Who will benefit from the human genome?

Comments by Dr Richard Nicholson for CAHGE Press Briefing, 14 June 2000

Mapping the human genome is a great human achievement, rather like climbing Mount Everest. Like climbing Mount Everest, it will benefit few people, leaving most untouched. But unlike climbing Mount Everest, it has the potential to damage large numbers of people. So it is important to cut through the exaggerated expectations and to assess the probable benefits and costs.

Benefits should arise through eventual identification of the tens of thousands of genes in the whole genome. As genes are identified they can be used for:

gene therapy
tailor made pharmaceutical products
predictive testing, either antenatally or later
to improve the understanding of disease mechanisms.

These possible benefits must be assessed, however, in the context of what medicine has actually achieved. Of 32 years improvement in life expectancy in the 20th century, just 10% was the result of advanced medical care (and half of that was due to childhood immunisation). Most of our good health - and being one of the rich countries of the world, we are one of the healthiest - has come from environmental improvements: clean water, modern sewage disposal, better housing and so on. Yet we spend 50 times as much per head of population on health care as is spent on the 5 billion people living outside OECD countries.

One reason for all the hype about the human genome project may be that recent medical research has produced little of value, and medical scientists are desperate for something dramatic. Clinical trials and meta-analyses get ever larger because such small improvements are looked for; many now are only designed to show equivalence: that the new drug is just about as good as what we have already. But virtually no research is done on the major tropical diseases that kill many millions each year: just 1% of the new drugs marketed in the last 25 years are useful in such diseases. And how is it that after 30 years of being fed a weekly diet by the main cancer charities of the latest greatest breakthroughs, there have been only marginal improvements in cancer cure and survival rates?

That medical research achieves so little may be because most is no longer done for the benefit of mankind. Most is now done for personal career advancement or to benefit the shareholders of pharma and biotech companies. This is seen par excellence in the human genome project. In research done for such motives there is no reason to allow the rest of society to keep up. If the research were genuinely intended to benefit humanity, researchers would ensure that those assessing its social and ethical issues, and the general public, could keep up.

Gene therapy: much has been made of the possibilities of curing diseases caused by single abnormal genes. But despite over a decade of hype, the worldwide score for gene therapy is: Cures: 0, Deaths: at least 5, Serious Adverse Events: at least 1,000. Mapping the human genome is unlikely to help gene therapy move beyond being only occasionally effective, in a few rare diseases, at great cost.

Pharmaceutical products: it is claimed that precise knowledge of the proteins coded for by specific genes will allow the creation of drugs more accurately aimed at specific proteins. In diseases caused by a variety of genes, each individual would be tested to see which gene he/she carried, and a precisely tailored drug could then be prescribed. The problem is that most chronic diseases, affecting enough Western people for the pharmaceutical industry to be interested in them, are multifactorial. Not only are several genes involved in the aetiology, but so is the environment. In the case of high blood pressure only about 30% of the disease burden is genetically determined. So it is reasonable to apply the general rule of drug development in pharmacogenetics:

the benefits of a new drug are overestimated before its use,
the risks of a new drug are underestimated before its use, and
the cost is greater than for existing drugs.

Genetic testing: there will be a relatively small number of instances in which testing in adult years will produce results that have an important influence on life decisions. For instance, a positive test for Huntington's Disease presymptomatically might lead to a decision not to have children. There is, however, a widespread assumption among many genetic researchers that, on the whole, people would rather know about their genes than not know. The evidence points the other way: most people prefer to remain in ignorance. A further problem is that even when people have been tested, they may find it difficult to make the lifestyle changes that the test results suggest are necessary, leading to anxiety or fatalism. Most testing will be done antenatally, but the only purpose is either to abort an affected fetus or not to implant an affected embryo, thus leading us ever further down the road to a negative eugenics.