NIH News Backgrounder
NATIONAL INSTITUTES OF HEALTH
National Institute of Child
Health and Human Development


FOR IMMEDIATE RELEASE
Wednesday, July 25, 2001
Contact: Melissa Braddock
or Robert Bock
(301) 496-5133

NICHD Fertility Researcher Receives Award for Listening to Patients

Lawrence Nelson, M.D., a fertility researcher at the National Institute of Child Health and Human Development, has received "The Art of Listening Award" from the Genetic Alliance for his ability to listen carefully to his patients when evaluating their conditions.

"Listening is a form of caring for others," Dr. Nelson said. "This award touches me deeply because it means our patients feel that our research team cares about them. But listening is not only the right thing to do to care for patients, it is also the right thing to do to advance research. As somebody once told me, you can learn a lot more by listening than you can by talking."

The Genetic Alliance, an international non-profit organization that works to help those impacted by genetic disorders, created this award to increase awareness of listening as an invaluable tool to increase medical understanding and help patients.

Dr. Nelson's principal research interest is in premature ovarian failure. This mysterious disorder affects young women, causing the ovaries to stop producing eggs and cutting off the hormones needed for bone strength and to ward off heart disease.

"Dr. Nelson deserves this honor," said Duane Alexander, M.D., Director of the NICHD. "He has doggedly pursued the causes of this frustrating disorder while at the same time focusing intensely on the patients whose condition he is studying."

Dr. Nelson developed his interest in premature ovarian failure as a gynecologist in private practice. Although menopause usually begins around age fifty, one of his patients, a woman in her thirties, was already undergoing menopause. The woman also suffered from an autoimmune disorder of the thyroid — a condition in which the immune system mysteriously attacks normal thyroid tissue. Could the woman's premature menopause, he wondered, have resulted from a similar immune onslaught against the ovaries?

A check of the medical literature yielded very little information on such a condition. Soon after, Dr. Nelson sold his practice and completed a series of research training appointments-including a stint at the prestigious Hammersmith Hospital in London. In 1988, he came to NICHD to set up the Institute's Unit on Gynecologic Endocrinology.

Since then, he and his coworkers have worked tirelessly to understand why an otherwise healthy young woman's ovaries would stop functioning by age forty. Over the years, he and his colleagues have searched for clues not just in patients, but also in a strain of mice that develop the condition after their thymus is removed shortly after birth.

Recently, Dr. Nelson and his colleagues in NICHD's Unit on Gynecologic Investigation uncovered what they hope is a major clue to the disorder. Their discovery may offer hope not just to the one percent of American women who have premature ovarian failure, but also provide new insight into the fundamental process by which a fertilized egg cell gives rise to a complex organism.

Publishing in the journal Nature Genetics, the researchers described the Mater (pronounced Mah-ter) gene, which they found in mice. The gene appears to make a protein that is essential for a fertilized egg to develop. Female mice lacking the gene produce eggs that cannot survive beyond the two-cell stage after fertilization.

The researchers located the gene because of clues provided by Nelson's earlier research with patients. The ovaries of some young women with premature ovarian failure showed evidence that their egg-producing machinery had been blighted by an attack from the immune system. While trying to gain insight into the nature of this attack, the Unit's postdoctoral fellow, Dr. Zhi-Bin Tong, isolated a protein from mice. The protein — a target of an immune attack — was abundant in egg cells as well as in fertilized eggs. Follow-up studies showed that mice lacking the gene for the Mater protein simply could not produce eggs capable of surviving after fertilization.

"The Mater protein is analogous to the mother's milk of the egg cell," Dr. Nelson said. "Without this maternal substance, the egg cannot survive on it's own."

Determining the function of the newly discovered gene is more appropriate for developmental biologists, Nelson said. Next, he and his colleagues will search for the human version of the gene and protein, to learn if it, too, is the target of an immune attack. He also hopes to find out whether defective copies of the gene are responsible for unexplained cases of infertility. He added that while it's important to search for the cause of the condition, it's also important to find more effective treatments to help women whose ovaries have ceased functioning.

"The ovary is more than just a sac of eggs," Nelson said. "It's a gland that produces hormones essential to the health of young women."

In a new study, he and his coworkers are trying to find out if combining the female hormones estrogen and progestin with the male hormone testosterone will help to avert the bone loss, loss of sex drive, and cardiovascular risks experienced by many ovarian failure patients.

Traditionally, he said, preparations to replace ovarian hormones have contained only female hormones. But testosterone, while produced in large quantities by the testes, is also produced in smaller quantities in the ovaries.

Nelson would like patients and their health care providers to be more aware of the endocrine function of the ovaries. Many of the patients with premature ovarian failure who have been referred to him began with a history of missed periods. Often patients delay seeking evaluation for this.

"Often the patients or their care providers dismiss the problem as due to stress," Nelson said. "But these days, who isn't under stress?"

Instead, Nelson said, patients who frequently miss their periods probably should be referred for additional tests of ovarian functioning. Currently, Dr. Nelson is seeking to establish a partnership with a software designer to develop a computer program that would help caregivers more accurately diagnose and treat amenorrhea — the lack of menstruation in reproductive age women.

"We believe the menstrual cycle is a vital sign of a women's health," Dr. Nelson said. "If it isn't functioning, we need to find out why."