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Biotech / Medical : VD's Model Portfolio & Discussion Thread -- Ignore unavailable to you. Want to Upgrade?

To: Henry Niman who wrote (4936)	5/18/1998 11:51:00 AM
From: Thomas M.	Respond to of 9719

redherring.com OUT OF SEQUENCE Science has its priorities backward: it should focus on proteins first, genes second, and the genome last. By Freeman Dyson What are we doing with genes and genomes? Three scientific activities are moving ahead vigorously and will be moving ahead vigorously for many years to come. First, the Human Genome Project, aiming to determine the exact sequence of the 3 billion base pairs in the genetic apparatus of a human being. This is an international program organized and paid for by governments. Second, the sequencing of individual genes, human and nonhuman, that are of interest for medicinal purposes. This is mostly paid for by pharmaceutical companies and done in their laboratories. Third, the determination of the three-dimensional shape and structure of protein molecules, the active chemical agents that our cells manufacture by following the instructions provided by our genes. This is mostly done at universities, with some help from the pharmaceutical industry and governments. Monomania These three activities are very different, with different aims and consequences. The public is generally unaware of that. The Human Genome Project has received more attention (see, for example, this magazine's biotech briefing in the May issue, beginning on page 47) than the other activities because it is big and glamorous and heavily politicized. The promoters of the project talk about it as if the complete sequencing of one human genome were of vital importance to science and medicine. In fact the completion of the genome sequence is a political, not scientific, necessity. For science and medicine, it does not matter much whether the sequence is complete. What matters is that the technology of sequencing should become cheap and rapid enough that we have a continuing capacity to sequence genomes of many kinds of men and women, animals and plants, and bacteria and viruses, without huge efforts and large expenditures. We want to be able to sequence genomes of individuals with various diseases and disabilities, to understand the subtle connections between the genome and the organism. The genome project ought to be developing cheaper and faster sequencing technology, rather than striving to complete a single sequence. The sequencing of individual genes offers more immediate benefit to science and medicine than the Human Genome Project, at lower cost. That is why the pharmaceutical industry is willing to pay for it. It's easier and cheaper to sequence genes separately than to sequence an entire genome. The existing, labor-intensive methods are cheap and fast enough for sequencing individual genes, since all the genes together constitute only 3 percent of the genome. It is likely that almost all the human genes will have been individually sequenced within a few years, before the genome project is finished. The remaining 97 percent of the genome may have important functions that are still unknown, but science has no reason to be in a hurry to sequence it. Job one Finally, the third activity, the structural analysis of proteins, is the most difficult and the most important. The only thing that most genes can do is make proteins, which in turn define what genes can do. Proteins make us sick or healthy. Proteins switch genes on and off. Most hereditary diseases are caused by the absence of essential proteins. To reach a deep understanding of a disease like cancer, we must understand the structure of the protein machinery that breaks down when a cell becomes malignant. We are still far from such a complete understanding. There are about 100,000 different proteins in a human cell, and only about 5,000 have known structures. At the present rate of progress, it will take 100 years to determine the structures of all the human proteins. The moral is that our priorities are upside down. The public has been led to believe that the Human Genome Project is at the cutting edge of science and medicine. In the view presented by the popular media, the sequencing of individual genes comes second and proteins a distant third. In reality it is the understanding of protein structure that is the greatest scientific challenge and also the most promising approach to the rational design of drugs. The order of priorities should be proteins first, individual genes second, and the genome last. It's likely that the correct order of priorities will gradually become established during the next 10 or 20 years. Proteins will emerge as the big problem and the big opportunity. With luck, someone will invent a new microscope or a new magnetic resonance imaging machine that will enable us to visualize protein molecules directly, with every atom in its place. After that, the structure of a protein will be determined by a student with a desktop machine in a few hours, instead of taking months of work by teams of experts. When this revolution in the technology of protein structure analysis occurs, it will have more profound effects than the Human Genome Project on the future of science and medicine. Our biotechnology and pharmaceutical industries should now be pushing forward to make the revolution happen and preparing to exploit the opportunities it will create. Freeman Dyson, the author of numerous scientific books and articles, is professor emeritus at the Institute for Advanced Studies' School of Natural Sciences at Princeton University. Tom