Editor’s Note: This story originally ran as part of our new show, “Sound Effect,” which airs on Saturdays at 10 a.m.
Before there was a birth control pill for women, there existed a pill for men. It showed a lot of promise — until whiskey ruined everything.
An Accidental Discovery
Back in the early 1960s, researchers from the University of Oregon and the University of Washington created a drug that stopped the production of sperm.
It came to be by mistake, as is the case with a number of drugs people use today (Viagra was originally intended to lower blood pressure). Doctors were developing a drug to treat worms in people. While testing it on lab animals, they noticed that the rats and mice weren’t able to reproduce.
“No one knew how they worked, but they thought this could be a wonderful male contraceptive,” said Doctor John Amory, a professor of medicine at the University of Washington.
Human testing showed the pill was free of side effects, says Amory, and researchers were thrilled.
“[We thought,] ‘Wonderful! Here, we have this drug, it seems to safely and effectively suppress sperm counts. And when we stop the drug, sperm levels come back,’” he said.
The drug was called WIN 18446.
Testing On Prison Inmates
How did scientists back in the early 1960s know that the pill worked on people? The researchers had a perfect control group, says Amory: prison inmates.
“They were thought to be ideal candidates. It was common at the time. It no longer is, but it was common at the time to do experiments on prisoners,” Amory said. “They were in one place. They wouldn’t disappear. If something happened, you’d know about it in terms of safety.”
Things seemed to be going well. Between 50 and 100 men were taking the drug for about a year, with no apparent severe side effects.
Then something happened.
“They discovered there was a real catch,” Amory said.
'That's When They Knew They Had A Real Problem'
That catch: alcohol.
WIN18446 did not mix well with alcohol, the researchers learned by coincidence.
“One of the inmates flagged down Dr. Albert Paulson and said, ‘You guys have a real problem. You can’t drink when you take this drug.’ And Dr. Paulson said, ‘Oh, come on, you were probably drinking cleaning fluid,’ The inmate shook his head and pulled out a flask of Jack Daniels whiskey that had been smuggled in, and that’s when they knew they had a real problem,” Amory said.
When WIN and alcohol combine, something called acetaldehyde, which is in the same family as formaldehyde, builds up in the body, making a person feel violently ill.
“You start sweating. You vomit,” Amory said. “Actually, a few people have even died from these reactions, so it’s not trivial. And no drug company would develop a drug like this. As one friend put it, if you couldn’t drink, then you wouldn’t need a male contraceptive.”
While the WIN pill was successfully stopping the production of sperm — bringing male testicles back to their prepubescent state, taking them from the size of kiwis down to small plums — it was also blocking an enzyme in the liver. The body couldn’t metabolize alcohol and flush it out.
What The Drug Was Doing Right
What about marijuana and other drugs? Amory is currently looking into an effective pill for men that can accommodate indulgences. After studying the original WIN experiments, Amory focused on what the drug did right — the chemistry that was stopping the male body form making sperm.
“What the WIN drug was doing was blocking the conversion of Vitamin A, something we all have in our diets, to its active form, retinoic acid,” he said.
Testicles need retinoic acid to make sperm. No retinoic acid? No sperm. And Amory says the testes won’t take up retinoic acid from the circulation; it must make it locally.
“And what does the testis do with retinoic acid? Well, we’re still learning about this, but we do know that with the absence of retinoic acid, we can’t make sperm,” Amory said. “That is now a target for developing novel drugs as male contraceptives that can reversibly suppress sperm production without causing the alcohol-related side effects.”
The drug Amory and his colleagues are trying to create would act as a key, turning off the production of retinoic acid and stopping the male reproductive system’s factory, which makes 1,000 sperm every minute.
Why Men's Pills Must Be Safer Than Women's
So when are we going to get a male pill?
"I think we are looking at least at five and 10 years,” Amory said. “If we can get a compound that’s effective with daily oral dosing, my next dream is to develop an implant based on the same molecular entity that could be put in a man and he could just forget about it for a couple of years. I have two young sons, 10 and 12, and I hope, oh God, wouldn’t it be great to send them to college with one of these four-year implants.”
Whatever comes to market will be safer than the option for women.
You see, women who take a pill or have a hormone implant have a greater chance of having a stroke or getting blood clots. In the world of pharmacogenetics, those risks are considered acceptable because the other option, pregnancy, puts a woman in a whole new category for potentially serious health problems.
Another way to look at it is, taking a pill is safer than being pregnant. For many women, the convenience birth control offers is worth the potential hazards. Amory says you can’t make the same justification for a man’s contraceptive.
“Because a man is not bearing the risks of pregnancy,” Amory said. “So the bar for safety for a male contraceptive is really high, because you're thinking about giving a drug to millions of otherwise healthy young men. So we can’t have things like blood clots and strokes, even in a very small percentage of those men.”
Could Reversing The Pill Help Treat Infertility?
Right now, Amory and his team are testing different drug concentrations out on mice. Once they figure out a dose that works, they’ll administer it to rabbits.
As Amory learns more about the role retinoic acid plays in the production of sperm, he is using his this knowledge thus far to try and help men who are infertile.
If taking retinoic acid out of the equation means no sperm, does that mean the body will make sperm if retinoic acid is added? For men whose infertility is not related to a hormonal imbalance, Amory thinks the answer will be yes.
Amory is currently conducting a study that involves men with low sperm counts taking the acne drug Accutane, which contains retinoic acid. He says the initial data look good, and he’ll know whether this treatment is truly a success in about nine months.
