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For half a century, Gursaran Pran Talwar has been developing what he hopes will be the next big thing in birth control. A nonagenarian who was once the director of India’s National Institute of Immunology, Talwar envisions bringing to market a new form of contraception that could block pregnancy without the usual trade-offs—an intervention that’s long-acting but reversible; cheap, discreet, and easy to administer; less invasive than an intrauterine device and more convenient than a daily pill. It would skip messy, sometimes dangerous side effects, such as weight gain, mood swings, and rare but risky blood clots and strokes. It would embody the sort of “set it and forget it” model that’s become a gold standard for health—and, in his words, be “accepted by the world over.”
Talwar’s invention is now in early-stage clinical trials. If all goes well, it could become humanity’s first contraceptive vaccine—one that would prevent pregnancies in a way distinct from any birth control ever cleared for human use. Whether they’re packaged as pills, patches, implants, or shots, most common medical contraceptives work by flooding the body with hormones to put a pause on ovulation. Talwar’s vaccine would do something different: It leaves the menstrual cycle unaltered, instead leveraging the powers of the immune system to keep unwanted pregnancies at bay.
But temporarily vaccinating against pregnancy is both brilliant in concept and devilishly difficult in execution, both scientifically and socially. Making a contraceptive vaccine effectively means “trying to immunize an animal against itself,” says Julie Levy, a feline-infectious-disease expert at the University of Florida who has worked on immunocontraceptives in animals. Which runs counter to the prime directive of immune systems, evolved over countless millennia to distinguish the foreign from the familiar and to leave the body’s most vital tissues alone. Solve that problem, and researchers will still be left with another: persuading people to take a fertility-hampering shot in an era of widespread vaccine hesitancy—while the specter of contraception’s problematic past still looms.
For many decades, the most stubborn barriers in contraception have been not about science, but about access and acceptance. Talwar remembers those issues crystallizing sharply for him in the 1970s, he told me, when he encountered several groups of women in the holy city of Varanasi, who told him they were struggling to feed their large families. Yet the women’s husbands weren’t eager to use condoms and they themselves weren’t satisfied with the pills and IUDs available at the time, which sometimes interfered with normal menstruation and ovulation, and triggered headaches and mood swings. “I wanted to make something free of all these problems,” Talwar told me.
Within a few years, he had cooked up a solution: a vaccine against hCG, a hormone exclusive to pregnancy that’s necessary for fertilized eggs to implant. Taught to neutralize hCG, Talwar reasoned, the immune system could stop a pregnancy from ever truly starting, without attacking other tissues. His hunch so far appears to have panned out. By the mid-1990s, his team had shown in small, early-stage clinical trials that most women receiving the shots could produce enough antibodies to prevent pregnancy for several months, in some cases more than a year. Of the 119 women in the trial whose antibody levels reached what Talwar deems a protective threshold, only one became pregnant over a period of almost two years. Several participants also went on to conceive after opting out of boosters, a sign that the shot’s effects were reversible.
Almost immediately, though, drawbacks appeared. Immune responses are infamously variable across individuals—a major reason that the effectiveness of many shots designed against pathogens tops out around 60 to 80 percent. About a fifth of the women who received the hCG vaccine didn’t produce enough antibodies to meet the protective threshold. Those stats would still be enough to slow the transmission of, say, a deadly respiratory virus. But the expectations for a contraceptive “have to be different,” says Neel Shah, the chief medical officer of Maven Clinic, a virtual clinic for women’s and family health. The top IUDs on the market prevent more than 99 percent of pregnancies, require one appointment to insert, and last for up to a decade.
For now, the hCG vaccine is more cumbersome than that. In its current iteration—a revamp of the successful ’90s recipe—it requires an initial series of at least three doses, spaced out over several weeks. It’s still unclear how people would figure out when, and how often, to boost without regular antibody tests. The answer will likely differ from person to person; that uncertainty alone could make these shots a tough sell, says Diana Blithe, a contraception expert at the National Institutes of Health. And although halting hormonal contraceptives can reset fertility back to baseline within days or weeks, some people with especially enthusiastic immune responses could end up waiting far longer for the hCG vaccine’s effects to wear off, says Aaron Hsueh, a reproductive biologist at Stanford. For that reason and more, Hsueh has said for years that he’s “not enthusiastic” about Talwar’s experimental shot.
There is some reason to think these issues aren’t insurmountable. Immunocontraceptives have been used for decades by wildlife scientists to prevent pregnancies in all sorts of mammals—among them deer, horses, elephants, pigs, and seals—as a more humane alternative to culling. And in that context, at least, researchers have found a way to circumvent the need for frequent boosts. Certain animals can be dosed with nanoparticles that slowly release the vaccine’s ingredients over months and years, repeatedly tickling the immune system without any additional jabs, says Derek Rosenfield, a veterinarian and wildlife biologist at the University of São Paulo. Work in wild creatures, though, has also shown how hard it is to persuade the body to target its own hormones. To get their shots to work, veterinarians have needed to include powerful adjuvants, or vaccine ingredients meant to rile up the immune system—“some of the most potent ones ever developed,” Levy told me. Which exacts a tax for the shots’ potency: In some animals, such as cats, the vaccines can cause worrying side effects, including injection-site reactions.
In humans, where safety standards must be stricter and effectiveness better, Talwar’s hCG vaccine has encountered some issues with tolerability, too. The shots so far do seem to be skirting the side effects of pills and IUDs. But some of the women in his team’s ongoing trials are developing painless but prominent nodules—a likely sign that the new recipe’s adjuvants are riling up the immune system a tad too much. To deliver on a discreet, low-maintenance contraceptive—something with, as Talwar puts it, “zero side effects”—they’ll need to tinker with dosing or ingredients.
Gaps in the contraceptive market do need to be filled. Technology has come a long way since Talwar first spoke with the women in Varanasi, but “we need more options,” says Debanjana Choudhuri, the director of programs and partnerships at India’s Foundation for Reproductive Health Services. Nearly half the world’s pregnancies are unplanned, and access to existing contraception is inconsistent, inequitable, and still stymied by stigma and misinformation; even in places where availability isn’t an issue, some people hesitate over the trade-offs. A temporary contraception, packaged into a super-safe vaccine, could offer convenience and privacy, with potential appeal for young urbanites, who have already been enthusiastic about injectable contraceptives and might not mind getting boosts, Choudhuri told me. Most important, adding a vaccine to the repertoire gives people “another choice.”
But for all its unique perks, a contraceptive vaccine could also come with social drawbacks. The history of contraception is riddled with abuses, often concentrated among poor populations, people struggling with mental-health issues, and communities of color. Vaccines’ primary purpose for centuries has been to fight infectious disease, and “pregnancy is not a disease,” Sanghamitra Singh, the policy-and-programs lead at the Population Foundation of India, told me. Implying—even unintentionally—that the condition is a problem to be eradicated could stigmatize the shot.
Deploying the vaccine primarily in under-resourced populations could also raise the specter of the eradication of fertility in society’s most vulnerable subsects. Lisa Campo-Engelstein, a reproductive bioethicist at the University of Texas Medical Branch, worries that even the vaccine’s ease of administration—an ostensible benefit—could be viewed as a downside: Administering a shot without a patient’s full understanding or consent is easier than coercively inserting an IUD or forcing a daily pill. And in this pandemic era, a contraceptive vaccine will likely be met with pushback from people already disinclined toward shots—especially amid false accusations that other immunizations compromise fertility. On top of all that, a shot that goes after hCG can prevent only implantation, not fertilization, a guaranteed sticking point for people who believe that life begins at conception, and may argue that the vaccine triggers abortion.
In part, the timing is just bad luck. Shortly after his original clinical trial results were published, in the ’90s, Talwar, already late into his 60s, was asked to retire from the National Institute of Immunology, he told me, and had to leave his vaccine behind. After he managed to revive his efforts with the help of independent funders, Indian regulators took nearly a decade to green-light a new recipe for clinical trials—just in time for the coronavirus pandemic to begin. Régine Sitruk-Ware, a reproductive endocrinologist at the Population Council’s Center for Biomedical Research, in New York, remembers the initial buzz around the human hCG vaccine when Talwar’s clinical-trial results were published. But in the absence of more progress, she and other researchers have moved on, she told me. Many now have their sights set on long-acting reversible male birth control, several new forms of which are now close to being publicly available, and could offer safe complements to female methods and make family planning more equitable.
Still, Talwar, who will turn 97 in October, hasn’t lost hope; to him, the nodules represent one of the last major hurdles, and should be resolved soon. As his 100th birthday ticks closer, he’s even thinking of how he can expand his approach—repurposing the hCG shot, for instance, into immunotherapy against certain cancers that aberrantly produce the hormone. “I am healthy and hearty,” he told me. “I just hope and pray,” he said, that his invention might clear its final hurdles “before I call it a day.”
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Katherine J. Wu
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