Stories of Self-Experimentation

What happens when the scientist...becomes the subject? Meet the medical mavericks who test their own bodies...
09 February 2021
Presented by Chris Smith, Phil Sansom
Production by Phil Sansom.


A table covered in conical flasks.


What happens when the scientist... becomes the subject? We're examining the strange world of self-experimentation, from the history of martyr medics and kooky romantics, to the modern biologists dosing themselves with DIY COVID vaccines in the months after the pandemic began. Plus, is mixing vaccines the best way to fight coronavirus? Scientists capture an elusive element, number 99... and the physics behind why wombats poo in cubes!


In this episode

A healthcare worker preparing a needle.

01:01 - COVID vaccines: delayed booster may help

Immunologist Peter Openshaw weighs in on vaccine mixing and spacing the doses...

COVID vaccines: delayed booster may help
Peter Openshaw, Imperial College London

It's been a week of Covid contrasts. On the one hand we mourned the passing of Captain Sir Tom Moore, whose 100 laps of his care home raised millions for the NHS; and at the same time we marked a vaccine milestone. More than 10 million people across the UK have received at least one vaccination for coronavirus. And one of those vaccines, AstraZeneca's, seems - based on a preliminary report - to do more than just prevent severe disease: it stops people spreading Covid as well. The report claims that nearly 70% fewer infections were picked up in people who'd had their first dose of the jab; which is good news because it suggests that as well as being protected themselves, vaccinated people are also helping to protect others by being less likely to pass on the infection.

Also this week, the government’s vaccine minister Nadhim Zahawi announced a new £7M study to look at the effect of using two different vaccines together. Mixing doses is likely to become a priority in the future, not least because - owing to the way they interact with the body - some of the vaccines we're using might not work more than once. The other big question that still remains unanswered is whether we've got the gap between doses right; the UK has introduced a policy of waiting 12 weeks to maximise the number of people who can be protected in the first instance. This was the first question Chris Smith put to immunologist Peter Openshaw when they spoke about the vaccine initiative earlier this week. He thinks that giving jabs too close together would be a bad idea...

Peter - Sometimes by giving too much of a thing, you can actually drive down the immune response. The new evidence coming out generally shows that you do get quite good protection from that first dose, which lasts all the way through until the three months' second dose. And indeed you may end up with a better immune response as a result of having delayed the second dose.

Chris - The data that we've got to go on - that's informing what you're saying - is based on AstraZeneca's vaccine. Does the same apply then to the Pfizer vaccine? Because one criticism people are leveling at the current strategy is that the Pfizer vaccine and the AstraZeneca vaccine are two quite different things, and therefore to assume that what goes for one will apply to the other is a misstep.

Peter - Some of the investigators have said that they don't think it's going to make any difference whether you make the spike protein of the coronavirus one way, or make it another. I think that's a reasonable hypothesis, but it absolutely needs to be tested. The other point to make is that the vaccines were developed at great speed. The very short interval between the first dose and the second dose was decided on largely in order to make sure that the vaccine studies could be done very fast. That doesn't mean to say that that was necessarily the best interval between the first dose and the second dose. And I've certainly... in vaccine studies that I've done myself, I've found that sometimes by giving the second dose too quickly, you can actually get a much weaker immune response.

Chris - A question which is also surfacing a lot is...people have got an eye on what's been happening in Europe, they've got an eye on the fact that the current bottleneck with vaccination appears to stem from a supply problem. We just can't get enough vaccines in the door fast enough. Therefore people are legitimately saying, "well, if I can't access a second dose of the thing I had the first time, and I have to use a different vaccine product, is that necessarily a bad thing?"

Peter - That actually might be a perfectly good strategy. There's many examples of vaccination regimes where a different vaccine has been used in the first and the second dose. And indeed some of the vaccines can't actually be repeated again and again, because they’re all within an adenovirus vector. So with some of these vaccines, it is actually a big advantage to be able to prime with one and boost with another.

Chris - So what you're saying is that because, say, AstraZeneca's vaccine is delivered by a disabled virus, to actually get the message about the spike of the coronavirus into the body in the first place, you're going to get an immune response to that disabled virus that's the Trojan horse. Are the government potentially in trouble then, if they need to revaccinate people, they wouldn't be able to use it - in people who've already had AstraZeneca vaccine, they couldn't use it again?

Peter - Yes, that is a potential problem. And I think it illustrates the reason why it's so good to have a rich pipeline of different types of vaccines.

Chris - How is it looking in terms of how the vaccines are thought to protect against the current slew of variants that we're seeing emerging in various geographies around the world?

Peter - Well, at the moment, things are looking quite good in terms of our own homegrown variant. It still seems to be susceptible to the immune response, but I think we're all expecting that over time, the main driver for evolution of the virus will become the host immune response, either due to vaccination or due to previous exposure to the virus. When that becomes the driving force, then we are going to have to actually reformulate the vaccines to match the currently circulating strains.

Berkeley Lab scientists Leticia Arnedo-Sanchez, Katherine Shield, Korey Carter, and Jennifer Wacker.

06:47 - Einsteinium: secrets of 99th element unlocked

Einsteinium is rare and short-lived. This week, chemists managed to capture it...

Einsteinium: secrets of 99th element unlocked
Kit Chapman

Einsteinium is one of the cleverer-sounding elements you’ll see on your periodic table, but it’s a lot further down the list than something like carbon, or gold, or mercury. While carbon is number 6, gold is number 79, and mercury is number 80, einsteinium is the 99th element! It’s also radioactive, meaning it doesn’t stick around for long before it breaks down into something else. That makes it hard to study, and even though it was discovered in the 50s, we know very little about it. But this week, scientists at the Lawrence Berkeley National Laboratory managed to capture some in a molecular cage. Kit Chapman didn’t work on the study but he did write the book on the periodic table, called 'Superheavy', and he took Adam Murphy through the discovery...

Kit - Einsteinium doesn't exist on Earth. Anything beyond uranium, which is element 92 - and remember einsteinium is 99 - just doesn't exist on Earth. And usually these are made through nuclear reactions or particle accelerators, but einsteinium and fermium were actually first discovered from the remains of a thermonuclear bomb explosion. There was a bomb explosion in the 1950s in the Pacific - they were testing this world's first hydrogen bomb - and they actually ordered fighter planes to fly inside the cloud and gather up debris. And from those filters, we managed to find einsteinium and fermium

Adam - Looking at that, can you give us kind of the rundown of what they've done here at the Los Alamos lab?

Kit - Well, this is really impressive because there isn't very much einsteinium in the world. As I mentioned, it just doesn't exist on Earth, you have to make it. And so they managed to get 200 nanograms, which is a tiny, tiny amount. And they started to look at its properties. Now because it's radioactive, we haven't done many experiments on einsteinium. What they did was they took an einsteinium atom and they wrapped it in a sort of molecular cage, and they looked at it from that angle. And they began to do some X-ray tests on it, and from that they could actually study the bonds, and how it bonds with this... what we call a ligand, this cage it's in. And what it found was that it didn't follow the pattern they expected: it doesn't behave like the other actinides, some of the lighter actinides next to it, it starts to behave a little bit differently. And that's really interesting.

Adam - I understand that we don't have very much of it, but how do you determine that this thing exists and then know so little about it for so long?

Kit - The problem is making it. So there isn't any use for einsteinium in the world. There's no practical applications. Californium, which is a bit lighter - that's element 98, the next one along - that's really useful for the oil industry and for a host of other different applications. And so there's a reason to make it. There's a reactor in Oak Ridge, in Tennessee, and a reactor in Russia; and they can actually create these elements, they have the ability to do so. And when they're making californium, they're probably going to make a little bit of einsteinium as well because of the way they're doing it; essentially they nudge things up the periodic table. And so it's only... almost as a byproduct that you're actually producing einsteinium, and that's why we just don't have much of it. It's also only got a half-life of, I think, 275 days, which is incredibly short. It's not the shortest - some of the ones even bigger have half-lifes of minutes or seconds - but it's not very long at all, which means that it rapidly degrades. So you've got to be very quick in terms of the experiments you do,

Adam - As you were saying there, einsteinium doesn't have any practical applications. So why does it matter that we can do this with this now?

Kit - It's one of the building blocks of the universe! And the more knowledge we have about the universe and how it works, the more we can understand things. Just because einsteinium doesn't exist on Earth, it doesn't mean it doesn't exist in nature. You'll find it inside supernovae; you'll find it inside of neutron stars colliding. And so the more that we can understand about how these building blocks work, how they interact with things, how what we call relativistic effects affect the way that chemicals work... really gives us a clearer picture of how the universe is constructed. And that means potentially we have all kinds of applications in the future that we just can't think about yet.

Adam - What's the next frontier in this kind of research? What's the next big thing that's coming out?

Kit - The next big thing really is hard to predict. We're hoping that it could be a new element. So if this stuff has gone over to Japan, and they've fired probably calcium into it - a very interesting isotope of calcium called calcium-48, which was used to create some other elements - then potentially we could have element 119. And if that's the case, then we have an entire new row of the periodic table starting, and that just opens up all kinds of possibilities.

A mouse.

11:33 - Sepsis: removing RNA gene protects mice

US researchers have pinpointed a region of the genetic code that can control the immune response to sepsis...

Sepsis: removing RNA gene protects mice
Susan Carpenter, UC Santa Cruz

When you’re infected with a microorganism, the machinery of the human immune system kicks in and a whole array of specialised chemicals and cells work together to kick out the invader. But sometimes the immune system overreacts and starts to do damage in its own right. This is called sepsis; it’s very hard to treat and can often lead to death. This week US researchers pinpointed a region of the genetic code that can control the immune response to sepsis: specifically, a bit of RNA - the stuff that normally carries the messages from your DNA. Martin Khechara spoke to Susan Carpenter...

Susan - We have identified this genetic material - actually an RNA gene - that when you remove it from an animal, that animal is now resistant; it does not get sepsis.

Martin - How did you find out actually what it does?

Susan - First we started working on this particular gene in human cells, and then we were very excited to see that it is conserved across species. And so we could take a mouse and remove this gene. And what we were really intrigued to find was that that mouse is protected from sepsis.

Martin - What would the molecule do in normal cells? Surely it's necessary?

Susan - We think like everything in the immune system, it's all about balance. This is a gene that's on in cells at high levels normally, and that during an inflammatory response, it goes rapidly down. And so we know that it's playing this role in helping to toggle the responses of that particular cell.

Martin - How can removing just this one thing have such a big effect?

Susan - It really kind of tells us something about the importance of this gene. There's so many genes involved in these responses that just removing this one in particular can have this strong impact. And it's not unusual, we see this with particular protein: if you remove them from the system, they can have positive impacts. So for example, many drugs are designed to target a particular protein during an inflammatory response, and that gives relief to patients.

Martin - If you took me and took this molecule away from my cells, could I still fight disease?

Susan - This story is in its very early phase, but what we can say right now is that with the immune system, everything is about timing. And so we think being able to manipulate the levels of this gene at particular times could have an impact in how you respond to infections.

Martin - When could this discovery one day help people suffering from sepsis?

Susan - Well, that is our ultimate goal with these projects: to get a better understanding, to be able to eventually have some therapeutic targets. And right now, this is in the very early stage. This is very basic research that we've done a lot of work on a mouse model. And our next phase is to move into understanding this better in humans and human cells, from patients with sepsis.

Artist's impression of the UAE's 'Hope' Mars orbiter.

15:32 - UAE Hope probe reaches Mars

The United Arab Emirates' first space mission has just arrived in orbit around the red planet...

UAE Hope probe reaches Mars
Sarah Al-Amiri, Emirates Mars Mission

This month a fleet of spacecraft from the United Arab Emirates, China, and the United States are reaching Mars. The missions have coincided because all three took advantage of a two-month launch window last year when Earth and Mars lined up just right in their orbits; this only happens once every two years. The missions are a first on many levels: it’s China’s first independent Mars landing, NASA’s Perseverance mission is taking a helicopter to Mars, it’s the UAE’s first space foray; their orbiter spacecraft is called Hope. Chair of the UAE Space Agency, Sarah Al-Amiri, joined Phil Sansom to explain the mission...

Sarah - We sent this probe to investigate the weather system of Mars throughout an entire Martian year, and to understand the weather dynamics more thoroughly than they've ever been studied before. The difference between this mission and other missions is that other missions have studied the weather system of Mars, but only during two times of the day, that's around 2:00 AM and 2:00 PM local time on Mars. What we're doing is understanding better the full dynamics; so for example, the phenomena of dust storms on Mars that start in a localised area and cover the entire planet.

Another piece of the puzzle that we'd like to fill in is: what role does Mars' weather system play in atmospheric loss? And therefore we're able to link the, for example, dust storms, especially global dust storms, to rates of escape of hydrogen and oxygen. And that fits in very well with the global understanding of what happened to Mars, especially what happened to Mars from the perspective of climate change.

Phil - Sarah, I'm quite shocked to hear that Mars has weather at all. Given not having an atmosphere, I'd imagine their forecast is a lot of, you know, “cold, very cold darkness of space”.

Sarah - It does have a very light atmosphere. There is a cloud system on Mars, there's water vapour that circulates around the planet. You've also got dust within the lower atmosphere of Mars where the weather system is. It's actually interesting, the weather system on Mars, and hence why we're understanding it better throughout an entire year, because that hasn't been covered extensively; and scientifically, it actually does have a good link into looking into Mars today, just to understand from the wider space of things as historically what happened to this planet.

Phil - So you've got sort of the traces of an atmosphere, and you've got some weather going on. Your Hope probe is going to be orbiting - if all goes well - around Mars. I assume it's not got a weather vane because that's pretty low tech. So what's your high-tech equivalent?

Sarah - We're orbiting around Mars in a very unique orbit. Like I said, the previous orbiters have orbited from the North to the South pole and they're very close to Mars. We're about 20,000 kilometres at our closest point and 43,000 kilometres at our furthest point. So we look at the lower atmosphere of Mars; that's where the weather is happening. We use the infrared spectrometer and that allows us to measure dust, it allows us to measure the cloud system and water vapour. Also an ultraviolet spectrometer, and that actually looks at how far a cloud of hydrogen and oxygen shrouds Mars; and that's where atmospheric escape happens, and that's what it measures.

Phil - All this stuff can't be cheap. So why is the UAE getting in on the science of Mars? Why send Hope now?

Sarah - The first and primary objective of this mission is to build capabilities. We're a country that's slowly transitioning into a nation that is based on science and technology. And space, especially planetary exploration, allows you to develop a lot of capabilities in just one programme in one mission. And today we have engineers who are able to design and develop a very complex and autonomous system, and it's already a very difficult mission to undergo. Only half of the missions have succeeded in their first time to get into orbit around Mars. And that gives us a sort of shift in mindset, and as a nation that was built on commodities and natural resources, it's a great transition point for us.


19:57 - How wombats poo cubes

Wombats make the most unusually-shaped poo. How do they do it? Their intestines have revealed the secret...

How wombats poo cubes
David Hu, Georgia Tech

You can’t fit a square peg through a round hole, as English writer Sydney Smith said in around 1805. But now it’s 2021, and scientists have shown how wombats can - using their cube-shaped poo! Eva Higginbotham spoke to scientist David Hu...

David - Wombats are marsupials: the size of an obese toddler, the face of a teddy bear, and the nose of a koala. And they don't like each other; they like to live in sort of separate territories. What people most know them for is the way they defend their territories, and they do it with little flags of faeces. They make latrines as tall as a wombat can climb with its short stubby legs, which is not very tall: usually a stump or a rock. And they'll get on top of this rock and defecate. They defecate about a hundred cubes a day and they'll leave about ten or so as a calling card.

Eva - I cannot believe that! A hundred times a day? And they're building essentially a tower of poo outside their house?

David - Yeah, they're separate latrines, and they'll dump a hundred cubes dispersed among the various latrines. For years people had known that these wombat faeces are different from all the other mammals, that they're cubic, but no one knew exactly how an animal can make anything that's this strangely shaped. They're kind of the size and colour of a Godiva chocolate or an Almond Joy minibar with one nut, but they smell like grassy poop, and are probably not very tasty.

Eva - Ha! Thank you. So what did you do?

David - Our first task was finding a good collaborator. So we sought out Scott Carver who's a wombat expert and works with wombats. And he shipped us intestines - full, intact intestines, and wombat faeces - through the mail. It was around Christmas time, so it was one of the best Christmas presents I've ever gotten, wombat intestines. We opened them up and they had tiny little presents inside. I was very happy to see them.

One of the first discoveries we made was that the cubes happen inside the wombat. They start out as a yoghurt-like slurry, and they eventually solidify, dry. In the last metre of the intestines or so they were just a factory line of cubes. And so it was amazing to see inside the body, going from a sort of amorphous and sort of strangely shaped solid, to something that had edges and flat faces.

The other thing that we noticed is that the cubes were arranged very nicely. When we hung the intestines from the ceiling, we noticed that after they finished swinging, all the corners and edges of the intestines aligned. And that meant that the cubes... they had a clock in the intestines that was telling them where to make the corners and where to make the flat faces. So we knew there was something in the intestines themselves that was communicating where to put the different parts of the cube. We performed these materials tests and measured how much it stretches, and we found that there are certain stripes on the intestines that stretch less than the others. So some parts of the intestines are four times as stretchy as the stiff parts. The rest we had to turn to mathematical modeling to basically simulate oscillation of the intestines, try to simulate the properties of faeces, and see how the two would interact until we got corners and flat faces.

Eva - So you went into the model knowing that, "okay, so the intestines have a more stretchy bit and a less stretchy bit." You input that into a computer algorithm. And then what happens?

David - We wrote the equations for how the intestine should move if they're contracted like a muscle. And over many, many contractions, we saw that the stiff sections would produce corners at their midpoint.

Eva - How long is wombat faeces inside the wombat?

David - So when we eat something, it's basically out of our bodies in one to two days, and a wombat is three to five days. And in part that's because they're very drought tolerant; they want to capture as much water as possible from the faeces before it leaves. And it's also that time that allows the intestines to do their sculpting work. Faeces, as it gets drier, gets very, very solid-like. The longer time it takes allows the corners to get formed a little bit more like a square.

Blood vessel network

24:08 - Mailbox: how do woven blood vessels work?

Paola asks: would 'woven' blood vessels be able to perform diffusion properly?

Mailbox: how do woven blood vessels work?

Time for the mailbox: the part of the show where we read out your correspondence! This question is from listener Paola, in reference to our story in January about making replacement blood vessels out of ‘knitted’ human tissue...

Chris - Paola, the scientist in question Nicolas L'Heureux says the answer is that gases and nutrients only diffuse through the walls of blood vessels, called capillaries, that are hundreds of times smaller than the ones that he’s making for bypass operations, so that won’t be a problem. And regarding 3-D printing, it can be a powerful tool to create very small patterns like the tiny blood vessels you may be thinking of; for his larger blood vessels, it is probably simpler to create tubes using other methods. Plus, 3D printing requires something liquid that can turn solid during printing; very difficult to do with biological materials!

Portrait of the French psychiatrist Jacques-Joseph Moreau de Tours.

25:39 - Self-experimentation: a scientific history

Throughout recorded history, scientists have made themselves their own test subjects. How - and why?

Self-experimentation: a scientific history
Barry Marshall; Katrin Solhdju; Mike Gibson

Self-experimentation has a long tradition; even helping Australian physician Barry Marshall win a Nobel Prize. Back in the 80s he was trying to prove certain bacteria cause stomach ulcers and cancer. He couldn’t get any results from infecting animals, so he decided the next best option would be to use himself…

Barry - I did drink the bacteria; a few tablespoons full, not very much. And it didn't really... well actually it's not published yet so I won't tell you what it tasted like. It wasn't too bad! So then I was just waiting to see what would happen. About five days later, I woke up and ran into the bathroom, started throwing up. And I was vomiting for about three days. The endoscopy was done and sure enough, I had millions of these bacteria. So that answered this question, it said: healthy people with nothing wrong with them could catch this bacteria and then get inflammation in the stomach called gastritis. So that was then the soil upon which an ulcer would form later in life.

This is one of the most famous examples of self-experimentation - winning Barry and his collaborator Robin Warren the 2005 Nobel Prize in Medicine - but we’re going to hear many others during our tour through the history of self-experimentation. Medical historian Katrin Solhdju told Phil Sansom that the idea goes way back, but started to become important to European science around the 18th Century...

Katrin - We can identify three traditions of self experimentation in the history of science, and more particularly in the history of medicine.

Phil - What's the first one?

Katrin - The self experimenter in this case is convinced that before you can start experimenting on other people with something that might be toxic, you should actually take the responsibility and be the one to try it on yourself first. At the end of the 18th century, there are big debates all over Europe about the legitimacy of experimenting, for example, on prisoners, which was something that had been done for a while. And so self experimentation, at least in a lot of cases, is also a stance against experimenting on these kinds of populations.

Phil - Who specifically is telling people: stop experimenting on these vulnerable people like prisoners; you should experiment on yourself?

Katrin - It's a Viennese doctor called Anton Storck, who was actually the first one to propose an actual procedure that consisted of four steps. The first step would be, as we still have it today, the chemical description of an element of nature; mainly those were plants at the time. The second step would be to experiment on animals; and then a phase of self-experimentation before actually experimenting on other people, so before going to the phase that today we would call clinical experimentation.

Phil - Okay, that's your first tradition. What's the second one?

Katrin - What we might want to call romantic self-experimentation. People that, at the end of the 18th century, were linked to what is now known as the romantic circles. One of their convictions was that there was one kind of principle that went throughout the entire whole of nature. And so experimenting on oneself could also teach one something about the organisation of the cosmos or of nature.

Phil - It sounds like you're talking about something that's almost poetic, and then even approaching on spirituality?

Katrin - Yes, it is. And they experimented on themselves for this. There is a kind of heroic figure, or strange figure in this, who was called Ritter. He looked into the sun for so long directly, he actually hurt his eyes in bad ways. But there is at least one third important tradition of self experimentation, where the object of research couldn't be accessed through anything else but through introspection, observing oneself. For example, there was a French psychiatrist called Jacques-Joseph Moreau ‘de Tours’ who, while actually traveling with a patient in North Africa, discovered hashish; and exported the drug, which didn't exist in Europe at the time; and then founded a kind of movement of self experimentation to, what was his conviction at least, render more clear what his psychiatric patients were going through.

Phil - Whatever reason people had for experiments on themselves, did it - do you think - more often go right and was helpful, or more often go wrong?

Katrin - I think that's quite undecided. There are self experiments which led to Nobel prizes in medicine, even in the 20th century; there are other self experiments who maybe were a little bit either dangerous or didn't bring any results. But I don't think it is really linked to the fact that those were self experiments. It's just the same thing for any kind of experiment, which always carries the risk of going wrong or not bringing any interesting results.

Phil - I wanted to ask you as well: you've been saying the word ‘he’ a lot, and based on talking to people, it does seem like almost all of these anecdotes are about men. Do you think that's because historically, a lot of scientists working in these fields were male, or is there something in the male ego - I don't know - that makes you want to do this kind of heroic thing, if that's why you're doing it?

Katrin - From the 18th and 19th century, there simply weren't any women scientists at the time. We can regret it, but we can really change it. This of course changed during the 20th century. The interest in maybe becoming a hero through this kind of act might play a role there. But then of course there is maybe something else that might play a role as well, and that is which kind of self experimentation is actually rendered public.

Phil - Do people still experiment on themselves, or has this kind of thing mostly died out?

Katrin - Nowadays it's something that is sort of off the record. Of course they can be publicised, but it's not something that can be recognised directly, at least within the scientific community. Except for, of course, it bringing about an incredible result that then can no longer be ignored.

These practices certainly did continue, in a form, well into the 20th century. Mike Gibson is former physician for the Royal Air Force who recalls how often it happened...

Mike - We tended to do experiments on ourselves for two main reasons: firstly to make sure that the apparatus was working properly, so that when we moved on to our colleagues, we could be sure that we were not going to waste an exposure or a run; and secondly, so that when you were persuading one of your colleagues to take part in one of your unpleasant experiments, you could turn around and say, “well, I've done it, it's not too bad, I'm still here!” One particular nasty experiment was to instrument someone with an esophageal temperature probe, an auditory canal probe, a rectal probe, and a radio pill, jumping into a hot bath at 42 celsius until their deep body temperature reached 38 and a half, and then jumping into a cold bath until their deep body temperature approached 35. And that was unpleasant... the first subject complained of an intense feeling of tumbling head over heels. I'm not sure how much it would be allowed now, particularly as most experiments have to go through an ethics committee, which we didn't have in those days.

Biohacker Josiah Zayner.

33:59 - The biohacker who edited his own genes

Self-experimentation still happens today - and biohackers like Josiah Zayner are pushing its limits...

The biohacker who edited his own genes
Josiah Zayner

Self-experimentation still happens today, and depending on your definition, it happens a lot - everything from off-the-record sanity checks in medical labs, to your average person trying out a new diet or drug! One person who’s testing the limits of what’s possible here is biohacker Josiah Zayner, who joined Chris Smith to explain what he does...

Josiah - A biohacker is just somebody who does science outside a traditional environment. Generally, I like to think of us as the rogues and the renegades of the scientific community.

Chris - But you are a traditional scientist as well; I mean you've been to university, you've done very high level training.

Josiah - Yeah, so I have a PhD and I was a scientist at NASA before I decided that the traditional scientific environment lacks the risk-taking that needs to be done to actually push science forward.

Chris - Speaking of which, are you supposed to be the first person who has actually done gene editing with this technology, CRISPR, on themselves?

Josiah - I am the first person to use CRISPR. CRISPR is this new modern gene editing technology that allows basically anybody to edit genes in most any organism inexpensively and fast. And for me, trying to get this technology to be used in humans so that we can push ahead and cure diseases is something that was big on my mind.

Chris - And what did you do to yourself?

Josiah - I injected myself with some DNA that was meant to modify the genes in my muscles, supposedly to give me bigger muscles. Now I wasn't able to actually detect that the gene editing worked, but the idea was that this is safe for humans, it's possible, and we should go forward.

Chris - I'm just looking at your picture on your Wikipedia page - was your hair that colour before you did CRISPR on yourself? Hopefully it was!

Josiah - Actually, I think the gene editing caused me to have different colour hair, but don't tell anybody; they'll try to buy it off me!

Chris - But talking of things that go funny colours, because you have taken this beyond just doing things that maybe some would regard as a bit outlandish, like self-inflicted gene editing... you have actually brewed up glowing green beers, haven't you?

Josiah - Yeah. So we are trying to make gene editing accessible and available to everybody. I think genetic engineering is one of the most powerful technologies we have. So making it so people can experience it in their everyday life, like editing yeast so they can change colour, or fluoresce - like glow in the dark. Or we've also worked on growing up chicken cells in petri dishes, and making like a chicken nugget grown in the lab. So there's a lot of science I think that people can do and experience in their everyday life that's amazing.

Chris - Did the beer actually glow?

Josiah - Yeah, it did. You have to keep the yeast in there because the yeast contained the glowing protein, but it does glow.

Chris - There are some cloudy beers where they do that on purpose so I could see that working. It got you into trouble though, didn't it? The FDA, the organisation that regulates food and drugs in America, had something to say about you doing that.

Josiah - Yeah, the FDA, the California Department of Public Health, and the state of California... everybody comes after me. I think when you're working with new technologies and pushing boundaries, people don't understand it completely. And so you get pushback from it. But to this date I'm talking to you not from jail so I think things are still pretty good.

Chris - Are you talking to me from the toilet though, because you also dabbled in doing a "trans-poosion"; you literally changed all of your bacteria in your intestines at one point, didn't you?

Josiah - Yeah. I had gut distress and IBS, and was suffering from gut issues, and I thought that maybe I could take matters into my own hands, because a lot of times the medical doctors would just tell me "oh, you're stressed out. Don't be stressed, exercise". And you're like, “how am I supposed to not be stressed? I don't get that!” And so I took faeces from a healthy donor and transplanted it into my body. Barry Marshall said the bacteria didn't taste that bad - eating faeces is a whole other story!

Chris - Well they say it's a crap-sule that you have to swallow, but maybe that's a story for another show. But look, the key thing is this is a show about self-experimentation. So why are you doing this? And why are you using yourself to do these things on?

Josiah - It gives me the ability to do things I normally wouldn't be able to do because experimenting on other people, especially things that are risky, I think is unethical to me.

Chris - You've also made a COVID vaccine. You quite famously teamed up with a bunch of others and you have made a COVID vaccine that you have self administered. Has it worked?

Josiah - Yeah. So we were able to detect neutralising antibodies in our blood to the protein that the virus makes. Whether it works or not is a very complicated question that would probably require a big clinical trial. But for all intents and purposes, we saw results that were very positive.

Chris - I just want to finish by asking you, really, whether you think this is responsible? Because obviously there are some pretty powerful things we can do in a garden shed with molecular biology these days. Do you think what you're doing is encouraging people to perhaps go beyond what's responsible and sensible?

Josiah - I could think there couldn't be something that was more responsible. Genetic engineering is the most powerful technology we have. We can literally engineer self-replicating matter. And to give that power to very few people in universities and big companies and to not let the public experience this technology I think is wrong. So I think the greatest responsibility I have is to allow people to use this technology.

A COVID-19 nasal vaccine bottle.

41:02 - DIY COVID vaccines: do they work?

Geneticist George Church took a COVID vaccine back in May. Has it succeeded?

DIY COVID vaccines: do they work?
George Church, Nebula Genomics

We’ve just heard from Josiah Zayner, who engineered a COVID vaccine back in May - and he’s not alone. Around the same time, a separate group of scientists formed an initiative called RaDVaC to quickly synthesise a coronavirus vaccine based on the available evidence. Instead of being a cutting-edge genetic vaccine like the current offerings from Pfizer and Moderna, they used small bits of coronavirus protein called ‘peptides’; and instead of injecting it, you just squirt it up your nose! Rather than going through clinical trials, RaDVaC say their vaccine is one you should make yourself and take yourself. That’s what over 100 geneticists have now done, among them Harvard's George Church. Phil Sansom asked him why...

George - Well there's a long history of...even the modern vaccines, the people developing them feeling that morally the right thing to do is not to test it on somebody that you're unwilling to test on yourself. We did not want to necessarily be first in line, but we felt that if there's any risk, we should take the risk first. These have intrinsically low risk because most of the parts had all been tested, and it's a less medical procedure if nothing else because you're not injecting with a needle.

Phil - Okay, crucial question: do you know if it's worked?

George - What we have so far - and it's very preliminary, not peer reviewed - is that it is safe. Well, safe at the scale that we're using it; sometimes you need to go to hundreds of thousands of people to find an occasional anaphylactic reaction, which there is for some of the messenger RNA doses that are happening with coronavirus. So it's safe, and it seems to be producing some kind of immune reaction in the nasal mucosa, but not in the blood. If you cover the nasal passages and the lungs, you're in great shape.

Phil - You've found some kind of reaction; you don't yet know whether you're immune to the coronavirus?

George - There's been relatively little intentional exposure, so we don't really know. We have the intention to make this go through FDA testing, but we wanted to make sure that it was as transparent as possible and as accessible as possible to everyone, in principle. We put a white paper on the internet that describes exactly how we make and how we test the vaccine. Now in practice, most people are not going to care or act on that.

Phil - Could someone like me make this coronavirus vaccine?

George - Most of it's like a kitchen recipe. The only part that's at all exotic is ordering the peptides; but that's something you order, so it's like you would place an order for any custom item, a photo mug or something. You just send them this recipe that we say, and they make it and they send it back to you. We estimate it's in the order of 50 cents a dose, probably less if it were manufactured at scale.

Phil - Is this sort of democratising the vaccine, or is it closer to trusting people with something that doesn't have the oversight of a state-run vaccine distribution, and that people might hurt themselves with?

George - Most vaccines, you find the negative consequences are quite rare, but you don't find that until you start treating millions of people. The same thing would happen with ours. As soon as we found the negative consequences we would either recommend that people be close to an EpiPen, or otherwise figure out whether they would be at risk or not. But that hasn't happened yet. So far, no negative reactions. I mean, so far we have a better safety record, but that could just be because we have a much smaller cohort size, so it would make too much of that. But I think the critical thing is that you're much safer getting vaccinated than getting exposed to the pathogen. And it's going to be quite a while before we have vaccinated everybody, and so it'd be really nice if you could do the redosing in a convenient way, where we don't have to go into a clinic full of sick people to get an injection.

A globe lying on a facemask with a syringe stuck into it.

45:57 - Why people won't trust DIY COVID vaccines

Is George Church's DIY vaccine a good idea? Bioethicist Arthur Caplan disagrees...

Why people won't trust DIY COVID vaccines
Arthur Caplan, New York University

Is George Church's DIY vaccine a good idea, or will it come to nothing? Bioethicist Arthur Caplan, from New York University, joined Chris Smith to weigh in on whether George Church is on shaky ground...

Arthur - Yeah, I do. I think he's on very shaky ground. Look, when you do vaccines, you're developing a product that you're planning to give to billions of people. You would have to have a manufacturing partner, you need to make sure you follow regulatory requirements, because the risk of something going wrong at huge numbers is just too great. I also think this notion of self experimentation, while it has some role to play in the history of medicine, we learned a lot about experimentation and we know that it matters… your health, your age, your gender. Just showing that something works on one person, or two people, or even ten people, proves nothing about what's going to work in the diversity of people that take drugs and vaccines today, not as it was in the 19th Century.

Chris - Even when it's somebody with a lot of reputation to lose, like George Church? And also, when you wrote your commentary in the journal Science last year, when a lot of this began to surface, you said, "do-it-yourself (DIY) vaccine research is morally troubling. It's an obstacle to securing trust." So why wouldn't people trust it if it's got somebody with a good reputation behind it?

Arthur - Well there's no doubt that George is a brilliant scientist, but that doesn't make people trust vaccines in particular. There are plenty of brilliant scientists who keep saying, "take a vaccine, trust vaccines," and many, many people around the world do not. They worry that people are promoting their pet ideas; they worry that they're out to boost their reputation; they worry that they're out to make money; they're worried that they're short-cutting the regulatory process. So if you're going to get people to trust that a vaccine is something they ought to accept, there may be a few here and there who would say, "if a leading scientists took it, then maybe I'll do it, or maybe I'll brew it up in my basement," but that doesn't cover the vast majority of people with doubts... hesitancy... and I think saying, "yes, it's a do it yourself vaccine! Go ahead, take it, trust in it," is not the path forward to getting a lot of people to take vaccines.

Chris - What did you make of what Josiah Zayner was saying when I put it to him that perhaps by encouraging people to do not just vaccines, but this sort of experimentation, with tools that in the wrong hands can do dangerous things, is there not some degree of irresponsibility? And he said, well, he thinks it's irresponsible that the technology is only in the hands of a small group of individuals, scientists, and academic institutions; corporate hands as well. Do you think he's got a point?

Arthur - No, it's not safe to take genetic engineering and have people who aren't necessarily properly trained to handle it muddling around in their own homes with no supervision or accountability. These are powerful techniques; many people around the world already don't trust things like genetically modified foods. And again, if you want to ruin the future of genetic engineering, which I don't - either medically, or for food, for animal use, or even in humans - then I think the easiest way to do that is to have people think that there are nuts in the basement doing what they want.

Chris - So your view is that at the moment there's a fragile trust, and that's easily broken, because if things go wrong because of a lack of regulation or people just stepping outside the boundaries of what's sensible - and then accidents do happen, let's face it - that will shatter what we do have left of that thread of trust, and we might not get it back?

Arthur - Absolutely right. I think it would take one leak of a modified organism, one death from a do-it-yourself vaccine or drug, and all of a sudden you have fundamentally damaged public trust in drugs and vaccines, or genetic engineering technology. It's seen as too risky, too dangerous, just to have it in the hands, if you will, of amateurs. Look, the public can barely trust it when it's in the hands of professionals, even when there's some oversight. I don't see it as doing anything but creating more mistrust.

Chris - Where do you stand on the point that we heard earlier from... the example given was the discovery of hashish, and the person then documented their own reactions to it, and so on. Obviously this sort of self-experimentation is going on all the time, around the world, with illicit drug use and things like that. People are experimenting; occasionally they might discover interesting things that actually turn out to have enormous therapeutic potential, which if we were not doing that kind of thing, we wouldn't necessarily discover.

Arthur - People do try things, taste things, chew on things; but that's different as a form of self-experimentation from saying, "let's try and disseminate a product, let's get people to pick up on a drug or a vaccine in a big way." Finding out that something might have a beneficial impact on your headaches by chewing a unusual substance is a baby step, and you're not going to stop that, nor should you. But trying to develop products that the world takes -  that's not going to happen through self-experimentation alone.

Chris - Has it not gone too far though? Because - and just very briefly - Barry Marshall, whom we heard earlier, has said he's doubtful, in the present regulatory environment, because of ethical controls and so on, that he would make the same discovery again.

Arthur - But if you will, what we're talking about is the need to produce products. And that's where the regulation is essential to cement that trust.

Musical scores.

52:33 - QotW: When will we run out of music?

Assuming there are a finite number of musical notes, how many years until no more music could be created?

QotW: When will we run out of music?

This week, Katie Haylor has been sounding out this musical musing from listener Dennis...

Katie - Well Dennis, this question certainly got us Naked Scientists chatting!

Eva - I just wonder if the premise is correct i.e. are there a finite number of musical notes?

Adam - There's no limit unless you put other constraints on. You could play C forever, then a D.

Phil - You could put a time limit on it - like how long would it take for us to run out of 3min pop songs or something?

Katie - And you’ve been mulling this over too. Listener Skip reckons that over a googol of tunes are possible. That’s 1 followed by 100 zeros! To add up the answer for us, here’s creative computing expert Rebecca Fiebrink from University of the Arts London.

Rebecca - Let’s start really simple – ignoring harmony and rhythm completely, sticking to the really boring melodies that can just be played on one octave of 8 white keys on a piano. Let’s also just consider melodies of 14 notes– the length of the first phrase of “twinkle, twinkle.” There are 8 to the 14th combinations of such notes – over 4 trillion possible melodies. If we play 100 notes a minute, it would take us over 1 million, 170 thousand years to play all these melodies.

Then, if we add very simple rhythm – the ability to have eighth notes, quarter notes, or half notes as durations, this balloons to over 6 trillion years.

Let’s make this just a bit more realistic – say, the ability to play up to 4 notes at a time, with 8 possible common durations between a 16th note and a whole note, and the ability to play any of the 88 notes on the piano. Even when the harmony and melody notes are restricted to have the exact same rhythm as each other, we’ll need far more than a quadrillion quadrillion quadrillion quadrillion years to play all possible 14-chord-long sequences.

You might call this an overestimate, since most of these sequences won’t sound very musical. And some are going to sound identical after we shift them up or down in key or change their tempo. But we’re ignoring so many other meaningful musical variations here – longer phrases and musical structures, more realistic rhythms, varying instrumentation or adding drums or synthesisers or studio effects… By any estimate I make, you’d have plenty of variations still left to try out by the time the universe potentially ends in 200 billion years. And at that point, whatever life forms are around will probably have very different ideas about what music is, anyway.

Katie - So Douglas Adams’ restaurant at the end of the universe should have some great tunes then - excellent! Thanks Rebecca. Here’s the question we’ll be answering next time, and it’s from David...

David - Would a foetus develop differently in zero gravity conditions?


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