The half-century-long quest to develop a male birth control pill has just received a boost from an unexpected corner: a Boston laboratory working to craft potent anticancer drugs.
Scientists found that by injecting mice with a compound originally used in cancer research, they could interfere with normal sperm development, rendering male mice infertile. But, importantly, when the mice were taken off the regimen, they could sire normal offspring.
Researchers are working to tweak the substance so that it will target only a protein found in the testicles, in hope the work could lead to an experimental drug and, in turn, a new form of birth control.
The work is early and still far from even being tested in men, but it provides a powerful starting point for efforts to develop a drug that could give men more responsibility and control over family planning.
Stopping sperm — decreasing their number and ability to move — would seem to have little in common with shrinking tumors. Indeed, unplanned pregnancies were far from Dr. James Bradner’s mind when the Dana-Farber Cancer Institute oncologist led an effort two years ago to craft a molecule researchers hoped would help spawn cancer-fighting drugs. But illustrating the serendipity that often underlies scientific progress, Bradner and collaborators reported Thursday in the journal Cell evidence that the experimental drug could prevent mice from siring offspring but that fertility returned when the regimen was stopped, with the offspring being normal.
With a slew of new efforts to interrupt the normal course of sperm development or to block its ability to fertilize the egg — driven by incidental findings from scientists studying cancer or neurobiology and by the revival of drugs designed for other reasons — scientists said they have a number of solid leads on how to shift more responsibility for family planning to men.
“Everybody would like a better solution than condoms and birth control pills,” said Dr. David Clapham, a professor of pediatric cardiology at Children’s Hospital Boston.
But the hurdles to male contraceptive development remain high. Because the drugs would be given to healthy men, researchers have to focus on safety and ensure that any eventual birth control medication does not have side effects. That will be especially important, Clapham said, considering that the molecule they are starting with was initially of interest for use in chemotherapy.
Female birth control pills, which transformed women’s control over their reproductive abilities, were in some ways tackling a simpler problem.
Dr. John Amory, a professor at the University of Washington School of Medicine who has worked on hormonal treatments for men and a drug that interferes with the maturation of sperm, said that in some ways it is a numbers game.
A birth control method for women must prevent just one egg a month from being fertilized. Men, though, with every heartbeat generate roughly 1,000 sperm, whose numbers would have to be reduced by 99 percent for a contraceptive to be effective.
“I was thrilled to see this work,” Amory said of the new study. “It’s a really good lead in terms of the nonhormonal approach to male contraception.”
Bradner normally sees patients with blood cancers and runs a laboratory aimed at cancer drug discovery. Two years ago, his laboratory created a molecule that targeted a particular gene that appeared to help cancer cells “remember” their identity. They called the compound JQ1, named after the scientist, Jun Qi, who developed the compound.
JQ1 seemed to be living up to its promise as a tool that could lead to eventual therapy. The research team found JQ1 could interfere with the activity of a particularly important cancer-causing gene. When the scientists were examining the drug, they saw a glimmer of activity against a protein similar to the one they were trying to disrupt in cancer. But this protein appeared only in the testicles.
Bradner began scouring the scientific literature to learn what he could about the protein and found that other researchers had uncovered hints that it was profoundly involved in male fertility. A scientist at Columbia University Medical Center, Debra Wolgemuth, had found that deleting a portion of instructions for the protein caused mice to become sterile. Bradner teamed up with Dr. Martin Matzuk, a reproductive biologist at the Baylor College of Medicine, to rigorously test whether the compound could interfere with the development of sperm.
It is only one of a handful of approaches being used. Wolgemuth and Amory are both working on different approaches to disrupt sperm development. Clapham is working on a technique that stops mature sperm in their tracks, by impeding what he calls the “turbo-thruster stage,” the hyperactive movement sperm’s tails use to move and fertilize the egg. Hormonal approaches are the furthest along, but they do not work in all men, and there has been worry about the long-term safety of taking such drugs.
“I don't think there’s been a lot of resources poured into it, quite frankly,” said Diana Blithe, director of the male contraceptive development program at the National Institute of Child Health and Human Development. “I think that a lot of companies feel it’s a zero-sum game, if they already have a lot at stake in female contraceptives, they’re just going to lose.”
Some of the hesitation about male birth control has focused on social questions. Would men take such a pill? Would women trust their sexual partners?
Steve Owens, a 40-year-old middle school teacher from Seattle, has participated in more than half-a-dozen trials over the last 11 years, from rubbing testosterone gel onto his shoulders to getting a hor monal implant in his arm. Periodically, he took time off from the studies, and he and his wife had two daughters, now 5 years old and 5 months old.
“My wife had been on the pill before our first daughter for 15 to 16 years; we didn’t want to have to go back on the pill,” Owens said.
He said his experience suggests men and women want more options, adding that he gets a lot of attention at parties. “Some of the dudes would be like, ‘There’s no way I would do that,’ ” he said. “And all the girls are like, ‘When is this thing going to be on the market?’ ”
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