As a species, we are prone to weaponizing. There is a famous anecdote from Wulf Schievenhovel, a German anthropologist who was working in the highlands of New Guinea studying a local tribe. One day, he offered two tribesmen a flight in an airplane. They duly accepted but showed up with two large stones. When he asked why, they told him that they wanted to drop them on a neighboring village. Ethologist Frans de Waal later remarked on this story that Schievenhovel had effectively "witnessed the invention of the bomb."
Today you don't have to be Putin or Kim Jong Un to pose an existential threat.
Modern technology has given us access to more than just rocks. In 2011, a Swedish man was arrested after attempting a nuclear fission in his kitchen. And in the inaugural issue of this magazine, my colleague Hank Greely raised a terrifying prospect:
"do-it-yourself hobbyists can use CRISPR [gene editing]… to change the genomes of whole species of living things – domestic or wild; animal, vegetable, or microbial – cheaply, easily, and before we even know it is happening."
In science fiction, it is typically governments that take over technologies and use them for evil. That risk is of course no fiction. It is an ongoing problem that we have addressed through institutions: democracies, constitutions, legal systems and international treaties, and groups working together as checks and balances. It isn't perfect, but it has worked (so far).
Today you don't have to be Putin or Kim Jong Un to pose an existential threat. We are rapidly acquiring the technological ability for individuals and groups not just to cause major harm, but to do so exactly as Hank said: "cheaply, easily, and before we even know it is happening."
How should we address this problem? Together with Ingmar Persson, a fellow philosophy professor at Gothenburg, Sweden, I have argued that while education, institutions and good policing are important, we may need to think more radically.
We could adapt our biology so that we can appreciate the suffering of foreign or future people in the same instinctive way we do our friends and neighbors.
We evolved, along with the New Guinea tribesmen, to care about our small group and to be suspicious of outsiders. We evolved to cooperate well within our group, at a size where we could keep an eye on free riders. And we evolved to have the ability, and occasionally the desire to harm others, but with a natural limit on the amount of harm we could do—at least before others could step in to prevent, punish or kill us.
Our limitations have also become apparent in another form of existential threat: resource depletion. Despite our best efforts at educating, nudging, and legislating on climate change, carbon dioxide emissions in 2017 are expected to come in at the highest ever following a predicted rise of 2 percent. Why? We aren't good at cooperating in larger groups where freeriding is not easily spotted. We also deal with problems in order of urgency. A problem close by is much more significant to us than a problem in the future. That's why even if we accept there is a choice between economic recession now or natural disasters and potential famine in the future, we choose to carry on drilling for oil. And if the disasters and famine are present day, but geographically distant, we still choose to carry on drilling.
So what is our radical solution? We propose that there is a need for what we call moral bioenhancement. That is, for seeking a biological intervention that can help us overcome our evolved moral limitations. For example, adapting our biology so that we can appreciate the suffering of foreign or future people in the same instinctive way we do our friends and neighbors. Or, in the case of individuals, in addressing the problem of psychopathy from a biological perspective.
There is no reason in principle why humans could not be genetically modified...to make them kinder, happier, more conscientious, altruistic and just.
We have been dramatically successful at modifying various moral characteristics of non-human animals. Over ten thousand years or so, we have turned wolves into dogs by selective breeding, and those dogs into breeds with behavioural as well as physical characteristics: certain breeds can be faithful, hard working, good tempered and intelligent (or the opposite). Scientists have manipulated the expression of genes in prairie voles to cause them to form a mate bond more quickly, and in monkeys to make them work harder. There is no reason in principle why humans could not be genetically modified using gene editing, or their brains modified in other ways, to make them kinder, happier, more conscientious, altruistic and just.
One objection is that this is a pipe dream: even if it is acceptable to do this, it is so unlikely to be achievable, it is not worth pursuing. However, research has shown that we are already morally modified. This is widely accepted when it comes to negative effects. For example, we all know that alcohol can lead people to aggressive or other destructive behaviours that they would not have countenanced sober. In a 2008 case, a retired UK teacher was cleared of child pornography charges after he successfully argued his behaviour was caused by a drug prescribed for his Parkinson's disease. There is also evidence that we can be morally modified in a more positive direction. For example, SSRIs like Prozac, a class of drugs widely used to treat depression, have been shown to act on healthy volunteers to make them more cooperative and less critical.
Another objection is that we need the negative aspects of our human character. We need people who can fight wars. We need to be able to blot out the suffering of the wider world: to experience it as we would if it applied to our nearest and dearest would be unbearable. This might be so. If aggressiveness and denial, or strong bonding to small communities, are important traits, it is important that we understand how, and to what degree, they should be controlled. It is unlikely that nature has dished out exactly the right levels of all morally relevant characteristics on an individual or population level. We don't claim to have all the answers to what characteristics we need to enhance, and what characteristics we need to diminish. But we see no reason to believe that the status quo is the optimum.
We haven't argued that we should go blindly in now with half-baked moral enhancers, or that we should forget about moral education, or legal solutions. Evolution has a built-in response to existential threats through adaptation. But adaptation takes generations and can't deal with threats that take out a whole population. Some threats are too important —and too urgent—to be left to chance.
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.