James Grifo '78

James Grifo '78 aims to prevent genetic damage before it occurs. As director of New York University Medical Center's division of reproductive endocrinology, he pioneered a technique of "preimplantation genetic diagnosis." Used in conjunction with in vitro fertilization (IVF), it analyzes embryos produced in the test tube for genetic defects before implanting them in mothers.

The technique offers promise for couples who have a high risk of conceiving a child with a severe genetic defect. Many have already borne a baby with a disease and want to ensure that further pregnancies result in healthy children. Currently, they can't learn whether their fetus has the genetic condition until several weeks after conception, when chemical monitoring techniques become feasible. If the disease is present, the parents face the uncomfortable choice of aborting their fetus or delivering a severely disabled child.

Preimplantation diagnosis removes that choice by testing an embryo fertilized in a test tube for the genetic condition before implanting it in the mother. "We were the second group in the world to take an eight-cell embryo, remove a single cell, test it, and transfer embryos not affected with the illness that the couple carries," says Grifo. "We've had over 35 babies from this procedure, out of more than 100 in the world."

The process isn't easy. "Couples must go through IVF, which is not as much fun as getting pregnant the old-fashioned way. And while we haven't charged for the embryo biopsy, the IVF costs in the $10,000 range." But parents have gone through the procedure because it gives them the opportunity to bear children guaranteed free of genetic diseases.

Another advance pioneered by Grifo and his colleagues promises to help a different group of would-be parents. As women get older, they have an increasing risk of producing defective eggs. Grifo's team determined that the defects occur in parts of an egg separate from and outside the nuclei that carry an egg's genetic information. The team reasoned that older women could increase their chances of bearing healthy children if their nuclei were transferred to younger eggs from donors. "We got permission to do this in two patients, and it worked. We transferred the embryos, although neither woman got pregnant," he says. "But we had to stop because of political pressure. Now we are focusing on animal work."

Grifo admits that his research has ethical and regulatory implications. "It's unfortunate that abortion politics has become confused with infertility research. The bottom line is that there are patients with horrible illnesses. Our goal is to help them have children and be happy patients. Most of the critics don't really have a healthy understanding of what's going on."


Tom Gelehrter '57 -- Wendy Uhlmann '83

Research in a broader segment of genetics promises to yield health benefits to the entire human population. Sparked by such programs as the Human Genome Project, human genetics "has the potential of really defining what we are," says Tom Gelehrter '57. "Understanding how genes switch on and off will enable us to know how our bodies work and how to fix them when they're broken."

That knowledge will lead to a strong practical payoff: "We will have the opportunity to individualize medical care in a way that we have not been able to do before," explains Gelehrter, who is professor and chair of human genetics and professor of internal medicine at the University of Michigan. "It is especially applicable to diseases that appear later in life, such as cancers and heart disease. And it opens the way to individualized therapy. We now give patients medications knowing that some proportion will develop side effects. Human genetics offers the chance to detect patients who are genetically predisposed to this."

In his own research, Gelehrter focuses on how genes are turned on and off--or how gene expression is regulated, in the technical language of genetics. A recent investigation involves a gene responsible for plasminogen, a substance that degrades certain blood clots. Controlling plasminogen is important in certain fibrotic diseases, such as lupus and inflammation of the kidneys. Doctors normally use two types of substances--a growth factor called TGF beta and a class of chemicals known as glucocorticoids--to treat those conditions. However, the two often interfere with each other's actions. Gelehrter and his colleagues have discovered a way to persuade the two compounds to work effectively in concert.

Beyond the laboratory, Gelehrter has long taken an interest in genetics education. His efforts include coauthoring the most popular textbook on medical genetics. "I'm interested in the need to increase genetic awareness among physicians and other medical providers, and more broadly among the general public," he says.

"The medical profession is less informed than it should be on genetics. Several studies show that a depressingly low number of medical professionals can correctly interpret test data. As patients are getting more sophisticated and demanding, they are often more up-to-date than their physicians. That could be a problem."

It's a problem that Gelehrter's colleague, Wendy Uhlmann '83, aims to overcome. A genetic counselor and clinic coordinator at the University of Michigan's division of medicine, Uhlmann advises patients on the risks they may face as a result of their genetic heritages. "Families will come to see us because they have a family history [of a certain type of disease]," she explains. "We can analyze their history for the chance that the genetic disease will occur. A lot of the work is risk assessment and genetic education--helping people to make the best decisions for themselves."

The profession presents ethical challenges aplenty. Among the toughest are those associated with Huntington's disease, whose most prominent victim was folk singer Woody Guthrie. This is a progressive neurological condition that affects men between the ages of 30 and 50 and eventually kills them. The gene responsible for it is a dominant one; a person who received the gene from a parent will inevitably fall victim to the disease. A team of researchers located that gene in 1995, making it possible to identify individuals with the disease long before they show obvious symptoms.

Since no cure exists, says Uhlmann, a lot of individuals at risk "don't want to know whether they have it. Others do, because if they have it they may choose not to have children, or to make a career move."

Uhlmann recalls a typical example of an ethical dilemma. A husband with a 50 percent risk of suffering Huntington's didn't want to know his genetic status. His wife, who was pregnant, wanted her fetus tested, and aborted if it had the disease. But if the disease showed up in the fetus, it would mean that the husband certainly had it also.

"We turned her down, as did every other center," says Uhlmann. Eventually, the husband relented and agreed to have himself and the fetus tested. Sadly, both had the Huntington's gene, and the pregnancy was terminated.

As geneticists locate the genes for other diseases, the breadth of genetic counseling widens. "We're doing a lot of cancer genetics, including breast and colon cancer," says Uhlmann. "Again, it's a matter of evaluating family histories. The most amazing thing is reassuring people whose mothers and grandmothers have a cancer that they don't have a 100 percent risk."

Doing the job effectively means keeping up with the scientific literature. "Over 4,000 genetic conditions have been identified," Uhlmann explains. "Sometimes you look in the paper and find that a new gene has been discovered, and might then get calls from people that day." But even as they keep up with public reports on genetics, genetic counselors must be sensitive to their patients' frequent need for privacy. Many individuals don't want their medical records available to their health insurance companies or their employers.

Oberlin played a significant formative role in the careers of these five geneticists. For these alumni, professors opened the way to productive careers in the tough world of academic science. "Dennis Luck was one of the most influential people in my career, as well as Peter Hawkins and Martin Ackermann," says Grifo. "I'm so grateful to them.

Lenski benefited particularly from his alma mater when he was deciding how to study evolution. "I recalled a course on microbial genetics taught by Richard Levin. I remembered how tremendously impressed I had been by some of the elegant experiments done several years ago with molecular genetics, and thought: Why could the same features not be used from an evolutionary perspective?" He started his postdoctoral work in the subdiscipline at the University of Massachusetts and realized that he had "discovered an open niche--an opportunity to do what no one else was doing."

Uhlmann also gives credit to Levin for introducing her to genetics. "He certainly had a big impact, along with my winter-term project," she says. She also regards her career as a reflection of her alma mater. "Oberlin prepared me well for this field. Genetic counseling is a perfect Oberlin profession in a lot of ways. It requires science, working with people, and a lot of ethical challenges that you try to do right."

Peter Gwynne is a freelance science writer based in Cape Cod, Massachusetts.

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