Birth-control research delves into the molecule

Birth control has been dominated for decades by hormones and barriers, or more specifically, pills, condoms and diaphragms. But the next generation of contraceptives may prevent pregnancy by blocking specific genes and proteins.

Using technological advances from the fields of molecular biology, genetics and genomics, researchers are identifying targets unique to reproductive cells. They hope to then block or manipulate the ones responsible for sperm and egg development, the fusion of eggs and sperm and the implantation of fertilized eggs in the uterine lining.

“Molecular contraception is going to be the next breakthrough of contraception,” said Dr. Kurt Barnhart, director of the reproductive research unit at the University of Pennsylvania’s Center for Reproductive Medicine and Surgery.

Fueling the new research is the enormous market for any resulting contraceptives. From 1995 to 2000, there were 300 million unplanned pregnancies worldwide and nearly 700,000 women died as a result, according to a 2002 report from the Global Health Council, a nonprofit organization that monitors world health problems. Although more than one-third died from problems related to pregnancy, labor and delivery, the majority died as a result of abortions carried out in unsafe, unsanitary and often illegal conditions, the report said.

Current contraceptives have side effects or simply don’t meet the specific needs of many men and women: Sterilization is hard to reverse, hormonal methods affect more than just reproductive organs and barrier devices can fail.

“There’s a huge unmet need, evidenced by the fact that hundreds of millions of women globally do not want to become pregnant but are not using contraception,” said Laneta Dorflinger, who oversees clinical trials of new contraceptives and microbicides for Family Health International, a nonprofit organization in Research Triangle Park, N.C.

Studies have found that, worldwide, as many as 60% of all pregnancies are unplanned. And of the estimated 50 million abortions performed worldwide each year, more than 1 million take place in the U.S.

“When you look at the spectrum of needs in contraceptives, it’s not a one-size-fits-all story,” said Dr. Jerome F. Strauss III, director of the Center for Research on Reproduction and Women’s Health at the University of Pennsylvania. Contraceptive needs vary depending upon age, marital status and risk of exposure to sexually transmitted diseases, as well as cultural and religious beliefs.

An Institute of Medicine committee, which Strauss chairs, convened an international symposium earlier this month in Washington, D.C., on improving contraceptive medicine.

The committee will issue a report next year summarizing new research targets, reviewing obstacles to bringing new contraceptives to market and recommending research and development priorities.

Because the Institute of Medicine advises the government, the report could influence federally sponsored contraceptive research.

Although delivery systems, such as pills, foams, implants or injections, have yet to be worked out, potential targets include molecules that control:

* Sperm development and maturation. Researchers have identified some of the myriad genes involved in production and growth of sperm cells in the testes and have done very early work on targeting carbohydrate molecules on the sperm surface.

* Egg development and maturation. Several genes that drive egg development inside the ovary and egg sac, or follicle, and in neighboring cells have been identified, offering hope that they might be turned on and off.

* Interference with sperm-and-egg fusion. Because changes in sperm proteins allow sperm to penetrate the egg’s outer layer, blocking these changes could prevent conception.

* Embryo implantation. Genes and proteins control how an embryo begins chemically communicating with the uterine lining, so manipulating them could prevent embryos from attaching.

High-tech contraceptives based on these theories are not expected to become reality for at least 10 and maybe 15 years, but consumers should expect other options in the interim.

Because of the AIDS pandemic, scientists are conducting clinical trials here and abroad of microbicides that protect against sexually transmitted infections while killing sperm.

Among a group of these compounds are Savvy, from the Philadelphia biotech firm Biosyn, that’s about to enter the final phase of clinical trials, and several gels that kill sperm, bacteria and viruses, including HIV, by maintaining acidity in the vagina but that don’t produce the irritation associated with current spermicides such as Nonoxynol-9.

Clinical trials are continuing for several male hormonal contraceptives that turn off the body’s production of testosterone and sperm.

“Contraceptive technology is the cheapest way to influence health,” Strauss said.