Which Meds are Safe When You’re Pregnant? Science Wants to Find Out
Sarah Mancoll was 22 years old when she noticed a bald spot on the back of her head. A dermatologist confirmed that it was alopecia aerata, an autoimmune disorder that causes hair loss.
Of 213 new drugs approved from 2003 to 2012, only five percent included any data from pregnant women.
She successfully treated the condition with corticosteroid shots for nearly 10 years. Then Mancoll and her husband began thinking about starting a family. Would the shots be safe for her while pregnant? For the fetus? What about breastfeeding?
Mancoll consulted her primary care physician, her dermatologist, even a pediatrician. Without clinical data, no one could give her a definitive answer, so she stopped treatment to be "on the safe side." By the time her son was born, she'd lost at least half her hair. She returned to her Washington, D.C., public policy job two months later entirely bald—and without either eyebrows or eyelashes.
After having two more children in quick succession, Mancoll recently resumed the shots but didn't forget her experience. Today, she is an advocate for including more pregnant and lactating women in clinical studies so they can have more information about therapies than she did.
"I live a very privileged life, and I'll do just fine with or without hair, but it's not just about me," Mancoll said. "It's about a huge population of women who are being disenfranchised…They're invisible."
About 4 million women give birth each year in the United States, and many face medical conditions, from hypertension and diabetes to psychiatric disorders. A 2011 study showed that most women reported taking at least one medication while pregnant between 1976 and 2008. But for decades, pregnant and lactating women have been largely excluded from clinical drug studies that rigorously test medications for safety and effectiveness.
An estimated 98 percent of government-approved drug treatments between 2000 and 2010 had insufficient data to determine risk to the fetus, and close to 75 percent had no human pregnancy data at all. All told, of 213 new pharmaceuticals approved from 2003 to 2012, only five percent included any data from pregnant women.
But recent developments suggest that could be changing. Amid widespread concerns about increased maternal mortality rates, women's health advocates, physicians, and researchers are sensing and encouraging a cultural shift toward protecting women through responsible research instead of from research.
"The question is not whether to do research with pregnant women, but how," Anne Drapkin Lyerly, professor and associate director of the Center for Bioethics at the University of North Carolina at Chapel Hill, wrote last year in an op-ed. "These advances are essential. It is well past time—and it is morally imperative—for research to benefit pregnant women."
"In excluding pregnant women from drug trials to protect them from experimentation, we subject them to uncontrolled experimentation."
To that end, the American College of Obstetricians and Gynecologists' Committee on Ethics acknowledged that research trials need to be better designed so they don't "inappropriately constrain the reproductive choices of study participants or unnecessarily exclude pregnant women." A federal task force also called for significantly expanded research and the removal of regulatory barriers that make it difficult for pregnant and lactating women to participate in research.
Several months ago, a government change to a regulation known as the Common Rule took effect, removing pregnant women as a "vulnerable population" in need of special protections -- a designation that had made it more difficult to enroll them in clinical drug studies. And just last week, the U.S. Food and Drug Administration (FDA) issued new draft guidances for industry on when and how to include pregnant and lactating women in clinical trials.
Inclusion is better than the absence of data on their treatment, said Catherine Spong, former chair of the federal task force.
"It's a paradox," said Spong, professor of obstetrics and gynecology and chief of maternal fetal medicine at University of Texas Southwestern Medical Center. "There is a desire to protect women and fetuses from harm, which is translated to a reluctance to include them in research. By excluding them, the evidence for their care is limited."
Jacqueline Wolf, a professor of the history of medicine at Ohio University, agreed.
"In excluding pregnant women from drug trials to protect them from experimentation, we subject them to uncontrolled experimentation," she said. "We give them the medication without doing any research, and that's dangerous."
Women, of course, don't stop getting sick or having chronic medical conditions just because they are pregnant or breastfeeding, and conditions during pregnancy can affect a baby's health later in life. Evidence-based data is important for other reasons, too.
Pregnancy can dramatically change a woman's physiology, affecting how drugs act on her body and how her body acts or reacts to drugs. For instance, pregnant bodies can more quickly clear out medications such as glyburide, used during diabetes in pregnancy to stabilize high blood-sugar levels, which can be toxic to the fetus and harmful to women. That means a regular dose of the drug may not be enough to control blood sugar and prevent poor outcomes.
Pregnant patients also may be reluctant to take needed drugs for underlying conditions (and doctors may be hesitant to prescribe them), which in turn can cause more harm to the woman and fetus than had they been treated. For example, women who have severe asthma attacks while pregnant are at a higher risk of having low-birthweight babies, and pregnant women with uncontrolled diabetes in early pregnancy have more than four times the risk of birth defects.
Current clinical trials involving pregnant women are assessing treatments for obstructive sleep apnea, postpartum hemorrhage, lupus, and diabetes.
For Kate O'Brien, taking medication during her pregnancy was a matter of life and death. A freelance video producer who lives in New Jersey, O'Brien was diagnosed with tuberculosis in 2015 after she became pregnant with her second child, a boy. Even as she signed hospital consent forms, she had no idea if the treatment would harm him.
"It's a really awful experience," said O'Brien, who now is active with We are TB, an advocacy and support network. "All they had to tell me about the medication was just that women have been taking it for a really long time all over the world. That was the best they could do."
More and more doctors, researchers and women's health organizations and advocates are calling that unacceptable.
By indicating that filling current knowledge gaps is "a critical public health need," the FDA is signaling its support for advancing research with pregnant women, said Lyerly, also co-founder of the Second Wave Initiative, which promotes fair representation of the health interests of pregnant women in biomedical research and policies. "It's a very important shift."
Research with pregnant women can be done ethically, Lyerly said, whether by systematically collecting data from those already taking medications or enrolling pregnant women in studies of drugs or vaccines in development.
Current clinical trials involving pregnant women are assessing treatments for obstructive sleep apnea, postpartum hemorrhage, lupus, and diabetes. Notable trials in development target malaria and HIV prevention in pregnancy.
"It clearly is doable to do this research, and test trials are important to provide evidence for treatment," Spong said. "If we don't have that evidence, we aren't making the best educated decisions for women."
Awash in a fluid finely calibrated to keep it alive, a human eye rests inside a transparent cubic device. This ECaBox, or Eyes in a Care Box, is a one-of-a-kind system built by scientists at Barcelona’s Centre for Genomic Regulation (CRG). Their goal is to preserve human eyes for transplantation and related research.
In recent years, scientists have learned to transplant delicate organs such as the liver, lungs or pancreas, but eyes are another story. Even when preserved at the average transplant temperature of 4 Centigrade, they last for 48 hours max. That's one explanation for why transplanting the whole eye isn’t possible—only the cornea, the dome-shaped, outer layer of the eye, can withstand the procedure. The retina, the layer at the back of the eyeball that turns light into electrical signals, which the brain converts into images, is extremely difficult to transplant because it's packed with nerve tissue and blood vessels.
These challenges also make it tough to research transplantation. “This greatly limits their use for experiments, particularly when it comes to the effectiveness of new drugs and treatments,” said Maria Pia Cosma, a biologist at Barcelona’s Centre for Genomic Regulation (CRG), whose team is working on the ECaBox.
Eye transplants are desperately needed, but they're nowhere in sight. About 12.7 million people worldwide need a corneal transplant, which means that only one in 70 people who require them, get them. The gaps are international. Eye banks in the United Kingdom are around 20 percent below the level needed to supply hospitals, while Indian eye banks, which need at least 250,000 corneas per year, collect only around 45 to 50 thousand donor corneas (and of those 60 to 70 percent are successfully transplanted).
As for retinas, it's impossible currently to put one into the eye of another person. Artificial devices can be implanted to restore the sight of patients suffering from severe retinal diseases, but the number of people around the world with such “bionic eyes” is less than 600, while in America alone 11 million people have some type of retinal disease leading to severe vision loss. Add to this an increasingly aging population, commonly facing various vision impairments, and you have a recipe for heavy burdens on individuals, the economy and society. In the U.S. alone, the total annual economic impact of vision problems was $51.4 billion in 2017.
Even if you try growing tissues in the petri dish route into organoids mimicking the function of the human eye, you will not get the physiological complexity of the structure and metabolism of the real thing, according to Cosma. She is a member of a scientific consortium that includes researchers from major institutions from Spain, the U.K., Portugal, Italy and Israel. The consortium has received about $3.8 million from the European Union to pursue innovative eye research. Her team’s goal is to give hope to at least 2.2 billion people across the world afflicted with a vision impairment and 33 million who go through life with avoidable blindness.
Their method? Resuscitating cadaveric eyes for at least a month.
If we succeed, it will be the first intact human model of the eye capable of exploring and analyzing regenerative processes ex vivo. -- Maria Pia Cosma.
“We proposed to resuscitate eyes, that is to restore the global physiology and function of human explanted tissues,” Cosma said, referring to living tissues extracted from the eye and placed in a medium for culture. Their ECaBox is an ex vivo biological system, in which eyes taken from dead donors are placed in an artificial environment, designed to preserve the eye’s temperature and pH levels, deter blood clots, and remove the metabolic waste and toxins that would otherwise spell their demise.
Scientists work on resuscitating eyes in the lab of Maria Pia Cosma.
Courtesy of Maria Pia Cosma.
“One of the great challenges is the passage of the blood in the capillary branches of the eye, what we call long-term perfusion,” Cosma said. Capillaries are an intricate network of very thin blood vessels that transport blood, nutrients and oxygen to cells in the body’s organs and systems. To maintain the garland-shaped structure of this network, sufficient amounts of oxygen and nutrients must be provided through the eye circulation and microcirculation. “Our ambition is to combine perfusion of the vessels with artificial blood," along with using a synthetic form of vitreous, or the gel-like fluid that lets in light and supports the the eye's round shape, Cosma said.
The scientists use this novel setup with the eye submersed in its medium to keep the organ viable, so they can test retinal function. “If we succeed, we will ensure full functionality of a human organ ex vivo. It will be the first intact human model of the eye capable of exploring and analyzing regenerative processes ex vivo,” Cosma added.
A rapidly developing field of regenerative medicine aims to stimulate the body's natural healing processes and restore or replace damaged tissues and organs. But for people with retinal diseases, regenerative medicine progress has been painfully slow. “Experiments on rodents show progress, but the risks for humans are unacceptable,” Cosma said.
The ECaBox could boost progress with regenerative medicine for people with retinal diseases, which has been painfully slow because human experiments involving their eyes are too risky. “We will test emerging treatments while reducing animal research, and greatly accelerate the discovery and preclinical research phase of new possible treatments for vision loss at significantly reduced costs,” Cosma explained. Much less time and money would be wasted during the drug discovery process. Their work may even make it possible to transplant the entire eyeball for those who need it.
“It is a very exciting project,” said Sanjay Sharma, a professor of ophthalmology and epidemiology at Queen's University, in Kingston, Canada. “The ability to explore and monitor regenerative interventions will increasingly be of importance as we develop therapies that can regenerate ocular tissues, including the retina.”
Seemingly, there's no sacred religious text or a holy book prohibiting the practice of eye donation.
But is the world ready for eye transplants? “People are a bit weird or very emotional about donating their eyes as compared to other organs,” Cosma said. And much can be said about the problem of eye donor shortage. Concerns include disfigurement and healthcare professionals’ fear that the conversation about eye donation will upset the departed person’s relatives because of cultural or religious considerations. As just one example, Sharma noted the paucity of eye donations in his home country, Canada.
Yet, experts like Sharma stress the importance of these donations for both the recipients and their family members. “It allows them some psychological benefit in a very difficult time,” he said. So why are global eye banks suffering? Is it because the eyes are the windows to the soul?
Seemingly, there's no sacred religious text or a holy book prohibiting the practice of eye donation. In fact, most major religions of the world permit and support organ transplantation and donation, and by extension eye donation, because they unequivocally see it as an “act of neighborly love and charity.” In Hinduism, the concept of eye donation aligns with the Hindu principle of daan or selfless giving, where individuals donate their organs or body after death to benefit others and contribute to society. In Islam, eye donation is a form of sadaqah jariyah, a perpetual charity, as it can continue to benefit others even after the donor's death.
Meanwhile, Buddhist masters teach that donating an organ gives another person the chance to live longer and practice dharma, the universal law and order, more meaningfully; they also dismiss misunderstandings of the type “if you donate an eye, you’ll be born without an eye in the next birth.” And Christian teachings emphasize the values of love, compassion, and selflessness, all compatible with organ donation, eye donation notwithstanding; besides, those that will have a house in heaven, will get a whole new body without imperfections and limitations.
The explanation for people’s resistance may lie in what Deepak Sarma, a professor of Indian religions and philosophy at Case Western Reserve University in Cleveland, calls “street interpretation” of religious or spiritual dogmas. Consider the mechanism of karma, which is about the causal relation between previous and current actions. “Maybe some Hindus believe there is karma in the eyes and, if the eye gets transplanted into another person, they will have to have that karmic card from now on,” Sarma said. “Even if there is peculiar karma due to an untimely death–which might be interpreted by some as bad karma–then you have the karma of the recipient, which is tremendously good karma, because they have access to these body parts, a tremendous gift,” Sarma said. The overall accumulation is that of good karma: “It’s a beautiful kind of balance,” Sarma said.
For the Jews, Christians, and Muslims who believe in the physical resurrection of the body that will be made new in an afterlife, the already existing body is sacred since it will be the basis of a new refashioned body in an afterlife.---Omar Sultan Haque.
With that said, Sarma believes it is a fallacy to personify or anthropomorphize the eye, which doesn’t have a soul, and stresses that the karma attaches itself to the soul and not the body parts. But for scholars like Omar Sultan Haque—a psychiatrist and social scientist at Harvard Medical School, investigating questions across global health, anthropology, social psychology, and bioethics—the hierarchy of sacredness of body parts is entrenched in human psychology. You cannot equate the pinky toe with the face, he explained.
“The eyes are the window to the soul,” Haque said. “People have a hierarchy of body parts that are considered more sacred or essential to the self or soul, such as the eyes, face, and brain.” In his view, the techno-utopian transhumanist communities (especially those in Silicon Valley) have reduced the totality of a person to a mere material object, a “wet robot” that knows no sacredness or hierarchy of human body parts. “But for the Jews, Christians, and Muslims who believe in the physical resurrection of the body that will be made new in an afterlife, the [already existing] body is sacred since it will be the basis of a new refashioned body in an afterlife,” Haque said. “You cannot treat the body like any old material artifact, or old chair or ragged cloth, just because materialistic, secular ideologies want so,” he continued.
For Cosma and her peers, however, the very definition of what is alive or not is a bit semantic. “As soon as we die, the electrophysiological activity in the eye stops,” she said. “The goal of the project is to restore this activity as soon as possible before the highly complex tissue of the eye starts degrading.” Cosma’s group doesn’t yet know when they will be able to keep the eyes alive and well in the ECaBox, but the consensus is that the sooner the better. Hopefully, the taboos and fears around the eye donations will dissipate around the same time.
As Our AI Systems Get Better, So Must We
As the power and capability of our AI systems increase by the day, the essential question we now face is what constitutes peak human. If we stay where we are while the AI systems we are unleashing continually get better, they will meet and then exceed our capabilities in an ever-growing number of domains. But while some technology visionaries like Elon Musk call for us to slow down the development of AI systems to buy time, this approach alone will simply not work in our hyper-competitive world, particularly when the potential benefits of AI are so great and our frameworks for global governance are so weak. In order to build the future we want, we must also become ever better humans.
The list of activities we once saw as uniquely human where AIs have now surpassed us is long and growing. First, AI systems could beat our best chess players, then our best Go players, then our best champions of multi-player poker. They can see patterns far better than we can, generate medical and other hypotheses most human specialists miss, predict and map out new cellular structures, and even generate beautiful, and, yes, creative, art.
A recent paper by Microsoft researchers analyzing the significant leap in capabilities in OpenAI’s latest AI bot, ChatGPT-4, asserted that the algorithm can “solve novel and difficult tasks that span mathematics, coding, vision, medicine, law, psychology and more, without needing any special prompting.” Calling this functionality “strikingly close to human-level performance,” the authors conclude it “could reasonably be viewed as an early (yet still incomplete) version of an artificial general intelligence (AGI) system.”
The concept of AGI has been around for decades. In its common use, the term suggests a time when individual machines can do many different things at a human level, not just one thing like playing Go or analyzing radiological images. Debating when AGI might arrive, a favorite pastime of computer scientists for years, now has become outdated.
We already have AI algorithms and chatbots that can do lots of different things. Based on the generalist definition, in other words, AGI is essentially already here.
Unfettered by the evolved capacity and storage constraints of our brains, AI algorithms can access nearly all of the digitized cultural inheritance of humanity since the dawn of recorded history and have increasing access to growing pools of digitized biological data from across the spectrum of life.
Once we recognize that both AI systems and humans have unique superpowers, the essential question becomes what each of us can do better than the other and what humans and AIs can best do in active collaboration. The future of our species will depend upon our ability to safely, dynamically, and continually figure that out.
With these ever-larger datasets, rapidly increasing computing and memory power, and new and better algorithms, our AI systems will keep getting better faster than most of us can today imagine. These capabilities have the potential to help us radically improve our healthcare, agriculture, and manufacturing, make our economies more productive and our development more sustainable, and do many important things better.
Soon, they will learn how to write their own code. Like human children, in other words, AI systems will grow up. But even that doesn’t mean our human goose is cooked.
Just like dolphins and dogs, these alternate forms of intelligence will be uniquely theirs, not a lesser or greater version of ours. There are lots of things AI systems can't do and will never be able to do because our AI algorithms, for better and for worse, will never be human. Our embodied human intelligence is its own thing.
Our human intelligence is uniquely ours based on the capacities we have developed in our 3.8-billion-year journey from single cell organisms to us. Our brains and bodies represent continuous adaptations on earlier models, which is why our skeletal systems look like those of lizards and our brains like most other mammals with some extra cerebral cortex mixed in. Human intelligence isn’t just some type of disembodied function but the inextricable manifestation of our evolved physical reality. It includes our sensory analytical skills and all of our animal instincts, intuitions, drives, and perceptions. Disembodied machine intelligence is something different than what we have evolved and possess.
Because of this, some linguists including Noam Chomsky have recently argued that AI systems will never be intelligent as long as they are just manipulating symbols and mathematical tokens without any inherent understanding. Nothing could be further from the truth. Anyone interacting with even first-generation AI chatbots quickly realizes that while these systems are far from perfect or omniscient and can sometimes be stupendously oblivious, they are surprisingly smart and versatile and will get more so… forever. We have little idea even how our own minds work, so judging AI systems based on their output is relatively close to how we evaluate ourselves.
Anyone not awed by the potential of these AI systems is missing the point. AI’s newfound capacities demand that we work urgently to establish norms, standards, and regulations at all levels from local to global to manage the very real risks. Pausing our development of AI systems now doesn’t make sense, however, even if it were possible, because we have no sufficient ways of uniformly enacting such a pause, no plan for how we would use the time, and no common framework for addressing global collective challenges like this.
But if all we feel is a passive awe for these new capabilities, we will also be missing the point.
Human evolution, biology, and cultural history are not just some kind of accidental legacy, disability, or parlor trick, but our inherent superpower. Our ancestors outcompeted rivals for billions of years to make us so well suited to the world we inhabit and helped build. Our social organization at scale has made it possible for us to forge civilizations of immense complexity, engineer biology and novel intelligence, and extend our reach to the stars. Our messy, embodied, intuitive, social human intelligence is roughly mimicable by AI systems but, by definition, never fully replicable by them.
Once we recognize that both AI systems and humans have unique superpowers, the essential question becomes what each of us can do better than the other and what humans and AIs can best do in active collaboration. We still don't know. The future of our species will depend upon our ability to safely, dynamically, and continually figure that out.
As we do, we'll learn that many of our ideas and actions are made up of parts, some of which will prove essentially human and some of which can be better achieved by AI systems. Those in every walk of work and life who most successfully identify the optimal contributions of humans, AIs, and the two together, and who build systems and workflows empowering humans to do human things, machines to do machine things, and humans and machines to work together in ways maximizing the respective strengths of each, will be the champions of the 21st century across all fields.
The dawn of the age of machine intelligence is upon us. It’s a quantum leap equivalent to the domestication of plants and animals, industrialization, electrification, and computing. Each of these revolutions forced us to rethink what it means to be human, how we live, and how we organize ourselves. The AI revolution will happen more suddenly than these earlier transformations but will follow the same general trajectory. Now is the time to aggressively prepare for what is fast heading our way, including by active public engagement, governance, and regulation.
AI systems will not replace us, but, like these earlier technology-driven revolutions, they will force us to become different humans as we co-evolve with our technology. We will never reach peak human in our ongoing evolutionary journey, but we’ve got to manage this transition wisely to build the type of future we’d like to inhabit.
Alongside our ascending AIs, we humans still have a lot of climbing to do.