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.

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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?

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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.

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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.

QUESTION 24

Choose the correct letter: A, B, C or D. Write the correct letter in box 24 on your answer sheet.

24. The reading passage highlights which particular aspect of Paul Berg as a scientist?

1. that he was a genetic engineer
2. that he created a new recombinant DNA
3. that he acted in an ethical manner instead of in his own interest
4. that he sought the opinion of other scientists on the possible outcomes of his research.

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QUESTIONS 25-28

Complete the following table outlining various research-related works or programs mentioned in the reading passage, using words and phrases from the box on the next page.
Write the appropriate letters A-H of your answers in boxes 25-28 on your answer sheet.

Year/date	Scientist/ researcher	Research on/work on
25		E. Coli and the virus 'lambda·
	Watson and Crick	DNA helix identified
Early 1970s	Paul Berg and team	26
27	28	Voluntary moratorium on rDNA research

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QUESTIONS 29-32

Label the parts of the diagram illustrating a process described in the reading passage.
Choose your labels from the box below the diagram.
Write your answers in boxes 29-32 on your answer sheet.

The process of forming a recombinant DNA (rDNA)

29	+	30	=	31	>>>>	32

A. The recipient living cell	B. A section of DNA from organism A
C. Injecting virus with genome	D. A section of DNA from organism B
E. Resulting genome within a virus

QUESTIONS 33-35

Choose the correct Letter: A, B, C or D. Write the correct Letter in boxes 33-35 on your answer sheet.

33. There were different responses when Paul Berg asked others how he should proceed with his research using Simian Virus 40 (SV40). Which of the following reactions from other scientists is not mentioned in the text?
    1. it was an ethical issue
    2. to continue his research even if it involved risks because it was an important study
    3. to stop his research as it was dangerous for him to work with cancer-causing agent
    4. to continue his research as there was no specific danger other than getting research too controlled.
34. What did Paul Berg eventually do after creating the new rDNA and after receiving different responses from other scientists?
    1. He continued his work using SV40 as he had planned.
    2. He stopped working as a scientist altogether.
    3. He started publishing articles on scientific topics.
    4. He temporarily stopped his work and asked others working in that area to do the same until the dangers involved in the work were clearer.
35. Which of these was NOT the outcome of what Paul Berg did in regard to his research with SV40?
    1. Genetic engineers openly discussed their research in a science conference.
    2. Genetic engineers wrote open letters in science journals.
    3. Strict rules were made about the making and using of rDNA.
    4. Berg lost a chance to win worldwide recognition for groundbreaking research.

QUESTIONS 36-40

Using information in the reading passage, match each of the items in List A with the related information in List B.
Write appropriate letters in boxes 36-40.

List A	List B
36 E. Coli	A a DNA fragment able to replicate independently
37 SV40	B a bacterium infecting the human body
38 Lambda	C combining two strands of DNA
39 splicing	D a virus infecting a bacterium
40 a plasmid	E a tumour-causing virus