How Smallpox Was Wiped Off the Planet By a Vaccine and Global Cooperation
For 3000 years, civilizations all over the world were brutalized by smallpox, an infectious and deadly virus characterized by fever and a rash of painful, oozing sores.
Doctors had to contend with wars, floods, and language barriers to make their campaign a success.
Smallpox was merciless, killing one third of people it infected and leaving many survivors permanently pockmarked and blind. Although smallpox was more common during the 18th and 19th centuries, it was still a leading cause of death even up until the early 1950s, killing an estimated 50 million people annually.
A Primitive Cure
Sometime during the 10th century, Chinese physicians figured out that exposing people to a tiny bit of smallpox would sometimes result in a milder infection and immunity to the disease afterward (if the person survived). Desperate for a cure, people would huff powders made of smallpox scabs or insert smallpox pus into their skin, all in the hopes of getting immunity without having to get too sick. However, this method – called inoculation – didn't always work. People could still catch the full-blown disease, spread it to others, or even catch another infectious disease like syphilis in the process.
A Breakthrough Treatment
For centuries, inoculation – however imperfect – was the only protection the world had against smallpox. But in the late 18th century, an English physician named Edward Jenner created a more effective method. Jenner discovered that inoculating a person with cowpox – a much milder relative of the smallpox virus – would make that person immune to smallpox as well, but this time without the possibility of actually catching or transmitting smallpox. His breakthrough became the world's first vaccine against a contagious disease. Other researchers, like Louis Pasteur, would use these same principles to make vaccines for global killers like anthrax and rabies. Vaccination was considered a miracle, conferring all of the rewards of having gotten sick (immunity) without the risk of death or blindness.
Scaling the Cure
As vaccination became more widespread, the number of global smallpox deaths began to drop, particularly in Europe and the United States. But even as late as 1967, smallpox was still killing anywhere from 10 to 15 million people in poorer parts of the globe. The World Health Assembly (a decision-making body of the World Health Organization) decided that year to launch the first coordinated effort to eradicate smallpox from the planet completely, aiming for 80 percent vaccine coverage in every country in which the disease was endemic – a total of 33 countries.
But officials knew that eradicating smallpox would be easier said than done. Doctors had to contend with wars, floods, and language barriers to make their campaign a success. The vaccination initiative in Bangladesh proved the most challenging, due to its population density and the prevalence of the disease, writes journalist Laurie Garrett in her book, The Coming Plague.
In one instance, French physician Daniel Tarantola on assignment in Bangladesh confronted a murderous gang that was thought to be spreading smallpox throughout the countryside during their crime sprees. Without police protection, Tarantola confronted the gang and "faced down guns" in order to immunize them, protecting the villagers from repeated outbreaks.
Because not enough vaccines existed to vaccinate everyone in a given country, doctors utilized a strategy called "ring vaccination," which meant locating individual outbreaks and vaccinating all known and possible contacts to stop an outbreak at its source. Fewer than 50 percent of the population in Nigeria received a vaccine, for example, but thanks to ring vaccination, it was eradicated in that country nonetheless. Doctors worked tirelessly for the next eleven years to immunize as many people as possible.
The World Health Organization declared smallpox officially eradicated on May 8, 1980.
A Resounding Success
In November 1975, officials discovered a case of variola major — the more virulent strain of the smallpox virus — in a three-year-old Bangladeshi girl named Rahima Banu. Banu was forcibly quarantined in her family's home with armed guards until the risk of transmission had passed, while officials went door-to-door vaccinating everyone within a five-mile radius. Two years later, the last case of variola major in human history was reported in Somalia. When no new community-acquired cases appeared after that, the World Health Organization declared smallpox officially eradicated on May 8, 1980.
Because of smallpox, we now know it's possible to completely eliminate a disease. But is it likely to happen again with other diseases, like COVID-19? Some scientists aren't so sure. As dangerous as smallpox was, it had a few characteristics that made eradication possibly easier than for other diseases. Smallpox, for instance, has no animal reservoir, meaning that it could not circulate in animals and resurge in a human population at a later date. Additionally, a person who had smallpox once was guaranteed immunity from the disease thereafter — which is not the case for COVID-19.
In The Coming Plague, Japanese physician Isao Arita, who led the WHO's Smallpox Eradication Unit, admitted to routinely defying orders from the WHO, mobilizing to parts of the world without official approval and sometimes even vaccinating people against their will. "If we hadn't broken every single WHO rule many times over, we would have never defeated smallpox," Arita said. "Never."
Still, thanks to the life-saving technology of vaccines – and the tireless efforts of doctors and scientists across the globe – a once-lethal disease is now a thing of the past.
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