Many faces of a gene-mapping project.

Many faces of a gene-mapping project

Only 36 years after scientists discovered the structure of DNA, molecular biologists now seek the exact sequence of all 3 billion nucleotide pairs that together encode every inherited human trait. The 15-year project promises to revolutionize disparate specialties within the life sciencies. Among them:

* Medicine. An understanding of the molecular basis of inherited diseases may lead to improved diagnosis and treatment. Leroy E. Hood of the California Institute of Technology in Pasadena, for example, makes synthetic bits of protein that resemble myelin -- the protective coating around nerve cells. By injecting these proteins into mice, he induces a white blood cell response against the rodents' natural myelin, causing a syndrome resembling multiple sclerosis. Recently he has found that synthetic proteins featuring minor molecular alterations have diffeent effects when injected. For instance, one variety performs the first step necessary to induce myelin damage but cannot convince white blood cells to finish the job. Another analog gets white cells so excited they overreact to the protein, inducing vaccine-like protection against subsequent exposures to myelin-damaging injections. Hood aims to use such experiments to reveal the critical differences between myelin-destroying white cells and their innocent cousins. Later, scientists might develop drugs that destroy only the former to halt the progression of multiple sclerosis.

* Evolution. Since DNA mutates at a fairly constant rate, DNA comparisons among different organisms provide a historical record of evolutionary changes over time. Further, a portion of each cell's DNA--called mitochondrial DNA--is inherited only from one's mother, allowing researchers to trace human maternal lineage to the one "modern" mother from whom we all descend. New York by Allan C. Wilson of the University of California, Berkeley, now indicates this original mother lived 140,000 years ago -- 60,000 years later than was thought -- and her closest living relatives are today's !King tribe in southern Africa. Wilson's genetic studies suggest the first major human migration northward from that region occurred about 70,000 years ago; 35,000 years later they brought their genes to Europe. All the world's populations "are just twigs on an African tree," Wilson says. "Basically, we are all !Kung."

* Comparative biology. The human body harbors about 100,000 proteins, and differences in a very few of these can account for all the recognizable variations among us. Indeed, DNA studies of bacteria, yeast, mice and cows indicate living things are much more alike than they are different. Scientists suggest that just as research findings in mice can shed new light on humans, other organisms may prove genetically enlightening and even easier to experiment with. For example, tomato cells and mouse cells have a lot in common, each featuring the same number of chromosomes and chromosomal arms. Moreover, says Eric S. Lander of the Whitehead Institute for Biomedical Research in Cambridge, Mass., a tomato "is roughly the same size as a mouse andis substantially easier to catch."

* Technology. The genome project will require significant technological advancements in areas of information storage and automated DNA analysis. Improvements made to date rate as a mixed blessing, however. For example, as techniques have become increasingly simplified, much of the DNA sequencing work traditionally performed by postdoctoral fellows has become intellectually mundane and repetitive. Unless robotic devices take over many of these tasks, says C. Thomas Caskey of the Baylor College of Medicine in Houston, "it's clear the postdocs are going to burn out very quickly."

Sydney Brenner of the MRC Molecular Genetics Unit in Cambridge, England, jokes that researchers convicted of scientific fraud should be sentenced to produce DNA megasequences in laboratory-equipped penal colonies.