by Jim Watson
Cold Spring Harbor Laboratory
United States
Never postpone experiments that
have clearly defined future benefits
for fear of dangers that cannot be
quantified. We can react rationally
only to real, not to hypothetical, risks.

When Francis Crick and I brainstormed the concept of the Double Helix in Cambridge's Cavendish Laboratory in 1953, I was in my mid 20s but had already known since 1946 what my life's work was to be. That year, at the University of Chicago, I decided my life's principal objective would be the genes along chromosomes that provide the instruction books for all forms of life.

Genes today too often get a bad press. This is not surprising because there are 'bad' genes as well as 'good' ones, and bad news grips readers more than good news. Bad genes are actually mutated good genes that, because of altered DNA messages, do not function normally. One particularly bad gene leads to Huntington's disease, which progressively destroys key nerve cells.

Until recently, there was no way to isolate and characterise bad genes. They were known only for their consequence disease. Now we have powerful new ways for studying DNA, which are releasing a flood of new information about the faulty genes implicated in virtually every major human disease: cancer, diabetes, asthma, etc.

With almost routine ways now available to test DNA samples for the presence of specific mutant genes there is increased anxiety that a person's genetic heritage may become vulnerable to unwanted prying. The DNA from a single hair may be enough to alert a prospective employer or insurer to a genetic predisposition to disease. We need broad privacy laws to prevent genetic tests without the informed consent of the person. Even so, dilemmas will arise when people fail to grasp the potential significance of such test results. They can warn but not cure. Who wants to know for sure they will contract a disease for which there is no cure?

Banishing genetic disability must therefore be our primary concern. We would not worry about testing for a predisposing gene for Alzheimer's disease if we had the cure. Such a test might allow drug therapy to begin before brain function is irreversibly diminished. The recent discovery of several genes whose malfunctioning leads to Alzheimer's disease offers the drug industry exciting new leads. We may never, however, be able to control even a majority of serious genetic diseases. All too many are likely to prove intractable to drug therapy as well as somatic to gene therapy, in which good genes are introduced into adult cells to compensate for bad ones. It may be particularly difficult to compensate for genes that malfunction during foetal development. If key genes controlling the networking of brain cells fail to come into action in the womb, no conceivable therapy is likely to rewire the brain later.

Illustration by John McFaul – depicts a
foreground figure symbolising all of
humanity and a background figure
representing the caring role of
medical science. A virtuous circle is
created by the intelligence of mankind
feeding the innovations of medical
science. The creative spark that
solves problems is portrayed by a
light bulb and the image radiates
enterprise.

Controversial
So should steps be taken to prevent the birth of genetically impaired children? This remains a very controversial topic. Many people are opposed for religious reasons to attempt to control the genetic destinies of children. Others, for political reasons, have an abhorrence of gene-based decisions.

But I strongly favour controlling our children's genetic destinies. Why should the lives of some families be dominated by the horrors of genetic disease? As a biologist, I know that such people are victims of unlucky throws of the genetic dice. Mutation has been – and always will be – an essential fact of life. It is through mistakes in gene replication that the positive genetic variants arise – the lifeblood of evolution. If gene copying were a perfect process life as we know it would never have come about. Genetic disease is the price we pay for the extraordinary process of evolution.

Working intelligently and wisely to see that good genes – not bad ones – dominate as many lives as possible is the truly moral way for us to proceed. Yet today our concept of the Double Helix, initially admired for its intellectual simplicity, is still seen by a large faction of the world's population as a double-edged sword. No sooner had scientists at Stanford University in 1973 begun rearranging DNA molecules in test tubes and reinserting the novel DNA segments back into living cells, than critics began likening these ‘recombinant-DNA’ procedures to the physicists’ power to break apart atoms. Might not some of the rearranged DNA molecules impart disease-causing capacity to their host cells? Soon there were cries from scientists as well as non-scientists that such research might best be ruled by stringent regulation – if not laws.

Science delayed
As a result, several years were to pass before the full power of recombinant-DNA technology – ‘genetic engineering’ – got into the hands of working scientists. By then they were itching to explore previously unattainable secrets of life, like the bad genes behind cancer. Happily, the proposals to control recombinant-DNA research through legislation never got close to enactment in the US or the UK. And when the doomsday scenarios failed to materialise, even the modestly restrictive government regulations began to wither away. To my knowledge, not one illness, much less fatality, has been caused by a genetically manipulated organism.

The moral I draw from this painful episode is this: Never postpone experiments that have clearly defined future benefits for fear of dangers that cannot be quantified. We can react rationally only to real, not to hypothetical, risks.

Most forms of DNA manipulation are now effectively unregulated. But one important potential goal remains blocked. Experiments aimed at learning how to insert functional genetic material into human germ cells – sperm and eggs – remain off limits for most of the world’s scientists. No governmental body wants to take responsibility for initiating steps that might help redirect the course of future human evolution.

These decisions reflect widespread concerns that we, as humans, may not have the wisdom to modify the most precious of all human treasures – our chromosomal instruction books. Dare we be entrusted with improving upon the results of several million years of Darwinian natural selection? Are human germ cells Rubicons that geneticists may never cross?

‘I say no’
Unlike many of my peers, I am reluctant to accept such reasoning. I believe one should never put off doing something useful for fear of evil that may never arrive . The first germ-line gene manipulations are unlikely to be attempted for frivolous reasons. Nor does the state of today’s science provide the knowledge that would be needed to generate ‘superpersons’ whose far-ranging talents would make those who are genetically unmodified feel redundant and unwanted. Such creations will remain denizens of science fiction, not the real world, far into the future.

When such experiments are eventually attempted, it will probably be to try to change a death sentence into a life verdict. For example, it might be tried to create children who are resistant to a deadly virus. This has already been done with plants.

Moving forward will not be for the faint of heart. But if this century witnesses failure, let it be because our science is not yet up to the job, and not because we don't have the courage to try to make less random the sometimes most unfair courses of human evolution.