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Mapping our genes: What it means

August 04, 2000|By Bob Maginnis

Mapping our genes: What it means



Earlier this summer, when network news and national print publications announced that the human genetic code had been cracked, there was lots of puzzled excitement, as if a lavish party were being thrown for someone who wasn't really that well known.

Many were cheering, but for what they weren't quite certain. And the statements of some leaders - like President Clinton's assertion that a cure for cancer wouldn't be far behind - seemed more like another campaign promise than science.

Fortunately for those of us who know little about this - including those like me who haven't been paying as much attention as we should to the last decade's new coverage of this topic - there's David Smith, a molecular biologist who, until he retired to Hagerstown, was in charge of hundreds of millions of dollars worth of federal research projects for the Department of Energy, including human genome research.

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It might seem strange that a department most associate with power and fuel would be involved in genetic research, but Smith explained that DOE is one of the largest supporters of basic research, with a budget comparable to that of the National Science Foundation.

Ever since the atomic bomb was dropped on Japan to end World War II, Smith said the Energy Department has had an ongoing project to study the effects of radiation on blast victims, and any genetic damage that might show up in their children.

But although the program had been fairly large for almost 50 years, Smith said "We could find no changes in the genes of children of exposed parents and were searching for better, more sensitive methods of detection."

This was so, said Smith, despite the fact that when laboratory animals like mice, which have many genetic similarities to humans, are exposed to radiation, it can be shown that ionizing radiation causes mutations.

What if, the scientists asked, they had the genetic maps of father and mother? Then they could theoretically predict what characteristics the child should have, and note any changes that might have been caused by radiation. At a December 1984 meeting in Alta, Utah, attended by "17 young molecular biology jocks," Smith said it was decided that mapping the human gene sequence was vital.

"At that meeting, we realized that if we could determine the genetic sequence of mother, father and kids, we'd have the most sensitive test that could be devised. That started us thinking about whether it was feasible to start such a project and what would be required for its success."

A year later came a new boss, Charles DeLisi, with a mandate to do "something big and wonderful with biology."

The human genome project was that big and wonderful thing, and after it passed muster with a National Academy of Sciences panel, the project began.

It was extraordinarily complicated, Smith said, and in the beginning, quite expensive, too. Human DNA is made up of about 3 billion bases, or letters, which contain the "entire directory of how to make a human being," Smith said.

"And at that time in the mid-1980s, we were talking about $5 just to sequence one base," Smith said, adding that it was only later advances in sequencing technology that made the program affordable.

But contrary to the gushing reports on network news shows, this historic beginning is just that - a beginning. The Time Magazine cover story for July 3 quotes Francis Collins, head of the National Institute of Health's Human Genome Project, as saying that while scientists now have assembled all the letters in the human genetic sequence into what amounts to a book of life, it may take decades to decipher the full meaning of the text.

As this deciphering process goes on, what kinds of things might happen as a result?

Smith said that differences in our gene sequences are one key factor in determining our individual ability to metabolize drugs, or to repair DNA. Though most humans have very effective DNA repair systems, some are better than others.

In dealing with cancer, for example, Smith said, the theory is that it takes, on average, five mutations in a cell to cause a malignancy. Knowing which "triggers" in the gene sequence to enhance might improve the body's ability to repair itself, he said.

Another possibility: The pharmaceutical companies have drugs that have been developed, but which can't be marketed because they have adverse side effects on a small percentage of the population.

Developing a test that would determine genetic markers for those adverse effects would allow companies to prescribe the drug safely for some, and withhold it from others, Smith said.

For many years, Smith said, doctors and drug makers have approached medicine like a man approaching a window with the shade pulled down. Using the tools available up until now, they took a shot with the treatments they had, making what amounted to educated guesses and hoping they would hit the mark. Now the shade has been removed, and the targeting process will be greatly improved, he said.

And, Smith said, through gene therapy, it might be possible to eliminate the harmful genes from mothers and fathers who might pass on inherited diseases like cystic fibrosis to their children.

"We're the product of a million years of evolution and with this development, we may be able to direct the future evolutions of our species," he said.

For reasons too complicated for me to explain in the space allotted here, that's unlikely to happen overnight. But articles already written have warned that it's possible that the have-nots will be left out and their diseases left uncured because they won't be able to afford the new medicines based on genetic research. Speaking for myself, I would rather face the dilemma of how to fund this therapy for everyone than to head into the future without it.

Bob Maginnis is editorial page editor of The Herald-Mail newspapers.

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