Controversial CRISPR scientist promises “no more gene-edited babies” until society comes around

He Jiankui, the Chinese biophysicist whose controversial 2018 experiment led to the birth of three gene-edited children, says he’s returned to work on the concept of altering the DNA of people at conception, but with a difference. 

This time around, he says, he will restrict his research to animals and nonviable human embryos. He will not try to create a pregnancy, at least until society comes to accept his vision for “genetic vaccines” against common diseases.

“There will be no more gene-edited babies. There will be no more pregnancies,” he said during an online roundtable discussion hosted by MIT Technology Review, during which He answered questions from biomedicine editor Antonio Regalado, editor in chief Mat Honan, and our subscribers.

During the interview, He defended his past research and said the “only regret” he had was the difficulties he had caused to his wife and two daughters. He spent three years in prison after a court found him guilty of breaking regulations, but since his release in 2022 he has sought to stage a scientific comeback.

He says he currently has a private lab in the city of Sanya, in Hainan province, where he works on gene therapy for rare disease as well as laboratory tests to determine how, one day, babies could be born resistant to ever developing Alzheimer’s disease.

The Chinese scientist said he’s receiving financial support from individuals in the US and China, and from Chinese companies, and has received an offer to form a research company in Silicon Valley. He declined to name his investors.

Read the full transcript of the event below.

Mat Honan: Hello, everybody. Thanks for joining us today. My name is Mat Honan. I’m the editor in chief here at MIT Technology Review. I’m really thrilled to host what’s going to be, I think, a great discussion today. I’m joined by Antonio Regalado, our senior editor for biomedicine, and He Jiankui, who goes by the name JK. 

JK is a biophysicist, He’s based in China, and JK used CRISPR to edit the genes of human embryos, which ultimately resulted in the first children born whose DNA had been tailored using gene editing. Welcome to you both.

To our audience tuning in today, I wanted to let you know if you’ve got questions for us, please do ask them in the chat window. We’ve got a packed discussion planned, but we will get to as many of those as we can throughout. Antonio, I think I’m going to start with you, if we can. You’re the one who broke this story six years ago. Why don’t you set the stage for what we’re going to be talking about here today, and why it’s important.

Antonio Regalado: Mat, thank you.

The subject is genome editing. Of course, it’s a technology for changing the DNA inside of individual cells, including embryos. It’s hard to overstate its importance. I put it up there with the invention of the transistor and artificial intelligence.

And why do I think so? Well, genome editing gives humans control, or at least the ability to try and direct the very processes that brought us about as a species. So it’s that profound.

Getting to JK’s story. In 2018 we had a scoop—he might call it a leak—in which we described his experiment, which, as Mat said, was to edit human embryos to delete a particular gene called CCR5 with the goal of rendering the children, of which there were three, immune to HIV, which their fathers had and which is a source of stigma in China. So that was the project.

Of course our story set off, you know, immediate chaos. Voices were raised all over the world—many critical, a few in support. But one of the consequences was that JK and his team, the parents and the doctors, did not have the ability to tell their own story—in JK’s case because he was, in fact, detained and has completed a term in prison. So we’re happy to have him here to answer my questions and those of our subscribers. JK, thank you for being here. 

Several people, including Professor Michael Waitzkin of Duke University, would like to know what the situation is with the three children. What do you know about their health, and where is this information coming from?

He Jiankui: Lulu, Nana, and the third gene-edited baby—they were healthy and are living a normal, peaceful, undisturbed life. They are as happy as any other people, any other children in kindergarten. I have maintained a constant connection with their parents.

Antonio Regalado: I see. JK, on X, you recently made a comment about one of the parents—now a single mother—who you said you were supporting financially. What can you tell us about that situation? What kind of obligations do you have to these children, and are you able to meet those obligations?

He Jiankui: So the third genetic baby—the parents divorced, so the girl is with her mother. You know, a single mother, a single-parent family—life is not easy. So in the last two years, I’m providing some financial support, but I’m not sure it’s the right thing to do or whether it’s ethical, because I’m a scientist or a doctor, and she is a volunteer or patient. For scientists or doctors to provide financial support to the volunteer or patient—it correct? Is it the right thing to do, and is it ethical? That’s something I’m not sure of. So I have this question, actually.

Antonio Regalado: Interesting. Well, there’s a lot of ethical dilemmas here, and one of them is about your publications, the scientific publications which you prepared and which describe the experiment. So a two-part question for you. 

First of all, setting the ethics aside, some people who criticized your experiment still want to know the result. They would like to know if it worked. Are the children resistant to HIV or not? So part one of the question is: Are you able to make a measurement on their blood, or is anybody able to make a measurement that would show if the experiment worked? And second part of the question: Do you intend to publish your paper, including as a preprint or as a white paper?

He Jiankui: So I always believe that scientific research must be open and transparent, so I am willing to publish my papers, which I wrote six years ago.

It was rejected by Nature, for some reason. But even today, I would say that I’m willing to publish these two papers in a peer-reviewed journal. It has to be peer-reviewed; that is the standard way to publish in a paper.

The other thing is whether the baby is resistant to HIV. Actually, several years ago, when we designed the experiment, we already collected the [umbilical] cord blood when they were born. We collected cord blood from the babies, and our original experiment design was to challenge the cord blood with the HIV virus to see whether they are actually resistant to HIV. But this experiment never happened, because when the news broke out, there has been no way to do any experiment since then. 

I would say I am happy to share my results to the whole world.

Mat Honan: Thanks, Antonio. Let me start with a question from a reader, Karen Jones. She asks, with so much controversy around breaking the law in China, she wanted to know about your credibility. And it reminds me of something that I’m curious about myself. What are the professional consequences of your work? Are you still able to work in China? Are you still able to do experiments with CRISPR?

He Jiankui: Yes, I continue my research in the lab. I have a lab in Sanya [Hainan province], and also previously a lab in Wuhan.

My current work is on gene editing to cure genetic disease such as Duchenne muscular dystrophy and several other genetic diseases. And all this is done by somatic gene therapy, which means this is not working on human embryos.

Mat Honan: I think that leads [to] a question that we have from another reader, Sophie, who wanted to know if you plan to do more gene editing in humans.

He Jiankui: So I have proposed a research project using human embryo gene editing to prevent Alzheimer’s disease. I posted this proposal last year on Twitter. So my goal is we’re going to test the embryo gene editing in mice and monkeys, and in human nonviable embryos. Again, it’s nonviable embryos. There will be no more gene-edited babies. There will be no more pregnancies. We’re going to stop at human nonviable embryos. So our goal is to see if we could prevent Alzheimer’s for offspring or the next generation, because Alzheimer’s has no cure currently.

Mat Honan: I see. And then my last question before I move it back to Antonio. I’m curious if you plan to continue working in China, or if you think that you will ultimately relocate somewhere else. Do you plan to do this work elsewhere? 

He Jiankui: Some investors from Silicon Valley proposed to invest in me to start a company in the United States, with research done both in the United States and in China. This is a very interesting proposal, and I am considering it. I would be happy to work in the United States if there’s good opportunity.

Mat Honan: Let me just remind our readers—if you do have questions, you could put them in the chat and we will try to get to them. But in the meantime, Antonio, back over to you, please.

Antonio Regalado: Definitely, I’m curious about what your plans are. Yesterday Stat News reported some of the answers to today’s questions. They said that you have established yourself in the province of Hainan in China. So what kind of facility do you have there? Do you have a lab, or are you doing research? And where is the financial support coming from?

He Jiankui: So here I have an independent private research lab with a few people. We get funding from both the United States and also from China to support me to carry on the research on the gene therapy for Duchenne muscular dystrophy, for high cholesterol, and some other genetic diseases. 

Antonio Regalado: Could you be more specific about where the funding is coming from? I mean, who is funding you, or what types of people are funding this research? 

He Jiankui:  There are people in the United States who made a donation to me. I’m not going to disclose the name and amount. Also the Chinese people, including some companies, are providing funding to me.

Antonio Regalado: I wonder if you could sketch out for us—I know people are interested—where you think all this [is] going to lead. With a long enough time frame—10 years, 20 years, 30 years—do you think the technology will be in use to change embryos, and how will it be used? What is the larger plan that you see?

He Jiankui: I would say in 50 years, like in 2074, embryo gene editing will be as common as IVF babies to prevent all the genetic disease we know today. So the babies born at that time will be free of genetic disease.

Antonio Regalado: You’re working on Alzheimer’s. This is a gene variant that was described in 2012 by deCode Genetics. This is one of these variants that is protective—it would protect against Alzheimer’s. Strictly speaking, it’s not a genetic disease. So what about the role of protective variants, or what could be called improvements to health?

He Jiankui: Well, I decided to do Alzheimer’s disease because my mother has Alzheimer’s. So I’m going to have Alzheimer’s too, and maybe my daughter and my granddaughter. So I want to do something to change it. 

There’s no cure for Alzheimer’s today. I don’t know for how many years that will be true. But what we can do is: Since some people in Europe are at a very low risk [for] Alzheimer’s, why don’t we just make some modifications so our next generation also have this protective allele, so they have a low risk of Alzheimer’s or maybe are free of Alzheimer’s. That’s my goal.

Antonio Regalado: Well, a couple of questions. Will any country permit this? I mean, genome editing, producing genome-edited children, was made formally illegal in China, I think in 2021. And it’s prohibited in the United States in another way. So where can you go, or where will you go to further this technology?

He Jiankui:  I believe society will eventually accept that embryo gene editing is a good thing because it improves human health. So I’m waiting for society to accept that. My current research is not doing any gene-edited baby or any pregnancy. What I do is a basic research in mice, monkeys, or human nonviable embryos. We only do basic research, but I’m certain that one day society will accept embryo gene editing.

Mat Honan: That raises a question for me. We’re talking about HIV or Alzheimer’s, but there are other aspects of this as well. You could be doing something where you’re optimizing for intelligence or optimizing for physical performance. And I’m curious where you think this leads, and if you think that there is a moral issue around, say, parents who are allowed to effectively design their children by editing their genes.

He Jiankui: Well, I advise you to read the paper I published in 2018 in the CRISPR Journal. It’s my personal thinking of the ethical guidelines for embryo gene editing. It was retracted by the CRISPR Journal. But I proposed that the embryo gene editing should only be used for disease. It should never be used for a nontherapeutic purpose, like making people smarter, stronger, or beautiful.

Mat Honan:  Do you not think that becomes inevitable, though, if gene-editing embryos becomes common?

He Jiankui: Society will decide that. 

Mat Honan: Moving on: You said that you were only working with animals or with nonviable embryos. Are there other people who you think are working with human embryos, with viable human embryos, or that you know of, or have heard about, continuing with that kind of work?

He Jiankui: Well, I don’t know yet. Actually, many scientists are keeping their distance from me. But there are people from somewhere, an island in Honduras or maybe some small East European country, inviting me to do that. And I refused. I refused. I will only do research in the United States and China or other major countries.

Mat Honan: So the short answer is, that sounded almost like a yes to me? You think that it is happening? Is that correct?

He Jiankui: I’m not answering that. 

Mat Honan: Okay, fair enough. I’m going to move on to some reader questions here while we have the time. You mentioned basically having society come around to seeing that this is necessary work. Ravi asks: What type of regulatory framework do you believe is necessary to ensure responsible development and applications of this technology? You had mentioned limiting to therapeutic purposes. Are there other frameworks you think should be in place?

He Jiankui: I’m not answering this question.

Mat Honan: What you think should be in place in terms of regulation?

He Jiankui: Well, there are a lot of regulations. I personally comply with all the laws, regulations, and international ethics for my work. 

Mat Honan: I see. Go ahead, Antonio. 

Antonio Regalado: Let me just jump in with a related question. You talked about offers of funding from the United States, from Silicon Valley—offers of funding to support you. Is that to create a company, and how would accepting investment from entrepreneurs to start a company change public perception about the technology?

He Jiankui: Well, it was designed as a company registered in the United States and headquartered in the United States.

Antonio Regalado: But do you think that starting a company will make people more enthusiastic or interested in this technology?

He Jiankui: Well, for me, I would certainly be more happy to get an offer from the United States [if it came] from a university or research institution. I would be happy for that, but it’s not happening. But, well, a company started doing some basic research, and that’s also a good contribution.

Antonio Regalado: Getting back to the initial experiment—obviously, it’s been criticized a great deal. And I am just wondering, looking back, which of those criticisms do you accept? Which do you disagree with? Do you have regrets about the experiment?

He Jiankui: The only regret I have is to my family, my wife and my two daughters. In the last few years, they are living in a very difficult situation. I won’t let that happen again.

Antonio Regalado: The technology is viewed as controversial. I’m talking about embryo editing. So it’s a little bit surprising to me that you would return to it. Surprising and interesting. So why is it that you have decided to pursue this vision, this project, despite the problems? I mean, you’re still working on it. What is your motivation?

He Jiankui: Our stance is always for us to do something to benefit mankind.

Antonio Regalado: Speaking of mankind, or humankind, I did have a question about evolution. The gene edits that you made to CCR5 and now are working on to another gene in Alzheimer’s—these are natural mutations that occur in some populations, you mentioned in Europe. They’ve been discovered through population genetics. Studies of a large number of people can find these genetic variations that are protective, or believed to be protective, against disease. In the natural course of evolution, those might spread, right? But it would take hundreds of thousands of years. So with gene editing, you can introduce such a change into an embryo, I guess, in a matter of minutes.

So the question I have is: Is this an evolutionary project? Is it human technology being used to take over from evolution?

He Jiankui: I’m not interested in evolution. Evolution takes thousands of years. I only care about the people surrounding me—my family, and also the patients who would come to find me. What I want to do is help those people, help people in this living world. I’m not interested in evolution.

Antonio Regalado: Mat, any other question from the audience you’d like to throw in?

Mat Honan: Yeah, let me get to one from Rez, who’s asking: What do you see as the major hurdles in advancing CRISPR to more general health-care use cases? What do you see as the big barriers there?

He Jiankui:  If you’re talking about somatic gene therapy, the bottleneck, of course, is delivery. Without breakthroughs in delivery technology, somatic gene therapy is heading toward a dead end. For the embryo gene editing, the bottleneck, of course, is: How long will it take people to accept new technology? Because as humans, we are always conservative. We are always worried about the new things, and it takes time for people to accept new technology. 

Mat Honan: I wanted to get a question from Robert that goes back to our earlier discussion here, which is: What was your initial motivation to take this step with the three children?

He Jiankui: So several years ago, I went to a village in the center of China where more than 30% of people are infected with HIV. Back to the 1990s, many years ago, people sold blood, and it did something [spread HIV]. When I was there, I saw that there’s a very small kindergarten, only designed for the children of HIV patients. Why did that happen? Other public schools won’t take them. I felt that there’s a kind of discrimination to these children. And what I want to do is to do something to change it. If the HIV patient—if their children are not just free from but actually immune to HIV, then it will help them to go back to the society. For me, it’s just like a vaccine. It’s one vaccine to protect them for a lifetime. 

Mat Honan: I see we’re running short on time here, and I do want to try to get to some more of our reader questions. I know Antonio has a last one as well. If you do have questions, please put them in the chat. And from Joseph, he wants to know: You say that you think that the society will come around. What do you think will be the first types of embryo DNA edits that would be acceptable to the medical community or to society at large?

He Jiankui: Very recently, a patient flew here to visit me in my office. They are a couple, they are over 40 years old. They want to have a baby and already did IVF. They have embryos, but the embryos have a problem with a chromosome. So this embryo is not good. So one thing, apparently, we could do to help them is to correct the chromosome problem so they can have a healthy embryo, so they can have children. We’re not creating any immunity to anything—it’s just to restore the health of the embryo. And I believe that would be a good start.

Mat Honan: Thank you, JK. Antonio, back over to you. 

Antonio Regalado:  JK, I’m curious about your relationship to the government in China, the central government. You were punished, but on the other hand, you’re free to continue to talk about science and do research. Does the government support you and your ideas? Are you a member of the political party? Have you been offered membership? What is your relationship to the government?

He Jiankui: Next question.

Antonio Regalado: Next question? Okay. Interesting. We’ll have to postpone that one for another day.

Mat, anything else? I think we’re coming up against time, and I’m wondering if we have reader questions. I have one here that I could ask, which is about the new technologies in CRISPR. People want to know where this technology is going, in terms of the methods. You used CRISPR to delete a gene. But CRISPR itself is constantly being improved. There are new tools. So in your lab, in your experiments, what gene-editing technology are you employing?

He Jiankui:  So six years ago, we were using the original CRISPR-Cas9 invented by Jennifer Doudna. But today, we are moving on to base editing, invented by David Liu. The base editing, it’s safe in embryos. It won’t cut the DNA or break it—just small changes. So we no longer use CRISPR-Cas9. We’re using base editing.

Antonio Regalado: And can you tell me the nature of the genetic change that you’re experimenting with or would like to make in these cells to make them resistant to Alzheimer’s? How big a change are you making with this base editor, or trying to make with it?

He Jiankui: So to make people protected against Alzheimer’s, we just need a single base change in the whole human 3 billion letters of DNA. We just change one letter of it to protect people from Alzheimer’s.

Antonio Regalado: And how soon do you think that this could be in use? I mean, it sounds interesting. If I had a child, I might want them to be immune to Alzheimer’s. So this is quite an interesting proposal. What is the time frame in years—if it works in the lab—before it could be implemented in IVF clinics?

He Jiankui: I would say there’s the basic research that could be finished in two years. I won’t move on to the human trial. That’s not my role. It’s determined by society whether to accept it or not. And that’s the ethical side. 

Antonio Regalado: A last question on this from a reader. The question is: How do you prove the benefits? Of course, you can make a genetic change. You can even create a person with a genetic change. But if it’s for Alzheimer’s, it’s going to take 70 years before you know and can prove the results. So how can you prove its medical benefit? Or how can you predict the medical benefit?

He Jiankui: So one thing is that we can observe it in the natural world. There are already thousands of people with this mutation. It helps them against Alzheimer’s. It naturally exists in the population, in humans, so that’s a natural human experiment. And also we could do it in mice. We could use Alzheimer’s model mice and then to modulate DNA to see the results.

You might argue that it takes many years to develop Alzheimer’s, but in society, we’ve done a lot with the HPV vaccine against certain women’s cancers. Cancer takes many years to happen, but they take the HPV vaccine at age eight or seven.

Mat Honan: Thank you so much. JK and Antonio, we are slightly past time here, and I’m going to go ahead and wrap it up. Thank you very much for joining us today, to both of you. And I also want to thank all of our subscribers who tuned in today. I do hope that we see you again next month at our Roundtable in August. It’s our subscriber-only series. And I hope you enjoyed today. Thanks, everybody. 

Antonio Regalado: Thank you, JK.

He Jiankui: Thank you. 

Why we need safeguards against genetic discrimination

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

A couple of years ago, I spat into a little plastic tube, stuck it in the post, and waited for a company to analyze markers on my DNA to estimate how biologically old I am. It’s not the first time I’ve shared my genetic data for a story. Over a decade ago, I shared a DNA sample with a company that promised to tell me about my ancestry.

Of course, I’m not the only one. Tens of millions of people have shipped their DNA off to companies offering to reveal clues about their customers’ health or ancestry, or even to generate tailored diet or exercise advice. And then there are all the people who have had genetic tests as part of their clinical care, under a doctor’s supervision. Add it all together, and there’s a hell of a lot of genetic data out there.

It isn’t always clear how secure this data is, or who might end up getting their hands on it—and how that information might affect people’s lives. I don’t want my insurance provider or my employer to make decisions about my future on the basis of my genetic test results, for example. Scientists, ethicists and legal scholars aren’t clear on the matter either. They are still getting to grips with what genetic discrimination entails—and how we can defend against it.

If we’re going to protect ourselves from genetic discrimination, we first have to figure out what it is. Unfortunately, no one has a good handle on how widespread it is, says Yann Joly, director of the Centre of Genomics and Policy at McGill University in Quebec. And that’s partly because scientists keep defining it in different ways. In a paper published last month, Joly and his colleagues listed 12 different definitions that have been used in various studies since the 1990s. So what is it?

“I see genetic discrimination as a child of eugenics practices,” says Joly. Modern eugenics, which took off in the late 19th century, was all about limiting the ability of some people to pass on their genes to future generations. Those who were considered “feeble minded” or “mentally defective” could be flung into institutions, isolated from the rest of the population, and forced or coerced into having procedures that left them unable to have children. Disturbingly, some of these practices have endured. In the fiscal years 2005-2006 and 2012-2013, 144 women in California’s prisons were sterilized—many without informed consent.

These cases are thankfully rare. In recent years, ethicists and policymakers have been more worried about the potential misuse of genetic data by health-care and insurance providers. There have been instances in which people have been refused health insurance or life insurance on the basis of a genetic result, such as one that predicts the onset of Huntington’s disease. (In the UK, where I live, life insurance providers are not meant to ask for a genetic test or use the results of one—unless the person has tested positive for Huntington’s.)

Joly is collecting reports of suspected discrimination in his role at the Genetic Discrimination Observatory, a network of researchers working on the issue. He tells me that in one recent report, a woman wrote about her experience after she had been referred to a new doctor. This woman had previously taken a genetic test that revealed she would not respond well to certain medicines. Her new doctor told her he would only take her on as a patient if she first signed a waiver releasing him of any responsibility over her welfare if she didn’t follow the advice generated by her genetic test.

“It’s unacceptable,” says Joly. “Why would you sign a waiver because of a genetic predisposition? We’re not asking people with cancer to [do so]. As soon as you start treating people differently because of genetic factors … that’s genetic discrimination.”

Many countries have established laws to protect people from these kinds of discrimination. But these laws, too, can vary hugely both when it comes to defining what genetic discrimination is and to how they safeguard against it. The law in Canada focuses on DNA, RNA, and chromosome tests, for example. But you don’t always need such a test to know if you’re at risk for a genetic disease. A person might have a family history of a disease or already be showing symptoms of it.

And then there are the newer technologies. Take, for example, the kind of test that I took to measure my biological age. Many aging tests measure either chemical biomarkers in the body or epigenetic markers on the DNA—not necessarily the DNA itself. These tests are meant to indicate how close a person is to death. You might not want your life insurance provider to know or act on the results of those, either.

Joly and his colleagues have come up with a new definition. And they’ve kept it broad. “The narrower the definition, the easier it is to get around it,” he says. He wanted to avoid excluding the experiences of any people who feel they’ve experienced genetic discrimination. Here it is:

“Genetic discrimination involves an individual or a group being negatively treated, unfairly profiled or harmed, relative to the rest of the population, on the basis of actual or presumed genetic characteristics.

It will be up to policymakers to decide how to design laws around genetic discrimination. And it won’t be simple. The laws may need to look different in different countries, depending on what technologies are available and how they are being used. Perhaps some governments will want to ensure that residents have access to technologies, while other may choose to limit access. In some cases, a health-care provider may need to make decisions about a person’s care based on their genetic results.

In the meantime, Joly has advice for anyone worried about genetic discrimination. First, don’t let such concerns keep you from having a genetic test that you might need for your own health. As things stand, the risk of being discriminated against on the basis of these tests is still quite small.

And when it comes to consumer genetic testing, it’s worth looking closely at the company’s terms and conditions to find out how your data might be shared or used. It is also useful to look up the safeguarding laws in your own country or state, which can give you a good idea of when you’re within your rights to refuse to share your data.

Shortly after I received the results from my genetic tests, I asked the companies involved to delete my data. It’s not a foolproof approach—last year, hackers stole personal data on 6.9 million 23andMe customers—but at least it’s something. Just this week I was offered yet another genetic test. I’m still thinking on it.


Now read the rest of The Checkup

Read more from MIT Technology Review’s archive:

As of 2019, more than 26 million people had undertaken a consumer genetic test, as my colleague Antonio Regalado found. The number is likely to have grown significantly since then.
 
Some companies say they can build a picture of what a person looks like on the basis of DNA alone. The science is questionable, as Tate Ryan-Mosley found when she covered one such company.
 
The results of a genetic test can have profound consequences, as Golda Arthur found when a test revealed she had a genetic mutation that put her at risk of ovarian cancer. Arthur, whose mother developed the disease, decided to undergo the prophylactic removal of her ovaries and fallopian tubes. 
 
Tests that measure biological age were selected by readers as our 11th breakthrough technology of 2022. You can read more about them here.
 
The company that gave me an estimate of my biological age later reanalyzed my data (before I had deleted it). That analysis suggested that my brain and liver were older than they should be. Great.

From around the web:

Over the past few decades, doctors have implanted electrodes deep into the brains of a growing number of people, usually to treat disorders like epilepsy and Parkinson’s disease. We still don’t really know how they work, or how long they last. (Neuromodulation)

A ban on female genital mutilation will be upheld in the Gambia following a vote by the country’s National Assembly. The decision “reaffirm[s the country’s] commitments to human rights, gender equality, and protecting the health and well-being of girls and women,” directors of UNICEF, UNFPA, WHO, UN Women, and the UN High Commissioner for Human Rights said in a joint statement. (WHO)

Weight-loss drugs that work by targeting the GLP-1 receptor, like Wegovy and Saxena, are in high demand—and there’s not enough to go around. Other countries could follow Switzerland’s lead to make the drugs more affordable and accessible, but only for the people who really need them. (JAMA Internal Medicine)

J.D. Vance, Donald Trump’s running mate, has ties to the pharmaceutical industry and has an evolving health-care agenda. (STAT)

Psilocybin, the psychedelic compound in magic mushrooms, can disrupt the way regions of our brains communicate with each other. And the effect can last for weeks. (The Guardian)

IVF alone can’t save us from a looming fertility crisis

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here. 

I’ve just learned that July 11 is World Population Day. There are over 8 billion of us on the planet, and there’ll probably be 8.5 billion of us by 2030. We’re continually warned about the perils of overpopulation and the impact we humans are having on our planet. So it seems a bit counterintuitive to worry that, actually, we’re not reproducing enough.

But plenty of scientists are incredibly worried about just that. Improvements in health care and sanitation are helping us all lead longer lives. But we’re not having enough children to support us as we age. Fertility rates are falling in almost every country.

But wait! We have technologies to solve this problem! IVF is helping to bring more children into the world than ever, and it can help compensate for the fertility problems faced by older parents! Unfortunately, things aren’t quite so simple. Research suggests that these technologies can only take us so far. If we want to make real progress, we also need to work on gender equality.

Researchers tend to look at fertility in terms of how many children the average woman has in her lifetime. To maintain a stable population, this figure, known as the total fertility rate (TFR), needs to be around 2.1.

But this figure has been falling over the last 50 years. In Europe, for example, women born in 1939 had a TFR of 2.3—but the figure has dropped to 1.7 for women born in 1981 (who are 42 or 43 years old by now). “We can summarize [the last 50 years] in three words: ‘declining,’ ‘late,’ and ‘childlessness,’” Gianpiero Dalla Zuanna, a professor of demography at the University of Padua in Italy, told an audience at the annual meeting of the European Society of Human Reproduction and Embryology earlier this week.

There are a lot of reasons behind this decline. Around one in six people is affected by infertility, and globally, many people aren’t having as many children as they would like. On the other hand, more people are choosing to live child-free. Others are delaying starting a family, perhaps because they face soaring living costs and have been unable to afford their own homes. Some hesitate to have children because they are concerned about the future. With the ongoing threat of global wars and climate change, who can blame them? 

There are financial as well as social consequences to this fertility crisis. We’re already seeing fewer young people supporting a greater number of older ones. And it’s not sustainable.

“Europe today has 10% of the population, 20% of gross domestic product, and 50% of the welfare expense of the world,” Dalla Zuanna said at the meeting. Twenty years from now, there will be 20% fewer people of reproductive age than there are today, he warned.

It’s not just Europe that will be affected. The global TFR in 2021 was 2.2—less than half the figure in 1950, when it was 4.8. By one recent estimate, the global fertility rate is declining at a rate of 1.1% per year. Some countries are facing especially steep declines: In 2021, the TFR in South Korea was just 0.8—well below the 2.1 needed to maintain the population. If this decline continues, we can expect the global TFR to hit 1.83 by 2050 and 1.59 by 2100.

So what’s the solution? Fertility technologies like IVF and egg freezing have been touted as one potential remedy. More people than ever are using these technologies to conceive. An IVF baby is born somewhere in the world every 35 seconds. And IVF can indeed help us overcome some fertility issues, including those that can arise for people starting a family after the age of 35. IVF is already involved in 5% to 10% of births in high-income countries. “IVF has got to be our solution, you would think,” said Georgina Chambers, who directs the National Perinatal Epidemiology and Statistics Unit at UNSW Sydney in Australia, in another talk at ESHRE.

Unfortunately, technology is unlikely to solve the fertility crisis anytime soon, as Chambers’s own research shows. A handful of studies suggest that the use of assisted reproductive technologies (ART) can only increase the total fertility rate of a country by around 1% to 5%. The US sits at the lower end of this scale—it is estimated that in 2020, the use of ART increased the fertility rate by about 1.3%. In Australia, however, ART boosted the fertility rate by 5%.

Why the difference? It all comes down to accessibility. IVF can be prohibitively expensive in the US—without insurance covering the cost, a single IVF cycle can cost around half a person’s annual disposable income. Compare that to Australia, where would-be parents get plenty of government support, and an IVF cycle costs just 6% of the average annual disposable income.

In another study, Chambers and her colleagues have found that ART can help restore fertility to some extent in women who try to have children later in life. It’s difficult to be precise here, because it’s hard to tell whether some of the births that followed IVF would have happened eventually without the technology.

Either way, IVF and other fertility technologies are not a cure-all. And overselling them as such risks encouraging people to further delay starting a family, says Chambers. There are other ways to address the fertility crisis.

Dalla Zuanna and his colleague Maria Castiglioni believe that countries with low fertility rates, like their home country Italy, need to boost the number of people of reproductive age. “The only possibility [of achieving this] in the next 20 years is to increase immigration,” Castiglioni told an audience at ESHRE.

Several countries have used “pronatalist” policies to encourage people to have children. Some involve financial incentives: Families in Japan are eligible for one-off payments and monthly allowances for each child,as part of a scheme that was recently extended. Australia has implemented a similar “baby bonus.”

“These don’t work,” Chambers said. “They can affect the timing and spacing of births, but they are short-lived. And they are coercive: They negatively affect gender equity and reproductive and sexual rights.”

But family-friendly policies can work. In the past, the fall in fertility rates was linked to women’s increasing participation in the workforce. That’s not the case anymore. Today, higher female employment rates are linked to higher fertility rates, according to Chambers. “Fertility rises when women combine work and family life on an equal footing with men,” she said at the meeting. Gender equality, along with policies that support access to child care and parental leave, can have a much bigger impact.

These policies won’t solve all our problems. But we need to acknowledge that technology alone won’t solve the fertility crisis. And if the solution involves improving gender equality, surely that’s a win-win.


Now read the rest of The Checkup

Read more from MIT Technology Review’s archive:

My colleague Antonio Regalado discussed how reproductive technology might affect population decline with Martin Varsavsky, director of the Prelude Fertility network of clinics, in a roundtable on the future of families earlier this year.

There are new fertility technologies on the horizon. I wrote about the race to generate lab-grown sperm and eggs from adult skin cells, for example. Scientists have already created artificial eggs and sperm from mouse cells and used them to create mouse pups. Artificial human sex cells are next.

Advances like these could transform the way we understand parenthood. Some researchers believe we’re not far being able to create babies with multiple genetic parents or none at all, as I wrote in a previous edition of The Checkup.

Elizabeth Carr was America’s first IVF baby when she was born in 1981. Now she works at a company that offers genetic tests for embryos, enabling parents to choose those with the highest health scores.

Some people are already concerned about maintaining human populations beyond planet Earth. The Dutch entrepreneur Egbert Edelbroek wants to try IVF in space. “Humanity needs a backup plan,” he told Scott Solomon in October last year. “If you want to be a sustainable species, you want to be a multiplanetary species.”

We have another roundtable discussion coming up with Antonio later this month. You can join him for a discussion about CRISPR and the future of gene editing. “CRISPR Babies: Six years later” takes place on Thursday, July 25, and is a subscriber-only online event. You can register for free.

From around the web

When a Bitcoin mining facility moved into the Granbury area in Texas, local residents started complaining of strange new health problems. They believe the noisy facility might be linked to their migraines, panic attacks, heart palpitations, chest pain, and hypertension. (Time)

In the spring of 1997, 20 volunteers agreed to share their DNA for the Human Genome Project, an ambitious effort to publish a reference human genome. They were told researchers expected that “no more than 10% of the eventual DNA sequence will have been obtained from [each person’s] DNA.” But when the draft was published in 2001, nearly 75% of it came from just one person. Ashley Smart reports on the ethical questions surrounding the project. (Undark)

How can you make cultured meat taste more like the real thing? Scientists have developed “flavor scaffolds” that can release a meaty taste when cultured meat is cooked. The resulting product looks like a meaty pink jelly. Bon appétit! (Nature)

Doctors can continue their medical education by taking courses throughout their careers. Some of these are funded by big tobacco companies. They really shouldn’t be, argue these doctors from Stanford and the University of California. (JAMA)

“Skin care = brain care”? Maybe, if you believe the people behind the burgeoning industry of neurocosmetics. (The Atlantic)

People can move this bionic leg just by thinking about it

When someone loses part of a leg, a prosthetic can make it easier to get around. But most prosthetics are static, cumbersome, and hard to move. A new neural interface connects a bionic limb to nerve endings in the thigh, allowing the limb to be controlled by the brain. The new device, which is described today in Nature Medicine, could help people with lower-leg amputations feel as if their prosthesis is part of them.

“When you ask a patient ‘What is your body?’ They don’t include the prosthesis,” says MIT biophysicist Hugh Herr, one of the lead authors on the study. The work is personal for him: he lost both his lower legs in a climbing accident when he was 17. He says linking the brain to the prosthesis can make it feel more like part of someone’s anatomy, which can have a positive emotional impact. 

Getting the neural interface hooked up to a prosthetic takes two steps. First, patients undergo surgery. Following a lower leg amputation, portions of shin and calf muscle still remain. The operation connects shin muscle, which contracts to make the ankle flex upward, to calf muscle, which counteracts this movement. The prosthetic can also be fitted at this point. Reattaching the remnants of these muscles can enable the prosthetic to move more dynamically. It can also reduce phantom limb pain, and patients are less likely to trip and fall. 

“The surgery stands on its own,” says Amy Pietrafitta, a para-athlete who received it in 2018. “I feel like I have my leg back.” But natural movements are still limited when the prosthetic isn’t connected to the nervous system. 

In step two, surface electrodes measure nerve activity from the brain to the calf and shin muscles, indicating an intention to move the lower leg. A small computer in the bionic leg decodes those nerve signals and moves the leg accordingly, allowing the patient to move the limb more naturally. 

“If you have intact biological limbs, you can walk up and down steps, for example, and not even think about it. It’s involuntary,” says Herr. “That’s the case with our patients, but their limb is made of titanium and silicone.” 

The authors compared the mobility of seven patients using a neural interface with that of patients who had not received the surgery. Patients using the neural interface could walk 41% faster and climb sloped surfaces and steps. They could also dodge obstacles more nimbly and had better balance. And they described feeling that the prosthetic was truly a part of their body rather than just a tool that they used to get around. 

“It’s a very forward-thinking approach,” says Hamid Charkhkar, a biomedical engineer at Case Western Reserve University, who was not involved in the study. “Our limbs are not like shoes. They’re not worn over our bodies. They are integrally attached to our bodies via bones, muscles, and nerves.” 

There are limitations. The surgery can be done during amputation or several years later, but it won’t work equally well for every patient. If it’s done later, for example, some people’s upper thigh muscles could have atrophied too severely for them to receive the full benefits. 

The surgery connecting the shin and calf muscles has become the standard of care at Brigham and Women’s Hospital in Boston. But the surface electrodes that give patients full neural control of their limbs are a few years away from being clinically implemented. Plus, the neural interfaces have only been used in laboratory settings, and it will be important to know how they hold up in the real world. 

Herr and his team at MIT hope to provide users with even greater control over their prosthetic limbs. In the future, their efforts will likely involve replacing the surface electrodes with magnetic spheres, which can more accurately track muscle dynamics. 

“The goal that we have is to really reconstruct bodies, to rebuild bodies,” says Herr. And to fully achieve that ambition, he says, “neural integration and embodiment is our long-term goal.” 

How AI video games can help reveal the mysteries of the human mind

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here. 

This week I’ve been thinking about thought. It was all brought on by reading my colleague Niall Firth’s recent cover story about the use of artificial intelligence in video games. The piece describes how game companies are working to incorporate AI into their products to create more immersive experiences for players.

These companies are applying large language models to generate new game characters with detailed backstories—characters that could engage with a player in any number of ways. Enter in a few personality traits, catchphrases, and other details, and you can create a background character capable of endless unscripted, never-repeating conversations with you.

This is what got me thinking. Neuroscientists and psychologists have long been using games as research tools to learn about the human mind. Numerous video games have been either co-opted or especially designed to study how people learn, navigate, and cooperate with others, for example. Might AI video games allow us to probe more deeply, and unravel enduring mysteries about our brains and behavior?

I decided to call up Hugo Spiers to find out. Spiers is a neuroscientist at University College London who has been using a game to study how people find their way around. In 2016, Spiers and his colleagues worked with Deutsche Telekom and the games company Glitchers to develop Sea Hero Quest, a mobile video game in which players have to navigate a sea in a boat. They have since been using the game to learn more about how people lose navigational skills in the early stages of Alzheimer’s disease.

The use of video games in neuroscientific research kicked into gear in the 1990s, Spiers tells me, following the release of 3D games like Wolfenstein 3D and Duke Nukem. “For the first time, you could have an entirely simulated world in which to test people,” he says.

Scientists could observe and study how players behaved in these games: how they explored their virtual environment, how they sought rewards, how they made decisions. And research volunteers didn’t need to travel to a lab—their gaming behavior could be observed from wherever they happened to be playing, whether that was at home, at a library, or even inside an MRI scanner.

For scientists like Spiers, one of the biggest advantages of using games in research is that people want to play them. The use of games allows scientists to explore fundamental experiences like fun and curiosity. Researchers often offer a small financial incentive to volunteers who take part in their studies. But they don’t have to pay people to play games, says Spiers.

You’re much more likely to have fun if you’re motivated. It’s just not quite the same when you’re doing something purely for the money. And not having to pay participants allows researchers to perform huge studies on smaller budgets. Spiers has been able to collect data on over 4 million people from 195 countries, all of whom have willingly played Sea Hero Quest.  

AI could help researchers go even further. A rich, immersive world filled with characters that interact in realistic ways could help them study how our minds respond to various social settings and how we relate to other individuals. By observing how players interact with AI characters, scientists can learn more about how we cooperate—and compete—with others. It would be far cheaper and easier than hiring actors to engage with research volunteers, says Spiers.

Spiers himself is interested in learning how people hunt, whether for food, clothes, or a missing pet. “We still use these bits of our brain that our ancestors would have used daily, and of course some traditional communities still hunt,” he tells me. “But we know almost nothing about how the brain does this.” He envisions using AI-driven nonplayer characters to learn more about how humans cooperate for hunting.

There are other, newer questions to explore. At a time when people are growing attached to “virtual companions,” and an increasing number of AI girlfriends and boyfriends are being made available, AI video-game characters could also help us understand these novel relationships. “People are forming a relationship with an artificial agent,” says Spiers. “That’s inherently interesting. Why would you not want to study that?”


Now read the rest of The Checkup

Read more from MIT Technology Review’s archive:

My fellow London-based colleagues had a lot of fun generating an AI game character based on Niall. He turned out to be a sarcastic, smug, and sassy monster.

Google DeepMind has developed a generative AI model that can generate a basic but playable video game from a short description, a hand-drawn sketch, or a photo, as my colleague Will Heaven wrote earlier this year. The resulting games look a bit like Super Mario Bros.

Today’s world is undeniably gamified, argues Bryan Gardiner. He explores how we got here in another article from the Play issue of the magazine.

Large language models behave in unexpected ways. And no one really knows why, as Will wrote in March.

Technologies can be used to study the brain in lots of different ways—some of which are much more invasive than others. Tech that aims to read your mind and probe your memories is already being used, as I wrote in a previous edition of The Checkup.

From around the web:

Bad night of sleep left you needing a pick-me-up? Scientists have designed an algorithm to deliver tailored sleep-and-caffeine-dosing schedules to help tired individuals “maximize the benefits of limited sleep opportunities and consume the least required amount of caffeine.” (Yes, it may have been developed with the US Army in mind, but surely we all stand to benefit?) (Sleep)

Is dog cloning a sweet way to honor the memory of a dearly departed pet, or a “frivolous and wasteful and ethically obnoxious” pursuit in which humans treat living creatures as nothing more than their own “stuff”? This feature left me leaning toward the latter view, especially after learning that people tend to like having dogs with health problems … (The New Yorker)

States that have enacted the strongest restrictions to abortion access have also seen prescriptions for oral contraceptives plummet, according to new research. (Mother Jones)

And another study has linked Texas’s 2021 ban on abortion in early pregnancy with an increase in the number of infant deaths recorded in the state. In 2022, across the rest of the US, the number of infant deaths ascribed to anomalies present at birth decreased by 3.1%. In Texas, this figure increased by 22.9%. (JAMA Pediatrics)

We are three months into the bird flu outbreak in US dairy cattle. But the country still hasn’t implemented a sufficient testing infrastructure and doesn’t fully understand how the virus is spreading. (STAT)

Is this the end of animal testing?

In a clean room in his lab, Sean Moore peers through a microscope at a bit of intestine, its dark squiggles and rounded structures standing out against a light gray background. This sample is not part of an actual intestine; rather, it’s human intestinal cells on a tiny plastic rectangle, one of 24 so-called “organs on chips” his lab bought three years ago.

Moore, a pediatric gastroenterologist at the University of Virginia School of Medicine, hopes the chips will offer answers to a particularly thorny research problem. He studies rotavirus, a common infection that causes severe diarrhea, vomiting, dehydration, and even death in young children. In the US and other rich nations, up to 98% of the children who are vaccinated against rotavirus develop lifelong immunity. But in low-income countries, only about a third of vaccinated children become immune. Moore wants to know why.

His lab uses mice for some protocols, but animal studies are notoriously bad at identifying human treatments. Around 95% of the drugs developed through animal research fail in people. Researchers have documented this translation gap since at least 1962. “All these pharmaceutical companies know the animal models stink,” says Don Ingber, founder of the Wyss Institute for Biologically Inspired Engineering at Harvard and a leading advocate for organs on chips. “The FDA knows they stink.” 

But until recently there was no other option. Research questions like Moore’s can’t ethically or practically be addressed with a randomized, double-blinded study in humans. Now these organs on chips, also known as microphysiological systems, may offer a truly viable alternative. They look remarkably prosaic: flexible polymer rectangles about the size of a thumb drive. In reality they’re triumphs of bioengineering, intricate constructions furrowed with tiny channels that are lined with living human tissues. These tissues expand and contract with the flow of fluid and air, mimicking key organ functions like breathing, blood flow, and peristalsis, the muscular contractions of the digestive system.

More than 60 companies now produce organs on chips commercially, focusing on five major organs: liver, kidney, lung, intestines, and brain. They’re already being used to understand diseases, discover and test new drugs, and explore personalized approaches to treatment.

As they continue to be refined, they could solve one of the biggest problems in medicine today. “You need to do three things when you’re making a drug,” says Lorna Ewart, a pharmacologist and chief scientific officer of Emulate, a biotech company based in Boston. “You need to show it’s safe. You need to show it works. You need to be able to make it.” 

All new compounds have to pass through a preclinical phase, where they’re tested for safety and effectiveness before moving to clinical trials in humans. Until recently, those tests had to run in at least two animal species—usually rats and dogs—before the drugs were tried on people. 

But in December 2022, President Biden signed the FDA Modernization Act, which amended the original FDA Act of 1938. With a few small word changes, the act opened the door for non-animal-based testing in preclinical trials. Anything that makes it faster and easier for pharmaceutical companies to identify safe and effective drugs means better, potentially cheaper treatments for all of us. 

Moore, for one, is banking on it, hoping the chips help him and his colleagues shed light on the rotavirus vaccine responses that confound them. “If you could figure out the answer,” he says, “you could save a lot of kids’ lives.”


While many teams have worked on organ chips over the last 30 years, the OG in the field is generally acknowledged to be Michael Shuler, a professor emeritus of chemical engineering at Cornell. In the 1980s, Shuler was a math and engineering guy who imagined an “animal on a chip,” a cell culture base seeded with a variety of human cells that could be used for testing drugs. He wanted to position a handful of different organ cells on the same chip, linked to one another, which could mimic the chemical communication between organs and the way drugs move through the body. “This was science fiction,” says Gordana Vunjak-Novakovic, a professor of biomedical engineering at Columbia University whose lab works with cardiac tissue on chips. “There was no body on a chip. There is still no body on a chip. God knows if there will ever be a body on a chip.”

Shuler had hoped to develop a computer model of a multi-organ system, but there were too many unknowns. The living cell culture system he dreamed up was his bid to fill in the blanks. For a while he played with the concept, but the materials simply weren’t good enough to build what he imagined. 

“You can force mice to menstruate, but it’s not really menstruation. You need the human being.”

Linda Griffith, founding professor of biological engineering at MIT and a 2006 recipient of a MacArthur “genius grant”

He wasn’t the only one working on the problem. Linda Griffith, a founding professor of biological engineering at MIT and a 2006 recipient of a MacArthur “genius grant,” designed a crude early version of a liver chip in the late 1990s: a flat silicon chip, just a few hundred micrometers tall, with endothelial cells, oxygen and liquid flowing in and out via pumps, silicone tubing, and a polymer membrane with microscopic holes. She put liver cells from rats on the chip, and those cells organized themselves into three-dimensional tissue. It wasn’t a liver, but it modeled a few of the things a functioning human liver could do. It was a start.

Griffith, who rides a motorcycle for fun and speaks with a soft Southern accent, suffers from endometriosis, an inflammatory condition where cells from the lining of the uterus grow throughout the abdomen. She’s endured decades of nausea, pain, blood loss, and repeated surgeries. She never took medical leaves, instead loading up on Percocet, Advil, and margaritas, keeping a heating pad and couch in her office—a strategy of necessity, as she saw no other choice for a working scientist. Especially a woman. 

And as a scientist, Griffith understood that the chronic diseases affecting women tend to be under-researched, underfunded, and poorly treated. She realized that decades of work with animals hadn’t done a damn thing to make life better for women like her. “We’ve got all this data, but most of that data does not lead to treatments for human diseases,” she says. “You can force mice to menstruate, but it’s not really menstruation. You need the human being.” 

Or, at least, the human cells. Shuler and Griffith, and other scientists in Europe, worked on some of those early chips, but things really kicked off around 2009, when Don Ingber’s lab in Cambridge, Massachusetts, created the first fully functioning organ on a chip. That “lung on a chip” was made from flexible silicone rubber, lined with human lung cells and capillary blood vessel cells that “breathed” like the alveoli—tiny air sacs—in a human lung. A few years later Ingber, an MD-PhD with the tidy good looks of a younger Michael Douglas, founded Emulate, one of the earliest biotech companies making microphysiological systems. Since then he’s become a kind of unofficial ambassador for in vitro technologies in general and organs on chips in particular, giving hundreds of talks, scoring millions in grant money, repping the field with scientists and laypeople. Stephen Colbert once ragged on him after the New York Times quoted him as describing a chip that “walks, talks, and quacks like a human vagina,” a quote Ingber says was taken out of context.

Ingber began his career working on cancer. But he struggled with the required animal research. “I really didn’t want to work with them anymore, because I love animals,” he says. “It was a conscious decision to focus on in vitro models.” He’s not alone; a growing number of young scientists are speaking up about the distress they feel when research protocols cause pain, trauma, injury, and death to lab animals. “I’m a master’s degree student in neuroscience and I think about this constantly. I’ve done such unspeakable, horrible things to mice all in the name of scientific progress, and I feel guilty about this every day,” wrote one anonymous student on Reddit. (Full disclosure: I switched out of a psychology major in college because I didn’t want to cause harm to animals.)

cross-section of a microfluidic chip with the top channel, epithelial cells, vacuum channel, porous membrane, endothelial cells and bottom channel indicated.
Emulate is one of the companies building organ-on-a-chip technology. The devices combine live human cells with a microenvironment designed to emulate specific tissues.
EMULATE

Taking an undergraduate art class led Ingber to an epiphany: mechanical forces are just as important as chemicals and genes in determining the way living creatures work. On a shelf in his office he still displays a model he built in that art class, a simple construction of sticks and fishing line, which helped him realize that cells pull and twist against each other. That realization foreshadowed his current work and helped him design dynamic microfluidic devices that incorporated shear and flow. 

Ingber coauthored a 2022 paper that’s sometimes cited as a watershed in the world of organs on chips. Researchers used Emulate’s liver chips to reevaluate 27 drugs that had previously made it through animal testing and had then gone on to kill 242 people and necessitate more than 60 liver transplants. The liver chips correctly flagged problems with 22 of the 27 drugs, an 87% success rate compared with a 0% success rate for animal testing. It was the first time organs on chips had been directly pitted against animal models, and the results got a lot of attention from the pharmaceutical industry. Dan Tagle, director of the Office of Special Initiatives for the National Center for Advancing Translational Sciences (NCATS), estimates that drug failures cost around $2.6 billion globally each year. The earlier in the process failing compounds can be weeded out, the more room there is for other drugs to succeed.

“The capacity we have to test drugs is more or less fixed in this country,” says Shuler, whose company, Hesperos, also manufactures organs on chips. “There are only so many clinical trials you can do. So if you put a loser into the system, that means something that could have won didn’t get into the system. We want to change the success rate from clinical trials to a much higher number.”

In 2011, the National Institutes of Health established NCATS and started investing in organs on chips and other in vitro technologies. Other government funders, like the Defense Advanced Research Projects Agency and the Food and Drug Administration, have followed suit. For instance, NIH recently funded NASA scientists to send heart tissue on chips into space. Six months in low gravity ages the cardiovascular system 10 years, so this experiment lets researchers study some of the effects of aging without harming animals or humans. 

Scientists have made liver chips, brain chips, heart chips, kidney chips, intestine chips, and even a female reproductive system on a chip (with cells from ovaries, fallopian tubes, and uteruses that release hormones and mimic an actual 28-day menstrual cycle). Each of these chips exhibits some of the specific functions of the organs in question. Cardiac chips, for instance, contain heart cells that beat just like heart muscle, making it possible for researchers to model disorders like cardiomyopathy. 

Shuler thinks organs on chips will revolutionize the world of research for rare diseases. “It is a very good model when you don’t have enough patients for normal clinical trials and you don’t have a good animal model,” he says. “So it’s a way to get drugs to people that couldn’t be developed in our current pharmaceutical model.” Shuler’s own biotech company used organs on chips to test a potential drug for myasthenia gravis, a rare neurological disorder. In 2022,the FDA approved the drug for clinical trials based on that data—one of six Hesperos drugs that have so far made it to that stage. 


Each chip starts with a physiologically based pharmacokinetic model, known as a PBPK model—a mathematical expression of how a chemical compound behaves in a human body. “We try and build a physical replica of the mathematical model of what really occurs in the body,” explains Shuler. That model guides the way the chip is designed, re-creating the amount of time a fluid or chemical stays in that particular organ—what’s known as the residence time. “As long as you have the same residence time, you should get the same response in terms of chemical conversion,” he says.

Tiny channels on each chip, each between 10 and 100 microns in diameter, help bring fluids and oxygen to the cells. “When you get down to less than one micron, you can’t use normal fluid dynamics,” says Shuler. And fluid dynamics matters, because if the fluid moves through the device too quickly, the cells might die; too slowly, and the cells won’t react normally. 

Chip technology, while sophisticated, has some downsides. One of them is user friendliness. “We need to get rid of all this tubing and pumps and make something that’s as simple as a well plate for culturing cells,” says Vunjak-Novakovic. Her lab and others are working on simplifying the design and function of such chips so they’re easier to operate and are compatible with robots, which do repetitive tasks like pipetting in many labs. 

Cost and sourcing can also be challenging. Emulate’s base model, which looks like a simple rectangular box from the outside,starts at around $100,000 and rises steeply from there. Most human cells come from commercial suppliers that arrange for donations from hospital patients. During the pandemic, when people had fewer elective surgeries, many of those sources dried up. As microphysiological systems become more mainstream, finding reliable sources of human cells will be critical.

“As your confidence in using the chips grows, you might say, Okay, we don’t need two animals anymore— we could go with chip plus one animal.”

Lorna Ewart, Chief Scientific Officer, Emulate

Another challenge is that every company producing organs on chips uses its own proprietary methods and technologies. Ingber compares the landscape to the early days of personal computing, when every company developed its own hardware and software, and none of them meshed well. For instance, the microfluidic systems in Emulate’s intestine chips are fueled by micropumps, while those made by Mimetas, another biotech company, use an electronic rocker and gravity to circulate fluids and air. “This is not an academic lab type of challenge,” emphasizes Ingber. “It’s a commercial challenge. There’s no way you can get the same results anywhere in the world with individual academics making [organs on chips], so you have to have commercialization.”

Namandje Bumpus, the FDA’s chief scientist, agrees. “You can find differences [in outcomes] depending even on what types of reagents you’re using,” she says. Those differences mean research can’t be easily reproduced, which diminishes its validity and usefulness. “It would be great to have some standardization,” she adds.

On the plus side, the chip technology could help researchers address some of the most deeply entrenched health inequities in science. Clinical trials have historically recruited white men, underrepresenting people of color, women (especially pregnant and lactating women), the elderly, and other groups. And treatments derived from those trials all too often fail in members of those underrepresented groups, as in Moore’s rotavirus vaccine mystery. “With organs on a chip, you may be able to create systems by which you are very, very thoughtful—where you spread the net wider than has ever been done before,” says Moore.

two platforms
This microfluidic platform, designed by MIT engineers, connects engineered tissue from up to 10 organs.
FELICE FRANKEL

Another advantage is that chips will eventually reduce the need for animals in the lab even as they lead to better human outcomes. “There are aspects of animal research that make all of us uncomfortable, even people that do it,” acknowledges Moore. “The same values that make us uncomfortable about animal research are also the same values that make us uncomfortable with seeing human beings suffer with diseases that we don’t have cures for yet. So we always sort of balance that desire to reduce suffering in all the forms that we see it.”

Lorna Ewart, who spent 20 years at the pharma giant AstraZeneca before joining Emulate, thinks we’re entering a kind of transition time in research, in which scientists use in vitro technologies like organs on chips alongside traditional cell culture methods and animals. “As your confidence in using the chips grows, you might say, Okay, we don’t need two animals anymore—we could go with chip plus one animal,” she says. 

In the meantime, Sean Moore is excited about incorporating intestine chips more and more deeply into his research. His lab has been funded by the Gates Foundation to do what he laughingly describes as a bake-off between intestine chips made by Emulate and Mimetas. They’re infecting the chips with different strains of rotavirus to try to identify the pros and cons of each company’s design. It’s too early for any substantive results, but Moore says he does have data showing that organ chips are a viable model for studying rotavirus infection. That could ultimately be a real game-changer in his lab and in labs around the world.

“There’s more players in the space right now,” says Moore. “And that competition is going to be a healthy thing.” 

Harriet Brown writes about health, medicine, and science. Her most recent book is Shadow Daughter: A Memoir of Estrangement. She’s a professor of magazine, news, and digital journalism at Syracuse University’s Newhouse School. 

Should social media come with a health warning?

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here. 

Earlier this week, the US surgeon general, also known as the “nation’s doctor,” authored an article making the case that health warnings should accompany social media. The goal: to protect teenagers from its harmful effects. “Adolescents who spend more than three hours a day on social media face double the risk of anxiety and depression symptoms,” Vivek Murthy wrote in a piece published in the New York Times. “Additionally, nearly half of adolescents say social media makes them feel worse about their bodies.”

His concern instinctively resonates with me. I’m in my late 30s, and even I can end up feeling a lot worse about myself after a brief stint on Instagram. I have two young daughters, and I worry about how I’ll respond when they reach adolescence and start asking for access to whatever social media site their peers are using. My children already have a fascination with cell phones; the eldest, who is almost six, will often come into my bedroom at the crack of dawn, find my husband’s phone, and somehow figure out how to blast “Happy Xmas (War Is Over)” at full volume.

But I also know that the relationship between this technology and health isn’t black and white. Social media can affect users in different ways—often positively. So let’s take a closer look at the concerns, the evidence behind them, and how best to tackle them.

Murthy’s concerns aren’t new, of course. In fact, almost any time we are introduced to a new technology, some will warn of its potential dangers. Innovations like the printing press, radio, and television all had their critics back in the day. In 2009, the Daily Mail linked Facebook use to cancer.

More recently, concerns about social media have centered on young people. There’s a lot going on in our teenage years as our brains undergo maturation, our hormones shift, and we explore new ways to form relationships with others. We’re thought to be more vulnerable to mental-health disorders during this period too. Around half of such disorders are thought to develop by the age of 14, and suicide is the fourth-leading cause of death in people aged between 15 and 19, according to the World Health Organization. Many have claimed that social media only makes things worse.

Reports have variously cited cyberbullying, exposure to violent or harmful content, and the promotion of unrealistic body standards, for example, as potential key triggers of low mood and disorders like anxiety and depression. There have also been several high-profile cases of self-harm and suicide with links to social media use, often involving online bullying and abuse. Just this week, the suicide of an 18-year-old in Kerala, India, was linked to cyberbullying. And children have died after taking part in dangerous online challenges made viral on social media, whether from inhaling toxic substances, consuming ultra-spicy tortilla chips, or choking themselves.

Murthy’s new article follows an advisory on social media and youth mental health published by his office in 2023. The 25-page document, which lays out some of known benefits and harms of social media use as well as the “unknowns,” was intended to raise awareness of social media as a health issue. The problem is that things are not entirely clear cut.

“The evidence is currently quite limited,” says Ruth Plackett, a researcher at University College London who studies the impact of social media on mental health in young people. A lot of the research on social media and mental health is correlational. It doesn’t show that social media use causes mental health disorders, Plackett says.

The surgeon general’s advisory cites some of these correlational studies. It also points to survey-based studies, including one looking at mental well-being among college students after the rollout of Facebook in the mid-2000s. But even if you accept the authors’ conclusion that Facebook had a negative impact on the students’ mental health, it doesn’t mean that other social media platforms will have the same effect on other young people. Even Facebook, and the way we use it, has changed a lot in the last 20 years.

Other studies have found that social media has no effect on mental health. In a study published last year, Plackett and her colleagues surveyed 3,228 children in the UK to see how their social media use and mental well-being changed over time. The children were first surveyed when they were aged between 12 and 13, and again when they were 14 to 15 years old.

Plackett expected to find that social media use would harm the young participants. But when she conducted the second round of questionnaires, she found that was not the case. “Time spent on social media was not related to mental-health outcomes two years later,” she tells me.

Other research has found that social media use can be beneficial to young people, especially those from minority groups. It can help some avoid loneliness, strengthen relationships with their peers, and find a safe space to express their identities, says Plackett. Social media isn’t only for socializing, either. Today, young people use these platforms for news, entertainment, school, and even (in the case of influencers) business.

“It’s such a mixed bag of evidence,” says Plackett. “I’d say it’s hard to draw much of a conclusion at the minute.”

In his article, Murthy calls for a warning label to be applied to social media platforms, stating that “social media is associated with significant mental-health harms for adolescents.”

But while Murthy draws comparisons to the effectiveness of warning labels on tobacco products, bingeing on social media doesn’t have the same health risks as chain-smoking cigarettes. We have plenty of strong evidence linking smoking to a range of diseases, including gum disease, emphysema, and lung cancer, among others. We know that smoking can shorten a person’s life expectancy. We can’t make any such claims about social media, no matter what was written in that Daily Mail article.

Health warnings aren’t the only way to prevent any potential harms associated with social media use, as Murthy himself acknowledges. Tech companies could go further in reducing or eliminating violent and harmful content, for a start. And digital literacy education could help inform children and their caregivers how to alter the settings on various social media platforms to better control the content children see, and teach them how to assess the content that does make it to their screens.

I like the sound of these measures. They might even help me put an end to the early-morning Christmas songs. 


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Bills designed to make the internet safer for children have been popping up across the US. But individual states take different approaches, leaving the resulting picture a mess, as Tate Ryan-Mosley explored.

Dozens of US states sued Meta, the parent company of Facebook, last October. As Tate wrote at the time, the states claimed that the company knowingly harmed young users, misled them about safety features and harmful content, and violated laws on children’s privacy.  

China has been implementing increasingly tight controls over how children use the internet. In August last year, the country’s cyberspace administrator issued detailed guidelines that include, for example, a rule to limit use of smart devices to 40 minutes a day for children under the age of eight. And even that use should be limited to content about “elementary education, hobbies and interests, and liberal arts education.” My colleague Zeyi Yang had the story in a previous edition of his weekly newsletter, China Report.

Last year, TikTok set a 60-minute-per-day limit for users under the age of 18. But the Chinese domestic version of the app, Douyin, has even tighter controls, as Zeyi wrote last March.

One way that social media can benefit young people is by allowing them to express their identities in a safe space. Filters that superficially alter a person’s appearance to make it more feminine or masculine can help trans people play with gender expression, as Elizabeth Anne Brown wrote in 2022. She quoted Josie, a trans woman in her early 30s. “The Snapchat girl filter was the final straw in dropping a decade’s worth of repression,” Josie said. “[I] saw something that looked more ‘me’ than anything in a mirror, and I couldn’t go back.”

From around the web

Could gentle shock waves help regenerate heart tissue? A trial of what’s being dubbed a “space hairdryer” suggests the treatment could help people recover from bypass surgery. (BBC)

“We don’t know what’s going on with this virus coming out of China right now.” Anthony Fauci gives his insider account of the first three months of the covid-19 pandemic. (The Atlantic)

Microplastics are everywhere. It was only a matter of time before scientists found them in men’s penises. (The Guardian)

Is the singularity nearer? Ray Kurzweil believes so. He also thinks medical nanobots will allow us to live beyond 120. (Wired)

Biotech companies are trying to make milk without cows

The outbreak of avian influenza on US dairy farms has started to make milk seem a lot less wholesome. Milk that’s raw, or unpasteurized, can actually infect mice that drink it, and a few dairy workers have already caught the bug. 

The FDA says that commercial milk is safe because it is pasteurized, killing the germs. Even so, it’s enough to make a person ponder a life beyond milk—say, taking your coffee black or maybe drinking oat milk.

But for those of us who can’t do without the real thing, it turns out some genetic engineers are working on ways to keep the milk and get rid of the cows instead. They’re doing it by engineering yeasts and plants with bovine genes so they make the key proteins responsible for milk’s color, satisfying taste, and nutritional punch.

The proteins they’re copying are casein, a floppy polymer that’s the most abundant protein in milk and is what makes pizza cheese stretch, and whey, a nutritious combo of essential amino acids that’s often used in energy powders.

It’s part of a larger trend of replacing animals with ingredients grown in labs, steel vessels, or plant crops. Think of the Impossible burger, the veggie patty made mouthwatering with the addition of heme, a component of blood that’s produced in the roots of genetically modified soybeans.

One of the milk innovators is Remilk, an Israeli startup founded in 2019, which has engineered yeast so it will produce beta-lactoglobulin (the main component of whey). Company cofounder Ori Cohavi says a single biotech factory of bubbling yeast vats feeding on sugar could in theory “replace 50,000 to 100,000 cows.” 

Remilk has been making trial batches and is testing ways to formulate the protein with plant oils and sugar to make spreadable cheese, ice cream, and milk drinks. So yes, we’re talking “processed” food—one partner is a local Coca-Cola bottler, and advising the company are former executives of Nestlé, Danone, and PepsiCo.

But regular milk isn’t exactly so natural either. At milking time, animals stand inside elaborate robots, and it looks for all the world as if they’re being abducted by aliens. “The notion of a cow standing in some nice green scenery is very far from how we get our milk,” says Cohavi. And there are environmental effects: cattle burp methane, a potent greenhouse gas, and a lactating cow needs to drink around 40 gallons of water a day

“There are hundreds of millions of dairy cows on the planet producing greenhouse waste, using a lot of water and land,” says Cohavi. “It can’t be the best way to produce food.”  

For biotech ventures trying to displace milk, the big challenge will be keeping their own costs of production low enough to compete with cows. Dairies get government protections and subsidies, and they don’t only make milk. Dairy cows are eventually turned into gelatin, McDonald’s burgers, and the leather seats of your Range Rover. Not much goes to waste.

At Alpine Bio, a biotech company in San Francisco (also known as Nobell Foods), researchers have engineered soybeans to produce casein. While not yet cleared for sale, the beans are already being grown on USDA-sanctioned test plots in the Midwest, says Alpine’s CEO, Magi Richani

Richani chose soybeans because they’re already a major commodity and the cheapest source of protein around. “We are working with farmers who are already growing soybeans for animal feed,” she says. “And we are saying, ‘Hey, you can grow this to feed humans.’ If you want to compete with a commodity system, you have to have a commodity crop.”

Alpine intends to crush the beans, extract the protein, and—much like Remilk—sell the ingredient to larger food companies.

Everyone agrees that cow’s milk will be difficult to displace. It holds a special place in the human psyche, and we owe civilization itself, in part, to domesticated animals. In fact, they’ve  left their mark in our genes, with many of us carrying DNA mutations that make cow’s milk easier to digest.  

But that’s why it might be time for the next technological step, says Richani. “We raise 60 billion animals for food every year, and that is insane. We took it too far, and we need options,” she says. “We need options that are better for the environment, that overcome the use of antibiotics, and that overcome the disease risk.”

It’s not clear yet whether the bird flu outbreak on dairy farms is a big danger to humans. But making milk without cows would definitely cut the risk that an animal virus will cause a new pandemic. As Richani says: “Soybeans don’t transmit diseases to humans.”


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Hungry for more from the frontiers of fromage? In the Build issue of our print magazine, Andrew Rosenblum tasted a yummy brie made only from plants. Harder to swallow was the claim by developer Climax Foods that its cheese was designed using artificial intelligence.

The idea of using yeast to create food ingredients, chemicals, and even fuel via fermentation is one of the dreams of synthetic biology. But it’s not easy. In 2021, we raised questions about high-flying startup Ginkgo Bioworks. This week its stock hit an all-time low of $0.49 per share as the company struggles to make … well, anything.

This spring, I traveled to Florida to watch attempts to create life in a totally new way: using a synthetic embryo made in a lab. The action involved cattle at the animal science department of the University of Florida, Gainesville.


From around the web

How many human bird flu cases are there? No one knows, because there’s barely any testing. Scientists warn we’re flying blind as US dairy farms struggle with an outbreak. (NBC)  

Moderna, one of the companies behind the covid-19 shots, is seeing early success with a cancer vaccine. It uses the same basic technology: gene messages packed into nanoparticles. (Nature)

It’s the covid-19 theory that won’t go away. This week the New York Times published an op-ed arguing that the virus was the result of a lab accident. We previously profiled the author, Alina Chan, who is a scientist with the Broad Institute. (NYTimes)

Sales of potent weight loss drugs, like Ozempic, are booming. But it’s not just humans who are overweight. Now the pet care industry is dreaming of treating chubby cats and dogs, too. (Bloomberg)

FDA advisors just said no to the use of MDMA as a therapy

On Tuesday, the FDA asked a panel of experts to weigh in on whether the evidence shows that MDMA, also known as ecstasy, is a safe and efficacious treatment for PTSD. The answer was a resounding no. Just two out of 11 panel members agreed that MDMA-assisted therapy is effective. And only one panel member thought the benefits of the therapy outweighed the risks.

The outcome came as a surprise to many, given that trial results have been positive. And it is also a blow for advocates who have been working to bring psychedelic therapy into mainstream medicine for more than two decades. This isn’t the final decision on MDMA. The FDA has until August 11 to make that ruling. But while the agency is under no obligation to follow the recommendations of its advisory committees, it rarely breaks with their decisions.  

Today on The Checkup, let’s unpack the advisory committee’s vote and talk about what it means for the approval of other recreational drugs as therapies.

One of the main stumbling blocks for the committee was the design of the two efficacy studies that have been completed. Trial participants weren’t supposed to know whether they were in the treatment group, but the effects of MDMA make it pretty easy to tell whether you’ve been given a hefty dose, and most correctly guessed which group they had landed in. 

In 2021, MIT Technology Review’s Charlotte Jee interviewed an MDMA trial participant named Nathan McGee. “Almost as soon as I said I didn’t think I’d taken it, it kicked in. I mean, I knew,” he told her. “I remember going to the bathroom and looking in the mirror, and seeing my pupils looking like saucers. I was like, ‘Wow, okay.’”

The Multidisciplinary Association for Psychedelic Studies, better known as MAPS, has been working with the FDA to develop MDMA as a treatment since 2001. When the organization met with the FDA in 2016 to hash out the details of its phase III trials, studies to test whether a treatment works, agency officials suggested that MAPS use an active compound for the control group to help mask whether participants had received the drug. But MAPS pushed back, and the trial forged ahead with a placebo. 

No surprise, then, that about 90% of those assigned to the MDMA group and 75% of those assigned to the placebo group accurately identified which arm of the study they had landed in. And it wasn’t just participants. Therapists treating the participants also likely knew whether those under their supervision had been given the drug. It’s called “functional unblinding,” and the issue came up at the committee meeting again and again. Here’s why it’s a problem: If a participant strongly believes that MDMA will help their PTSD and they know they’ve received MDMA, this expectation bias could amplify the treatment effect. This is especially a problem when the outcome is based on subjective measures like how a person feels rather than, say, laboratory data.

Another sticking point was the therapy component of the treatment. Lykos Therapeutics (the for-profit spinoff of MAPS) asked the FDA to approve MDMA-assisted therapy: that’s MDMA administered in concert with psychotherapy. Therapists oversaw participants during the three MDMA sessions. But participants also received three therapy sessions before getting the drug, and three therapy sessions afterwards to help them process their experience. 

Because the two treatments were administered together, there was no good way to tell how much of the effect was due to MDMA and how much was due to the therapy. What’s more, “the content or approach of these integrated sessions was not standardized in the treatment manuals and was mainly left up to the individual therapist,” said David Millis, a clinical reviewer for the FDA, at the committee meeting. 

Several committee members also raised safety concerns. They worried that MDMA’s effects might make people more suggestible and vulnerable to abuse, and they brought up allegations of ethics violations outlined in a recent report from the Institute for Clinical and Economic Review

Because of these issues and others, most committee members felt compelled to vote against MDMA-assisted therapy. “I felt that the large positive effect was denuded by the significant confounders,” said committee member Maryann Amirshahi, a professor of emergency medicine at Georgetown University School of Medicine, after the vote. “Although I do believe that there was a signal, it just needs to be better studied.”

Whether this decision will be a setback for the entire field remains to be seen. “To make it crystal clear: It isn’t MDMA itself that was rejected per se, but the specific, poor data set provided by Lykos Therapeutics; in my opinion, there is still a strong chance that MDMA, with a properly conducted clinical Phase 3 trial program that addresses those concerns of the FDA advisory committee, will get approved.” wrote Christian Angermayer, founder of ATAI Therapeutics, a company that is also working to develop MDMA as a therapy.

If the FDA denies approval of MDMA therapy, Lykos or another company could conduct additional studies and reapply. Many of the committee members said they believed MDMA does hold promise, but that the studies conducted thus far were inadequate to demonstrate the drug’s safety and efficacy. 

Psilocybin is likely to be the next psychedelic therapy considered by the FDA, and in some ways, it might have an easier path to approval. The idea behind MDMA is that it alleviates PTSD by helping facilitate psychotherapy. The therapy is a crucial component of the treatment, which is problematic because the FDA regulates drugs, not psychotherapy. With psilocybin, a therapist is present, but the drug appears to do the heavy lifting. “We are not offering therapy; we are offering psychological support that’s designed for the patient’s safety and well-being,” says Kabir Nath, CEO of Compass Pathways, the company working to bring psilocybin to market. “What we actually find during a six- to eight-hour session is most of it is silent. There’s actually no interaction.”

That could make the approval process more straightforward. “The difficult thing … is that we don’t regulate psychotherapy, and also we don’t really have any say in the design or the implementation of the particular therapy that is going to be used,” said Tiffany  Farchione, director of the FDA’s division of psychiatry, at the committee meeting. “This is something unprecedented, so we certainly want to get as many opinions and as much input as we can.” 

Another thing

Earlier this week, I explored what might happen if MDMA gets FDA approval and how the decision could affect other psychedelic therapies. 

Sally Adee dives deep into the messy history of electric medicine and what the future might hold for research into electric therapies. “Instead of focusing only on the nervous system—the highway that carries electrical messages between the brain and the body—a growing number of researchers are finding clever ways to electrically manipulate cells elsewhere in the body, such as skin and kidney cells, more directly than ever before,” she writes. 


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Psychedelics are undeniably having a moment, and the therapy might prove particularly beneficial to women, wrote Taylor Majewski in this feature from 2022.

In a previous issue of The Checkup, Jessica Hamzelou argued that the psychedelic hype bubble might be about to burst.

MDMA does seem to have helped some individuals. Nathan McGee, who took the drug as part of a clinical trial, told Charlotte Jee that he “understands what joy is now.” 

Researchers are working to design virtual-reality programs that recreate the trippy experience of taking psychedelics. Hana Kiros has the story

From around the web

In April I wrote about Lisa Pisano, the second person to receive a pig kidney. This week doctors removed the kidney after it failed owing to lack of blood flow.

Bird flu is still very much in the news.

–   Finland is poised to become the first country to start administering bird flu vaccine—albeit to a very limited subset of people, including poultry and mink farmers, vets, and scientists who study the virus  (Stat)

–   What are the most pressing questions about bird flu? They revolve around what’s happening in cows, what’s happening in farm workers, and what’s happening to the virus. (Stat)

– A man in Mexico has died of H5N2, a strain of bird flu that has never before been reported in humans. (CNN)

Biodegradable, squishy sensors injected into the brain hold promise for detecting changes following a head injury or cancer treatment. (Nature)

A synthetic version of a hallucinogenic toad toxin could be a promising treatment for mental-health disorders. (Undark)

What’s next for MDMA

MIT Technology Review’s What’s Next series looks across industries, trends, and technologies to give you a first look at the future. You can read the rest of them here.

MDMA, sometimes called Molly or ecstasy, has been banned in the United States for more than three decades. Now this potent mind-altering drug is poised to become a badly needed therapy for PTSD.

On June 4, the Food and Drug Administration’s advisory committee will meet to discuss the risks and benefits of MDMA therapy. If the committee votes in favor of the drug, it could be approved to treat PTSD this summer. The approval would represent a momentous achievement for proponents of mind-altering drugs, who have been working toward this goal for decades. And it could help pave the way for FDA approval of other illicit drugs like psilocybin. But the details surrounding how these compounds will make the transition from illicit substances to legitimate therapies are still foggy. 

Here’s what to know ahead of the upcoming hearing. 

What’s the argument for legitimizing MDMA? 

Studies suggest the compound can help treat mental-health disorders like PTSD and depression. Lykos, the company that has been developing MDMA as a therapy, looked at efficacy in two clinical trials that included about 200 people with PTSD. Researchers randomly assigned participants to receive psychotherapy with or without MDMA. The group that received MDMA-assisted therapy had a greater reduction in PTSD symptoms. They were also more likely to respond to treatment, to meet the criteria for PTSD remission, and to lose their diagnosis of PTSD.

But some experts question the validity of the results. With substances like MDMA, study participants almost always know whether they’ve received the drug or a placebo. That can skew the results, especially when the participants and therapists strongly believe a drug is going to help. The Institute for Clinical and Economic Review (ICER), a nonprofit research organization that evaluates the clinical and economic value of drugs, recently rated the evidence for MDMA-assisted therapy as “insufficient.

In briefing documents published ahead of the June 4 meeting, FDA officials write that the question of approving MDMA “presents a number of complex review issues.”

The ICER report also referenced allegations of misconduct and ethical violations. Lykos (formerly the Multidisciplinary Association for Psychedelic Studies Public Benefit Corporation) acknowledges that ethical violations occurred in one particularly high-profile case. But in a rebuttal to the ICER report, more than 70 researchers involved in the trials wrote that “a number of assertions in the ICER report represent hearsay, and should be weighted accordingly.” Lykos did not respond to an interview request.

At the meeting on the 4th, the FDA has asked experts to discuss whether Lykos has demonstrated that MDMA is effective, whether the drug’s effect lasts, and what role psychotherapy plays. The committee will also discuss safety, including the drug’s potential for abuse and the risk posed by the impairment MDMA causes. 

What’s stopping people from using this therapy?

MDMA is illegal. In 1985, the Drug Enforcement Agency grew concerned about growing street use of the drug and added it to its list of Schedule 1 substances—those with a high abuse potential and no accepted medical use. 

MDMA boosts the brain’s production of feel-good neurotransmitters, causing a burst of euphoria and good will toward others. But the drug can also cause high blood pressure, memory problems, anxiety, irritability, and confusion. And repeated use can cause lasting changes in the brain

If the FDA approves MDMA therapy, when will people be able to access it?

That has yet to be determined. It could take months for the DEA to reclassify the drug. After that, it’s up to individual states. 

Lykos applied for approval of MDMA-assisted therapy, not just the compound itself. In the clinical trials, MDMA administration happened in the presence of licensed therapists, who then helped patients process their emotions during therapy sessions that lasted for hours.

But regulating therapy isn’t part of the FDA’s purview. The FDA approves drugs; it doesn’t oversee how they’re administered. “The agency has been clear with us,” says Kabir Nath, CEO of Compass Pathways, the company working to bring psilocybin to market. “They don’t want to regulate psychotherapy, because they see that as the practice of medicine, and that’s not their job.” 

However, for drugs that carry a risk of serious side effects, the FDA can add a risk evaluation and mitigation strategy to its approval. For MDMA that might include mandating that the health-care professionals who administer the medication have certain certifications or specialized training, or requiring that the drug be dispensed only in licensed facilities. 

For example, Spravato, a nasal spray approved in 2019 for depression that works much like ketamine, is available only at a limited number of health-care facilities and must be taken under the observation of a health-care provider. Having safeguards in place for MDMA makes sense, at least at the outset, says Matt Lamkin, an associate professor at the University of Tulsa College of Law who has been following the field closely.: “Given the history, I think it would only take a couple of high-profile bad incidents to potentially set things back.”

What mind-altering drug is next in line for FDA approval?

Psilocybin, a.k.a. the active ingredient in magic mushrooms. This summer Compass Pathways will release the first results from one of its phase 3 trials of psilocybin to treat depression. Results from the other trial will come in the middle of 2025, which—if all goes well—puts the company on track to file for approval in the fall or winter of next year. With the FDA review and the DEA rescheduling, “it’s still kind of two to three years out,” Nath says.

Some states are moving ahead without formal approval. Oregon voters made psilocybin legal in 2020, and the drug is now accessible there at about 20 licensed centers for supervised use. “It’s an adult use program that has a therapeutic element,” says Ismail Ali, director of policy and advocacy at the Multidisciplinary Association for Psychedelic Studies (MAPS).

Colorado voted to legalize psilocybin and some other plant-based psychedelics in 2022, and the state is now working to develop a framework to guide the licensing of facilitators to administer these drugs for therapeutic purposes. More states could follow. 

So would FDA approval of these compounds open the door to legal recreational use of psychedelics?

Maybe. The DEA can still prosecute physicians if they’re prescribing drugs outside of their medically accepted uses. But Lamkin does see the lines between recreational use and medical use getting blurry. “What we’re seeing is that the therapeutic uses have recreational side effects and the recreation has therapeutic side effects,” he says. “I’m interested to see how long they can keep the genie in the bottle.”

What’s the status of MDMA therapies elsewhere in the world? 

Last summer, Australia became the first country to approve MDMA and psilocybin as medicines to treat psychiatric disorders, but the therapies are not yet widely available. The first clinic opened just a few months ago. The US is poised to become the second country if the FDA greenlights Lykos’s application. Health Canada told the CBC it is watching the FDA’s review of MDMA “with interest.” Europe is lagging a bit behind, but there are some signs of movement. In April, the European Medicines Agency convened a workshop to bring together a variety of stakeholders to discuss a regulatory framework for psychedelics.