How Can We Decide If a Biomedical Advance Is Ethical?
"All fixed, fast-frozen relations, with their train of ancient and venerable prejudices and opinions, are swept away, all new-formed ones become antiquated before they can ossify. All that is solid melts into air, all that is holy is profaned…"
On July 25, 1978, Louise Brown was born in Oldham, England, the first human born through in vitro fertilization, through the work of Patrick Steptoe, a gynecologist, and Robert Edwards, a physiologist. Her birth was greeted with strong (though not universal) expressions of ethical dismay. Yet in 2016, the latest year for which we have data, nearly two percent of the babies born in the United States – and around the same percentage throughout the developed world – were the result of IVF. Few, if any, think of these children as unnatural, monsters, or freaks or of their parents as anything other than fortunate.
How should we view Dr. He today, knowing that the world's eventual verdict on the ethics of biomedical technologies often changes?
On November 25, 2018, news broke that Chinese scientist, Dr. He Jiankui, claimed to have edited the genomes of embryos, two of whom had recently become the new babies, Lulu and Nana. The response was immediate and overwhelmingly negative.
Times change. So do views. How will Dr. He be viewed in 40 years? And, more importantly, how should we view him today, knowing that the world's eventual verdict on the ethics of biomedical technologies often changes? And when what biomedicine can do changes with vertiginous frequency?
How to determine what is and isn't ethical is above my pay grade. I'm a simple law professor – I can't claim any deeper insight into how to live a moral life than the millennia of religious leaders, philosophers, ethicists, and ordinary people trying to do the right thing. But I can point out some ways to think about these questions that may be helpful.
First, consider two different kinds of ethical commands. Some are quite specific – "thou shalt not kill," for example. Others are more general – two of them are "do unto others as you would have done to you" or "seek the greatest good for the greatest number."
Biomedicine in the last two centuries has often surprised us with new possibilities, situations that cultures, religions, and bodies of ethical thought had not previously had to consider, from vaccination to anesthesia for women in labor to genome editing. Sometimes these possibilities will violate important and deeply accepted precepts for a group or a person. The rise of blood transfusions around World War I created new problems for Jehovah's Witnesses, who believe that the Bible prohibits ingesting blood. The 20th century developments of artificial insemination and IVF both ran afoul of Catholic doctrine prohibiting methods other than "traditional" marital intercourse for conceiving children. If you subscribe to an ethical or moral code that contains prohibitions that modern biomedicine violates, the issue for you is stark – adhere to those beliefs or renounce them.
If the harms seem to outweigh the benefits, it's easy to conclude "this is worrisome."
But many biomedical changes violate no clear moral teachings. Is it ethical or not to edit the DNA of embryos? Not surprisingly, the sacred texts of various religions – few of which were created after, at the latest, the early 19th century, say nothing specific about this. There may be hints, precedents, leanings that could argue one way or another, but no "commandments." In that case, I recommend, at least as a starting point, asking "what are the likely consequences of these actions?"
Will people be, on balance, harmed or helped by them? "Consequentialist" approaches, of various types, are a vast branch of ethical theories. Personally I find a completely consequentialist approach unacceptable – I could not accept, for example, torturing an innocent child even in order to save many lives. But, in the absence of a clear rule, looking at the consequences is a great place to start. If the harms seem to outweigh the benefits, it's easy to conclude "this is worrisome."
Let's use that starting place to look at a few bioethical issues. IVF, for example, once proven (relatively) safe seems to harm no one and to help many, notably the more than 8 million children worldwide born through IVF since 1978 – and their 16 million parents. On the other hand, giving unknowing, and unconsenting, intellectually disabled children hepatitis A harmed them, for an uncertain gain for science. And freezing the heads of the dead seems unlikely to harm anyone alive (except financially) but it also seems almost certain not to benefit anyone. (Those frozen dead heads are not coming back to life.)
Now let's look at two different kinds of biomedical advances. Some are controversial just because they are new; others are controversial because they cut close to the bone – whether or not they violate pre-established ethical or moral norms, they clearly relate to them.
Consider anesthesia during childbirth. When first used, it was controversial. After all, said critics, in Genesis, the Bible says God told Eve, "I will greatly multiply Your pain in childbirth, In pain you will bring forth children." But it did not clearly prohibit pain relief and from the advent of ether on, anesthesia has been common, though not universal, in childbirth in western societies. The pre-existing ethical precepts were not clear and the consequences weighed heavily in favor of anesthesia. Similarly, vaccination seems to violate no deep moral principle. It was, and for some people, still is just strange, and unnatural. The same was true of IVF initially. Opposition to all of these has faded with time and familiarity. It has not disappeared – some people continue to find moral or philosophical problems with "unnatural" childbirth, vaccination, and IVF – but far fewer.
On the other hand, human embryonic stem cell research touches deeper issues. Human embryos are destroyed to make those stem cells. Reasonable people disagree on the moral status of the human embryo, and the moral weight of its destruction, but it does at least bring into play clear and broadly accepted moral precepts, such as "Thou shalt not kill." So, at the far side of an individual's time, does euthanasia. More exposure to, and familiarity with, these practices will not necessarily lead to broad acceptance as the objections involve more than novelty.
The first is "what would I do?" The second – what should my government, culture, religion allow or forbid?
Finally, all this ethical analysis must work at two levels. The first is "what would I do?" The second – what should my government, culture, religion allow or forbid? There are many things I would not do that I don't think should be banned – because I think other people may reasonably have different views from mine. I would not get cosmetic surgery, but I would not ban it – and will try not to think ill of those who choose it
So, how should we assess the ethics of new biomedical procedures when we know that society's views may change? More specifically, what should we think of He Jiankui's experiment with human babies?
First, look to see whether the procedure in question violates, at least fairly clearly, some rule in your ethical or moral code. If so, your choice may not be difficult. But if the procedure is unmentioned in your moral code, probably because it was inconceivable to the code's creators, examine the consequences of the act.
If the procedure is just novel, and not something that touches on important moral concerns, looking at the likely consequences may be enough for your ethical analysis –though it is always worth remembering that predicting consequences perfectly is impossible and predicting them well is never certain. If it does touch on morally significant issues, you need to think those issues through. The consequences may be important to your conclusions but they may not be determinative.
And, then, if you conclude that it is not ethical from your perspective, you need to take yet another step and consider whether it should be banned for people who do not share your perspective. Sometimes the answer will be yes – that psychopaths may not view murder as immoral does not mean we have to let them kill – but sometimes it will be no.
What does this say about He Jiankui's experiment? I have no qualms in condemning it, unequivocally. The potential risks to the babies grossly outweighed any benefits to them, and to science. And his secret work, against a near universal scientific consensus, privileged his own ethical conclusions without giving anyone else a vote, or even a voice.
But if, in ten or twenty years, genome editing of human embryos is shown to be safe (enough) and it is proposed to be used for good reasons – say, to relieve human suffering that could not be treated in other good ways – and with good consents from those directly involved as well as from the relevant society and government – my answer might well change. Yours may not. Bioethics is a process for approaching questions; it is not a set of universal answers.
This article opened with a quotation from the 1848 Communist Manifesto, referring to the dizzying pace of change from industrialization and modernity. You don't need to be a Marxist to appreciate that sentiment. Change – especially in the biosciences – keeps accelerating. How should we assess the ethics of new biotechnologies? The best we can, with what we know, at the time we inhabit. And, in the face of vast uncertainty, with humility.
A new injection is helping stave off RSV this season
In November 2021, Mickayla Wininger’s then one-month-old son, Malcolm, endured a terrifying bout with RSV, the respiratory syncytial (sin-SISH-uhl) virus—a common ailment that affects all age groups. Most people recover from mild, cold-like symptoms in a week or two, but RSV can be life-threatening in others, particularly infants.
Wininger, who lives in southern Illinois, was dressing Malcolm for bed when she noticed what seemed to be a minor irregularity with this breathing. She and her fiancé, Gavin McCullough, planned to take him to the hospital the next day. The matter became urgent when, in the morning, the boy’s breathing appeared to have stopped.
After they dialed 911, Malcolm started breathing again, but he ended up being hospitalized three times for RSV and defects in his heart. Eventually, he recovered fully from RSV, but “it was our worst nightmare coming to life,” Wininger recalled.
It’s a scenario that the federal government is taking steps to prevent. In July, the Food and Drug Administration approved a single-dose, long-acting injection to protect babies and toddlers. The injection, called Beyfortus, or nirsevimab, became available this October. It reduces the incidence of RSV in pre-term babies and other infants for their first RSV season. Children at highest risk for severe RSV are those who were born prematurely and have either chronic lung disease of prematurity or congenital heart disease. In those cases, RSV can progress to lower respiratory tract diseases such as pneumonia and bronchiolitis, or swelling of the lung’s small airway passages.
Each year, RSV is responsible for 2.1 million outpatient visits among children younger than five-years-old, 58,000 to 80,000 hospitalizations in this age group, and between 100 and 300 deaths, according to the Centers for Disease Control and Prevention. Transmitted through close contact with an infected person, the virus circulates on a seasonal basis in most regions of the country, typically emerging in the fall and peaking in the winter.
In August, however, the CDC issued a health advisory on a late-summer surge in severe cases of RSV among young children in Florida and Georgia. The agency predicts "increased RSV activity spreading north and west over the following two to three months.”
Infants are generally more susceptible to RSV than older people because their airways are very small, and their mechanisms to clear these passages are underdeveloped. RSV also causes mucus production and inflammation, which is more of a problem when the airway is smaller, said Jennifer Duchon, an associate professor of newborn medicine and pediatrics in the Icahn School of Medicine at Mount Sinai in New York.
In 2021 and 2022, RSV cases spiked, sending many to emergency departments. “RSV can cause serious disease in infants and some children and results in a large number of emergency department and physician office visits each year,” John Farley, director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research, said in a news release announcing the approval of the RSV drug. The decision “addresses the great need for products to help reduce the impact of RSV disease on children, families and the health care system.”
Sean O’Leary, chair of the committee on infectious diseases for the American Academy of Pediatrics, says that “we’ve never had a product like this for routine use in children, so this is very exciting news.” It is recommended for all kids under eight months old for their first RSV season. “I would encourage nirsevimab for all eligible children when it becomes available,” O’Leary said.
For those children at elevated risk of severe RSV and between the ages of 8 and 19 months, the CDC recommends one dose in their second RSV season.
The drug will be “really helpful to keep babies healthy and out of the hospital,” said O’Leary, a professor of pediatrics at the University of Colorado Anschutz Medical Campus/Children’s Hospital Colorado in Denver.
An antiviral drug called Synagis (palivizumab) has been an option to prevent serious RSV illness in high-risk infants since it was approved by the FDA in 1998. The injection must be given monthly during RSV season. However, its use is limited to “certain children considered at high risk for complications, does not help cure or treat children already suffering from serious RSV disease, and cannot prevent RSV infection,” according to the National Foundation for Infectious Diseases.
Until the approval this summer of the new monoclonal antibody, nirsevimab, there wasn’t a reliable method to prevent infection in most healthy infants.
Both nirsevimab and palivizumab are monoclonal antibodies that act against RSV. Monoclonal antibodies are lab-made proteins that mimic the immune system’s ability to fight off harmful pathogens such as viruses. A single intramuscular injection of nirsevimab preceding or during RSV season may provide protection.
The strategy with the new monoclonal antibody is “to extend protection to healthy infants who nonetheless are at risk because of their age, as well as infants with additional medical risk factors,” said Philippa Gordon, a pediatrician and infectious disease specialist in Brooklyn, New York, and medical adviser to Park Slope Parents, an online community support group.
No specific preventive measure is needed for older and healthier kids because they will develop active immunity, which is more durable. Meanwhile, older adults, who are also vulnerable to RSV, can receive one of two new vaccines. So can pregnant women, who pass on immunity to the fetus, Gordon said.
Until the approval this summer of the new monoclonal antibody, nirsevimab, there wasn’t a reliable method to prevent infection in most healthy infants, “nor is there any treatment other than giving oxygen or supportive care,” said Stanley Spinner, chief medical officer and vice president of Texas Children’s Pediatrics and Texas Children’s Urgent Care.
As with any virus, washing hands frequently and keeping infants and children away from sick people are the best defenses, Duchon said. This approach isn’t foolproof because viruses can run rampant in daycare centers, schools and parents’ workplaces, she added.
Mickayla Wininger, Malcolm’s mother, insists that family and friends wear masks, wash their hands and use hand sanitizer when they’re around her daughter and two sons. She doesn’t allow them to kiss or touch the children. Some people take it personally, but she would rather be safe than sorry.
Wininger recalls the severe anxiety caused by Malcolm's ordeal with RSV. After returning with her infant from his hospital stays, she was terrified to go to sleep. “My fiancé and I would trade shifts, so that someone was watching over our son 24 hours a day,” she said. “I was doing a night shift, so I would take caffeine pills to try and keep myself awake and would end up crashing early hours in the morning and wake up frantically thinking something happened to my son.”
Two years later, her anxiety has become more manageable, and Malcolm is doing well. “He is thriving now,” Wininger said. He recently had his second birthday and "is just the spunkiest boy you will ever meet. He looked death straight in the eyes and fought to be here today.”
Story by Big Think
For most of history, artificial intelligence (AI) has been relegated almost entirely to the realm of science fiction. Then, in late 2022, it burst into reality — seemingly out of nowhere — with the popular launch of ChatGPT, the generative AI chatbot that solves tricky problems, designs rockets, has deep conversations with users, and even aces the Bar exam.
But the truth is that before ChatGPT nabbed the public’s attention, AI was already here, and it was doing more important things than writing essays for lazy college students. Case in point: It was key to saving the lives of tens of millions of people.
AI-designed mRNA vaccines
As Dave Johnson, chief data and AI officer at Moderna, told MIT Technology Review‘s In Machines We Trust podcast in 2022, AI was integral to creating the company’s highly effective mRNA vaccine against COVID. Moderna and Pfizer/BioNTech’s mRNA vaccines collectively saved between 15 and 20 million lives, according to one estimate from 2022.
Johnson described how AI was hard at work at Moderna, well before COVID arose to infect billions. The pharmaceutical company focuses on finding mRNA therapies to fight off infectious disease, treat cancer, or thwart genetic illness, among other medical applications. Messenger RNA molecules are essentially molecular instructions for cells that tell them how to create specific proteins, which do everything from fighting infection, to catalyzing reactions, to relaying cellular messages.
Johnson and his team put AI and automated robots to work making lots of different mRNAs for scientists to experiment with. Moderna quickly went from making about 30 per month to more than one thousand. They then created AI algorithms to optimize mRNA to maximize protein production in the body — more bang for the biological buck.
For Johnson and his team’s next trick, they used AI to automate science, itself. Once Moderna’s scientists have an mRNA to experiment with, they do pre-clinical tests in the lab. They then pore over reams of data to see which mRNAs could progress to the next stage: animal trials. This process is long, repetitive, and soul-sucking — ill-suited to a creative scientist but great for a mindless AI algorithm. With scientists’ input, models were made to automate this tedious process.
“We don’t think about AI in the context of replacing humans,” says Dave Johnson, chief data and AI officer at Moderna. “We always think about it in terms of this human-machine collaboration, because they’re good at different things. Humans are really good at creativity and flexibility and insight, whereas machines are really good at precision and giving the exact same result every single time and doing it at scale and speed.”
All these AI systems were in put in place over the past decade. Then COVID showed up. So when the genome sequence of the coronavirus was made public in January 2020, Moderna was off to the races pumping out and testing mRNAs that would tell cells how to manufacture the coronavirus’s spike protein so that the body’s immune system would recognize and destroy it. Within 42 days, the company had an mRNA vaccine ready to be tested in humans. It eventually went into hundreds of millions of arms.
Biotech harnesses the power of AI
Moderna is now turning its attention to other ailments that could be solved with mRNA, and the company is continuing to lean on AI. Scientists are still coming to Johnson with automation requests, which he happily obliges.
“We don’t think about AI in the context of replacing humans,” he told the Me, Myself, and AI podcast. “We always think about it in terms of this human-machine collaboration, because they’re good at different things. Humans are really good at creativity and flexibility and insight, whereas machines are really good at precision and giving the exact same result every single time and doing it at scale and speed.”
Moderna, which was founded as a “digital biotech,” is undoubtedly the poster child of AI use in mRNA vaccines. Moderna recently signed a deal with IBM to use the company’s quantum computers as well as its proprietary generative AI, MoLFormer.
Moderna’s success is encouraging other companies to follow its example. In January, BioNTech, which partnered with Pfizer to make the other highly effective mRNA vaccine against COVID, acquired the company InstaDeep for $440 million to implement its machine learning AI across its mRNA medicine platform. And in May, Chinese technology giant Baidu announced an AI tool that designs super-optimized mRNA sequences in minutes. A nearly countless number of mRNA molecules can code for the same protein, but some are more stable and result in the production of more proteins. Baidu’s AI, called “LinearDesign,” finds these mRNAs. The company licensed the tool to French pharmaceutical company Sanofi.
Writing in the journal Accounts of Chemical Research in late 2021, Sebastian M. Castillo-Hair and Georg Seelig, computer engineers who focus on synthetic biology at the University of Washington, forecast that AI machine learning models will further accelerate the biotechnology research process, putting mRNA medicine into overdrive to the benefit of all.
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.