The Eccentric Engineer
Justin Pollard
Genetic engineering gets a bad press with talk of 'playing God' and 'Frankenstein foods'. But in
truth this had always been an area of engineering where precautionary principle has held sway
that, in the absence of scientific consensus, the burden of proof lies in showing that an intended
action is not harmful. This is largely thanks to one man.
In early 1971 Paul Berg and his team at Stanford University in California were working at the very
edges of biological science. Following the pioneering work of Crick and Watson identifying the DNA
helix, they were now looking at ways of splicing together sections of DNA from different organisms
and then using a virus to inject the resulting genome into a living cell- a technique known today
as Recombinant DNA (rDNA). This held out the prospect of identifying the effects of genes and
perhaps later taking particular beneficial genes from one creature and inserting them into another.
During the 1960s a lot of work had been done using the bacterium every handwash manufacturer
loves to hate, E. Coli, and the virus 'lambda' which infects it. What had not been attempted was
expanding this research into studying mammalian cells and the viruses that might be used to insert
new genetic material into them. In the early 1970s, Berg wondered whether it might be possible to
use the Simian Virus 40 (SV40) to carry novel DNA sequences into mammalian cells.
The problem with SV40 was that it was tiny- only 5000 base pairs long, encoding just five
genes- so he realised he would have to tinker with it to enable it to pick up other genes and
carry them into a living cell. To achieve this he decided to try to splice together SV40 DNA with
a DNA fragment that could replicate independently a cell's genome (a plasmid) constructed
from his old friend the lambda virus and three E. Coli genes. This recombinant DNA would then
be inserted into living E. Coli cells.
Explaining this development to other pioneering genetic engineers at the Cold Spring Harbor
Laboratory Tumor Virus Workshop, Long Island, in 1971, Berg's research assistant Janet Metz
gained a reaction she was perhaps not expecting. Microbiologist Robert Pollack observed that the
agent they were using, SV40, was a tumour-causing virus, which they had now given the ability to
splice itself into the genome of E. Coli. E. Coli was, in turn, a very common bacterium resident in the
human intestine. In an urgent call to Berg, Pollack asked: 'What if the E. Coli in your lab escaped into
the environment and into people? It would be a real disaster if one of the agents now being handled
in research should in fact be a real human cancer agent.' Could they have created a Frankenstein
bacterium- a common human parasite now with the deadly ability to spread a cancer plague?
The deadly possibilities of recombinant DNA had suddenly become clear: so what was to be
done? Concerned that Pollack was over-reacting, Berg canvassed more opinion. Many argued
that the work was so vital that risks were worthwhile, others that it was a matter of ethics. One
group claimed that the technique posed no particular threat and that 'over-regulating' research
would be more dangerous.
It was a delicate situation. The first steps of Berg's work had been completed; the rDNA had
been painstakingly created. All that remained was to insert it into a living cell. But what would
result? A miracle or a monster or just something interesting in between? With the certainty that
executing the last step in the experiment would be Nobel-worthy stuff, many would have carried
on regardless, leaving the theoretical problems for others, but Berg chose not to. On 26 July
1974 he published an open letter in Science calling for a voluntary moratorium on some areas
of rDNA research (including his own) until the risks were better understood.
This was followed up the next year at the Conference on Biohazards in Biological Research.
Here genetic engineers openly discussed the possible outcomes of their research, bringing the
subject to public and government attention and leading to the laying down of strict guidelines
on the creation and use of rDNA. In the meantime another team had successfully spliced a
gene from a toad into an E. Coli bacterium, effectively stealing Berg's thunder.
But Berg's insistence on being an ethical engineer did bear fruit, ushering in a new era of
openness in science. Far from restricting research, it also brought the ideas and terminology of
genetic engineering into the public domain where they belong.
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