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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.

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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.

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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:

  • 1953: Double helix structure of DNA was first described by Watson and Crick.

  • 1973: Cohen and Boyer develop genetic engineering techniques to “cut & paste” segments of DNA and reproduce (clone) the new DNA in bacteria.

  • 1976: The first working synthetic gene was developed.

  • 1977: The first human protein (somatostatin) was produced in a bacterium (E.coli).

  • 1978: Human insulin was produced in bacterium.

  • 1980: First major patent issued by the US Patent Office in the Recombinant DNA technology field.

  • 1982: Recombinant human insulin (the first biopharmaceutical protein) was marketed.

  • 1983: Polymerase chain reaction (PCR) technique was conceived. It will become a major means of  copying genes and gene fragments.

  • 1985: Human growth hormone produced in bacterium was marketed to treat growth deficiency in children.

  • 1990: Human Genome Project (HGP), an international effort to map all the genes in the human cell, was launched.

  • 1994: BRCA1, the first breast cancer susceptibility gene, was discovered.

  • 1995: The first full gene sequence of a living organism was completed for the bacterium, Haemophilus influenzae.

  • 2000: First draft of human genome sequence was completed.

  • 2003: The final sequence of the human genome was produced.

Published on 31st Dec, 2003

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