In a black-and-white film, sperm cells swim furiously in all directions, crashing into one another on their frantic journey to reproduction. In a second film, the sperm cells are barely moving.
What’s the difference between the two? Poison.
In what could be the next great hope in contraceptive research, a team at the University of Minnesota has found a way to halt the movement of sperm by adapting a molecule from an ancient African plant that warriors once used to poison the tips of their arrows. If their research takes them successfully through clinical trials and eventually to market, a warrior’s poison could become the first male birth control pill.
It’s about time, said the scientists behind this discovery.
“An agent like this would be helpful to couples to better plan their families when they want to have children, and it would not be all on the woman,” said Gunda Georg, head of the Department of Medicinal Chemistry at the U’s College of Pharmacy and one of the national leaders in the search for a male contraceptive.
Nearly 60 years after the introduction of an oral contraceptive for women, men still have just three birth control options: one that requires extreme precision and has more limited effectiveness (withdrawal); one that many men say they find inconvenient (condoms); and one that is surgical and not completely reversible (vasectomy). The latter two methods were both developed in the late 19th century.
Since World War II, more than a dozen contraceptives have been developed for women, including implants, patches, shots, sponges, rings, caps, diaphragms, intrauterine devices and the pill, which is still considered the most revolutionary.
So why are men so far behind when it comes to contraception? The motivation to control one’s fertility boils down to one key difference in the sexes.
“The obvious reason is that men don’t get pregnant,” said Elaine Tyler May, an American studies professor at the U and author of “America and the Pill: A History of Promise, Peril, and Liberation.” While women have been pumping their bodies full of hormones for decades, pharmaceutical companies have questioned whether men would be willing to do the same.
“A man can walk away from a pregnancy in ways that women can’t,” May said, “so the stakes are much higher for women.”
Another factor is side effects. Methods of controlling fertility in men have been studied for as long as the female birth control pill. But side effects from depression to impotence have proven to be an obstacle. When the men taking the drugs are otherwise healthy, and have no risk of getting pregnant, the tolerance for side effects plummets.
“Why would you take a birth control method that would make you unable to have normal sex?” May said.
In the decades since the female pill became ubiquitous, pharmaceutical companies gradually shut down their research on male contraceptives.
“There wasn’t an obvious demand, at least from the industry’s perspective,” said Dominique Tobbell, director and associate professor of the History of Medicine program at the U. “You have to really make the case to companies that it’s a drug that’s got real potential and that there’s a market there for it.”
But the industry may have underestimated men’s interest. A study published in 2016 in the Journal of Clinical Endocrinology and Metabolism found that nearly 90 percent of the men who participated in an injectable hormonal contraceptive trial were satisfied with the method. And a 2005 multinational survey by the Berlin Center for Epidemiology and Health Research found that a majority of the 9,000 men interviewed were willing to use a hormonal male contraceptive.
‘Exploring all possible options’
Georg, U chemist Shameem Syeda and Gustavo Blanco, a chemist at the University of Kansas, have been working with the compound ouabain for nearly a decade, finding a way to chemically alter it from a heart-stopping toxin to a non-hormonal sperm paralyzer. The team’s findings land this month on the cover of the Journal of Medicinal Chemistry, of which Georg is editor-in-chief.
A little brown bottle with an orange skull and crossbones contains the white powder that Syeda has coaxed from poison to possible pill. The process involves nine chemical reactions, which takes about 6 to 8 weeks. The final result, which has been tested in rats, has shown to be effective in reducing sperm motility enough to consider them infertile — seemingly without side effects.
Ouabain is just one of a handful of male contraceptive projects that Georg and Syeda are working on simultaneously. They also are researching retinoic acid receptors — which can repress or activate gene expression — and CatSper ion channels, among other targets of male fertility. “We are exploring all possible options,” Syeda said.
The next step for Georg’s team is a mating trial, in which long-lasting effects on generations of rat fertility will be examined. Then, the compound would have to undergo clinical trials on humans, which would be costly.
‘Clearly a leader’ in innovation
Given the dearth of funding and minimal interest from pharmaceutical companies, a new male contraceptive could still be 10 years away from medicine cabinets.
Much of Georg’s funding comes from the Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD), which has a branch devoted to contraceptive research. About 30 percent of the $10 million to $12 million in research grants and contracts that are administered by the branch to support contraceptive development are currently awarded to the U and led by Georg.
“The University of Minnesota is clearly a leader in the development of new and innovative methods of contraception,” said Daniel S. Johnston, chief of NICHD’s contraception research branch. “I think that the drug target their recent paper is focused on is extremely promising, and the project is one of the most advanced in our portfolio.”
But the support of the federal government is still not enough, when compared to the financial might of the pharmaceutical industry.
“As far as I know, there is not a single company that is actually pursuing the drug discovery of a male contraceptive agent,” Georg said. “In a company, you put a team of 20, 30, 50 people on a project. And we can maybe put 2 on. So think about what the pace is going to be. We’re doing what we can, but it is slowing us down.”
All the researchers can do is stay on the front lines and hope that their findings pique the interest of pharmaceutical companies and non-industry groups. They recently got a boost from a small grant from the Male Contraceptive Initiative, which comes from private sources.
With the recent article on ouabain, “there is some excitement,” Georg said.
Despite pessimism from the industry, May said she believes the introduction of a male pill could be as revolutionary as the female pill when it hit the market in 1960. “It would be a very big deal if there was really an effective and acceptable method of birth control,” May said, “because it kind of levels the playing field. It makes it possible for women to say, ‘Your turn.’ ”