Is Sex for Reproduction About to Become Extinct?
There are lots of great reasons we humans have sex. We mostly do it to pair bond, realize our primal urges, and feel good. Once in a while, we also do it to make babies. As the coming genetic revolution plays out, we'll still have sex for most of the same reasons we do today. But we'll increasingly not do it to procreate.
Protecting children from harm is one of the core responsibilities of parenting.
Most parents go to great lengths to protect their children from real and imagined harms. This begins with taking prenatal vitamins during pregnancy and extends to having children immunized and protected from exposures to various diseases and dangers. Most of us look askance for good reason at mothers who abuse controlled substances during their pregnancies or parents who choose to not immunize their children. Protecting children from harm is one of the core responsibilities of parenting.
In the United States today, up to two percent of babies are estimated to be born with rare genetic diseases caused by single gene mutations. Sickle cell disease, Tay-Sachs, and Huntington's disease are among the more well-known examples of these, but the list runs to the thousands. Many babies born with these disorders suffer terribly, some die young, and nearly all spend big chunks of their lives struggling through the medical system.
Increasingly, however, many of these single-gene mutation diseases and other chromosomal disorders like Down syndrome are being identified in non-invasive prenatal tests performed on expectant mothers at the end of their first trimester of pregnancy. Knowing the hardship that children born with these types of disorders will likely face, majorities of these women in countries around the world are choosing to terminate pregnancies once these diagnoses have been made. Whatever the justification and whatever anyone's views on the morality of abortion, these decisions are inherently excruciating.
A much smaller number of prospective mothers, however, are today getting this same information about their potential future children before their pregnancies even begin. By undergoing both in vitro fertilization (IVF) and preimplantation genetic testing (PGT), these women are able to know which of the eggs that have been surgically extracted from them and fertilized with their partner or donor's sperm will carry the dangerous mutations. The in vitro embryos with these disorders are simply not implanted in the expectant mother's womb.
It would be monstrous to assert that an existing person with a deadly disease has any less right to thrive than anyone else. But it would also be hard to make a case that parents should affirmatively choose to implant embryos carrying such a disease if given the option. If prospective parents are already today choosing not to implant certain embryos based on our preliminary understanding of disease risk, what will happen when this embryo selection is based on far more information than just a few thousand single gene mutation diseases?
Our ability and willingness to make genetic alterations to our future children will grow over time along with our knowledge and technological ability.
When the first human genome was sequenced in 2003, the race to uncover the mysteries of human genetics had only just begun. Although we still know very little about our genetics relative to the complexity of the genome and even less compared to the broader ecosystem of our biology, the progress toward greater understanding is astounding. Today, the number of single gene mutation diseases and relatively simple genetic traits that can be predicted meaningfully from genetic data alone is already significant.
In the not-distant future, this list will grow to include complex diseases and disease propensities, percentage probabilities of living a long and healthy life, and increasingly the genetic component of complex human attributes like height, IQ, and personality style. This predictive power of genetic analysis will funnel straight into our fertility clinics where prospective parents choosing embryos will be making ever more consequential decisions about the genetic components of the future lives, health, and capabilities of their children.
Our understanding of what the genes extracted from early stage pre-implanted embryos are telling us will be only one of the rocket boosters driving assisted reproduction forward. Another will be the ability to induce adult cells like skin and nucleated blood cells into stem cells and then turn those stem cells into egg progenitor cells and then ultimately eggs. This will not only eliminate the need for hormone treatments and surgery to extract human eggs but also make it easy and cheap to generate an unlimited number of eggs from a given woman.
The average woman has around fifteen eggs extracted during IVF but imagine what generating a thousand eggs will do to the range of possibilities that could be realized through pre-implantation embryo selection. Each of these thousand eggs would be the natural offspring of the two parents, but the variation between them would make it possible to choose the ones with the strongest expression of the genetic component of a particular desired trait – like those with the highest possible genetic IQ potential.
Another rocket booster will be the application of gene editing technologies like CRISPR to edit the genomes of pre-implanted embryos or of the sperm and eggs used to create them. Just this week, Chinese researchers announced they had used CRISPR to edit the CCR5 gene in the pre-implanted embryos of a pair of Chinese twins to make them immune to HIV, the first ever case of gene editing humans and a harbinger of our genetically engineered future. The astounding complexity of the human genome will put limits on our ability to safely make too many simultaneous genetic changes to human embryos, but our ability and willingness to make these types of alterations to our future children will grow over time along with our knowledge and technological ability.
With so much at stake, prospective parents will increasingly have a stark choice when determining how to conceive their children. If they go the traditional route of sex, they will experience both the benign wisdom and unfathomable cruelty of nature. If they use IVF and increasingly informed embryo selection, they will eliminate most single gene mutation diseases and likely increase their children's chances of living a longer and healthier life with more opportunity than their unenhanced peers. But the optimizing parents could also set up their children for misery if these children don't particularly enjoy what they have been optimized to become or see themselves as some type of freakish consumer product with emotions.
Conceiving though sex will come to be seen more and more like not immunizing your children is today, a perfectly natural choice that comes with a significant potential risk and expense.
But although there will be pros and cons on each side, the fight between conception through good old-fashioned sex and conception in the lab will ultimately not be fair. Differences and competition within and between societies will pressure parents and societies to adopt ever more aggressive forms of reproductive technology if they believe doing so will open possibilities and create opportunities for the next generations rather than close them.
Conception through sex will remain as useful as it has always been but lab conception will only get more advantageous. Over time, only zealots will choose to roll the dice of their future children's health and well-being rather than invest, like parents always have, in protecting their children from harm and helping optimize their life potential. Conceiving though sex will come to be seen more and more like not immunizing your children is today, a perfectly natural choice that comes with a significant potential risk and expense to yourself, your children, and your community.
As this future plays out, the genetics and assisted reproduction revolutions will raise enormous, thorny, and massively consequential questions about how we value and invest in diversity, equality, and our own essential humanity – questions we aren't remotely prepared to answer. But these revolutions are coming sooner than most of us understand or are prepared for so we had better get ready.
Because where this trail is ultimately heading goes well beyond sex and toward a fundamental transformation of our evolutionary process as a species – and that should be everybody's business.
MILESTONE: Doctors have transplanted a pig organ into a human for the first time in history
Surgeons at Massachusetts General Hospital made history last week when they successfully transplanted a pig kidney into a human patient for the first time ever.
The recipient was a 62-year-old man named Richard Slayman who had been living with end-stage kidney disease caused by diabetes. While Slayman had received a kidney transplant in 2018 from a human donor, his diabetes ultimately caused the kidney to fail less than five years after the transplant. Slayman had undergone dialysis ever since—a procedure that uses an artificial kidney to remove waste products from a person’s blood when the kidneys are unable to—but the dialysis frequently caused blood clots and other complications that landed him in the hospital multiple times.
As a last resort, Slayman’s kidney specialist suggested a transplant using a pig kidney provided by eGenesis, a pharmaceutical company based in Cambridge, Mass. The highly experimental surgery was made possible with the Food and Drug Administration’s “compassionate use” initiative, which allows patients with life-threatening medical conditions access to experimental treatments.
The new frontier of organ donation
Like Slayman, more than 100,000 people are currently on the national organ transplant waiting list, and roughly 17 people die every day waiting for an available organ. To make up for the shortage of human organs, scientists have been experimenting for the past several decades with using organs from animals such as pigs—a new field of medicine known as xenotransplantation. But putting an animal organ into a human body is much more complicated than it might appear, experts say.
“The human immune system reacts incredibly violently to a pig organ, much more so than a human organ,” said Dr. Joren Madsen, director of the Mass General Transplant Center. Even with immunosuppressant drugs that suppress the body’s ability to reject the transplant organ, Madsen said, a human body would reject an animal organ “within minutes.”
So scientists have had to use gene-editing technology to change the animal organs so that they would work inside a human body. The pig kidney in Slayman’s surgery, for instance, had been genetically altered using CRISPR-Cas9 technology to remove harmful pig genes and add human ones. The kidney was also edited to remove pig viruses that could potentially infect a human after transplant.
With CRISPR technology, scientists have been able to prove that interspecies organ transplants are not only possible, but may be able to successfully work long term, too. In the past several years, scientists were able to transplant a pig kidney into a monkey and have the monkey survive for more than two years. More recently, doctors have transplanted pig hearts into human beings—though each recipient of a pig heart only managed to live a couple of months after the transplant. In one of the patients, researchers noted evidence of a pig virus in the man’s heart that had not been identified before the surgery and could be a possible explanation for his heart failure.
So far, so good
Slayman and his medical team ultimately decided to pursue the surgery—and the risk paid off. When the pig organ started producing urine at the end of the four-hour surgery, the entire operating room erupted in applause.
Slayman is currently receiving an infusion of immunosuppressant drugs to prevent the kidney from being rejected, while his doctors monitor the kidney’s function with frequent ultrasounds. Slayman is reported to be “recovering well” at Massachusetts General Hospital and is expected to be discharged within the next several days.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.