GENES, DREAMS, AND REALITIES

Prof B M Hegde

The popular press seems to have a hay day reporting all kinds of exciting possibilities, some even frightening, with reference to the new path-breaking research by Ian Wilmut, at the Roslin Institute in Edinburgh, Scotland, of "cloning" to produce an adult ewe, wherein he fused an egg cell with the DNA derived from an "adult body cell" of the mammary gland of a sheep by the "jolt of electric current", eliminating the role of the father in procreation.

Hello, Hello, hold on ! this is not that exciting as it is made out, neither does this experiment send God packing back to his abode in heaven, leaving mankind to make copies of themselves without having to go through normal sexual reproduction yet! Far from it!

This experiment is not even the first one in the field of cloning. Robert Briggs and Thomas J. King, in Philadelphia, had transplanted nuclear material way back in 1952. This was first done in amphibians, then extended to insects and fishes, later in 1980 to mammals. The oldest living cloner is DiBerardino, who claims that she devised this experiment long ago. I am sure the Swedish Nobel Academy will have a tough time deciding who should get the Nobel this time around; as most of this bench experiments are done to bag a Nobel Prize! I only hope that the wrong person does not get it as had happened in the past. To quote only one example in 1927 the Nobel for medicine went to Wagner Juregg, who claimed that he had developed a new fever therapy, using malarial parasites, for curing the then dreaded disease, general paralysis of the Insane (GPI) of syphilis.

In fact, Juregg was not the first to describe fever therapy, (it was done by Hippocrates, the father of modern medicine) and he had killed, in the bargain, twice as many, as he claimed to have saved unknowingly. The world of awards and prizes will always be the same. The really deserving would miss the bus time and again!

Be that as it may, let us quickly settle the fear in the minds of many that human copying is not far away. One can never clone a "self". A human being is much more than his genetic material. Even the genetic material in Dolly, the ewe produced by Ian Wilmut, is not complete vis-à-vis sexual reproduction. Dolly was the result of nuclear transplant of DNA derived from the adult mammary gland cell of a sheep (unfortunately Wilmut does not know whether the cell was an embryonic pleuripotent cell or a mature divided functional cell) on to the unfertilized egg cell with a jab of electric current. That shows that the whole male cell (spermatazoa) was not transplanted on to the egg cell. This leaves quite a few other DNA material from not only the nucleus but from the all-powerful ‘organelle’ which are inside all our cells and they fuel all our metabolic demands. So Dolly is not a full lamb in the genetic sense.

That apart the offspring is not wholly the genetic material of the parents! The genetic material derived from the parents has to change a lot in the environment before it penetrates to show its characteristics, called gene penetrance. Man, ultimately, is the product of genes and his environment. One could easily quote the study of "identical twins", derived from one single egg cell of the mother, (uniovular twins), if brought up separately immediately after birth, develop different characteristics. The genetic similarity between siblings is only around 50%. Hold on! it is not yet possible to produce human beings with their "consciousness" using cloning experiments.

Cloning in Greek means a twig. A twig will not always be the same as the parent tree. As the environment) bends the twig so the tree also will grow bent. Another curious factor is that the ‘organelles’ referred to earlier have their own "consciousness" inside our cells. They are genetically not ours! They are closer cousins of other microorganisms in the world! Adult DNA, which Wilmut used, differs from the foetal DNA substantially and, can never produce an offspring like its parents. Nature does not show all her cards to scientists. We only scratch the surface and when we get to know a small fraction of the way Nature works, we get excited and claim to have divine powers!

"Man, proud man,
Dress’d with a brief sense of authority,
His glassy essence like an angry ape,
Performs such fantastic tricks against high heavens,
That even make the Angels weep"

said Shakespeare. He was absolutely right with reference not only to politicians, but also scientists!

Having thus disposed of the Frankenstein’s monster, let us look at the brighter side of this experiment. Cloning would certainly help improve the process of animal husbandry. It will enable us to breed genetically desirable traits more efficiently. One could possibly clone the best milch cows. Even here one will have doubts. "Cloning will never replace selective breeding as a method of genetic engineering" was the opinion of Prof. Jon W. Gordon, at the department of Obstetrics, at Mount Sinai Medical School in New York City. He is right ! Cloning halts further progress. When one has cloned a cow, the same cow cannot breed further in the same cloning fashion.  Dolly has delivered normally with a male, of course! So do not worry, you can not clone a Hitler and make more Hitlers!

It may, however, help in cancer research! Even that is a premature hope. Every cell holds within it the capacity to form every other cell in the body, but in the process, some messages are lost and others developed. If one could use cloning to suppress the cancer message, well and good. Let us hope for the best.

No need to panic. We have gone too far in our fear. Senator John J. Marchi of New York is ready with a bill in the senate that would make it a felony to do human cloning. Dear senator Marchi do not panic, it is not that bad after all! Church also seems to be agitated that man is assuming the role of God. Never!

The people who have a field day and make tons of money are the science fiction writers selling their books by the millions CJ Cherryli’s book Cyteen, Ira Levine’s book The Boys from Brazil, Arthur Clarke’s Imperial Earth, Ben Bora’s The Multiple Man, and Nancy Freedman’s Joshua, son of None, are a few. Make hay when the sun shines, boys! Cloning is exciting but poses no danger. "God gives and forgives. Man gets and forgets" !

We move on to the other areas of molecular biology especially, genetic engineering. It looks like a very exciting field. Everyone in medical research is looking up to genes to unravel the mysteries of diseases.Man has, basically, three important components, his genotype, his phenotype, about which we have been talking and doing lot of things in the past, and his mind, which at the present moment is unfathomable.

Most of our evidence-based medicine, the fashion today, is based on human phenotype only.Consequently it has now turned out to be the evidence-burdened medicine. The controlled trials, which were thought to be the be all and end all of the progress in scientific medicine, are heavily flawed, in retrospect, as they did not take into consideration the genotype of groups that were matched.

The human genome is likely to be mapped completely in the next four to five years.  Although it gives us a lot of satisfaction, it carries with it the great problems of confidentiality and the attendant fear – psychosis for the healthy person who gets to know his bad genome.

Prior knowledge of one’s genes may not be as pleasant as we hope it to be.Nature, in his wisdom, has kept the future secrets hidden from man, helping him thereby to live happily, on hope.Clinical medicine seems to consist of a few things we know, a few things we think we know (but probably don’t), and lots of things we do not know at all.“The play of uncertainty can be shown quantitatively when formal decision analysis is used as a tool to compare the clinical strategies.The outcome is often either a toss-up that rests squarely in the Grey zone or highly dependent on assumptions about one or more poorly defined variables in the model” wrote David Naylor.⁽¹⁾

In the realm of curative medicine, this kind of uncertainty could be tolerated.When it comes to preventive screening it becomes very difficult to accept uncertainty, predominantly because we do not know the gene type, the preventive procedure may have very little predictive value.William Osler once said “ good clinical medicine will always blend the art of uncertainty with the science of probability”.

Genetics has come to forensic medicine in a big way.There was a recent Ciba Symposium on genes and criminal behaviour in London. In a murder case in the USA attempt was made to mention an anti-social gene as an mitigating evidence.The evidence for and against the genetic basis is fraught with danger.As the debate about nature Vs nurture is still on, combining multiple technologies into daily practice is also dangerous, resulting in the Malthusian growth of uncertainty.

Howletts zoo had a tiger called Balkash, which killed one of the zoo keepers.In a suit in the court Mr John Aspinall, the owner of the zoo, had in his defense genetic fault in the tiger “ There may be a faulty gene, an abnormal gene, which criss crossed on to him so that he has a mean streak in his gene type that surfaces; human beings have learnt that inherited characteristics could come out even eight generations later”.

Michael Lyons from Boston reported on a study of twins called Vietnam War Twining Registry. He concluded that anti-social behaviour in children is mainly affected by the environmental contribution.Contrast that with the findings of Mednick from Los Angeles who looked at the adoption cohorts in Denmark. between 1924 and 1948, a total of 14,427 adoptees.This study showed that environmental influences are very small in criminality.Both these studies have enough flaws to be extrapolated to the population at large.

The role of genes in disease causation, and also in treating some of the rare diseases is being explored extensively.It is premature to say what has the future in store for us in this area.Evidence-based medicine offers very little help in many areas of clinical practice.It would be good for humanity if all these hi-tech medicines could be put into rigorous scientific scrutiny, but in practice this is very expensive, and is never done that way.If evidence cannot guide practice, people like me will advocate minimalism but, many others will favour intervention based on inference. The Grey area keeps on widening in medicine daily.Our dreams, about the genes may be far from realities^.(2)

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