Clinical cures aren't enough

July 26, 2002

Our continuing attack on pathogens is great, says John Sulston in the latest in our series of Big Science Questions, but wouldn't it be better if we just applied the expertise we've acquired so far to help the developing world?

By the standards of some poor communities, the prosperous sector of the world has abolished most disease already. Thanks to developments in public health and antibiotics, in cancer treatment and in heart surgery, we have gone from disease being normal to disease being abnormal. But this is of no comfort to the people who still become ill. Therefore, much effort continues to go into tackling the problem.

Sequencing the human genome has been a striking and hyperbolically reported step forward in this effort. Just as crucial from the point of view of disease is the sequencing of genomes of pathogens (bacteria, viruses and other parasites) and of other animal genomes that will help us to understand our own. From a long-term perspective, the excitement is justified by the fundamental importance of collecting these codes. But what can we expect from them?

Pathogen sequencing will reveal new targets for drug and antibody attack. This will help not only to solve old problems but also to deal with the growing threat of antibiotic-resistant strains that are appearing.

In human genomics, the emphasis is now on analysing people's variants of the code and comparing them with individual health and medical problems. Widespread genetic testing raises issues of privacy and human rights that must be dealt with, but the benefits are great. Interaction of genetic variants with diet and other aspects of lifestyle will become well known, allowing doctors to give people accurate advice. Diagnosis of hereditary disease will become increasingly precise and common as quick and cheap testing methods are developed. So will diagnosis of susceptibility to drug treatments and their side-effects. This means that, at least in critical cases, treatment could be made more efficacious by helping the selection of existing drugs or by the design of new ones. Some feel that, in the early years, these areas of pharmaco-genomics and pharmaco-genetics are likely to have more influence on clinical practice than anything else.

Accurate diagnosis opens the possibility of prenatal selection through implantation or abortion. This will allow serious hereditary disease to be avoided, which in itself is immensely desirable. But we must decide what is allowed, what is desirable and what is abnormal. Society is now grappling with the ethics of embryo choice. On one side, we have people who argue that these activities are wrong under any circumstances. On the other, we have children who are suing their parents for allowing them to be born disabled. As more genetic markers become known, the boundaries of permissible selection will have to be drawn ever more clearly to protect medical practitioners. Some parents will want selection to be very stringent and even extended to traits such as intelligence. Conversely, many disabled people campaign for the absolute rights of the unborn on the understandable ground that under some criteria of normality, they themselves would have been aborted.

Great efforts are going into gene therapy - the replacement of a faulty gene with a good copy. This is difficult because of the problems involved in delivering the healthy gene to the cells that need it and in getting it to work correctly and stably. But it is beginning to work for diseases of the immune system, where cells are relatively accessible to manipulation, and there will be many more successes in the future.

One of the most terrifying diseases is cancer. Many other causes of death have been eliminated, but this still strikes while we are in our prime. Great strides have been made in treatment, but it is reasonable to suppose that detailed genetic analysis of tumours, leading to accurate targeting of toxic drugs to the offending cells, will result in a surge of improvement in the next decade or so.

The most important aspect of reading the human genome is that it is a key step towards total understanding of our bodies. Possession of the code is not so much a problem-solver in itself, but a resource, a reference to aid and guide research on the systems of the body. This is why it must be freely available to everyone. Physiological pathways are vastly complex and require insight and experimentation far beyond the code itself. Access to the basic instructions empowers and sets limits on the hunt.

Although doubts surfaced about the significance of the role of genes after the revelation that humans have only about 30,000-40,000, it is not their number but their multiple interactions and the combination of their variants - an inconceivably large number - that must be considered in evaluating the possibilities of the human body.

Greater understanding of our bodies prompts new questions. Old age itself can be a disease, for many people the most devastating disease of their lives. It is no good prolonging life without considering its quality, so there is great interest in tackling all aspects of senility. But what of death? Is that a disease, too? And do we want to abolish it? For me, the answer is absolutely not. For others, however, immortality is an irresistible dream. How might it be achieved?

One line of thought is reflected in the fascination with the idea and practice of human cloning. But quite apart from practical and ethical difficulties, genetic cloning is in no way a re-creation of oneself as an individual. To clone oneself is to give rise to one's identical twin - but a twin born in another age, with its own pressures and ideas, and so a new personality. More logical, though as yet fanciful, is the notion of scanning one's thought processes into a computer that controls a robot. In principle, the transferred mind would be much more nearly akin to a replica of the personality than would a genetic clone.

Should we keep the bodies we have, how will we fix them if diseased? Methods of repair will become ever more subtle and perfect. Gene manipulation will not be the only product of the Human Genome Project. The consequences of really understanding how our bodies work will mean that soon there will be no gap in the spectrum from surgery to biochemistry. Every ailment will be tackled by a combination of tools, and prosthetic devices will be ever more commonplace, effective and unobtrusive.

But how much non-biological hardware can we hook up to a human body and still call it human? This is no joke. Once the prosthesiologists have solved the problem of making a reasonably stable connection between the nervous system and computers - and we are approaching that point - there will surely be a demand for various sorts of brain extension. We are good at learning to use tools, and the experiences of those who have cochlear implants or play with virtual reality devices is an early indicator of what is to come. A little more memory perhaps? More processing power? Why not? And if so, perhaps a kind of immortality is just around the corner.

All this discussion is largely from the perspective of the rich. The endless struggle with pathogens is much more apparent in the developing world, where they are still the major cause of disease. The proportion of research funding spent on tropical diseases is minute. The three most profitable products for the pharmaceuticals companies are all antidepressants. There is no profit in drugs for poor people. Unless this situation can be corrected, the world will be not only unjust but also immensely unstable. Market forces alone will not be able to level the global playing field. It demands a deliberate search for justice. One contribution to the search is the free release, by the Wellcome Trust and its partners, of genome sequences, which ensures that this fundamental information is available to all.

There are signs of growing inequality within rich countries, too. Although it is rarely discussed, everyone knows that there will be increasing difficulties with the equitable distribution of healthcare. Again, conscious democratic decisions will be required if the benefits of new technology are to be shared rather than auctioned.

To end disease is an admirable objective. I think a more urgent one, though, is to distribute more fairly the expertise that we already have. Life will continue to improve as we gain more and more understanding and keep trying to fix things. The dangers ahead are from inequality much more than from a failure to solve medical problems.

Sir John Sulston is former director of the Sanger Centre, Hinxton, Cambridgeshire, where he led the UK contribution to the Human Genome Project.

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