, vaccines.

Biomedical Sciences on the other hand covers a wide range of subjects from molecules to microbes to medicine, from body systems to medical devices, and from human genome to health issues.

Global Biotechnology CompaniesThere are more than 3000 BT companies worldwide.

However, reliable sources indicate that only about 100 out of these are commercially viable.

Over 70% of these BT companies are US Companies.Based on the revenues generated, only one from China

and one from India are listed in the top 100 BT companies in Wikipedia.

The annual revenues generated by BT companies range from few millions to over 15,000 million (Genzyme, USA).

Biotechnology Industry is capital intensive. Like Pharmaceutical Industry, needs cGLP and cGMP facilities to develop products for the Global Market.

India’s Achievements in BiotechnologyPost independent achievements include in the area of animal

sciences, agriculture sciences, medical sciences and Industry.Scientific developments of dairy industry resulted in

increased production of dairy products ( Number One Milk Producer)

Scientific developments in Agriculture resulted in improved sugar cane production ( Number One in Sugar production) as well as production of Potatoes (Number two in the World).

Industrial application of BT included production of antibiotics, vaccines (60% of Global Vaccine), enzymes and fermentation products (Ethanol: Number four in the World).

Indian Vaccines are exported to 151 countries across Globe.Pharmaceutical Industry is 3rd largest. Herbal Products

revenue is greater than a billion dollars.

India’s Achievements in BiotechnologyPriority areas in BT application include: Basic Biology,

biomedicine, bio-agriculture, bio-animal science, biodiversity, bioenvironmental technologies, bio-safety.

Government of India has established a Bio-tech park in Lucknow and has approved the development of such parks in Karnataka, Gujarat, Himachal Pradesh, Andhra Pradesh, and Kerala.

UP is the home for 70% of the livestock population in the country

In view of this importance the Institute of Human Genetics in the Electronic City, Bangalore is studying the water buffalo genomics under the leadership of Prof Sharath Chandra.

India’s Achievement in BiotechnologyVarious National Laboratories contributed to the

success of Biotechnology in India.National Dairy Institute, Karnal, Haryana

(Original Imperial Institute of Animal Husbandry and Dairying at Bangalore, 1923)

Indian Sugarcane Committee, Lucknow (1952) later Govt. of India took it over.

Potato Research Institute, Patna (1949) moved to Simla(1956)

Serum Research Institute of India, Pune (privately owned)

Biotechnology: Global (US) PerspectiveIn the list of top 100 companies listed in Wikipedia more

than 70% are US Companies.There are over 2000 BT companies in the USA and they

offer employment to over 60% of the worldwide workforce.Bioscience research and development is valued at 50

Billion in annual revenues.There are more than 5.5 million scientists, engineers and

technicians supporting this platform.Implementing this technology in the USA has resulted in

the generation of over 110 billion dollars for the year 2010.The total estimated revenue of all sources of Biosciences

exceeds 300 billion dollars this year in the USA.

Biotechnology Parks (Clusters)Directory of Biotek parks developed by Argos

Biotech list only 50 parks worldwide.The only park listed from India, is the Biotech Park

in Lucknow.William Hoffman’s Map of the Bio-clusters of the

World list only three sites in India, Biocon, Bangalore; Shantha Biotech, Hyderabad and an unknown site in New Delhi.

This world map of biotech clusters does not list the park in Lucknow or the one in Pune.

Biotech ClustersConceptually, the Biotech Clusters are, “geographic centers

of competing, complementary, or independent firms and industries that do business with each other and/or have common needs for talent, technology, funds and infrastructure”

Critical factors for cluster development include: strong science base, entrepreneurial culture, growing company base, ability to attract key staff, availability of finance, premises and infrastructure, business support services, presence of large companies in related areas, skilled workforce, effective networks, and supportive policy environment.

Successful examples in the USA include, San Diego Metropolitan area; Boston, Raleigh-Durham, NC; San Jose, CA and Washington DC.

Biotechnology: Global (China/India) Perspective

Globalization of the economy dictates improvement of science and technology and competition for the world market.

China which was isolated for decades from the rest of the world. Now it has realized the advantages of international scientific collaborations.

China has initiated exchange program with 152 countries and signed M o U with 96 countries.

China has 150 drugs in Clinical Trials. They have developed 20 Bio-Parks and 500 Bio-enterprises and 300 Biomedicine facilities.

India has only 1.5% of the share of over 2000 clinical Trials, although it has over 8000 drug manufacturing units and is the 3rd largest producer of generic drugs.

India, which is also competing for the Global Market has 340 biotech companies, of which 180 are in Bangalore.

Biotechnology: India PerspectiveDepartment of Biotechnology, Government of India

describes the BT growth in India as follows: “The Indian biotechnology sector has, over the past decades, taken shape through a number of scattered and sporadic academic and industrial initiatives”.

Successful Biotech companies with significant revenues in India are all privately owned by entrepreneurs: Biocon, Bangalore; Shantha Biotech, Hyderabad; Glandpharma, Hyderabad; Dr Reddy’s Laboratory, Hyderabad; Serum Research Institute of India, Pune.

DBT admits that the time is now ripe, to integrate these efforts through a pragmatic National Biotechnology Development Strategy like China.

Contributions of Modern Medicine : Genetics The Chicken Genome Sequencing Consortium is working

on sequencing Chicken genome for the improvement of poultry products.

University of Illinois has received a USD 10 million grant for sequencing swine genome, to improve pork products.

Institute of Human Genetics in Bangalore, has received several million dollars worth of funds for sequencing buffalo genome to improve dairy products.

Researchers have developed ‘biotech pigs’ that produce high levels of Omega 3 fatty acids, by inserting the “fat-1” gene that increases the levels of this fatty acid.

Omega 3 fatty acid-rich eggs are already available in the USA

Biotechnology and BiomedicineMedical Biotechnology is the largest component of

BiotechnologyKey products include; biological drugs, vaccines, in-vitro

diagnostics, Bio-markers and molecular markers, rDNA and cDNA applications.

Biotechnology derived medicines are valued at over 70 billion dollars.

Just a list of medical products developed by one company, Genentech, USA, indicates the significance of this sector: Bio-Oncology: Avastin for metastatic colo-rectal cancer, Herceptin for HER-2 positive cancer, Rituxan, for non-Hodgkin's lymphoma, Xolair for persistent asthma, Activase for heart attack and stroke, TNKase for the same, Pulmozyme for cystic fibrosis, CathfloActivase for increased blood flow.

Biotechnology: Biomedical EngineeringIn the area of biomedical engineering, cellular and

molecular therapies are gaining importance.Kyoto University researchers have developed engineering

skills to turn skin cells into pluripotent stem cells (iPS cells). These genetically programmed cells behave like embryonic stem cells.

When these programmed cells are transfused to mouse with blood disorders, the transfused cells behave like bone marrow cells and produce normal healthy blood cells.

Cellular Dynamics International (CDI) of Wisconsin has been manufacturing cardiomyocytes for in vitro studies.

Narayana Nethralaya of Bangalore, is testing limbal cell transplantation for the repair of retinal disorders.

Biomedicine: Genomics and Gene EditingApart form the use of engineered cells for cellular and

molecular therapies, there is considerable interest in gene-editing applications for therapeutic purposes.

Researchers have used a novel method of “editing” the genome to treat mice with hemophilia by replacing the defective gene with one that promotes blood clotting.

By engineering different zinc fingers and attaching them to a gene-cutting enzyme, they have created tools that can snip the genome at specific sites and repair the defective target gene

After such a treatment, the mice with hemophilia produced enough of blood clotting protein to speed clotting process.

Biomedicine: Tissue Engineering ApplicationsAt Center of Cardiovascular Repair, University of

Minnesota, Prof Doris Taylor and associates have created bio-artificial hearts using a novel approach.

Pig or Rat hearts are chemically stripped of all the cells and the extracellular matrix is used as scaffold for tissue engineering using isolated cardiomyocytes in a bio-reactor providing needed cues like pressure and electrical stimulus.

Genzyme of Cambridge, MA and Medtronic Inc of Minnesota, have a huge federal grant for the development of an ongoing phase-2 clinical trial investigating the use of cell therapy to repair damaged heart.

Biomedicine: Bio-artificial OrgansAnother approach to address problems associated with

organ transplantation is to develop bio-artificial organs.Researchers at the University of Minnesota have been

working on such projects for several decades.A bio-engineering company from Minnesota (Excorp

Medical Inc) has developed a bio-artificial liver using genetically engineered pig liver cells. The device has been approved as an orphan device by the US FDA.

An Indian Company based in Hyderabad has acquired the rights to manufacture these in India. Basically pig liver cells are cultured on a disposable scaffold and used similar to kidney dialysis, to assist the sick liver to recover.

Biomedicine: Use of mRNA, rRNA, rDNA etc.Vascular diseases including Heart disease are triggered by

inflammation of the vessel wall.MIT researchers have developed techniques to curb inflammation

by using interference mRNA technology, which disrupts the flow of genetic information from the cells nucleus to protein-building machinery.

In an animal model they delivered strands of mRNA that turns down the inflammatory response by blocking activity of a specific gene in white blood cells called monocytes.

Packaged in nano-particles made from liposome or lipoids, the micro RNA successfully reduced inflammation in a mice model.

The RNA snippets targeted CCR2 receptor, a protein on the surface of cells, mice treated with this type of micro RNA showed much lower levels of inflammation in atherosclerosis, cancer and faster recovery from heart attack.

Biomedical Technology: Cutting-Edge ResearchBiomedicine today is a multidisciplinary specialtyScripps Research Institute, CA researchers have

developed a method for predicting acute vascular events by monitoring the circulating endothelial cells in the blood.

According to them, the number of circulating endothelial cells four times greater in patients with heart attacks than healthy individuals.

They used flow cytometer to follow the circulating cells as well as to follow the morphology of these cells.

Similar studies with appropriate biomarkers can be used to monitor “at risk” patients for developing acute vascular events.

Biomedicine: Lab on a CHIP ApproachPharmacology on a CHIP was the dream of PharmacologistsMIT scientists have developed MicroCHIPS that are under

clinical trial for the treatment of osteoporosis. The CHIP senses the need for the drug and delivers a controlled level of the drug Tetraparatide.

The MiniMed Paradigm, REAL-Time Revel System of Medtronic Inc, Minnesota combines glucose sensor with an insulin pump to achieve controlled drug delivery.

Brain-computer Interface Team at Singapore has developed a brain-computer interface, that offers hope for stroke rehabilitation by nearly rewiring their damaged nerves in the brain (Hand-held stimulators for pain control are available).

Biomedicine: Future Directions

Introduction of the “Pill Camera”, a small oral capsule that can video-record the images of gastrointestinal tract ushered new era in biomedical imaging.

MIT researchers are now taking this concept much further by giving the capsule greater capabilities like treading for movement and remote control for manipulations. Such modification will open the door for advanced robotic surgical procedures.

Developing “nanosensors” patrolling the blood stream for detecting the first sign of an imminent acute vascular event like heart attack or stroke, capable of releasing anti-clotting or anti-platelet or anti-inflammatory drugs to stop it, would revolutionize the areas of biomedicine and biomedical technology.