Hartwell: Genome technologies may be difficult to exploit

Science Article

Is the complete sequence of the 50,000 to 100,000 human genes a crystal ball into our future? Or have the media raised false hope and alarm in the public with exaggerated reporting of genetic discoveries?

Those questions were explored by Dr. Lee Hartwell, Hutch president and director, who presented the keynote address at a Jan. 5 conference in Tacoma, "Learning to Live with the Human Genome: Well Reasoned Prudence or Future Shock?"

The meeting was hosted by several state agencies, including the Board of Health, Department of Health and the state Supreme Court, as well as University of Washington School of Public Health and Community Medicine.

In addition to his speech, Hartwell and Dr. Wylie Burke, a scientist in the Public Health Sciences Division and a professor at the University of Washington, chaired a panel on research, public health and privacy issues.

Genetic engineering

Two concepts that have been espoused by both the media and the entertainment industry, Hartwell said, are that we will be able to control our genetic choices by genetic engineering and that our genes determine all of our characteristics.

"Genetic engineering is possible and is part of our future," Hartwell said.

"It's been done with mice, and those same capabilities exist for humans."

But Hartwell challenged the idea of genetic determinism, which holds that if each of our genetic profiles were known, we could predict all of our disease risk, health problems and proclivities.

"This will be much harder to achieve than the press has led the public to believe," he said.

Hartwell detailed four reasons why the power afforded by the human genome sequence and new technologies may be difficult to exploit in order to cure disease:

• Many diseases arise due to defects in one of many different genes. Scientists already know that common diseases like heart disease, diabetes and cancer are not caused by defects in single genes.
• A combination of variant genes leads to disease. Each of the 50,000 or so human genes exists in many variant forms. Only particular variants, when present in combination, may lead to a disease state.
• The ability to identify disease genes when multiple genes are involved has been largely intractable. Hartwell said that there are scant cases in which scientists can point to the interaction of two or more variations that lead to a disease.
• Genes are not completely determinants of fate, as numerous studies of twins have shown. Environmental factors, as well as the role of chance in development, influence and modulate genetic factors. Development of the immune system, which results from random genetic rearrangements that occur after birth, is a striking example of the role of chance.

Hartwell predicted that at best, for many diseases, individuals will learn only whether they are predisposed to increases in disease risk.

"For example, except for diseases where only one gene is involved, like Huntington's disease, a patient might be told they have a two-fold risk relative to the rest of the population," he said.

Unfounded fears

For this reason, Hartwell said, the fears raised about insurance coverage denial as a result of genetic information may prove unfounded.

"We already discriminate on the basis of health conditions, even in the absence of genetic testing," he said.

"Smokers pay higher insurance rates, risk of heart disease can be determined by checking blood pressure, and unprotected sex leads to risk of AIDS. People have been segregated for having tuberculosis. I'm not sure that genetic information poses completely new societal risks."

But Hartwell pointed to some legitimate future concerns raised by the new technology.

Misguided applications of genetic engineering might include frivolous uses to enhance beauty or development of biological warfare agents by the U.S. Defense Department or other groups.

Such concerns, Hartwell said, might not be easily minimized by legislative means.

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