(upbeat music) - Hello I am Suresh Subramani a Professor in the section of molecular biology and the Director of the Tata Institute for Genetics in Society at U.C. San Diego. Thank you to all of the
viewers for tuning in to this program, on the biology
and evolution of COVID-19. So we are gathered here today
to discuss the coronavirus pandemic that has
engulfed the entire globe in just three months
since it was first brought to the attention of the
World Health Organization on New Year's Eve of 2019. There are three primary
reasons why the world is so concerned about this new virus, to which no one to our
knowledge has natural immunity. So first is the rapid spread of the virus. In just three months it has
spread to over 200 countries. The second is that it
poses significant morbidity and mortality that threatens to overwhelm the global healthcare systems. So since the first report of
this virus in Wuhan, China, as of March 30th there
were over 750,000 cases and 36,000 deaths worldwide,
which is a mortality of about four and half
percent, which is higher than that of flu virus and even as we air this particular program,
the USA leads the world as the hotspot for COVID-19. The third reason is a
huge reservoir of carriers of this particular disease. It is estimated that
there may be tenfold more asymptomatic carriers without
symptoms of the disease which means then that could
be over seven and a half billion carriers worldwide. So, in summary then, this is
a disease that is spreading very rapidly across the globe, with the number of cases doubling
every three to four days, and it has sewn fear and
unpredictability across the globe, requiring the implementation
of social distancing and lockdown policies. Stressing our medical
capabilities to the extreme and causing severe economic
fallout that is still unfolding. How long all of this will
last is completely unknown, is anybody's guess. So we've gathered here
today, a panel of biologists who work and teach broadly
about infectious diseases, how they arise, evolve and
spread to infect human beings around the globe by evading our otherwise robust immune systems. So, these faculty are incurred
to share their knowledge regarding the biology of the virus. Why this pandemic has brought
the world to its knees and they will also discuss
the implications of infectious diseases broadly in our lives. They're here specifically
to talk about a biology of the viruses but not
to provide medical advice or policy matters relating
to this particular virus. So let me introduce our
panel of three speakers, which consists of three faculty from the Division of Biological
Sciences at U.C. San Diego. They are doctors Emily
Troemel, Matt Dougherty and Justin Meyer. I will introduce them one
at a time, following which they will each give a
short presentation and then at the end of the presentations
we will have a round table discussion on topics of interest. So let's begin with our first
panelist, Dr. Emily Troemel is a professor in section of
cell and developmental biology. Her lab studies host pathogen interactions and in particular she focuses
on intracellular pathogens that are completely dependent on the host for their replication. These include fungal parasites,
called microsporidia, as well as viruses that
have genomes that consist of ribonucleic acid as opposed
to the deoxyribonucleic acid that most organisms have. And coronaviruses by the way
have of these ribonucleic acid or RNA genomes. So she is going to address
the topics as follows. The basic biology of
cornonaviruses, how we test whether someone is infected with this
virus that is called SARS, COVID-2 and how scientists
predict and model the spread of this particular
virus in the population. So Emily, I'm going to turn it over to you to do, to give us your presentation first. - All right Suresh, thanks so
much for that introduction. And thanks for the
opportunity to share with you some of the basic biology of coronavirus and how that relates to COVID-19 disease. So I'm gonna tell you about three different aspects of COVID-19. The first of which is just defining how the COVID-19 diseases relates to this virus called SARS-CoV-2. Next I'm gonna tell you how
we test for the presence of the SARS-CoV-2 infection. And then I'm gonna share
with you what we've learned about SARS-Co-V2 genome. Suresh mentioned it's an RNA genome and how we're able to look
at changes in the sequence in this genome and that's
enabling us to track the spread of this virus around the globe and it's really part of an
amazing open science effort with sort of an unprecedented
level of information acquisition and information
sharing among researchers. So first off I just want
to clarify how COVID-19 relates to SARS-Co-V2. So COVID-19 is the disease
that's part of this pandemic and it's caused by a virus that's recently been named SARS-Co-V2. And there's a connection here
you can think of in terms of the disease of AIDS being
caused by the virus HIV. Similarly back in 2002 and
2003 there was this severe acute respiratory called
SARS, the disease, that was caused by a virus
that's called SARS-Co-V now called CoV-1. And since the virus of this
current pandemic is related and sequenced it's been named SARS-Co-V2. And so SARS-Co-V1 and two
are part of this group of viruses called
coronaviruses, which are named because of the appearance
of the viral particle, as you can see in an
electron micrograph here, where these red blobs
are the spiked proteins on the outside of the
viral particle that form kind of a halo around corona, a crown. And so that's the source
of the name, coronavirus, and it's abbreviated CoV. So, as many of you know viruses
are completely dependent on their hosts for replication. So, unlike many disease causing
agents like most bacterial pathogens or the fungal pathogens
that are able to replicate on their own, viruses
absolutely need a host present. And it's for this reason
that the social distancing measures that we've been hearing
about and been implementing can be so effective. Because while the virus
can survive in the case of SARS-Co-V2 maybe two
to three days outside of a host, it cannot make more of itself without getting inside of a host cell. So that process of getting
inside of a host cell and making more of
itself is diagrammed here with this rectangle
representing a host cell, for example a cell in a human lung where outside of the cell a virus, such as this green hexagon here. If it is able to find a
proper receptor on the surface of the cell combined to that
receptor and be taken up into the cell. The virus will then release
its genome to enable gene expression to happen. Replication of its genome
and late expression to enable the formation of new viral particles. And here we've got one virus coming in, and then three new viruses
being made that are released to go and infect new hosts. And in fact, you can have a
much larger replication number than this, for example
some viruses can have tens to thousands of new viral
particles made from a cell. And also as Suresh mentioned,
the genome for the coronavirus is actually different from
the genome of most life. So most life like bacteria
in humans the blueprints to make more of ourselves, the genome, is the molecule called DNA. And some viruses do use DNA,
so this generalized life cycle here is showing sort of
a DNA being made into RNA which is made into protein. But many viruses use RNA for their genome and in particular coronaviruses
are single stranded RNA viruses that are positive
sense, which means that they can rapidly hijack the host
protein synthesis machinery, to start making proteins and
in this way really rapidly hijack and take over a host cell. So knowing that the coronavirus
has RNA in it genome helps us understand how
we test for the presence of the coronavirus. So you may have heard about
the need for more testing, we've had an extreme shortage
of tests and there were some problems with the original
tests that were availible and its really critical that
we get more of these tests and I just want to explain
how these tests work. The most common of which is a RT-PCR test, which stands for Reverse
Transcription-Polymerase Chain Reaction, also sometimes
called a real time test. So the way this test works is
that a sample from a patient is isolated, the RNA is
extracted, and then it's reverse transcribed into DNA. This DNA is then amplified
with this polymerase chain reaction to enable
detection of one segment of the viral RNA genome. So, this RNA detection then
enables us to determine who is currently infected with the virus. This kind of a RT-PCR test however, will miss infections that
have already been cleared. And so a related test
will be able to detect those infections that
occurred in the past. And this kind of test is a serology test that measures antibodies
that were generated against the presence of that virus. And the antibodies that are
generated against the virus can be detected if somebody
is currently infected and is mounting an immune
response or somebody who was infected in the past
and has cleared the virus but still has those antibodies, because they can last for
years and even decades. And so with the combination
of these two tests where the RT-PCR test is
able to detect the presence of viral RNA in current
infections together with the serology test that
measures the immune response we can determine who has the infection but hasn't yet mounted for some
reason an antibody response, maybe because the infection
is still so early, people who have both the
infection and have mounted an immune response and
people who no longer have the infection but had it
in the past and mounted an immune response and
potentially those antibodies cleared the infection. So this RT-PCR test is
detecting RNA from just one gene in the viral genome, but
the virus has a number of different genes that
are made into proteins, that are part of its entire
genome and that's represented here with this line the
different colors representing different gene made
into different proteins. And because the technology
has gotten so much better, we're really rapidly acquiring
and cheaply acquiring sequence information,
we're able to sequence the entire genome of this virus, from many, many different samples. And it's really been an
amazing, kind of unprecedented rate at which we're
acquiring this information, sharing this information and
analyzing this information. And a lot of this
information so it's basically getting samples from
patients around the globe that are sending information
to a website called GISAID, that's run by the German government, originally organized to
acquire influenza information. Now being adapted for coronavirus. That information is
rapidly ported to a website call Nextstrain.org that
has these really wonderful visualization tools so we
can look at how the sequence of the genome is changing. And this, a I mentioned,
this is increasingly there's more and more genome
information every time you look at this website. So this morning there
was over 2,000 genomes from 2,000 different infected patients that were analyzed and compared. And the way they're compared
is in sort of the family tree shown here, with on the
X axis here is time, and the colors are
representing where the virus was isolated from. For example, purple represents
isolated from China, red represented virus
isolated from the Americas, and then the branch links
of these trees are telling us how closely related
this different viruses are, so you can see that viruses
from China are very closely related to some viruses that were isolated from people in the Americas. From this information we
can learn that somebody in China transmitted the virus
to somebody in the Americas. And not only are we now
able to track how this virus has spread by this kind of
fingerprint of the mutations and the changes in the viral genome, but we also, because of what
we know from the biology of this virus can learn
about how the biology of the virus is changing, how
it may be altering the way it interacts with host
cells and also potentially different ways that we could treat it. And it's I think, a real
success story in terms of the power of open science
and the power of sharing information among researchers
so that we can better able understand how this virus
is spread around the globe, how its biology is
changing and also hopefully how we can treat it. So with that information I
think this should provide some foundation for Matt to
next talk about evolution of this virus and Justin more about spread and I'll thank you very
much for your attention and hand it back to Suresh. - So thank you so much Emily. Our next speaker is Matt Daugherty. He is an assistant
professor in the section of molecular biology. He studies evolutionary
arms race in adaptations of the host's immune
systems on the one hand and the surface proteins of
their pathogens on the other. He will discuss how viruses evolve to become human pathogens, how
they jump from their natural animal hosts to humans and
why human immune systems cannot cope with the new strain of virus that has never been seen
before by the immune system. - Thank you Suresh for the
introduction and thanks to Emily for the great
introduction to coronaviruses. So what I wanna talk about
in the next few minutes is how this virus SARS-Co-V2, which is causing the COVID-19 pandemic, fits into the context of other
viruses that are circulating within the human population, or have caused previous epidemics. Because we as a species
are always being exposed to viruses as is illustrated
very nicely in this image of Alice from Lewis
Carroll's famous books chased by all sorts of viruses and pathogens. So using this perspective, I'd
like address three questions about SARS-Co-V2, first, how
do viruses such as SARS-Co-V2 enter the human population
become pandemics, second how does this virus actually relate to currently circulating
as well as past and present epidemic human viruses, and third, based on all this
information, what does this tell us about what we
could expect for our future existence with this virus in
terms of potential long-term immunity or coexistence with his virus. So first, it's important
to point out that every human pandemic virus that
we know of in recent times has originated from another species, which is something we called zoonotic transmission or zoonosis. And I'm showing you here
a case where we're saying it's coming from a bat, which
we call a reservoir species. For SARS-Co-V2 bats were
likely the original reservoir, but of course many different animals serve as reservoir species for zoonotic viruses as we'll discuss as in a moment. But the zoonotic transmission
into a single human is only the first step. There's also a very important second step, which is the virus then
needs to be able to have sustained human to human transmission. So these two steps together really result in a virus that has pandemic potential. Now if we look at this in
the context of coronaviruses we know there are plenty of
circulating human coronaviruses that cause mild systems
that we often refer to as common colds, and
up to about 20 years ago people didn't really pay
too much attention to these viruses because again,
they were just one of many types of viruses that cause a common cold. What we've also learned
in the last say 20 years is that in fact within animal populations, again, especially among bats, there are many, many
circulating coronaviruses. And again, we assume that
because these are resonate in these animal populations
these have pretty low case fatality rates. So where the danger comes
is when infected bats or some intermediate host
comes in contact with humans and we have what's
called a spillover event. These spillovers result
in zoonotic viruses in the human population,
but fortunately many times these have limited or no
real ability to transmit human to human. And within the coronavirus
family we have an example of this, where starting
in about 2012 we started seeing cases of a virus known
as Middle Eastern Respiratory Syndrome Coronavirus or MERS-CoV. We've seen about 2,500 cases
of this virus and as is common with these type of zoonotic
viruses the case fatality rate is really quite high
which is pretty alarming. But again, human to human
transmission appears to be low. But for other viruses, once
that spillover event occurs, either because the virus was
initially adapted to do it or rapidly adapted to do it,
it's now able to have sustained human-to-human transmission. So these are the viruses
that have massive pandemic potential and this is where
we are with SARS-Co-V2. In this case, the very first
cases appear to have been detected in November or December of 2019 and as of March 30th
we're rapidly approaching one million cases globally. What we also see is that
the case fatality rate is much lower than you see with MERS, which again is pretty common
with viruses that have sustained human-to-human transmission, although it's certainly much
higher than we're seeing with circulating coronaviruses. And as Emily also mentioned,
there was previous case of this occurring in coronaviruses
where in 2002 there was an outbreak of a virus that
was known as SARS-Co-V. And fortunately it was stopped
before it spread globally but was also quite deadly. So we already knew that
there was pandemic potential in this family of viruses, but of course SARS-Co-V2
has really emerged on a much larger scale. So if we want to
understand how this happens we really need to understand
the evolution of viruses and hosts at a molecular level. So what leads to the
emergence of pandemics? So it's important to not
just think about the species but actually the viruses
within those species. And as Emily has already
nicely introduced, viruses mutate and so that
we know that the virus that's circulating in humans
is only about five percent different compared to known
circulating bat viruses. And if we wanna know how
these differences changed the virus, we need to think
back to what Emily introduced about the viral life cycle. All these points of contact shown here in the schematic Emily
used, between the virus and host along the life
cycle can be barriers that the virus needs to jump
to get into the new population. The one I'm gonna focus on now is the step by which the virus enter
the cell which is binding to the cellular receptor which is mediated by an interaction between
this viral protein that's called Spike and the
host cell protein called ACE2. And we often schematize these interactions as basically a key that
needs to fit into a lock, but of course the real interactions look much more like this,
with a three dimensional structural interaction of
the Spike protein that then interacts with this ACE receptor. So now if we go back to our
bats, we know that the bat virus must have had a spike
protein that could interact with Bat ACE2 but a circulating bat virus may not necessarily be able
to interact with Human ACE2. Which it would need to be
able to do to jump species. And I've drawn ACE2 as looking
different because we know that host proteins that
interface with viruses tend to themselves evolve very
quickly across host species, presumably because of these high stakes host virus conflicts. And again, as Emily introduced
viruses mutate a lot, so we imagine that within
the bat population a variant of this virus arose that
could utilize human ACE2 and if that right virus
encountered a human virus that could transmit it to humans. So the final thing to say
about this is to just reiterate that Spike and ACE2 were only
one piece of this puzzle, and for a virus to be successful, it needs to adapt to many
of the genetic differences between humans and the reservoir species. So for instance we already
know that there are many coronaviruses circulating in bats, that can already utilize human ACE2, but presumably haven't
made the jump into humans because there's some other
molecular barrier to replication. So having talked about
coronaviruses such as SARS-Co-V2 can and have entered the human population, I want to return to this
question of how SARS-Co-V2 relates to other circulating
epidemic genome viruses. As I mentioned in my earlier
slide there are coronaviruses that span this whole range
of steps in human viral emergence from animal
viruses to zoonotic viruses to circulating human viruses. But of course, we know many human viruses, and have had many human pandemics. For instance, of one of the
common things we're hearing about now is how these
relate to influenza viruses. Partly that's because the
influenza virus causes respiratory symptoms like coronaviruses, but partly there's also just
a very clear analogy here in terms of the various influenza viruses in the categories shown here. So at the pandemic level,
we've all heard of these major pandemic flus, from 1928 the
so called Spanish Influenza in 1968 and even as recently as 2009. But of course we know
that in addition to these pandemic strains of flu
there are several seasonal flu strains of influenza
that we have to deal with every year as well as strains
of viruses that transmit from birds and have very
high case fatality rates but so far have limited
human-to-human transmission. And as with MERS, one of
the big concerns is that if any of these viruses, like
H7N9, gain human-to-human transmission we really
need to worry about that. And we also know that the
real reservoir of this virus is the many, many strains
of avian and swine influenza that circulate within animal populations. And at the same time there
are many other pandemic viral strains outside of influenza, many which come from some
animal reservoir at some point. So for instance, Smallpox
and HIV and Ebola have all caused epidemics in humans,
and we know for instance that HIV transmitted into
the human population several independent times from primate reservoirs, only a little over a 100 years ago. Of course we also have plenty
of circulating human viruses like measles and polio that
probably had some zoonotic transmission deep in their
ancestry but wasn't quite as recent as any of these,
as well as viruses in this category of zoonotic transmission
with high case fatality. Among these is rabies virus,
which is essentially 100% fatal if left untreated, but doesn't
transmit person-to-person and also Nipah virus which
has a very high case fatality rate and is also famous for
being the virus people used as the model for the movie "Contagion". And finally, and this is
where some basic virology surveillance has taken place,
we know that there are many, many viruses circulating in
reservoir species that have an unknown number of
evolutionary steps away from being zoonotic transmissible. So one thing I take comfort
in about all these other viruses is that we aren't
constantly dealing with influenza pandemics and Smallpox
and other pandemic viruses and that's because of the
largely effective role of our immune system that Suresh mentioned in dealing with these viruses once the immune system has
actually been prepared. And so with that, we'll
start talking about this last question of what we might
expect for SARS-Co-V2 in the long term. I'll start off by saying we
don't actually really know much about the long term
immunity to SARS-Co-V2, because of all this information
is only recently emerging. So for instance, we
don't know whether people that have been infected are now resistant to secondary infection,
which is sort of the hallmark to long term protective adaptive immunity. But we can get a hint from
some of these other viruses that we talked about. So the good news is is that
we have long term protective immunity against many viruses
and you'll see that all of these are vaccine targets,
some of these are pandemic viruses like Smallpox, some
have limited transmission in humans and some are
circulating human viruses. So we have really good ways
of making effective vaccines and the hope is that this will
hope for SARS-Co-V2 as well. Although the development of vaccines of course take some time. We also know in the case
of something like Ebola where we don't know yet
know we have a good vaccine, but we know we can take blood
from people that have been infected and then cleared the infection and use antibodies from
that infected person to administer to people
that are currently infected. And this can actually be quite protective, so with SARS-Co-V2 we expect
this might be a limited but effective way to
treat current infections. Of course there's also
several viruses where we have limited short-term or unknown
levels of protective immunity, unfortunately for instance
one thing we don't now because circulating
coronaviruses are not incredibly well studied, we don't
actually know whether people have long term immunity to
these common cold coronaviruses. Some work actually suggests
that there can be short-term immunity, maybe for a year or two, but people can eventually be
reinfected with essentially the same strain of coronavirus. So this could have implications
for what we could expect from SARS-Co-V2. Also we know that we need
a new vaccine every year against influenza virus. This has less to do with
how effective the vaccine is and more to do with the vast
rate of influenza evolution. The upside here is that
even with limited immunity, but because of viral evolution
we know that pandemic strains of flu with high case fatality
rate don't endure, right? They essentially turn into
seasonal flus in future years. And so I think overall this is
encouraging in the precedent with other viruses suggest
that once we can get in front of this virus on the public health level, we might expect effective
productive immunity, protective immunity against SARS-Co-V2. And while we don't yet know
what the long term future holds, many of these other
viruses can be contained by either effective vaccines
or protective human immunity. So I'll just summarize before
I turn things back to Suresh and Justin, by saying first
that SARS-Co-V2 is just one of many viruses that we know has entered the human population and
will continue to enter the human population. And for all of these reasons
our best defenses at this point are surveillance, the ability
to rapidly mount an effective public health response and of
course as Emily pointed out, you know these collaborative
scientific efforts like we're seeing now with
this pandemic that are really gonna push us toward developing effective vaccines and treatments. And finally I take some comfort
in knowing that these types of pandemics do pass and
we will get through this, many people will no doubt
become sick, but still the hope and expectation is that
perfective immunity will emerge and we'll see that this
disease becomes less severe or goes away altogether. So with that, I will
turn it back to Suresh and look to more discussions in a bit. - Thank you so much Matt. Our final speaker is Dr. Justin
Meyer who is an assistant professor in the section of
Ecology, Behavior and Evolution. He studies the evolution of
viral host recognition systems and the strategies that
are used by the two, and he also observes in the
laboratory how viruses evolve and he studies their
adaptations at various scales. So you heard from Emily about
the mutations in the genome of the viruses, this actually
translates to changes in the properties of the
viral surface proteins like code protein that are
encountered by and targeted by the host immune system. So he's going to discuss the
variables that contribute to the infectivity of
the pathogens in humans. Whether such epidemics and
pandemics are more likely with increasingly
environmental encroachments and climate change, and finally where else in
the world such hot spots are likely to occur. In this case you saw
that it came from China, but he will probably tell
you that it can happen anywhere in the world. So, Justin I'm going to turn
this over to you please. - Thank you Suresh, and
thank you Emily and Matt for the great introduction to viruses. So for my section I want to
talk about three subjects that relate to our ability
to predict the next pandemic. The first are the
variables that contribute to the spread of pathogens, and when we learn about
these variables and we think about how the world is
changing, we actually find out that we predict that there's
an increased likelihood of pandemics in the future. So while that's kind of
grim, we can also use those variables as well as other
science to actually predict where in the world we can
expect the next pandemic. And so if we can predict
where it might happen, we might be able to stop
it before it does happen. So rather than just giving
you a long list of variables that either enhance viral
spread or diminish viral spread, I'd like to give you a larger
framework to understand how those factors work so that
as you encounter different factors in the news or so forth,
you can have that framework to put that factor in and
understand how it actually works. So, I wanna go over this
concept in epidemiology it's a variable called R naught. R naught is a reproductive
potential of a pathogen and what that variable is, it's a number, that epidemiologists
calculate and it's the number of susceptible individuals
that one infected individual is likely to spread the disease to. So in this diagram here,
that disease is being spread to 2.5 people. So the way that R naught works is that when you have an R naught value that's greater than one, that is a case where a pathogen
can spread exponentially through a population. However, if that R
naught is less than one, that's the case where the
pathogen will over time infect fewer and fewer
people until eventually it goes extinct in the population. So what is the R naught of SARS-Co-V2? So it's actually estimated to be 2.5. This means that this virus
can spread rapidly through populations and as you
see around the globe it's expanding exponentially
in many, many countries. So what exactly goes into
calculating R naught? R naught, the actual math
to calculate this variable is pretty complex, but
the concept in the math really boils down to R naught
being a function of two terms. The first term is infectivity, this is basically the
probability that a person will spread the disease to another person times the infection period. So the longer that a person
is infected with this virus, the more potential the virus has to spread from one person to the next person. So these are sort of these
larger concepts infectivity and infection period where
a lot of different variables affect the infectivity of the
virus or the infection period. And so two of the main
drivers of what enhance the infectivity of a
virus is how contagious the virus is. So this says if a virus can
be transmitted through aerosol instead of droplets of water in the air then that makes the virus very contagious. Whereas if it's spread
through bodily fluids it's less contagious. Also what goes into infectivity
is the number of contacts an infected person has
with susceptible people. Infection period is the length
of time in which the virus can be transmitted from one
person to another person. Theoretically, if humans get a virus, that virus could stay
with a human for the rest of their lives. But two main factors can
intervene to limit that time period, and one is that
the human can gain immunity to the virus, making
them curing themselves, and then making them immune
from any future infections. So when this happens then
the virus can no longer be spread from that person. Also, if the virus is deadly
enough it can cause mortality. And when mortality happens,
when the person dies, the virus can no longer
spread from that person and so that actually limits
the infection period. Often, people associate
viruses with mortality and that association makes
people think mortality of the host is good for
the virus, but in fact the mortality of the host is really bad. So basically by sinking the ship, the virus goes down with the ship. So, viruses such as Ebola have
these really high mortality rates and that's actually
why they tend to have a much lower R naught than SARS-Co-V2, because basically they just
burn through all of their population, and no more people
can spread it any further. So, this is the concept of R naught, and R naught is an intrinsic
property of the virus. However, there's another
concept which is effective R. This is the reproductive
potential after intervention. So we know that we can
change our behaviors, we can change the way
the society functions in ways to influence whether
or not the virus can spread. So ideally while R naught
might be 2.5 for SARS-Co-V2, we can hopefully change our
behaviors in ways that would reduce that R below one so
that the virus could eventually go extinct from our populations. And so, there's a number of measures that we'll walk through,
first is we can affect how contagious somebody who's
infected by the disease is by simply having them wear masks. This actually creates an
actual barrier so that viral particles get caught
and can't be transmitted to other people. We can practice social
distancing and quarantining and this obviously influences
the number of contacts the infected patient has with other susceptible people. And lastly, with good
healthcare we can actually speed up recovery so that
the patient doesn't have as much opportunity to spread the disease. So these are the measures that we can take against this disease right now. However, hopefully in the
future, we have technology that we can apply such as
vaccines or medications. And so vaccines we all
think that vaccines are very good for us because they
make our cells immune, but they also have these
larger population effects such that when you apply
a vaccine to a number of individuals, they become
immune, they're no longer susceptible, so basically
you're changing this variable, the number of contacts
and you're diminishing R and hopefully helping drive the
virus out of the population. By administering drugs you
actually kind of have dual effects at the population scale. You're increasing the rate
at which patients recover so they don't spread the disease anymore, and then you are also if the
drug is stopping the viral replication then an individual
who has the pathogen, who is infected, won't make
as many viral particles and so those individuals
will be less contagious. So these measures that help
preserve our own lives, also have these population
wide effects that will help drive out the disease. So, next like I said, given
everything that we know from these lectures and some other science is predicted that there's
an increased likelihood of pandemics in the future. So this is due to a number of factors that I wanna walk through. First, we have increased
exposure to non-human pathogens. Like Matt pointed out,
viruses that are new to humans are not really new they're just
coming from another species and so there's a number of
ways that we have augmented our behaviors around the
world to actually heighten our interactions with other
animals and then obviously their viruses as well,
increasing the chance of that host shift. And so we have increased meat consumption, this means that we have
larger farms of chickens and pigs and these are giant reservoirs for possible pathogens. We have increased
encroachment on natural areas and obviously as we
move into these forests to deforest them we are being
exposed to a huge diversity of mammals, a huge diversity
of animals that have viruses that potentially
could jump into our population and of course if we have
increased exotic animal trade that's a very close, direct
interaction with animal and a diversity of animals
that could foster emergence of a new virus. Another problem is urbanization. So as we grow as human
populations grow around the world and since our Earth is
limited in resources we have to be very conservative
and so it's best for us to live in cities to preserve resources, however, urbanization also
leads to the average person having more contacts with other people and so thinking about in terms of R naught and those calculations that
increases the potential for viruses to spread. Globalization is also a
problem, so much global travel means that a local epidemic
can turn into a pandemic relatively quickly as
we've seen with COVID-19. The fourth factor is climate change. We are augmenting the
temperature of the Earth and environments in a way
that we're making ourselves more susceptible to diseases. For example, when we warm the
Earth we create more habitats for mosquitoes that carry
bacterias like Malaria and by increasing their
range they can spread to new human populations that are
not impacted by Malaria. By increasing temperatures
we're increasing flooding, and there's many pathogens
that are water born, such as cholera which
we will be exposing more and more people to. So while this all is pretty
grim, we can take these factors and we can actually
predict where in the world are these new emerging
diseases likely to occur and then hopefully begin to intervene. So, now next I'd like to ask where will the next disease emerge? This is a map of the globe obviously. This was produced by EcoHealth-Alliance. It was published in 2017
in Nature Communications and it shows us where there are
hotspots where we anticipate future pandemics to start from. So where disease emergence happens. You can see that where this
new SARS virus came from, is actually a hotspot,
but you can see that also in North America in southern California, and in New York areas those
are also other hot spots. I should say that these are
just statistical predictions, we don't know exactly where
a disease is going to emerge. Why these regions are
hotspots is they factored in all those things that I talked about. These are regions where
you have lots of people, you have people being
exposed to biodiversity, and also you have people
that are more sensitive to global climate change. So, while this is
something of a warning sign and certainly what we're
going through right now is horrible, and we don't
wanna go through that again. I think that having these
kinds of efforts to predict and like Matt was talking
about to surveil populations of viruses and as Emily has
said with sequencing efforts we can bring all of that
information together to be able to predict where
emergence is gonna happen and hopefully intervene, change
behaviors, change society in ways that diminishes the
chance of having a new pandemic. So, thank you Suresh and thank you guys. - So thank you so much Justin. So now we are going to turn
over to the discussion section of the panel. I'm gonna throw out some
questions and our speakers can just chime in and give us their wisdom on these particular topics. So, let me just start with
the, all of you pointed out that coronavirus is
actually a very common virus which often causes common
colds and I think about 30% of the common colds are
caused by coronaviruses, so they're relatively
harmless most of the time, so what is it that this
virus, the SARS-Co-V2, particularly to the lungs that makes it so much more dangerous? - I think it's probably,
again, I think we're all still trying to figure all of this out, if we take examples of
other seasonal viruses and pandemic viruses for
instance the 1918 flu versus seasonal influenza
one big piece of this, or one big piece of
that one was the amount of inflammation that was being caused, and in particular where in
the lung it was replicating. So, for seasonal influenza it's usually in the upper lung, for the
pandemic influenza it was able to easily access the lower lung. I think the early reports on
this coronavirus look similar and I think there's also a
greater amount of inflammation that is the result of
infection in the lung. With this virus rather than
the seasonal coronaviruses. Again, we have much less
information about the seasonal coronaviruses than we do
about seasonal influenza virus and we obviously have much
less information about SARS-Co-V2, but I think in
a lot of cases what we see with these viruses that
aren't adapted to the human population is just that
the inflammatory response is just very, very, very
strong and as a result of that we get things like fluid
leakage which results in things like pneumonia emerging in the lungs much more likely than we do in
these viruses that are maybe a little bit more well adapted
to the host population. - Yeah, that's very
interesting Matt, you pointed to this inflammatory response
and I just want to have someone comment on the fact
that at some point the body, our immune system turns against
these cells in trying to protect this immune response
till all hell breaks loose just at that point, so
aggravates the whole situation to the point where there
is severe lung damage and breathing difficulties, right? So, does anyone else want to comment on that particular point? - Yeah, I guess just
following on what Matt says, what we're trying to
understand about SARS-Co-V2 is based a lot on SARS-Co-V1,
where like Matt said it causes this aggravated
inflammation and what's called a cytokine storm where
there's all these signals in the body being sent
to recruit immune cells and what's an over exuberant
response that causes tissue damage and my
understanding is also that I guess SARS-Co-V1 is able to inhibit
some antiviral responses and it's predicted that
SARS-Co-V2 could do that as well. So you're getting this inflammation, but it's not necessarily a
productive immune response, but rather is damaging. And it's where that immune
system comes in as being kind of this double edged
sword that is oftentimes described as something that
can both help us and harm us. - Yes. Very good. So we talked a little bit
about potential possibility of developing a vaccine or drugs, so can we talk a little bit
about what is the appropriate vaccine target in this case? And in what time frame
is the vaccine likely? Someone could walk us
through the steps of starting from a target how long it
takes to make the vaccine, test it and get it validated
and approved by FDA, this will be very useful
for the audience I think. - Yeah, so again, I think one
of the reasons I brought up the Spike protein is that I
think this is gonna be one of the main targets for vaccination. And I think in terms of the
steps that need to happen, I think a big part of it
is actually figuring out in people that have been infected already, what are their antibodies
targeting, right? So, we can really use the
diversity of immune responses that people mount in these
several hundred thousand people that been, have cleared the infection. We can actually look to
see where their antibodies are targeting and we can
use that then as a lead to generate kind of good
targets for vaccination. Timing wise, Tony Fauci
said a year to 18 months and I think that's
probably pretty reasonable. I mean, a big issue about
vaccines is they need to be insanely safe, right? You can't vaccinate people,
you can't put something into healthy people that even has any chance of being potentially risky. And I think that is a big
issue with vaccination, is that at there needs to
be a lot of testing in a lot of people before we really
determine that that vaccine is safe to distribute
widely in areas that, where still the probability
at least as it currently stands the probability of
getting sick or certainly of dying of this infection are quite low. So you don't wanna do
more damage with a vaccine than you do with the disease itself. - Yes, that's a very good point. There has been, there have
been arguments in the press as to if we have a vaccine
candidate that's ready, why can't we skip all the steps in between and go directly to people? And this point that you've
made about sometimes some of the vaccines can
actually make it worse for the individual if
they're not tested properly so we need to have most
models and before we get to the final dissemination of the vaccine. Now Emily, both you and Matt
talked a little bit about the various steps in
the entry of the virus and the replication and
how it packages itself back into virus particles
and then leaves the cell, and of course each one of
those steps is a potential for a drug target, that if you could interfere with that step then potentially have a target
and you also pointed out that there are many other viruses, including other coronaviruses
that although they might bind different receptors,
going by the same mechanism, they replicate in general
by the same mechanism so can one begin to look at
drug targets where things have been developed for other
related viruses and try to use those and are those likely
again in the same time frame or is that more likely that
we could come up on a drug in less time than a year for example? - Yeah, I guess I would
comment in terms of what Suresh is saying about using drugs
against related viruses, there's, Ebola's another RNA
virus where there's a drug it's called Remdesivir and
that's basically gonna interfere with replication of the
virus and my understanding is that Gilead is trying to
test that and there's a single patient that was treated and recovered, but of course an equals
one doesn't mean very much and so you know we really
have to do thorough testing just to make sure we're
not gonna cause more harm than benefits that we generate. There's also been a lot
of hype about Chloroquine which is an anti-malarial
drug, it's also used for, to relieve rheumatoid arthritis
and that's still in sort of the early stages of
determining with really carefully controlled studies is that
gonna be a good treatment. Yeah I can hand it over to
Justin if there's other drugs you want to comment on. - Yeah, so, I don't
know of any other drugs that are under development right now. I do think that we have to
consider not just if they have bad side effects but how
likely the virus is to mutate around the drug. So if we give everybody a
drug that a single mutation in the virus can confer resistance to it, given the size of the
population of viruses within a single patient and
its high mutation rates, it's not as high as some
viruses but it has pretty high mutation rates we're gonna
develop resistance almost immediately and our drugs
aren't gonna be useful. So I think that studying
sort of not just whether or not it's effective today
but whether or not it'll be effective tomorrow is important. And then I think coming up
with strategies like drug cocktails where we have
a couple different drugs to target a couple different
steps in the replication process that may be really helpful. To go back to the discussion of vaccines, I do know that they're
beginning to test vaccines, so we are along the ways, it
will be a long ways but I am pretty confident that something
will break through here. We have a lot of attention, a
lot of very bright scientists working on that. - That's terrific. And Justin, you brought up
this idea that if you have a drug, the virus is continuously mutating at it's own natural rate and so I just want to
contrast a little bit when DNA replicates there is
the machinery that is involved in replication also has
a proofreading function, so it corrects mistakes that are made, but the enzymes that
replicate RNA don't have this proofreading function so
they end up making mutations that are more prevalent
than in DNA genomes. So is there any evidence that
SARS-Co-V2 has a mutation rate that is extraordinarily high, anyone comment on that particular point? - It appears that its mutation
rate it's high like an RNA virus typically is, but not
as high as other RNA viruses. So it's not an outlier
in the world of viruses. And it does appear that while
the machinery that replicates RNA is very error prone,
that means that it causes lots of mutations, there is
some proofreading capacity in this virus, although I
don't know too much about the mechanism myself. - Matt, do you have a comment? - Yeah, so there's an additional component to the preliminaries in
this family of viruses, that's unlike any other RNA
virus where they do have proofreading capabilities,
so part of that is that these viruses are two to three
times bigger than most other RNA viruses and without
that proofreading capability if they were making
mistakes at the same rate as polio virus or HIV they would presumably run into this sort of error catastrophe, where the virus would basically
have too many mutations to survive so what we see in coronaviruses is that because they're
a little bit bigger, they actually have a lower
error rate than most RNA viruses and that's due to this added preliminary proofreading activity. It's still way, way, way
more error prone than we see for our polymerases or you now know, a bacterial polymerase or something like that, the
error rate is still quite high. - So I gather from what
Emily said that this virus is evolving in real time,
meaning that, Emily have we seen evidence of this
from what you presented of mutations that are happening
in realtime in the genomes of these viruses from
different parts of the world? - Yeah, so we're able to
like Matt and Justin said, see that the mutation
rate for this virus while as in keeping with RNA
viruses in general is higher than DNA viruses it doesn't
seem like it's as high as for example as influenza,
and I think kind of touching back on this topic about how
this may connect with vaccine development, influenza which
is an incredibly sloppy virus that in terms of replication
errors there's been efforts to try to make a vaccine
against what's common among the different influenza
strains so that's something I think also that going forward with making a vaccine against SARS-Co-V2 we wanna keep an eye to
try to dedicate efforts toward making a vaccine against,
I mean first any vaccine but then again a vaccine
against something that's common against different strains of the virus. And in terms of the rate it
which, the places in which SARS-Co-V2 is mutating,
I can hand that either to Matt or Justin. - So I actually wanna, before
we get into that again, sort of connect something
you just said Emily and something that Matt said earlier. Matt suggested that we
might wanna create a vaccine that targets the Spike
proteins, but we also know that these Spike proteins
evolve the fastest and have the most variation
between different SARS strains or different coronavirus strains. So, Matt is that just because
they're on the outside, and so they're just--
- Yep. - A bright target--
- Yep. - For immune system? - And that's presumably
also why the Spike protein is evolving so fast is
just that it's you know, it is the main epitope that the immune, or the sort of main surface
antigen that the immune system can see and so we see this
with many other viruses, that those surface proteins
because that's the thing that antibodies respond to,
which is generally what we're talking about, when we're
talking about creating a vaccine response that those proteins
are being driven to evolve fast by that selection
from the immune system. You now, we don't have many
other targets on the outside of the virus that we can
use for stimulation of the antibody response at the very least. So. - And yet, along the lines,
yeah my understanding for this universal influenza
vaccine that there's this effort to try to target things that aren't changing as much. So I guess that must be
some part of a virus protein that just constrain because
it cannot change without losing its basic function. - Yep. Yeah, yeah, yeah. It's the same thing as we see with HIV. Where people that develop
these, what are called broadly neutralizing antibodies against HIV, they're still targeting
these rapidly evolving surface proteins but
they're targeting regions of those rapidly evolving
surface proteins that most antibodies can't reach, but
these ones for whatever reason can, and they are, they're
very highly conserved. So presumably that's the
approach that we would use for flu, and potentially
also here for coronavirus. - So Matt, I have a
follow-up question too, I think you kind of presenting
an evolutionary dilemma, where our immune systems
are driving the evolution of these host recognition proteins, and then we know genetic
variation those host recognition proteins is what helps
pathogens jump from one species to the other species, so you
know, do you think there's some kind of interesting dilemma or feedback between these things? That the balanced immune
system's essentially are driving the evolution that leads to
the emergence of the pathogen? - Yeah, it's an interesting question. I mean, I think that what's
driving evolution of the recognition aspect of the
Spike protein, so in many of these cases the recognition
parts of the protein aren't necessarily the
same, so the part of Spike that is recognizing ACE2,
isn't necessarily the thing that the antibodies
are recognizing, right? And so, I think it's actually
probably separate surfaces. I don't know enough about
what the antibody response is to coronaviruses to know
that in that particular case, but in many of these other
cases you know you have this sort of surface protein
of a virus that is targeting some receptor here and
antibodies are actually sticking to other parts, not necessarily
at that direct interface. - Okay.
- While we're on the topic, because I think yeah, Justin
Matt and I all really like this topic of the interaction
between the surface protein of the virus and the host receptor. Matt, you had mentioned
the bat ACE2 receptor, that's used by coronavirus in bats. Given that it's so much harder
to do research with bats and genetic manipulation
et cetera, it's possible there's other receptors--
- Yeah. - And I'm curious what's
known about what there may be other receptors in bats which
may tell us about what other receptors may be achieving. - Yeah, so, to my knowledge we don't know of any other receptors for a given coronavirus we don't know of any other receptors, in other species, so it always seems to be with these, things like SARS1 and
SARS2, it seems to be ACE2, and all the related bat viruses. There are other coronaviruses
that use other surface receptors right, and so you
could imagine that there would be, there would be the possibility of sort of that particular jump and of course that's
stuff that Justin pays a lot of attention too, right? It's how you utilize a new receptor. But I think in the case
of this, what is happening is not these big jumps in terms of what receptor's being used, but actually sort of small,
fine tuning of when a given bat species has a couple
of amino acid changes on its surface, the Spike
protein just basically needs to adapt to that in order to
replicate in the new species of bat and the same holds
of course for humans. But again, I think this
point, and there was a study that came out a couple of years ago, that really was sampling a
lot of these coronaviruses from bats and many of them could actually utilize human ACE2. So I think that jump in many
respects has already been made, and so it's gonna be a
lot of these other things like modulation of the
immune response and things like that that are probably
gone be responsible for that kind of fine tuning. - So, as this disease
spreads around the world, we want to separate fact from fiction. And there are people in
some parts of the world who believe that they are not
as susceptible to this virus, either because they have
intrinsic immunity or because the climate there is warmer or whatever. So I wanted to just talk
a little bit about this, let's talk a little bit about
expectations for natural human variance that might be
resistant to this particular virus, what do we know
about this from studies with other viruses and how can one relate that to SARS-Co-V2? - Yeah, maybe I'll start
and then Justin and Matt can chime in in more detail. You know the lesson from
HIV was that there were natural variants in the human
population that had a change in the receptor, in that
case it was this receptor called CCR5, used by HIV to enter the cell and people that had two mutant copies of that receptor were quite resistant, I think there was,
correct me if I'm wrong, like sex workers in Africa
that kept getting exposed and weren't infected. And so the question then
is, yeah what is the natural human variation
for this ACE2 receptor, among other factors that
are gonna regulate infection by coronavirus and you know,
I think the short answer is that the jury is still
out but maybe I'll leave it to Matt and Justin to
expand how much we know at this point. - Yeah, so I actually think
this is a really cool topic that we understand almost nothing about, in terms of infectious diseases. So Emily brought up this case of HIV, there was a couple of other
cases where we can map human genetic variance to differences in disease susceptibility,
but it's really, really rare. Very different than the way
that for instance we can say someone has a high risk of
breast cancer susceptibility or Alzheimer's disease
or things like that, and so you know I think we
don't know as Emily mentioned and you know I also
mentioned, all of these points where the virus is
interacting with the host could be points where
variation in human proteins could really have an effect. I think it's one of the
potential things that may, good things that may come out of this, that we could really start
to map the genome types of the virus to the
genotypes of the person to the actual outcome of the infection. And really, you know maybe
start to get into some of that level of detail. But, I think so far, I think actually ACE2 is
not particularly polymorphic in the population but a
lot of the other proteins that these viruses interact
with are quite polymorphic in the human population
and some of those could be actually determining
susceptibility to disease. Excuse me. And some of them could
just be random, right? - And I guess along those
lines a related phenomenon from studying HIV infection
was that there are these things called restriction factors, and this is what Matt was referring too, different steps along the way
that viruses can be blocked and a particular restriction factor it's called a ubiquitin
ligase the name was TRIM5 that present, is able to
basically degrade parts of HIV in certain primate
species that humans lack, or have a different version of. And so it can be things, that
not just like the receptor that changes, but also whether
or not there is something that will recognize the virus
as something that's non-self, something that's foreign
that needs to defeated. And that will also be
interesting to see how that varies in the human population. - I think it was Matt who
talk about normal immunity and vaccines and so on so
at some point then depending on the particular virus and
the vaccine you get this thing called herd immunity
where even those who are not immunized have the
protection because the virus cannot find so many hosts
to transmit the disease to. So, is that likely, so I
often wonder in very, very densely populated regions around the world in India, Africa being examples
where social distancing is just physically impractical
for a variety of reasons, whether there will be a
combination of herd immunity and a social distancing
that will end up creating a final balance. So at what point can one
expect herd immunity? Can we talk a little bit more about that? - I can follow up based on
that concept of R naught. So that concept of R naught
comes from this epidemiological model called an SIR model and those models do predict herd immunity. I think that we will rely
on herd immunity when we have a vaccine, but
hopefully not before that. So, for herd immunity
to work you have to have a large fraction of your
population being immune to the pathogen and so
basically that just means that there's just all these people around that it can't spread to so
it just has a harder time spreading and then its R
naught will defer to R, it will drop below one and
it will leave the population. But that fraction of people
that have to be immune for it to not spread is really
high and that would mean that if we had that
effect happening before we had a vaccine it would
mean that this pandemic has gotten completely out of control, something like you know 30
to 60% of the population of the world has experienced
it and are now immune, but because of the high
mortality rate of this virus so not as high as Ebola
but higher than influenza that would mean millions and
millions of people dying. So I think in the end, I
think we are going to have to distance ourselves, isolate ourselves. And then ride out the
clock so that eventually when we have the vaccine we
can begin to become immune to this at a really large
scale and then herd immunity will suppress the COVID-19. - I do want to just chime in on this topic of immunity in terms of
kind of a cautionary tale, it think my understanding
with efforts to develop a vaccine against one
strain of Dengue Fever actually led people to be more
susceptible to other strains, and I think there was maybe
some preliminary results that suggested the SARS-Co-V
may have similarly effect. So just again, I think
there's an amazing amount of hope for vaccine, at the
same time it really does require that we do careful
testing and make sure that we're not creating more
problems than we're solving. - Yes, so, you know
this brings me to this, the active debate going on
about how long we should practice social distancing
and the government has considered in some circles
whether we should get back to work by Easter and of course
now that has been extended. So, you want, Justin you
talk beautifully about the factors that go into and
why social distancing works in terms of R naught and
what it does, so can you say how long you think the
social distancing is necessary at least with the USA in context? - Yeah, so I guess I wanna
respond with the caveat that I'm an evolutionary biologist, and I teach about epidemiology, but I'm not an epidemiologist. What do I tell my family and
friends that are freaking out? I think that's sort of the best way to go about answering this. I tell them to take each day at at time, that we have to continue
social distancing. I tell them that hopefully we
do have a break around June, there are some ideas that
maybe in the summertime this thing won't spread as much, but also by June what that
does is it gives us an opportunity to all socially distance, for the, especially in the
United States for within each of the individual
states they hit their peak and then to be dropping
down in the number of patients with disease
and then for us to sort of mellow out. But at June, what does that mean? Does that mean that we all
immediately go back to work and immediately go back to the
bars and immediately go back to normal life? That's not what we should do. We will have to then asses
at June sort of okay, we had this very strict
measure that helped us stop the exponential spread of this virus, but now how do we go
forward so that we don't reignite that exponential spread again? So I think it's gonna have to
take careful consideration, but it's gonna be awhile till
life gets back to normal. I know that that's terrible news. And I think to cope with
it, just live each day and be as careful as you
can at preventing catching this disease and spreading this disease. - So this, Justin you brought
up an interesting point that was implicit in your statements, and that is that for this
to work the entire world has to practice social
distancing so that we stop the virus cold, right? But, if you don't and you
do this in different parts of the world with different
start dates and stop dates and so on then they could
be this, running on the risk of a ricochet effect. So you think you've flattened
the curve in one area and then the neighboring
country or state or whatever is still transmitting the
virus and then you can get it back again. So, and there have been
cases even in China where after they saw the cases
drop, now there are cases coming in from outside. So, how does one manage
this at a global level? - So again, I'll give the
same caveat that Justin did, which is I studied evolution
of hosts and viruses, so I am not an epidemiologist,
but in some of the reading I've done I think there's
a couple of things to talk about here. One, we do see, in fact
even in, there was a nice "National Geographic"
article just recently about this ricochet effect that
you were talking about during the 1918 pandemic
in different US cities. And one really take home
message from that is even when there was ricochet or
this sort of bounce back, the cities that were doing the
strongest social distancing overall had the lowest mortality rate. And so, the idea is that
by flattening this curve we can allow things to catch up, right? We can allow the health
system to catch up, we can allow, I mean one big
thing about how we can move forward from this lock
down of everybody is if we actually knew who was infected, right? If we had effective testing
or effective serology like Emily was talking about
then we could actually much faster respond to these
sort of localized potential bounce back effects from reintroduction or something like that. So I think a lot of it is
just allowing the system, allowing the science, allowing
society to really catch up to being able to deploy
the public health measures that makes sense of terms
of containing the disease but are also less disruptive to society and the economy and everybody's
sort of mental health. So. - I wanna follow on that
exactly what Matt was saying, I agree that we really
need better testing. And I also wanna follow on
I guess I just learned about a study, also from the
1918 influenza pandemic where, that addresses this
issue I think that people have proposed that we're
either choosing to save lives or save the economy. And they did this sort of
study comparing which cities did the earlier, stronger,
more intense social distancing that saved lives, those
were also the cities that did better economically. And so by saving lives,
you're actually helping the economy and I think that's
such an important message to drive home and make
sure that people know. - Yeah, very good point. - So Emily you began your
presentation by talking about the open science and how all
the governments in the world now are looking to scientists,
technologists and medical professionals to find
the fastest, cheapest and the scalable testing
tools as well as cures for this particular disease right? So let's talk a bit about
the concept of open science and the creation of platforms
for sharing results of studies in realtime rather than
waiting for the slow process of peer reviewed publications
and getting manuscripts out and so on. This is a crisis of
unprecedented proportions and we just need, the whole
world needs to get together to solve this problem as fast as possible, so let's throw this out for discussion. - Yeah.
- Actually if we could start with you Emily. - Yeah, wonderful topic. It's so inspiring to, just
over the last month or two to learn about yeah, these resources where the entire genome's
information is available. That GSAID, I'm not sure
how they pronounce it, that website that within
an hour the information gets ported to NextStream. All of that information
is freely available. People can download it,
they can analyze it, they can do their particular
form of assessment and that is one form of this open sharing and then also there's this
open sharing that's really been transforming the publication world and one aspect of that is preprint servers and there's a preprint
server called bioRxiv, there's one called medRxiv
so when people submit their paper to a journal,
they can post that information there as well. And so anybody can look at
it, they can comment on it and the information gets
out much more rapidly than it would if we were waiting. And we still of course want
to wait for peer review, I think everybody has different opinions, I still think that's absolutely critical, we need to have experts
asses the data and so that we only have really well well scrutinized results
that are being published. But yeah, if you look
at bioRxiv and medRxiv I think there's now
almost a thousand papers between the two that are
related to coronavirus just from the last few
months and several journals are also providing coronavirus
information and coverage freely available, so I think that's, that's really gonna change science. The more people can share
information the more progress we're gonna make. - Yeah, and I'll just
add one thing to that, which is just all of these
social networking tools that have been developed
in the last, I don't know, 10 years, right, of Twitter
and Slack and Zoom, right? And the ability to actually
have these conversations in real time has really
been transformative. I mean, even within the
San Diego community right, there's this huge group
of people that have set up all these resources that
are just firing messages back and forth to each other
saying hey I need this thing or do you have an, do you
have access to this piece of equipment or something
like that, right? And that has really been,
I mean it's been kind of overwhelming to be part of,
but it's also been really, I mean it's just everything
is moving so much faster. - This is truly a silver
lining to this otherwise dark cloud that is flowing over us.
- Yeah. - Justin, do you have comments
about this open science? - Yeah, I mean, so of
course I'm also inspired by all of this. I'm gonna have to say that
I'm about to teach a course on evolution of infectious
disease and COVID-19 will be a big part of the course, because that's what
students are most interested in right now. And it can, it can only be
such a big part of the course because of these
resources, these databases and where people are doing
real time analysis on the most recent up to date data and because of the open source publication or the sorry, the preprint
publications where we can look at what is the most modern science and I can present it in my class. And so, then the dissemination
is not just among scientists but it is to students and
to the public really quickly and so as a whole we're
much more informed. So I do, I find it-- - Yeah, and I should add
that this goes way beyond just the science, because
with everyone sitting at home all kinds of thought,
and the thousands of jobs and professionals need
to get their work done, so people are just being
exceptionally creative about finding ways to communicate,
reach out to help each other from medical help and so
one social connections. And I know I personally
have called more people in the last two weeks than
I've done in the last two years so you know at least
world's coming together. So let me just before we finish throw out, just talk about some of the
lessons, that each of you has learned from this particular pandemic that will prepare us for the next one that hopefully is some
distance away but you never know what's around the corner. - Yeah, I guess I would just
you know, kind of reiterating what we said before about
open science, open sharing, but being able to track
where that virus has spread, where it came from, where
it's going, how it's changing, like that's, that has
just been so inspiring and I think it really will
be crucial to the next time this happens, because it's
gonna continue to happen. This is like what Matt had in
his presentation about that the Red Queen, it's just
we're continually running, keeping up with the
pathogens and they're trying to keep up with us. And I guess I would also say
that you know I really hope that our government takes
this seriously that there was a pandemic response team
that had been established and that was disbanded and
that we need those kind of resources and support
in order to better prepare going forward, because as
soon as we have effective testing we can so much
rapidly contain, track and learn how to treat
these kinds of diseases. - Similar I guess to
what Emily was saying, I think one thing we've learned from this is
that we are a hundred years advanced from where we
were with the 1918 flu, and yet we're still being
brought to our knees by this virus and I think one
thing is that public health is really, really, really
critical for these sorts of rapid deployment of
intelligently designed, well executed, public health
is really critical to this. It's, you know we can say
we're gonna develop a vaccine in 12 to 18 months or
we're gonna develop drugs in that amount of time,
but really these ideas of social distancing,
containing and testing and all of that is really
the key to this rapid emergence of these viruses, because Emily's picture
of the virus going in and a hundred going out is
similar to Justin's picture of a virus going into one
person and getting three out and that's what gives us
this exponential curve and no matter how smart science is, the way a lot of times to
contain viral infection seems to be these sorts of
measures and that has been very effective in some cases
that fortunately we haven't heard, became pandemics so. The 2009 Swine Flu, there
have been some cases of the Avian Influenza that people were really worried about. Even SARS1, I think that
the measures were effective at containing those viruses
even with all those flaws and so I think one thing
to really learn is what can we do to make sure that
those are always there, even as the science is trying to catch up. - Justin? - Yeah, so, what I've
learned personally is, people need to take
these things seriously. We knew that this was a
possibility for a very long time. I start the first last of my
evolution of disease course by pointing out that the same
slide, or a similar slide as I showed you during my
presentation that the world is changing in a way that
these are much more likely to happen again and again and again. And so, we can't brush them off, and we do see that there's a
new disease spreading somewhere in the globe, even if we
think that it's very far away from us, and so we
have to take it seriously, and I think that the other
thing that we could really gain a lot from is better
surveillance of diseases in bat populations. In other mammal populations
knowing what's out there, maybe even what has the
potential to move into humans, and I think there's also
just a lot of fundamental knowledge that we need to learn as well. We don't know what precisely
the genetic mutations are that might have aided
this virus's emergence into humans and so it'd
be nice to actually know more about the basic
biology and the evolution so we will be able to
predict what kinds of genetic variants might be more problematic. I mean to be honest,
in our lab we have seen evolution that's very
similar to this happening, it's in a very different virus, but there's a lot of common themes. Now of course that might
just be the human brain making these connections, but there might actually
be something there. And so the strain that emerged in humans, this SARS-Co-V2, it has
deletions in a key protein that we have shown the
same, the analogous protein in our virus when there are
these deletions in this region tends to drive host range changes. And so, if we start putting
together more and more information from more and more viruses and having controlled experiments
and looking at natural variation perhaps we could
better predict what the bad potential diseases are and
intervene at an earlier step before the emerge into our population. Of course I agree what Matt is saying, that once they emerge you
have fast acting containment strategies, that's really
critical and of course in the end having a way to create
vaccines quickly is another preventive measure or way
dealing with these things, but I also think we can even
stop at an earlier step. - Well, I must thank all of you for a truly fascinating conversation. We started off just eager
to disseminate some of our teaching skills and
information for our students and faculty and anyone
who wants to listen, but I've learned a great deal
from this conversation myself, lots of fascinating questions in biology that remain to be answered
and if the audience loves this and wants us to talk about
other related things, please let us know through the feedback and we'd be happy to do more of this. So thank you all for being
a part of this conversation and stay safe all of you. (upbeat music)
