Three state-of-the-art birth control methods for women have annual pregnancy rates below 1 in 500, and the user doesn’t have to think about them for years at a time. By contrast, the best option available to men (short of sterilization) has an annual pregnancy rate of about 1 in 6 and has to be rolled onto an erect penis during each sexual encounter. A new generation of researchers would like to change that — but change takes money.
Why the Neglect?
During the last 70 years, billions of dollars have gone into research on female contraception. While pharmaceutical companies are reluctant to invest in innovation, public health dollars and private philanthropists have funded research at university medical schools or nonprofits like the Population Council to fill the gap. As a consequence, family planning options and outcomes have improved, sometimes dramatically. Pills contain less hormones, IUDs now protect against disorders like endometriosis and several methods offer lighter, less frequent periods or other bonus health benefits.
But during the same time, research into male-controlled methods received paltry attention, largely because funders believed men weren’t interested. That may have been true 70 years ago. But many men today say they are perfectly willing to share the responsibility of family planning and in fact want the means to manage their own fertility.
Young Men Feel It
In the 1970s the typical man was about 21 years old when his first child was born. Since then, that age has shifted by almost a decade — 10 years in which many young men prefer to focus on education and launching a career before launching into parenthood. The more a young man cares about being a good partner and father (someday), and the more he cares about his own future, the more he is likely to feel stressed about the potential for unwanted pregnancy. Consider some of the following comments:
- Being self-reliant is important to me. Condoms are pretty much awful, and it's just not good enough for me to have to trust a partner to consistently & effectively address the birth-control question. I know of too many firsthand accounts of instances in which doing so just didn't work out. It's time for men to have reliable options like women do. –Adam
- It's absolutely terrible to have no other option as a male. I'm just 17, and thinking that I'll have to spend 50 years using the condom with no other possibility? That would be awful. I want something new! --Samuel
- I'd like something with the convenience and reliability of The Pill. Pop one in and don't worry about it. The key word here is choice and being free of worry. –Alan
- I simply want to be able to take control into my own hands instead of relying on my partner who doesn't like having synthetic hormones coursing through her.—Adam
- I've been active in discussing and promoting the legalization of abortions, and it's a real pain to see the dismissal of male reproductive rights from the very same people who fight for women. It saddens me to hear the very same arguments the antiabortion camp uses against women. Like "If they're afraid of having unwanted kids, men should get vasectomies," or "Just keep it in your pants." –Facundo Cesa
- Males put their financial future in their hands as we have to pay child support for any pregnancy we father, no matter the circumstance. –Gustavo
- Normally a man just can't know, and he doesn't even have a right to know what's the fertility status of a woman he has sex with. He doesn't know when she had her last period, if she's on the pill, if she has been taking it regularly, if she had antibiotics that might interfere, if she's on some other kind of birth control, if she had a hysterectomy, if she's trans and what's her stance on abortion, or even the morning-after pill (she's under no obligation to tell him ANY of that). That being the case, he just can't make an informed decision when he has sex. –Facundo Cesa
- I want reliable control over my fertility, so I can control the timing and spacing when I have children. At this time in human history, it is a basic right. –Derek
Derek’s comment about family planning as a basic human right strikes home for many. And yet, an upcoming (and much welcome) conference on the Human Right to Family Planning has not a single session devoted to better birth control for men.
In an ideal world, every child would be created with the mutual consent of both biological parents. State of the art “set-and-forget” contraceptives coupled with safe abortion make that future a reality for the female half of the human population, at least for those privileged females who have access to the best money can buy. But guys who have sex (that’s most of them) are still rolling the dice. A woman today may be using a method with a high failure rate. She may not be using contraception consistently enough. She may lie. And if a pregnancy occurs, she has the final say in whether to carry it forward.
Better birth control for men is a moral imperative and a matter of gender justice, as well as making good practical sense. We don’t often talk about it this way, primarily because we’re accustomed to females being the underdogs in the justice equation. For millennia, girls and women had little right to decline either sex or pregnancy, and in much of the world that is still the case. And yet, a young man’s dreams, hopes, and family plans can be shattered by a surprise pregnancy. For those who care deeply about being good fathers, an ill-conceived pregnancy can be devastating. If we are going to help young men become loving, engaged parents, we need to ensure that they father a child only when they feel ready for partnership and nurturing.
The Male Contraception Initiative
Frustrated by the lack of progress on male birth control, attorney Aaron Hamlin founded the Male Contraception Initiative at the beginning of 2015. The mission of MCI is to inform and mobilize the public and secure funding in order to accelerate better birth control for men. The MCI website features and follows a wide range of birth control methods in various phases of research. "We have to cast a wide net," says Hamlin. Even so, almost immediately, the MCI board and staff got excited about the molecular research of a small biotechnology company, Spacefill Discovery, which became the focus of their first, exploratory crowd-funding campaign. After raising $12,000 from 200 donors this summer, MCI has been working with Spacefill Discovery to secure additional grant and venture funding.
Innovation Depends on Small Biotech
Early stage contraceptive research is a wide funnel, meaning many projects need to be funded for one to achieve success. In the past, a pharmaceutical company might have invested hundreds of millions of dollars over literally decades — mostly in dead ends — before taking a new drug to market. One male contraceptive, a bimonthly hormone injection, got as far as international clinical trials before being canceled abruptly in 2011 due to mood changes, depression and increased libido in some trial participants. Long lead times, high financial risks, complex regulations and liability make R & D of this type unattractive to the institutional investor and big pharma. Consequently, contraceptive innovation has largely been abandoned by established pharmaceutical companies, which mostly opt instead to make minor tweaks in existing lucrative franchises in order to extend patent protections. Today, 14 products drive 80 percent of revenue in the female contraceptive market, all of them using hormone formulations that were identified and synthesized a generation ago.
But fundamental changes in bench science have made early stage biotech research cheaper and faster, allowing small players to enter the field, particularly if they can garner support from mission-driven investors. While Johnson & Johnson, Bayer and Merck dominate the market for branded contraceptives (currently all female-focused), the roll call of those involved in early research is largely a list of unknowns: Ligand, Bio Pro, ASKA, Orient Europharma, Hydra Biosciences, Pantarhei ... and of course, the one that caught the eye of the Male Contraception Initiative, Spacefill Discovery.
"It is through science that we prove, but through intuition that we discover." -- H. Poincare
Technological breakthroughs often happen when the unexpected is explored — when the unfettered curiosity of academics and the compulsive tinkering instinct of inventors collide, between the public good and the profit motive, between the joy of discovery and the need to commercialize inventions. Spacefill Discovery is no exception.
I spoke with co-founder Dr. David Brandt to learn more about their male contraception project. “This is a story of how science can happen when you are open to it and not putting blinders on and being too focused on a specific goal,” Dr. Brandt said.
Dr. Brandt was literally minding his own business — cancer research — when he got a call from an old colleague, semi-retired medicinal chemist Dr. Gary Flynn. “I think I’ve discovered something new,” said Flynn. "Medicinal chemist" means Flynn designs medicines at a molecule level. I’m not sure what "retired" means in this context, because Dr. Flynn spends his waking hours designing compounds and then using 3-D modeling techniques, docking them into proteins. Dr. Flynn’s “something new” was a kind of chemical scaffold that binds to a class of proteins known as kinases. Kinases are proteins that control virtually all cell activities, and they are key drug targets. Flynn had found a way, at least in theory, to block them in a new manner.
One Thing Leads to Another
At this point, Drs. Flynn and Brandt had no intention of embarking on the elusive quest for male birth control; they were interested in possible new treatments for cancer. So, they started tinkering with the scaffolding, trying to figure out what kinds of cancer processes Flynn’s compounds could inhibit. The work went slowly; it was a side project. In the meantime, Flynn began excavating the electronic library stacks, searching for related content. He came across a proposal by Dr. James Chen, a Stanford professor who was researching one of the kinases that Flynn’s compounds could block very specifically. That’s when they got excited. I’ll have to leave the technical description in Brandt’s words:
We reached out to Dr. Chen and learned he was working on mechanisms inside the developing sperm cell that this kinase may control. He got excited when he learned that we had very potent and selective inhibitors of this kinase from our cancer research.
Why the excitement? Because the presence of this kinase is 10,000 higher in the testes than anywhere else in the body. That is an ideal situation that we almost never find in drug discovery. Usually a drug’s action on its protein target will affect several tissues and organs in the body, and that is one reason drugs have side effects.
One of the big challenges of developing a male pill is that ... with the female reproductive system if you perturb it the system shuts down. With men the primary hormone regulating sperm production is testosterone which is also plays a key role in normal behavior and metabolic ability — it affects sugars, lipids and muscle tone, so you don’t want to block it. What’s really exciting about this kinase is that, if you look at the entire pathway of spermatogenesis, it is found only in the later stages not at the germ cell line stage. In mice if you knock out this gene they are healthy but sterile. So it has a very narrow function, and hitting late stages makes reversibility more probable. And it’s non-hormonal!
Fizz or Fizzle?
Have Drs. Brandt, Flynn and Chen found a way forward? I remind myself of the cautionary mantras: Early stage biomedical research is a big funnel. Most start-ups fail. That’s why angel investing and venture capital are high risk.
But the few that succeed have the power to change individual lives and shape the future. That’s why angel investing and venture capital are also high reward.
Brandt himself is chomping at the bit. “We have been working on it at a very low level out of our own pockets. Now we are looking for funding to ramp it up from a side research project. If it is properly funded — the time frame is really driven by funding — we could be in the clinic in three years.” he says. That’s clinical trials, not your local Planned Parenthood, and that’s only if all the ducks line up, but it would be huge.
Will it happen? That’s hard to say. Spacefill Discovery’s funders are focused on cancer. Drs. Flynn and Chen submitted a grant to the National Institutes of Health, but didn’t get it. They came out at the top of the Male Contraception Initiative’s competition for crowd-funding, but MCI is barely off the ground itself.
Even so, to Brandt’s mind — as to mine — the imperative is clear. A 2012 survey of 40,000 men who were asked about their desire for better male birth control came back with a resounding "Yes!" Dr. Brandt conducts an informal survey of his own among friends who ask about his work. “I get dramatic responses,” he says. “No way or where can I get it? Nothing in between. About 70 percent of guys in my network say 'Where can I get it?', and the other 30 percent say 'No way.' That’s only my social network. I would like to see the data in the 18- to 35-year-old demographic, because right now the only really effective protection is a vasectomy, which is permanent. What if your life changes and later you want to have a child?”
Dr. Brandt recalls the stress of being a single man, the lack of options, the edge of worry — even after marriage — that life might be dramatically altered by an unanticipated child. He talks about his two daughters and what it’s like as a dad to hope your daughter’s dreams and ambitions won’t get derailed by a surprise pregnancy, and how parents of young men feel the same way. We need more conversation about male birth control, he says. It would change the dynamic between men and women. It would change lives. Advocate Facundo Cesa agrees. “A friend of mine just got a vasectomy. He chose to forget all about ever having children. His peace of mind was worth it, he says.” Worth it, maybe, but why should young men have to make that hard choice? Surely we can do better.