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.
After spaceflight record, NASA looks to protect astronauts on even longer trips
At T-minus six seconds, the main engines of the Atlantis Space Shuttle ignited, rattling its capsule “like a skyscraper in an earthquake,” according to astronaut Tom Jones, describing the 1988 launch. As the rocket lifted off and accelerated to three times the force of Earth's gravity, “It felt as if two of my friends were standing on my chest and wouldn’t get off.” But when Atlantis reached orbit, the main engines cut off, and the astronauts were suddenly weightless.
Since 1961, NASA has sent hundreds of astronauts into space while working to making their voyages safer and smoother. Yet, challenges remain. Weightlessness may look amusing when watched from Earth, but it has myriad effects on cognition, movement and other functions. When missions to space stretch to six months or longer, microgravity can impact astronauts’ health and performance, making it more difficult to operate their spacecraft.
Yesterday, NASA astronaut Frank Rubio returned to Earth after over one year, the longest single spaceflight for a U.S. astronaut. But this is just the start; longer and more complex missions into deep space loom ahead, from returning to the moon in 2025 to eventually sending humans to Mars. To ensure that these missions succeed, NASA is increasing efforts to study the biological effects and prevent harm.
The dangers of microgravity are real
A NASA report published in 2016 details a long list of incidents and near-misses caused – at least partly – by space-induced changes in astronauts’ vision and coordination. These issues make it harder to move with precision and to judge distance and velocity.
According to the report, in 1997, a resupply ship collided with the Mir space station, possibly because a crew member bumped into the commander during the final docking maneuver. This mishap caused significant damage to the space station.
Returns to Earth suffered from problems, too. The same report notes that touchdown speeds during the first 100 space shuttle landings were “outside acceptable limits. The fastest landing on record – 224 knots (258 miles) per hour – was linked to the commander’s momentary spatial disorientation.” Earlier, each of the six Apollo crews that landed on the moon had difficulty recognizing moon landmarks and estimating distances. For example, Apollo 15 landed in an unplanned area, ultimately straddling the rim of a five-foot deep crater on the moon, harming one of its engines.
Spaceflight causes unique stresses on astronauts’ brains and central nervous systems. NASA is working to reduce these harmful effects.
NASA
Space messes up your brain
In space, astronauts face the challenges of microgravity, ionizing radiation, social isolation, high workloads, altered circadian rhythms, monotony, confined living quarters and a high-risk environment. Among these issues, microgravity is one of the most consequential in terms of physiological changes. It changes the brain’s structure and its functioning, which can hurt astronauts’ performance.
The brain shifts upwards within the skull, displacing the cerebrospinal fluid, which reduces the brain’s cushioning. Essentially, the brain becomes crowded inside the skull like a pair of too-tight shoes.
That’s partly because of how being in space alters blood flow. On Earth, gravity pulls our blood and other internal fluids toward our feet, but our circulatory valves ensure that the fluids are evenly distributed throughout the body. In space, there’s not enough gravity to pull the fluids down, and they shift up, says Rachael D. Seidler, a physiologist specializing in spaceflight at the University of Florida and principal investigator on many space-related studies. The head swells and legs appear thinner, causing what astronauts call “puffy face chicken legs.”
“The brain changes at the structural and functional level,” says Steven Jillings, equilibrium and aerospace researcher at the University of Antwerp in Belgium. “The brain shifts upwards within the skull,” displacing the cerebrospinal fluid, which reduces the brain’s cushioning. Essentially, the brain becomes crowded inside the skull like a pair of too-tight shoes. Some of the displaced cerebrospinal fluid goes into cavities within the brain, called ventricles, enlarging them. “The remaining fluids pool near the chest and heart,” explains Jillings. After 12 consecutive months in space, one astronaut had a ventricle that was 25 percent larger than before the mission.
Some changes reverse themselves while others persist for a while. An example of a longer-lasting problem is spaceflight-induced neuro-ocular syndrome, which results in near-sightedness and pressure inside the skull. A study of approximately 300 astronauts shows near-sightedness affects about 60 percent of astronauts after long missions on the International Space Station (ISS) and more than 25 percent after spaceflights of only a few weeks.
Another long-term change could be the decreased ability of cerebrospinal fluid to clear waste products from the brain, Seidler says. That’s because compressing the brain also compresses its waste-removing glymphatic pathways, resulting in inflammation, vulnerability to injuries and worsening its overall health.
The effects of long space missions were best demonstrated on astronaut twins Scott and Mark Kelly. This NASA Twins Study showed multiple, perhaps permanent, changes in Scott after his 340-day mission aboard the ISS, compared to Mark, who remained on Earth. The differences included declines in Scott’s speed, accuracy and cognitive abilities that persisted longer than six months after returning to Earth in March 2016.
By the end of 2020, Scott’s cognitive abilities improved, but structural and physiological changes to his eyes still remained, he said in a BBC interview.
“It seems clear that the upward shift of the brain and compression of the surrounding tissues with ventricular expansion might not be a good thing,” Seidler says. “But, at this point, the long-term consequences to brain health and human performance are not really known.”
NASA astronaut Kate Rubins conducts a session for the Neuromapping investigation.
NASA
Staying sharp in space
To investigate how prolonged space travel affects the brain, NASA launched a new initiative called the Complement of Integrated Protocols for Human Exploration Research (CIPHER). “CIPHER investigates how long-duration spaceflight affects both brain structure and function,” says neurobehavioral scientist Mathias Basner at the University of Pennsylvania, a principal investigator for several NASA studies. “Through it, we can find out how the brain adapts to the spaceflight environment and how certain brain regions (behave) differently after – relative to before – the mission.”
To do this, he says, “Astronauts will perform NASA’s cognition test battery before, during and after six- to 12-month missions, and will also perform the same test battery in an MRI scanner before and after the mission. We have to make sure we better understand the functional consequences of spaceflight on the human brain before we can send humans safely to the moon and, especially, to Mars.”
As we go deeper into space, astronauts cognitive and physical functions will be even more important. “A trip to Mars will take about one year…and will introduce long communication delays,” Seidler says. “If you are on that mission and have a problem, it may take eight to 10 minutes for your message to reach mission control, and another eight to 10 minutes for the response to get back to you.” In an emergency situation, that may be too late for the response to matter.
“On a mission to Mars, astronauts will be exposed to stressors for unprecedented amounts of time,” Basner says. To counter them, NASA is considering the continuous use of artificial gravity during the journey, and Seidler is studying whether artificial gravity can reduce the harmful effects of microgravity. Some scientists are looking at precision brain stimulation as a way to improve memory and reduce anxiety due to prolonged exposure to radiation in space.
Other scientists are exploring how to protect neural stem cells (which create brain cells) from radiation damage, developing drugs to repair damaged brain cells and protect cells from radiation.
To boldly go where no astronauts have gone before, they must have optimal reflexes, vision and decision-making. In the era of deep space exploration, the brain—without a doubt—is the final frontier.
Additionally, NASA is scrutinizing each aspect of the mission, including astronaut exercise, nutrition and intellectual engagement. “We need to give astronauts meaningful work. We need to stimulate their sensory, cognitive and other systems appropriately,” Basner says, especially given their extreme confinement and isolation. The scientific experiments performed on the ISS – like studying how microgravity affects the ability of tissue to regenerate is a good example.
“We need to keep them engaged socially, too,” he continues. The ISS crew, for example, regularly broadcasts from space and answers prerecorded questions from students on Earth, and can engage with social media in real time. And, despite tight quarters, NASA is ensuring the crew capsule and living quarters on the moon or Mars include private space, which is critical for good mental health.
Exploring deep space builds on a foundation that began when astronauts first left the planet. With each mission, scientists learn more about spaceflight effects on astronauts’ bodies. NASA will be using these lessons to succeed with its plans to build science stations on the moon and, eventually, Mars.
“Through internally and externally led research, investigations implemented in space and in spaceflight simulations on Earth, we are striving to reduce the likelihood and potential impacts of neurostructural changes in future, extended spaceflight,” summarizes NASA scientist Alexandra Whitmire. To boldly go where no astronauts have gone before, they must have optimal reflexes, vision and decision-making. In the era of deep space exploration, the brain—without a doubt—is the final frontier.
A newly discovered brain cell may lead to better treatments for cognitive disorders
Swiss researchers have discovered a third type of brain cell that appears to be a hybrid of the two other primary types — and it could lead to new treatments for many brain disorders.
The challenge: Most of the cells in the brain are either neurons or glial cells. While neurons use electrical and chemical signals to send messages to one another across small gaps called synapses, glial cells exist to support and protect neurons.
Astrocytes are a type of glial cell found near synapses. This close proximity to the place where brain signals are sent and received has led researchers to suspect that astrocytes might play an active role in the transmission of information inside the brain — a.k.a. “neurotransmission” — but no one has been able to prove the theory.
A new brain cell: Researchers at the Wyss Center for Bio and Neuroengineering and the University of Lausanne believe they’ve definitively proven that some astrocytes do actively participate in neurotransmission, making them a sort of hybrid of neurons and glial cells.
According to the researchers, this third type of brain cell, which they call a “glutamatergic astrocyte,” could offer a way to treat Alzheimer’s, Parkinson’s, and other disorders of the nervous system.
“Its discovery opens up immense research prospects,” said study co-director Andrea Volterra.
The study: Neurotransmission starts with a neuron releasing a chemical called a neurotransmitter, so the first thing the researchers did in their study was look at whether astrocytes can release the main neurotransmitter used by neurons: glutamate.
By analyzing astrocytes taken from the brains of mice, they discovered that certain astrocytes in the brain’s hippocampus did include the “molecular machinery” needed to excrete glutamate. They found evidence of the same machinery when they looked at datasets of human glial cells.
Finally, to demonstrate that these hybrid cells are actually playing a role in brain signaling, the researchers suppressed their ability to secrete glutamate in the brains of mice. This caused the rodents to experience memory problems.
“Our next studies will explore the potential protective role of this type of cell against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here,” said Andrea Volterra, University of Lausanne.
But why? The researchers aren’t sure why the brain needs glutamatergic astrocytes when it already has neurons, but Volterra suspects the hybrid brain cells may help with the distribution of signals — a single astrocyte can be in contact with thousands of synapses.
“Often, we have neuronal information that needs to spread to larger ensembles, and neurons are not very good for the coordination of this,” researcher Ludovic Telley told New Scientist.
Looking ahead: More research is needed to see how the new brain cell functions in people, but the discovery that it plays a role in memory in mice suggests it might be a worthwhile target for Alzheimer’s disease treatments.
The researchers also found evidence during their study that the cell might play a role in brain circuits linked to seizures and voluntary movements, meaning it’s also a new lead in the hunt for better epilepsy and Parkinson’s treatments.
“Our next studies will explore the potential protective role of this type of cell against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here,” said Volterra.