Crispr, Eugenics And “Three Generations Of Imbeciles Is Enough.” (#GotBitcoin?)
As new gene editing tools raise the prospect of engineering desired human traits, researchers are determined to educate the public.
The recent rise of Crispr, a powerful gene editing tool, has given scientists the ability to more easily and quickly manipulate DNA in the laboratory, allowing them to alter the traits of animals and plants—and, potentially, of human embryos as well. Gene editing offers the prospect of finding cures for intractable diseases, but it has also raised concerns that it might one day be used to engineer humans who are more intelligent, beautiful or athletic. “Eugenics,” says Henry T. Greely, director of Stanford Law School’s Center for Law and the Biosciences, is “the ghost at the table.”
In the early decades of the 20th century, prominent American scientists and physicians were involved in the eugenics movement, promoting reproduction among those seen as being more genetically fit. They also helped to lobby state legislatures to pass laws compelling the involuntary sterilization of people deemed genetically inferior. In the 1927 case of Buck v. Bell, the U.S. Supreme Court upheld the constitutionality of Virginia’s program. As Justice Oliver Wendell Holmes, Jr. , notoriously declared in the decision, “Three generations of imbeciles is enough.”
In time, however, eugenics lost credibility and support, having become associated with atrocities committed by the Nazis. Many came to see the idea that humans might change their DNA to control the genetic future as both scientifically unlikely and immoral.
The invention of Crispr has now brought that power into the realm of the possible, and from the start, excitement about its potential to do good has been tempered by fear about the possibility of causing irrevocable harm. “Geneticists have a historical burden,” says Mr. Greely. “Their science was used in ways that turned out to be deeply unscientific.” He does not think scientists should be blamed for such misuse, “but they should be held responsible for giving some thought to how this might go wrong, and talking about how to maximize benefits and minimize risks.”
Jennifer Doudna, a professor at the University of California, Berkeley, is one of the inventors of the Crispr tool. She has recounted a nightmare she had about the technology. In the dream, a colleague told her that somebody wanted to talk to her about gene editing. When she entered the room, the person waiting to meet her was Adolf Hitler. Dr. Doudna and her colleagues hoped Crispr might ultimately save lives, she wrote. But the nightmare was a reminder of “all of the ways in which our hard work might be perverted.”
Daniel Kevles, a professor of history emeritus at Yale University and the author of a history of eugenics, says that in current discussions about Crispr, people recoil from any association with eugenics, because the term is so closely linked to state-sponsored abuses. In the U.S., involuntary programs like the one in Buck v. Bell continued through the 1970s, sterilizing at least 60,000 people. But in the Crispr era, Prof. Kevles says, the moral dilemmas surrounding genetic manipulation are less likely to be caused by government initiatives than by “private eugenics”: consumers who want to use Crispr or other genetic technologies to give their children advantages in life.
Despite advances in genetic technology, scientists still do not have a reliable way to “manipulate human heredity to guarantee the birth of a child that can put a basketball through a hoop at 30 feet or perform in Carnegie Hall,” says Prof. Kevles. “If and when that happens, people will want to make use of it. We live in a consumer culture, and people want the best for their kids.”
Many of the institutions involved in research on genetic engineering are already doing outreach to the public, explaining how gene editing works. But now they are trying to do more on the ethical front, too. In one high-profile effort, Harvard Medical School’s Personal Genetics Education Project has initiated a Genetics Consortium, whose activities will include offering education programs across the country, from rural high schools to urban churches.
Ting Wu, a professor of genetics at Harvard Medical School and one of the leaders of the Genetics Consortium, says that for the pilot effort, they focused on seven institutions that have played important roles in the current genetic revolution. As it turned out, some of them have historical connections to the eugenics movement. A 1914 article in the Journal of Heredity, for example, included a list of colleges and universities that offered courses on eugenics, and Consortium members such as Harvard, the University of California and the University of Washington were on the list.
Michael Snyder, chairman of the department of genetics at Stanford University School of Medicine and a member of the Consortium, says that its initial focus is going to be on educating people about what genetic technology can and cannot do. Using Crispr to change complicated traits is still not imminent, he said. This month, three reports were published by scientists arguing over whether researchers successfully used Crispr to edit out a single gene mutation in human embryos linked to a deadly heart disease. To significantly manipulate someone’s intelligence or athletic ability, Dr. Snyder says, likely would require thousands of gene changes. And even then, genetics remains only part of the story. Diet, environment and training also play a role.
Still, Dr. Snyder says, these are questions that the Consortium will need to address. If it becomes possible, he could imagine parents wanting to tweak the genome of an embryo with, say, a growth hormone deficiency, in order to make the future child taller. But who gets to decide what sort of height deficiency justifies intervention? What, he asks, if “you are not impaired in any way other than you are not going to be the center of the basketball team?”
At Harvard’s Personal Genetics Education Project, the Buck v. Bell sterilization case is discussed in a lesson plan designed for use in classrooms and teacher training workshops. The case not only highlights how science can be misused but the conviction of many proponents of eugenics that “they were doing good,” says Dr. Wu. “Do I think there are people who are going to do things that 100 years from now we will be shocked they did but today they believe it is the right thing to do?” she asks. “Sure, I think that’s a possibility. The more eyes we have on this, the more arguments about this, the better we will all be.”
Crispr Used To Repair Gene Mutation in Dogs With Muscular Dystrophy
Gene-editing tool holds potential to edit DNA of patients with deadly disease.
Researchers used a gene-editing tool to repair a gene mutation in dogs with Duchenne muscular dystrophy, an important step in efforts to someday use the tool to edit DNA in people with the same fatal disease.
In a study published Thursday in the journal Science, researchers at UT Southwestern Medical Center in Dallas and the Royal Veterinary College in London reported that they used the Crispr gene-editing system in four dogs to restore production of dystrophin, a protein crucial for healthy muscle function.
Duchenne is caused by gene mutations that prevent production of dystrophin. Without enough dystrophin, patients’ muscles deteriorate. Patients typically lose the ability to walk by their early teens and die by their 20s and 30s. About 20,000 children, mostly boys, are diagnosed around the world every year with Duchenne.
Scientists have tried many approaches to stop the disease. In 2016, the U.S. Food and Drug Administration approved the first drug, Sarepta Therapeutics Inc.’s Exondys 51, a weekly injection that treats a particular form of Duchenne.
More recently, small numbers of people have been dosed with experimental gene therapies that attempt to bolster dystrophin production by delivering a form of the protein to cells. There are over 45 companies pursuing strategies to treat Duchenne or its symptoms, says Pat Furlong, CEO of the nonprofit Parent Project Muscular Dystrophy, which supported some of UT Southwestern’s early Crispr work in mice.
What makes the Crispr gene-editing approach in the dog study so alluring to many in the field is the prospect of tackling the underlying genetic cause of Duchenne. “Crispr is the next step,” says Ms. Furlong, “because it can permanently change people’s DNA.”
Crispr, which stands for clustered regularly interspaced short palindromic repeats, serves as the immune system of bacteria. Scientists adapted Crispr and the Cas9 enzyme it produces to cut DNA at specific points, allowing a repair or insertion of a new genetic sequence. Its development has raised hopes for curing genetic diseases, but has also sparked concerns about unintentional cuts and deletions of DNA.
Stanley F. Nelson, father of a boy with Duchenne and professor and co-director of the Center for Duchenne Muscular Dystrophy at UCLA, said much more data is needed before moving from dogs to having a clinical trial with people.
“You can’t be certain at this point that in trying to repair billions and billions of muscle cells, you won’t induce other catastrophic problems,” he said. Dr. Nelson also consults for Solid Biosciences Inc., a company pursuing gene therapy for Duchenne. He wasn’t involved in the dog study.
In the Science study, scientists programmed the Crispr system to cut the dogs’ DNA at a precise spot on the dystrophin gene. The cells repaired the cut, enabling dystrophin production to be restored to levels that ranged from 3% to 90% of normal, depending on the muscle. Most importantly, the gene edit restored dystrophin production in both the heart and diaphragm, essential for breathing.
“It’s like putting a good spare tire on a car. It’s not as good as the original, but it gets you where you want to go,” said Eric Olson, director of UT Southwestern’s Hamon Center for Regenerative Science and Medicine and senior author of the paper.
Dr. Olson, who is also founder and chief scientific adviser of Exonics Therapeutics Inc., which licensed the technology from UT Southwestern and helped fund the dog studies, said next steps involve testing Crispr in more dogs and observing them for a year or more. If the approach works in the dogs, he said researchers hope to try Crispr in a clinical trial with people with Duchenne.
Related Article: Meet The Scientists Bringing Extinct Species Back From The Dead (#GotBitcoin?)