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Urge
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[04/27/00]

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I'm sitting in front of a laptop with Tomlinson, director of strategic marketing for a suburban Washington company called Gene Logic. We're scrolling through a list of body parts -- stomach, skin, heart, pancreas, etc. -- in a remarkably sophisticated genetic database that the company believes can revolutionize biomedical research. Subscribers, such as scientists and drug companies, can conduct virtual research by tapping into this vast storehouse of knowledge about genes and disease.

"Uh -- breast?" I blurt out, wondering as I do whether I'm thinking about the breast cancer in my family, or just being a guy.

"OK," Tomlinson says, "that's fairly standard."

We click on breast, and it is like no breast I have clicked on before.

It isn't an actual breast, but a list of all the genes active in the breasts of several dozen women. We have the option of looking at the breasts of alcoholics, tobacco users, pre- and post-menopausal women, blacks and whites -- more than 100 variables in all.

Because I'm stymied about which to choose, Tomlinson does a quick search on about a dozen women in their 50s.

A human has about 100,000 genes. At any time, in any tissue, only a limited number of them are expressed, or "turned on" to send cells the messages that guide fundamental biological processes, like growth. In the breast sample, 7,300 to 8,600 genes are activated -- and only about 5,000 of the genes are the same throughout the sample. When Tomlinson calls up a sample of breast cancer patients, their patterns of gene expression are entirely different.

It has often been noted that the DNA sequences of any two people are more than 99 percent similar. Even a chimpanzee's DNA is close to 98 percent similar to that of the average human. Gene Logic seems to have captured something interesting, which could be valuable for treating disease. This database shows that people with nearly identical DNA can have vast differences in genetic expression.

It also shows how uninformative, for all its grandeur, is the raw sequencing of the 3 billion base pairs, the building blocks in our DNA. The Human Genome Project, which is getting massive media attention as its nears completion, is just a first, crude step. The research that has the potential to change medicine, to produce new treatments and alter our very notions of disease, is happening largely out of the limelight, at places like Gene Logic.

When the sequencing effort got officially underway in 1990, at the beginning of the Human Genome Project, it inspired awe. Nobel laureate Walter Gilbert said reading the genome would allow us to "know what it means to be human." Newsmagazines fantasized about a "Gattaca"-esque future in which a doctor would swab your cheek for a DNA sample, pop it into a machine and produce a genetic readout of your future health and potential.

The genome project has sped discoveries about disease and human evolution and criminal forensics. But the completion of this encyclopedia has become a largely symbolic milestone -- it's come down to a horse race between a company, Celera, and a government-funded consortium. Neither the public nor the private versions of the genome will tell us what all that DNA does. The bracing truth about molecular biology is that the more we learn, the more we realize what we don't know. To understand the contribution that a company like Gene Logic may yet make, you have to start with that deflating realization.

Although we now have the letters of this so-called human alphabet, we've identified only about a third of the genes it spells. Fully grasping what these genes do will take decades because most diseases and traits result from a combination of many genetic and environmental influences. Too, different genes are turned on in different quantities, in different tissues of the body at different times.

It's no wonder, then, that the genome project has not yet had much impact on health. "The effect on clinical medicine has been small up to now," acknowledges Francis Collins, the director of the genome institute of the National Institutes of Health. But he adds, optimistically, "There will be an explosion of clinical applications in the next 10 years."

That is certainly an optimist's view, yet many biologists hold it.

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