He Wants to Eliminate Inherited Diseases in Embryos. Congress Just Said No (Again).
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Biologist Shoukhrat Mitalipov is famous—and controversial--in the world of cutting-edge fertility treatments. A decade ago, he pioneered mitochondrial replacement therapy, paving the way for the world's first "three-parent" babies to be born free of a devastating inherited disease.
He sees his work toward embryo gene therapy as not only moral, but necessary.
In 2017, he shocked the world again when his group at Oregon Health and Science University became the first to repair a genetic mutation causing heart disease in dozens of human embryos. The embryos were later destroyed a part of the experiment; current policy in the U.S. prohibits such research from moving into clinical trials.
And that policy doesn't look like it's going to change anytime soon, despite recent political wavering. Last month, a House subcommittee dropped the ban that has blocked the Food and Drug Administration since 2015 from considering any clinical trials of genetically altered embryos intended to create a baby. The move raised the hopes of supporters who want to see such research move forward and angered critics who feel that the science is getting ahead of the ethics. But yesterday, a House committee decided to restore the ban on gene-edited babies after all.
As for Mitalipov, he told leapsmag that he sees his work toward embryo gene therapy as not only moral, but necessary. This interview has been edited and condensed for clarity.
What motivates you to pursue this line of research, even though it is highly controversial?
It's my expertise, I'm an embryologist. We study early development in humans -- sperm, egg, and the first five days of development -- and try to use our knowledge to treat human diseases, particularly in that early stage. This is how IVF started, as a treatment for infertility. It's a very successful cell therapy treatment, with millions of children born. [Now the idea is] to actually to use this IVF platform not as much to treat infertility, but also to treat heritable genetic diseases, because this is a very important stage when gametes from either dad or mom will transmit mutations. This is the bottleneck where we could actually interfere and repair that mutation.
Many people are hesitant to support embryo editing because of "designer babies," yet polls do show that Americans are more open to embryo editing for the purpose of disease prevention. Where should society draw a line?
Yeah, I agree with most Americans that we don't have to edit -- meaning you could make all kind of changes. Instead we do gene repair, which is a therapeutic application.
Gene repair is quite different than gene editing. It involves [focusing on] already known disease-causing mutations and how we can turn them back to normal.
Thousands of gene mutations cause human diseases, like Crohn's, for example, or mutations causing cancer, heart disease. These are well-described, well-studied cause-and-effect diseases and we need to do something about it because otherwise it's impossible to treat once the mutation is already passed to a child.
Early intervention is the best in any disease, but in genetics, "early" means you have to do it at the time of fertilization. That's when we are dealing with one copy of the mutation or maybe two, versus when you have a whole body with billions of cells in solid tissues that we cannot really access and target. So this is the most efficient way of preventing thousands and thousands of genetic diseases. I understand that we have to make sure that it's very safe, of course, and efficient as well. But at the same time, I think this is the future. We have to work toward developing these technologies.
"If we continue banning the research everywhere and not funding it, maybe 100 years will not be enough."
What's your opinion of Dr. He Jiankui and the Chinese CRISPR'ed babies?
This is a case where he was doing gene editing, not gene repair. He hasn't corrected anything, he induced a mutation to normal human genes, hoping that this would somehow confer resistance to HIV, which is still unclear.
I think such straightforward editing is unacceptable specifically for human embryos. He's approach has also never been tested in an animal model. That's why the reaction from the public and scientists was very negative, because this is the case where the doctor does this without any expertise in this area, without knowing probably much about what he is doing, and he acquired it without any oversights, which is troubling. And of course, it negatively affects the legitimate research that is going on in some labs.
What might the future of embryo gene therapy look like?
Hopefully in 10 years from now, thousands and thousands of families that know they carry germline mutations…could go through IVF and we would correct it, and they could have healthy children.
Right now, we have some tools. We cannot correct, but we can select. So what happens is the parents become pregnant and then at about three months along, we can biopsy the amniotic fluid and say, "Hey unfortunately you passed on this mutation." And that means this child, if it's born, will be affected, so we give parents a choice of terminating the pregnancy.
Or we could do it much earlier, so parents go to the IVF clinic where we retrieve about ten eggs, after stimulating a woman's ovaries. Each of them will be fertilized so we have ten embryos that develop. We have a five-day window where we can keep them in the lab. And we basically reap a few cells, we do a biopsy from each of these ten, and we say, "Hey embryo number 1 and number 4 are not mutant, but the others are."
Then we can take these two and the other eight usually will be thrown away. That's the technology that we have now. Some ethicists argue on religious grounds that we have this selection technology available, so why do we need germline gene therapy [i.e. repairing the disease-causing mutations in an embryo]?
I don't understand the moral argument there, because all the available technology is based on selective destruction of the embryo.
With [IVF gene therapy], we will take ten embryos and every embryo we'll make healthy because we can get rid of the mutations. How could embryo destruction be morally superior?
How long do you think it will take for this technology to be available to prospective parents?
It depends how many legitimate labs with expertise can get into this field and resolve all the scientific questions. If we continue banning the research everywhere and not funding it, maybe 100 years will not be enough.
So far, I think that my lab is the only one legitimately working on it. But we would like five, 10, maybe 100 labs in this country and Europe really working. Because we have scientific challenges that we need to resolve before we could say, "Hey now we know how to correct [a given mutation] and now this could be efficient, and there are no side effects or very little." And then we could say, "Okay, I think we've done everything we could in petri dishes and in animals, and now we are ready to transplant this embryo in a patient and see what happens."
"There's just no way you could sink your head into the sand and say, 'Oh, we just ban it and then hopefully everything will go away.'"
Does banning emerging technology actually work?
Banning it usually means it will leak out to a gray area where there's no regulation and many private IVF clinics will just use it while it is still premature. So I think we have to regulate the clinical testing. There's just no way you could sink your head into the sand and say, "Oh, we just ban it and then hopefully everything will go away." That's not going to happen.
If this technology does become feasible and legal in the future, do you think that more and more couples will choose IVF and gene therapy versus the natural method of rolling the dice?
As sequencing technology is becoming available, like 23andMe, more and more parents will realize what kind of mutations they carry. And if your spouse carries the same mutation on the same locus, now you have very high chance of transmitting it. Most of the time today, we find out these families carry it once they have one or two children with that condition.
Of course, parents can just do it naturally in the bedroom and have a chance of transmitting or not transmitting mutations, but hopefully eventually we can say, "Hey, because of your condition, you don't want to play this Russian Roulette. Let's just do IVF." And hopefully the government will cover that kind of treatment because right now IVF is not covered in most states. And we do this therapy and then they have a healthy child.
We have 10,000 different mutations in the human population. That means probably billions of people carry mutations. And unless they go through this gene therapy through IVF, they will keep transmitting them. And we're going to keep having millions and millions of children with diseases. We have to do something about it.
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Niklas Anzinger is the founder of Infinita VC based in the charter city of Prospera in Honduras. Infinita focuses on a new trend of charter cities and other forms of alternative jurisdictions. Healso hosts a podcast about how to accelerate the future by unblocking “stranded technologies”.This spring he was a part of the network city experiment Zuzalu spearheaded by Ethereum founder Vitalik Buterin where a few hundred invited guests from the spheres of longevity, biotechnology, crypto, artificial intelligence and investment came together to form a two-monthlong community. It has been described as the world’s first pop-up city. Every morning Vitalians would descend on a long breakfast—the menu had been carefully designed by famed radical longevity self-experimenter Bryan Johnson—and there is where I first met Anzinger who told me about Prospera. Intrigued to say the least, I caught up with him later the same week and the following is a record of our conversation.
Q. We are sitting here in the so-called pop-up network state Zuzalu temporarily realized in the village of Lusticia Bay by the beautiful Mediterranean Sea. To me this is an entirely new concept: What is a network state?
A. A network state is a highly aligned online community that has a level of in-person civility; it crowd-funds territory, and it eventually seeks diplomatic recognition. In a way it's about starting a new country. The term was coined by the crypto influencer and former CTO of Coinbase Balaji Srinivasan in a book by the same title last year [2022]. What many people don't know is that it is a more recent addition or innovation in a space called competitive governance. The idea is that you have multiple jurisdictions competing to provide you services as a customer. When you have competition among governments or government service providers, these entities are forced to provide you with a better service instead of the often worse service at higher prices or higher taxes that we're currently getting. The idea went from seasteading, which was hardly feasible because of costs, to charter cities getting public/private partnerships with existing governments and a level of legal autonomy, to special economic zones, to now network states.
Q. How do network states compare to charter cities and similar jurisdictions?
A. Charter cities and special economic zones were legal forks from other existing states. Dubai, Shenzhen in China, to some degree Hong Kong, to some degree Singapore are some examples. There's a host of other charter cities, one of which I'm based in myself, which is Prospera located in Honduras on the island Roatán. Charter cities provide the full stack of governance; they provide new laws and regulations, business registration, tax codes and governance services, Estonia style: you log on to the government platform and you get services as a citizen.
When conceptualizing network states, Balagi Srinivasan turns the idea of a charter city a bit on its head: he doesn't want to start with this full stack because it's still very hard to get these kinds of partnerships with government. It's very expensive and requires lots of experience and lots of social capital. He is saying that network states could instead start as an online community. They could have a level of alignment where they trade with each other; they have their own economy; they meet in person in regular gatherings like we're doing here in Zuzulu for two months, and then they negotiate with existing governments or host cities to get a certain degree of legal autonomy that is centered around a moral innovation. So, his idea is: don't focus on building a completely new country or city; focus on a moral innovation.
Q. What would be an example of such a moral innovation?
A. An example would be longevity—life is good; death is bad—let's see what we can do to foster progress around that moral innovation and see how we can get legal forks from the existing system that allow us to accelerate progress in that area. There is an increasing realization in the science that there are hallmarks of aging and that aging is a cause of other diseases like cancer, ALS or Alzheimer's. But aging is not recognized as a disease by the FDA in the United States and in most countries around the world, so it's very hard to get scientific funding for biotechnology that would attack the hallmarks of aging and allow us potentially to reverse aging and extend life. This is a significant shortcoming of existing government systems that groups such as the ones that have come together here in Montenegro are now seeking alternatives too. Charter cities and now network states are such alternatives.
Q. Would it not be better to work within the current systems, and try to improve them, rather than abandon them for new experimental jurisdictions?
A. There are numerous failures of public policies. These failures are hard, if not impossible, to reverse, because as soon as you have these policies, you have entrenched interests who benefit from the regulations. The only way to disrupt incumbent industries is with start-ups, but the way the system is set up makes it excessively hard for such start-ups to become big companies. In fact, larger companies are weaponizing the legal system against small companies, because they can afford the lawyers and the fixed cost of compliance.
I don't believe that our institutions in many developed countries are beyond hope. I just think it's easier to change them if you could point at successful examples. ‘Hey, this country or this zone is already doing it very successfully’; if they can extend people’s lifespan by 10 years, if they can reduce maternal mortality, and if they have a massive medical tourism where people come back healthier, then that is just very embarrassing for the FDA.
Q. Perhaps a comparison here would be the relationship between Hong Kong and China?
A. Correct, so having Hong Kong right in front of your door … ‘Hey, this capitalism thing seems to work, why don't we try it here?’ It was due to the very bold leadership by Deng Xiaoping that they experimented with it in the development zone of Shenzhen. It worked really well and then they expanded with more special economic zones that also worked.
Próspera is a private city and special economic zone on the island of Roatán in the Central American state of Honduras.
Q. Tell us about Prospera, the charter city in Honduras, that you are intimately connected with.
A. Honduras is a very poor country. It has a lot of crime, never had a single VC investment, and has a GDP per capita of 2,000 per year. Honduras has suffered tremendously. The goal of these special economic zones is to bring in economic development. That's their sole purpose. It's a homegrown innovation from Honduras that started in 2009 with a very forward-thinking statesman, Octavio Sanchez, who was the chief of staff to the president of Honduras, and then president. He had his own ideas about making Honduras a more decentralized system, where more of the power lies in the municipalities.
Inspired by the ideas of Nobel laureate economist Paul Romer, who gave a famous Ted Talk in 2009 about charter cities, Sanchez initiated a process that lasted for years and eventually led to the creation of a special economic zone legal regime that’s anchored in the Hunduran constitution that provides the highest legal autonomy in the world to these zones. There are today three special economic zones approved by the Honduran government: Prospera, Ciudad Morazan and Orchidea.
Q. How did you become interested and then involved in Prospera?
A. I read about it first in an article by Scott Alexander, a famous rationalist blogger, who wrote a very long article about Prospera, and I thought, this is amazing! Then I came to Prospera and I found it to be one of the most if not the most exciting project in the world going on right now and that it also opened my heart to the country and its people. Most of my friends there are Honduran, they have been working on this for 10 or more years. They want to remake Honduras and put it on the map as the place in the world where this legal and governance innovation started.
Q. To what extent is Prospera autonomous relative to the Honduran government?
A. What's interesting about the Honduran model is that it's anchored within the Honduran constitution, and it has a very clear framework for what's possible and what's not possible, and what's possible ensures the highest degree of legal autonomy anywhere seen in the world. Prospera has really pushed the model furthest in creating a common law-based polycentric legal system. The idea is that you don't have a legislature, instead you have common law and it's based on the best practice common law principles that a legal scholar named Tom W. Bell created.
One of the core ideas is that as a business you're not obligated to follow one regulatory monopoly like the FDA. You have regulatory flexibility so you can choose what you're regulated under. So, you can say: ‘if I do a medical clinic, I do it under Norwegian law here’. And you even have the possibility to amend it a bit. You're still required to have liability insurance, and have to agree to binding arbitration in case there's a legal dispute. And your insurance has to approve you. So, under that model the insurance becomes the regulator and they regulate through prices. The limiting factor is criminal law; Honduran criminal law fully applies. So does immigration law. And we pay taxes.
Q. Is there also an idea of creating a kind of healthy living there, and encourage medical tourism?
A. Yes, we specifically look for legal advantages in autonomy around creating new drugs, doing clinical trials, doing self-medication and experimentation. There is a stem cell clinic here and they're doing clinical trials. The island of Roatán is very easily accessible for American tourists. It's a beautiful island, and it's for regulatory reasons hard to do stem cell therapies in the United States, so they're flying in patients from the United States. Most of them are very savvy and often have PhDs in biotech and are able to assess the risk for themselves of taking drugs and doing clinical trials. We're also going to get a wellness center, and there have been ideas around establishing a peptide clinic and a compound pharmacy and things like that. We are developing a healthcare ecosystem.
Q. This kind of experimental tourism raises some ethical issues. What happens if patients are harmed? And what are the moral implications for society of these new treatments?
A. As a moral principle we believe in medical freedom: people have rights over their bodies, even at the (informed) risk of harm to themselves if no unconsenting third-parties are harmed; this is a fundamental right currently not protected effectively.
What we do differently is not changing ethical norms around safety and efficacy, we’re just changing the institutional setup. Instead of one centralized bureaucracy, like the FDA, we have regulatory pluralism that allows different providers of safety and efficacy to compete under market rules. Like under any legal system, common law in Prospera punishes malpractice, fraud, murder etc. This system will still produce safe and effective drugs, and it will still work with common sense legal notions like informed consent and liability for harm. There are regulations for medical practice, there is liability insurance and things like that. It will just do so more efficiently than the current way of doing things (unless it won’t, in which case it will change and evolve – or fail).
A direct moral benefit ´to what we do is that we increase accessibility. Typical gene therapies on the market cost $1 million dollars in the US. The gene therapy developed in Prospera costs $25,000. As to concern about whether such treatments are problematic, we do not share this perspective. We are for advancing science responsibly and we believe that both individuals and society stand to gain from improving the resiliency of the human body through advanced biotechnology.
Q. How does Prospera relate to the local Honduran population?
A. I think it's very important that our projects deliver local benefits and that they're well anchored in local communities. Because when you go to a new place, you're seen as a foreigner, and you're seen as potentially a danger or a threat. The most important thing for Prospera and Ciudad Morazan is to show we're creating jobs; we're creating employment; we're improving people's lives on the ground. Prospera is directly and indirectly employing 1,100 people. More than 2/3 of the people who are working for Prospera are Honduran. It has a lot of local service workers from the island, and it has educated Hondurans from the mainland for whom it's an alternative to going to the United States.
Q. What makes a good Prosperian citizen?
A. People in Prospera are very entrepreneurial. They're opening companies on a small scale. For example, Vehinia, who is the cook in the kitchen at Prospera, she's from the neighboring village and she started an NGO that is now funding a school where children from the local village can go to instead of a school that's 45 minutes away. There's very much a spirit of ‘let's exchange and trade with each other’. Some people might see that as a bit too commercial, but that's something about the culture that people accept and that people see as a good thing.
Q. Five years from now, if everything goes well, what do we see in Prospera?
A. I think Prospera will have at least 10,000 residents and I think Honduras hopefully will have more zones. There could be zones with a thriving industrial sector and sort of a labor-intensive economy and some that are very strong in pharmaceuticals, there could also be other zones for synthetic biology, and other zones focused on agriculture. The zones of Prospera, Ciudad Morazan and Orchidea are already showing the results we want to see, the results that we will eventually be measured by, and I'm tremendously excited about Honduras.
How to Measure Your Stress, with Dr. Rosalind Picard
Today’s podcast guest is Rosalind Picard, a researcher, inventor named on over 100 patents, entrepreneur, author, professor and engineer. When it comes to the science related to endowing computer software with emotional intelligence, she wrote the book. It’s published by MIT Press and called Affective Computing.
Dr. Picard is founder and director of the MIT Media Lab’s Affective Computing Research Group. Her research and engineering contributions have been recognized internationally. For example, she received the 2022 International Lombardy Prize for Computer Science Research, considered by many to be the Nobel prize in computer science.
Through her research and companies, Dr. Picard has developed wearable sensors, algorithms and systems for sensing, recognizing and responding to information about human emotion. Her products are focused on using fitness trackers to advance clinical quality treatments for a range of conditions.
Meanwhile, in just the past few years, numerous fitness tracking companies have released products with their own stress sensors and systems. You may have heard about Fitbit’s Stress Management Score, or Whoop’s Stress Monitor – these features and apps measure things like your heart rhythm and a certain type of invisible sweat to identify stress. They’re designed to raise awareness about forms of stress such as anxieties and anger, and suggest strategies like meditation to relax in real time when stress occurs.
But how well do these off-the-shelf gadgets work? There’s no one more knowledgeable and experienced than Rosalind Picard to explain the science behind these stress features, what they do exactly, how they might be able to help us, and their current shortcomings.
Dr. Picard is a member of the National Academy of Engineering and a Fellow of the National Academy of Inventors, and a popular speaker who’s given over a hundred invited keynote talks and a TED talk with over 2 million views. She holds a Bachelors in Electrical Engineering from Georgia Tech, and Masters and Doctorate degrees in Electrical Engineering and Computer Science from MIT. She lives in Newton, Massachusetts with her husband, where they’ve raised three sons.
In our conversation, we discuss stress scores on fitness trackers to improve well-being. She describes the difference between commercial products that might help people become more mindful of their health and products that are FDA approved and really capable of advancing the science. We also talk about several fascinating findings and concepts discovered in Dr. Picard’s lab including the multiple arousal theory, a phenomenon you’ll want to hear about. And we explore the complexity of stress, one reason it’s so tough to measure. For example, many forms of stress are actually good for us. Can fitness trackers tell the difference between stress that’s healthy and unhealthy?
Show links:
- Dr. Picard’s book, Affective Computing
- Dr. Picard’s bio
- Dr. Picard on Twitter
- Dr. Picard’s company, Empatica - https://www.empatica.com/ - The FDA-cleared Empatica Health Monitoring Platform provides accurate, continuous health insights for researchers and clinicians, collected in the real world
- Empatica Twitter
- Dr. Picard and her team have published hundreds of peer-reviewed articles across AI, Machine Learning, Affective Computing, Digital Health, and Human-computer interaction.
- Dr. Picard’s TED talk
Rosalind Picard