How Should Genetic Engineering Shape Our Future?
Terror. Error. Success. These are the three outcomes that ethicists evaluating a new technology should fear. The possibility that a breakthrough might be used maliciously. The possibility that newly empowered scientists might make a catastrophic mistake. And the possibility that a technology will be so successful that it will change how we live in ways that we can only guess—and that we may not want.
These tools will allow scientists to practice genetic engineering on a scale that is simultaneously far more precise and far more ambitious than ever before.
It was true for the scientists behind the Manhattan Project, who bequeathed a fear of nuclear terror and nuclear error, even as global security is ultimately defined by these weapons of mass destruction. It was true for the developers of the automobile, whose invention has been weaponized by terrorists and kills 3,400 people by accident each day, even as the more than 1 billion cars on the road today have utterly reshaped where we live and how we move. And it is true for the researchers behind the revolution in gene editing and writing.
Put simply, these tools will allow scientists to practice genetic engineering on a scale that is simultaneously far more precise and far more ambitious than ever before. Editing techniques like CRISPR enable exact genetic repairs through a simple cut and paste of DNA, while synthetic biologists aim to redo entire genomes through the writing and substitution of synthetic genes. The technologies are complementary, and they herald an era when the book of life will be not just readable, but rewritable. Food crops, endangered animals, even the human body itself—all will eventually be programmable.
The benefits are easy to imagine: more sustainable crops; cures for terminal genetic disorders; even an end to infertility. Also easy to picture are the ethical pitfalls as the negative images of those same benefits.
Terror is the most straightforward. States have sought to use biology as a weapon at least since invading armies flung the corpses of plague victims into besieged castles. The 1975 biological weapons convention banned—with general success—the research and production of offensive bioweapons, though a handful of lone terrorists and groups like the Oregon-based Rajneeshee cult have still carried out limited bioweapon attacks. Those incidents ultimately caused little death and damage, in part because medical science is mostly capable of defending us from those pathogens that are most easily weaponized. But gene editing and writing offers the chance to engineer germs that could be far more effective than anything nature could develop. Imagine a virus that combines the lethality of Ebola with the transmissibility of the common cold—and in the new world of biology, if you can imagine something, you will eventually be able to create it.
The benefits are easy to imagine: more sustainable crops; cures for terminal genetic disorders; even an end to infertility. Also easy to picture are the ethical pitfalls.
That's one reason why James Clapper, then the U.S. director of national intelligence, added gene editing to the list of threats posed by "weapons of mass destruction and proliferation" in 2016. But these new tools aren't merely dangerous in the wrong hands—they can also be dangerous in the right hands. The list of labs accidents involving lethal bugs is much longer than you'd want to know, at least if you're the sort of person who likes to sleep at night. The U.S. recently lifted a ban on research that works to make existing pathogens, like the H5N1 avian flu virus, more virulent and transmissible, often using new technologies like gene editing. Such work can help medicine better prepare for what nature might throw at us, but it could also make the consequences of a lab error far more catastrophic. There's also the possibility that the use of gene editing and writing in nature—say, by CRISPRing disease-carrying mosquitoes to make them sterile—could backfire in some unforeseen way. Add in the fact that the techniques behind gene editing and writing are becoming simpler and more automated with every year, and eventually millions of people will be capable—through terror or error—of unleashing something awful on the world.
The good news is that both the government and the researchers driving these technologies are increasingly aware of the risks of bioterror and error. One government program, the Functional Genomic and Computational Assessment of Threats (Fun GCAT), provides funding for scientists to scan genetic data looking for the "accidental or intentional creation of a biological threat." Those in the biotech industry know to keep an eye out for suspicious orders—say, a new customer who orders part of the sequence of the Ebola or smallpox virus. "With every invention there is a good use and a bad use," Emily Leproust, the CEO of the commercial DNA synthesis startup Twist Bioscience, said in a recent interview. "What we try hard to do is put in place as many systems as we can to maximize the good stuff, and minimize any negative impact."
But the greatest ethical challenges in gene editing and writing will arise not from malevolence or mistakes, but from success. Through a new technology called in vitro gametogenesis (IVG), scientists are learning how to turn adult human cells like a piece of skin into lab-made sperm and egg cells. That would be a huge breakthrough for the infertile, or for same-sex couples who want to conceive a child biologically related to both partners. It would also open the door to using gene editing to tinker with those lab-made embryos. At first interventions would address any obvious genetic disorders, but those same tools would likely allow the engineering of a child's intelligence, height and other characteristics. We might be morally repelled today by such an ability, as many scientists and ethicists were repelled by in-vitro fertilization (IVF) when it was introduced four decades ago. Yet more than a million babies in the U.S. have been born through IVF in the years since. Ethics can evolve along with technology.
These new technologies offer control over the code of life, but only we as a society can seize control over where these tools will take us.
Fertility is just one human institution that stands to be changed utterly by gene editing and writing, and it's a change we can at least imagine. As the new biology grows more ambitious, it will alter society in ways we can't begin to picture. Harvard's George Church and New York University's Jef Boeke are leading an effort called HGP-Write to create a completely synthetic human genome. While gene editing allows scientists to make small changes to the genome, the gene synthesis that Church and his collaborators are developing allows for total genetic rewrites. "It's a difference between editing a book and writing one," Church said in an interview earlier this year.
Church is already working on synthesizing organs that would be resistant to viruses, while other researchers like Harris Wang at Columbia University are experimenting with bioengineering mammalian cells to produce nutrients like amino acids that we currently need to get from food. The horizon is endless—and so are the ethical concerns of success. What if parents feel pressure to engineer their children just so they don't fall behind their IVG peers? What if only the rich are able to access synthetic biology technologies that could make them stronger, smarter and longer lived? Could inequality become encoded in the genome?
These are questions that are different from the terror and errors fears around biosecurity, because they ask us to think hard about what kind of future we want. To their credit, Church and his collaborators have engaged bioethicists from the start of their work, as have the pioneers behind CRISPR. But the challenges coming from successful gene editing and writing are too large to be outsourced to professional ethicists. These new technologies offer control over the code of life, but only we as a society can seize control over where these tools will take us.
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.