How WHO planned and failed the COVID-19
pandemic
One morning in February
2018, a group of 30 microbiologists, zoologists and public-health experts from
around the world met at the headquarters of the World Health Organisation in
Geneva. The group had been established by the WHO in 2015 to create a priority
list of dangerous viruses – specifically, those for which no vaccines or drugs
were already in development. The consensus among those in the room was that as
populations and global travel continued to grow, and development increasingly
pushed into wild areas, it was almost inevitable that once-containable local
outbreaks of diseases such as SARS or ebola could become global disasters.
“The meeting was in a big
room, with all the tables arranged around the edge, facing each other,” one of
the group’s members, Peter Daszak, recalls. “It was a very formal process. Each
person was asked to present the case for including a particular disease on the
list of top threats. And everything you said was being taken down, and checked
factually, and recorded.”
Daszak, president of the
US pandemic prevention group EcoHealth Alliance and chairman of the Forum on
Microbial Threats at the National Academies of Sciences, Engineering and Medicine,
had been given the task of presenting on SARS, a coronavirus that killed
roughly 800 people after it emerged in 2002. “We’d done a lot of research on
coronaviruses, so we knew they were a clear and present danger,’’ he tells me.
“High mortality, no drugs or vaccines in the pipeline, with new variants that
could still be emerging.’’
The discussion was
intense. “Everyone else in the room knew the facts already, they’d read all the
research,’’ Daszak says. But for each pathogen, the speaker had to convince the
room that it presented a significant threat – “that this disease really could
take off, and that we should concentrate on it rather than on Lassa fever or
something else. So, you argue the case, then people vote. And sometimes it gets
quite heated. I remember that monkey pox was an issue, because there are
outbreaks but there’s really nothing we can do about them. It was a really
rigorous, really excellent debate and then afterwards, we went and had
fondue.’’
The final list, which did
contain SARS and MERS, along with seven other respiratory, hemorrhagic or
otherwise lethal viruses, also included something the WHO dubbed “Disease X” –
a stand-in for all the unknown pathogens, or devastating variations on existing
pathogens, that had yet to emerge. Daszak describes Covid-19 – the disease
caused by the virus SARS-CoV-2, responsible for the current pandemic gripping
the world – as exactly the kind of threat that Disease X was meant to
represent: a novel, highly infectious coronavirus, with a high mortality rate
and no existing treatment or prevention. “The problem isn’t that prevention was
impossible,” Daszak tells me. “It was very possible. But we didn’t do it. Governments
thought it was too expensive. Pharmaceutical companies operate for profit. And
the WHO, for the most part, had neither the funding nor the power to enforce
the large-scale global collaboration necessary to combat it.”
As Covid-19 has spread
around the world, overwhelming hospitals and even mortuaries, there has been
widespread dismay over how we could have been caught so flat-footed by a virus.
Given all the shining advances of high-tech medicine – computer-controlled
surgery, unprecedented immunotherapies, artificial-intelligence programs for
assessing heart-disease risk – this failure feels utterly baffling. How could
the entire world remain so powerless? More important, what could be done
differently next time?
According to some
infectious-disease experts, the scientific tools already exist to create a kind
of viral-defence department, one that would allow us to pursue a broad range of
vital global projects, from developing vaccines and drugs that work against a
wide range of pathogens to monitoring disease hot spots and identifying
high-risk viruses, both known and unknown. “We really did miss the wake-up
call,’’ Daszak says. “The alarm went off with SARS, and we hit the snooze
button. And then we hit it again with ebola, with MERS, with Zika. Now that
we’re awake, we should think about where to go from here.”
In late March, Vincent
Racaniello, host of the podcast This
Week in Virology and a professor at Columbia University, conducted an
interview with Mark Denison, a paediatric infectious disease expert who
teaches at Vanderbilt University Medical Centre in Tennessee. Denison led a
team that developed one of the most promising current treatments for Covid-19:
the drug remdesivir, currently being tested by the pharmaceutical company
Gilead Sciences.
On the show, Denison
noted that because it is almost impossible to predict which virus might cause
the next pandemic, researchers had long argued that it was essential to design
panviral drugs and vaccines that would be effective against a wide range of
strains: all types of influenza, for instance, or a substantial group of
coronaviruses rather than just one. When his lab was first applying for a
grant to study remdesivir, Denison recalled, that was already the goal. “We
don’t want to work with a compound unless it inhibits every coronavirus we
test,” Denison said. “Because we’re worried about MERS, we’re worried about
SARS-1, but they’re not really our problem. The future is the problem.’’
Panviral drugs – ones
that work broadly within or across virus families – are harder to make than
broad-spectrum antibiotics, largely because viruses work by hijacking the
machinery of our cells, harnessing their key functions in order to replicate. A
drug that blocks one of those functions (eg, the production of a particular
protein) is often also disrupting something that our own cells need to survive.
Researchers have begun to find ways around that problem, in part by refining
which process a drug targets. But they’ve also begun to test existing drugs
against a wider array of viruses. It was in just such a follow-up test that
Gilead discovered that remdesivir, originally developed to treat hepatitis C and
later tried against ebola, might be effective against coronaviruses.
(Favipiravir, an influenza drug developed in Japan, is another broad-spectrum
candidate.) The reason drugs sometimes work in very different diseases – in,
say, ebola and coronaviruses and flu – is that they block some common
mechanism. “It’s definitely possible to make a drug that would work across a
good range of coronaviruses,’’ Racaniello says. “We honestly should have had
one long ago, since SARS in 2003. It would have taken care of this outbreak in
China before it got out. And the only reason we didn’t is because there wasn’t
enough financial backing.’’
For years, Racaniello
notes, the real obstacle to making panviral drugs or vaccines has been that no
one was willing to pay for their development. For pharmaceutical companies,
panviral vaccines are simply a terrible business proposition: companies would
have to spend hundreds of millions of dollars to develop a shot that people
would get once a year at most, and not at all in years when no particular
disease is ascendant.
Panviral drug treatments
are unprofitable for similar reasons. For one, the course of treatment is
short, usually just a few weeks. (One person noted that Gilead’s stock price
actually dropped after the company produced a revolutionary hepatitis C drug;
because the treatment completely cured patients, the market for it started to
shrink, undermining the company’s bottom line.)
The other problem is that
there’s currently no way to quickly test for most viruses. As a result,
Racaniello says, it’s a chicken-and-egg situation: “No one is developing drugs
for these viruses because there’s no way to test for them. And no one is
developing tests, because there aren’t any drugs to prescribe.”
Governments, meanwhile,
have been reluctant to fund panviral development because it’s expensive and
because the rewards can feel remote, especially as many diseases originate in
other countries. “We don’t prevent well; we respond well,’’ Daszak notes.
“Remember when Obama got $5 billion for the ebola outbreak in West Africa, and
US troops went to help fix the problem? That’s heroic. How heroic is it, three
years before ebola, to say, ‘We’re going to fund a massive program in West
Africa to help these poor countries get ready in case an outbreak happens?’
He’d be laughed out of the room!’’
Global non-profits such
as the Bill & Melinda Gates Foundation have tried to step into this funding
void. And the Coalition for Epidemic Preparedness Innovations (CEPI), an NGO,
was founded in 2017 to co-ordinate and finance the development of new vaccines
for diseases that might lead to a pandemic. It works by identifying the most
promising research, and then connecting it to industry and government
resources, in order to bring multiple sets of candidate vaccines through
initial clinical trials. The goal is to create a stockpile of potential
treatments for known coronaviruses, hemorrhagic fevers and other global
threats that could quickly go into production in the event of an epidemic. The
group also funds technologies aimed at Disease X (the potentially pandemic
viruses that we have yet to discover) with the goal of faster vaccine
development should a new threat emerge. As Jake Glanville, whose company,
Distributed Bio, received a grant from the Gates Foundation to create a
universal flu vaccine, told me, “This is how we win the forever war, and not
just battles against these pathogens.”
Despite these efforts,
there is still one overarching problem: how little is known about the planet’s
viral threats. Viruses make up roughly two-thirds of all newly discovered human
pathogens, far more than either bacteria or fungi. Over the course of human
evolution, we’ve been exposed to so many that about 8 per cent of the human
genome is made up of retroviral DNA sequences that have inserted themselves into
the gene pool, often to our benefit. (An ancient virus is thought to be
responsible for the development of the human placenta, for example.)
Perversely, viruses get
no advantage from making people seriously ill; it’s simply a byproduct of the
encounter. Over the years, or sometimes centuries, viruses and hosts usually
reach an accommodation; they coexist. Typically, the most dangerous viruses are
those that have jumped into humans from other species, as happened with
Covid-19. That’s partly because the disease is new, so our immune system hasn’t
had a chance to create antibodies. But it’s also because an unfamiliar virus
is more likely to throw our immune system into overdrive, potentially fatally.
For anyone hoping to
identify where the next pandemic is coming from, the difficulty is that there
are literally millions of viruses to analyse. One paper recently estimated that
there were 1.6 million potentially zoonotic viruses, of which fewer than 1 per
cent have even been identified.
Hoping to get a more accurate
estimate of which viruses could be a threat, Daszak recently travelled to rural
Yunnan province in China and took blood samples from people who live there,
looking for antibodies that would show how often they had been exposed to bat
coronaviruses. (Detectable antibodies typically last two to three years after
an infection.) “This was bat coronaviruses alone, not all the other stuff
that’s out there,” Daszak said. “And we found that 3 per cent of the population
had been exposed, which tells me that these things are spilling over at an
incredible rate, as part of everyday business in rural China.”
Which means, Daszak says,
that between one million and seven million people a year in South-East Asia
pick up bat coronaviruses. “For most of them, it probably doesn’t even cause
illness. There may have been some little outbreaks that never got noticed, or
cases where people even die, and it gets put down to influenza or something.”
He pauses. “But that is a huge level of spillover. It’s not difficult to imagine
one of those infections mutating a bit and becoming Covid-19.”
Policing points of
potential spillover is challenging, and the effort needed to rigorously track
and test wildlife even more so. As Racaniello observes, “We’ve known since SARS
that bats harbour dangerous coronaviruses. So bats are an obvious place to
look. But even then it’s not easy to do. You have to crawl into a bat cave, you
have to catch them somehow. It’s tedious, costly work.”
One challenge for
pandemic hunters is understanding which animals are most likely to be the
source of viruses. Bats are the original carriers for many zoonotic viruses
(one study found that bats in China harbour more than 500 different
coronaviruses, as well as paramyxoviruses, influenza and hemorrhagic viruses
like ebola), but they rarely pass those diseases to humans directly. More
often, Daszak explains, bats infect another animal, which then infects us.
Racaniello points to the Hendra virus outbreak in Australia in the 1990s that
was caused when bats began frequenting a racehorse stable, infecting the
horses, which then passed the disease on to human trainers. In Malaysia, Nipah
virus emerged from pigs, on farms in an area that harboured fruit bats. In the
Middle East, the MERS coronavirus is thought to have passed from bats to
camels, which at some point started passing it on to people.
“Before that outbreak, it
wouldn’t have occurred to anyone to look in camels for a pandemic virus,’’
Racaniello says. “The same is true for a lot of things. For instance, we knew
that bats carried SARS-like coronaviruses, but it was only when they started
looking for the cause of the first SARS outbreak that they found it had jumped
from bats to civet cats, which is how we got it. But as to all the other
animals in the world, we pretty much have no idea! So, I think you just need to
cast a very wide net.”
THEAUSTRALIAN.COM.AU2:44
The World
in Crisis
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How did we get here?
To do that, Daszak has
helped found an ambitious venture called the Global Virome Project, which
seeks to identify 70 per cent of the estimated 1.6 million potentially zoonotic
viruses over 10 years at a cost of $1.2 billion. “We found the closest relative
to the current SARS-CoV-2 in a bat in China in 2013. We sequenced a bit of the
genome, and then it went in the freezer; because it didn’t look like SARS, we
thought it was at a lower risk of emerging. With the Global Virome Project, we
could have sequenced the whole genome, discovered that it binds to human cells
and upgraded the risk. And maybe then when we were designing vaccines for SARS,
those could have targeted this one too, and we would have had something in the
freezer ready to go if it emerged.”
Another risk factor is
simply how likely we are to come into contact with a particular animal, from
activities that include logging, the wildlife trade and farming. (Measles is
thought to have arisen out of the domestication of cattle, while pigs and chickens
carry swine flu and bird flu.)
In the wake of the
Covid-19 pandemic, more systems of global
co-operation and investment have started to emerge. In late March, the Bill
& Melinda Gates Foundation set up a Covid-19 Therapeutics Accelerator to
screen a vast number of existing drugs and compounds that hadn’t made it to
market, in order to test whether they might work on the current pandemic.
The willingness to share
proprietary compounds is “pretty unprecedented”, says Gates Foundation CEO Mark
Suzman. And after the current crisis has passed, that same collection could be
screened for more ambitious projects such as a broad-spectrum anti-coronavirus
drug. Monalisa Chatterji, a microbiologist who is part of the foundation’s
drug-discovery arm, agrees. “The conversation has started for future pandemics,”
she says. “Should there be a standing shared library of unused drugs that
research labs can test? Should similar things be done around diagnostics?
Should there at least be an agreement where every company has already agreed to
provide access to its library in a pandemic situation? That sounds small, but
it’s these small things that eat up time when it matters.”
The big question,
according to nearly everyone I speak with, is whether this political and
financial will can last. Racaniello and Daszak both remember being sure that
after SARS and ebola, pandemic prevention would be a priority; instead, each
outbreak was quickly forgotten. “We don’t think twice about the cost of
protecting against terrorism,” Daszak says. “We go out there, we listen to the
whispers, we send out the drones, we have a whole array of approaches. We need
to start thinking about pandemics the same way.”
Originally published in
New York Times Magazine
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