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Biotechnology and Society---Part
XII
Ongoing DNA revoltuion
Intellectuals solve problems. Geniuses prevent them.
---Albert Einstein (1879-1955), scientist, philosopher
Although several scientists in
reputed academic institutions performed controlled genetic engineering
experiments in their laboratories safely and with the expected results, many of
them thought that discretion should prevail before the experiments took on a
commercial application. Any scientific finding is worth only when there is a
benefit to humanity. This field of genetic engineering held immense promise for
medicine, agriculture and industry. However, regulations need to be in place so
that any commercial work can be carried out safely without any deleterious
effects on current or future population as well as the environment and to make
sure that the technology does not fall into the hands of miscreants to the
detriment of society.
Asilomar Conference: In 1972,
Paul Berg, a Stanford University biochemist, used the new restriction enzymes
(see the previous article in this series - part XI) and joined together DNA
fragments from a monkey virus into the common gut bacterium E. coli in the first
successful recombinant DNA experiment. The following year, the safety of such
experiments was discussed in a conference. The conference leaders decided to
request the National Academy of Sciences to appoint a study committee to examine
such recombinant DNA experiments.
Paul Berg was duly appointed as
the chair of the committee and he asked for a temporary moratorium on certain
types of research and called for an international conference to discuss
potential problems. In February 1975 such a conference, now known as the
Asilomar Conference, was held in Asilomar, California. Guidelines with respect
to physical and biological containment were drawn at that conference to
effectively self-police the scientist community doing such research. It was a
landmark event in the history of recombinant DNA. Subsequently, the National
Institutes of Health, the funding agency for life science research in the US and
elsewhere, developed its own guidelines modelled on those of Asilomar
Conference. These guidelines, tempered by further research in progress, have
remained the touchstone for researchers in the genetic engineering field.
In the meantime, an important
discovery was made by Howard Temin (University of Wisconsin) and David Baltimore
(Massachusetts Institute of Technology) which disclosed the presence of an
enzyme called reverse transcriptase which enabled some RNA viruses (also known
as retroviruses of which the HIV virus is a member) to make DNA copies of their
own RNAs. The viral DNA would then integrate with the nucleus of the host cell
which then transformed into a cancer cell. This discovery would have important
repercussions in cancer research and also in AIDS research. In addition, this
discovery demolished the essential premise of the central dogma of molecular
biology which stated ‘DNA makes RNA makes protein’. Now it is possible that
RNA is equally capable of making DNA with the help of reverse transcriptase. In
the 1980s, it was discovered that the human immunodeficiency virus (HIV) invaded
the immune cells using its RNA and reverse transcriptase thereby causing the
wasting disease. This led to the design of inhibitors of reverse transcriptase
to arrest the process of HIV propagation, which is now a standard drug cocktail
known as protease inhibitors for HIV patients.
The breakthrough: In 1972,
Stanley Cohen of Stanford University and Herbert Boyer of University of
California, San Francisco, used a specific restriction enzyme called Eco R1
(discovered by Boyer in 1970) and the enzyme DNA ligase to make engineered
plasmids capable of producing foreign proteins in bacteria. By 1973 they
produced their first recombinant plasmids which involved taking a plasmid from a
bacterium, cutting it at a specific site with the restriction enzyme, and
inserting a gene for a foreign protein using the same technique and then fusing
the foreign gene and the plasmid together using DNA ligase.
The year 1975 also saw the
development of methodology to determine the sequence of DNA (the order in which
the bases A, T, G, and C, are strung together) in a quick and easy way,
replacing the laborious and time-consuming methods of the past. This was another
milestone that hastened the progress in genetic engineering.
The next big breakthrough in
the recombinant DNA field occurred in the 1980s. That was the polymerase chain
reaction (PCR). It was first reported in 1985 by Kary Mullis and his colleagues
at a company called Cetus Corporation, which was the world’s first
biotechnology company. This technique, using a heat-stable enzyme called DNA
polymerase, enabled scientists to replicate a selected segment or segments of
DNA. PCR is a Nobel-prize winning DNA amplification technology that allows
minute quantities of genetic material to be amplified into billions of copies in
just a few hours, facilitating, for example, detection of the DNA or RNA of
disease-causing organisms in a short time. It has enabled many significant
advances in the Human Genome Project, DNA fingerprinting (in forensic cases) and
in the diagnosis of diseases such as AIDS and hepatitis.
By
the end of the 1980s all the abovementioned techniques had been highly
automated, enabling quick progress in genomic research. The stage was
thus set for commercialisation of genetic engineering and development
of biotechnology as an industry to make useful pharmaceutical products
for mankind.
Let us take a look at the
business side of biotechnology in the next article. Here is a list of
achievements and timelines in the development of biotechnology:
Significant milestones in
biotechnology in the last 50 years:
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1953: Double helix structure of DNA was first described by Watson and Crick.
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1973: Cohen and Boyer develop genetic engineering techniques to “cut & paste” segments of DNA and reproduce (clone) the new DNA in bacteria.
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1976: The first working synthetic gene was developed.
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1977: The first human protein (somatostatin) was produced in a bacterium
(E.coli).
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1978: Human insulin was produced in bacterium.
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1980: First major patent issued by the US Patent Office in the Recombinant DNA technology field.
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1982: Recombinant human insulin (the first biopharmaceutical protein) was marketed.
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1983: Polymerase chain reaction (PCR) technique was conceived. It will become a major
means of copying genes and gene fragments.
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1985: Human growth hormone produced in bacterium was marketed to treat growth deficiency in children.
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1990: Human Genome Project (HGP), an international effort to map all the genes in the human cell, was launched.
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1994: BRCA1, the first breast cancer susceptibility gene, was discovered.
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1995: The first full gene sequence of a living organism was completed for the bacterium, Haemophilus
influenzae.
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2000: First draft of human genome sequence was completed.
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2003: The final sequence of the human genome was produced.
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