The future of non-hormonal birth control: Antibodies can stop sperm in their tracks
Unwanted pregnancy can now be added to the list of preventions that antibodies may be fighting in the near future. For decades, really since the 1980s, engineered monoclonal antibodies have been knocking out invading germs — preventing everything from cancer to COVID. Sperm, which have some of the same properties as germs, may be next.
Not only is there an unmet need on the market for alternatives to hormonal contraceptives, the genesis for the original research was personal for the then 22-year-old scientist who led it. Her findings were used to launch a company that could, within the decade, bring a new kind of contraceptive to the marketplace.
It’s Suruchi Shrestha’s research — published in Science Translational Medicine in August 2021 and conducted as part of her dissertation while she was a graduate student at the University of North Carolina at Chapel Hill — that could change the future of contraception for many women worldwide. According to a Guttmacher Institute report, in the U.S. alone, there were 46 million sexually active women of reproductive age (15–49) who did not want to get pregnant in 2018. With the overturning of Roe v. Wade last year, Shrestha’s research could, indeed, be life changing for millions of American women and their families.
Now a scientist with NextVivo, Shrestha is not directly involved in the development of the contraceptive that is based on her research. But, back in 2016 when she was going through her own problems with hormonal contraceptives, she “was very personally invested” in her research project, Shrestha says. She was coping with a long list of negative effects from an implanted hormonal IUD. According to the Mayo Clinic, those can include severe pelvic pain, headaches, acute acne, breast tenderness, irregular bleeding and mood swings. After a year, she had the IUD removed, but it took another full year before all the side effects finally subsided; she also watched her sister suffer the “same tribulations” after trying a hormonal IUD, she says.
For contraceptive use either daily or monthly, Shrestha says, “You want the antibody to be very potent and also cheap.” That was her goal when she launched her study.
Shrestha unshelved antibody research that had been sitting idle for decades. It was in the late 80s that scientists in Japan first tried to develop anti-sperm antibodies for contraceptive use. But, 35 years ago, “Antibody production had not been streamlined as it is now, so antibodies were very expensive,” Shrestha explains. So, they shifted away from birth control, opting to focus on developing antibodies for vaccines.
Over the course of the last three decades, different teams of researchers have been working to make the antibody more effective, bringing the cost down, though it’s still expensive, according to Shrestha. For contraceptive use either daily or monthly, she says, “You want the antibody to be very potent and also cheap.” That was her goal when she launched her study.
The problem with contraceptives for women, Shrestha says, is that all but a few of them are hormone-based or have other negative side effects. In fact, some studies and reports show that millions of women risk unintended pregnancy because of medical contraindications with hormone-based contraceptives or to avoid the risks and side effects. While there are about a dozen contraceptive choices for women, there are two for men: the condom, considered 98% effective if used correctly, and vasectomy, 99% effective. Neither of these choices are hormone-based.
On the non-hormonal side for women, there is the diaphragm which is considered only 87 percent effective. It works better with the addition of spermicides — Nonoxynol-9, or N-9 — however, they are detergents; they not only kill the sperm, they also erode the vaginal epithelium. And, there’s the non-hormonal IUD which is 99% effective. However, the IUD needs to be inserted by a medical professional, and it has a number of negative side effects, including painful cramping at a higher frequency and extremely heavy or “abnormal” and unpredictable menstrual flows.
The hormonal version of the IUD, also considered 99% effective, is the one Shrestha used which caused her two years of pain. Of course, there’s the pill, which needs to be taken daily, and the birth control ring which is worn 24/7. Both cause side effects similar to the other hormonal contraceptives on the market. The ring is considered 93% effective mostly because of user error; the pill is considered 99% effective if taken correctly.
“That’s where we saw this opening or gap for women. We want a safe, non-hormonal contraceptive,” Shrestha says. Compounding the lack of good choices, is poor access to quality sex education and family planning information, according to the non-profit Urban Institute. A focus group survey suggested that the sex education women received “often lacked substance, leaving them feeling unprepared to make smart decisions about their sexual health and safety,” wrote the authors of the Urban Institute report. In fact, nearly half (45%, or 2.8 million) of the pregnancies that occur each year in the US are unintended, reports the Guttmacher Institute. Globally the numbers are similar. According to a new report by the United Nations, each year there are 121 million unintended pregnancies, worldwide.
The early work on antibodies as a contraceptive had been inspired by women with infertility. It turns out that 9 to 12 percent of women who are treated for infertility have antibodies that develop naturally and work against sperm. Shrestha was encouraged that the antibodies were specific to the target — sperm — and therefore “very safe to use in women.” She aimed to make the antibodies more stable, more effective and less expensive so they could be more easily manufactured.
Since antibodies tend to stick to things that you tell them to stick to, the idea was, basically, to engineer antibodies to stick to sperm so they would stop swimming. Shrestha and her colleagues took the binding arm of an antibody that they’d isolated from an infertile woman. Then, targeting a unique surface antigen present on human sperm, they engineered a panel of antibodies with as many as six to 10 binding arms — “almost like tongs with prongs on the tongs, that bind the sperm,” explains Shrestha. “We decided to add those grabbers on top of it, behind it. So it went from having two prongs to almost 10. And the whole goal was to have so many arms binding the sperm that it clumps it” into a “dollop,” explains Shrestha, who earned a patent on her research.
Suruchi Shrestha works in the lab with a colleague. In 2016, her research on antibodies for birth control was inspired by her own experience with side effects from an implanted hormonal IUD.
UNC - Chapel Hill
The sperm stays right where it met the antibody, never reaching the egg for fertilization. Eventually, and naturally, “Our vaginal system will just flush it out,” Shrestha explains.
“She showed in her early studies that [she] definitely got the sperm immotile, so they didn't move. And that was a really promising start,” says Jasmine Edelstein, a scientist with an expertise in antibody engineering who was not involved in this research. Shrestha’s team at UNC reproduced the effect in the sheep, notes Edelstein, who works at the startup Be Biopharma. In fact, Shrestha’s anti-sperm antibodies that caused the sperm to agglutinate, or clump together, were 99.9% effective when delivered topically to the sheep’s reproductive tracts.
Going forward, Shrestha thinks the ideal approach would be delivering the antibodies through a vaginal ring. “We want to use it at the source of the spark,” Shrestha says, as opposed to less direct methods, such as taking a pill. The ring would dissolve after one month, she explains, “and then you get another one.”
Engineered to have a long shelf life, the anti-sperm antibody ring could be purchased without a prescription, and women could insert it themselves, without a doctor. “That's our hope, so that it is accessible,” Shrestha says. “Anybody can just go and grab it and not worry about pregnancy or unintended pregnancy.”
Her patented research has been licensed by several biotech companies for clinical trials. A number of Shrestha’s co-authors, including her lab advisor, Sam Lai, have launched a company, Mucommune, to continue developing the contraceptives based on these antibodies.
And, results from a small clinical trial run by researchers at Boston University Chobanian & Avedisian School of Medicine show that a dissolvable vaginal film with antibodies was safe when tested on healthy women of reproductive age. That same group of researchers last year received a $7.2 million grant from the National Institute of Health for further research on monoclonal antibody-based contraceptives, which have also been shown to block transmission of viruses, like HIV.
“As the costs come down, this becomes a more realistic option potentially for women,” says Edelstein. “The impact could be tremendous.”
This article was first published by Leaps.org in December, 2022. It has been lightly edited with updates for timeliness.
From ROBOTS AND THE PEOPLE WHO LOVE THEM: Holding on to Our Humanity in an Age of Social Robots by Eve Herold. Copyright © 2024 by the author and reprinted by permission of St. Martin’s Publishing Group.
Could the use of robots take some of the workload off teachers, add engagement among students, and ultimately invigorate learning by taking it to a new level that is more consonant with the everyday experiences of young people? Do robots have the potential to become full-fledged educators and further push human teachers out of the profession? The preponderance of opinion on this subject is that, just as AI and medical technology are not going to eliminate doctors, robot teachers will never replace human teachers. Rather, they will change the job of teaching.
A 2017 study led by Google executive James Manyika suggested that skills like creativity, emotional intelligence, and communication will always be needed in the classroom and that robots aren’t likely to provide them at the same level that humans naturally do. But robot teachers do bring advantages, such as a depth of subject knowledge that teachers can’t match, and they’re great for student engagement.
The teacher and robot can complement each other in new ways, with the teacher facilitating interactions between robots and students. So far, this is the case with teaching “assistants” being adopted now in China, Japan, the U.S., and Europe. In this scenario, the robot (usually the SoftBank child-size robot NAO) is a tool for teaching mainly science, technology, engineering, and math (the STEM subjects), but the teacher is very involved in planning, overseeing, and evaluating progress. The students get an entertaining and enriched learning experience, and some of the teaching load is taken off the teacher. At least, that’s what researchers have been able to observe so far.
To be sure, there are some powerful arguments for having robots in the classroom. A not-to-be-underestimated one is that robots “speak the language” of today’s children, who have been steeped in technology since birth. These children are adept at navigating a media-rich environment that is highly visual and interactive. They are plugged into the Internet 24-7. They consume music, games, and huge numbers of videos on a weekly basis. They expect to be dazzled because they are used to being dazzled by more and more spectacular displays of digital artistry. Education has to compete with social media and the entertainment vehicles of students’ everyday lives.
Another compelling argument for teaching robots is that they help prepare students for the technological realities they will encounter in the real world when robots will be ubiquitous. From childhood on, they will be interacting and collaborating with robots in every sphere of their lives from the jobs they do to dealing with retail robots and helper robots in the home. Including robots in the classroom is one way of making sure that children of all socioeconomic backgrounds will be better prepared for a highly automated age, when successfully using robots will be as essential as reading and writing. We’ve already crossed this threshold with computers and smartphones.
Students need multimedia entertainment with their teaching. This is something robots can provide through their ability to connect to the Internet and act as a centralized host to videos, music, and games. Children also need interaction, something robots can deliver up to a point, but which humans can surpass. The education of a child is not just intended to make them technologically functional in a wired world, it’s to help them grow in intellectual, creative, social, and emotional ways. When considered through this perspective, it opens the door to questions concerning just how far robots should go. Robots don’t just teach and engage children; they’re designed to tug at their heartstrings.
It’s no coincidence that many toy makers and manufacturers are designing cute robots that look and behave like real children or animals, says Turkle. “When they make eye contact and gesture toward us, they predispose us to view them as thinking and caring,” she has written in The Washington Post. “They are designed to be cute, to provide a nurturing response” from the child. As mentioned previously, this nurturing experience is a powerful vehicle for drawing children in and promoting strong attachment. But should children really love their robots?
ROBOTS AND THE PEOPLE WHO LOVE THEM: Holding on to Our Humanity in an Age of Social Robots by Eve Herold (January 9, 2024).
St. Martin’s Publishing Group
The problem, once again, is that a child can be lulled into thinking that she’s in an actual relationship, when a robot can’t possibly love her back. If adults have these vulnerabilities, what might such asymmetrical relationships do to the emotional development of a small child? Turkle notes that while we tend to ascribe a mind and emotions to a socially interactive robot, “simulated thinking may be thinking, but simulated feeling is never feeling, and simulated love is never love.”
Always a consideration is the fact that in the first few years of life, a child’s brain is undergoing rapid growth and development that will form the foundation of their lifelong emotional health. These formative experiences are literally shaping the child’s brain, their expectations, and their view of the world and their place in it. In Alone Together, Turkle asks: What are we saying to children about their importance to us when we’re willing to outsource their care to a robot? A child might be superficially entertained by the robot while his self-esteem is systematically undermined.
Research has emerged showing that there are clear downsides to child-robot relationships.
Still, in the case of robot nannies in the home, is active, playful engagement with a robot for a few hours a day any more harmful than several hours in front of a TV or with an iPad? Some, like Xiong, regard interacting with a robot as better than mere passive entertainment. iPal’s manufacturers say that their robot can’t replace parents or teachers and is best used by three- to eight-year-olds after school, while they wait for their parents to get off work. But as robots become ever-more sophisticated, they’re expected to perform more of the tasks of day-to-day care and to be much more emotionally advanced. There is no question children will form deep attachments to some of them. And research has emerged showing that there are clear downsides to child-robot relationships.
Some studies, performed by Turkle and fellow MIT colleague Cynthia Breazeal, have revealed a darker side to the child-robot bond. Turkle has reported extensively on these studies in The Washington Post and in her book Alone Together. Most children love robots, but some act out their inner bully on the hapless machines, hitting and kicking them and otherwise trying to hurt them. The trouble is that the robot can’t fight back, teaching children that they can bully and abuse without consequences. As in any other robot relationship, such harmful behavior could carry over into the child’s human relationships.
And, ironically, it turns out that communicative machines don’t actually teach kids good communication skills. It’s well known that parent-child communication in the first three years of life sets the stage for a very young child’s intellectual and academic success. Verbal back-and-forth with parents and care-givers is like fuel for a child’s growing brain. One article that examined several types of play and their effect on children’s communication skills, published in JAMA Pediatrics in 2015, showed that babies who played with electronic toys—like the popular robot dog Aibo—show a decrease in both the quantity and quality of their language skills.
Anna V. Sosa of the Child Speech and Language Lab at Northern Arizona University studied twenty-six ten- to sixteen- month-old infants to compare the growth of their language skills after they played with three types of toys: electronic toys like a baby laptop and talking farm; traditional toys like wooden puzzles and building blocks; and books read aloud by their parents. The play that produced the most growth in verbal ability was having books read to them by a caregiver, followed by play with traditional toys. Language gains after playing with electronic toys came dead last. This form of play involved the least use of adult words, the least conversational turntaking, and the least verbalizations from the children. While the study sample was small, it’s not hard to extrapolate that no electronic toy or even more abled robot could supply the intimate responsiveness of a parent reading stories to a child, explaining new words, answering the child’s questions, and modeling the kind of back- and-forth interaction that promotes empathy and reciprocity in relationships.
Most experts acknowledge that robots can be valuable educational tools. But they can’t make a child feel truly loved, validated, and valued. That’s the job of parents, and when parents abdicate this responsibility, it’s not only the child who misses out on one of life’s most profound experiences.
We really don’t know how the tech-savvy children of today will ultimately process their attachments to robots and whether they will be excessively predisposed to choosing robot companionship over that of humans. It’s possible their techno literacy will draw for them a bold line between real life and a quasi-imaginary history with a robot. But it will be decades before we see long-term studies culminating in sufficient data to help scientists, and the rest of us, to parse out the effects of a lifetime spent with robots.
This is an excerpt from ROBOTS AND THE PEOPLE WHO LOVE THEM: Holding on to Our Humanity in an Age of Social Robots by Eve Herold. The book will be published on January 9, 2024.
Story by Big Think
In rare cases, a woman’s heart can start to fail in the months before or after giving birth. The all-important muscle weakens as its chambers enlarge, reducing the amount of blood pumped with each beat. Peripartum cardiomyopathy can threaten the lives of both mother and child. Viral illness, nutritional deficiency, the bodily stress of pregnancy, or an abnormal immune response could all play a role, but the causes aren’t concretely known.
If there is a silver lining to peripartum cardiomyopathy, it’s that it is perhaps the most survivable form of heart failure. A remarkable 50% of women recover spontaneously. And there’s an even more remarkable explanation for that glowing statistic: The fetus‘ stem cells migrate to the heart and regenerate the beleaguered muscle. In essence, the developing or recently born child saves its mother’s life.
While this process has not been observed directly in humans, it has been witnessed in mice. In a 2015 study, researchers tracked stem cells from fetal mice as they traveled to mothers’ damaged cardiac cells and integrated themselves into hearts.
Evolutionarily, this function makes sense: It is in the fetus’ best interest that its mother remains healthy.
Scientists also have spotted cells from the fetus within the hearts of human mothers, as well as countless other places inside the body, including the skin, spleen, liver, brain, lung, kidney, thyroid, lymph nodes, salivary glands, gallbladder, and intestine. These cells essentially get everywhere. While most are eliminated by the immune system during pregnancy, some can persist for an incredibly long time — up to three decades after childbirth.
This integration of the fetus’ cells into the mother’s body has been given a name: fetal microchimerism. The process appears to start between the fourth and sixth week of gestation in humans. Scientists are actively trying to suss out its purpose. Fetal stem cells, which can differentiate into all sorts of specialized cells, appear to target areas of injury. So their role in healing seems apparent. Evolutionarily, this function makes sense: It is in the fetus’ best interest that its mother remains healthy.
Sending cells into the mother’s body may also prime her immune system to grow more tolerant of the developing fetus. Successful pregnancy requires that the immune system not see the fetus as an interloper and thus dispatch cells to attack it.
But fetal microchimerism might not be entirely beneficial. Greater concentrations of the cells have been associated with various autoimmune diseases such as lupus, Sjogren’s syndrome, and even multiple sclerosis. After all, they are foreign cells living in the mother’s body, so it’s possible that they might trigger subtle, yet constant inflammation. Fetal cells also have been linked to cancer, although it isn’t clear whether they abet or hinder the disease.
A team of Spanish scientists summarized the apparent give and take of fetal microchimerism in a 2022 review article. “On the one hand, fetal microchimerism could be a source of progenitor cells with a beneficial effect on the mother’s health by intervening in tissue repair, angiogenesis, or neurogenesis. On the other hand, fetal microchimerism might have a detrimental function by activating the immune response and contributing to autoimmune diseases,” they wrote.
Regardless of a fetus’ cells net effect, their existence alone is intriguing. In a paper published earlier this year, University of London biologist Francisco Úbeda and University of Western Ontario mathematical biologist Geoff Wild noted that these cells might very well persist within mothers for life.
“Therefore, throughout their reproductive lives, mothers accumulate fetal cells from each of their past pregnancies including those resulting in miscarriages. Furthermore, mothers inherit, from their own mothers, a pool of cells contributed by all fetuses carried by their mothers, often referred to as grandmaternal microchimerism.”
So every mother may carry within her literal pieces of her ancestors.