cc >> Welcome, everyone, to
Wednesday Nite at the Lab. I'm Tom Zinnen.
I work here at the University of Wisconsin Madison Biotechnology
Center, and I also work for UW Extension Cooperative Extension
And on behalf of those folks and our other sponsors, Wisconsin
Public Television, the Wisconsin Alumni Association, and the
Science Alliance, thanks for coming to Wednesday Nite at the
Lab. We do this every Wednesday
night, 50 times a year. Tonight, I'm delighted to be
able to introduce to you Rebecca Moritz.
She's a Research Compliance Specialist and an Alternate
Responsible Official for UW-Madison's
Select Agent Program. I told her I would tell a joke
about being a compliance specialist and asked if she
could come and talk to my children.
[LAUGHTER] I think my children would
talk about alternate responsibilities.
[LAUGHTER] In addition, Rebecca is a
certified biosafety professional with the American Biological
Safety Association and a specialist microbiologist
with the National Registry of Certified Microbiologists.
She's from Manitowoc. She received a bachelor of
science in bacteriology and a master of science in medical
immunology, excuse me, medical microbiology and immunology,
both here from UW Madison. She has conducted research in
academic and private sector laboratories where she developed
a knack for biosafety, biosecurity, and research
compliance. Her title tonight: "Biosafety,
Compliance, and UW Influenza Research: The Real Story."
Please join me in welcoming Rebecca to Wednesday Nite at the
Lab. [APPLAUSE]
Okay, my battery is green, can everybody hear me?
Okay, so I apologize, first of all, this picture, the PC to Mac
inverse didn't really work very well.
I've been invited to talk to you this evening because there's
been a significant amount of media attention regarding two
influenza research studies. The first one was conducted here
at the University of Wisconsin Madison in the laboratory of
Dr. Yoshi Kawaoka. Now, that manuscript was
submitted to the journal Nature, and the second manuscript was
done in the laboratory of Dr. Ron Fouchier at the Erasmus
Medical Center in Rotterdam, the Netherlands.
Now, these studies have been in the spotlight since November of
2011 when the National Scientific Advisory Biosecurity
Board reviewed both manuscripts and came to the unprecedented
decision that the journals should not publish all the
scientific information. Now, they came to this
conclusion based upon the dual use potential of this work to be
used as a biological weapon. There have been many attention
grabbing headlines, of which I have chosen a few to show you.
Too Dangerous for Words. Contagion.
Now, the New York Times in an editorial referred to these
viruses as the Dooms Day viruses.
And some journalists have gone as far as comparing this work to
the Manhattan Project. Now, this unprecedented decision
and resulting media attention has caused debates among various
scientific circles, among influenza experts themselves,
government's biosafety and biosecurity circles, and the end
results of these debates we obviously don't know yet.
We're still in the middle of everything.
But it will not only affect the research in these two
manuscripts but will also affect all research going forward with
potential dual use concerns. So tonight we're going to cover
a couple different topics. We're going to go over some
brief information about UW's Select Agent Program, exactly
what it is. We're going to talk about
influenza virus in general, a little bit about the
manuscripts, what I can tell you, the time line, the National
Scientific Advisory and Biosecurity Board, and then
we're going to get into biosafety and biosecurity.
My goal this evening is to show you what is not routinely being
discussed in the media. Most importantly, the tremendous
amount of oversight involved in this research, and what we do to
mitigate influenza research risks here at UW.
There's been a lot of misinformation and omission of
facts regarding these studies. I hope to set the record
straight about this research, and I'm going to give you what
is hopefully enough information so you can come to your own
conclusion about this research. So I think the best place to
begin this unprecedented journey is to say exactly how I'm
involved with it. So you know that I'm the
Research Compliance Specialist for UW's Select Agent Program,
and I'm one of two Alternate Responsible Officials.
So what is this program? Now, after the 2001 anthrax
attacks, the federal government set up a program that requires
all registered laboratories and entities that work with select
agents to be preregistered. Now, this list of select agents
is comprised of various bacteria, viruses, and toxins.
As a result, UW created their own Select Agent Program.
Currently, we're comprised of just under 200 individuals who
are registered to either work directly or indirectly support
the laboratories of seven principle investigators who work
with bacteria, toxins, and viruses, including highly
pathogenic avian influenza virus.
Now, each entity is required to have a Responsible Official, and
our Responsible Official is Dr. Bill Mellon who is the
Associate Dean for Research Policy, and, in his absence,
myself and another individual, as Alternate Responsible
Officials, have the authority to act if necessary.
Now, essentially, my job is to manage the day to day operations
of the Select Agent Program and to make sure we are in
compliance wit the regulations at all times.
At the same time, I need to be able to help our researchers do
their research that they want to do safely.
So I wear many different hats to be able to do this.
I have to know microbiology. I have to know the regulations
and guidelines. I have to know permitting,
training, containment, and even from time to time I have to be
able to speak engineering. So what happens if I do not do
my job correctly and we have a violation of the regulations?
Well, worst case scenario, Dr. Bill Mellon could go to
jail. There could be a hefty fine or
select agent research as a whole on campus could be stopped.
Now, it is a privilege to be a registered entity and to work
with select agents, and that privilege can be taken away at
any time. Now we're going to get on to the
bug of the hour. We're going to talk a little
about influenza virus. Now, UW Madison has a long
history of ground-breaking influenza research starting in
the late 1940s. Swine influenza viruses were
first isolated here, and it was also shown by Dr. Easterday,
who's sitting right there, that swine influenza viruses could go
from pigs to humans, and from humans to pigs.
Now, influenza virus is a single-stranded, negative-sense
RNA virus. Now, its genome is comprised of
eight genes, which you see here. Now, these eight genes are
translated into 10 to 11 proteins depending upon the
virus. Now, like all viruses, it has
proteins coming off of the virus particle.
Now, in the case of influenza virus, you have spikes coming
off of the particle. Now, this rod-shaped spike is
known as the hemagglutinin, otherwise known as the HA.
Now, it is responsible for attachment of the virus to cell
and then an initial penetration of the cell during infection.
Now, the sequence of this HA, the hemagglutinin, determines
what type of cell it can attach to, albeit a human cell, a pig
cell, a poultry cell. Now, there are 16 different
subtypes of hemagglutinin that exist and have been found in
nature so far. Now, this mushroom-shaped spike
right here is the neuraminidase, which is also known as the NA.
Now, the NA plays a role in release and spread of new
viruses. Now, there are nine different
subtypes of neuraminidase that have been isolated in nature so
far, and a subset of antiviral compounds are the target of
those compounds is the neuraminidase.
Now, influenza viruses are named by their hemagglutinin and their
neuraminidase subtypes. So, H1N1 is type 1 of the
hemagglutinin and type 1 of the neuraminidase.
H5N1 or H3N2, for example. Now, because these stick outside
of the virus particle, this is what our bodies form an immune
response to. When we get infected with
influenza virus, our body forms the immune response to the HA
and the NA. When we get the influenza
vaccine, if you actually get the shot, you are getting certain
sequences of the HA protein and then the NA protein.
Now, what happens if two different influenza viruses
infect one cell? Albeit, a human cell, an animal
cell, or a poultry cell. As you can see, the two
particles, they infected the same cell and none of the
resulting virus particles look like parents.
Now, when this happens in nature, there are technically
256 different types of virus particles that can be created.
Now, this does not take into account the fact that every
single time influenza virus replicates, mutations occur
because there the viruses do not have the capability to fix
replication errors like our cells do.
So this is where the potential for scary things to happen
exists. This is how viruses are
generated that create, that have resistance to antiviral
compounds. A mutant virus arises that is
resistant to antiviral compounds because there is a selective
pressure, say that person is taking an antiviral drug, and a
virus, one of these mutants occurs and it can keep growing.
So the virus develops resistance to the antiviral compound.
Now, this is also how mutant or reassortant viruses could arise.
For example, how an H5N1 virus could arise that could transmit
from person to person. Now, influenza viruses have been
around a long time. There have been episodes of
respiratory illness back to the middle ages and before.
Now, a pandemic virus is a virus that has the ability to
sustainably and efficiently transmit among humans.
In the 20th and 21st century there have been four pandemics,
most notably the Spanish influenza pandemic of 1918.
Now, this pandemic killed between 20 million and 40
million people with a mortality rate of roughly about 2.5%.
And most recently was the 2009 pandemic virus, which actually
was a virus that was a reassortant of three different
swine viruses. Two of the viruses they've been
able to figure out what they were, and one of them they have
not. Now, the majority of the human
population has only ever been exposed to the H1, the H2 and
the H3. Now, also people of the younger
generation have not even been exposed to H2 because the
dominant seasonal influenza strains right now are H3N2 and
H1N1. Now, influenza viruses are
currently known to infect many different mammals.
For example, humans, horses, dogs, pigs, poultry, and most
recently influenza viruses have been isolated from bats.
Now, a virus that infects one species might not be able to
infect another because of the sequence of the receptor of that
hemagglutinin gene. But selective pressure can cause
this jump. An example is a few years ago in
Florida at a racetrack you had horses and greyhounds in close
proximity to each other and because of selective pressure, a
virus that infected horses was able to mutant and infect
canines, and as a result, we have canine influenza
circulating across the United States.
Now, bird flu, what is the big deal about bird flu?
Now, in 1997, bird flu first infected humans in a poultry
market in Hong Kong. Now, there were 18 cases with
six deaths, and the only thing that these people had in common
was the fact that they had been at a live poultry market the
week earlier. As a result, Hong Kong
authorities ended up culling 1.5 million poultry to remove
the source of the virus. Now, since the virus'
reemergence in 2003, it has spread from Asia to Europe and
Africa. Now, bird flu has become
entrenched in poultry populations of some countries,
resulting in millions of poultry infections.
Now, in these countries the poultry infections have impacted
the livelihood of the economy and international trade.
Now, as of early February of this year, there have been 584
confirmed cases of H5N1, otherwise known as bird flu,
that have led to 345 deaths. Now, that is a mortality rate of
roughly 59%. Now, the three hardest hit
countries have been Indonesia, Egypt, and Vietnam, in that
order. As of December 15th of 2011,
Indonesia had 182 cases with 150 deaths.
Egypt had 155 cases with 53 deaths.
And Vietnam had 119 cases with 59 deaths.
So you have sick poultry and a human comes into contact with
that poultry, and then they get sick.
Currently, there has been very limited human to human
transmission of bird flu viruses.
There have been a few cases of direct contact when an
individual has been taken care of by a close family member or
also a caregiver. Now, in these instances, the
sick individual that passed it on to the second individual has
had extremely high titers of virus in their bodies.
Now, some influenza experts debate whether or not it is even
possible for bird flu to transmit from one person to
another person, but H5N1 viruses could transmit from person to
person, we would have another pandemic because the majority of
the human population has never seen that type 5 hemagglutinin,
thus, it's critical to know whether or not these viruses can
be transmitted. In 2006, the National Institutes
of Allergy Infectious Disease had an influenza panel, and the
panel determined that more work needed to be done to understand
the transmission of influenza viruses.
Then in 2009, the World Health Organization published their
research agenda for influenza and said this exact type of
research needed to be done. So what would make bird flu
transmissible in humans? Now, this was one of the main
goals of Dr. Kawaoka's research. One of his research projects was
to determine what was required for bird flu to transmit from
person to person. Now, this work began in 2006
when Dr. Kawaoka received a grant from the National
Institutes of Health entitled The Pandemic Potential of H5N1
Influenza Viruses. Now, in 2009 he also received an
additional grant from the Gates Foundation to identify influenza
virus amino acids that are responsible for human to human
transmission. So what did Dr. Kawaoka do?
So they took H5N1 virus and then they took the pandemic 2009
influenza virus and they made a reassortant virus.
Now, the HA, the hemagglutinin gene was from the H5N1 virus,
and the remaining seven genes were from the pandemic 2009
virus. Now, they took that virus and
they infected ferrets. One day later, they put another
ferret next to the infected ferret.
Now, the only way for this other ferret, this uninfected ferret
to get infected with influenza virus is through respiratory
droplets. Now, these ferrets are right
next to each other, but they are not touching.
So the only way the one ferret could infect the other ferret is
through respiratory droplets. Now, what were the results of
this experiment? Well, with this reassortant
virus, there was no transmission amongst the ferrets.
So they made a second virus where they made mutations in
that H5 hemagglutinin gene and infected ferrets.
Now, this time all six contact ferrets were positive for
influenza virus. Now, why use ferrets to do this
research? Ferrets have a similar
respiratory tract to humans, and they also have very similar
symptoms when human and ferrets get influenza.
While the ferret model is a good model to study the influenza
transmission, it is not a good model to study transmission of
influenza viruses amongst humans.
Now, the ferrets used in these experiments are incredibly
susceptible to influenza. They are screened to make sure
that they have zero antibodies to influenza virus before the
experiments start. Whereas, us humans, we have
antibodies to influenza virus. But since it is scientifically
unethical to do experiments on humans, the ferret model is the
best model we have. So what does this data tell us?
This data suggests that it could be possible for H5N1 bird flu
viruses to transmit from person to person via respiratory
droplets. So let's go ahead and go into
the time line of events. So the manuscript was submitted
to the journal Nature at the end of August of 2011.
Now, internally we were worried about putting out a manuscript
that talked about the potential of a virus to transmit from
person to person when a movie called Contagion was coming out
which talks about a killer virus that spreads around the world
and panic ensues. Well, luckily, we didn't have to
worry about that, but we had a different matter to deal with.
So instead of being published initially, the manuscripts went
to the National Scientific Advisory Biosecurity Board.
Now, what is this board? This board was established in
2004, and its first meetings began in 2005.
Now, their charter is to provide advice, guidance, and leadership
regarding biosecurity oversight of dual use research, which is
defined as biological research with legitimate scientific
purpose that may be misused to pose a biological threat to
public health and/or national security.
Now, currently, the NSABB has 23 voting members
and 18 non-voting members. The members are appointed by the
Secretary of Health and Human Services in consultation with
other federal departments that have an interest in life science
research. Now, the NSABB members serve for
four overlapping years, and the members provide expertise in a
wide variety of areas. I would name all the areas off
but there are 20 different areas that are listed on the NIH
Office of Biological Activities website.
But, essentially, they cover microbiology, infectious
disease, public health, intelligence, security,
biodefense, etc. nd the NSABB also has ex officio
members from 15 agencies and departments which are very on
law enforcement, national security, things like that.
Now, the NSABB's roles as it's stated in the charter is to be
an advisory board. They do not review manuscripts
unless there is extenuating circumstances, and this is the
first time to my knowledge the NSABB has reviewed a manuscript,
and it is most certainly the first time there's ever been a
manuscript that significant data should be withheld from.
So, the NSABB came out with their statement on December 20th
that the manuscripts, as a whole, should not be published.
Those mutations that are required for transmission should
not be published, but the information should be
disseminated to individuals who need it.
Now, that posed the question, how do you disseminate
information to the surveillance teams that need this but make
sure it doesn't get to anybody else?
But as the saga unfolds, on January 20th, 39 influenza
researchers published a commentary that they would
voluntarily give up this research for 60 days.
And I don't think it is fair of me to paraphrase their words, so
I'm going to read a little bit from their commentary.
"We recognize that we and the rest of the scientific community
need to clearly explain the benefits of this important
research and the measures taken to minimize its possible risks.
We propose to do so in an international forum in which the
scientific community comes together to discuss and debate
these issues. We realize that organizations
and governments around the world need to find the best time to
find the best solutions for opportunities and challenges
that stem from the work. To provide time for these
discussions, we have agreed to a voluntary pause of 60 days on
any research involving highly pathogenic avian influenza H5N1
viruses leading to the generation of viruses that are
more transmissible in mammals. In addition, no experiments with
live H5N1 or H5HA reassortant viruses already shown to be
transmissible in ferrets will be conducted during this time.
We will continue to assess the transmissibility of H5N1
influenza viruses that emerge in nature and can pose a continuing
threat to human health." Now, up until this point,
Dr. Kawaoka had not spoken publicly about his research.
He requested and received permission from Nature to
discuss a few key details of his study in a commentary that was
published in Nature. Now, the first and most
important, the H5N1 transmissible virus here at the
University of Wisconsin does not kill ferrets.
I'm going to repeat that again. Our virus does not kill ferrets.
Our virus is also susceptible to current antiviral compounds and
also currently available vaccines.
The second piece of critical information is that a subset of
the mutations that are required for transmission are already
circulating in nature. And then the last piece of
information was that Dr. Kawaoka's data suggests that
influenza transmission is more complex than anticipated,
involves not only the receptor binding properties of the
hemagglutinin, but also other biological and physical
properties. Now, the first step in trying to
bridge the gap between these varying opinions occurred
February 16th and 17th when the World Health Organization had a
meeting in Geneva, Switzerland. Now, this meeting was an
invitation-only meeting. The people that were invited
were influenza researchers from around the world, including
Dr. Kawaoka and Dr. Fouchier, the chair of the NSABB, the head
of NIH, and then the heads of the WHO Influenza Surveillance
Centers, and also the editor from the journal Nature.
Now, again, I'm going to read a little bit of the WHO news
release. "The result of this new research
have made it clear that H5N1 viruses have the potential to
transmit more easily between humans, underscoring the
critical importance of continued surveillance and research with
the virus." Now, this meeting, there were
four key points that came out of it.
First of all, the group decided that this research must
continue. They agreed to extend the
moratorium on the research for an unknown amount of time.
They also agreed that delayed publication of the entire
manuscript would be more beneficial than urgently
publishing a partial manuscript. And that, lastly, there needed
to be increased public awareness and understanding of the
research through communication and review of biosafety and
biosecurity aspects. Then last week another incident
was thrown into the loop, I guess.
So, the American Society for Microbiology had their annual
biodefense in emerging disease conference.
Now, during this conference, they had a panel discussion
which had the chair of the NSABB, another NSABB member, the
director of the National Institutes of Allergy and
Infectious Disease, the editor of Science magazine, and then
also Dr. Fouchier. Dr. Fouchier gave a few key
pieces of information also about his research.
Most importantly that his virus as well does not kill ferrets
when it is passed through transmission experiments.
But when he inoculated that virus directly into the trachea,
so basically directly inoculating the virus into the
lungs, it did kill ferrets. And also during this meeting,
this discussion, it was announced by the director of
NIAID that he has asked the NSABB to review these
manuscripts again and also to review new data that has come to
light. So they are hoping that the
NSABB will look at these manuscripts again at the end of
this month. So keep paying attention.
We'll see where this goes. So, that brings us to, looking
at my notes, that brings us to biosecurity and biosafety.
Now, what measures are taken here at the University of
Wisconsin Madison to mitigate risk with influenza research?
Now, there's a tremendous amount of oversight involved with H5N1
research or any influenza research on this campus that
falls underneath the select agent regulations.
Now, this research is under a microscope at both the
institutional and the federal level.
Now, the first level of oversight applies to the entire
university. All laboratories that work with
recombinant DNA at UW Madison must abide by the NIH
recombinant DNA guidelines. Now, these guidelines lay out
the framework for how work with recombinant DNA should be
conducted, but then also how an institution should review this
type of research. So each laboratory conducting
recombinant DNA research must have a biosafety protocol.
Now, this protocol describes the research, including genes, the
vectors, organisms, cell lines, plants, animals, facilities,
exposure response, and then also where the research falls in the
recombinant DNA guidelines. Then this protocol is submitted
to the Office of Biological Safety, and then the Office of
Biological Safety works with that principal investigator to
work out all the details of the protocol and to make sure
everything looks right. Then that protocol is submitted
to the UW's Institutional Biosafety Committee.
Now, the Institutional Biosafety Committee is comprised of
subject matter experts. There are public members, and
this committee also has a group of consultants at its disposal,
of which I am one. Now, the IBC will determine if
the protocol and the risk assessment meet the NIH
recombinant DNA guidelines. And they will also take into
account the CDC's Biosafety and Microbiological and Biomedical
Laboratories, which is also known as BMBL, and those also
are a set of guidelines. Now, this protocol will either
be approved or it will be sent back to the PI for revisions
depending upon what the IBC determines.
Now, no research on this campus with recombinant DNA can be done
without and approval from the Institutional Biosafety
Committee. Now, just as a side note, animal
research on this campus is not reviewed by the Institutional
Biosafety Committee. It is actually reviewed by one
of the five Institutional Animal Care and Use Committees that
exist on this campus. Now, the second level of
oversight comes from the federal Select Agent Program.
The Centers for Disease Control and Protection and the Animal
and Plant Health Inspection Service, which is part of the
USDA, are in charge of the federal Select Agent Program.
Now, the Criminal Justice Information Service, which is a
division of the FBI, does the background checks for everybody
that works in this program. Now, all registered individuals
must pass that background check before they can work with select
agents. Our file is held by the CDC, but
we also have oversight from APHIS because we have agents
that fall underneath both categories.
Now, an entity is registered for a limited amount of time which
is no more than three years. And at the end of that renewal,
I'm sorry, at the end of that registration time, a renewal
inspection has to occur, and federal inspectors come in.
They look at our facilities, they look at our documents, they
look at our training, and they follow checklists that are based
on the NIH recombinant DNA guidelines and the CDC's BMBL
guidelines to determine whether or not our renewal, our
registration should be renewed. Now, renewal of an entity's
registration is never a given, and, also, at any point in time
during that registration period, the federal inspectors can come
in unannounced and to go through the facilities.
Now, at the heart of both of these levels of oversight is
something called biological safety.
Now, biological safety is the discipline of addressing the
safe handling and containment of infectious microorganisms and
hazardous biological materials. The two main principles of
biosafety are containment and risk assessment.
Now, the goal is to protect the laboratory worker, the
environment, and the public from exposure to infectious
microorganisms that are handled and stored in the laboratory.
Now, how does biosafety do this? Biosafety does this with layers.
Now, the first control of biosafety is engineering, and
when I'm talking about engineering, I'm not just
talking about the facility itself, but I'm also talking
about equipment used inside the facility that is used as primary
containment when working with an agent.
Now, you know you want conduct work with H5N1 influenza
viruses, what type of facility do you need?
Well, if you look at the NIH recombinant DNA guidelines, it
states that this work needs to be done at biosafety level 3
with enhancements. If you look at the CDC's BMBL
guidelines, it states that this work needs to be done at
biosafety level 3 with a shower out and a clothing change.
And it also states that infected loose-housed animals need to be
worked with at BSL 3 agriculture.
Now, what do these mean? Now, biosafety level 3 has a
large range of requirements depending upon the agent.
There are a few things that are required, and then depending
upon the agent, other things are added.
Now, the goal of a biosafety level 3 is that everything stays
inside the laboratory. An individual goes into the
laboratory, equipment goes into the laboratory, materials goes
into the laboratory, everything that goes in is contamination
free. Now, everything that comes back
out of that facility, including the worker, equipment,
materials, waste, including air, water, or solid waste, is also
all contamination free. So what is required for a
biosafety level 3? Well, first of all, you need to
have controlled access. Not just anybody can get into
this area. The doors have to be
self-closing. Work has to be done inside of a
biosafety cabinet which is considered primary containment
for working with an agent. It collects all the aerosols.
There has to be directional air flow in the facility.
So air basically flows from clean to dirty, never the
reverse. Always clean to dirty.
Now, that air, to get out of the laboratory, has to go through a
HEPA filter which will remove all bacteria or viruses that are
in the air. All penetrations in the facility
are sealed. So electrical outlets, screw
holes, nail holes, all of those are caulked so air cannot get in
or out. There has to be an autoclave.
Now, an autoclave uses heat and pressure to kill bacteria in
solid waste and viruses in solid waste.
Now, another piece of safety equipment is centrifuges.
They have those O rings around, let's see if you can see, right
here. That's an O ring to help keep
any aerosols inside the centrifuge.
Then also, you see that worker's got a special cup in their hand.
Now, that cup itself has an O ring going around.
So that cup can be taken out, taken into the biosafety
cabinet, and then opened. So any aerosols that were
generated when those tubes were centrifuged stays inside the
biosafety cabinet is not exposed to the worker.
Now, we said that this work according to the NIH and CDC
guidelines had to be done at something called biosafety level
3 enhanced. Now, what is enhanced mean?
So there has to be a personal change and a shower room.
So you can't just walked into the lab.
The doors have to be lockable. The doors are also interlocked
so that outside door and that inside door can never be opened
at the same time. Only one door can be opened at
any given time. There has to be bio-seals on an
interlocked double-door autoclave.
So this is an example of a large bulk autoclave that animal cages
can get pushed in to. So we're looking at the clean
side right now, and on the other side of the autoclave it opens
up into the containment facility.
There has to be independent air and exhaust, and our facilities
have redundant systems. So if one system fails, we have
a second system to back it up. There has to be a visible means
of displaying the pressure differential.
So when I said there had to be directional air flow, so to make
air flow directional, it goes from an area of higher pressure
to lower pressure. Now, this gauge will tell you
when you walk into a room that that pressure of the room you're
going into is negative and exactly what it should be.
Now, we're also required to collect liquid waste, like I
said, that come out of facility. Now, we go one step ahead of a
normal BSL 3 enhanced and we have something that's called an
effluent decontamination system. Now, this large tank here
collects all the waste from the laboratories, and these smaller
two tanks down here are used to cook, essentially boil and
sterilize, all the liquid waste that come out at the facility.
Now, all the duct work that leads up to those HEPA filters
in the exhaust system, we have to make sure that there are
absolutely no leaks in that duct work.
So the only way for that air to get out is to go through the
HEPA filter. And lastly, our facility has
backup power. Now, this was the level of the
facility that was used to generate the transmissible H5N1
viruses, just the actual propagation of the virus.
Now, what is the BSL 3 agriculture suite.
Now, BSL 3 agricultural suite builds upon a BSL 3 enhanced
suite and just takes it to a whole new level.
Now, this facility is considered primary containment.
It is designed to be a box within a box.
So take a shoe box and inside of that shoe box, you have another
box. And inside of that little box,
you have an animal that is in a cage.
A pig, a horse, a cow. That's what these facilities are
designed for. The walls of our facility are
18 inches of a continuously poured concrete.
They have overlapping layers of three-quarter inch rebar
throughout the entire walls. Now, on the inside of those
walls they are epoxy-coated so that nothing can get through the
walls and everything will wash off of them.
Now, to get into the facility you don't just enter into one
room and go into the laboratory. You actually have to go through
a series of rooms to get into the laboratories.
Also, all the doors for the perimeter are air-locked doors.
As you can see, they kind of look like submarine doors.
The black right here are actually redundant seals, that
air gaskets that fill with air, and that is how the containment
seal is made. So the facility and the duct
work itself are also pressure decay test which means a
facility has to hold air within a certain for a certain period
of time. So basically, you blow up a
balloon and that balloon holds that air for a certain amount of
time. That's what these containment
facilities have to be able to do except you do the reverse.
You pull it negative and make sure that there are no leaks and
the facility can hold the pressure for a certain amount of
time. Now, the requirement of BSL 3 is
an EDS system which is why all of our containment facilities
are connected, all of our containment laboratories are
connected to it. We also went one step ahead and
instead of having loose-housed animals inside, when we do our
ferret experiments inside of this facility, they're actually
in isolator cages that have HEPA filters on the cages that
collect all the virus particles. And then, lastly, we have to be
able to gas decontaminate this entire facility, and, for us, we
use chlorine dioxide. Now, the higher level of a
containment that a laboratory is, the more expensive it is.
Containment facilities are incredibly expensive to build,
operate, and maintain. It is also difficult to find
qualified personnel who know how to work in these facilities and
also facility engineers that actually understand how these
facilities operate and how to perform the maintenance.
Now, since the select agent regulations went into effect,
the cost to do one research paper on Ebola virus, which is a
biosafety level 4 virus, went from $59,000 to $333,000 to make
one peer reviewed journal article.
Now, all those systems in our facility are redundant.
Now, with redundancy comes a high price tag.
Our BSL 3 and our BSL 3 agricultural suites were built
exactly for highly pathogenic avian influenza virus.
We built this facility explicitly to do this type of
research. In the end, our building costs
were roughly $12.5 million. So we have the environment that
is protected. Now, what about the worker
working inside the facility? Now, this is personal protective
equipment comes into place. You need to protect the portals
of entry for a virus. Now, in nature influenza virus
infects somebody through the inhalation of respiratory
droplets. So the most important piece of
personal protective equipment for a worker working with
influenza virus is the respirator.
Now, in this instance we use something called PAPRs which are
powered air purifying respirators.
But also in the laboratory you are working with agents at a
high concentration and you are manipulated them.
So you also have to protect your others portals of entry.
So individuals working in these types of facilities take off all
their street clothes, and they put on scrubs.
Then they put on a Tyvek jumpsuit.
They put on booties inside and outside of garden clogs.
They have double gloves on, and they have their PAPR respirator.
So it basically looks like you're wearing sort of like a
space suit. So now you have the environment
protected and you have the laboratory worker protected.
Now, how else can we mitigate risk inside the laboratory?
Now, we use something called standard operating procedures
which basically help prevent practices that could potentially
put a worker at risk. Now, an SOP needs to get
different individuals doing one thing the same way and achieving
the same outcome. Now, when you think about it
that way, it's actually quit difficult to write an SOP
because every one who reads it must understand it, interpret it
the same way, and have the same outcome when performing the same
procedure. So SOPs are written for all
aspects of the containment facility, including entry and
exit, how to shower out of the facility, I kid you not, there
is an SOP for how to shower, working with viruses in animals,
moving equipment, how to decontaminate facility
equipment, and all aspects of emergency response.
Now, the last element of biosafety is the administrative
side which puts engineering, the personal protective equipment,
and SOPs together and into practice.
Now, one of the first and most important administrative tasks
is training. I cannot emphasize to you how
important hands-on training is. We're required to give program
and laboratory specific training on at least an annual basis, and
when the CDC and APHIS inspectors come in, they look
through all of our training documentation to ensure that
every registered individual has received the appropriate
training. Now, I'd like to note that to
work in one of our containment facilities with an H5N1 virus
you have to go through an extensive mentoring program
before you're aloud to work in these facilities with these
viruses by yourself. Now, documentation is another
large task for the Select Agent Program.
There is a significant amount of paperwork involved in every
single thing that we do, and a large majority of time there is
always additional approvals to start new types of work or to
just do a simple task even. We're required to do inspections
on an annual basis. So myself and the other
Alternate Responsible Official, we go through all of our
registered facilities. We look at the laboratories.
We go through their documentation.
We look at their mechanical spaces.
Just like we were the CDC and APHIS inspectors, and we use
their exact checklists as well. Now, lastly, we have a few
administrative policies in place to mitigate any additional risk.
All of our staff that work with H5N1 influenza viruses have to
get seasonal influenza virus to prevent symptoms and infection
with seasonal flu. In addition, individuals cannot
have pet birds. There is a quarantine policy,
and if you were in the containment facility, you cannot
go to a zoo or a petting zoo where there could be birds for
five days post-working in the containment facility.
And also, we have an immunocompromise policy which
asks you to disclose any health changes you have to your
principal investigator that would make you more susceptible
to the bugs you work with. Now, our influenza program has
an excellent track record, and as part of our entity Select
Agent Program we have invested a significant amount of training,
oversight, and engineering into this program.
Now, a lot of the questions we've been getting from the
media are what-ifs. What if this happened?
What if that happens? What are you going to do?
So I can tell you we have a written incident response plan
that covers all natural and man-made disasters from fires to
blizzards to earthquakes, gas leaks, floods, tornadoes,
explosions, and power outages. Now, we are required to review
and revise and conduct drills on this incident response plan on
an annual basis. For any incidents in a select
agent facility, the Responsible Official and the Alternate
Responsible Officials are notified immediately, either by
the principal investigator or by the UW Police Department
depending upon the nature of the emergency.
Now, it is the responsibility of the Responsible Official then to
immediately contact the CDC and let them know we have an
emergency. Now, what about medical
emergencies? Staff are trained how to handle
medical emergencies such as heart attacks or if somebody
falls. Staff know how to move a
conscious or unconscious individual out of the
containment facility, remove their PPE, decontaminate them,
and hand them off to emergency personnel.
Now, because of the risk to first responders, they will
never enter our containment facilities that work with H5N1
influenza viruses. We have conducted drills with
the Madison Fire Department using a neutral hand-off site
that works best for both parties.
Now, I can also assure you there are medical plans in place to
deal with potential exposures or in quarantining staff who have
influenza symptoms. Now, another question we've
gotten about criminal acts. We also have plans in place to
deal with suspicious packages, thefts, bomb threats, suspicious
people, work place violence, and cyber security.
And, again, these plans we're required to review, revise, and
drill on an annual basis. We teach our registered
individuals what type of threats to look for.
What type of people, insiders, outsiders, visitors, people in
inclusion, and also what type of actions these people could take
against our facilities. Safe guarding our people, our
inventory, our facilities and documents is absolutely
essential. The main intent of the select
agent regulations is to protect inventories from theft, loss,
and release. Now, because of this, our Select
Agent Program works incredibly closely with the UW Madison
Police Department, and we also have a good working relationship
with our local FBI officials. Now, this brings us to
biosecurity. Now, biosecurity is a term that
is becoming more prevalent in recent years.
It is the protection of microbial agents from loss,
theft, diversion, or intentional misuse.
Now, we do not publicly talk about the security measures we
have in place for our Select Agent Program, but what I can
tell you is that the UW Madison Police Department does a
thorough security risk assessment of all our facilities
that house select agents before they are occupied.
We have multiple physical barriers in place, our
facilities are monitored extensively, and we also have
cyber security. We run drills each year to test
security, to test staff training procedures and also other
measures. Now, UW Madison has something
that, from what we know, is very unique, and it's called the
Biosecurity Task Force. Now, the Biosecurity Task Force
was established by former chancellor John Wiley as an
advisory tool to the Responsible Official.
Now, this task force is chaired by the Responsible Official and
is comprised of key individuals from around campus who have a
vested interest in the security of our select agents.
Now, represented on this task force are the Alternate
Responsible Officials, representatives from the
colleges that have select agents, the Environmental Health
and Safety including the Office of Biological Safety and
Occupational Medicine, I'm sorry, Occupational Health and
also the director of Environmental Health and Safety,
UW Communications, Legal, UW Police Department, IT staff, the
Wisconsin State Laboratory of Hygiene, and also the Wisconsin
Veterinary Diagnostic Laboratory.
Now, the Biosecurity Task Force meets monthly to discuss all
issues pertaining to select agents on campus with a focus on
security and constantly improving the program.
We have been told by multiple federal agencies that this is
the best practice. Now, we've talked about the how,
the what, the where, but not necessarily the why.
There's been a little bit of why in between.
So why do this research? Well, the answer is quite
simple: it is for the overall benefit of global public health
by preventing disease. Now, outbreaks and pandemics
happen. They happen quickly and we do
not have years to figure them out.
The goal is to figure out what could happen in nature so we
will be prepared in case it does happen.
Now, it is only a matter of time before this map is covered with
more orange and more poultry are culled and death tolls increase.
Since this graph was published by the journal Nature in the
beginning of February, there have been at least three more
deaths, two in Vietnam and one in Bangladesh with additional
infections in Vietnam, Bangladesh and Egypt.
And also most recently as of this week, it appears that
there's an outbreak in the live bird market in Bangladesh.
In addition, in the state of Bihar in India there are crows
that are dying from bird flu. Now, the H5N1 study done here
shows that the possibility exists that bird flu could
mutate and transmit from person to person, and we already know
that a subset of these mutations required for transmission is
already circulating in nature. Now, this research shows that it
is absolutely essential that surveillance teams know what
mutations to look for and that countries stockpile antiviral
compounds and vaccines that are effective against these
mutations. Now, with that, I would like to
have a few acknowledgments. First of all, I would like to
thank UW Madison for investing in the Select Agent Program.
When the regulations went into effect many institutions stopped
the research that would eventually become select agents.
Now we have one of the larger programs in the country, and we
have very good support from our administration.
I would like to thank our Responsible Official, Bill
Mellon, for sharing his knowledge, his vast expertise,
and allowing me to grow into my role in the UW Madison Select
Agent Program. I'd also like to thank my fellow
Alternate Responsible Official, Darren Berger.
He's listening hopefully. He is a facility engineer, and,
in a nutshell, I could not fully do my job without his help and
expertise. I'd like to thank Dr. Kawaoka.
It's not always easy being a forerunner in science and doing
cutting-edge research. He has embrace biosafety and
biosecurity and made it the number one focus in his
laboratory. And I would also like to thank
his lab managers who, from what I understand, are also watching
online. You guys do a wonderful job of
making sure everything runs smoothly.
I'd like to thank the Office of Biological Safety and
Environmental Health and Safety. They are a knowledgeable group
of coworkers who work hard and are always willing to help, but
also, at the same time, they know how to have fun and laugh.
But lastly, and certainly not least, I want to thank Terry
Devitt and Jill Sakai from UW Communications.
I really cannot thank them enough for their help and
guidance and trust during these last six months.
They have handled every single media request that has come into
this university during this unprecedented journey in an
exceptional manner. From all of us involved in this
saga, it has been truly unlike anything we have ever
encountered before. And needless to say, it has been
educational for all of us. And with that, I will take any
questions that you guys have. [APPLAUSE]