Destiny rides again

All meetings on the human genome include at least one talk, and often an entire session, devoted to discussing the ethical, social and legal aspects of genome research. The questions are always the same. If it is true that we can read the futures of people from their genes, should we be doing genome research? And, if we are going ahead anyway, what will be the consequences for society? Some years ago I compared genomics to astronomy and thought it should be called genonomy. Like astronomy, genonomy is an observational science and mapping genes in the genome is not unlike mapping stars in the heavens. Both activities are similar in that they allow us to look backwards in time and offer possibilities for the reconstruction of the long vanished past — cosmology for the physical world and evolution for biology. It has only recently dawned on me that other parallels may exist as well. Astronomy is a science that generated two different theories about its observations. One, cosmology, deals with esoteric matters, such as the beginning of the universe, black holes and the birth and death of stars. Even if they get things wrong sometimes, the practitioners are constrained by laws of physics. The other theory is astrology, which some people find much more down to earth, and which proposes that the destinies of humans are controlled by the stars, and that events in individuals’ lives can be predicted from the conjunctions of constellations at the times of their birth. I was about to write that genonomers should be careful to avoid creating a genology equivalent to astrology, when I realised that it has already happened. It was called eugenics and was based on the belief that the causes of social illnesses, such as poverty and crime, were to be found in the genes of people, and that the cure for such diseases could be effected by genome eradication. That this could be the case, seemed as plausible to our Victorian predecessors as the theory that the stars controlled our lives must have appeared to early astronomers. Of course, we can argue that genes undoubtedly specify the structure and function of organisms and that stellar determination of our destinies is total nonsense; but in actual fact there could be a connection — day and night, the ebb and flow of tides, and the succession of seasons are all caused by the motions of heavenly bodies and all undoubtedly affect us. Most of the problems in genonomy stem from a relatively new subject called predictive medicine, which is, if you like, the modern form of genology. Although there are genetic diseases for which clear cut predictions can be made from the genome, there are others which can only be probabilistic. While the bad news is that some common complex diseases show 50% concordance in identical twins, this is also the good news, in that there is a huge environmental contribution. The main difficulty in this area is that probability has no meaning for the individual. If you tell the man in the street he has a 60% chance of getting a disease, he will ask you whether he is in the 60% or the 40% class. By contrast, social institutions, such as governments, insurance companies and large corporations, live by probabilities and do not really care about individuals. This is the singular dilemma of human genetic studies: looking at the genes is different from measuring blood pressure or doing urine analysis. These are products of both your genes and the life you have led, whether you have eaten too much or too little, or have been too stressed or too relaxed. But the genes are forever, and the idea that we could cast a ‘somoscope’, and say that the conjunction of a polymorphism in gene 47,384 with allele 8 of marker D-878 makes it likely that you will be both a first class jockey and a concert violinist, is ridiculous in the extreme. And yet some people insist that we could do this and clone such genomes, so that everybody could win the Kentucky Derby while playing a Mozart violin concerto. We also have to deal with the lawyers. In America, where everything is settled by litigation, and increasingly so elsewhere, we can imagine the following situation. A man is denied health insurance, promotion at his work and his wife obtains a divorce on the grounds that his somoscope shows he has a probability of 60% of a heart attack before the age of 45. Following legal advice, he sues his parents for giving him bad genes and exposing him to the terrible life he has to endure. They should have known this, he claims, and taken care of that zygotic event. Had they done so, however, the plaintiff himself would not have been cured of the genetic stigmata; rather, he would be somebody else, and as the law only recognises persons and not genomes there would be no case to meet and the judge should throw the case out of court. Last but not least, we have to remember that the bad genes singled out today were good genes a long time ago when they were selected by nature for our survival. The trouble is that nowadays winter never comes to Southern California. R591