This citadel is located in the
Berlin district of Spandau. Wildlife pathologist Gudrun Wibbelt
studies infectious diseases in small animals such
as squirrels and bats. Alex Greenwood is
a Professor of Wildlife Diseases in
the German capital. Their joint research shows that
a bat colony like this one could be the incubator
for the next pandemic. Almost all known diseases,
especially viral diseases, come from
wildlife. These viruses are
millions of years old, and the animals have
been around forever. What has changed is how
we interact with nature. The citadel’s
basement is home to tropical bats in a
special enclosure. Some of the 1,400 bat
species worldwide seem to be perfect
virus carriers. Bats are mammals like us, and
they live in large groups. Some fly about fifteen
kilometers in the wild, so they can spread
pathogens far. It’s inevitable that pandemics
will keep occurring. All of humanity has had
to deal with pandemics and will continue
to do so. And the further we encroach into
the habitats of wild animals, the more likely
it becomes. Until now, the animals
were left on their own, and we didn’t
interact with them. Viruses pose a major threat to
humans and other organisms. But viruses can
also heal us. Throughout the
course of evolution, they’ve majorly
impacted life on Earth. The larger and more densely
packed an animal population is, the more likely it is for dangerous
virus mutations to occur. Viruses evolve to
spread faster. And some are then
transmitted to humans. The problem
right now is, when we have a pandemic or outbreak,
we focus on the human side. How can we prevent people
from getting sick? How can we
treat people? Rightfully
so! But if we want to be proactive
in preventing outbreaks, we need to understand how
animals deal with pathogens. If we understand why they
survive certain viruses — like rabies
or SARS — and then take that functionality
and apply the knowledge to humans, we’ll
benefit. Some tropical bat species
transmit Ebola and rabies. And many other animals, like
rodents, pigs, and chickens, are perfect virus
carriers too. The virus that caused COVID-19
passed through one or more unknown intermediate
hosts before reaching us. And it mutated several
times along the way to become dangerous
to humans. Viruses are adept
at surviving. How can we best
describe them? Viruses are infectious,
organic structures. They have no metabolism
and can only reproduce in the cells of a
suitable host. Unlike bacteria, viruses
aren’t living organisms and they’re about one
hundred times smaller. Several thousand
viruses are known, but more than one hundred
million probably exist. Gudrun Wibbelt is
examining a bat at the Leibniz Institute for Zoo
and Wildlife Research. The animal was found dead in the
parking lot of a Berlin hospital. The pathologist’s research
aims to identify early on which virus makes its host
and potential carrier sick. And whether the virus
poses a risk for humans. This is the
little heart. These are the
kidneys. Here’s the
liver. Here you see the intestine
and there’s the stomach. The intestines look too
enlarged, too voluminous to me. I assume the bat probably
had intestinal inflammation and perhaps died of a
diarrhea-related illness. Attacks by viruses,
including the coronavirus, always follow the
same pattern. A virus “docks” onto a cell,
releases genetic information and forces the host cells
to produce new viruses. The new ones then
attack other cells, also forcing them
to reproduce. The infected cell dies
about two days later. At the same time, our immune
system attacks the virus. Gudrun Wibbelt wants
to find out how the bat died and which
viruses it carried. Some of them could
be dangerous for us, because these animals are
ideal hosts for viruses. They have a strong
immune response. That means, bats can carry pathogens
without getting sick themselves, making them the
perfect hosts. You can be infected
with a virus and later expel it without
anything happening. Or you can be
infected by a virus, and the immune system responds
by forming antibodies, but without you
getting sick. Or you might get infected
by a virus and get sick. Those are the
three ways. There are bats and the coronavirus
— and also Ebola, for instance. The viruses manage to reproduce in
the animals and get expelled again. But even a large viral
load doesn’t hurt bats. In fact, they’re known
as reservoir hosts, meaning they carry infections
that don’t bother them. But then there are others who
get sick from the virus. Bats carry a predecessor of the
virus that causes COVID-19, but as far as we know, they didn’t
directly infect us with SARS-CoV2. I understand that people find bats
a little too dark and mysterious. It’s a bit unfortunate
that they’ve been around for so long and have such
an affinity for viruses. But it’s no reason to
worry when you see a bat. In fact, they eat
all the moths and mosquitoes that bother
us and farmers. If we didn’t
have bats, then we’d need a lot more
pesticides for farming. Bats are useful to us in a lot of
ways that people don’t realize. Still, it’s undeniable
that in recent years, viruses are increasingly being
transmitted from animals to humans. In 1997 there was the bird
flu, in 2009 the swine flu, and the first case of COVID-19
was recorded at the end of 2019. Virologists like Alex
Greenwood think there will be more such
diseases in the future. We've been for
a long time, more and more invading the
spaces where wildlife lives and also wildlife that we
normally wouldn't have contact with through the
destruction of forests, conversion of land, the
use of wet markets where we eat and
consume wildlife. And there's no
reason to think that that couldn't happen again
if we are caught by the wrong pathogen at the wrong
time, in the wrong place. Alex Greenwood thinks
we still know too little about diseases
in wildlife. Because there’s not enough
funding for systematic research, it’s often by chance that scientists
discover new viruses in animals. We need to invest in figuring
out what are these pathogens, why are
they there? Where? In what
species? What are they
doing there? Are they doing
something good? We don't have
these answers. We didn't see this
pandemic coming. We didn't see the
last pandemic coming. We don't know when Ebola
will break out again. We don't really know what the next
viral outbreak will be in people. It could happen right now, even
in the middle of a pandemic. In Hamburg, just a stone’s throw
away from the city’s harbor, is the Bernhard Nocht Institute
for Tropical Medicine. It contains a high-security wing
with a database of viruses. Lisa Östereich works in a
biosafety level four laboratory, the highest
security level. There are four such labs in Germany
and about fifty worldwide. Here, scientists study
deadly pathogens, most of which don’t have
vaccines or effective therapies. We have a filter in the suit,
or “pressure relief valves.” We connect a tube and then
air is blown into the suit, with overpressure
if necessary. The gloves are firmly
attached to the suit. The boots are tightly
secured too. The suit’s interior is
subject to overpressure, so when we’re in the lab, air
only flows outward and never in. The suit is completely
airtight, so we’re protected. The institute’s collection includes
one hundred different viruses. One of the latest
additions to the biosafety level four
laboratory is the Ebola virus. Lisa Östereich traveled
to Western Africa to help diagnose potential
cases in a mobile lab. Scientists here in
Hamburg are constantly analyzing and
cataloging new viruses. Viruses have a relatively
simple structure. They’re very small and
have few components. Still, we don’t really know how
to prevent or modify sicknesses, or at least how to
make them less severe. That’s why we have to
continually re-exam viruses. Because they’re so small,
they have few weak spots. And they’re so highly
specialized that no two viruses are
completely alike. The surfaces of many
viruses exhibit appendages resembling
spikes or thorns. Underneath is often an envelope
around the genetic material. The genetic information
lies on the DNA’s double helix or usually
single-stranded RNA. There are many RNA
viruses especially that can be dangerous
to humans. Ebola and the Lassa virus are
both examples of RNA viruses. But there’s also hemorrhagic
fever viruses — meaning viruses that
cause bleeding — such as Crimean-Congo
hemorrhagic fever. Or the dengue virus, which you
can contract traveling in Asia — that’s also
an RNA virus. So is yellow
fever. So there are
quite a few. Coronaviruses are
also RNA viruses. RNA is almost always
single-stranded and more chemically
susceptible than DNA, meaning errors occur more
often when it’s copied. The virus
mutates. But the human immune
system is slow to respond, which makes vaccine
development more difficult. Virologist Stephan Günther
identified the SARS virus in 2003 — a close relative of the
virus that causes COVID-19. The viruses we
work with have a high chance of killing
you if you get infected. But the viruses that are
actually thriving are influenza, the Spanish flu, or COVID today
— they’re highly contagious. Or there are viruses like HIV
where you don’t even realize you’re infected but can
be a carrier anyway. Ebola kills one out of
three infected people, but the right contact restrictions
work to stop the spread. By February 2021,
SARS-CoV-2 had infected one hundred million people and
killed two million worldwide. Never before had virologists’
work received so much attention. Lisa Östereich uses
fluorescent substances that react to certain DNA sequences
to identify pathogens. Viruses have simple structures
and can be replicated in labs. But recreating such infectious,
organic structures is difficult. Viruses generally
evolve to become the “evolutionary optimum,”
so to speak. Usually when you start to change
something about the virus, you’ll end up worsening
its properties and decreasing its chance of survival
rather than improving it. Nature has already
created the optimum. And if you synthesize it, the
result is usually worse. The coronavirus is from
nature — not from a lab. A research team from the US and the
UK proved that in February 2020. Amid the pandemic, it’s become clear
that global information sharing offers a chance to
defeat deadly viruses. At Lake Constance in
southern Germany, researchers are trying to better
understand the role of viruses. Christian Voolstra and his team
from the University of Konstanz regularly take water samples
and study them in the lab. What impact do pathogens
have on aquatic ecosystems? Christian Voolstra is investigating
the interactions between viruses, bacteria and
larger animals. This is lake
water... This here is about 100
milliliters, or half a glass. What we know is that
there are about 100 million viruses per
milliliter of lake or seawater. That means there’s
100 times that here. And when you
think about it, there are more viruses inside
here than people on Earth. And if you now look at the lake
as a whole and think about how many “100
milliliters” is in it, you get an idea of the
magnitude we’re talking about. There’s no place on
Earth without viruses. All ecosystems are
built on them. Christian Voolstra
discovered that corals for instance benefit
from viruses, because they kill off
dangerous bacteria. The same is true
for humans. Viruses can help
us by killing harmful bacteria in
our digestive system, for
example. I think it’s important to
understand that nothing is “good” or “bad”
in nature. And viruses and bacteria
are everywhere. Plus, when you take the number of
pathogenic viruses compared to all viruses, it’s really
a very small fraction. Viruses are an integral
part of nature and keep our
ecosystem balanced. Only a small number of viruses
are dangerous, and many help us. They’re even
part of us. The human
genome contains virus fragments left over
from past pandemics. How viruses become embedded
in our genomes and the ensuing effects is plain
to see in another species. Six koalas live in
the Duisburg Zoo. And just
like humans, they’re accustomed now
to contact restrictions. They are not allowed
to meet other koalas. A pandemic threatens the
survival of the entire species. Koalas and their viruses are
Alex Greenwood’s specialty. He is collaborating closely
with biologist Volker Grün, who coordinates breeding for
all koalas in European zoos. Alex Greenwood is researching
a special family of viruses: retroviruses. They infiltrate the
koalas’ genes. And this “gene defect”
causes diseases years later. So, we're in the middle
of a pandemic right now. But koalas have been going through a
pandemic for the last 50,000 years. The difference being that it's
not just a pandemic where the virus infects
individual to individual. It's actually gotten
into their genome. So the viruses managed to invade
the genome of these animals and then be spread from
parents to offspring. Like other viruses,
retroviruses attack cells and force them to produce
more retroviruses. And that’s just the first
stage of the attack. Retroviruses also embed
themselves in genetic material. The same can
happen in humans — they become part of us, and we can
pass them on to our offspring. But not many viruses
manage that. Each retrovirus in
our genome conceals countless failed attempts
by other viruses. And this has been happening
through the animal world for millions and
millions of years. And so that most animals,
including humans, have maybe 10 percent of
their genomes made out of retroviruses that have
gone through this process. The koalas are basically the
beginning of this process. And so they're facing
what we must have faced millions and millions
of years ago. And we're seeing
in real time unfolding before our
eyes in these animals. Volker Grün is worried about
the koala population. After all, the animals in
European zoos have not yet been infected by the
koala retrovirus — but should a new animal
join them from Australia, that could
change fast. We had a case where
animals were imported. Everything had been
approved by the Australians and the nature
conservation authorities. But then we tested them here in
Europe and they were positive. So of course,
we said stop, we’re not going to put them
together with our animals, because we were of course
afraid they might infect them. That would obviously
ruin everything. That was the right
thing to do. They should
always be tested. As soon as it’s in
the population, in an enclosure with multiple
koalas, they can infect each other. Even if just one
animal is positive. In a few years,
they’ll maybe all be. And that would
be bad. What if we were
to mate them? They’d have an increased
risk of cancer. And it’s not just
the cancer itself. They’d get it
relatively early on and then wouldn’t be
able to reproduce. Too many animals would die
before producing offspring. Maintaining the population
would be impossible. The virus in the genome not
only causes cancer but makes them more vulnerable
to other pathogens. We can’t predict the effects of
retroviruses on individual koalas. But overall, the viruses
threaten the whole population. If all koalas were to become
infected with the koala retrovirus, they could
die out. It's as if koalas are
hardcore smokers. So it doesn't mean they're
going to get cancer, but you're
increasing the risk. And so the koala
retrovirus is like smoking 20 to 30 packs of
cigarettes a day, because it's putting
so much pressure — so many possible places where it
can land and do something bad. We humans and our ancestors
were also attacked by retroviruses over millions of
years throughout our evolution. These and other viruses managed
to anchor themselves in our germline and make up
47 percent of our DNA. Just 2 percent determine
our bodies’ composition, while 51 percent controls how and
when genes are read — or activated. Just like with the koalas,
it’s not clear how retroviruses will impact
humans in the long term. That’s because they take root
differently in each person’s genome. And it’s difficult
to distinguish the viral effects from
environmental ones. For humans, the last of our
retroviruses to have gone through this happened a very,
very long time ago. There's evidence that our
retroviruses that we have sometimes may be involved
in or lead to cancer. There is there are studies
that suggest that they still retain a little bit of
their cancer-causing potential. So, but these are sort of these
after-effects that have to do with the virus being a little
bit virus-like still after all these
millions of years. But it's nothing like
the koala retrovirus, which is still much more virus-like
and causing much more direct, acute problems, also at
the individual level, than you would see in other
species, including humans. There are also retroviruses in the
genetic material of extinct animals, such as
dinosaurs. And the role played by retroviruses
is only just being researched. One pioneer of retrovirus
research in humans is virologist Joachim Denner from the
Free University of Berlin. I don’t think dinosaurs
have been well-examined, but I’m sure they also had
endogenous retroviruses. They were just a dead-end
track in evolution. But they left behind
a lot, of course. And we can see
that behind us. Joachim Denner is
researching how to cut retroviruses out
from the genome. And he wants to better
determine their effects. I think retroviruses are the
most interesting viruses around. They’re called retroviruses
because they have an enzyme that can transform
the viral genome — or RNA — into DNA and then
implant this DNA copy into the genome of the host
cell using another enzyme. The process is called
reverse transcriptase. The single-stranded RNA turns
into double-stranded DNA. And only then can it
slip into our genome. The foreign genes then remain,
like parasites in a host. Just like the parasites
being exhibited here in the Museum of Natural History in Berlin,
retroviruses have diverse effects. We often only see the
negative properties of parasites,
bacteria, or viruses. But Joachim Denner is focused
on the positive impact of the thirty different retrovirus
families in our genome. I wouldn’t call
them parasites, because that implies
they’re harmful. They just ended up
in our genomes. They basically
just stay there, so for a long time we called
them genetic junk, or garbage. And we now know
they’re harmless. But they fulfilled important
functions throughout our evolution, and they play a vital
role in the placenta. An enzyme formed by a particular
retrovirus enables the placenta to appear in the uterus in the first
place and an embryo to develop. Animals related to us also carry
this type of retrovirus in them. This endogenous retrovirus enabled
more advanced mammals to develop. That means without these
endogenous retroviruses, which may have been involved
in the development of placental animals maybe 380 million
years ago, we wouldn’t exist. How can we harness the
good aspects of viruses? In Europe in early 2020, COVID-19
began spreading first in Italy. And it hit the
population hard. In Rome, at the biotech
company ReiThera, about 60 people are working
on a COVID-19 vaccine. The vaccine utilizes non-replicating
viruses as transport capsules. Marco Soriani is the Project
Director at ReiThera. This is the team that was involved
in the isolation of the vector. A vector is a
virus shell. And the shell is used as a
transport capsule for the vaccine. The challenge is to
find a virus shell the human body doesn’t
already know, so the immune system doesn’t
attack the transport capsule. Angelo Raggioli found a potential
candidate in January 2020. He was examining a
gorilla’s stool. Angelo is actually the
person that isolated the wildlife virus from the
stool of a gorilla. It is a gorilla kept
in captivity in a zoo. And then what actually Angelo
did was able to get the virus by several passages and
cleaning of the material. The vector comes from a species
of very close to human, but not the
human species. This has allowed us to
actually reduce the risk of pre-existing immunity
against the vector itself. The researchers removed the genetic
information from the “gorilla virus” and inserted the
spike protein’s DNA, found on the outer shell
of the coronavirus. The coronavirus uses this protein
to dock onto cells and invade them. The modified gorilla virus
works as a vaccine by forcing our cells to produce
the corona-spike protein. So the virus causes
our bodies to create antibodies without
making us sick. Then if the “real”
coronavirus attacks, these antibodies stick
onto the spike proteins. And the virus can no longer
dock onto the cells. ReiThera can manufacture eighty to
one hundred million doses per year. And the vaccine can be stored
in normal refrigerators. This is actually the room
in which we will produce the initial lots of
our COVID-19 vaccine. I have a
vial here. This is the
vaccine. As you can see, it is a
transparent solution. In phase two trials,
the vaccine is tested on about one
thousand volunteers. It appears safe so far.
Gabriele Nastasi from Verona, in northern Italy, took part in the
phase one trial in fall of 2020. Some of my friends think
it’s great I volunteered. Others said I
was crazy. They said, “Why
would you do that? You have no idea what’s
in the vaccine.” Gabriele Nastasi was one of ninety
volunteers in the phase one trial. After being vaccinated, he
had to log observations on his heath every
day for a month. Starting from the day
we’re vaccinated, we write down everything
in a journal for a month. And every day, we check the
injection spot for swelling, redness, or
localized pain. Worldwide, there are more
than ninety vaccine trials where testing is
underway on humans. Currently, there are four
different approaches to develop a vaccine against
COVID-19. Viral vector vaccines
such as ReiThera are made out of other
existing viruses. Their advantage is they’re
highly effective. But the drawback is that the
vaccine doesn’t work if people are immune to the
viral vector. One viral vector vaccine from the
UK was already approved in the EU. Inactivated virus vaccines
are a classic choice. They’re easy to develop and
proven to be effective. But it’s time-consuming to produce
them in large quantities. The third type
is a newcomer. The RNA genetic
material isolated from the coronavirus is
injected into the muscles. This stimulates the immune
system to produce antibodies. Millions of people are currently
being vaccinated with the Pfizer-BioNTech
vaccine. The fourth method
is also new. It involves injecting only the
coronavirus spike protein. Our immune system then forms
antibodies against the virus. It’s crucial to continue developing
these different approaches to keep up with the
constantly changing virus. And initial findings show the
ReiThera vaccine is effective. If it all works out, it
would be awesome to say, I contributed to advancing this
research that might really be a game-changer and take us
a step closer to normal life. That would be
immensely gratifying. So viruses help us fight
other viral pathogens. But we can use reprogrammed viruses
in completely other ways, too. Virotherapy is used
to treat cancer. Here in Tübingen in
southwest Germany, Ulrich Lauer is researching
this medical revolution. He’s testing drugs for different
types of cancer because viruses also attack
cancerous cells. This has been a known
fact for 50 years. In 1971, a doctor
observed a sort of “miraculous healing”
of a boy in Uganda. He had a tumor
on his eye. But after he came
down with measles, the tumor disappeared
within a month. The virus had
eliminated the cancer. And we also know that
when cancer patients have had been infected
by a virus, in rare cases
the cancer can completely disappear
within a few weeks. And of
course, virus-induced destruction
of cancer cells can occur. And the idea now is to optimize
safe viral vector vaccines for destroying cancer and
strengthen their immune response
to cancer cells. Ulrich Lauer takes herpes
viruses and reprograms them. These genetically
modified viruses don’t attack healthy cells
in the body anymore, but instead specifically
target tumor cells. After a day or two, the
growing viral load in the cancer cells
causes them to burst. And when they burst, the cancer
cells break into many pieces and the immune system
recognizes them as foreign. Prior to that, the immune
system had trouble recognizing the cancer cells and didn’t
respond sufficiently, but now it has a
sharpened sense and specifically targets
the cancer cells. So virotherapy
has two effects. First off, the viruses
attack the cancer cells directly and
destroy them. Secondly, the
vaccination with the modified virus activates
the immune system, putting it into
alarm mode. At the Tübingen
University Hospital, doctors are already
treating patients with melanoma skin cancer using
approved virotherapy. The medicine is called Imlygic
and requires long-term storag at minus 80 degrees Celsius,
similar to some COVID-19 vaccines. Helmut Fischer is Thomas
Eigentler’s patient. Despite chemotherapy
and immunotherapy, the skin cancer continued
spreading on his leg. About twenty thousand
people in Germany develop this aggressive type
of cancer every year. Virotherapy may be
a game-changer. Looking back at the side
effects, what struck you? Anything
serious? Not at all with
the virotherapy. I felt slight discomfort,
but I wasn’t nauseated and didn’t have a fever like
with previous treatments. So I was determined to
complete the therapy. So far, virotherapy is approved
for patients like Helmut Fischer who fail to respond to
more-established treatments. But that might
change soon. It was a real ray of hope for
me to be offered virotherapy, and it was a breakthrough, because
after months of treatment, I noticed that the spots
were getting paler. At the end, the doctors didn’t know
where else to inject anything. And samples showed no more
melanoma cells could be detected. So the virus attacked the
cells and did a great job. In Tübingen, Heidelberg and at
other institutes worldwide, virotherapies are being developed to
help fight other types of cancer. These cost-effective vaccines
could then supplement — or even
replace — costly chemo- and
immunotherapies. I think in the next
five to ten years, besides the virotherapy currently
used only for skin cancer, many more virotherapies will
crop up, for every type of tumor — more
or less. The next step will be to
vaccinate against cancer before it even
becomes visible. Then we could provide
lifelong prevention by permanently strengthening the
immune system and reducing the likelihood that cancer even
breaks out in the first place. Back to Lake Constance, the water
reservoir for southern Germany. Biologist Christian Voolstra
regularly examines the lake, which is teeming
with viruses. Similar to almost any
body of water on Earth, the lake contains 100 million
viruses per milliliter. And these viruses form
the basis of life. They’re necessary for
all life on Earth. But humankind has only very
recently become aware of this fact. Some people are terrified by sharks,
and others love them — like I do. And that’s what we would
call an apex predator. It’s at the top of
the food chain and keeps everything in
check from there. It’s what scientists refer
to as top-down control. There’s also control from the
bottom, called bottom-up. And that’s what
viruses do. Viruses are basically there
keeping the bacteria in check. Otherwise, we’d be swimming or
living in a bacterial soup. Viruses kill bacteria
so that we can live. And the dead bacteria
also become nourishment. Every minute, viral attacks
in the water generate one hundred million tons
of biomass worldwide. Throughout the
planet’s oceans — the cradle of life — there
wouldn’t be enough space or nutrients for advanced
lifeforms without viruses. Without the constant viral
attacks upon bacteria, Earth would have fewer
species and less abundance. We are highly dependent on
viruses doing their job so that we
can do ours. Viruses remain a major
threat to humans. But they’re also
a part of us. We wouldn’t exist
without viruses. Nor would the world
as we know it.