June 27, 2000

THE DOCTOR'S WORLD

Genomic Chief Has High Hopes, and Great Fears, for Genetic Testing

By LAWRENCE K. ALTMAN, M.D.

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	The Genome Project What are the implications of a decoded human genome? Predict the uses humankind will find for this knowledge. "Scientists should think carefully before 'discovering' a gene for IQ, sexuality, obesity, etc. Making these illnesses solidifies discrimination, intolerant worldviews, and implies that we need to cure people." "We will be able to see more clearly those things about us that are nature and those that are nurture." Add your thoughts and see more reader comments in Abuzz.

ithin 10 years, tests for genetic predisposition to 25 major causes of illness and death in this country will be widely available if predictions of Dr. Francis S. Collins, head of the Human Genome Project of the National Institutes of Health, prove correct.

But most people will shun genetic testing unless effective therapies exist to prevent potential hazards from the particular disorders, Dr. Collins said in an interview.

The project will map each of the estimated 50,000 human genes and spell out each letter in the book of the DNA, the thread of life, in the genes. But as scientists race to write the final chapter, they have little comprehension of the book's instructions and the changes they might bring to society.

Nevertheless, in a recent lecture after receiving a prestigious award from the Association of American Physicians, Dr. Collins made predictions about the project's impact on medical practice over the next 40 years, answering the question he said he was asked most: where will all the research lead? In doing so, he plunged into territory where few other scientific leaders tread.

Using genetics to tailor and improve health care will be the genome project's main legacy if effective laws are passed to protect privacy, prevent use of genetic information to deprive an individual of health insurance or a job, and prohibit other forms of genetic discrimination, Dr. Collins said.

Also, he urged closer scrutiny to determine when genetic tests are ready for wide use, given that commercial pressures may persuade patients and doctors to use tests before their medical value is established.

Even if only a few predictions prove true, major political and economic problems would follow. For example, the new genetic information's power to change medical practice could aggravate international tensions by widening inequalities in access to health care within countries and between those in the developed and third worlds.

Among Dr. Collins's predictions:

BY 2010, the genome will help identify people at highest risk of particular diseases, so monitoring efforts can focus on them.

A disorder of iron metabolism is likely to become the model for such screening. The condition, hemachromatosis, affects 1 in 300 people and in the early stages often goes undetected, which is unfortunate because simple treatments, like periodic blood-letting to remove excess iron, can prevent complications like cirrhosis. By 2010, studies will have found the most effective combination of biochemical and genetic tests to detect people who are susceptible.

In cancer, genetic tests will identify those at highest risk for lung cancer from smoking. Genetic tests for colon cancer will narrow colonoscopy screening to people who need it most. A genetic test for prostate cancer could lead to more precise use of the prostate specific antigen, or P.S.A., test by identifying those men in whom the cancer is most likely to progress fastest. Additional genetic tests would guide treatment of breast and ovarian cancer.

Three or four genetic tests will help predict an individual's risk for developing coronary artery disease, thus helping to determine when to start drugs and other measures to reduce need for bypass operations.

Tests predicting a high risk for diabetes should help encourage susceptible individuals to exercise and control their weight. Those at higher risk might start taking drugs before they develop symptoms.

Scientists have a partial insight into the genetics of osteoporosis. With further research, Dr. Collins said, "you could imagine combining that kind of a test with a decision to start calcium and vitamin D therapy early on to try to prevent bone loss before it is clinically apparent, although we don't yet have evidence" that such therapy will benefit individuals at high risk for osteoporosis.

Tests to detect many potential problems will be performed before birth, or even as part of in vitro fertilization before an embryo is implanted in the womb.

But these tests will raise troubling issues: the technology is prone to error, and at least initially, the tests will be hard to get and expensive.

As the accuracy improves and costs drop, many will demand the tests to reduce the chances of bearing a child who is at risk of developing conditions that are not actually debilitating, but just "undesirable." If so, there will be debates about the morality.

The explosion of information about the new genetics will create a huge problem in health education. "Most physicians in practice have had not a single hour of education in genetics and are going to be severely challenged to pick up this new technology and run with it," Dr. Collins said.

More than 120 medical and nursing societies representing virtually every specialty have formed a coalition to develop an educational program combining the Internet and traditional courses. "They all recognize this train is coming," Dr. Collins said.

BY 2020, doctors will rely on individual genetic variations in prescribing new and old drugs and choosing the dose.

Pharmaceutical companies will take a second look at some drugs that were never marketed, or were taken off the market, because some people who took them suffered adverse reactions. It will take many years to develop such drugs and tests.

Cancer doctors will use drugs that precisely target a tumor's molecular fingerprint. One such gene-based designer drug, Herceptin, is already marketed for treating advanced breast cancer.

The genome project holds promise for the mental health field. "One of the greatest benefits of genomic medicine will be to unravel some biological contributions to major mental illnesses like schizophrenia and manic depressive disease" and produce new therapies, Dr. Collins said.

BY 2030, death will still be inevitable, but clinical trials relying on information from the genome will be under way to extend human life spans. Human genes like those involved in the aging of flies, worms and mice will be identified and fully catalogued.

Scientists working with the genome will develop full computer models of human cells and analyze all human genes, proteins and their interactions. As a result, many experiments now done with laboratory animals or even human subjects will be completed entirely on computers. Dr. Collins said that if he were now a graduate student, he would join this field.

Groups opposed to technology will be alarmed by these developments and will act to halt them. "We have to be prepared for that," Dr. Collins said.

BY 2040, gene therapy and gene-based drugs will be available for most diseases. Using information derived from the genes for aging, the average human life span will reach 90 in the year when Dr. Collins would reach that age.