Why the Panic Over "Designer Babies" Is the Wrong Worry
BIG QUESTION OF THE MONTH: Should we use CRISPR, the new technique that enables precise DNA editing, to change the genes of human embryos to eradicate disease--or even to enhance desirable traits? LeapsMag invited three leading experts to weigh in.
CRISPR is producing an important revolution in the biosciences, a revolution that will change our world in fundamental ways. Its implications need to be discussed and debated, and not just by scientists and ethicists. Unfortunately, so far we are debating the wrong issues.
Controversy has raged about editing human genes, particularly the DNA of embryos that could pass the changes down to their descendants. This technology, human germline editing, seems highly unlikely to be broadly available for at least the next few decades; if and when it is, it may well be unimportant.
Human germline editing is unlikely to happen soon because it has important safety risks but almost no significant benefits.
Human germline editing is unlikely to happen soon because it has important safety risks but almost no significant benefits. The risks – harm to babies – are compelling. We care a lot about babies. A technology that worked 95 percent of the time (and produced disabled or dying infants "only" five percent of the time) would be a disaster. Our concern for babies will lead, at the least, to rigorous legal requirements for preapproval safety testing. Many countries will just impose flat bans.
But these risks also have implications beyond safety regulation. For this technology to take off, physicians, assisted reproduction clinics, and geneticists will have to be willing to put their reputations – and their malpractice liability – on the line. And prospective mothers will have to be willing to take unknown risks with their children.
Sometimes, large and unknown risks are worth taking, but not here. For the next few decades, human germline editing offers almost no substantial benefits, for health or for enhancement.
Prospective parents already have a tried and true alternative to avoid having children with genetic diseases: preimplantation genetic diagnosis (PGD). In PGD, clinicians remove cells from three- to five-day-old embryos. Those cells are then tested to see which embryos would inherit the disease and which would not. This technology has been in use for over 27 years and is safe and effective. Rather than engaging in editing an embryo's disease-causing DNA, parents can just select embryos without those DNA variations. For so-called autosomal recessive diseases, three out of four embryos, on average, will be disease free; for autosomal dominant diseases, half will be.
Only a handful of prospective parents would need to use gene editing to avoid genetic disease.
Couples where each has the same recessive condition (cystic fibrosis) or where one of them has the terrible luck to have two copies of the DNA variant for a dominant disease (Huntington's disease). In those cases, the prospective parents would need to stay alive long enough to be able, and be sufficiently healthy to want, to have children. In a world of 7.3 billion humans, there will be some such cases, but they will probably be no more than a few thousand – or hundred.
People are also concerned about germline editing for genetic enhancement. But this is also unlikely anytime soon. We know basically nothing about genetic variations that enhance people beyond normal. For example, we know hundreds of genes that, when damaged, affect intelligence – but these all cause very low intelligence. We know of no variations that non-trivially increase it.
Over the next few decades, we might (or might not) learn about complex diseases where several genes are involved, making embryo selection less useful. And we might (or might not) learn about genetic enhancements involving DNA sequences not typically found in prospective parents and so not available to embryo selection. By that time, the safety issues could be resolved.
And, even then, how worried should we be – and about what? A bit, but not very and not about much.
"The human germline genome is not the holy essence of humanity."
The human germline genome is not the holy essence of humanity. For one thing, it doesn't really exist. There are 7.3 billion human germline genomes; each of us has a different one. And those genomes change every generation. I do not have exactly the same genetic variations my parents received from my grandparents; my children do not have exactly the ones I received from my parents. The DNA changed, through mutation, during each generation.
And our editing will usually be insignificant in the context of the whole human genome. For medical purposes, we will change some rare DNA variations that cause disease into the much more common DNA variations that do not cause disease. Rare, nasty variants will become rarer, but civilization changes these frequencies all the time. For instance, the use of insulin has increased the number of people with DNA variations that predispose people to type 1 ("juvenile") diabetes – because now those people live long enough to reproduce. Even agriculture changed our DNA, leading, for example, to more copies of starch-digesting genes. And, in any event, what is the meaningful difference between "fixing" a disease gene in an embryo or waiting to fix it with gene therapy in a born baby . . . other than avoiding the need to repeat the gene therapy in the next generation?
If genetic enhancement ever becomes possible in a non-trivial way, it would raise important questions, but questions about enhancement generally and not fundamentally about genetics. Enhancement through drugs, prosthetics, brain-computer interfaces, genes, or tools (like the laptop I wrote this on) all raise similar ethical issues. We can use the decades we will have to try to think more systematically about the ethical and policy issues for all enhancements. We should not panic about germline genetic enhancement.
One superficially appealing argument is that we are not wise enough to change our own genomes. This ignores the fact that we have been changing our genomes, inadvertently, since at least the dawn of civilization. We do not have to be wise enough to change our genome perfectly; we just need to be wise enough to change it better than the random and unforeseen ways we change it now. That should not be beyond our power.
Human germline editing will not be a concern for several decades and it may never be an important concern. What should we be paying attention to?
Non-human genome editing. Governments, researchers, and even do-it-yourself hobbyists can use CRISPR, especially when coupled with a technique called "gene drive," to change the genomes of whole species of living things – domestic or wild; animal, vegetable, or microbial – cheaply, easily, and before we even know it is happening. We care much less about mosquito babies than human ones and our legal structures are not built for wise and nuanced regulation of this kind of genome editing. Those issues demand our urgent attention – if we can tear ourselves away from dramatic but less important visions of "designer babies."
Editor's Note: Check out the viewpoints expressing condemnation and enthusiastic support.
How sharing, hearing, and remembering positive stories can help shape our brains for the better
Across cultures and through millennia, human beings have always told stories. Whether it’s a group of boy scouts around a campfire sharing ghost stories or the paleolithic Cro-Magnons etching pictures of bison on cave walls, researchers believe that storytelling has been universal to human beings since the development of language.
But storytelling was more than just a way for our ancestors to pass the time. Researchers believe that storytelling served an important evolutionary purpose, helping humans learn empathy, share important information (such as where predators were or what berries were safe to eat), as well as strengthen social bonds. Quite literally, storytelling has made it possible for the human race to survive.
Today, neuroscientists are discovering that storytelling is just as important now as it was millions of years ago. Particularly in sharing positive stories, humans can more easily form relational bonds, develop a more flexible perspective, and actually grow new brain circuitry that helps us survive. Here’s how.
How sharing stories positively impacts the brain
When human beings share stories, it increases the levels of certain neurochemicals in the brain, neuroscientists have found. In a 2021 study published in Proceedings of the National Academy of Sciences (PNAS), Swedish researchers found that simply hearing a story could make hospitalized children feel better, compared to other hospitalized children who played a riddle game for the same amount of time. In their research, children in the intensive care unit who heard stories for just 30 minutes had higher levels of oxytocin, a hormone that promotes positive feelings and is linked to relaxation, trust, social connectedness, and overall psychological stability. Furthermore, the same children showed lower levels of cortisol, a hormone associated with stress. Afterward, the group of children who heard stories tended to describe their hospital experiences more positively, and even reported lower levels of pain.
Annie Brewster, MD, knows the positive effect of storytelling from personal experience. An assistant professor at Harvard Medical School and the author of The Healing Power of Storytelling: Using Personal Narrative to Navigate Illness, Trauma, and Loss, Brewster started sharing her personal experience with chronic illness after being diagnosed with multiple sclerosis in 2001. In doing so, Brewster says it has enabled her to accept her diagnosis and integrate it into her identity. Brewster believes so much in the power of hearing and sharing stories that in 2013 she founded Health Story Collaborative, a forum for others to share their mental and physical health challenges.“I wanted to hear stories of people who had found ways to move forward in positive ways, in spite of health challenges,” Brewster said. In doing so, Brewster believes people with chronic conditions can “move closer to self-acceptance and self-love.”
While hearing and sharing positive stories has been shown to increase oxytocin and other “feel good” chemicals, simply remembering a positive story has an effect on our brains as well. Mark Hoelterhoff, PhD, a lecturer in clinical psychology at the University of Edinburgh, recalling and “savoring” a positive story, thought, or feedback “begins to create new brain circuitry—a new neural network that’s geared toward looking for the positive,” he says. Over time, other research shows, savoring positive stories or thoughts can literally change the shape of your brain, hard-wiring someone to see things in a more positive light.How stories can change your behavior
In 2009, Paul Zak, PhD, a neuroscientist and professor at Claremont Graduate University, set out to measure how storytelling can actually change human behavior for the better. In his study, Zak wanted to measure the behavioral effects of oxytocin, and did this by showing test subjects two short video clips designed to elicit an emotional response.
In the first video they showed the study participants, a father spoke to the camera about his two-year-old son, Ben, who had been diagnosed with terminal brain cancer. The father told the audience that he struggled to connect with and enjoy Ben, as Ben had only a few months left to live. In the end, the father finds the strength to stay emotionally connected to his son until he dies.
The second video clip, however, was much less emotional. In that clip, the same father and son are shown spending the day at the zoo. Ben is only suggested to have cancer (he is bald from chemotherapy and referred to as a ‘miracle’, but the cancer isn’t mentioned directly). The second story lacked the dramatic narrative arc of the first video.
Zak’s team took blood before and after the participants watched one of the two videos and found that the first story increased the viewers’ cortisol and oxytocin, suggesting that they felt distress over the boy’s diagnosis and empathy toward the boy and his father. The second narrative, however, didn’t increase oxytocin or cortisol at all.
But Zak took the experiment a step further. After the movie clips, his team gave the study participants a chance to share money with a stranger in the lab. The participants who had an increase in cortisol and oxytocin were more likely to donate money generously. The participants who had increased cortisol and oxytocin were also more likely to donate money to a charity that works with children who are ill. Zak also found that the amount of oxytocin that was released was correlated with how much money people felt comfortable giving—in other words, the more oxytocin that was released, the more generous they felt, and the more money they donated.
How storytelling strengthens our bond with others
Sharing, hearing, and remembering stories can be a powerful tool for social change–not only in the way it changes our brain and our behavior, but also because it can positively affect our relationships with other people
Emotional stimulation from telling stories, writes Zak, is the foundation for empathy, and empathy strengthens our relationships with other people. “By knowing someone’s story—where they come from, what they do, and who you might know in common—relationships with strangers are formed.”
But why are these relationships important for humanity? Because human beings can use storytelling to build empathy and form relationships, it enables them to “engage in the kinds of large-scale cooperation that builds massive bridges and sends humans into space,” says Zak.
Storytelling, Zak found, and the oxytocin release that follows, also makes people more sensitive to social cues. This sensitivity not only motivates us to form relationships, but also to engage with other people and offer help, particularly if the other person seems to need help.
But as Zak found in his experiments, the type of storytelling matters when it comes to affecting relationships. Where Zak found that storytelling with a dramatic arc helps release oxytocin and cortisol, enabling people to feel more empathic and generous, other researchers have found that sharing happy stories allows for greater closeness between individuals and speakers. A group of Chinese researchers found that, compared to emotionally-neutral stories, happy stories were more “emotionally contagious.” Test subjects who heard happy stories had greater activation in certain areas of their brains, experienced more significant, positive changes in their mood, and felt a greater sense of closeness between themselves and the speaker.
“This finding suggests that when individuals are happy, they become less self-focused and then feel more intimate with others,” the authors of the study wrote. “Therefore, sharing happiness could strengthen interpersonal bonding.” The researchers went on to say that this could lead to developing better social networks, receiving more social support, and leading more successful social lives.
Since the start of the COVID pandemic, social isolation, loneliness, and resulting mental health issues have only gotten worse. In light of this, it’s safe to say that hearing, sharing, and remembering stories isn’t just something we can do for entertainment. Storytelling has always been central to the human experience, and now more than ever it’s become something crucial for our survival.
Want to know how you can reap the benefits of hearing happy stories? Keep an eye out for Upworthy’s first book, GOOD PEOPLE: Stories from the Best of Humanity, published by National Geographic/Disney, available on September 3, 2024. GOOD PEOPLE is a much-needed trove of life-affirming stories told straight from the heart. Handpicked from Upworthy’s community, these 101 stories speak to the breadth, depth, and beauty of the human experience, reminding us we have a lot more in common than we realize.
A new type of cancer therapy is shrinking deadly brain tumors with just one treatment
MRI scans after a new kind of immunotherapy for brain cancer show remarkable progress in one patient just days after the first treatment.
Few cancers are deadlier than glioblastomas—aggressive and lethal tumors that originate in the brain or spinal cord. Five years after diagnosis, less than five percent of glioblastoma patients are still alive—and more often, glioblastoma patients live just 14 months on average after receiving a diagnosis.
But an ongoing clinical trial at Mass General Cancer Center is giving new hope to glioblastoma patients and their families. The trial, called INCIPIENT, is meant to evaluate the effects of a special type of immune cell, called CAR-T cells, on patients with recurrent glioblastoma.
How CAR-T cell therapy works
CAR-T cell therapy is a type of cancer treatment called immunotherapy, where doctors modify a patient’s own immune system specifically to find and destroy cancer cells. In CAR-T cell therapy, doctors extract the patient’s T-cells, which are immune system cells that help fight off disease—particularly cancer. These T-cells are harvested from the patient and then genetically modified in a lab to produce proteins on their surface called chimeric antigen receptors (thus becoming CAR-T cells), which makes them able to bind to a specific protein on the patient’s cancer cells. Once modified, these CAR-T cells are grown in the lab for several weeks so that they can multiply into an army of millions. When enough cells have been grown, these super-charged T-cells are infused back into the patient where they can then seek out cancer cells, bind to them, and destroy them. CAR-T cell therapies have been approved by the US Food and Drug Administration (FDA) to treat certain types of lymphomas and leukemias, as well as multiple myeloma, but haven’t been approved to treat glioblastomas—yet.
CAR-T cell therapies don’t always work against solid tumors, such as glioblastomas. Because solid tumors contain different kinds of cancer cells, some cells can evade the immune system’s detection even after CAR-T cell therapy, according to a press release from Massachusetts General Hospital. For the INCIPIENT trial, researchers modified the CAR-T cells even further in hopes of making them more effective against solid tumors. These second-generation CAR-T cells (called CARv3-TEAM-E T cells) contain special antibodies that attack EFGR, a protein expressed in the majority of glioblastoma tumors. Unlike other CAR-T cell therapies, these particular CAR-T cells were designed to be directly injected into the patient’s brain.
The INCIPIENT trial results
The INCIPIENT trial involved three patients who were enrolled in the study between March and July 2023. All three patients—a 72-year-old man, a 74-year-old man, and a 57-year-old woman—were treated with chemo and radiation and enrolled in the trial with CAR-T cells after their glioblastoma tumors came back.
The results, which were published earlier this year in the New England Journal of Medicine (NEJM), were called “rapid” and “dramatic” by doctors involved in the trial. After just a single infusion of the CAR-T cells, each patient experienced a significant reduction in their tumor sizes. Just two days after receiving the infusion, the glioblastoma tumor of the 72-year-old man decreased by nearly twenty percent. Just two months later the tumor had shrunk by an astonishing 60 percent, and the change was maintained for more than six months. The most dramatic result was in the 57-year-old female patient, whose tumor shrank nearly completely after just one infusion of the CAR-T cells.
The results of the INCIPIENT trial were unexpected and astonishing—but unfortunately, they were also temporary. For all three patients, the tumors eventually began to grow back regardless of the CAR-T cell infusions. According to the press release from MGH, the medical team is now considering treating each patient with multiple infusions or prefacing each treatment with chemotherapy to prolong the response.
While there is still “more to do,” says co-author of the study neuro-oncologist Dr. Elizabeth Gerstner, the results are still promising. If nothing else, these second-generation CAR-T cell infusions may someday be able to give patients more time than traditional treatments would allow.
“These results are exciting but they are also just the beginning,” says Dr. Marcela Maus, a doctor and professor of medicine at Mass General who was involved in the clinical trial. “They tell us that we are on the right track in pursuing a therapy that has the potential to change the outlook for this intractable disease.”