TEOTWAWKI 4) Pandemics, Natural and Bioengineered (2017 Podcast Script)

Author’s note: Clearly I wasn’t right about everything — the focus on vaccines as a preventative now seems quite naive compared to spending money on prevention and disease monitoring and surveillance, and I didn’t note the ticking time-bomb that was a novel coronavirus like MERS— but the fact that a not-particularly-intelligent 21-year-old physics undergrad could, after a few days’ reading, blatantly see the need to invest much, much more in an insurance policy for a pandemic, and the frankly huge potential economic cost of not doing so, gives me a lot of pause now, as I write this in the Year of Our Virus 2020.

TEOTWAWKI 4: Super-virus

One of the things that’s very easy to forget, while writing about the end of the world, is that — of course — it’s already happened.

In 1348, Agnolo di Tura was living his life as a shoemaker and tax collector in the beautiful town of Siena, in Italy. He was a literate man — which was pretty unusual at the time, and liked to describe the goings-on in Siena, as well as his own life, his marriage, and his five children. And then, in that year, he witnessed the end of the world:

“Father abandoned child, wife husband, one brother another; for this illness seemed to strike through the breath and sight. And so they died. And none could be found to bury the dead for money or friendship. Members of a household brought their dead to a ditch as best they could, without priest, without divine offices … great pits were dug and piled deep with the multitude of dead. And they died by the hundreds both day and night … And as soon as those ditches were filled more were dug … And I, Agnolo di Tura, called the Fat, buried my five children with my own hands. And there were also those who were so sparsely covered with earth that the dogs dragged them forth and devoured many bodies throughout the city. There was no one who wept for any death, for all awaited death. And so many died that all believed it was the end of the world.”

We are talking, of course, about the plague that would become known simply as The Black Death, that swept through Europe in the Middle Ages, killing somewhere between 75 and 200 million people. At the time, that was 30–60% the population of Europe. Imagine it, for a second; imagine your family, and your friends, and the people you know barely anything about: from the guy who runs the corner shop to the teacher you disliked in primary school. Everyone you know. Now imagine a third of them, half of them — dead in the space of a few years. Dying in a horrible, protracted, vicious and painful way — and leaving behind chaos in society.

Now imagine that you had no real concept of what was going on — no knowledge about what caused sickness and what could keep you safe. Listen to what Agnolo di Tura is describing. Lots of people thought the plague was caused by some pestilent fog, or the “miasma” — which is pretty close to reality — but just as many people would have thought that people were being infected just by looking at a victim. Families, so desperate, having seen the suffering and the horror — abandoning each other. Like that heart-rending scene in every zombie movie ever where the hero has to shoot her lover, or his father: there’s nothing for it. They’ve been infected. It’s too late for them; any ties of love or sentimentality could kill us all. And this was a time when nearly everyone’s views about the world were completely dictated by a very dogmatic form of religion. Since they had been born, the smartest people they knew, the authority figures, the learned men of letters had been telling them that one day God would return his gaze to the Earth, to punish the wicked and save the righteous. This is what you believe; you look around and see half the population dying, society fragmenting, the end of days — and what else could it possibly be, except the end of the world?

We have short, short memories as a species — and so we’ve forgotten almost what it was like to be threatened by mass death from a pandemic like this. The diseases we’re used to are more of the degenerative variety — heart disease, cancer — horrendous and heartbreaking when they happen to the ones we love, but unlikely to strike multiple people we know at the same time, unless we’re really unlucky. And, crucially, this kind of disease isn’t infectious. There’s nothing like the same kind of fear and terror that arises from this. In the West, it’s almost unimaginable; and, for most of us, thankfully, our contact with this kind of sickness is limited to a few doses of flu; feeling rotten for a couple of days, but not dying en masse.

The influenza virus should remind us that, even though we now understand that diseases are caused by pathogens — viruses, bacteria, fungi — and we can kill them, and treat and mitigate the symptoms. But we can’t stop ourselves from becoming infected in the first place; even though we often know exactly what precautions to take. In the modern era, we’re bound to look on the people who suffered from the plague as people who are far more primitive than ourselves — even though outbreaks of infectious diseases still kill plenty of people, and the Spanish flu killed millions in Europe and the so-called civilized world as late as 1919…

People were unsure who to blame. A chronicle from the time gives you all of the mythology and superstition that you’d expect to surround such an apocalyptic event:

In the month of August,1348, after Vespers when the sun was beginning to set, a big and very bright star appeared above Paris, toward the west. It did not seem, as stars usually do, to be very high above our hemisphere but rather very near. As the sun set and night came on, this star did not seem to me or to many other friars who were watching it to move from one place. At length, when night had come, this big star, to the amazement of all of us who were watching, broke into many different rays and, as it shed these rays over Paris toward the east, totally disappeared and was completely annihilated. It is, however, possible that it was a presage of the amazing pestilence to come, which, in fact, followed very shortly in Paris and throughout France and elsewhere, as I shall tell. All this year and the next, the mortality of men and women, of the young even more than of the old, in Paris and in the kingdom of France, and also, it is said, in other parts of the world, was so great that it was almost impossible to bury the dead. People lay ill little more than two or three days and died suddenly …. He who was well one day was dead the next and being carried to his grave. Nothing like the great numbers of 1348 or 1349 had been heard of or written of in the past. In many places not two out of twenty remained alive.

The chronicler may not have read of the great plagues of Justinian in the Roman era, or the Antonine plague, which killed similar numbers of people in the Roman Empire — at least in terms of the fraction of the population — although they didn’t bring about the same levels of societal collapse. But they were brought about by the same pestilence, the same pathogen, the same disease, hundreds of years apart.

And while society has obviously changed dramatically in the intervening years, one thing that hasn’t changed is human nature. And we can imagine that our reactions to a similar apocalyptic event, if it happened now, wouldn’t be all that different… once the thin veneer of civilization is stripped away… human nature is the same. We might react in the same way.

After all, when things go wrong, don’t we still cast around looking for people to blame? Jean de Venette, who survived the plague in France:

“Some said that this pestilence was caused by infection of the air and waters, since there was at this time no famine nor lack of food supplies, but on the contrary great abundance. As a result of this theory of infected water and air as the source of the plague, the Jews were suddenly and violently charged with infecting wells and water and corrupting the air. The whole world rose up against them cruelly on this account. In Germany and other parts of the world where Jews lived, they were massacred and slaughtered by Christians, and many thousands were burned everywhere, indiscriminately. The unshaken . . . constancy of the men and their wives was remarkable. For mothers hurled their children first into the fire that they might not be baptized and then leaped in after them to burn with their husbands and children.”

The Black Death changed society in a lot of fundamental ways, such was the death toll. One of the things that it did manage to do, although chroniclers of the time didn’t always realize it, was fundamentally shift the economy of the Middle Ages. The poorest class actually became wealthier as a result of the pandemic — because there were fewer labourers around, and because the plague disproportionately struck the young and healthy, an individual peasant was suddenly worth a lot more to the market. They could charge more for their labour. A small recompense, you might think, for half of the people you know dying in agony. The scars of the Black Death remain on Europe, even today; aerial photographs can show the remnants of entire villages and towns that used to exist, but were completely depopulated by the plague.

The Black Death was an example of a disease that spread via “vectors” — animals that spread diseases from person to person. In the case of the plague, it was the fleas that lived on the rats that swarmed in the cities which spread the disease so quickly. And this is a dangerous thing to note: it was the changing living styles, and gradually increasing urbanization, that meant you had major population centers in towns like Siena. With these population centers came rubbish and food waste, and with these things came the rats, the fleas, and the pestilence. It’s no coincidence that the plague struck the Roman Empire, with its sprawling, cramped cities, particularly hard. Changing ways of human life open up new opportunities to pathogens, who long to exploit them.

[TALK ABOUT THE MODERN RISKS OF A PANDEMIC]

Amazingly, the ancient romans were probably more hygienic and practiced better medicine, in some ways, than people did in the West a thousand years later. The Ancient Romans loved their running water — yes, the aqueduct was one of the things they did for us — and cleaned the filth from their streets. Hot water, and bathing regularly, were the marks of civilization. By our standards, they may still have reeked in the cities, but they were far cleaner than the generations that followed. By the 14th century, this was no longer fashionable. The aqueducts had been wrecked centuries before by the invading Goths, who likely didn’t appreciate the way the water interfered with their eyeliner. (Sorry not sorry.) But the theories about medicine could be… counter-productive. Take the theory that bathing in hot water ‘opened the pores and allowed miasmas into the body.’ King Henry III’s surgeon stated that “Steam-baths and bath-houses should be forbidden. When one emerges, the flesh is softened, the pores open, and as a result, pestiferous vapor can rapidly enter the body and cause certain death.” This was written in 1568, and led many bath-houses — which had survived as a luxury in some cases — to be closed.

The medical malpractice didn’t end there. In the Victorian era, the great plague in the West was cholera. Quoting from Sonia Shah’s excellent “Pandemic”;

“Cholera took hold of Paris in late March 1832. Without the benefit of modern medicine, it killed half of those whom it infected, causing a set of uniquely horrifying symotoms. Without hours, cholera’s dehydrating effect shriveled victim’s faces, wrinkling skin and hollowing cheeks, drying up tear ducts. Fluid blood turned tarry, clotting in the bloodstream. Muscles, deprived of oxygen, shuddered so violently they sometimes tore. As the organs collapsed in turn, victims fell into acute shock, all the while fully conscious and expelling massive amounts of liquid stool…

In the evenings during that terrible spring, Paris’ elite attended elaborate masquerade parties, where, in defiance, they danced to cholera waltzes, dressed as the ghoulish corpses many would soon become. Every now and then, one of the revelers would rip of his mask, face purpled, and collapse. Cholera killed them so fast they went to their graves still clothed in their costumes.”

And then, the treatment was far worse than the disease. Noticing the effect of dehydration making the blood thick and clotted, blood-letting was popular to “let the bad blood out.” Other treatments included inducing vomit, which only deprived the victim of more fluids. Everyone believed that diseases spread due to bad smells, and miasmas — which make sense, because the body instinctively reacts and feels ill when a rotten smell is present, so you can see what they’re saying. Of course, our bodies are in fact conditioned by evolution to warn us about the presence of bacteria which cause the real damage. But in order to get rid of the bad smells, 19th century high society flushed their waste into the rivers — the same rivers which provided the drinking water, and led to the spread of cholera.

Listening to this, you’re probably convinced that our better understanding of diseases has prevented us from engaging in such stupidity today. And while it’s true that we have cures that — you know — actually work — there is still a fair deal of stupidity in the way they’re used. A key case study here is the antibiotic. When several different medical practitioners (although Fleming gets all the credit) noticed that fungi produced a substance that could kill bacteria, it wasn’t long before some very clever scientists managed to concoct a synthetic version. Dorothy Crowfoot Hodgkin, the British X-ray crystallographer, managed to establish the atomic structure of penicillin in some groundbreaking work that allowed it to be synthesized. It was perhaps one of the greatest gifts that science has given to the human race. She would later determine the structure of insulin, after thirty-five years of efforts in that direction, and she won the Nobel Prize.

Penicillin saved millions of lives. But soon it will no longer be effective. The issue is one of evolution. As antibiotics are used in a more and more widespread way, any little bacteria that have mutated to resist their effects become more and more strongly favoured by natural selection. Soon enough, the only ones that survive are the resistant strains, and the antibiotic is no longer effective. This is a natural process, and kind of unavoidable — but we have made things worse in the way we use antibiotics. Experts have said that, if properly stewarded, these substances could have protected us for centuries to come — but instead, we take them when they’re not really needed, almost as a placebo. We even give them to animals to promote their growth and prevent disease outbreaks in factory farms. And, as a result, the efficacy of these weapons has been considerably reduced. Big pharmaceutical companies, although they do research into new antibiotics, realize that a drug that you take for a few weeks and then stop is nowhere near as lucrative as a drug you must take forever, and so they concentrate their resources in these other areas. Besides, there are only so many antibiotics that will be effective to pathogens without harming humans.

There are other ways in which we’ve rendered ourselves more vulnerable to a pandemic than we need to be. In the modern era, global transportation networks mean that outbreaks don’t have to be geographically limited any more. In the Middle Ages, a single infected person might infect a few others in their town, or village; that’s bad enough. In the modern era, if that person travels through an airport, they could seed simultaneous outbreaks in different corners of the globe. In 2003, this happened with SARS (Sudden Acute Respiratory Syndrome) — a Chinese doctor who was initially infected stayed in a hotel with many other guests in Hong Kong. The guests themselves became infected and the disease spread to Vietnam, China, Taiwan, and Thailand. Before too long it was infecting people in Canada, as well. The reaction to the outbreak, at least initially, was telling — reports that came out of China were cloudy as, to avoid panic, specific cases or suspected cases went under-reported until the government was forced into disclosing them via media attention. Thankfully, the SARS outbreak was contained by the tireless efforts of the healthcare workers involved, and dozens of doctors lost their lives containing the outbreak.

We can’t stop people from travelling on planes. And, although airports have systems that claim to be able to detect elevated body temperature and flu-like symptoms, I am skeptical about how effective they are. For a start, the viruses can often incubate in the body for a while with no symptoms — and you’d expect a really virulent pandemic to be like this — and, secondly, I went through one of these scanners once with a dreadful cold and it didn’t seem to notice. Now, obviously that’s anecdotal evidence — and probably they’re unmanned if there’s no outbreak that people are concerned about — but by the time the authorities react and ground flights, it will probably already be too late to prevent multiple outbreaks in multiple countries from taking place.

We can’t de-globalize the world. But one of the key things to point out here is that the human race as a whole is not responding to potential threats of pandemics in the most effective way possible. These diseases often arise from places where, due to poverty, or disruptions such as civil wars, the distribution of healthcare is severely disrupted or non-existent. The best chance of fighting some new pathogen is to nip it in the bud, at the place of origin, with a highly concentrated effort. We saw this with the incredible effort to stop the last outbreak of Ebola, which just about managed to contain the disease — although not before thousands died across three countries. Yet the time-lag between the first death, and the outbreak being reported to the World Health Organization, was nearly four months. If there was greater equality in the healthcare system throughout the world, there would not be such a huge risk to our society. In a globalized world, regions that have insufficient healthcare — at least when it comes to virulent diseases like this — are a risk for everyone. I’m not saying that foreign aid money is always spent wisely by governments; that’s a political issue where I’d have to do a lot more research — but in principle, the price we pay for ease of travel around the world should be making sure that we have a flexible, global system that can find these pandemics and stamp them out before they get too serious, wherever they occur.

You’ll probably notice, if you pay attention to reports of viruses in the media, that many of the pandemics that cause the most fear are the ones that are transmitted from other species into humans. Examples include HIV/AIDS, which we believe originated in monkeys, and probably spread to the humans that hunted them for bushmeat via the infected blood. Similarly contaminated meat and blood may be responsible for the transmission of ebola and SARS. And there was recently a big storm in the media about a potential swine flu pandemic; before that, people were concerned about bird flu. Why is it that these diseases that jump from animals are such a big concern?

As you probably won’t be surprised to hear — the answer, again, is related to evolution. The reason that viruses that transmit across the species are most dangerous is because they haven’t yet adapted to humans properly. For a start, a virus that’s transmitting a new strain to humans may well be unstable and prone to mutations. But it’s often the very high fatality rate that makes these diseases so scary. For example — rabies, which is transmitted via animal bites, is fatal in nearly all cases unless it’s treated. Illnesses like Ebola can kill anywhere between 25% and 80% of people who become infected. Part of this is down to the fact that a new virus crossing over into humans doesn’t have established treatments that work for the virus, but a big part of it is down to evolution. Ideally, a pathogen doesn’t kill the host; after all, the host is home to all of those bacteria. The pathogen really doesn’t have too much interest in killing its host; ideally, it uses the host as a means to spread itself as far as wide and possible. Can’t do that if you’re dead. That’s why mild strains of influenza, that cause you to infect plenty of other people if your boss makes you go into work, are far more successful and prominent diseases compared to those that kill in 100% of cases.

But a disease that’s recently crossed over from animals hasn’t yet adapted not to kill the host; so the concern is an illness that’s both highly contagious, airborne or transmitted from person to person, and highly fatal. And, in the first few strains that cross over into humans, you may well have exactly that.

In the case of a virus like Ebola or SARS, the only reason they’re not even more deadly than they are today and a bigger threat to the species is that — although highly fatal — they can only be transmitted by fairly close contact with an infected person; and, because the person is only contagious for a brief time before visible symptoms start, something like quarantine can be effective against these viruses. But nightmare mutations that could render these diseases much harder to combat might be either a disease that incubates for a longer time — allowing people to travel and disperse before becoming contagious. A disease that was contagious before major symptoms started would make it impossible to quarantine people, who might not realize that they’re spreading a deadly pandemic. And, if such a disease could become easily airborne or waterborne — far more contagious and more easily infecting people — then it would also be far harder to deal with. And mutations that might cause this could occur at any time.

When you think about pandemics, you can start to get into this weird ‘apocalypse as an insurance policy’ type of thinking. Personally, I think the threat from pandemics is a huge argument for giving money to organizations like the UN, and charities like Medicines sans Frontiers. Our only hope is to ensure that the monitoring and outbreak control occurs all over the world; if a truly nasty pathogen hits, it won’t be possible for any one nation to act unilaterally. And what would the cost be of a truly awful pandemic?

Looking at the insurance risks, it may reassure you to learn — for example — that recently, at the world economic forum in Davos, famous for its skiing and its capitalism, world governments pledged $500 million towards developing vaccines for diseases that the world health organization has identified as potentially leading to pandemics. This has to be separate from the World Health Organization — which can’t muster the funds to do their own vaccine research and development on this scale; and, also, it has to assess whether the vaccines are up to scratch, so there’s a bad conflict of interest in developing the drugs you’re also assessing. Hence, the creation of this independent group to research vaccines, and the $500m in funding. This sounds like a reassuring step, until you realize the scale of the problem that we’re talking about, and how small $500m actually could be.

Let’s take the 1918 flu as an example. Often called the forgotten pandemic, the influenza outbreak of 1918 — sometimes called Spanish Flu, although this is incorrect as it didn’t actually originate in Spain — was particularly bad: it killed people by triggering an overzealous response in their own immune system. This meant that the young and healthy, who had the best immune systems, were hardest hit by the autoimmune response. That pandemic killed 5–10% of the people who were infected; high enough to be a serious concern, but low enough that the pandemic isn’t self-limiting. It was very contagious, however, and infected 500 million people; meaning that between fifty and a hundred million people worldwide are estimated to have died from the 1918 Spanish Flu. That was 2–3% of the world’s population.

Let’s say that this is the worst we can possibly expect from a naturally occurring pandemic. That still means that in the modern era, 140 million people could die of such a pandemic. A bit of cheap and cheerful arithmetic suggests that we’re therefore spending around $3.50 to prevent each death; and, suddenly, it doesn’t seem like such a big bargain.

I’m sick of seeing statistics and human lives measured in terms of economic productivity, but, if we’re going to measure everything by these stupid yardsticks, let’s use it for good as well as evil. As I type this — probably a few weeks back when you hear it — there’s about to be a big eclipse in North America. The estimate is that, due to the people watching the eclipse, the economy will lose $700m in ‘productivity’. (Of course, this doesn’t take into account the benefits of people going to see the eclipse and spending money, or the kids who will be inspired to take up science as a result, etc., etc.; if you’re listening from the US, I hope you got to see it, and I hope you enjoyed it.) The point is that these things scale up in a pretty impressive way. People taking a few minutes out of their day to watch the eclipse nominally costs more than the amount of money that the world pledged — at least in this scheme — on vaccines to prevent pandemics.

Then there’s the economic impact of the pandemics themselves. Ebola, as horrifying as it was, killed 11,000 people. The Zika virus, as terrible as it is, has killed far fewer — perhaps a few dozen. Yet each of these has already cost the global economy not millions, but billions of dollars. Pandemics cost $60bn a year; that’s more than 100x what was invested towards these vaccines, every year. And this is without a major global outbreak. If a pandemic like the one I imagined- with historical precedents not so long ago — arose… it would cost us trillions. Economist Larry Summers argues that one of the best investments ever made was in 1938, when $26m was invested by the US government to help create the polio vaccine. The reason this investment was so good? The vaccine saved $180bn in expensive treatments down the road, alongside saving many lives, and averting much suffering. Every dollar spent on that vaccine saved nearly $7000. The solution is obvious, and it’s something we’ve known for a really long time: an ounce of prevention is better than a gram of cure.

So, if this is such a slam-dunk, why aren’t the big pharmaceutical companies doing anything about it? The issue for them is one of profit, as it is for all companies. Yes, the same driver that led Martin Shkreli to jack up the price of his drugs to be completely unaffordable. Big pharma companies don’t necessarily want to spend millions of dollars researching vaccines for viruses that may never become pandemics. When a disease becomes ‘famous’ — like Swine Flu — the race is on to rapidly develop vaccines against these illnesses, and be the first one with a product they can sell. Indeed, in the Swine Flu case, they had a vaccine fairly quickly. But the most successful model for disease control — keeping a store of vaccines for every strain that could become a threat, and distributing them quickly and effectively to small, localized outbreaks… This would work very well at controlling diseases, saving lives and dollars. But it’s a terrible business model. Most of your R&D is for products that never get used; and the vaccines that do get used are only used on tiny numbers of people. Better to focus your research budget on medicines that need to be taken daily or weekly by large numbers of people.

I don’t want to bash big pharma too unnecessarily. This is the correct and profitable thing to do; if you don’t do it, you will be outcompeted and your company will fold. It’s just an example of how unfettered, unlimited capitalism is terrible at solving certain kinds of problem, in the same way as totalitarian state control of everything brings about its own problems.

I think there’s a good argument that the amount we spend on these vaccines should be brought into line with the ridiculous military budgets that exist in some places in the world. In the US, $1.4bn gets spend on vaccine research and development each year — half of that is made back from the sales of the vaccines, and another chunk comes from venture capitalists — so taxpayers contribute around $500m. The US military budget is over 1000x more than that, and far more people die of preventable diseases than military conflicts. You might say: “That’s only because the military is so well-funded that we don’t have any major conflicts.” Sure, if that’s how you want to put it: I just want to have a world where we can say the same thing about diseases which could be vaccinated.

Thanks for listening! This was the first part of a two-part series…

Supervirus Part II: The Human Threat

There is, of course, a threat from humans, as well. In the process of developing biotechnology, we have the potential to cause a healthcare revolution that would render antibiotics obsolete. For example; a genetically modified virus that could distinguish between cancerous and non-cancerous cells, and bolster our own immune systems. But, like every new technology, with greater benefits there are also greater risks. The Future of Humanity Institute is concerned with bio-engineered viruses, which could self-replicate and spread uncontrollably if they were ever allowed out of the lab. Smallpox has been eradicated through vaccination — this disease that killed hundreds of millions of people in the 20th century is no longer transmitted in the wild. And yet, despite orders from the World Health Organization, the US and Russia continue to maintain stockpiles of the smallpox virus. Both sides argue that the viruses are kept for research, in case a pandemic breaks out due to some surviving viruses in nature — and it’s true that viruses can remain infectious for a very long time — but many medical experts argue that there’s no public health benefit to keeping smallpox viruses around. The stockpiles that exist may be the most likely sources of any transmission to humans, as occurred in Birmingham in 1978. Smallpox has been used as a bioweapon since the French and Indian wars, or even earlier: if any of my fellow Brits are feeling especially patriotic about the Empire, it’s good to remember that the British Empire had a deliberate policy of trying to infect Native Americans with smallpox. The Soviet Union, testing a weaponized version of smallpox in the 1970s, unleashed a deadly version of the virus on an island in 1971 that killed three people before it could be contained.

I’ll say two things on this: the first is that I imagine if smallpox wasn’t so deadly, and couldn’t be used as a bioweapon, the authorities in the US and Russia probably wouldn’t give a damn if it was destroyed. The second is that, sadly, the question has been made moot by modern technology. The genetic information of the smallpox virus is out there, available online. In 2017, Canadian scientists recreated an extinct horsepox virus — to demonstrate that, with a small lab, $100,000, and a few canny scientists, someone could pretty easily recreate the smallpox virus if they wanted to. At the height of the Cold War, the Soviets were working on some pretty nasty stuff. In 1979, they accidentally released hundreds of spores of weaponised anthrax near Sverdlovsk. The exact death toll will probably never be known, because the KGB descended and suppressed much of the evidence, but well over 100 people are likely to have died. Chris Impey, in his wonderful book “How It Ends”, discusses the Soviet weapons program.

“What little we know is worrisome enough. For 20 years, Sergei Popov was one of the top scientists at a Siberian research facility, where he worked on genetically altered pathogens. In Project Bonfire, he created plague bacteria that were resistant to 10 types of antibiotics, and anthrax modified to resist all vaccines. In the very scary Hunter Program, whole genomes of viruses were combined to produce hybrid and untreatable viruses. Interviewed for a 2001 Nova Special, he said “Imagine a bacterial agent that contains inside its cells a virus. The virus stays silent until the bacterial cells get treated. So, if the bacterial cells get recognised and treated with an antibiotic, there would be a release of the virus — so after the initial bacterial disease is completely cured, there would be a viral disease on top of this. It could be smallpox. It could be Ebola. These were on the list of potential agents.”

Evolution through thousands of generations of viruses has created tailor-made weapons that are better at killing humans than most weapons we could dream of designing — and, now, it seems, it’s getting to the point where the bioweapon genie will be well and truly out of the bottle.

Perhaps one of the things that has saved us from bioweapons in the past is that — despite humanity’s propensity to split into groups that hate each other — to viruses, we’re all the same. No state could unleash this kind of weapon without risking their own destruction. This is, of course, the same tenuous logic that keeps us “safe” from nuclear weapons. But, as we’ve just established, this technology is about to get widespread enough that, unlike nuclear weapons, it won’t just be a state that can concoct this kind of bioweapon. Small companies or individuals, with the proper equipment, could manage it. Psychological profiling is not a requirement for people who work at biotechnology firms; the world is filled with startups looking to leverage our new abilities to their advantage, and regulations will need to keep up with the pace of change. This is why it’s more necessary than ever to have scientists working in government — or, at the very least, a government that is not skeptical of science! So, scenarios where a disgruntled individual releases a bioweapon, or it’s accessed by an apocalyptic death cult, or where it simply ends up escaping by accident due to improper safety regulations in the rush to harness the power of biotechnology; all of these are scenarios that the Centre for Existential Risk people need to consider. Some have already had precedents — the Aum Shinrikyo cult in Japan were working on anthrax and released sarin gas into the public subways in a horrible attack. They tried to locate the Ebola virus but were luckily unsuccessful. Take someone like Ted Kaczynski — most of you probably know him as the Unabomber, a highly intelligent but deranged individual who used his mathematical and engineering abilities to manufacture bombs that killed innocent people, as part of his radical political ideology. If he was at large today, you imagine he’d be looking at biotechnology. With these sorts of weapons, one person could conceivably lead to the deaths of millions. Even the modifications need not be intentional — for example, there was a research study that aimed to change mousepox to make mice sterile as a means of pest control, but it ended up creating a virus that was fatal even to vaccinated mice. Those that are intentional could be far worse — such as the Soviet research that demonstrated that the Ebola virus could be made to spread in an airborne way. An airborne Ebola virus is every health worker’s worst nightmare.

The biotech revolution, if it turns out to be all it’s cracked up to be, is going to be unavoidable — the kind of progress that you can’t afford to miss out on, as a civilization. And it’s not like we’re ever able to put technologies back in the box, if we decide they’re too dangerous: from the internet to nuclear weapons to guns…

There’s a lot of hype at the moment about CRISPR. I’m not a biologist, but I will try to explain as best I can. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. They were first discovered in bacteria; they noticed these DNA sequences that were palindromic, the same forward and backward, in the bacteria. It was later discovered that this was actually the self-defence mechanism for the bacteria, like the bacteria’s own immune system. When the bacterium was attacked by a virus, it would take a snippet of the virus’ DNA, and use that snippet to automatically target and destroy future viruses it encountered. They have discovered that you can use the techniques and the enzymes employed by the bacteria to edit the *human* genome, by putting in the bit of the DNA as interest as an appropriate CRISPR. A molecule of “guide RNA” is used to tell the enzymes where to go; the enzymes act as “scissors” that snip away part of the DNA. What’s more, when the body discovers that DNA is damaged, it attempts repair; and scientists believe we’ll soon be able to control this to introduce whatever kind of mutations we want.

This is the cheapest, most versatile and effective method of editing genomes that has yet been discovered. And it could lead to incredible breakthroughs in medical science. The “CRISPR toolkit” that allows a well-maintained lab to start genome editing with CRISPR could end up costing as little as $50; in other words, it’s far cheaper than anything that came before. For a start — with the ability to edit an individual gene, we can actually figure out precisely what traits each gene controls, which has previously been something you had to try and figure out by statistically analysing the properties of the genomes of people with the trait you’re interested in. I guess it’s the difference between watching a master pianist playing a symphony — and from that footage, trying to work out what the middle note C sounds like. Now we can just go to the piano, and play the note. Once we have a better understanding of what all these genes are doing, we’ll know about the health risks that people have. And, of course, then there’s all of the crazy sci-fi aspects: you can EDIT the human genome? It only starts with removing genetic vulnerabilities and repairing genetic flaws that lead to inherited diseases or defects. By the way, this can obviously help to solve the Malthusian crisis by creating strains of wheat and other crops that are invulnerable to diseases. There is a whole world of bizarre consequences to think about: genetically-engineered humans. The genetic information that makes you up as a registered trademark. And, because we’re talking about the apocalypse, presumably, more ruthless and efficient ways of killing people.

CRISPR needs to be improved before it can be used on humans — especially in the case of the targeting mechanism; as you can imagine, if it’s even slightly off, there could be terrible unintended consequences. But they have already successfully used it on human embryos to remove a gene that causes heart disease. It’s been used to completely remove HIV from living cells. They have edited genes to make people less susceptible to cancer. They have edited genes to make superviruses destroy themselves, and to make mosquitos infertile so they can’t spread Zika or malaria. The Bill and Melinda Gates foundation are already investing in CRISPR research that might prevent mosquitos from transmitting malaria — or drive them to extinction, which scientists think may well be possible. As if we need a more efficient way to make species go extinct! They have used CRISPR to edit out Huntingdon’s disease, a nasty acquired genetic condition, from mice. And they have even used it to engineer a semi-synthetic form of life — artificial life — by modifying E. Coli. Bacteria. Just as I was writing this, I read a stunning article; using CRISPR, scientists have successfully encoded a computer virus into human DNA. When the DNA strands are “read” by a computer as part of DNA sequencing, they were able to shut down the sequencer and execute a few commands on the computer. DNA is an incredibly efficient mechanism for storing information; could it be possible that, in the future, viruses could attack both the biological and non-biological parts of a cyborg human at the same time?

In the rush to exploit all of the possible — and wonderful — benefits from this new technology, though, or one like it — naturally there are concerns that it could fall into the wrong hands: or, that through sheer overenthusiasm or accident, we could wreak catastrophe in an attempt to help people. The US Defense Advanced Research Projects Agency (DARPA) — yes, the people behind the internet — invested $65 million in a project called “safe genes,” designed to improve the accuracy and safety of CRISPR. The seven research teams will remove engineered genes from environments to return them to baseline “natural” levels. Let’s hope that all future developments in this exciting but terrifying field are equally well-regulated, and that we have some checks and balances to harness the best side of this technology while avoiding the danger. One thing is for sure: whether it’s CRISPR or some other technique, the potential upsides — and REVENUE — that can be generated from this technology is going to make it irresistible for us to develop and investigate. It’s here to stay, and it will become increasingly normal…

One of the reasons that the bioweapon possibility is the most threatening is that, in the case of naturally occurring diseases… there is a natural incentive not to kill the host. If you look at influenza, probably one of the most successful viruses in human history — very few strains have high death rates, allowing one carrier to transmit strains to multiple humans. It’s only the types that recently make the jump to infecting humans — bird flu and swine flu — that still haven’t adapted not to be fatal to humans. And, if the disease relies on person-to-person transmission, there’s a limit to how many people it could kill before it stops spreading quickly enough. This is not the case in viruses that are transmitted by carriers — like malaria, for example — but, of course, if the virus has a carrier, it can only transmit itself to humans that live in close proximity to the carrier. Humans can kill the carriers and stop the spread of the virus, and that’s far easier to do than killing a pathogen. But in an interconnected society like the one we have, death tolls like the ones seen in the Black Death — one in three — would easily be enough to destroy the world as we know it.

A bioweapon doesn’t have these limitations. For example, you could imagine that someone could create a bioweapon that is specifically tailored to kill humans — a pathogen that’s airborne, but doesn’t have any really noticeable or fatal symptoms for about a month. One that’s contagious before it starts being deadly. That way, it could spread to millions of people before we even realized there was a problem beyond the common cold.

Even so, though, you might think that there would probably be enough variation in the human population to allow some of us to be immune — even in the case of something like HIV, which was transmitted to humans, populations have built up immunity. The genetic diversity is out there. Studies have generally suggested that even the most virulent pathogen could probably only kill about 96% of a human population. (Which, let’s be honest, is not exactly reassuring.) But what about a pathogen that targeted our food crops? They can be far less genetically diverse. The same Green Revolution that allowed us to feed our advanced population may mean that crops like wheat or rice are more vulnerable to viruses or fungal infections than they ever were. Bioweapons that targeted these crops would wreak havoc on our food supplies. The only really reassuring thing I can think of to say at this point is that, while this capacity has been available for over fifty years, no-one has seen fit to use it yet — save in a couple of isolated incidents which were luckily involving groups of humans too small to make a major difference.


We have made incredible advances in medical technology. For many thousands of years, the only recourse our civilization had when plagues arrived was to pray and to wait for them to burn out; often in ways that killed huge swathes of the population. Even in 1919, the Spanish Flu was the deadliest pandemic in history. Somewhere between 50 and 100 million people were killed by this pandemic — exceeding the death toll in the First World War. This pandemic is nowhere near as notorious as it should be, given how recent it was — and the fact that global transport meant that vast swathes of people were killed in countries as far apart as India and the United States. One reason is perhaps that the First World War was raging, and reporting on the pandemic was suppressed to keep morale higher; only in neutral countries such as Spain would governments allow proper reporting to take place, which is why it’s referred to as the Spanish Flu. Even the King of Spain — along with 500 million other people — were infected by the flu. Its impact was exacerbated by soldiers moving around during the First World War — indeed, some people think its origins may have stemmed from unhygienic conditions at the front line. What’s worse, a quirk of the virus meant that it killed people through an exaggerated, unhealthy autoimmune response. This means that the people who died were those with the most robust immune systems: the young and healthy.

Yet now, for the first time, we have genuine hopes and aspirations to take back control. We have eradicated diseases that have killed people for millenia. Others, like the bubonic plague, break out in extreme conditions and can be contained; only around a hundred people a year die from the bubonic plague thanks to modern medical science and hygiene. We are beginning to dream of curing long-term, degenerative diseases like cancer and heart disease, and extending the human life-span in unprecedented ways. I do not want to demonize biologists; one day, the work of biotechnologists like this may well extend or save my life and yours. Just as the physicists had their dangerous revolution with nuclear energy and nuclear weapons, we are on the cusp of a similar, biological revolution — and it could be great for the human race. But as the lines between biology and technology become more and more blurred, and we see once again that the power of our technology is rapidly outpacing advances in our intellect and morality, we are reaching yet another dangerous tipping point in human society. These things are irreversible, so it’s crucial that we are aware of the risks and make informed decisions. Mass transport and the way we live now, in vast cityscapes, can render natural threats more dangerous than ever. We could have a future where widespread healthcare renders pandemics a bad dream for our species and a civilization — or one where the pathogens we’ve designed prove more deadly than anything nature came up with.

One upside to all the doom and gloom; when I described the Black Death at the start, I noted that human nature hasn’t really changed. And all of the chroniclers who talk about the plague say that the people who did, somehow, manage to survive — well, they were elated. After all, they’d just made it through the end of the world. The man who buried his five songs, Agnolo di Tura:

“The city of Siena seemed almost uninhabited for almost no one was found in the city. And then, when the pestilence abated, all who survived gave ‘themselves over to pleasures: monks, priests, nuns, and lay men and women all enjoyed themselves, and none worried about spending and gambling. And everyone thought himself rich because he had escaped and regained the world, and no one knew how to allow himself to do nothing ….”

So, you know, if you do happen to be one of the few survivors, and I make it through as well — let’s throw an apocalypse survivor’s party. Drinks are on me. Just don’t come if you’re feeling unwell.

Thanks for listening etc.

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