Society Needs Regulations to Prevent Research Abuses
A tension exists between scientists/doctors and government regulators.
[Editor's Note: Our Big Moral Question this month is, "Do government regulations help or hurt the goal of responsible and timely scientific innovation?"]
Government regulations help more than hurt the goal of responsible and timely scientific innovation. Opponents might argue that without regulations, researchers would be free to do whatever they want. But without ethics and regulations, scientists have performed horrific experiments. In Nazi concentration camps, for instance, doctors forced prisoners to stay in the snow to see how long it took for these inmates to freeze to death. These researchers also removed prisoner's limbs in order to try to develop innovations to reconnect these body parts, but all the experiments failed.
Researchers in not only industry, but also academia have violated research participants' rights.
Due to these atrocities, after the war, the Nuremberg Tribunal established the first ethical guidelines for research, mandating that all study participants provide informed consent. Yet many researchers, including those in leading U.S. academic institutions and government agencies, failed to follow these dictates. The U.S. government, for instance, secretly infected Guatemalan men with syphilis in order to study the disease and experimented on soldiers, exposing them without consent to biological and chemical warfare agents. In the 1960s, researchers at New York's Willowbrook State School purposefully fed intellectually disabled children infected stool extracts with hepatitis to study the disease. In 1966, in the New England Journal of Medicine, Henry Beecher, a Harvard anesthesiologist, described 22 cases of unethical research published in the nation's leading medical journals, but were mostly conducted without informed consent, and at times harmed participants without offering them any benefit.
Despite heightened awareness and enhanced guidelines, abuses continued. Until a 1974 journalistic exposé, the U.S. government continued to fund the now-notorious Tuskegee syphilis study of infected poor African-American men in rural Alabama, refusing to offer these men penicillin when it became available as effective treatment for the disease.
In response, in 1974 Congress passed the National Research Act, establishing research ethics committees or Institutional Review Boards (IRBs), to guide scientists, allowing them to innovate while protecting study participants' rights. Routinely, IRBs now detect and prevent unethical studies from starting.
Still, even with these regulations, researchers have at times conducted unethical investigations. In 1999 at the Los Angeles Veterans Affairs Hospital, for example, a patient twice refused to participate in a study that would prolong his surgery. The researcher nonetheless proceeded to experiment on him anyway, using an electrical probe in the patient's heart to collect data.
Part of the problem and consequent need for regulations is that researchers have conflicts of interest and often do not recognize ethical challenges their research may pose.
Pharmaceutical company scandals, involving Avandia, and Neurontin and other drugs, raise added concerns. In marketing Vioxx, OxyContin, and tobacco, corporations have hidden findings that might undercut sales.
Regulations become increasingly critical as drug companies and the NIH conduct increasing amounts of research in the developing world. In 1996, Pfizer conducted a study of bacterial meningitis in Nigeria in which 11 children died. The families thus sued. Pfizer produced a Nigerian IRB approval letter, but the letter turned out to have been forged. No Nigerian IRB had ever approved the study. Fourteen years later, Wikileaks revealed that Pfizer had hired detectives to find evidence of corruption against the Nigerian Attorney General, to compel him to drop the lawsuit.
Researchers in not only industry, but also academia have violated research participants' rights. Arizona State University scientists wanted to investigate the genes of a Native American group, the Havasupai, who were concerned about their high rates of diabetes. The investigators also wanted to study the group's rates of schizophrenia, but feared that the tribe would oppose the study, given the stigma. Hence, these researchers decided to mislead the tribe, stating that the study was only about diabetes. The university's research ethics committee knew the scientists' plan to study schizophrenia, but approved the study, including the consent form, which did not mention any psychiatric diagnoses. The Havasupai gave blood samples, but later learned that the researchers published articles about the tribe's schizophrenia and alcoholism, and genetic origins in Asia (while the Havasupai believed they originated in the Grand Canyon, where they now lived, and which they thus argued they owned). A 2010 legal settlement required that the university return the blood samples to the tribe, which then destroyed them. Had the researchers instead worked with the tribe more respectfully, they could have advanced science in many ways.
Part of the problem and consequent need for regulations is that researchers have conflicts of interest and often do not recognize ethical challenges their research may pose.
Such violations threaten to lower public trust in science, particularly among vulnerable groups that have historically been systemically mistreated, diminishing public and government support for research and for the National Institutes of Health, National Science Foundation and Centers for Disease Control, all of which conduct large numbers of studies.
Research that has failed to follow ethics has in fact impeded innovation.
In popular culture, myths of immoral science and technology--from Frankenstein to Big Brother and Dr. Strangelove--loom.
Admittedly, regulations involve inherent tradeoffs. Following certain rules can take time and effort. Certain regulations may in fact limit research that might potentially advance knowledge, but be grossly unethical. For instance, if our society's sole goal was to have scientists innovate as much as possible, we might let them stick needles into healthy people's brains to remove cells in return for cash that many vulnerable poor people might find desirable. But these studies would clearly pose major ethical problems.
Research that has failed to follow ethics has in fact impeded innovation. In 1999, the death of a young man, Jesse Gelsinger, in a gene therapy experiment in which the investigator was subsequently found to have major conflicts of interest, delayed innovations in the field of gene therapy research for years.
Without regulations, companies might market products that prove dangerous, leading to massive lawsuits that could also ultimately stifle further innovation within an industry.
The key question is not whether regulations help or hurt science alone, but whether they help or hurt science that is both "responsible and innovative."
We don't want "over-regulation." Rather, the right amount of regulations is needed – neither too much nor too little. Hence, policy makers in this area have developed regulations in fair and transparent ways and have also been working to reduce the burden on researchers – for instance, by allowing single IRBs to review multi-site studies, rather than having multiple IRBs do so, which can create obstacles.
In sum, society requires a proper balance of regulations to ensure ethical research, avoid abuses, and ultimately aid us all by promoting responsible innovation.
[Ed. Note: Check out the opposite viewpoint here, and follow LeapsMag on social media to share your perspective.]
Podcast: A Nasal Spray COVID Booster Shot, With Dr. Akiko Iwasaki
Dr. Akiko Iwasaki, an immunologist at Yale, is working on creating a nasal spray booster after the primary mRNA shots.
The "Making Sense of Science" podcast features interviews with leading medical and scientific experts about the latest developments and the big ethical and societal questions they raise. This monthly podcast is hosted by journalist Kira Peikoff, founding editor of the award-winning science outlet Leaps.org.
Real-world data shows that protection against Covid-19 infection wanes a few months after two or three shots of mRNA vaccines (while protection against severe disease remains high). But what if there was another kind of booster that could shore up the immune response in your nose, the "door" to your body? Like bouncers at a club, a better prepared nasal defense system could stop the virus in its tracks -- mitigating illnesses as well as community spread. Dr. Akiko Iwasaki, an immunologist at Yale, is working on such a booster, with fantastic results recently reported in mice. In this episode, she shares the details of this important work.
Listen to episode
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Technology is Redefining the Age of 'Older Mothers'
Scientists are working on technologies that would enable more 70-year-old women to have babies.
In October 2021, a woman from Gujarat, India, stunned the world when it was revealed she had her first child through in vitro fertilization (IVF) at age 70. She had actually been preceded by a compatriot of hers who, two years before, gave birth to twins at the age of 73, again with the help of IVF treatment. The oldest known mother to conceive naturally lived in the UK; in 1997, Dawn Brooke conceived a son at age 59.
These women may seem extreme outliers, almost freaks of nature; in the US, for example, the average age of first-time mothers is 26. A few decades from now, though, the sight of 70-year-old first-time mothers may not even raise eyebrows, say futurists.
“We could absolutely have more 70-year-old mothers because we are learning how to regulate the aging process better,” says Andrew Hessel, a microbiologist and geneticist, who cowrote "The Genesis Machine," a book about “rewriting life in the age of synthetic biology,” with Amy Webb, the futurist who recently wondered why 70-year-old women shouldn’t give birth.
Technically, we're already doing this, says Hessel, pointing to a technique known as in vitro gametogenesis (IVG). IVG refers to turning adult cells into sperm or egg cells. “You can think of it as the upgrade to IVF,” Hessel says. These vanguard stem cell research technologies can take even skin cells and turn them into induced pluripotent stem cells (iPSCs), which are basically master cells capable of maturing into any human cell, be it kidney cells, liver cells, brain cells or gametes, aka eggs and sperm, says Henry T. “Hank” Greely, a Stanford law professor who specializes in ethical, legal, and social issues in biosciences.
Mothers over 70 will be a minor blip, statistically speaking, Greely predicts.
In 2016, Greely wrote "The End of Sex," a book in which he described the science of making gametes out of iPSCs in detail. Greely says science will indeed enable us to see 70-year-old new mums fraternize with mothers several decades younger at kindergartens in the (not far) future. And it won’t be that big of a deal.
“An awful lot of children all around the world have been raised by grandmothers for millennia. To have 70-year-olds and 30-year-olds mingling in maternal roles is not new,” he says. That said, he doubts that many women will want to have a baby in the eighth decade of their life, even if science allows it. “Having a baby and raising a child is hard work. Even if 1% of all mothers are over 65, they aren’t going to change the world,” Greely says. Mothers over 70 will be a minor blip, statistically speaking, he predicts. But one thing is certain: the technology is here.
And more technologies for the same purpose could be on the way. In March 2021, researchers from Monash University in Melbourne, Australia, published research in Nature, where they successfully reprogrammed skin cells into a three-dimensional cellular structure that was morphologically and molecularly similar to a human embryo–the iBlastoid. In compliance with Australian law and international guidelines referencing the “primitive streak rule," which bans the use of embryos older than 14 days in scientific research, Monash scientists stopped growing their iBlastoids in vitro on day 11.
“The research was both cutting-edge and controversial, because it essentially created a new human life, not for the purpose of a patient who's wanting to conceive, but for basic research,” says Lindsay Wu, a senior lecturer in the School of Medical Sciences at the University of New South Wales (UNSW), in Kensington, Australia. If you really want to make sure what you are breeding is an embryo, you need to let it develop into a viable baby. “This is the real proof in the pudding,'' says Wu, who runs UNSW’s Laboratory for Ageing Research. Then you get to a stage where you decide for ethical purposes you have to abort it. “Fiddling here a bit too much?” he asks. Wu believes there are other approaches to tackling declining fertility due to older age that are less morally troubling.
He is actually working on them. Why would it be that women, who are at peak physical health in almost every other regard, in their mid- to late- thirties, have problems conceiving, asked Wu and his team in a research paper published in 2020 in Cell Reports. The simple answer is the egg cell. An average girl in puberty has between 300,000 and 400,000 eggs, while at around age 37, the same woman has only 25,000 eggs left. Things only go downhill from there. So, what torments the egg cells?
The UNSW team found that the levels of key molecules called NAD+ precursors, which are essential to the metabolism and genome stability of egg cells, decline with age. The team proceeded to add these vitamin-like substances back into the drinking water of reproductively aged, infertile lab mice, which then had babies.
“It's an important proof of concept,” says Wu. He is investigating how safe it is to replicate the experiment with humans in two ongoing studies. The ultimate goal is to restore the quality of egg cells that are left in patients in their late 30s and early- to mid-40s, says Wu. He sees the goal of getting pregnant for this age group as less ethically troubling, compared to 70-year-olds.
But what is ethical, anyway? “It is a tricky word,” says Hessel. He differentiates between ethics, which represent a personal position and may, thus, be more transient, and morality, longer lasting principles embraced across society such as, “Thou shalt not kill.” Unprecedented advances often bring out fear and antagonism until time passes and they just become…ordinary. When IVF pioneer Landrum Shettles tried to perform IVF in 1973, the chairman of Columbia’s College of Physicians and Surgeons interdicted the procedure at the last moment. Almost all countries in the world have IVF clinics today, and the global IVF services market is clearly a growth industry.
Besides, you don’t have a baby at 70 by accident: you really want it, Greely and Hessel agree. And by that age, mothers may be wiser and more financially secure, Hessel says (though he is quick to add that even the pregnancy of his own wife, who had her child at 40, was a high-risk one).
As a research question, figuring out whether older mothers are better than younger ones and vice-versa entails too many confounding variables, says Greely. And why should we focus on who’s the better mother anyway? “We've had 70-year-old and 80-year-old fathers forever–why should people have that much trouble getting used to mothers doing the same?” Greely wonders. For some women having a child at an old(er) age would be comforting; maybe that’s what matters.
And the technology to enable older women to have children is already here or coming very soon. That, perhaps, matters even more. Researchers have already created mice–and their offspring–entirely from scratch in the lab. “Doing this to produce human eggs is similar," says Hessel. "It is harder to collect tissues, and the inducing cocktails are different, but steady advances are being made." He predicts that the demand for fertility treatments will keep financing research and development in the area. He says that big leaps will be made if ethical concerns don’t block them: it is not far-fetched to believe that the first baby produced from lab-grown eggs will be born within the next decade.
In an op-ed in 2020 with Stat, Greely argued that we’ve already overcome the technical barrier for human cloning, but no one's really talking about it. Likewise, scientists are also working on enabling 70-year-old women to have babies, says Hessel, but most commentators are keeping really quiet about it. At least so far.