The Brave New World Of Genetics

AFTER the reading of the human genome, there are daily advances that research on genetics is reporting: from chimpanzee-human differences to a new world free of disabilities, superior intelligence and human happiness, all implanted into our genes. The hype of genetic technology and its promise of course is very much a marketing drive of global multi-nationals investing billions of dollars in genetic research: they are more solutions in search of problems rather problems that were awaiting a solution.

First the good news. Human beings are much closer to chimpanzees than we thought earlier. A new genetic study in Nature has shown that the pictures showing George Bush making faces and in postures very similar to chimpanzees (www.bushorchimp.com) is not merely fortuitous but a clear result of our genetic affinity to our closest cousins, the chimps. As an aside, these pictures recently appeared in a Belgian official police manual showing the importance of body language in reading of humans, much to the anger of the US administration and embarrassment of the Belgian government. The study in Nature (put on-line by Nature but not yet published) titled “Genetic evidence for complex speciation of humans and chimpanzees” by Patterson et al, shows that the split of human population from the chimpanzee one was of a longer duration than thought earlier, with the split becoming complete only about 5.4 to 6.3 million years ago. This not only reduces the time of the split from about 7 million years ago as thought earlier, but also shows that there were considerable gene flows (mating) between the two sets of populations for about a million years.

COMPLEX TREE OF EVOLUTION

Why is this so startling? Previously, it was believed that the split between two sets of populations tend to be sharp and the hybrid population generally tends to be sterile. The above study shows that this is not really the case and for quite some time, at least for the proto human and proto chimpanzee population, this did not hold true. The basis of these conclusions is also interesting. The team calculated the genetic distance of various sites on the two populations and found that the X chromosome had the smallest distance or the most similarity, consistent with the hypothesis that the two populations mated with each other even after starting to separate. Any two species that mate would be expected to have similar X chromosomes as long as hybridisation continued. A messy divorce rather than a clean break!

The other impact of this chimp human split is that it spoils the party for those that believe that there is a uni-linear model of development in which the human population evolved from the lower apes and we are at the top of the evolutionary tree. There is a hominid population which pre dates this break showing that the current branch split later from the chimpanzee family than some of the other hominid branches. The tree of evolution is considerably more complex than a simple model in which nature worked over billions of years to produce us as the apex of evolution. That we are more successful is incidental: nature had no specific plans for us as different for what it had for chimpanzees or any other species.

While the genetic research has much to say about the past, the big bucks are in the future and not in finding out about migration patterns and chimpanzee. While genetic tools are indeed powerful, laying bare the genome of humans to mice (as also plants), the promise of immediate technology is not proving as fruitful. We will not look at agriculture and genetically modified organisms in this article but look at the new genetic technology in terms of what it holds for the immediate future of the human species.

UNNECESSARY HYPE

The common fallacy in the world of science is that any great scientific advance must immediately yield substantial dividend in terms of utilisable technologies. It is this utilitarian model of science (and also technology) that governs much of the debate on funding as well as the hype regarding science. It is this same hype which convinced the world that since we know E = MC2, we must also be able to utilise this knowledge either through nuclear fission or fusion to give us inexhaustible source of energy. This was the basis of predictions of eminent scientists that by the end of 20th century, there will be no need to metre energy, as it will become virtually free. I am afraid this is the same hype that biotechnology is seeing today.

The ability to read the genetic code and being able to modify it are two different things. Genetic engineering promises to rectify defects in the genetic code by inserting a healthy gene, therefore the concept of gene therapy. While it is possible some day this might become feasible, it is clear that this cannot be done with existing technologies in the near future. All the techniques we have today, take a shotgun approach in which the healthy gene is virtually sprayed into the patient’s cell nucleus (using generally therapeutic DNA combined with a virus as a vector) and this attaches to various different sites than the gene’s actual position. In the only on-going trials for gene therapy thought to be successful, out of the original 10 children suffering from SCID (severe combined immune deficiency) of whom 9 had been cured, 4 have now developed leukaemia. SCID leads to children being born with no immune system forcing such children to live in sterile “bubbles”. While it may be argued that leukaemia and living in a normal environment is preferable to living within a sterile bubble, that leukaemia has resulted on such a large scale indicates the limited utility of current methods of gene therapy. The studies with laboratory mice also show similar high incidence of cancer in those undergoing gene “therapy”.

ISSUES OF RISK AND ETHICS

It is clear that the current gene therapies have seen limited success. But that is not the only issue in gene therapy. New issues are risk and also new ethical concerns. Risks arise in gene therapies, as we have no data from the past for such experiments and the persistence of such agents through the patient’s offsprings. Gene replacement can lead to modifications in what are called germ-line cells – sperm cells or ova – and therefore once inserted represents a long-term risk. As viruses are used as vectors, they also introduce additional risks of their own. The other issue is the ethical one whether we can make modifications for future generations who have not given their consent. Any modifications that are passed on to future generations involve this new ethical issue that we have not addressed in the past. The good thing is that we have some time here still as we have yet to find effective tools for gene transfer without the problems described above. Designer babies bred to outperform the rest and the rich growing more and more distant from such directed evolution is still the stuff of science fiction or media hype. But if we are able to bring about such gene transfers in which we can bind the healthy gene to the specific site where the defective gene lies, then we will have to address the above issues of risk and ethics.

The more immediate issue is one of genetic screening of foetuses – prenatal genetic diagnosis. This is not very dissimilar from issues that already exist: when there is prejudice against the girl child, ultrasonography leads to large-scale abortion of the girl child and sharp distortion in sex ratios. The genetic tests on foetus would not only lead to worsening of the sex ratios as genetic tests are even more conclusive than ultrasound methods, but a whole host of variations in the human gene pool may get filtered out.

The prenatal genetic tests can identify known genetic disorders, particularly if the parents are known to be carriers of such defects. Such tests can help the parents make a choice whether they would like to continue or abort the foetus. In any case, most genetic defects lead to spontaneous abortions. While there may be issues of ethical nature – by doing this are we not weeding out a possible Steven Hawkins or a Homer – the problem becomes far more serious when we look at the way genetic diagnostics is being talked of today.

Genetic diagnostics is now being offered as a solution not for known genetic abnormalities but also for what are seen as statistical risks. These statistical risks are again not related to any known cause and effect mechanisms but a view of genetics in which disease and human behaviour are seen to be largely governed by genes. This brings us back to the old debate that a genetic disposition is only one of the factors in disease and environment which determines whether the predisposition is converted to an actual disease or not. Further, disease is rarely traceable to a single gene: quite often it is a complex of genes and a combination of environmental factors that determine what actually happens. If we try and screen out genetic factors by such crude genetic theories, the result would not be very different than that of finding criminals by looking at their skull type, the favourite of phrenologists of the late 19th and early 20th centuries.

A NEW EUGENIC PROGRAMME?

The danger of all this lies in the simple fact that having invested in this sunrise area of biotechnology, capital is desperately looking for paybacks. Just addressing a small percentage of cases of infertility or genetic abnormalities will not produce large returns. If a mass market is to be developed, mass screening of the population is required. This biotech lobby is joined by the insurance lobby that believes that all statistical correlation with disease should lead to aborting the foetus so that they have to pay out a lot less for medical treatment of the persons insured. They can then use the refusal of screening as a basis for refusing insurance. All this is driving genetic testing in a direction that would fit into a eugenic framework, a framework that was never rejected intellectually by many in the west. It became illegitimate only after Hitler’s genocidal ethnic cleansing of “inferior” races.

The problem with weeding out such variations leaves out the reason why such variation exists in the first place. Quite often, the additional burden of such variation arises from some other evolutionary advantage that exists. If we weed out some of these variations, we may also take out some advantages that this variation gives us. The less the variation in the gene pool, more vulnerable is the population in case there are large-scale environmental changes.

The brave new world of genetically designed future may still be some distance away, but the threat of its insidious arrival through selective abortion and consequent reducing heterogeneity of the gene pool still remains. The heart of this is the belief that all human characteristics are genetically determined –– from disease to obesity. If we press the right buttons and take out these genes, the human population would be better off: this is the new eugenics program. It is time that society wakes up to what is on offer and takes a reasoned stand on this. With large parts of today’s scientific community getting co-opted into this new genetic wisdom and with billions of dollars in profits from their patents, the scientific community cannot be the sole arbiter of such decisions.

There is an urgent need for an informed public debate on the pros and cons of techniques that biotech companies are seeking to market. We need to separate the good from the bad in biotechnology so that good science can proceed and the bad science, like bad money, does not drive out the good from circulation. We therefore also require a strong regulatory framework to address the scope of such techniques and to address the issues of risks and ethics. In India the risks are even more. India could become the happy hunting ground of dangerous clinical trials for this new technology with its people being offered as guinea pigs.