A panel of leading experts gathered this week at a sold-out event in downtown Manhattan to talk about the science and the ethics of enhancing human beings -- making people "better than well" through biomedical interventions. Here are the ten most memorable quotes from their lively discussion, which was organized by the New York Academy of Sciences, the Aspen Brain Institute, and the Hastings Center.
1) "It's okay for us to be enhanced relative to our ancestors; we are with the smallpox vaccine." —Dr. George Church, iconic genetics pioneer; professor at Harvard University and MIT
Church was more concerned with equitable access to enhancements than the morality of intervening in the first place. "We missed the last person with polio and now it's spread around the world again," he lamented.
Discussing how enhancements might become part of our species in the near-future, he mentioned the possibility of doctors slightly "overshooting" an intervention to reverse cognitive decline, for example; or younger people using such an intervention off-label. Another way might be through organ transplants, using organs that are engineered to not get cancer, or to be resistant to pain, pathogens, or senescence.
2) "All the technology we will need to fundamentally transform our species already exists. Humans are made of code, and that code is writable, readable and hackable." —Dr. Jamie Metzl, a technology futurist and geopolitical expert; Senior Fellow of the Atlantic Council, an international affairs think tank
The speed of change is on an exponential curve, and the world where we're going is changing at a much faster rate than we're used to, Metzl said. For example, a baby born 1000 years ago compared to one born today would be basically the same. But a baby born 1000 years in the future would seem like superman to us now, thanks to new capabilities that will become embedded in future people's genes over time. So how will we get from here to there?
"We will line up for small incremental benefits. By the time people are that changed, we will have adapted to a whole new set of social norms."
But, he asked, will well-meaning changes dangerously limit the diversity of our species?
3) "We are locked in a competitive arms race on both an individual and communal level, which will make it very difficult to put the brakes on. Everybody needs to be part of this conversation because it's a conversation about the future of our species." —Jamie Metzl
China, for one, plans to genetically sequence half of all newborns by 2020. In the U.S., it is standard to screen for 34 health conditions in newborns (though the exact number varies by state). There are no national guidelines for newborn genomic screening, though the National Institutes of Health is currently funding several research studies to explore the ethical concerns, potential benefits, and limitations of doing so on a large scale.
4) "I find freedom in not directing exactly how my child will be." —Josephine Johnston, Director of Research at the Hastings Center, the world's oldest bioethics research institute
Johnston cautioned against a full-throttled embrace of biomedical enhancements. Parents seeking to remake nature to serve their own purpose would be "like helicopter parenting on steroids," she said. "It could be a kind of felt obligation, something parents don't want to do but feel they must in order to compete." She warned this would be "one way to totally ruin the parenting experience altogether. I would hate to be the kind of parent who selects and controls her child's traits and talents."
Among other concerns, she worried about parents aiming to comply with social norms through technological intervention. Would a black mom, for example, feel pressure to make her child's skin paler to alleviate racial bias?
5) "We need to seriously consider the risks of a future if a handful of private companies own and monetize a map of our thoughts at any given moment." – Meredith Whittaker, Research Scientist, Open Research Lead at Google, and Co-Director of New York University's AI Now Institute, examining the social implications of artificial intelligence
The recent boom in AI research is the result of the consolidation of the tech industry's resources; only seven companies have the means to create artificial intelligence at scale, and one of the innovations on the horizon is brain-computer interfaces.
Facebook, for example, has a team of 60 engineers working on BCIs to let you type with your mind. Elon Musk's company Neuralink is working on technology that is aiming for "direct lag-free interactions between our brains and our devices."
But who will own this data? In the future, could the National Security Agency ask Neuralink, et al. for your thought log?
6) "The economic, political, and social contexts are as important as the tech itself. We need to look at power, who gets to define normal, and who falls outside of this category?" – Meredith Whittaker
Raising concerns about AI bias, Whittaker discussed how data is often coded by affluent white men from the Bay Area, potentially perpetuating discrimination against women and racial minorities.
Facial recognition, she said, is 30 percent less accurate for black women than for white men. And voice recognition systems don't hear women's voices as well as men's, among many other examples. The big question is: "Who gets to decide what's normal? And how do we ensure that different versions of normal can exist between cultures and communities? It is impossible not see the high stakes here, and how oppressive classifications of normal can marginalize people."
From left: George Church, Jamie Metzl, Josephine Johnston, Meredith Whittaker
7) "We might draw a red line at cloning or germline enhancements, but when you define those or think of specific cases, you realize you threw the baby out with the bathwater." —George Church, answering a question about whether society should agree on any red lines to prohibit certain interventions
"We should be focusing on outcomes," he suggested. "Could enhancement be a consequence of curing a disease like cognitive decline? That would concern me about drawing red lines."
8) "We have the technology to create Black Mirror. We could create a social credit score and it's terrifying." —Meredith Whittaker
In China, she said, the government is calculating scores to rank citizens based on aggregates of data like their educational history, their friend graphs, their employment and credit history, and their record of being critical of the government. These scores have already been used to bar 12 million people from travel.
"If we don't have the ability to make a choice," she said, "it could be a very frightening future."
9) "These tools will make all kinds of wonderful realities possible. Nobody looks at someone dying of cancer and says that's natural." —Jamie Metzl
Using biomedical interventions to restore health is an unequivocal moral good. But other experts questioned whether there should be a limit in how far these technologies are taken to achieve normalcy and beyond.
10) "Cancer's the easy one; what about deafness?" —Josephine Johnston, in retort
Could one person's disability be another person's desired state? "We should be so suspicious" of using technology to eradicate different ways of being in the world, she warned. Hubris has led us down the wrong path in the past, such as when homosexuality was considered a mental disorder.
"If we sometimes make mistakes about disease or dysfunction," she said, "we might make mistakes about what is a valid experience of the human condition."
In November 2020, messenger RNA catapulted into the public consciousness when the first COVID-19 vaccines were authorized for emergency use. Around the same time, an equally groundbreaking yet relatively unheralded application of mRNA technology was taking place at a London hospital.
Over the past two decades, there's been increasing interest in harnessing mRNA — molecules present in all of our cells that act like digital tape recorders, copying instructions from DNA in the cell nucleus and carrying them to the protein-making structures — to create a whole new class of therapeutics.
Scientists realized that artificial mRNA, designed in the lab, could be used to instruct our cells to produce certain antibodies, turning our bodies into vaccine-making factories, or to recognize and attack tumors. More recently, researchers recognized that mRNA could also be used to make another groundbreaking technology far more accessible to more patients: gene editing. The gene-editing tool CRISPR has generated plenty of hype for its potential to cure inherited diseases. But delivering CRISPR to the body is complicated and costly.
"Most gene editing involves taking cells out of the patient, treating them and then giving them back, which is an extremely expensive process," explains Drew Weissman, professor of medicine at the University of Pennsylvania, who was involved in developing the mRNA technology behind the COVID-19 vaccines.
But last November, a Massachusetts-based biotech company called Intellia Therapeutics showed it was possible to use mRNA to make the CRISPR system inside the body, eliminating the need to extract cells out of the body and edit them in a lab. Just as mRNA can instruct our cells to produce antibodies against a viral infection, it can also teach them to produce the two molecular components that make up CRISPR — a guide molecule and a cutting protein — to snip out a problem gene.
"The pandemic has really shown that not only are mRNA approaches viable, they could in certain circumstances be vastly superior to more traditional technologies."
In Intellia's London-based clinical trial, the company applied this for the first time in a patient with a rare inherited liver disease known as hereditary transthyretin amyloidosis with polyneuropathy. The disease causes a toxic protein to build up in a person's organs and is typically fatal. In a company press release, Intellia's president and CEO John Leonard swiftly declared that its mRNA-based CRISPR therapy could usher in a "new era of potential genome editing cures."
Weissman predicts that turning CRISPR into an affordable therapy will become the next major frontier for mRNA over the coming decade. His lab is currently working on an mRNA-based CRISPR treatment for sickle cell disease. More than 300,000 babies are born with sickle cell every year, mainly in lower income nations.
"There is a FDA-approved cure, but it involves taking the bone marrow out of the person, and then giving it back which is prohibitively expensive," he says. It also requires a patient to have a matched bone marrow done. "We give an intravenous injection of mRNA lipid nanoparticles that target CRISPR to the bone marrow stem cells in the patient, which is easy, and much less expensive."
Meanwhile, the overwhelming success of the COVID-19 vaccines has focused attention on other ways of using mRNA to bolster the immune system against threats ranging from other infectious diseases to cancer.
The practicality of mRNA vaccines – relatively small quantities are required to induce an antibody response – coupled with their adaptable design, mean companies like Moderna are now targeting pathogens like Zika, chikungunya and cytomegalovirus, or CMV, which previously considered commercially unviable for vaccine developers. This is because outbreaks have been relatively sporadic, and these viruses mainly affect people in low-income nations who can't afford to pay premium prices for a vaccine. But mRNA technology means that jabs could be produced on a flexible basis, when required, at relatively low cost.
Other scientists suggest that mRNA could even provide a means of developing a universal influenza vaccine, a goal that's long been the Holy Grail for vaccinologists around the world.
"The mRNA technology allows you to pick out bits of the virus that you want to induce immunity to," says Michael Mulqueen, vice president of business development at eTheRNA, a Belgium-based biotech that's developing mRNA-based vaccines for malaria and HIV, as well as various forms of cancer. "This means you can get the immune system primed to the bits of the virus that don't vary so much between strains. So you could actually have a single vaccine that protects against a whole raft of different variants of the same virus, offering more universal coverage."
Before mRNA became synonymous with vaccines, its biggest potential was for cancer treatments. BioNTech, the German biotech company that collaborated with Pfizer to develop the first authorized COVID-19 vaccine, was initially founded to utilize mRNA for personalized cancer treatments, and the company remains interested in cancers ranging from melanoma to breast cancer.
One of the major hurdles in treating cancer has been the fact that tumors can look very different from one person to the next. It's why conventional approaches, such as chemotherapy or radiation, don't work for every patient. But weaponizing mRNA against cancer primes the immune cells with the tumor's specific genetic sequence, training the patient's body to attack their own unique type of cancer.
"It means you're able to think about personalizing cancer treatments down to specific subgroups of patients," says Mulqueen. "For example, eTheRNA are developing a renal cell carcinoma treatment which will be targeted at around 20% of these patients, who have specific tumor types. We're hoping to take that to human trials next year, but the challenge is trying to identify the right patients for the treatment at an early stage."
Repairing Damaged mRNA
While hopes are high that mRNA could usher in new cancer treatments and make CRISPR more accessible, a growing number of companies are also exploring an alternative to gene editing, known as RNA editing.
In genetic disorders, the mRNA in certain cells is impaired due to a rogue gene defect, and so the body ceases to produce a particular vital protein. Instead of permanently deleting the problem gene with CRISPR, the idea behind RNA editing is to inject small pieces of synthetic mRNA to repair the existing mRNA. Scientists think this approach will allow normal protein production to resume.
Over the past few years, this approach has gathered momentum, as some researchers have recognized that it holds certain key advantages over CRISPR. Companies from Belgium to Japan are now looking at RNA editing to treat all kinds of disorders, from Huntingdon's disease, to amyotrophic lateral sclerosis, or ALS, and certain types of cancer.
"With RNA editing, you don't need to make any changes to the DNA," explains Daniel de Boer, CEO of Dutch biotech ProQR, which is looking to treat rare genetic disorders that cause blindness. "Changes to the DNA are permanent, so if something goes wrong, that may not be desirable. With RNA editing, it's a temporary change, so we dose patients with our drugs once or twice a year."
Last month, ProQR reported a landmark case study, in which a patient with a rare form of blindness called Leber congenital amaurosis, which affects the retina at the back of the eye, recovered vision after three months of treatment.
"We have seen that this RNA therapy restores vision in people that were completely blind for a year or so," says de Boer. "They were able to see again, to read again. We think there are a large number of other genetic diseases we could go after with this technology. There are thousands of different mutations that can lead to blindness, and we think this technology can target approximately 25% of them."
Ultimately, there's likely to be a role for both RNA editing and CRISPR, depending on the disease. "I think CRISPR is ideally suited for illnesses where you would like to permanently correct a genetic defect," says Joshua Rosenthal of the Marine Biology Laboratory in Chicago. "Whereas RNA editing could be used to treat things like pain, where you might want to reset a neural circuit temporarily over a shorter period of time."
Much of this research has been accelerated by the COVID-19 pandemic, which has played a major role in bringing mRNA to the forefront of people's minds as a therapeutic.
"The pandemic has really shown that not only are mRNA approaches viable, they could in certain circumstances be vastly superior to more traditional technologies," says Mulqueen. "In the future, I would not be surprised if many of the top pharma products are mRNA derived."
"Making Sense of Science" is a monthly podcast that features interviews with leading medical and scientific experts about the latest developments and the big ethical and societal questions they raise. This episode is hosted by science and biotech journalist Emily Mullin, summer editor of the award-winning science outlet Leaps.org.