How Should Genetic Engineering Shape Our Future?
Terror. Error. Success. These are the three outcomes that ethicists evaluating a new technology should fear. The possibility that a breakthrough might be used maliciously. The possibility that newly empowered scientists might make a catastrophic mistake. And the possibility that a technology will be so successful that it will change how we live in ways that we can only guess—and that we may not want.
These tools will allow scientists to practice genetic engineering on a scale that is simultaneously far more precise and far more ambitious than ever before.
It was true for the scientists behind the Manhattan Project, who bequeathed a fear of nuclear terror and nuclear error, even as global security is ultimately defined by these weapons of mass destruction. It was true for the developers of the automobile, whose invention has been weaponized by terrorists and kills 3,400 people by accident each day, even as the more than 1 billion cars on the road today have utterly reshaped where we live and how we move. And it is true for the researchers behind the revolution in gene editing and writing.
Put simply, these tools will allow scientists to practice genetic engineering on a scale that is simultaneously far more precise and far more ambitious than ever before. Editing techniques like CRISPR enable exact genetic repairs through a simple cut and paste of DNA, while synthetic biologists aim to redo entire genomes through the writing and substitution of synthetic genes. The technologies are complementary, and they herald an era when the book of life will be not just readable, but rewritable. Food crops, endangered animals, even the human body itself—all will eventually be programmable.
The benefits are easy to imagine: more sustainable crops; cures for terminal genetic disorders; even an end to infertility. Also easy to picture are the ethical pitfalls as the negative images of those same benefits.
Terror is the most straightforward. States have sought to use biology as a weapon at least since invading armies flung the corpses of plague victims into besieged castles. The 1975 biological weapons convention banned—with general success—the research and production of offensive bioweapons, though a handful of lone terrorists and groups like the Oregon-based Rajneeshee cult have still carried out limited bioweapon attacks. Those incidents ultimately caused little death and damage, in part because medical science is mostly capable of defending us from those pathogens that are most easily weaponized. But gene editing and writing offers the chance to engineer germs that could be far more effective than anything nature could develop. Imagine a virus that combines the lethality of Ebola with the transmissibility of the common cold—and in the new world of biology, if you can imagine something, you will eventually be able to create it.
The benefits are easy to imagine: more sustainable crops; cures for terminal genetic disorders; even an end to infertility. Also easy to picture are the ethical pitfalls.
That's one reason why James Clapper, then the U.S. director of national intelligence, added gene editing to the list of threats posed by "weapons of mass destruction and proliferation" in 2016. But these new tools aren't merely dangerous in the wrong hands—they can also be dangerous in the right hands. The list of labs accidents involving lethal bugs is much longer than you'd want to know, at least if you're the sort of person who likes to sleep at night. The U.S. recently lifted a ban on research that works to make existing pathogens, like the H5N1 avian flu virus, more virulent and transmissible, often using new technologies like gene editing. Such work can help medicine better prepare for what nature might throw at us, but it could also make the consequences of a lab error far more catastrophic. There's also the possibility that the use of gene editing and writing in nature—say, by CRISPRing disease-carrying mosquitoes to make them sterile—could backfire in some unforeseen way. Add in the fact that the techniques behind gene editing and writing are becoming simpler and more automated with every year, and eventually millions of people will be capable—through terror or error—of unleashing something awful on the world.
The good news is that both the government and the researchers driving these technologies are increasingly aware of the risks of bioterror and error. One government program, the Functional Genomic and Computational Assessment of Threats (Fun GCAT), provides funding for scientists to scan genetic data looking for the "accidental or intentional creation of a biological threat." Those in the biotech industry know to keep an eye out for suspicious orders—say, a new customer who orders part of the sequence of the Ebola or smallpox virus. "With every invention there is a good use and a bad use," Emily Leproust, the CEO of the commercial DNA synthesis startup Twist Bioscience, said in a recent interview. "What we try hard to do is put in place as many systems as we can to maximize the good stuff, and minimize any negative impact."
But the greatest ethical challenges in gene editing and writing will arise not from malevolence or mistakes, but from success. Through a new technology called in vitro gametogenesis (IVG), scientists are learning how to turn adult human cells like a piece of skin into lab-made sperm and egg cells. That would be a huge breakthrough for the infertile, or for same-sex couples who want to conceive a child biologically related to both partners. It would also open the door to using gene editing to tinker with those lab-made embryos. At first interventions would address any obvious genetic disorders, but those same tools would likely allow the engineering of a child's intelligence, height and other characteristics. We might be morally repelled today by such an ability, as many scientists and ethicists were repelled by in-vitro fertilization (IVF) when it was introduced four decades ago. Yet more than a million babies in the U.S. have been born through IVF in the years since. Ethics can evolve along with technology.
These new technologies offer control over the code of life, but only we as a society can seize control over where these tools will take us.
Fertility is just one human institution that stands to be changed utterly by gene editing and writing, and it's a change we can at least imagine. As the new biology grows more ambitious, it will alter society in ways we can't begin to picture. Harvard's George Church and New York University's Jef Boeke are leading an effort called HGP-Write to create a completely synthetic human genome. While gene editing allows scientists to make small changes to the genome, the gene synthesis that Church and his collaborators are developing allows for total genetic rewrites. "It's a difference between editing a book and writing one," Church said in an interview earlier this year.
Church is already working on synthesizing organs that would be resistant to viruses, while other researchers like Harris Wang at Columbia University are experimenting with bioengineering mammalian cells to produce nutrients like amino acids that we currently need to get from food. The horizon is endless—and so are the ethical concerns of success. What if parents feel pressure to engineer their children just so they don't fall behind their IVG peers? What if only the rich are able to access synthetic biology technologies that could make them stronger, smarter and longer lived? Could inequality become encoded in the genome?
These are questions that are different from the terror and errors fears around biosecurity, because they ask us to think hard about what kind of future we want. To their credit, Church and his collaborators have engaged bioethicists from the start of their work, as have the pioneers behind CRISPR. But the challenges coming from successful gene editing and writing are too large to be outsourced to professional ethicists. These new technologies offer control over the code of life, but only we as a society can seize control over where these tools will take us.
Here's how one doctor overcame extraordinary odds to help create the birth control pill
Dr. Percy Julian had so many personal and professional obstacles throughout his life, it’s amazing he was able to accomplish anything at all. But this hidden figure not only overcame these incredible obstacles, he also laid the foundation for the creation of the birth control pill.
Julian’s first obstacle was growing up in the Jim Crow-era south in the early part of the twentieth century, where racial segregation kept many African-Americans out of schools, libraries, parks, restaurants, and more. Despite limited opportunities and education, Julian was accepted to DePauw University in Indiana, where he majored in chemistry. But in college, Julian encountered another obstacle: he wasn’t allowed to stay in DePauw’s student housing because of segregation. Julian found lodging in an off-campus boarding house that refused to serve him meals. To pay for his room, board, and food, Julian waited tables and fired furnaces while he studied chemistry full-time. Incredibly, he graduated in 1920 as valedictorian of his class.
After graduation, Julian landed a fellowship at Harvard University to study chemistry—but here, Julian ran into yet another obstacle. Harvard thought that white students would resent being taught by Julian, an African-American man, so they withdrew his teaching assistantship. Julian instead decided to complete his PhD at the University of Vienna in Austria. When he did, he became one of the first African Americans to ever receive a PhD in chemistry.
Julian received offers for professorships, fellowships, and jobs throughout the 1930s, due to his impressive qualifications—but these offers were almost always revoked when schools or potential employers found out Julian was black. In one instance, Julian was offered a job at the Institute of Paper Chemistory in Appleton, Wisconsin—but Appleton, like many cities in the United States at the time, was known as a “sundown town,” which meant that black people weren’t allowed to be there after dark. As a result, Julian lost the job.
During this time, Julian became an expert at synthesis, which is the process of turning one substance into another through a series of planned chemical reactions. Julian synthesized a plant compound called physostigmine, which would later become a treatment for an eye disease called glaucoma.
In 1936, Julian was finally able to land—and keep—a job at Glidden, and there he found a way to extract soybean protein. This was used to produce a fire-retardant foam used in fire extinguishers to smother oil and gasoline fires aboard ships and aircraft carriers, and it ended up saving the lives of thousands of soldiers during World War II.
At Glidden, Julian found a way to synthesize human sex hormones such as progesterone, estrogen, and testosterone, from plants. This was a hugely profitable discovery for his company—but it also meant that clinicians now had huge quantities of these hormones, making hormone therapy cheaper and easier to come by. His work also laid the foundation for the creation of hormonal birth control: Without the ability to synthesize these hormones, hormonal birth control would not exist.
Julian left Glidden in the 1950s and formed his own company, called Julian Laboratories, outside of Chicago, where he manufactured steroids and conducted his own research. The company turned profitable within a year, but even so Julian’s obstacles weren’t over. In 1950 and 1951, Julian’s home was firebombed and attacked with dynamite, with his family inside. Julian often had to sit out on the front porch of his home with a shotgun to protect his family from violence.
But despite years of racism and violence, Julian’s story has a happy ending. Julian’s family was eventually welcomed into the neighborhood and protected from future attacks (Julian’s daughter lives there to this day). Julian then became one of the country’s first black millionaires when he sold his company in the 1960s.
When Julian passed away at the age of 76, he had more than 130 chemical patents to his name and left behind a body of work that benefits people to this day.
Therapies for Healthy Aging with Dr. Alexandra Bause
My guest today is Dr. Alexandra Bause, a biologist who has dedicated her career to advancing health, medicine and healthier human lifespans. Dr. Bause co-founded a company called Apollo Health Ventures in 2017. Currently a venture partner at Apollo, she's immersed in the discoveries underway in Apollo’s Venture Lab while the company focuses on assembling a team of investors to support progress. Dr. Bause and Apollo Health Ventures say that biotech is at “an inflection point” and is set to become a driver of important change and economic value.
Previously, Dr. Bause worked at the Boston Consulting Group in its healthcare practice specializing in biopharma strategy, among other priorities
She did her PhD studies at Harvard Medical School focusing on molecular mechanisms that contribute to cellular aging, and she’s also a trained pharmacist
In the episode, we talk about the present and future of therapeutics that could increase people’s spans of health, the benefits of certain lifestyle practice, the best use of electronic wearables for these purposes, and much more.
Dr. Bause is at the forefront of developing interventions that target the aging process with the aim of ensuring that all of us can have healthier, more productive lifespans.