When Are We Obligated To Edit Wild Creatures?
Combining CRISPR genome editing with the natural phenomenon of gene drive allows us to rewrite the genomes of wild organisms. The benefits of saving children from malaria by editing mosquitoes are obvious and much discussed, but humans aren't the only creatures who suffer. If we gain the power to intervene in a natural world "red in tooth and claw," yet decline to use it, are we morally responsible for the animal suffering that we could have prevented?
Given the power to alter the workings of the natural world, are we morally obligated to use it?
The scenario that may redefine our relationship with the natural world begins with fine clothing. You're dressed to the nines for a formal event, but you arrived early, and it's such a beautiful day that you decided to take a stroll by the nearby lake. Suddenly, you hear the sound of splashing and screams. A child is drowning! Will you dive in to save them? Or let them die, and preserve your expensive outfit?
The philosopher Peter Singer posited this scenario to show that we are all terrible human beings. Just about everyone would save the child and ruin the outfit... leading Singer to question why so few of us give equivalent amounts of money to save children on the other side of the world. The Against Malaria Foundation averages one life saved for every $7000.
But despite having a local bias, our moral compasses aren't completely broken. You never even considered letting the child drown because the situation wasn't your fault. That's because the cause of the problem simply isn't relevant: as the one who could intervene, the consequences are on your head. We are morally responsible for intervening in situations we did not create.
There is a critical difference between Singer's original scenario and the one above: in his version, it was a muddy pond. Any adult can rescue a child from a muddy pond, but a lake is different; you can only save the child if you know how to swim. We only become morally responsible when we acquire the power to intervene.
Few would disagree with either of these moral statements, but when they are combined with increasingly powerful technologies, the implications are deeply unsettling. Given the power to alter the workings of the natural world, are we morally obligated to use it? Recent developments suggest we had best determine the answer soon because, technologically, we are learning to swim. What choices will we make?
Gene drive is a natural phenomenon that occurs when a genetic element reliably spreads through a population even though it reduces the reproductive fitness of individual organisms. Nature has evolved many different mechanisms that result in gene drive, so many that it's nearly impossible to find an organism that doesn't have at least one driving element somewhere in its genome. More than half of our own DNA comprises the broken remnants of gene drives, plus a few active copies.
Scientists have long dreamed of harnessing gene drive to block mosquito-borne disease, with little success. Then came CRISPR genome editing, which works by cutting target genes and replacing them with a new sequence. What happens if you replace the original sequence with the edited version and an encoded copy of the CRISPR system? Gene drive.
CRISPR is a molecular scalpel that we can use to cut, and therefore replace, just about any DNA sequence in any cell. Encode the instructions for the CRISPR system adjacent to the new sequence, and genome editing will occur in the reproductive cells of subsequent generations of heterozygotes, always converting the original wild-type version to the new edited version. By ensuring that offspring will all be born of one sex, or by arranging for organisms that inherit two copies of the gene drive to be sterile, it's theoretically possible to cause a population crash.
(Credit: Esvelt)
When my colleagues and I first described this technology in 2014, we initially focused on the imperative for early transparency. Gene drive research is more like civic governance than traditional technology development: you can decline a treatment recommended by your doctor, but you can’t opt out when people change the shared environment. Applying the traditional closeted model of science to gene drive actively denies people a voice in decisions intended to affect them - and reforming scientific incentives for gene drive could be the first step to making all of science faster and safer.
But open gene drive research is clearly aligned with virtually all of our values. It's when technology places our deepest moral beliefs in conflict that we struggle, and learn who we truly are.
Two of our strongest moral beliefs include our reverence for the natural world and our abhorrence of suffering. Yet some natural species inherently cause tremendous suffering. Are we morally obligated to alter or even eradicate them?
To anyone who doubts that the natural world can inflict unimaginable suffering, consider the New World screwworm.
Judging by history, the answer depends on who is doing the suffering. We view the eradication of smallpox as one of our greatest triumphs, clearly demonstrating that we value human lives over the existence of disease-causing microorganisms. The same principle holds today for malaria: few would argue against using gene drive to crash populations of malarial mosquitoes to help eradicate the disease. There are more than 3500 species of mosquitoes, only three of which would be affected, and once malaria is gone, the mosquitoes could be allowed to recover. It would be extremely surprising if African nations decided not to eradicate malaria.
The more interesting question concerns our moral obligations to animals in the state of nature.
To anyone who doubts that the natural world can inflict unimaginable suffering, consider the New World screwworm, Cochyliomyia hominivorax. Female screwworm flies lay their eggs in open wounds, generating maggots that devour healthy tissue, gluttonously burrowing into the flesh of their host until they drop, engorged and sated, to metamorphose. Yet before they fall, the maggots in a wound emit a pheromone attracting new females, thereby acting as both conductors and performers in a macabre parade that consumes the host alive. The pain is utterly excruciating, so much so that infested people often require morphine before doctors can even examine the wound. Worst of all, the New World screwworm specializes in devouring complex mammals.
Every second of every day, hundreds of millions of animals suffer the excruciating agony of being eaten alive. It has been so throughout North and South America for millions of years. Until 2001, when humanity eradicated the last screwworm fly north of Panama using the “sterile insect technique�. This was not done to protect wild animals or even people, but for economic reasons: the cost of the program was small relative to the immense damage wrought by the screwworm on North American cattle, sheep, and goats. There were no obvious ecological effects. Despite being almost completely unknown even among animal rights activists, the screwworm elimination campaign may well have been one of the greatest triumphs of animal well-being.
Unfortunately, sterile insect technique isn't powerful enough to eradicate the screwworm from South America, where it is more entrenched and protected by the rougher terrain. But gene drive is.
Contrary to news hype, gene drive alone can't cause extinction, but if combined with conventional measures it might be possible to remove targeted species from the wild. For certain species that cause immense suffering, we may be morally obligated to do just that.
(Credit: Esvelt)
South Americans may well decide to eradicate screwworm for the same economic reasons that it was eradicated from North America: the fly inflicts $4 billion in annual damages on struggling rural communities that can least afford it. It need not go extinct, of course; the existence of the sterile insect facility in Panama proves that we can maintain the screwworm indefinitely in captivity on already dead meat.
Yet if for some reason humanity chooses to leave the screwworm as it is - even for upstanding moral reasons, whatever those may be - the knowledge of our responsibility should haunt us.
Tennyson wrote,
Are God and Nature then at strife,
That Nature lends such evil dreams?
So careful of the type she seems,
So careless of the single life.
Evolution by natural selection cares nothing for the single life, nor suffering, nor euphoria, save for their utility in replication. Theoretically, we do. But how much?
[Editor's Note: This story was originally published in May 2018. We are resurfacing archive hits while our staff is on vacation.]
Bivalent Boosters for Young Children Are Elusive. The Search Is On for Ways to Improve Access.
It’s Theo’s* first time in the snow. Wide-eyed, he totters outside holding his father’s hand. Sarah Holmes feels great joy in watching her 18-month-old son experience the world, “His genuine wonder and excitement gives me so much hope.”
In the summer of 2021, two months after Theo was born, Holmes, a behavioral health provider in Nebraska lost her grandparents to COVID-19. Both were vaccinated and thought they could unmask without any risk. “My grandfather was a veteran, and really trusted the government and faith leaders saying that COVID-19 wasn’t a threat anymore,” she says.” The state of emergency in Louisiana had ended and that was the message from the people they respected. “That is what killed them.”
The current official public health messaging is that regardless of what variant is circulating, the best way to be protected is to get vaccinated. These warnings no longer mention masking, or any of the other Swiss-cheese layers of mitigation that were prevalent in the early days of this ongoing pandemic.
The problem with the prevailing, vaccine centered strategy is that if you are a parent with children under five, barriers to access are real. In many cases, meaningful tools and changes that would address these obstacles are lacking, such as offering vaccines at more locations, mandating masks at these sites, and providing paid leave time to get the shots.
Children are at risk
Data presented at the most recent FDA advisory panel on COVID-19 vaccines showed that in the last year infants under six months had the third highest rate of hospitalization. “From the beginning, the message has been that kids don’t get COVID, and then the message was, well kids get COVID, but it’s not serious,” says Elias Kass, a pediatrician in Seattle. “Then they waited so long on the initial vaccines that by the time kids could get vaccinated, the majority of them had been infected.”
A closer look at the data from the CDC also reveals that from January 2022 to January 2023 children aged 6 to 23 months were more likely to be hospitalized than all other vaccine eligible pediatric age groups.
“We sort of forced an entire generation of kids to be infected with a novel virus and just don't give a shit, like nobody cares about kids,” Kass says. In some cases, COVID has wreaked havoc with the immune systems of very young children at his practice, making them vulnerable to other illnesses, he said. “And now we have kids that have had COVID two or three times, and we don’t know what is going to happen to them.”
Jumping through hurdles
Children under five were the last group to have an emergency use authorization (EUA) granted for the COVID-19 vaccine, a year and a half after adult vaccine approval. In June 2022, 30,000 sites were initially available for children across the country. Six months later, when boosters became available, there were only 5,000.
Currently, only 3.8% of children under two have completed a primary series, according to the CDC. An even more abysmal 0.2% under two have gotten a booster.
Ariadne Labs, a health center affiliated with Harvard, is trying to understand why these gaps exist. In conjunction with Boston Children’s Hospital, they have created a vaccine equity planner that maps the locations of vaccine deserts based on factors such as social vulnerability indexes and transportation access.
“People are having to travel farther because the sites are just few and far between,” says Benjy Renton, a research assistant at Ariadne.
Michelle Baltes-Breitwisch, a pharmacist, and her two-year-old daughter, Charlee, live in Iowa. When the boosters first came out she expected her toddler could get it close to home, but her husband had to drive Charlee four hours roundtrip.
This experience hasn’t been uncommon, especially in rural parts of the U.S. If parents wanted vaccines for their young children shortly after approval, they faced the prospect of loading babies and toddlers, famous for their calm demeanor, into cars for lengthy rides. The situation continues today. Mrs. Smith*, a grant writer and non-profit advisor who lives in Idaho, is still unable to get her child the bivalent booster because a two-hour one-way drive in winter weather isn’t possible.
It can be more difficult for low wage earners to take time off, which poses challenges especially in a number of rural counties across the country, where weekend hours for getting the shots may be limited.
Protect Their Future (PTF), a grassroots organization focusing on advocacy for the health care of children, hears from parents several times a week who are having trouble finding vaccines. The vaccine rollout “has been a total mess,” says Tamara Lea Spira, co-founder of PTF “It’s been very hard for people to access vaccines for children, particularly those under three.”
Seventeen states have passed laws that give pharmacists authority to vaccinate as young as six months. Under federal law, the minimum age in other states is three. Even in the states that allow vaccination of toddlers, each pharmacy chain varies. Some require prescriptions.
It takes time to make phone calls to confirm availability and book appointments online. “So it means that the parents who are getting their children vaccinated are those who are even more motivated and with the time and the resources to understand whether and how their kids can get vaccinated,” says Tiffany Green, an associate professor in population health sciences at the University of Wisconsin at Madison.
Green adds, “And then we have the contraction of vaccine availability in terms of sites…who is most likely to be affected? It's the usual suspects, children of color, disabled children, low-income children.”
It can be more difficult for low wage earners to take time off, which poses challenges especially in a number of rural counties across the country, where weekend hours for getting the shots may be limited. In Bibb County, Ala., vaccinations take place only on Wednesdays from 1:45 to 3:00 pm.
“People who are focused on putting food on the table or stressed about having enough money to pay rent aren't going to prioritize getting vaccinated that day,” says Julia Raifman, assistant professor of health law, policy and management at Boston University. She created the COVID-19 U.S. State Policy Database, which tracks state health and economic policies related to the pandemic.
Most states in the U.S. lack paid sick leave policies, and the average paid sick days with private employers is about one week. Green says, “I think COVID should have been a wake-up call that this is necessary.”
Maskless waiting rooms
For her son, Holmes spent hours making phone calls but could uncover no clear answers. No one could estimate an arrival date for the booster. “It disappoints me greatly that the process for locating COVID-19 vaccinations for young children requires so much legwork in terms of time and resources,” she says.
In January, she found a pharmacy 30 minutes away that could vaccinate Theo. With her son being too young to mask, she waited in the car with him as long as possible to avoid a busy, maskless waiting room.
Kids under two, such as Theo, are advised not to wear masks, which make it too hard for them to breathe. With masking policies a rarity these days, waiting rooms for vaccines present another barrier to access. Even in healthcare settings, current CDC guidance only requires masking during high transmission or when treating COVID positive patients directly.
“This is a group that is really left behind,” says Raifman. “They cannot wear masks themselves. They really depend on others around them wearing masks. There's not even one train car they can go on if their parents need to take public transportation… and not risk COVID transmission.”
Yet another challenge is presented for those who don’t speak English or Spanish. According to Translators without Borders, 65 million people in America speak a language other than English. Most state departments of health have a COVID-19 web page that redirects to the federal vaccines.gov in English, with an option to translate to Spanish only.
The main avenue for accessing information on vaccines relies on an internet connection, but 22 percent of rural Americans lack broadband access. “People who lack digital access, or don’t speak English…or know how to navigate or work with computers are unable to use that service and then don’t have access to the vaccines because they just don’t know how to get to them,” Jirmanus, an affiliate of the FXB Center for Health and Human Rights at Harvard and a member of The People’s CDC explains. She sees this issue frequently when working with immigrant communities in Massachusetts. “You really have to meet people where they’re at, and that means physically where they’re at.”
Equitable solutions
Grassroots and advocacy organizations like PTF have been filling a lot of the holes left by spotty federal policy. “In many ways this collective care has been as important as our gains to access the vaccine itself,” says Spira, the PTF co-founder.
PTF facilitates peer-to-peer networks of parents that offer support to each other. At least one parent in the group has crowdsourced information on locations that are providing vaccines for the very young and created a spreadsheet displaying vaccine locations. “It is incredible to me still that this vacuum of information and support exists, and it took a totally grassroots and volunteer effort of parents and physicians to try and respond to this need.” says Spira.
Kass, who is also affiliated with PTF, has been vaccinating any child who comes to his independent practice, regardless of whether they’re one of his patients or have insurance. “I think putting everything on retail pharmacies is not appropriate. By the time the kids' vaccines were released, all of our mass vaccination sites had been taken down.” A big way to help parents and pediatricians would be to allow mixing and matching. Any child who has had the full Pfizer series has had to forgo a bivalent booster.
“I think getting those first two or three doses into kids should still be a priority, and I don’t want to lose sight of all that,” states Renton, the researcher at Ariadne Labs. Through the vaccine equity planner, he has been trying to see if there are places where mobile clinics can go to improve access. Renton continues to work with local and state planners to aid in vaccine planning. “I think any way we can make that process a lot easier…will go a long way into building vaccine confidence and getting people vaccinated,” Renton says.
Michelle Baltes-Breitwisch, a pharmacist, and her two-year-old daughter, Charlee, live in Iowa. Her husband had to drive four hours roundtrip to get the boosters for Charlee.
Michelle Baltes-Breitwisch
Other changes need to come from the CDC. Even though the CDC “has this historic reputation and a mission of valuing equity and promoting health,” Jirmanus says, “they’re really failing. The emphasis on personal responsibility is leaving a lot of people behind.” She believes another avenue for more equitable access is creating legislation for upgraded ventilation in indoor public spaces.
Given the gaps in state policies, federal leadership matters, Raifman says. With the FDA leaning toward a yearly COVID vaccine, an equity lens from the CDC will be even more critical. “We can have data driven approaches to using evidence based policies like mask policies, when and where they're most important,” she says. Raifman wants to see a sustainable system of vaccine delivery across the country complemented with a surge preparedness plan.
With the public health emergency ending and vaccines going to the private market sometime in 2023, it seems unlikely that vaccine access is going to improve. Now more than ever, ”We need to be able to extend to people the choice of not being infected with COVID,” Jirmanus says.
*Some names were changed for privacy reasons.
What causes aging? In a paper published last month, Dr. David Sinclair, Professor in the Department of Genetics at Harvard Medical School, reports that he and his co-authors have found the answer. Harnessing this knowledge, Dr. Sinclair was able to reverse this process, making mice younger, according to the study published in the journal Cell.
I talked with Dr. Sinclair about his new study for the latest episode of Making Sense of Science. Turning back the clock on mouse age through what’s called epigenetic reprogramming – and understanding why animals get older in the first place – are key steps toward finding therapies for healthier aging in humans. We also talked about questions that have been raised about the research.
Show links:
Dr. Sinclair's paper, published last month in Cell.
Recent pre-print paper - not yet peer reviewed - showing that mice treated with Yamanaka factors lived longer than the control group.
Dr. Sinclair's podcast.
Previous research on aging and DNA mutations.
Dr. Sinclair's book, Lifespan.
Harvard Medical School