The world’s oldest virus research lab | DW Documentary

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Riems — an island in the Bay of Greifswald
in northeast Germany.
It measures just 1-point-3 kilometers long
and three hundred meters wide —
and is home to the oldest virological research institute
in the world.
The Friedrich Loeffler Institute.
The FLI is unique in Europe
and one of just three facilities world-wide
where research is carried out on large animals
at the highest level of biosecurity.
80 different animal diseases are under investigation here,
including pathogens requiring
the strictest level of containment.
And those deadly germs cannot be allowed
to escape from the lab under any circumstances.
Climate change and globalization
are among the factors driving the advance of diseases,
such as the West Nile Virus spread by mosquitoes,
and Borna Disease.
Researchers work in laboratories and animals sheds
that are hermetically sealed off from the outdoors.
Working under the highest biosafety conditions, BSL-4,
their aim is to protect animals from deadly diseases.
They need to strike a delicate balance
between immediate animal welfare
and the long-term necessities of research.
But the impact of diseases on humans is, of course,
also an issue.
That's why the experts are doing all they can
to gain insights into the ways — or vectors —
via which the pathogens spread.
It's a battle against an invisible enemy
as well as a race against time.
In October 2020 Sandra Blome, laboratory supervisor
at the FLI's Institute of Diagnostic Virology,
received a package with extremely hazardous contents.
The delivery had to be handled with the utmost caution.
It contained tissue samples from a dead wild boar.
It was possible the animal had died from a plague
that has recently been spreading in Germany.
The ominous news first came in September 2020.
The carcass of a wild boar was discovered to the east of Berlin,
close to the Polish border.
The animal seemed to have died of a disease
that infects domestic and wild pigs —
and is nearly always fatal.
The news came as a shock, but not as a surprise.
It's a virus that has been rampaging
in Eastern Europe for years, including in Poland.
Tens of thousands of domestic and wild pigs
had already died from it.
The virus was African Swine Fever, or ASF.
For humans: it's not a threat.
In Africa, ASF is transmitted by ticks from warthogs
and bush pigs to domestic pigs.
The animals become infected through direct contact,
mainly via the blood of infected members
of the same species.
Viruses of this kind are comprised only of a protein shell
and their genetic material — so from DNA or RNA.
They aren't able to reproduce on their own.
To do that, they need a living host — such as a pig.
The pathogen penetrates what is called the “host cell”.
Once inside, the genetic material then
programs the cell to produce more, new viruses.
The cell dies and releases thousands of pathogens
that go in search of new host cells.
Frequently, the animal can ward off the invader
and only becomes slightly ill — if at all.
But sometimes, the virus encounters a host
whose immune system is overwhelmed by the virus.
The disease is one among many in Africa
that might make warthogs and bush pigs sick —
but not fatally so.
But Eurasian pigs have yet to adapt to the pathogen.
If an animal becomes infected,
it will die in practically every case.
The new tissue sample from the dead wild boar
in Germany was analyzed in the lab.
If it turned out to be positive for the virus,
that meant the disease was spreading further westward.
And the sample was positive.
The disease was on the march.
The virus's journey to Europe began in 2007.
A freighter from East Africa was heading for Georgia.
In the port of Poti, it unloaded meat scraps
at a rubbish dump.
Soon, more and more domestic pigs in the region
were becoming seriously sick.
And a short time later, wild boars
— here marked in blue — fell ill as well.
Since then the plague has spread relentlessly —
via Russia and the Baltic states toward Western Europe.
In Germany, alarm bells started ringing in 2019,
when the first cases were detected in western Poland.
To prevent the virus spreading further,
the authorities set up electric fencing
near the border to keep out wild boars.
But by 2018, the virus had already reached Belgium —
after seemingly “jumping” over Germany.
And even today, France is disease-free.
Humans likely made a contribution to the pathogen
skipping certain countries in Europe.
Researchers suspect that the virus spreads in food —
because the ASF is particularly stable.
Even in processed pork, it can remain infectious for months.
But there is still no definitive proof.
Nevertheless, it's highly probable the disease
reached Belgium in just that way —
via left-over meat transported by humans.
Wild boars are omnivorous —
and don't turn their snouts up at meaty scraps.
And there was a conspicuously higher rate of
outbreaks of ASF along transregional routes.
In the end, the precautions failed to help.
African Swine Fever reached the eastern
German states of Brandenburg and Saxony in September ...
and October 2020.
Up to now, the disease has only spread
among wild boar in Germany,
but the risk is great that the virus will eventually infect
hog fattening farms.
An outbreak would be an economic disaster for Germany,
which is the world's third largest producer of pork.
But how can the further spread of ASF be prevented?
Because of a warm winter and an increase in available fodder,
the numbers of wild boar in Europe have mushroomed.
There are more than 90 thousand of them
in Brandenburg alone.
Authorities there have been relying on a radical strategy
to stem the tide of wild boars — via culling ...
and using unconventional methods.
By the end of April 2020,
ASF had been raging for months
on the Polish side of the river Oder —
which infected animals were able to cross
without too much trouble.
Egbert Gleich is a wildlife biologist
who works for the local authorities in Brandenburg.
He's also an expert in very special “hunting” techniques.
The method he uses is ideally suited
to rapidly decimating wild boar populations —
like the one overrunning the Oder Valley.
He's one of the few specialists
who hunt with cage traps.
Trapping is controversial.
But criticism takes a back seat —
given the spread of the plague
and the unmatched effectiveness of the method.
Here in these areas, we want to get the wild boar
population down as low as possible.
So we've got to take measures that for now
essentially mean the elimination
of the wild boar population.
Thinning out the wild boar population is vital
in the bid to slow the spread of the virus.
But ultimately, ASF can only really be stopped
by a vaccine for wild boars and domestic pigs.
There have been years of research, but so far in vain.
The virus that causes African Swine Fever
is a tough and tricky foe.
ASF is a very large virus
with a very, very, complex structure.
The virus is — as I always tell students —
a battleship.
It's loaded with factors that allow it to alter
the immune system in favor of the virus.
That makes it all extremely difficult.
So ... Sandra Blome and her team
are investing their hopes in a new strategy.
They're using genetically altered viruses.
We've taken certain characteristics
from the viruses we're using as vaccine candidates.
For one, they outwit the immune system,
making it difficult for the immune system
to recognize the virus.
Then there are “virulence factors”, which are
— or we hope they are —
what ultimately makes the animal sick.
The pathogen that causes ASF has tools
that prevent the immune system from recognizing it.
They're called immune modulators,
and allow the virus to reproduce unhindered.
To create a vaccine,
the researchers are using genetically altered viruses
with the help of this “camouflage”.
The result — after just a short time,
the immune defenses recognized the altered viruses.
They block multiplication
and form immune cells and anti-bodies.
When the body is then confronted with genuine pathogens,
the immune system has learned to dodge the ruse
and strike back.
The potential vaccine has proved to be
very promising in the lab.
The next step: trials on live pigs.
It's the only way Sandra Blome and her team
can find out if the vaccine really does protect animals
from the virus.
With camera teams not allowed in the bio-secure lab,
the scientists filmed the experiments themselves.
Half of the pigs were injected
with the genetically altered virus.
A control group was left unvaccinated.
Three weeks later, the researchers would infect
the animals with the genuine
and up to now deadly virus.
Egbert Gleich has been waiting for two hours
to sight wild boars in the Lower Oder Valley.
And suddenly, they appear.
The morsels of grain have lured eight specimens into the trap.
The young animals still don't suspect a thing.
Now Egbert Gleich has to move fast,
so that their suffering is kept to a minimum.
It takes him less than two minutes to get from the car
to the trap.
A minute later the animals are dead.
This is not “hunting.” It's execution.
But the wild boars' speedy demise
could save thousands of their taxonomic cousins
from an otherwise agonizing death caused by ASF.
Egbert Gleich and a colleague now check
whether the wild boars that have been killed
are indeed carrying the African Swine Fever virus.
They draw blood from the cadavers
and take the samples to the local veterinary inspection office.
What counts for the researchers, however,
is the appearance of the internal organs.
They indicate whether the animal was sick or not.
The spleen is totally flat, with normal coloring.
If swollen, the color would tend to be darker.
And here we have the kidneys.
Usually they're light-colored,
and there would be loads of little spots on them.
So there aren't any noticeable signs in this animal.
Back at the institute on Riems,
three weeks have gone by ...
Sandra Blome and her team are getting ready
to infect pigs, who've been vaccinated once:
with the real, deadly virus.
The virus kills almost all unprotected domestic hogs —
after days of torment from high fever, diarrhea,
breathing difficulties and hemorrhaging.
Most of the vaccinated pigs show no symptoms —
while the unvaccinated animals in the control group
become severely ill.
Sandra Blome has also tested vaccines on wild boars.
But another strategy is needed to prevent
the spread of the virus in the wild.
You can't really tell wild boars
that they've got an appointment to be vaccinated,
so we always need a vaccine
that can be administered orally.
We need a safe live virus vaccine
that is nevertheless effective,
so the genetically altered organisms
need to be tested for a long time before
we can really release them in the field.
The researchers say they'll have a functioning vaccine
by 2022 at the earliest.
The history of “plague island” is closely linked
to another devastating animal disease.
At the end of the 19th century,
Germany's farmyards were haunted
by a devastating specter.
Hundreds of thousands of cattle and hogs were killed
by a mysterious sickness — foot and mouth disease.
The cause was unknown.
In 1897, the then Prussian government commissioned
virologist Friedrich Loeffler to research the disease.
Loeffler set up sheds in two arches
underneath Berlin's elevated railway
and began his experiments.
Loeffler was a pupil of the famous bacteriologist,
Robert Koch.
And at first, he and his colleagues
were searching for bacteria.
But they soon observed that the usual filters
failed to stop the pathogen,
which therefore had to be much smaller than bacteria.
The scientists had discovered a new,
previously unknown type of microbes —
viruses.
Loeffler was aiming to find a cure for foot and mouth disease.
He continued his experiments in Greifswald
at a farm on the city's outskirts.
But the disease repeatedly spread to neighboring farms.
The government stopped the research.
Loeffler needed a place
where he could carry out his experiments without risk,
and found it on the island of Riems,
off the German Baltic coast.
In 1910, he set up laboratory buildings and barns.
The new institute was cordoned off,
and could only be reached by boat.
Friedrich Loeffler had founded the world's first
virological research institute.
He died in 1915.
But work on Riems continued after his death —
and really gained momentum in the 1920s,
with new labs, animal sheds, living quarters
and entertainment facilities for the institute's workers.
As in the past, foot and mouth disease
was the primary focus of research.
But they were joined in in the 1930s
by other viral livestock diseases,
such as avian — or bird — flu and classic swine fever.
But the first vaccine against foot and mouth disease
wasn't finalized until the end of the 1930s.
Nevertheless, there were repeated outbreaks
of the disease after the Second World War.
In 1950, East Germany became the first country
to require vaccination against the viral illness.
There haven't been any cases in Germany
for more than three decades.
In neighboring France, the last outbreaks were seen in 2001.
Today, on Riems, the “plague island,”
researchers are also examining viruses
hailing from other parts of the world —
because in the meantime,
the pathogens have become globetrotters.
Doctoral candidate Lorenz Ulrich
is setting up an experiment that needs to take place
at the highest biosecurity level,
because this virus is active and highly infectious.
The new coronavirus pandemic
has cost the lives of millions of people —
with further millions infected.
SARS-CoV-2 — an RNA virus from the coronavirus family.
It's believed to have originally infected a species of bats
and “jumped” to humans via an intermediate host.
But can the disease travel in reverse —
from human to animal?
We know that it infects humans primarily.
We know that it emerged from an animal source,
probably from bats, and maybe came to infect humans
via an intermediate animal host.
But we don't know if other species of animals
can become infected.
So can the virus jump from humans to animals?
In the meantime, it's known this is possible with cats.
From experimental studies we know
that household cats can be infected by strays.
But we're waiting for more field data.
At the moment, we're examining the statistical
distribution of feline samples
in order to get an idea of how many cats
really have become infected.
What percentage of them have actually
been exposed to SARS-CoV-2?
But what about livestock —
with hogs or cattle for example?
We want to know if this virus can infect pigs,
chickens and cattle.
If the virus can spread in the animal,
then we would have a new reservoir,
and in some cases a very large reservoir.
So there might again be the threat
of infection from animal to human.
There are almost a billion cattle in the world —
many of them in close contact with humans.
Can the animals catch the Sars-CoV-2 virus?
Researchers at the Friedrich Loeffler Institute
have been looking at how great the risk is.
Experiments on cattle are conducted
in a high-security area of the institute.
For safety reasons,
filming is only allowed until the researchers
go through the decontamination station.
After that, the scientists record their experiments themselves.
There are nine test cattle in the high-security shed.
Six of them are set to be infected.
The virologists want to find out if the pathogen
will multiply.
Three additional calves serve as contact animals,
to see if the virus can move from animal to the other.
The researchers administer the virus
to the animals' nasal mucosa
as humanely as possible.
After a six-day incubation period the researchers
will test the animals to determine
whether the virus has multiplied,
and if the cattle are already exhibiting symptoms.
Just how serious the effects of the virus
can be on animals is shown by the example
of the white mink.
It's been proved that some have been infected
via contact with humans.
Scientists have also discovered that the virus
can mutate once it is in the mink —
and then spread back to humans again.
At least twelve people in Denmark became infected
with this new variant of the virus.
Millions of the fur-farm animals
then had to be culled in Denmark.
Meanwhile, back at the bio-security facility in Germany,
after six days the cattle aren't showing
any apparent symptoms of the disease.
The researchers are now interested
in the viral load in tissue samples.
Have the pathogens reproduced?
They also take blood samples to detect antibodies.
Their presence would indicate
that the immune system had been activated.
Everything is painstakingly disinfected after the testing -
to ensure none of the pathogens escape.
Over in the lab, other researchers
are tracking the virus genome.
That would also indicate
whether the virus has multiplied
in an infected animal.
And by checking antibodies, they are able to determine
if the animal had contact with the virus
even after a longer time period —
and also when the pathogen is no longer present.
In the end the results showed that the virus did
multiply in the cattle's bodies —
but only in two of the six that were infected.
The scientists also detected antibodies,
although the infected animals
did not spread the pathogen.
Plagues like the coronavirus pandemic
are by no means uncontrollable natural events.
On the contrary:
humans themselves often create ideal conditions
for the spread of viruses from animals to humans
by intervening in natural processes.
Studies show that the destruction of habitats
and the loss of global biodiversity
are decisive forces driving the transmission of new pathogens.
Human encroachment on previously untouched
ecosystems and the constantly growing,
global movement of people and goods are a toxic mix.
They contribute significantly to diseases
spreading further and further and ever more rapidly.
Seventy percent of all new infectious diseases
come from animals.
A majority of them are carried and transmitted by viruses.
Mandy Schäfer and Helge Kampen
are hunting mosquitoes.
Now, at the beginning of fall,
as the mosquito season comes to an end,
the entomologists have trapped a few of the insect pests.
There are similar traps in 35 places across Germany.
The scientists from Riems want to find out
how the mosquito population is changing in the country.
For some time now,
they've been seeing a growing number
of mosquitos that didn't used to be present here.
Over the last ten years,
the two entomologists have identified six
of these invasive species:
including the Asian bush mosquito,
the Korean bush mosquito
and the Asian tiger mosquito.
Among the viruses carried by the Asian tiger mosquito
are Dengue, chickungunya, and zika —
plus another pathogen
that most people will not have heard of.
In early autumn 2020,
Berlin was getting ready
to face the second coronavirus wave.
With attention focused on the pandemic,
another development went largely unnoticed.
A man was diagnosed with a disease
that likewise came from a new virus.
The case was the seventh in Germany.
Yet the scientists estimate that the real number
is about 100 times higher.
The disease only becomes severe
— resulting in fever, encephalitis, and even death —
in only some of those infected.
The disease is caused by the West Nile Virus or WNV.
It's generally spread by mosquitoes.
WNV originated in Africa, but in recent years it's spread
from southern to central Europe —
probably and first and foremost by migratory birds.
Previously in Germany, those infected
were just travelers who came back
from tropical regions with the disease.
But this time it's different.
All of the patients picked up the disease in Germany.
How did a tropical pathogen like WNV
become settled in Germany?
And is there a connection to the Asian tiger mosquito?
In the insectarium at the Friedrich Loeffler Institute,
new generations of the Asian tiger mosquito
are being bred for research purposes.
To ensure that they grow and thrive
— and above all reproduce in big numbers —
entomologist Mandy Schäfer feeds them
with fresh animal blood.
The researchers on Riems
want to improve their understanding
of this species of mosquito.
The insects from the tropics
are currently settling in Germany,
as they've been doing for years in southern France.
Thanks to the increasingly warm summers,
the Asian tiger mosquito is feeling
increasingly at home here, too.
Above all in southern Germany,
where stable populations have already formed.
But West Nile fever broke out
in the northeast of the country ...
in 2018 in animals and then in the following two years
in people for the first time — marked here in orange.
But there aren't actually any
Asian tiger mosquito populations up here.
Research showed that by contrast,
another species of mosquito was spreading the virus —
the common house mosquito.
So how was it able to transmit a “foreign” virus?
The solution to the apparent enigma
was that the West Nile Virus
isn't foreign to the common house mosquito —
because this species came from Africa too.
Except that in Europe,
virus and insect hadn't yet had the chance to meet.
And that's precisely what's happening now,
driven by warming temperatures.
Plus, it's merely a question of time
until the other viruses carried by mosquitoes
begin to spread as well.
In October 2019 in Bavaria, a girl we'll call “Lisa”
was on her way to sports practice.
The thirteen-year-old had had a bad headache
since the morning.
Lisa was a good archer —
but that day, things were different.
She was unable to focus on the target,
and was experiencing double vision.
It was clear something was very wrong,
and the coach sent the girl home.
On the way home, the headache got worse.
Then Lisa collapsed and lost consciousness.
The doctors diagnosed acute encephalitis.
Lisa never regained consciousness.
She died after two days in a coma.
Lisa's death was one of several
that had gone unexplained after running a similar course —
sudden encephalitis, followed by coma and death.
The cause remained unknown.
But there IS a virus that has similar symptoms
of brain dysfunction.
It's called Bornavirus or B-o-D-V-1.
It's long been known that the disease infects horses —
but for humans, Borna disease
was thought to pose no threat.
Researchers know that the actual reservoir of infection
is another, smaller animal — the bicolored shrew.
In Germany, shrews that carry the virus
can be found in the states of Bavaria, Thuringia
and Brandenburg.
That's also where the deaths have been occurring.
In France, for example, there have been no signs of it
in either animals or people.
Researchers on Riems have been looking for clues
together with virologist Martin Beer.
And they've managed to identify the Borna disease
virus in tissue samples from the fourteen people who've died,
including young Lisa.
Once it's reached the human brain,
it becomes a deadly virus.
That's when those who've been infected
have about a 90 percent chance of dying.
The good news is that the event of actually
reaching the brain is evidently very rare.
This is the brain of a bicolored shrew from Bavaria.
If it tests positive for the virus,
this is where the researchers would expect to find it.
They want to find out how the pathogen
jumps from the shrews to humans.
Has the virus changed genetically?
The genetic material from the virus in the shrew
is compared with tissue from the human victims —
using a new, more comprehensive method.
It turns out that the bicolored shrew was positive —
and, more importantly, that the virus type
is the same one that led to the death of Lisa.
That said, however ...
We still don't know what the precise route was —
for example if there was direct contact,
because they picked up a dead shrew in the garden
or the cat brought one in ...
Another theory would be that the bicolored shrew
excretes the virus, including in its urine,
and that people were then infected
by eating freshly picked lettuce or herbs,
or maybe hanging around outside in the garden.
We've also seen a pattern in the patients —
that they actually did do outdoor activities
and lived in very rural areas.
But that's no reason to lock yourself indoors.
We also know that the virus stays in specific areas —
the precise dispersal area of the bicolored shrew ...
So it's a very deadly virus that is apparently
only rarely transferred and then not very easily.
Unlike Borna disease,
the pathogens for African Swine Fever can't jump to humans.
Nevertheless, the disease threatens the livelihoods
of many people — and the lives of millions of pigs.
The Friedrich Loeffler Institute
has teamed up with the Bavarian Forest National Park
to gain more information on how the virus spreads.
Carolina Probst and Marco Heurich
are looking for clues that would indicate
how long ASF has been present in a region
and how far it may have spread.
They've picked various sites in the national park
for their experiment — places that are as far as possible
from streets and hiking trails.
This dead boar is one of several
being used for their field study.
We suspect that wild boar carcasses
play a very central role in the epidemiology
of this animal plague.
And we're using these experiments
to try to find out how the process of decay occurs.
That will show us how long the ASF virus
can remain alive in a carcass.
How quickly does a dead wild boar decompose
in different surroundings —
on dry or moist earth, for example.
And: how long is it a source of infection?
We know that unlike other viruses,
this one stays stable out in nature for a very long time —
perhaps even for months.
The virus is present in large amounts,
in tissue and especially in the blood and muscles.
These are places well-supplied with blood.
Also the spleen, for example,
and other internal organs.
A camera documents the decay of the wild boar.
It takes one image a day ...
After seven days of warm weather,
the carcass is already in an advanced state of decay —
thanks to swarms of insects and their maggots.
One key finding is that after several weeks have passed,
only one specific part of the cadaver
remains dangerous as a source of infection.
The bones are our big worry, especially the ribs.
And preceding studies show that the ribs
are very appetizing for other wild boar,
especially for young animals
because their bones are still growing.
And that's our biggest concern:
that ASF will remain in the wild boar population
for a very long period in an affected region.
It will till take months for the research to be complete.
But one thing is already clear —
wild boar carcasses are viral time bombs.
And in order to stem the spread of African Swine Fever,
it's necessary to defuse them as fast as possible.
That's easier said than done —
because the dead boars often lie undetected
for weeks or months in the undergrowth.
This is the site of an outbreak
in the Brandenburg region of northeast Germany.
Teams working with dogs
are trying to find wild boar that have died of ASF.
They also have high-tech tools at their disposal.
Former soldier Steffen Franzeck
is using a drone in an attempt
to find wild boar in the forest — dead or alive.
The drone is fitted with a normal camera,
and a thermal imaging device.
Look, there's something lying back there in the corner.
Yep, and it's still warm, too. Eleven degrees.
They are indeed boars — albeit still very much alive.
In normal mode, you can often see wild boars.
There's one right up there.
Wildlife expert Julian Dorsch is also in the team.
There are three lying there.
The camera images show that the animals
are apparently still healthy.
But the thermal imaging device can find cadavers as well.
Even days after an animal has died,
the body can emit extremely high
decomposition temperatures.
It's very likely the animal died of African Swine Fever —
and is as such an infection reservoir
that would've remained hidden for weeks or months
without the help of the drone.
The researchers at the virological institute on Riems
will have plenty of work to do in the years to come.
Because viruses have long since become global agents.
On “Plague Island” and in the field,
the scientists are doing all they can
to beat them at their own game.