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November 21, 2018 57 mins

Natural viruses and bacteria can be deadly enough; the 1918 Spanish Flu killed 50 million people in four months. But risky new research, carried out in an unknown number of labs around the world, are creating even more dangerous humanmade pathogens. (Original score by Point Lobo.) 

Interviewees: Beth Willis, former chair, Containment Laboratory Community Advisory Committee; Dr Lynn Klotz, senior fellow at the Center for Arms Control and Non-Proliferation.

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Episode Transcript

Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:03):
Probably more than any other field that poses an existential risk.
The dangers of the biotech field are the easiest to understand.
The field deals with bugs, viruses, bacteria, pathogens that can
kill us if we're infected by them. And every one
of us has experienced infectious disease firsthand, like the preschooler

(00:24):
catching the flu and bringing it home and making the
whole family sick, or having to cancel your vacation because
the place you were going has become a zeke a
hot spot. It's pretty basic stuff, and it's relatable to us.
But when you dig deeper into the biotech field, it
becomes clear that the risks it poses are maybe the

(00:45):
most immediate of all the existential risks. The pathogens the
field studies in the hopes of creating vaccines that can
save lives pose a pretty severe threat as they are
not too long ago. Wild viruses like small pox and
influenza killed a lot of people, as we'll see in
this episode, and bugs like that can still kill a

(01:07):
lot of people, and that's threat enough. But the existential
threat from biotech comes from the type of research that
began to proliferate in the early twenty one century. When
high containment labs begin to mushroom around the world, and
a type of research called gain of function really took off.

(01:28):
No longer were researchers dealing with wild viruses and bacteria.
They were forcing evolution in them by speeding up mutations
and altering them genetically to be deadlier and more contagious.
This kind of research is extremely dangerous. If a genetically
altered bug escapes from a lab, it could kill a

(01:49):
potentially staggering amount of people before it is contained. If
it is contained, but if done right, the risks from
these experiments can be minimized. The trouble is they're frequently
not done right. As you'll see, the biotech field has
a shocking track record of accidents and a willingness to
take huge, possibly unnecessary risks. And what's most unsettling is

(02:14):
that there is precious little oversight on the risky experiments
being carried out around the world. Even seemingly innocuous experiments
have the potential to produce catastrophic results. And I can
show you now if you'll follow me to Canberra, the
capital of Australia. We're back in two thousand. A pair
of researchers named Ron Jackson and Ian Ramshaw are unpleasantly

(02:37):
surprised with the results of an experiment they've just conducted.
Australia has a significant mouse problem. Mice were probably introduced
to the country as stowaways among the ships of the
British settlers in the eighteenth century, and when they arrived,
they began to spread and grow to unusually large numbers.

(02:59):
Especial slee in the southeast, where Australia grows its grain.
During what the country calls its mouse plagues, farms are
overrun with mice that streamed from seemingly everywhere. The ground
ripples with them. The mice are so abundant and aggressive
that they can chew through the tires of farm equipment,

(03:20):
and they attack pigs and poultry. On mouse plague caused
nearly one hundred million dollars worth of damage to crops
and farms. What Ramshaw and Jackson were looking for was
a way to sterilize female mice by training their immune
systems to attack their own eggs. To do that, the

(03:40):
two biologists created a vaccine that contained a gene which
codes for the production of something called inter luken four,
which is a naturally occurring protein i L four stimulates
mammals to produce antibodies to deliver the genes to the
mice's DNA. The researchers used a virus because of a

(04:01):
virus's unique ability to insert its own genetic information into
a cell's DNA and hijack a cells normal processes. They
make ideal vehicles to deliver the main ingredient in a vaccine.
The virus adds it into the cells genetic code along
with its own genetic material. The cell produces whatever it

(04:22):
finds in its genetic code, whether it was added there
by a virus or by a human. It's pretty impressive
researchers hijack a virus's ability to hijack a cell. Jackson
and Ramshaw chose the virus that causes mousepox ectromelia as
the vehicle for their vaccine. Normally, mousepox would kill a

(04:42):
lot of the mice that were exposed to it in
the study, but the researchers were using mice that had
been previously vaccinated against mousepox, along with other mice that
had been genetically altered to be totally immune to the disease. Few,
if any, of the mice used in the study works
to die from exposure to the mousepox, but within nine

(05:04):
days of receiving the vaccine, every single mouse in the
study was dead. The mousepox had a one hundred percent
mortality rate. It killed every mouse that had been exposed
to it. The researchers found that the i L for
gene had indeed increased anybody production in the mice as intended,

(05:26):
but the increased inner lucan had another unanticipated effect. It
also suppressed the mice's cell mediated response, a function of
the immune system which wards off infections by viruses. By
adding the i L four gene to the mouse pox virus,
the surge of inter luken told the mice's immune system

(05:46):
to lay down its arms, which paved the way for
total annihilation by the mousepox virus, even among mice that
had been genetically designed to be immune to the disease.
Jackson and Ramshaw had x dently created a perfect killer
of mice. Mousepox bears a resemblance to smallpox and humans.

(06:08):
The two viruses are distantly related, and it was not
lost on Ramshaw and Jackson what would happen if their
technique was used with smallpox instead of mousepox. Jackson told
new scientists, it would be safe to assume that if
some idiot did put human ill four into human smallpox,
they'd increase the lethality quite dramatically. Something like that would

(06:31):
be monumentally bad. Smallpox is caused by the very ola virus.
It's an ancient virus that has plagued humans for possibly
as long as ten thousand years, and it's believed to
have made the jump from either camels or gerbils, or
possibly some extinct animal we don't know about, over to
humans and spread along trade routes that crossed the Middle

(06:54):
East to Asia and then eventually west over to Europe.
Our earliest defend native evidence of smallpox dates back at
least three thousand years, found on mummies of people who
lived millennia ago, including the Egyptian pharaoh Ramsey's the fifth
Ramsey's appears to bear the sign of the virus, the
pox marks that are left behind when the pustules that

(07:16):
cover the body scab and fall off. Those pustules come
at the final stage of a very difficult disease. Within
a couple of days of being exposed to smallpox for
the first time, you will be leveled by a fever
and flu like symptoms that incapacitate you for days. Sores

(07:37):
develop in your mouth and they fill with fluid, and
just as you overcome the fever and begin to feel better,
the mouth sores erupt, which releases the virus filled fluid
into the rest of your body, where it reappears as
those pustules masses of tiny bumps that cover the skin
and concentrate around your extremities. The uestull scab over and

(08:01):
eventually they fall off, and when the last one falls,
you are no longer contagious. If you survived the disease
that is, smallpox kills by overwhelming your immune system with
the protein that counteracts anybodies that would normally prevent infected
cells from replicating the virus. To catch smallpox, it takes

(08:23):
close contact with a person who is actively suffering from it,
which meant that people who cared for the ill were
usually the ones who came down with it. Once a
person comes down with smallpox and survives, they are conferred
a lifelong immunity to the disease, and even though they
may still carry the virus, they aren't contagious to others.
Even people who have never had smallpox before. By the

(08:47):
Middle Ages, smallpox had settled into Europe, becoming endemic, which
means it settled into the human population kind of made
itself comfortable. It went into hiding and made the rounds
when new comers who had never been exposed to the
virus entered the towns of people who are already immune
to it. So in Europe smallpox became mostly a disease

(09:08):
of children and immigrants. The local adults had all either
died from it or survived it and become immune. Once
it became endemic, the mortality rate for smallpox hovered around
It killed about three out of every ten people who
came in contact with it. But in the fifteenth century,

(09:29):
Europe began to spill over its banks, and it brought
the disease to places that had never encountered it before.
West Africa was first visited by slave traders from Portugal
and Spain, who brought pandemics with them. Many of the
villages that were rated had never been exposed to the disease,
and so it spread quickly. The people suffering those outbreaks

(09:52):
were stolen from their homes and they were taken to
holding camps along the coast, where the disease spread even
more quickly. Those people were forced onto ships while they
were actively ill, making the horrific experience of being enslaved
even more brutal. Each time a ship set sail from
Africa to the America's over stuffed with people ill from smallpox,

(10:15):
it was like tossing a lit match onto a powder cake.
At first, the ships were too slow to make it
to the New World before the smallpox burned itself out.
The human cargo aboard were either no longer contagious what
We're dead from it by the time they made land.
But as ocean going technology improved, those ships got faster,

(10:37):
and eventually one of those matches stayed lit and it
set off the powder keg of the America's It is
difficult to overstate the effect that European disease had on
North and South America. Not just smallpox, but a number
of contagious disease began to rage at once, forming overlapping

(10:58):
epidemics called sindemics. The Native Americans had never been exposed
to these kinds of pathogens, and so they had no
natural defenses against them, which allowed the diseases to spread
at unimaginable rates. And kill untold numbers of people. It

(11:22):
appears to have all started in what is now Mexico City.
The Aztecs suffered losses of up to half of their
population when the Spanish brought smallpox. A short An African
slave whose name is lost to history, was suffering from
smallpox when he landed with an expedition led by the
conquistador Panfello de Navarrees. In writing five years after the

(11:46):
outbreak began, a Spanish fire who traveled to Mexico wrote
of the devastation the diet inhapes like bed box. Many
all theirs died of a starvation, because I said, we're
all taken secret of more. And they could not care
for each other, nor was there anyone to give them
bread or anything else. In many places it happened that

(12:08):
everyone in the house died, and as it was impossible
to vary the great number of dead, they pulled down
their houses over them in order to check the stinch
that rushed from the dead bodies, so that their homes
became their tombs. The disease spread like wildfire into the
interior of the American continent. In the America's smallpox found

(12:32):
what's called Virgin Territory a population that had no immunity,
so everyone who came in contact with it fell ill.
This left no one to care for people suffering from
the disease, which increased the mortality right even further. As
the sick fled their dead villages to look for helping
others nearby, they brought the infection with them, and the

(12:54):
cycle of disease began again and again. This happened over
and over for centuries, leaving the Great Native American cultures
in rubble. Explorers who came in later waves found destroyed,
abandoned settlements filled with the dead. In places the virus appeared,

(13:22):
the population fell by half two thirds. In some places,
nine out of every ten members of the Native American
groups in contact with the Massachusetts Bay settlers died from
sixteen seventeen to sixteen nineteen. The English Puritans, who arrived
the following year took it that God had cleared the

(13:43):
land for them. During the sixteen thirties, half of the
Iroquois Confederation and the Huron around the Great Lakes died
half in a decade. A single seventeen thirty eight outbreak
killed half of the Cherokee tribe in the Carolinas and
george Ja. In real numbers, these epidemics killed hundreds of

(14:04):
thousands to millions of people at a time. Imagine a
disease that can kill off of the people in your town.
It's no wonder, then, that smallpox is considered one of
the deadliest viruses in the history of humanity. It is
credited with killing half a billion people in the twentieth

(14:25):
century alone, the first eight tenths of the twentieth century,
I should say. Back in nineteen sixty six, the World
Health Organization of the u N led a global vaccination
campaign and by it declared smallpox eradicated from planet Earth.
This is a pretty big deal. Along with a cattle

(14:46):
disease called render pest that's related to the virus that
causes measles and humans, smallpox is the only contagious disease
humanity has ever managed to eradicate. Right now, there is
no living person earth who has a case of smallpox.
But that's not to say that the very ola virus
isn't still alive and well after the eradication campaign, the

(15:11):
u N persuaded the global scientific community to give up
its stocks of smallpox, and they were almost entirely successful,
save for two nations which just happened to be the
two most powerful on the planet, the nuclear superpowers the
Soviet Union in the United States. Those two nations decided
that it would be better for them to keep their

(15:32):
stocks rather than destroy them. Ostensibly this was for scientific research,
but both nations have been known to run illegal biological
warfare programs, and the idea of them maintaining stocks of
smallpox made the rest of the world uneasy. But this
being the height of the Cold War, no other nation

(15:52):
was in much of a position to argue, so all
smallpox samples on Earth would be stored under secure conditions
in two occasions. In Russia, they are stored at the
State Center for Research on Virology and Biotechnology in Siberia.
In the US, they are held at the Centers for
Disease Control and Prevention in Atlanta. Those two stockpiles still

(16:16):
exist today. On a number of occasions, the U n
again called for those stockpiles to be destroyed in two
thousand seven and most recently in two thousand eleven, and
it also tried to create a global agreement that once
those final stocks were destroyed, any nation caught with smallpox

(16:36):
could be charged with the crime against humanity. Unfortunately, in
all cases, the un failed and the smallpox stocks remained intact.
Contagious disease researchers are divided on the wisdom of keeping
these stocks. The US and Russia continue to argue that
we need to study Bariola so we can understand how

(16:58):
the virus coevolved with our immune system. Hopefully we can
use that knowledge to cure and prevent other diseases. The
logic goes that if nature made smallpox from say, camel pox,
it could create another pox on humanity. Studying smallpox could
help us prepare for that. To plenty of other researchers, though,

(17:20):
eradicating the very ola virus from the wild only to
keep hundreds of samples of it in laboratories is madness.
But regardless of where contagious disease researchers fall on the matter,
most dismissed the idea of a small pox epidemic as
being a genuine threat to humanity. It could be utterly

(17:40):
catastrophic for any community where the virus showed up, true,
and that is bad enough. But because smallpox requires close
contact for transmission, it would be relatively easy to contain
an outbreak and cut off the possibility of a pandemic.
It almost certainly does not pose an existential threat to humanity.

(18:00):
One that does, the one that keeps researchers awake at night,
is the flu. Influenza is a common virus among humans.
It also infects a lot of other animals too, like pigs, birds, seals, bats, horses, rodents,

(18:27):
among others. The different types of flu are described and
classified based on the two types of proteins found on
the viruses outer envelope he magluten in and neuraminides. It's
called the h X n Y naming convention, so you
end up with flu names like H five and two.

(18:49):
The flu typically has one of two traits when it
comes to infecting us. It's either extremely deadly or it's
extremely contagious. But once in a while, those two traits
co evolved within a single virus, and the results can
be catastrophic. November eleventh, nineteen eighteen, was a chilly, drizzly

(19:13):
day in Compiegne, a town in the north of France,
where representatives of the Allied Nations met with the leaders
of Germany to sign the armistice that ended the First
World War from nineteen fourteen and nineteen eighteen, what was
then called the Great War, claimed the lives of more
than eighteen million people, soldiers and civilians. But as the

(19:37):
armistice was being signed, another even deadlier killer than warfare
was making short work of human lives around the globe.
Type A H one and one influenza, the Spanish flu.
In the span of just four months from September through
December eighteen, fifty million people perhaps more died around the

(20:03):
world from this new and deadly strain of flu. It
killed like a bird flu and spread like a seasonal flu,
and those two qualities combined made it an extraordinarily dangerous virus.
As much as one third of the entire population of
the world was infected by it that season. It took

(20:25):
its heaviest toll on the young people under twenty five,
whose immune systems had never been exposed to an H
one and one strain before. Many young people who had
been the picture of health just days before died suffocating
on a bloody froth that they were too weak to
cough from their airways. In some cases, people died within

(20:47):
hours of their symptoms first appearing, then just as fast
as it began. The epidemic ended by the summer of
nineteen the flu had burned itself through the global population,
and it disappeared. It almost certainly evolved into a new
strain of flu that was far less deadly, and for
all intents and purposes, the Spanish flu that had been

(21:10):
such a killer of people went extinct. Where the Spanish
flu came from remains a mystery. Initially, it was thought
to have originated in Spain, hence the name. Other research
that came later implicated China. China and Southeast Asia are
commonly the source of bird flues the type that includes

(21:31):
the Spanish flu. But one theory traces the eighteen flu
back to Haskell County, Missouri, to one of the area's
plentiful chicken farms, where it disappeared to is equally mysterious.
For decades, researchers pined for a sample of the eighteen
strain to study in search of answers to questions about it.

(21:53):
The Spanish flu was the one that got away, a
vicious killer that the epidemiological and medical communities were helpless
to defend against, leaving no trace of itself aside from
the dead in its wake. And then in nine microbiologist
Johann Holton recovered a sample of the nineteen eighteen Spanish

(22:14):
flu from where it was entombed in the Alaskan tundra.
The tiny town of Brevig Mission, Alaska, had just eighty
residents when the Spanish flu came to town in nineteen eighteen,
mostly Native and up at Eskimos. In just a couple
of months, seventy two of the eighty died. A group

(22:35):
of gold miners were hired by the survivors to come
dig a mass grave for the bodies and enter them
in the perma frost. They lay undisturbed until nineteen fifty one.
That year, Johan Holton arrived and asked the tribe's permission
to break the grave open. In their frozen tomb, the
victims were preserved mummified in a way, and Holton reasoned

(23:00):
that the flu virus that killed them maybe as well.
Through a slow process. In nineteen fifty one and then
again in Holton opened the grave twice. He built a
fire to thaw the permafrost below, Then he excavated the
thawed soil. When he reached frozen ground again, he built
another fire. Finally, on his second attempt, in he managed

(23:24):
to call a living sample of the H one and
one virus from the lung tissue of one of its
preserved victims. In a few years, researchers cobbled together the
genome of the virus. They synthesized it, and inserted the
genetic material into a living cell. The Spanish flu lived

(23:46):
once more. That researcher thought that was a useful line
of inquiry, and there were other researchers who vehemently disagreed
and thought it was a um an extraordinarily reckless thing
to do. That is Beth Willis. She founded an organization

(24:06):
that agitated for increased transparency from the government's biological labs
in Frederick, Maryland, her community. The biotech field is not
like other fields that pose existential risks. Like other fields,
the research is dual use. It can be used to
help or harm humanity. But unlike research in other fields

(24:29):
like AI, which has yet to become clear to most
people that it poses an existential risk, working with deadly
pathogens is understood as dangerous work by people inside the
biotech field and out. There's no ambiguity. But despite the
inherent danger of working with deadly pathogens. The field has

(24:50):
shown that it's willing to take potentially catastrophic risks in
the name of research, and it's frequently divided over what
risks are acceptable and which are not. One area that
divides the field is gain of function research. Wherever the
Spanish flu came from, it almost certainly evolved from an

(25:11):
avian variety of flu that mixed with one more common
to humans through a process called reassortment. That's the ability
of viruses to swap genetic material with other viruses that
are also living in the same host. What comes out
can be a virus that is a genetic failure, which
may be unable to survive or copy itself, or it

(25:33):
could produce a deadly inefficient killer of humans. It's a
genetic crap shoot. When a virus mutates or adapts in
some way that makes it more efficient at infecting hosts,
it is said to have gained function. Studying these mutations,
how they take place, what mutations lead to which characteristics.
That's gain of function research. By studying how influenza evolves,

(25:58):
epidemiologists can get better at predicting what flu viruses have
pandemic potential before they reach that level of deadliness, and
there are two ways to do this. The most common
method is to capture wild flu viruses in store them
in a state of suspended animation, which usually involves freezing them.

(26:19):
Later on, when new viruses are caught that have evolved
from that same genetic line, researchers can compare the genomes
of the older strain to the current strain and see
how the virus has mutated. This is slow and laborious
work and frustrating lee it relies on the rate of
nature for evolutionary changes to take place, so some researchers

(26:42):
are increasingly using another method where they hasten evolution and
they forced the mutation of new and novel flu strains
to study gain a function. Research itself is uh effort
by researchers to increase the virulence or the infectiousness of
a panthogen and potentially to decrease its ability to respond

(27:09):
to countermeasures to treatment. That second, riskier method has become
a hot button issue in microbiology lately. In two thousand eleven,
two separate research groups working independently, one Dutch and one American,
stunned the world when they announced that each had forced
the mutation of an extremely deadly strain of flu, the

(27:33):
H five and one avian flu, and created an entirely
new version that is easily transmitted from mammal to mammal.
In nature, the H five N one virus mainly infects birds.
It has rarely made the jump to humans, and even
then only to those who have spent prolonged periods in
close contact with sick birds, like poultry workers when it

(27:58):
has made the jump. Though the virus has been astoundingly lethal,
H five and one has a mortality rate among humans
of between sixty eight. The only upside to H five
and one is that it doesn't easily spread among people.
In the late nine nineties, the world held its breath

(28:18):
when several hundred cases of H five and one avian
flu broke out among poultry workers in Asia, but the
global avian flu pandemic never came, and aside from the
obvious that the virus just simply lack the ability to
transmit from person to person, researchers couldn't exactly say why
the pandemic never happened, So microbiologists began to look for

(28:42):
answers by forcing a gain of function in H five
and one. One of the two groups that did this
was from the University of Rotterdam in the Netherlands. They
forced multiple mutations within the virus, speeding up its evolution,
and then inserted the mutated virus into the noses of ferrets.

(29:04):
Ferrets are commonly seen as one of the best animals
to model humans. Then they transferred nasal fluid from those
infected ferrets to the noses of other ferrets. That second
group of ferrets became sick as expected, but alarmingly, the
second group passed the virus along to others without the
aid of researchers through sneezes and costs, just like humans would.

(29:30):
That really alarmed the virology community. I would say that
at least four to one people are against doing that
kind of research. This is Dr Lynn Clots. He's a
senior Science Fellow for Biosecurity at the Center for Arms
Control and Non Proliferation. Those two labs had brought to
life a novel lab created strain of one of the

(29:50):
deadliest flus known on Earth and given it the entirely
new ability to pass easily from person to person, and
now it's sat in their freezers. When the labs announced
their experiments, outrage erupted. In reaction, the field of microbiology

(30:11):
issued a two year long ban on high risk experiments
with flu viruses, and the fault line developed between scientists
who believed that force mutation gain of function research was
needed and necessary to stave off potential pandemics and those
who considered the research unjustifiably risky. The people who carried

(30:32):
out these experiments were cowboys, in the words of one microbiologist.
There was also the issue of censorship. Both of the
experiments were expected to be published, which would provide, in
the opinion of some researchers, essentially a how to guide
to creating the experimental extraordinarily deadly virus. So there were

(30:55):
calls for the two major English language scientific journals, Science
and Nature not to publish the studies, and those calls
were heated for a time. But scientists tend to bristle
at the idea of science being censored, and understandably so,
findings are meant to be shared among everyone in order

(31:15):
to advance human understanding. That's how science works. The trouble is,
once it's out there, the information can be accessed by anyone,
including people who would use it to inflict harm, and
in the case of the detailed description of exactly how
to transform H five and one virus into one that
is easily transmitted among mammals, that harm could be profound.

(31:39):
The experiments were the very definition of dual use research.
But repressed knowledge has a way of getting out, regardless
of our greatest efforts, a point that was proven shortly
after the moratorium ended when a team of microbiologists in
China announced they had successfully crossed the hive and one

(32:00):
virus with the less deadly but easily transmitted H one
and one virus, creating a genetically altered superbug of their own.
If any of the virus is created by the Chinese,
American or Dutch groups were introduced into the general population,
the effects would be monumentally bad, potentially on the order

(32:23):
of an extinction level event for humanity, and so with
the aim of preventing just such a catastrophe, the field
of biosecurity has emerged to consider how something like that
could happen. There is the obvious, the ever looming specter
of terrorism. A radicalized lab employee or one who is

(32:44):
desperate for money, a disgruntled researcher or someone looking to
prove their abilities. Any of these people could make an
excellent candidate for the release of what are called potential
pandemic pathogens, which are exactly what they sound like. Some
biosecurity experts are also concerned that some of the smallpox

(33:04):
in the Soviet Union stockpiles was lost after the country dissolved. Really, though,
a bio terrorists doesn't need to have access to a
lab that stockpiles pathogens. The main concern over publishing that
H five and one how to Guide the journal Science
eventually published it in full, was that the information would

(33:25):
fall into the hands of someone well versed in microbiology
with enough resources and few enough scruples to create the
virus outside of any formal lab or oversight and then
release it. That idea is rather unsettling, but many microbiologists
considered it barely more than an urban legend, something the

(33:47):
media ran with to scare the public into watching the news.
That is until two thousand and sixteen, when scientists from
the University of Alberta announced that they had created the
virus that as his horse pox from scratch, using only
snippets of genetic material called oglio nucleotides that they ordered

(34:08):
retail over the internet. It costs the team a hundred
thousand dollars and took six months to create a living,
infectious virus. The University of Alberta experiment showed that it
was now possible for a d I Y biologist to
create viruses in bacteria through the emerging field of synthetic biology.

(34:31):
Rather than attempting expensive and time consuming experiments to force
mutations in a virus over and over and hope that
it evolves in a way that you wanted to, synthetic
biology allows researchers to create exactly the kind of organism
they're looking for by designing and building it denovo, which
essentially means in Latin from scratch. Synthetic biology emerged from

(34:55):
genetic engineering, which revolutionized the world by creating the ability
to cut and splice genes between organisms. Synthetic biology combines
genetic engineering with the goal of streamlining life into a
more predictable, reliable, efficient version of what's found in nature.
What synthetic biology does actually is make literal use of

(35:19):
the building blocks of life. Eventually, synthetic biology aims to
create a database of genomic codes that, when inserted into
an organism will produce a predictable trait. So this snippet
is a gene that codes for proteins that creates bioluminescence,
and when you insert it into E. Col I, it

(35:39):
will make the bacterium glow like a firefly, which is
pretty neat. The common analogy is lego bricks. The synthetic
biology community calls their genetic snippets bio bricks, but instead
of plastic blocks, synthetic biologists use genes snapped together, as
it were, to radically alter existing species, or to even

(36:02):
create entirely new ones that have never existed before. Synthetic
biology will eventually democratize biotechnology, making it easier for people
to enter the field, and this effort is already underway.
M I T maintains a database of bio bricks that
anyone can access. Find the gene that produces the trade

(36:25):
you're looking for, copy the genomic code of that gene,
and paste it into the order form of an online
genetic synthesis lab. They will produce those snippets of DNA
or glio nucleotides from simple sugars, which you can then
insert into a host organism, transforming it into a creation
utterly outside of nature. This ability to create organisms from

(36:49):
scratch at home basically could be very beneficial for humanity,
but it also poses huge new risks that have yet
to be explored. Still, the idea of something like a
rogue biologist creating a lethal virus DiNovo and releasing it
under the human population occupies a very small place among

(37:14):
the worries of people in the bio security field. An
accidental release, they say, is much more likely. Imagine that
you're working in a bio safety level for research lab

(37:37):
that's the highest level containment facilitians, and you don't notice
that the space suit you're wearing in the lab has
a small terr in it. While you're working with a
genetically altered virus. You don't notice that it comes in
contact with the bare skin of your hand. After leaving
the lab, you take off your suit and you scratch

(37:58):
an itch around your nostril with your infected hand, and
the virus makes its toy into your body. You are
now infected. This particular virus has been altered to have
a short incubation period, the time between when you're infected
and when you can infect other people. Inside your lung tissue,

(38:21):
the virus has entered a respiratory cell and injected its
own genetic material. The cell begins to replicate the virus.
In the matter of a second, a million or more
copies of the virus are produced. They rupture the hijack
cell and spread out, infecting other nearby respiratory cells, where

(38:41):
the process begins again. Now you're contagious. With each breath
you expel respiratory aerosols water vapor laced with the virus
from your body into the air where others breathe. Your
saliva and your nasal fluid are both infectious, but with
this particular virus. The time between when you become infectious

(39:05):
and the padrome, the time when you first begin to
feel symptoms, is more than twenty four hours, And during
that time you live your life. You take the subway
to work and back. You hold onto poles in the
train cars. You chat and laugh with your coworkers. You
spend time with friends in a crowded bar. All the

(39:27):
while you shake hands, give hugs, touch door handles, breathe, laugh,
You spread the virus to other people. By the time
the first signs of illness appear, you have infected five
of the people you've come in contact with. Each of
those people spread out and infect an average of three

(39:47):
more people, and so on and so on. Some of
those infected people have business overseas in Europe, South America, Asia,
they leave the country, they cough in airplanes, they shake
hands too, they drink from cups that get cleared away.
They spread the virus to other people around the world.

(40:11):
Each of the infected people creates a new branch in
an ever expanding chain of infection that epidemiologists have a
very short time to contain. If that genetically altered virus
is easily spread, the epidemiologists may fail a pandemic magnite,

(40:32):
and if that virus is also highly virulent with a
high mortality rate, the pandemic could be an existential threat.
What makes this worst case scenario so unnerving is the
biotech field's real life track record of accidental releases. In
addition to a willingness to take huge risks in its research,

(40:55):
the field is also dangerously accident prone. That very situation
I've just described happened in two thousand four when a
worker handling the coronavirus at a c DC lab in
Beijing became infective with Stars, a deadly and contagious respiratory illness.
Although the virus killed only one person, it managed to

(41:18):
make it all the way to Hong Kong and Canada
before it was contained. The two thousand four Stars outbreak
resulted from an incorrectly inactivated virus in a biosafety level
three or four lab. The suits that workers have to
wear and the safety equipment they have to use is

(41:39):
cumbersome to say the least, but those protocols are necessary
for handling the deadliest pathogens, both to prevent the people
working with those pathogens from getting infected and to prevent
the pathogens from escaping the lab. So to get around
those highest level safety protocols, labs sometimes kill the path

(42:00):
legions they're working with, say by exposing them to dry
heat or changing their pH but the virus or bacterium
itself remains intact, so since it's now dead, it can
be rendered non infectious and studied in a lower level
containment lab, where safety requirements are much less stringent, making

(42:21):
the pathogen easier to work with. The problem is inactivation
isn't always effective. Some viruses simply don't die, and the
process is prone to human error. Accidental releases of incorrectly
inactivated viruses is disturbingly common. In fact, labs that work

(42:44):
with potential pandemic pathogens have a breathtakingly bad record of
accidental releases of all kinds. Just to pick a few,
in the flu season featured a strain of H one
and one that was almost genetically identical to a strain
that had last made the rounds about three decades earlier.

(43:08):
In evolutionary terms for a virus, three decades is an
epoch to us, any strain related to one from NIF
should have mutated so many times that it was no
longer even remotely possible it could be genetically identical to
the previous one. For years, scientists puzzled over this surprise reappearance,

(43:30):
considering and discarding theories, until they finally came to an
unsettling conclusion. The only reasonable way such a thing could
have happened as if the virus had entered some form
of suspended animation and then made its way back into nature,
and the most reasonable explanation for that was that it

(43:52):
had been frozen and kept in a lab and then released.
Researchers eventually settled on the theory that the strain had
probably been released in a vaccine that wasn't inactivated properly.
The result created a pandemic. Fortunately it was not a
particularly deadly one. Exactly what lab the virus came from

(44:15):
has never been fully proven. The next year, a photographer
working at the University of Birmingham Medical School in the
UK caught smallpox and her mother, who cared for her, died.
She had contracted it from a lab one floor below.
The smallpox had traveled through the air duct into her office.

(44:37):
And in nine in the Soviet city of Sverdlovsk, sixty
four people died of anthrax infections after an air filter
was removed and not immediately replaced in a lab that
was working on illegal weaponized anthrax bacteria, which was carried
into a village down wind. It was ex it's like

(45:00):
these that led to the creation of those high biosafety
level labs and the use of space suits when conducting
research with the deadliest pathogens, which makes sense in the
U s Department of Agriculture created a list of the
deadliest pathogens, which the U S d A calls biological

(45:20):
and select agents, and the Centers for Disease Control took
responsibility for monitoring the labs that work with them. But
it wasn't until two thousand one that bs L three
and bs L four labs really began to spread. There
weren't very many of them until two thousand and one
and after the anthrax letters, which came from Frederick, where

(45:44):
I live, which is how I got engaged in this issue.
After that time we went from just a few labs
to a large number, a very large number of labs.
It mushroomed tremendously UM with the assumption that um, we
had to do a lot of research because of the

(46:05):
threat of bioterrorism. But of course the only incidents we've
ever experience came from one of our own labs. In
two thousand one, just a week after the September eleventh attacks,
members of Congress and the media began receiving strange letters
with a white powder. Inside the powder was spores of

(46:28):
Bacillus and thracis, the bacterium that causes anthrax. It had
been weaponized to make it more easily inhaled and therefore infectious.
Twenty two people were infected by the spores, and five
of them died. In in America already gripped by panic.
The anthrax letters had a profound impact on the country's psyche,

(46:52):
and it turns out that the source of the anthrax
was actually a a lab at for Dietrich a scientists
there who really was somewhat mentally unstable, and I think
people should have known it. Uh, he was responsible for
spreading that anthrax. I think that just scared the hell
out of everybody. The problem is that even with the

(47:12):
creation of BSL three and four labs, with their astounding
array of precautionary equipment and procedures, the twenty one century
has still seen a lot of high profile accidents from
these labs. Between two thousand four and two, there were
six hundred and thirty nine reported accidental releases of pathogens

(47:35):
found on the U s d A's list of Biological
select agents and toxins. Bacteria and viruses like the Ebola
virus and the bacteria that causes the plague the virus
that causes stars are all on the list. Those six
hundred and thirty nine accidents represent just the ones that
were reported, and only then among those publicly funded labs

(48:00):
that are required to report such accidents. Labs that don't
receive public funding like those run by corporations or private groups,
don't have to report accidents like that at all. Back
in two thousand fourteen, a National Institutes of Health lab
in Bethesda, Maryland, discovered six fials of live Bariola, the

(48:23):
smallpox virus, in an unsecured freezer. The vials were labeled
Bariola and have been stored in the nineteen fifties in
a lab that had gone unused since the nineteen seventies.
The f d A, which had taken custody of the
lab from the NAH way back in, had lost track

(48:44):
of the stocks with smallpox and failed to destroy the
Bariola or submitted to the CDC as part of that
eradication campaign. It had just sat forgotten in the freezer.
Also in two thousand fourteen, a c DC workers ship
live strains of the bacteria that causes typhoid fever to

(49:05):
another lab in a reused box that wasn't marked for
hazardous material. Not to mention, the box was broken open
in the corner and it was sent using regular ups delivery.
Some specimens broke during shipping, although the Typhus vile remained
intact and sealed again. These are just a few randomly

(49:28):
selected examples, like those ships that carried smallpox between Africa
and the America's. Each accident involving potential pandemic pathogens is
like tossing a lit match on a powder keg. Each
one has a chance for an outbreak to take hold.
The problem is as more BSL three and four labs

(49:50):
come online, more of this risky research is being conducted.
More labs conducting more of this risky research compounds the
probability of an accidental release of a pathogen that can
cause a catastrophic pandemic. Even worse, BSL three and four
labs have mushroomed to a point where no one, not

(50:14):
the U. S. Government, not the Centers for Disease Control,
not the National Institutes of Health, not the World Health Organization,
no one can definitively say how many high containment labs
are operating around the world. In the US, even there's
no certainty about how many there are, it has become
something of a status symbol among nations, universities, and corporations

(50:39):
to operate high level containment labs. So some people in
the biotech and bio security fields have called for an
end to gain a function research of any kind. The
trouble is there's no regulatory framework overseeing high containment labs.
In the US. The National the Institutes for Health is

(51:01):
the agency that provides funding for this type of work,
and they have adopted guidelines for best practices and safety,
but there's no penalty for labs that don't follow those guidelines.
The most potent weapon the NIH has to curtail reckless
experiments is to deny funding for further research, and this

(51:23):
only applies to labs that receive public funding. Privately funded labs,
like again those found inside corporations, as well as labs overseas,
operate utterly outside of any jurisdiction. But even if American
labs had a flawless safety record, which they definitely do not,

(51:43):
other countries across the rest of the world operate with
a patchwork of regulations, if any at all. There is
no global oversight of research with deadly pathogens, and there's
really no one to say what constitutes a reckless experiment anyway,
Aside from the institution the researcher is affiliated with. There's

(52:03):
no one empowered to decide which experiments are simply too
risky to carry out, and in most cases, the institutions
that can make that decision air on the side of
their researchers, since highly visible work that gets lots of
press brings their institutions prestige. What's probably most disturbing is

(52:25):
the tendency to downplay or even totally fail to report
lab accidents. A culture of silence and opaqueness pervades the
bio labs in the US. For all of the existential
risk involved, there is almost no public scrutiny of the
field of biotechnology. If science is never to be censored,

(52:48):
doesn't that also require it to be fully transparent. There
are ways to make the system in place safer. Some
microbiology to argue that the same results can be found
by using non infectious proteins to study the functions of viruses,
that those live altered viruses that some labs are creating

(53:11):
are not only reckless but also totally unnecessary. Others say
that researchers could be required to add genetic traits to
their altered specimens that make them reliant on conditions in
the lab to survive, so that they cannot spread in nature,
kind of like the dinosaurs in Jurassic Park. Perhaps they

(53:33):
could engineer a kill switch like a self destruct mechanism
that is triggered once the cell divides a prescribed number
of times. In other areas, labs that synthesize DNA and
RNA could be required to compare the sequences of orders
that come in against the database of known pathogens and

(53:54):
report any of those orders that set off alarms to authorities,
and propose souls. For research that has dual use imposes
a low probability, high consequence threat to the public could
undergo review and approval based on its relative benefit to
science as part of funding requests, and labs both public

(54:17):
and private in the US and abroad could be put
under an international regulatory body that both respects and understand science,
but also equally value safety for humankind. There are holes
in these safeguards, yes, but even this handful of ideas

(54:37):
are still vastly better than what's currently in place. When
you combine the increasing number of labs around the world
carrying out research on potential pandemic pathogens with the history
of accidental releases in human error in the biotech field,
it is extraordinarily difficult not to conclude that the potential

(55:00):
for an existential threat posed by the release of a
deadly pathogen is real. This is not a far off
field of existential risk. It surrounds us right now. Dr
Lynn Clots, who you met earlier, calculated the probability of
a lab acquired infection that followed that worst case scenario

(55:22):
I described based on the current track record of accidental
releases over the course of a ten year period. Considering
ten labs with an average safety record, Dr Clots calculated
that there is a twenty seven percent chance of an
undetected lab acquired infection creating a global pandemic in the

(55:44):
next decade. That's better than a one in four chance
of an existential catastrophe. And that's just considering ten labs.
No one knows how many labs there actually are. Risk
is product of two things, the likelihood of something happening
times consequence. The likelihood of something happening is small, very

(56:07):
small per lab per year, but you do things in
enough labs for enough years, it gets bigger. Uh. And
the consequences, potential consequences are huge in the worst case scenario,
perhaps killing a large percentage of the world's population. And
we just don't know. So I just don't think it's
worth taking the chance on the next episode of the

(56:38):
End of the World with Josh Clark. Particle physics works
at the leading edge of human knowledge, at the leading
edge of theory. That's the whole point of it. Particle
physics is where science touches the fabric of the universe,
and it puts us in a dilemma to know if
the experiments that we're running inside of particle colliders are safe.
We have to run the experiments in the first place,

(57:01):
but hoping for the best is not a good strategy
for an existential risk that could theoretically end the universe
as we know it. M

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