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.
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 canâ€™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 â€œsterile insect techniqueâ€. 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.
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.
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.]
On the evening of November 28, 1942, more than 1,000 revelers from the Boston College-Holy Cross football game jammed into the Cocoanut Grove, Boston's oldest nightclub. When a spark from faulty wiring accidently ignited an artificial palm tree, the packed nightspot, which was only designed to accommodate about 500 people, was quickly engulfed in flames. In the ensuing panic, hundreds of people were trapped inside, with most exit doors locked. Bodies piled up by the only open entrance, jamming the exits, and 490 people ultimately died in the worst fire in the country in forty years.
"People couldn't get out," says Dr. Kenneth Marshall, a retired plastic surgeon in Boston and president of the Cocoanut Grove Memorial Committee. "It was a tragedy of mammoth proportions."
Within a half an hour of the start of the blaze, the Red Cross mobilized more than five hundred volunteers in what one newspaper called a "Rehearsal for Possible Blitz." The mayor of Boston imposed martial law. More than 300 victims—many of whom subsequently died--were taken to Boston City Hospital in one hour, averaging one victim every eleven seconds, while Massachusetts General Hospital admitted 114 victims in two hours. In the hospitals, 220 victims clung precariously to life, in agonizing pain from massive burns, their bodies ravaged by infection.
The scene of the fire.
Boston Public Library
Tragic Losses Prompted Revolutionary Leaps<p>But there is a silver lining: this horrific disaster prompted dramatic changes in safety regulations to prevent another catastrophe of this magnitude and led to the development of medical techniques that eventually saved millions of lives. It transformed burn care treatment and the use of plasma on burn victims, but most importantly, it introduced to the public a new wonder drug that revolutionized medicine, midwifed the birth of the modern pharmaceutical industry, and nearly doubled life expectancy, from 48 years at the turn of the 20<sup>th</sup> century to 78 years in the post-World War II years.</p><p>The devastating grief of the survivors also led to the first published study of post-traumatic stress disorder by pioneering psychiatrist Alexandra Adler, daughter of famed Viennese psychoanalyst Alfred Adler, who was a student of Freud. Dr. Adler studied the anxiety and depression that followed this catastrophe, according to the <em>New York Times</em>, and "later applied her findings to the treatment World War II veterans."</p><p>Dr. Ken Marshall is intimately familiar with the lingering psychological trauma of enduring such a disaster. His mother, an Irish immigrant and a nurse in the surgical wards at Boston City Hospital, was on duty that cold Thanksgiving weekend night, and didn't come home for four days. "For years afterward, she'd wake up screaming in the middle of the night," recalls Dr. Marshall, who was four years old at the time. "Seeing all those bodies lined up in neat rows across the City Hospital's parking lot, still in their evening clothes. It was always on her mind and memories of the horrors plagued her for the rest of her life."</p><p>The sheer magnitude of casualties prompted overwhelmed physicians to try experimental new procedures that were later successfully used to treat thousands of battlefield casualties. Instead of cutting off blisters and using dyes and tannic acid to treat burned tissues, which can harden the skin, they applied gauze coated with petroleum jelly. Doctors also refined the formula for using plasma--the fluid portion of blood and a medical technology that was just four years old--to replenish bodily liquids that evaporated because of the loss of the protective covering of skin.</p>
From Forgotten Lab Experiment to Wonder Drug<p>In 1928, Alexander Fleming discovered the curative powers of penicillin, which promised to eradicate infectious pathogens that killed millions every year. But the road to mass producing enough of the highly unstable mold was littered with seemingly unsurmountable obstacles and it remained a forgotten laboratory curiosity for over a decade. But Fleming never gave up and penicillin's eventual rescue from obscurity was a landmark in scientific history. </p><p>In 1940, a group at Oxford University, funded in part by the Rockefeller Foundation, isolated enough penicillin to test it on twenty-five mice, which had been infected with lethal doses of streptococci. Its therapeutic effects were miraculous—the untreated mice died within hours, while the treated ones played merrily in their cages, undisturbed. Subsequent tests on a handful of patients, who were brought back from the brink of death, confirmed that penicillin was indeed a wonder drug. But Britain was then being ravaged by the German Luftwaffe during the Blitz, and there were simply no resources to devote to penicillin during the Nazi onslaught.</p><p>In June of 1941, two of the Oxford researchers, Howard Florey and Ernst Chain, embarked on a clandestine mission to enlist American aid. Samples of the temperamental mold were stored in their coats. By October, the Roosevelt Administration had recruited four companies—Merck, Squibb, Pfizer and Lederle—to team up in a massive, top-secret development program. Merck, which had more experience with fermentation procedures, swiftly pulled away from the pack and every milligram they produced was zealously hoarded.</p><p>After the nightclub fire, the government ordered Merck to dispatch to Boston whatever supplies of penicillin that they could spare and to refine any crude penicillin broth brewing in Merck's fermentation vats. After working in round-the-clock relays over the course of three days, on the evening of December 1<sup>st</sup>, 1942, a refrigerated truck containing thirty-two liters of injectable penicillin left Merck's Rahway, New Jersey plant. It was accompanied by a convoy of police escorts through four states before arriving in the pre-dawn hours at Massachusetts General Hospital. Dozens of people were rescued from near-certain death in the first public demonstration of the powers of the antibiotic, and the existence of penicillin could no longer be kept secret from inquisitive reporters and an exultant public. The next day, the <em>Boston Globe</em> called it "priceless" and <em>Time</em> magazine dubbed it a "wonder drug."</p><p>Within fourteen months, penicillin production escalated exponentially, churning out enough to save the lives of thousands of soldiers, including many from the Normandy invasion. And in October 1945, just weeks after the Japanese surrender ended World War II, Alexander Fleming, Howard Florey and Ernst Chain were awarded the Nobel Prize in medicine. But penicillin didn't just save lives—it helped build some of the most innovative medical and scientific companies in history, including Merck, Pfizer, Glaxo and Sandoz. </p><p>"Every war has given us a new medical advance," concludes Marshall. "And penicillin was <em>the</em> great scientific advance of World War II."</p>
Conner Curran was diagnosed with Duchenne's muscular dystrophy in 2015 when he was four years old. It's the most severe form of the genetic disease, with a nearly inevitable progression toward total paralysis. Many Duchenne's patients die in their teens; the average lifespan is 26.
But Conner, who is now 10, has experienced some astonishing improvements in recent years. He can now walk for more than two miles at a time – an impossible journey when he was younger.
In 2018, Conner became the very first patient to receive gene therapy specific to treating Duchenne's. In the initial clinical trial of nine children, nearly 80 percent reacted positively to the treatment). A larger-scale stage 3 clinical trial is currently underway, with initial results expected next year.
Gene therapy involves altering the genes in an individual's cells to stop or treat a disease. Such a procedure may be performed by adding new gene material to existing cells, or editing the defective genes to improve their functionality.
Conner Curran holding a football post gene therapy treatment.
Courtesy of the Curran family