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.]
Nobel Prize goes to technology for mRNA vaccines
When Drew Weissman received a call from Katalin Karikó in the early morning hours this past Monday, he assumed his longtime research partner was calling to share a nascent, nagging idea. Weissman, a professor of medicine at the Perelman School of Medicine at the University of Pennsylvania, and Karikó, a professor at Szeged University and an adjunct professor at UPenn, both struggle with sleep disturbances. Thus, middle-of-the-night discourses between the two, often over email, has been a staple of their friendship. But this time, Karikó had something more pressing and exciting to share: They had won the 2023 Nobel Prize in Physiology or Medicine.
The work for which they garnered the illustrious award and its accompanying $1,000,000 cash windfall was completed about two decades ago, wrought through long hours in the lab over many arduous years. But humanity collectively benefited from its life-saving outcome three years ago, when both Moderna and Pfizer/BioNTech’s mRNA vaccines against COVID were found to be safe and highly effective at preventing severe disease. Billions of doses have since been given out to protect humans from the upstart viral scourge.
“I thought of going somewhere else, or doing something else,” said Katalin Karikó. “I also thought maybe I’m not good enough, not smart enough. I tried to imagine: Everything is here, and I just have to do better experiments.”
Unlocking the power of mRNA
Weissman and Karikó unlocked mRNA vaccines for the world back in the early 2000s when they made a key breakthrough. Messenger RNA molecules are essentially instructions for cells’ ribosomes to make specific proteins, so in the 1980s and 1990s, researchers started wondering if sneaking mRNA into the body could trigger cells to manufacture antibodies, enzymes, or growth agents for protecting against infection, treating disease, or repairing tissues. But there was a big problem: injecting this synthetic mRNA triggered a dangerous, inflammatory immune response resulting in the mRNA’s destruction.
While most other researchers chose not to tackle this perplexing problem to instead pursue more lucrative and publishable exploits, Karikó stuck with it. The choice sent her academic career into depressing doldrums. Nobody would fund her work, publications dried up, and after six years as an assistant professor at the University of Pennsylvania, Karikó got demoted. She was going backward.
“I thought of going somewhere else, or doing something else,” Karikó told Stat in 2020. “I also thought maybe I’m not good enough, not smart enough. I tried to imagine: Everything is here, and I just have to do better experiments.”
A tale of tenacity
Collaborating with Drew Weissman, a new professor at the University of Pennsylvania, in the late 1990s helped provide Karikó with the tenacity to continue. Weissman nurtured a goal of developing a vaccine against HIV-1, and saw mRNA as a potential way to do it.
“For the 20 years that we’ve worked together before anybody knew what RNA is, or cared, it was the two of us literally side by side at a bench working together,” Weissman said in an interview with Adam Smith of the Nobel Foundation.
In 2005, the duo made their 2023 Nobel Prize-winning breakthrough, detailing it in a relatively small journal, Immunity. (Their paper was rejected by larger journals, including Science and Nature.) They figured out that chemically modifying the nucleoside bases that make up mRNA allowed the molecule to slip past the body’s immune defenses. Karikó and Weissman followed up that finding by creating mRNA that’s more efficiently translated within cells, greatly boosting protein production. In 2020, scientists at Moderna and BioNTech (where Karikó worked from 2013 to 2022) rushed to craft vaccines against COVID, putting their methods to life-saving use.
The future of vaccines
Buoyed by the resounding success of mRNA vaccines, scientists are now hurriedly researching ways to use mRNA medicine against other infectious diseases, cancer, and genetic disorders. The now ubiquitous efforts stand in stark contrast to Karikó and Weissman’s previously unheralded struggles years ago as they doggedly worked to realize a shared dream that so many others shied away from. Katalin Karikó and Drew Weissman were brave enough to walk a scientific path that very well could have ended in a dead end, and for that, they absolutely deserve their 2023 Nobel Prize.
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.
Scientists turn pee into power in Uganda
At the edge of a dirt road flanked by trees and green mountains outside the town of Kisoro, Uganda, sits the concrete building that houses Sesame Girls School, where girls aged 11 to 19 can live, learn and, at least for a while, safely use a toilet. In many developing regions, toileting at night is especially dangerous for children. Without electrical power for lighting, kids may fall into the deep pits of the latrines through broken or unsteady floorboards. Girls are sometimes assaulted by men who hide in the dark.
For the Sesame School girls, though, bright LED lights, connected to tiny gadgets, chased the fears away. They got to use new, clean toilets lit by the power of their own pee. Some girls even used the light provided by the latrines to study.
Urine, whether animal or human, is more than waste. It’s a cheap and abundant resource. Each day across the globe, 8.1 billion humans make 4 billion gallons of pee. Cows, pigs, deer, elephants and other animals add more. By spending money to get rid of it, we waste a renewable resource that can serve more than one purpose. Microorganisms that feed on nutrients in urine can be used in a microbial fuel cell that generates electricity – or "pee power," as the Sesame girls called it.
Plus, urine contains water, phosphorus, potassium and nitrogen, the key ingredients plants need to grow and survive. Human urine could replace about 25 percent of current nitrogen and phosphorous fertilizers worldwide and could save water for gardens and crops. The average U.S. resident flushes a toilet bowl containing only pee and paper about six to seven times a day, which adds up to about 3,500 gallons of water down per year. Plus cows in the U.S. produce 231 gallons of the stuff each year.
Pee power
A conventional fuel cell uses chemical reactions to produce energy, as electrons move from one electrode to another to power a lightbulb or phone. Ioannis Ieropoulos, a professor and chair of Environmental Engineering at the University of Southampton in England, realized the same type of reaction could be used to make a fuel from microbes in pee.
Bacterial species like Shewanella oneidensis and Pseudomonas aeruginosa can consume carbon and other nutrients in urine and pop out electrons as a result of their digestion. In a microbial fuel cell, one electrode is covered in microbes, immersed in urine and kept away from oxygen. Another electrode is in contact with oxygen. When the microbes feed on nutrients, they produce the electrons that flow through the circuit from one electrod to another to combine with oxygen on the other side. As long as the microbes have fresh pee to chomp on, electrons keep flowing. And after the microbes are done with the pee, it can be used as fertilizer.
These microbes are easily found in wastewater treatment plants, ponds, lakes, rivers or soil. Keeping them alive is the easy part, says Ieropoulos. Once the cells start producing stable power, his group sequences the microbes and keeps using them.
Like many promising technologies, scaling these devices for mass consumption won’t be easy, says Kevin Orner, a civil engineering professor at West Virginia University. But it’s moving in the right direction. Ieropoulos’s device has shrunk from the size of about three packs of cards to a large glue stick. It looks and works much like a AAA battery and produce about the same power. By itself, the device can barely power a light bulb, but when stacked together, they can do much more—just like photovoltaic cells in solar panels. His lab has produced 1760 fuel cells stacked together, and with manufacturing support, there’s no theoretical ceiling, he says.
Although pure urine produces the most power, Ieropoulos’s devices also work with the mixed liquids of the wastewater treatment plants, so they can be retrofit into urban wastewater utilities.
This image shows how the pee-powered system works. Pee feeds bacteria in the stack of fuel cells (1), which give off electrons (2) stored in parallel cylindrical cells (3). These cells are connected to a voltage regulator (4), which smooths out the electrical signal to ensure consistent power to the LED strips lighting the toilet.
Courtesy Ioannis Ieropoulos
Key to the long-term success of any urine reclamation effort, says Orner, is avoiding what he calls “parachute engineering”—when well-meaning scientists solve a problem with novel tech and then abandon it. “The way around that is to have either the need come from the community or to have an organization in a community that is committed to seeing a project operate and maintained,” he says.
Success with urine reclamation also depends on the economy. “If energy prices are low, it may not make sense to recover energy,” says Orner. “But right now, fertilizer prices worldwide are generally pretty high, so it may make sense to recover fertilizer and nutrients.” There are obstacles, too, such as few incentives for builders to incorporate urine recycling into new construction. And any hiccups like leaks or waste seepage will cost builders money and reputation. Right now, Orner says, the risks are just too high.
Despite the challenges, Ieropoulos envisions a future in which urine is passed through microbial fuel cells at wastewater treatment plants, retrofitted septic tanks, and building basements, and is then delivered to businesses to use as agricultural fertilizers. Although pure urine produces the most power, Ieropoulos’s devices also work with the mixed liquids of the wastewater treatment plants, so they can be retrofitted into urban wastewater utilities where they can make electricity from the effluent. And unlike solar cells, which are a common target of theft in some areas, nobody wants to steal a bunch of pee.
When Ieropoulos’s team returned to wrap up their pilot project 18 months later, the school’s director begged them to leave the fuel cells in place—because they made a major difference in students’ lives. “We replaced it with a substantial photovoltaic panel,” says Ieropoulos, They couldn’t leave the units forever, he explained, because of intellectual property reasons—their funders worried about theft of both the technology and the idea. But the photovoltaic replacement could be stolen, too, leaving the girls in the dark.
The story repeated itself at another school, in Nairobi, Kenya, as well as in an informal settlement in Durban, South Africa. Each time, Ieropoulos vowed to return. Though the pandemic has delayed his promise, he is resolute about continuing his work—it is a moral and legal obligation. “We've made a commitment to ourselves and to the pupils,” he says. “That's why we need to go back.”
Urine as fertilizer
Modern day industrial systems perpetuate the broken cycle of nutrients. When plants grow, they use up nutrients the soil. We eat the plans and excrete some of the nutrients we pass them into rivers and oceans. As a result, farmers must keep fertilizing the fields while our waste keeps fertilizing the waterways, where the algae, overfertilized with nitrogen, phosphorous and other nutrients grows out of control, sucking up oxygen that other marine species need to live. Few global communities remain untouched by the related challenges this broken chain create: insufficient clean water, food, and energy, and too much human and animal waste.
The Rich Earth Institute in Vermont runs a community-wide urine nutrient recovery program, which collects urine from homes and businesses, transports it for processing, and then supplies it as fertilizer to local farms.
One solution to this broken cycle is reclaiming urine and returning it back to the land. The Rich Earth Institute in Vermont is one of several organizations around the world working to divert and save urine for agricultural use. “The urine produced by an adult in one day contains enough fertilizer to grow all the wheat in one loaf of bread,” states their website.
Notably, while urine is not entirely sterile, it tends to harbor fewer pathogens than feces. That’s largely because urine has less organic matter and therefore less food for pathogens to feed on, but also because the urinary tract and the bladder have built-in antimicrobial defenses that kill many germs. In fact, the Rich Earth Institute says it’s safe to put your own urine onto crops grown for home consumption. Nonetheless, you’ll want to dilute it first because pee usually has too much nitrogen and can cause “fertilizer burn” if applied straight without dilution. Other projects to turn urine into fertilizer are in progress in Niger, South Africa, Kenya, Ethiopia, Sweden, Switzerland, The Netherlands, Australia, and France.
Eleven years ago, the Institute started a program that collects urine from homes and businesses, transports it for processing, and then supplies it as fertilizer to local farms. By 2021, the program included 180 donors producing over 12,000 gallons of urine each year. This urine is helping to fertilize hay fields at four partnering farms. Orner, the West Virginia professor, sees it as a success story. “They've shown how you can do this right--implementing it at a community level scale."