Johns Hopkins Magazine -- November 1997
Johns Hopkins Magazine


H E A L T H    &    M E D I C I N E

The ethics of embryonic stem cells... bringing home the Lasker... colon cancer breakthrough... tumor-fighting broccoli sprouts

Photo by John D. Gearhart
Confronting biology's ethical implications
John D. Gearhart recently reported that he had cultured human embryonic stem cells, the undifferentiated progenitors of virtually all human tissue. The finding broaches both a new area of biology and of bio-ethics. Now, Gearhart, a professor of gynecology and obstetrics at the School of Medicine, is grappling with tough questions raised by his research.

Rather than eschew controversy, says Gearhart, he prefers to confront and explore it openly. Thus, he announced his finding last July, at an international symposium on the ethics of human cloning and stem cells. He issued the "progress report" of his research before it had been published, he says, to spark discussion about establishing guidelines for the ethical use of such cells.

Gearhart has also personally taken time to reflect on the import of his work. As testament to that fact, an open paperback copy of Brave New World rests on top of the papers cluttering his desk one recent morning. In between advising postdocs and writing grants, Gearhart has been rereading Aldous Huxley's novel, the story of a utopian society that selects babies for biologically superior "Alphas" and "Betas" or inferior "Deltas," "Gammas," and "Epsilons." He plans to lead his lab group in a discussion of the book during an upcoming dinner meeting, and hopes it will help his team sort through sticky ethical questions raised by their recent research.

But first, the biology. Gearhart's team, which includes postdoctoral fellow Michael Shamblott, extracted immature germ cells from 5- to 8-week-old embryos donated anonymously by women undergoing therapeutic abortions. The scientists placed the cells in plastic dishes and added factors that enable the germ cells to continue dividing while remaining in a state of suspended development so that they do not differentiate.

In theory, embryonic stem cells could be used for remarkable ends: to replace diseased or injured tissue. A neurosurgeon, for example, might use them to replenish nerve tissue damaged by stroke. Similar accomplishments have already been achieved in animals. Gearhart's initial purpose, however, was to develop a tool for studying Down syndrome.

Coaxing stem cells to grow in culture, though requiring technical expertise, is relatively straightforward compared to addressing the ethical ramifications of the research. Following Gearhart's announcement at July's International Congress of Developmental Biology in Snowbird, Utah, news reports raised Huxleyish scenarios. Stories pointed out that it may be possible to introduce foreign genes into embryonic stem cells, implant the cells into a woman's womb, and create a genetically engineered person.

"I have no interest in altering the germ line," Gearhart states firmly. "It is not ethically acceptable." But, agitated by the news reports, he and the members of his lab group wanted to talk at length about the ethics of biological research such as theirs. So Gearhart planned the dinner meeting/book discussion.

Huxley's theme is one that Gearhart believes in. "Biology, like any science, can be used or misused to attain political objectives. Biology is a means to an end," he says.

Gearhart says he and his colleagues have done their best to assure that their technique is not misused. One control is through an ethics board at Geron Corporation, a Menlo Park, California, company that helps support Gearhart's research and has purchased licensing rights for the technology. The board screens requests for use of embryonic stem cells, with an eye toward the researchers' final intentions.

Gearhart hopes that his recent announcement will help "set in motion an awareness that other guidelines be set for use of this material." --MH

Photo by Ron Haisfeld
Bringing home the Lasker
Hopkins scientists Victor McKusick, the "father of medical genetics," and Alfred Sommer, who uncovered and ardently promoted the life-saving powers of vitamin A, won two of this year's three Lasker Medical Research Awards. The
Lasker is a coveted honor bestowed upon clinical or basic medical researchers who have made huge strides in vanquishing illness. Historically, the awards have often foreshadowed a future Nobel Prize. In fact, 56 past Lasker recipients--more than half the total--have gone on to win Nobels, most within two years of winning the Lasker.

McKusick, 75, University Professor of Medical Genetics at the School of Medicine (left), won the foundation's special achievement award for his lifetime work. He pioneered the study of the genetics behind disease and afflictions. During more than half a century at Hopkins, he unraveled the genetics of Marfan syndrome, dwarfism, and other conditions. He also proposed that scientists undertake to map all the human genes, a plan now manifest in the international Human Genome Project.

Al Sommer, 54, dean of the School of Public Health (right), received the Lasker award for clinical research. He discovered that simple capsules of vitamin A can save the lives of millions of poor children threatened by malnutrition and disease. Based on Sommer's studies in developing nations, the World Health Organization and UNICEF now aim to stamp out vitamin A deficiency.

Molecular biologist Mark Ptashne, of New York's Memorial Sloan-Kettering Cancer Center, received the third Lasker. --MH

New gains against colon cancer
Johns Hopkins oncologists recently discovered a new mutation among Ashkenazi Jews that increases the risk of familial colorectal cancer (FCC), and have developed a blood test for the mutation. People who test positive for the mutation have a 20 to 30 percent lifetime risk of developing colorectal cancer, compared to a 5 percent lifetime risk among the general population, says molecular biologist Steven Laken. He is first author of a paper on the findings, which appears in the September 1 Nature Genetics.

The study indicates that at least half a million Ashkenazi Jews appear to carry the mutation, which makes it the most common mutation linked to cancer yet identified.

People with familial colorectal cancer, which is believed to be the most common form of inherited colorectal cancer, have at least one first-degree relative with a history of colon cancer or precancerous polyps. The disease typically strikes when patients are in their 50s or 60s. Cells lining the colon and rectum start to grow wildly and form polyps that at first may be benign. Approximately 130,000 new cases of colorectal cancer (both hereditary and non-hereditary) are diagnosed each year in the United States.

Bert Vogelstein, Clayton Professor of Oncology and a Howard Hughes Medical Institute investigator, and associate professor of oncology Kenneth Kinzler co-directed the study.

The new mutation lies within the APC gene, which is the same gene that the researchers previously linked to another form of inherited colon cancer. In their earlier work, the scientists discovered that the APC gene is truncated in patients with familial adenamatous polyposis (FAP), a deadlier and rarer form of inherited colon cancer.

The researchers recommend that Ashkenazi Jews with a family history of colorectal cancer be tested for the new mutation associated with FCC. Those who test positive should have an examination of the colon every two years, beginning at age 35, or five to 10 years before the age at which colon cancer or polyps first appeared in a family member, say the researchers. "What makes colon cancer unique is that it can be identified in a pre-cancerous state, and removed," says Laken.

The researchers do not recommend the test for people who are not Ashkenazi Jews. They tested blood samples from more than 200 non-Jewish people and did not find the mutation in any of them.

Testing for the mutation is available through the Hopkins Hereditary Colorectal Cancer Clinic and Registry, for a fee of $200. All patients receiving the test through Hopkins are required to be seen by a genetic counselor. Information is available at (410) 955-4041. --MH

Photo by David Harp
Broccoli sprouts pack a wallop
More dinner menus have included broccoli over the past few years, since Paul Talalay reported that the bushy veggie contains a powerful cancer-preventing compound. Now, on the 13th floor of Hopkins Hospital's Blalock Building, Talalay is growing a new crop: sprouted broccoli seeds. As his team reports in the September 16 Proceedings of the National Academy of Sciences, the sprouts contain far more of the compound than does broccoli.

Just a block away, at Hopkins's Oncology Center, patients receive chemotherapy and radiation treatments.Talalay hopes that daily spoonfuls of broccoli sprouts will decrease the need for such centers. Clinical trials are now under way to test the sprouts' protective effects. Talalay's team has already shown that rats fed sprout extract and exposed to a carcinogen get fewer tumors than rats who don't get extract.

The team, which includes plant physiologist Jed Fahey and postdoctoral fellow Yuesheng Zhang, may market the sprouts and plan to donate any profits they make to the non-profit Brassica Foundation, which Talalay established to support research in chemoprotection, or decreasing the risk of cancer through diet.

"Prevention is going to have to be the future of cancer research," says Talalay, J.J. Abel Distinguished Service Professor of Pharmacology at the School of Medicine. "If a woman has a two-centimeter tumor in her breast, a disease process has been going on for 10 to 25 years." Researchers should look to prevent earlier stages from leading to malignancy, he says.

In 1992, Talalay and fellow researchers reported that a compound called sulforaphane dramatically boosts cancer-preventing enzymes. They also found high levels of a precursor to sulforaphane in vegetables of the brassica genus--cabbage, brussels sprouts, cauliflower, and most notably broccoli. But when they tested broccoli from many different stores and farms, they discovered that levels of the compound varied widely from one head to the next. And, even the richest stalks contained relatively little. People would need to eat broccoli for every meal to get an adequate dose.

Then the scientists tested three-day-old broccoli sprouts--and discovered that, ounce for ounce, they contain 20 to 50 times the amount of sulforaphane as mature broccoli. "Our feeling is the public should have fresh sprouts out there," says Talalay. Before growing your own, he warns, be aware that broccoli seeds sold for planting are generally coated with insecticides. --MH