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Biotechnology and Society---Part
XIII
The business of biotechnology
I saw the angel in the marble and carved until I set him free.
---Michelangelo Buonarroti (1475-1564), sculptor, painter
Britain, for a long time, was
known as a “nation of shopkeepers”. The East India Company had a specific
charter to conduct trade and only trade. However, events turned out differently
when they got into political tangles with various kings in India and we all know
how Britain got to colonise India.
We have a different scenario
for biotechnology. Biotechnology started out as a scientific discipline and
remained so for quite some time. But the aim of all science is not just
curiosity alone but to use that knowledge for the benefit of mankind. The US
government supported and still supports basic research in all scientific
disciplines, including biotechnology. However, it takes a different kind of
approach to translate the discoveries into useful products and services for
mankind. That is where the private business comes into play. Like the East India
Company, the charter of the biotechnology industry was to do business and make a
profit in it. But unlike the East India Company, the biotech industry has its
mission concentrated only in business. Let us examine how the modern
biotechnology industry got established.
DNA, the money tree: Let us
refresh our memories on some of the terms that we encounter often. Recombinant
DNA is DNA created in the laboratory. This is DNA from two or more sources
incorporated into a single recombinant molecule. Plasmids are small circular
pieces of DNA containing a few genes usually hosted by yeast and bacteria.
Plasmids are the basis of recombinant DNA technology. Restriction enzymes (also
known as restriction endonucleases) are used to cut DNA specifically at a given
site. DNA ligase is the enzyme used to splice (rejoin) DNA segments from
different sources cut by the restriction enzymes.
As we noted in the previous
article, the process for joining and replicating DNA from different species was
developed during 1973-74. Stanford University applied for a patent on this
invention in the name of Stanley Cohen (Stanford University) and Herbert Boyer
(University of California, San Francisco) in November 1974. The patent, titled,
‘Process for Producing Biologically Functional Molecular Chimeras’, was
issued by the US Patent Office in 1980. The process involved plasmid biology,
bacterial restriction enzymes, splicing, and cloning. The ability to isolate and
amplify any gene or DNA segment and move it with controlled precision to allow
analysis of gene structure and function in various organisms presented a huge
commercial opportunity. Bacteria could be transformed into factories for the
production of drugs.
The very first biotechnology
company, Cetus Corporation, was founded in Emeryville, California, in 1971.
Unfortunately, that company does not exist any more, having been acquired by
Chiron Corporation, in 1991. However, the polymerase chain reaction (PCR) DNA
amplification was done in Cetus Corporation. This invention has the unique
distinction of having been the only one generated in a biotech company that got
the Nobel Prize. The next biotechnology company that made waves and is still a
mighty force today is Genentech, Inc. Genentech was founded in April 1976 by
Herbert Boyer (UCSF) and Robert Swanson (a venture capitalist). It went public
and got listed on the stock exchange in 1980. Since then the biotech industry
has grown by leaps and bounds as innovative ideas yielded life-altering and
life-saving products.
Following Genentech, several
other companies were started mainly around Boston, San Francisco, Los Angeles,
San Diego and Washington DC. Some of them prospered well and are giant companies
now such as Chiron (founded in 1977), Biogen (1978), Amgen (1980),
and Genzyme
(1981). Others fell by the wayside either due to the projects chosen not
materialising or lack of financing or both. Some other companies could not
function independently and got merged with others.
The first biopharmaceutical
product to be marketed was recombinant human insulin developed by Genentech and
licensed to the pharmaceutical company Eli Lilly & Co. In 1985, the FDA
approved the first recombinant pharmaceutical product to be manufactured and
marketed by a biotechnology company: Genentech’s first product, Protropin, a
human growth hormone to treat dwarfism in children.
As of 2003 there were over
1,500 biotechnology companies in the US of which about 450 are publicly traded
(on the stock market) companies. An equal number of companies operate in Europe.
Other countries where the biotechnology industry is present to a significant
extent are Japan, Australia, South Korea, Singapore, China and India. The
products of the industry are not only drugs but also research tools, supplies,
services, and informatics. About 140 biotech products have so far been approved
by the US FDA and another 350 are in late stage clinical trials.
Some of the notable biotech
drugs that are currently marketed include: Activase (for breaking blood clots),
Herceptin (breast cancer), Rituxan (Non-Hodgkin’s lymphoma), Neutropin, and
Humatrope (growth hormone deficiency), Xolair (allergic asthma), Raptiva, and
Amevive (psoriasis), Epogen, and Procrit (for anemia), Neupogen (white cell
growth promoter), Enbrel. Humira, and Remicade (rheumatoid arthritis),
Avonex,
and Betaseron (multiple sclerosis), Intron A (anticancer/antiviral),
Recombivax
(hepatitis B), Proleukin (cancer), Regranex (diabetic foot ulcer),
Synagis
(respiratory synctial virus infection in infants), Flumist (flu vaccine),
Humulin (type I diabetes), Reopro (anti-clotting), Xigris (sepsis), and
Forteo
(osteoporosis).
The top 10 biotech companies
(in the US) by market capitalisation as of November 2003 are: Amgen ($ 78.5
billion), Genentech ($ 41.3 billion), Gilead Sciences ($ 11.5 billion),
Chiron
($ 10.4 billion), Genzyme ($ 10.4 billion), Medimmune ($ 6.6 billion),
Biogen ($
5.6 billion), Applied Biosystems ($ 4.7 billion), Ivax ($ 3.5 billion), and
Celgene ($ 3.2 billion).
In addition, several companies
such as Dupont, Monsanto, Dow Chemical and several other smaller companies are
heavily involved in plant biotechnology. Plant biotechnology deals with genetic
modification of plants to make them drought-resistant, saline-resistant,
cold-tolerant and pest-resistant in cereal grains and cash crops such as wheat,
rice, corn, soybeans and cotton. Attempts are also being made to express
pharmaceutical proteins in plant tissues and seeds in plants such as tobacco and
corn. Transgenic biotechnology using cows, sheep and chicken to express human
therapeutic proteins in milk and egg are also undertaken by several companies (GTC
Biotherapeutics, PPL Therapeutics, Avigen).
Biotechnology industry in
India: India has recognised that in addition to information technology, there is
a tremendous opportunity in the biotechnology area too to get into the global
market. Today, India is home to approximately 150 biotechnology companies, of
which three-quarters started functioning in the last five years. Many of them
are located in or near the two cities in the south, Bangalore and Hyderabad.
Bangalore has the enviable reputation of being billed as ‘The Biotech City’
in India based on the number of biotech companies located there. As is the norm
in the US, these companies flourish around reputed academic centres. The
companies concentrate on contract R&D services, bioinformatics,
biotherapeutics, vaccines, genetically-modified crops, and drug development.
Stem cell research is permitted in India and genetically-modified cotton (to
resist boll weevil, patented by Monsanto Corporation) is approved for commercial
planting.
Perhaps the oldest biotech
company in India is Biocon (Bangalore). In addition to traditional biotechnology
such as fermentation and enzyme production, the company also has subsidiaries
such as Syngene (New Delhi), a contract research firm, and Clingene (Bangalore)
which specialises in clinical trials. A bioinformatics company, Strand Genomics
(Bangalore), designs software for drug discovery. Another bioinformatics
company, Gemeiosys (Chennai), is also involved in contract R&D in the areas
of software development for drug discovery and some clinical trials.
Shantha Biotechnics (Hyderabad)
developed India’s first recombinant hepatitis B vaccine which is certified by
the World Health Organization for use by UN agencies. The company also developed
a recombinant human interferon a-2B, cloned and expressed in the yeast Pichia
pastoris, to treat leukemia and other cancers. There is an attempt to set up a
biotech incubator in Hyderabad to establish itself as a premier biotech centre.
A couple of agro-biotechnology
companies, Avestha Gengraine Technologies (Bangalore), and Metahelix Life
Sciences (Bangalore), are involved in contract plant genomic research and
contract computational biology services for crop improvement, respectively.
India
has the knowledge base and a trained workforce to undertake
biotechnology projects in a big way. However, availability of capital
and the infrastructure for clinical trials, and regulatory controls
are the limiting factors right now which prevent any explosive growth
in the area as opposed to what happened in the IT area. Just like the
generic drug market, India is perhaps waiting to capitalise on the
generic biopharmaceutical market too. At present, the government is
inclined to support agri-biotech research mainly for crop improvement,
a sort of tech-revolution to augment the green revolution of the
1960s.
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