GENES, DREAMS, AND REALITIES.
Posted by bmhegde on 1
Mankind, or for that matter, any other living organism on this planet, has its basic unit, the gene, inside each chromosome, in every cell. There is a total of about 10 14 human cells in all. Each chromosome is supposed to contain around 100,000 genes, the primary unit. Others put it at 150,000 per chromosome. The genes have kept us going for well over 900,000 years, in more than 50,000 generations. They have made us survive all the adversities in life, including the scarcity of food. They mutated several times over to keep us alive. The one mutation that has been the bane of the present civilization with a food-plenty environment is the thrifty gene of the past, which has not been able to keep pace with the present food-plenty atmosphere. This gene-environment mismatch seems to be at the root of many degenerative diseases.1
Medical scientists called the period the end of history, when the controlled studies were designed to test the various interventions in medicine, including surgical procedures.2 Beginning with Fibiger’s controlled studies on the diphtheria serum in 1898, one hundred years ago,3 followed by the now famous randomized controlled studies of Richard Doll and Austin Bradford Hill in 1948, the medical world came to believe that all that we need to know in medical science could be known by the controlled studies, the latter were even hailed as the water mark for all scientific studies.4 The whole trend used to disturb me a lot. We have been barking up the wrong tree in trying to predict the unpredictable future of man, using these controlled studies.5 The controlled studies control only the phenotype. Man is not his phenotype alone. In fact, phenotype is only a small portion of man, as an organism. His genotype and his consciousness are the other important parts of man. The future predictions could only be successful when one knows the total initial state of the organism.6 This is impossible at the moment, although we are making big strides in research into the genetic background of man! “The next 50 years of randomized evidence will not fulfill the promise of 50 years ago, when properly randomized controlled trial was first published” 7
Dreams:
Scientists have been successful in unraveling the whole of the genome of the single yeast cell. The six thousand odd genes in this single cell should help map the human genome. The polymerase chain reaction (PCR) technique has been able to help us map the genes. Many researchers, mainly in Boston and London, have been able to get at many of the human genes. Almost daily a new one would have come to light. They have recently succeeded in finding out the total genome of a multi-cellular worm, caenorhabditis. This makes it even easier to map the human genome. We can hope and dream of a day, not in the too distant a future, when all the genes in the human cell could be mapped. (They have been done now!) Like the horoscope, the genome would be very popular in the near future to predict the future of mankind. Many of the diseases have now been associated with one or more genes. The oncogenes, the athras gene, the myocardial infarction gene, hypertension related genes, the diabetic related genes, cystic fibrosis gene, and so on and so forth, have all been shown to be related to diseases. This morning newspapers (December 1998) carried the good news of our Indian Medical Research Council, having made the discovery of the “sick” gene associated with the poor man’s common disease in India, rheumatic fever.8
The Rosalind Institute in Edinburgh shook the world by the first cloning of Dolly the lamb, by a team of researchers led by Ian Wilmot, a little while ago. This opened up many dreams of genetic engineering possibilities to benefit mankind even in the field of diagnosis. Clone is only a twig, and possibly could not reproduce the whole tree. Researchers have been successful in teaching germs to produce vital drugs, the easy way, by the genetic technology of replication. This was the lesson taught to mankind by the AIDS viruses, the retroviruses, which are capable of making human cells reproduce them in large numbers in a very short time. Cashing in on this we have been able to make human insulin and many other drugs and vaccines. Now that we have been able to study many of the disease related genes, we may soon be able to engineer them to prevent diseases in those susceptible to the disease! We may also be able to identify individuals with the bad genes to be targeted for primordial prevention of diseases, long before primary and secondary prevention begin to give any benefit to mankind.
Realities:
Our enthusiasm here should be tempered with caution, as it is not rosy all the way as it looks. In reality, our dreams could not all be realized so far even in the limited field of genetic engineering. There is also the possibility of a special kind of Eugenics being practised by the vested interests in medical science. Today most research is driven by the monetary economy of benefit to the sponsors. It may not be surprising if many of them opt to help eugenics with disastrous consequences for man. Did not the German medical scientists very quickly get onto Adolph Hitler’s bandwagon for eugenics, when the going was good? Does man change that quickly? It was William Shakespeare that wrote that “man whether in a castle or a cottage; palace or a pad; is governed by the same emotions and passions”. How very true? Ethical dilemmas in the field of human cloning need to be addressed very carefully, and the debate is going on now in the West. We Indians, have a different philosophy and, our culture has been sustained not only by the knowledge of man alone, but that of the divine as well; para and Apara vidyas. The human consciousness, the human mind, plays a vital role in disease. This is slowly dawning on the western world now.9
The debate would not be easy even for the West. Americans, have already, banned experiments on human cloning; as usual, a knee jerk reaction. There seems to be more sober note in Europe, where they are likely to allow research into cloning in the limited area of treatment of diseases. Thank God, we have been able to map the genome of the pluri-potent stem cell, the mother of all body cells. This might help us to engineer the mother cell to prevent diseases in future!10
Children and adolescents will have one more problem to deal with. Their genomes, traced in the beginning, might contain dangerous disease carrying genes. That, of course, does not mean that they will get the disease, as gene penetrance depends, to a very great extent, on the environment.11 However, the fear of the presence of the gene, might add to the anxiety, the king pin of human problems, making life miserable for both the doctor and the patient, to say the least!12
This could be compared to the menace of the coronary angiograms of the present day. Scientifically, the angiogram is not the gold standard for the diagnosis of coronary artery disease, as coronary artery disease is not synonymous with coronary artery blocks.13 However, the business of arteriograms to frighten patients to succumb to the false notion that a bypassed vessel is a cure for the disease, makes very good business sense even in the advanced West!14 The good news is that a new gene for vessel growth, VEGF 165 , has been shown to make new vessels grow where they are needed. The Tufft’s University researchers did try this on peripheral vessels with success. Recent American Heart Association meeting had seven papers on this gene’s use in coronary artery disease. Dr. Valentine Fuster, the president of the American Heart Association, was very confident during the press meet, that this gene, when introduced either proximal to the block in the vessels or injected into the heart muscle directly, could quickly make new vessels grow, to improve the patient’s symptoms remarkably. (The new vessels were all blind though and did not have any lumen for the blood to flow!)
Similar scenario could be visualized for the genome mapping. This could even make the insurance companies and the prospective in-laws to ask for the genome before insuring the life or arranging the marriages. Astrologers might lose their business in the latter event! Genetic research, which has made great strides in the last one decade, is a big feather in the cap of the scientists. Molecular biology is in the driving seat in medicine these days, which will bring in greater rewards in the not too distant future. That said, I must share a note of caution.
Just like the controlled studies, which were hailed as the end of history in medical research, let us not be too hasty in concluding that genetic research will be the real end of history in medical research! Already there are warning bells ringing loud and clear. Recent studies published even in the West 15,16 have brought to fore the main role played by the human mind in human disease. Although this was known to William Harvey in the seventeenth century, and repeatedly pointed out by thinking scientists, it was all but swept under the carpet in the West so far. 17
Hartman and colleagues carried out a retrospective analysis of 950 women who underwent prophylactic mastectomy to avoid cancer, predicted by their genetic mapping, at the Mayo Clinic between 1980-1993. The Gail model predicted seventy-six cancers during the 17 years follow up, whereas the actual number of cancers was only seven. 18 Prophylactic mastectomy’s role, based on genetic mapping, is not known. “It is more of a delusion than deliverance” feels, Professor Ian S. Fentiman, professor of surgical oncology, at the Guy’s hospital, London.17 Indian wisdom of Ayurveda, had proclaimed to the world thousands of years ago that anger, greed, pride, hostility, and great sorrow (depression) are the main risk factors of major killer diseases, western medical media is repeating the same now. 15,16 Man, proud man, do not be too proud. Science could, at best, unravel the mysteries of Nature, but never could understand Nature in toto. Scientific discoveries should not be taken as inventions! Little child is said to have clarified the difference between discovery and invention very well, when asked to use the two words in a sentence thus: “My father discovered my mother and then invented me.” How nice! Humility is the essence of good education!
BIBILIOGRAPHY:
1. Wetherall D. The Science of Medicine and its Quiet Art. Oxford University Press 1995.
2. Kunz R Oxman AD. The Unpredictability Paradox: Randomized and Non-Randomized trials. BMJ 1998;317:1188-90.
3. Hrobjartsson A, Gotzsche PC, & Glund C. The controlled trial turns 100 years. BMJ 1998; 317:1243-45.
4. Richard Doll. Controlled Trials: the 1948 watershed. BMJ 1998;317:1217-20.
5. Firth WJ. Chaos – predicting the unpredictable. BMJ 1911;303:1565-8.
6. Hegde BM. Chaos – a new concept in science. Jr.Assoc.Physi.India. 1996;44:167-168.
7. Peto R & Baigent C. Controlled Trials: the next 50 years. BMJ 1998;317:1170-71.
8. Ganguly. ICMR data. Conference in Chandigarh 1998, 12th December.
9. Stuart AE. On being conscious. Proc.Roy.Coll.Physi.Edinb. 1997;27:68-78.
10. Emmas R. Cloning OK to treat disease. The Assoc.Press. www.abcnews/cloning/health 98.
11. Hegde BM. Gene, Dreams, & Realities. How to Maintain Good Health.1993. UBSPD Delhi. (Book).
12. Naylor CD: Grey Zones in Clinical Practice: some limits to evidence based medicine. Lancet 1995;345:840-42.
13. Treasure T. US doubts about angiography. Lancet 1993;341:154.
14. Graboys TB, Biegelson B, Lamprest S et.al. Results of second opinion trial among patients recommended for angiography. JAMA 1992;268:2537-40.
15. Hippisley–Cox J, Fielding K, & Pringle M. Depression as a risk factor for IHD. BMJ 1998;316:1714-16.
16. Whiteman MC & Fowkes FGR. Hostility & Heart. BMJ 1997; 317:379-80.
17. Fentiman IS: Prophylactic mastectomy: deliverance or delusion? BMJ 1998;317:1402-3.
18. Hartmann L, Jenkins R, Schaid D, and Yang P. Prophylactic mastectomy. Proc. Am.Assoc.Cancer.Res. 1997;38:1123.