Carl Zimmer: Genetically Editing Humans Should Not Be Our Biggest Worry
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Carl Zimmer, the award-winning New York Times science writer, recently published a stellar book about human heredity called "She Has Her Mother's Laugh." Truly a magnum opus, the book delves into the cultural and scientific evolution of genetics, the field's outsize impact on society, and the new ways we might fundamentally alter our species and our planet.
"I was only prepared to write about how someday we would cross this line, and actually, we've already crossed it."
Zimmer spoke last week with editor-in-chief Kira Peikoff about the international race to edit the genes of human embryos, the biggest danger he sees for society (hint: it's not super geniuses created by CRISPR), and some outlandish possibilities for how we might reproduce in the future. This interview has been edited and condensed for clarity.
I was struck by the number of surprises you uncovered while researching human heredity, like how fetal cells can endure for a lifetime in a mother's body and brain. What was one of the biggest surprises for you?
Something that really jumped out for me was for the section on genetically modifying people. It does seem incredibly hypothetical. But then I started looking into mitochondrial replacement therapy, so-called "three parent babies." I was really surprised to discover that almost by accident, a number of genetically modified people were created this way [in the late 90s and early 2000s]. They walk among us, and they're actually fine as far as anyone can tell. I was only prepared to write about how someday we would cross this line, and actually, we've already crossed it.
And now we have the current arms race between the U.S. and China to edit diseases out of human embryos, with China being much more willing and the U.S. more reluctant. Do you think it's more important to get ahead or to proceed as ethically as possible?
I would prefer a middle road. I think that rushing into tinkering with the features of human heredity could be a disastrous mistake for a lot of reasons. On the other hand, if we completely retreat from it out of some vague fear, I think that we won't take advantage of the actual benefits that this technology might have that are totally ethically sound.
I think the United Kingdom is actually showing how you can go the middle route with mitochondrial replacement therapy. The United States has just said nope, you can't do it at all, and you have Congressmen talking about how it's just playing God or Frankenstein. And then there are countries like Mexico or the Ukraine where people are doing mitochondrial replacement therapy because there are no regulations at all. It's a wild west situation, and that's not a good idea either.
But in the UK, they said alright, well let's talk about this, let's have a debate in Parliament, and they did, and then the government came up with a well thought-through policy. They decided that they were going to allow for this, but only in places that applied for a license, and would be monitored, and would keep track of the procedure and the health of these children and actually have real data going forward. I would imagine that they're going to very soon have their first patients.
As you mentioned, one researcher recently traveled to Mexico from New York to carry out the so-called "three-parent baby" procedure in order to escape the FDA's rules. What's your take on scientists having to leave their own jurisdictions to advance their research programs under less scrutiny?
I think it's a problem when people who have a real medical need have to leave their own country to get truly effective treatment for it. On the other hand, we're seeing lots of people going abroad to countries that don't monitor all the claims that clinics are making about their treatments. So you have stem cell clinics in all sorts of places that are making all sorts of ridiculous promises. They're not delivering those results, and in some cases, they're doing harm.
"Advances in stem cell biology and reproductive biology are a much bigger challenge to our conventional ideas about heredity than CRISPR is."
It's a tricky tension for sure. Speaking of gene editing humans, you mention in the book that one of the CRISPR pioneers, Jennifer Doudna, now has recurring nightmares about Hitler. Do you think that her fears about eugenics being revived with gene editing are justified?
The word "eugenics" has a long history and it's meant different things to different people. So we have to do a better job of talking about it in the future if we really want to talk about the risks and the promises of technology like CRISPR. Eugenics in its most toxic form was an ideology that let governments, including the United States, sterilize their own citizens by the tens of thousands. Then Nazi Germany also used eugenics as a justification to exterminate many more people.
Nobody's talking about that with CRISPR. Now, are people concerned that we are going to wipe out lots of human genetic diversity with it? That would be a bad thing, but I'm skeptical that would actually ever happen. You would have to have some sort of science fiction one-world government that required every new child to be born with IVF. It's not something that keeps me up at night. Honestly, I think we have much bigger problems to worry about.
What is the biggest danger relating to genetics that we should be aware of?
Part of what made eugenics such a toxic ideology was that it was used as a justification for indifference. In other words, if there are problems in society, like a large swath of people who are living in poverty, well, there's nothing you can do about it because it must be due to genetics.
If you look at genetics as being the sole place where you can solve humanity's problems, then you're going to say well, there's no point in trying to clean up the environment or trying to improve human welfare.
A major theme in your book is that we should not narrow our focus on genes as the only type of heredity. We also may inherit some epigenetic marks, some of our mother's microbiome and mitochondria, and importantly, our culture and our environment. Why does an expanded view of heredity matter?
We should think about the world that our children are going to inherit, and their children, and their children. They're going to inherit our genes, but they're also going to inherit this planet and we're doing things that are going to have an incredibly long-lasting impact on it. I think global warming is one of the biggest. When you put carbon dioxide into the air, it stays there for a very, very long time. If we stopped emitting carbon dioxide now, the Earth would stay warm for many centuries. We should think about tinkering with the future of genetic heredity, but I think we should also be doing that with our environmental heredity and our cultural heredity.
At the end of the book, you discuss some very bizarre possibilities for inheritance that could be made possible through induced pluripotent stem cell technology and IVF -- like four-parent babies, men producing eggs, and children with 8-celled embryos as their parents. If this is where reproductive medicine is headed, how can ethics keep up?
I'm not sure actually. I think that these advances in stem cell biology and reproductive biology are a much bigger challenge to our conventional ideas about heredity than CRISPR is. With CRISPR, you might be tweaking a gene here and there, but they're still genes in an embryo which then becomes a person, who would then have children -- the process our species has been familiar with for a long time.
"We have to recognize that we need a new language that fits with the science of heredity in the 21st century."
We all assume that there's no way to find a fundamentally different way of passing down genes, but it turns out that it's not really that hard to turn a skin cell from a cheek scraping into an egg or sperm. There are some challenges that still have to be worked out to make this something that could be carried out a lot in labs, but I don't see any huge barriers to it. Ethics doesn't even have the language to discuss the possibilities. Like for example, one person producing both male and female sex cells, which are then fertilized to produce embryos so that you have a child who only has one parent. How do we even talk about that? I don't know. But that's coming up fast.
We haven't developed our language as quickly as the technology itself. So how do we move forward?
We have to recognize that we need a new language that fits with the science of heredity in the 21st century. I think one of the biggest problems we have as a society is that most of our understanding about these issues largely comes from what we learned in grade school and high school in biology class. A high school biology class, even now, gets up to Mendel and then stops. Gregor Mendel is a great place to start, but it's a really bad place to stop talking about heredity.
[Ed. Note: Zimmer's book can be purchased through your retailer of choice here.]
The cover of Zimmer's new book about genetics.
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
A new type of cancer therapy is shrinking deadly brain tumors with just one 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.”
Since the early 2000s, AI systems have eliminated more than 1.7 million jobs, and that number will only increase as AI improves. Some research estimates that by 2025, AI will eliminate more than 85 million jobs.
But for all the talk about job security, AI is also proving to be a powerful tool in healthcare—specifically, cancer detection. One recently published study has shown that, remarkably, artificial intelligence was able to detect 20 percent more cancers in imaging scans than radiologists alone.
Published in The Lancet Oncology, the study analyzed the scans of 80,000 Swedish women with a moderate hereditary risk of breast cancer who had undergone a mammogram between April 2021 and July 2022. Half of these scans were read by AI and then a radiologist to double-check the findings. The second group of scans was read by two researchers without the help of AI. (Currently, the standard of care across Europe is to have two radiologists analyze a scan before diagnosing a patient with breast cancer.)
The study showed that the AI group detected cancer in 6 out of every 1,000 scans, while the radiologists detected cancer in 5 per 1,000 scans. In other words, AI found 20 percent more cancers than the highly-trained radiologists.
Scientists have been using MRI images (like the ones pictured here) to train artificial intelligence to detect cancers earlier and with more accuracy. Here, MIT's AI system, MIRAI, looks for patterns in a patient's mammograms to detect breast cancer earlier than ever before. news.mit.edu
But even though the AI was better able to pinpoint cancer on an image, it doesn’t mean radiologists will soon be out of a job. Dr. Laura Heacock, a breast radiologist at NYU, said in an interview with CNN that radiologists do much more than simply screening mammograms, and that even well-trained technology can make errors. “These tools work best when paired with highly-trained radiologists who make the final call on your mammogram. Think of it as a tool like a stethoscope for a cardiologist.”
AI is still an emerging technology, but more and more doctors are using them to detect different cancers. For example, researchers at MIT have developed a program called MIRAI, which looks at patterns in patient mammograms across a series of scans and uses an algorithm to model a patient's risk of developing breast cancer over time. The program was "trained" with more than 200,000 breast imaging scans from Massachusetts General Hospital and has been tested on over 100,000 women in different hospitals across the world. According to MIT, MIRAI "has been shown to be more accurate in predicting the risk for developing breast cancer in the short term (over a 3-year period) compared to traditional tools." It has also been able to detect breast cancer up to five years before a patient receives a diagnosis.
The challenges for cancer-detecting AI tools now is not just accuracy. AI tools are also being challenged to perform consistently well across different ages, races, and breast density profiles, particularly given the increased risks that different women face. For example, Black women are 42 percent more likely than white women to die from breast cancer, despite having nearly the same rates of breast cancer as white women. Recently, an FDA-approved AI device for screening breast cancer has come under fire for wrongly detecting cancer in Black patients significantly more often than white patients.
As AI technology improves, radiologists will be able to accurately scan a more diverse set of patients at a larger volume than ever before, potentially saving more lives than ever.