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>> Dr. Robert Dijkgraaf: Good morning, and welcome to day two.
I think you probably all collapsed yesterday evening
after very intense day, but this is the second half, and,
of course, today's very exciting because we actually are not only
having a very interesting fifth panel, but then we also tried
to bring the -- the raw material being presented at the various
panels together in a final session,
and try to bring some synthesis to this.
So, without further ado, I will just not give the word
to my co-chair, Dr. Fineberg, to actually introduce
this morning's panel.
>> Dr. Harvey Fineberg: Thank you very much, Dr. Dijkgraaf.
This morning's panel has a very interesting assignment,
and it is, basically, on the assumption that there will be
gain-of-function research conducted; precisely under what
conditions should this research be actually carried out?
The panel is going to have an overview and a discussion of
this topic that we will cover in our first session, our plan for
the day following the discussion by the panel and some open
discussion with our audience in attendance.
We're then going to take our break, which is late morning,
early lunch break, and then we'll come back to reassemble
after that for the final panel of the day.
For this session, this morning, I'm very pleased to be able
to introduce the co-moderators, who will lead the discussion.
They are Dr. Kirsten Jacobsen, who is the manager of Biosafety
Risk Assessment in the Pathogen Regulation Directorate for
the Public Health Agency of Canada, and Dr. Zarifah Reed,
who's medical director
of Sentinext Therapeutics based in Malaysia.
Thank you very much.
I now turn the program over to our co-moderators.
>> Dr. Kirsten Jacobsen: Good morning, thank you
for introduction.
We have the fortune, or maybe the misfortune, actually, of
following four excellent panels yesterday and trying to tease
out the elements that weren't already captured from this
discussion we've been having.
Today we will address the biosafety and biosecurity
requirements applicable to HPAI, H5N1, gain-of-function research,
and discuss the conditions, if any, under which this type of
research could be supported and conducted, try to do some work
to identify the specific standards that should be
in place for future research in this area.
So, without further ado, I'll pass over to my co-moderator,
who will lead the panelist presentations.
>> Dr. Zarifah Reed: Thank you, Kirsten.
So, our first speaker is Dr. Robbin Weyant,
who's the director, Division of Select Agents and Toxins
at the coordinating office for Terrorism Preparedness
and Emergency Response at the Centers for Disease Control
and Prevention in the U.S.
Dr. Weyant.
>> Dr. Robbin Weyant: Thank you, Dr. Reed.
Since I'm the -- sort of the leadoff hitter of this group of
deep thinkers, I thought that I might focus my remarks on sort
of helping to set the table for the discussion, and so I have
some general remarks on the concepts
of biosafety and biosecurity.
And also, I'd like to update you on some regulatory initiatives
that the CDC has ongoing in this area.
When one thinks of microbes as hazards, we're in a very --
as I'm sure most of you, if not all of you in this room know,
we're in a very complex arena.
As a hazard, a microbe has some challenging characteristics.
The fact that they are self-replicating, that there are
such a wide variety of them, and that there's such a wide variety
of hazard, so in establishing any kind of a security, safety,
or control program around this type of hazard, one really needs
to take a risk assessment approach.
If you look at any of the authoritative references
in this area, including the WHO manual, the Canadian biosafety
guidelines, here in the United States we use a book called the
Biosafety and Microbiological
Biomedical l Laboratories manual.
Even the recently promulgated ICN guidelines are all based
on risk assessment.
So what are sort of the key pieces
of a biosafety risk assessment?
And, typically, they focus on three areas.
One needs to look at and understand the characteristics
of the agent that we're attempting to contain
and protect folks from: its transmissibility,
its pathogenicity, its virulence.
Also, one needs to look at what you intend to do with the agent,
what sort of processes are going to be applied to the agent,
so the characteristics of the processes also need
to be a consideration in the risk assessment.
And the third primary piece of biosafety risk assessment
has to do with who's going to work with the agent?
How well trained is the staff?
What's the immune level of the staff in the environment
around this agent?
So those are -- when one attempts to do a biosafety plan
based on risk assessment, those are three primary areas
that are looked at.
In the area of biosecurity, although a lot of the tools that
are used are similar to what would be used in a biosafety
risk assessment, there are some fundamental differences.
In the realm of biosecurity, the agent is not the hazard.
The hazard is the people working with the agent
and the environment around the agent.
And that's fundamental to a biosecurity risk assessment.
Sort of there are three fundamental pieces
to a biosecurity risk assessment.
One is to look at the threats that are present that would
impact the misuse of this asset.
In this case the agent is not the hazard now.
The agent is an asset you're trying to protect.
These threats may be external or internal.
If you plan on working with the agent near an ocean,
for example, one needs to consider the possible impact
of a hurricane in a biosecurity risk assessment.
The second piece, are vulnerabilities.
What's in place at your agent that would increase
the risk of misuse.
And the third thing that one needs to look at
in a biosecurity risk assessment is consequence.
What would conceivably happen if this agent
were misused or released?
And in my final few seconds, I would like to just update you on
an assessment that we're doing at CDC related to whether
or not these new viruses with gain-of-function should be
regulated as HHS select agents.
This past October we published a notice in the United States
federal register asking for input from the public on whether
or not these viruses were significant threats to public
health and safety, and if so, under what conditions
they could safely be worked with.
We have determined that we will extend the comment period
for this notice until the end of January 2013.
So we would welcome any comments that you may have for issues
that we should consider.
Comments can either be sent to the CDC address in the federal
record notice, or electronically to the federal register.
Thank you.
>> Dr. Zarifah Reed: Thank you very much, Dr. Weyant.
Our next speaker is Dr. Joseph Kanabrocki, who's the assistant
dean of biosafety and associate professor microbiology
at the University of Chicago.
>> Dr. Joseph Kanabrocki: Thank you, good morning.
So, I want to follow up on Rob's comments.
In my mind, obviously, the risk assessment function
is central to biosafety oversight.
And I thought it would be a good place to begin this discussion
is to talk about risk assessment and risk groups in particular.
And so I went looking to see where I could find definitions
of risk groups from around the globe, and I found, you know,
the World Health Organization, obviously.
We have the NIH and CDC risk groups,
the Australia and New Zealand risk groups,
Canadian Laboratory Safety Guidelines describe risk groups,
as does the European economic community.
And when you read these definitions of these various
risk groups, one thing that really jumped out at me for risk
group four, and that is, that there's -- the common element
is that generally effective treatments and or preventive
therapies are not available for agents assigned
to risk group four.
So we've had this interesting discussion about
what containment level would be appropriate for viruses --
influenza viruses gain-of-function, and again,
in my mind, the availability of therapeutic agents for these
viruses is critical, and in my opinion, don't warrant
assignment of these pathogens to risk group four.
Now I'll come back to this a little bit later.
Obviously, we're talking about a risk-benefit balance,
and how important it is that the important research be conducted.
My worry is that if we restrict these viruses to containment
at level four much of the work will not get done.
It's already restricted in a great sense to,
even when you restrict to BSL-3 enhanced, or BSL-3Ag, so.
But again, I'll come back to that because I wanted to move
along and talk about some other aspects of risk management from
a biosafety perspective that I view to be very important.
Now, again, common elements is you know, question one,
what are some of the common principles, and that's really
what I focused my comments on here this morning.
And, obviously, there's the aspect of physical containment,
and when we're talking about physical containment we're
talking about engineering controls contributed by the
facility itself, the engineering controls contributed by
equipment and personal protective equipment, and then
of course, most importantly, the practices and competency of
staff that work on these agents.
Another thing I found interesting in terms of common
elements is the role
of the Institutional Biosafety Committee.
Under the NIH guidelines, here in the U.S., of course, IBCs
are required for research that involves recombinant DNA,
if that institution receives funding for recombinant DNA
research from the NIH.
And so that role of the IBC is very important, but when you
look at World Health Organization and Health Canada,
for example, they expand the scope of the IBC to include not
only recombinant organisms but also any infectious organisms,
infections to animals, infectious to man.
And I very definitely support that expansion of the role
of the IBC; I think it's really critical to have an
institutional local oversight.
So, again, I think another really important paradigm here
is that there be local oversight at the level of the IBC, that
there be federal oversight, and again, here in the U.S.,
for this type of research we're talking about the select agent
program, and I think it's really important to have international
harmonization on some of these aspects.
Another common element that I find, another thing that you
find, that run through the various guidelines that you
read, are there's an element of biological contaminant, again,
as I did this, prepared for this presentation, I was struck by
so many of the themes that were originally discussed
at a Asilomar so many years ago are being revisited here.
Risk assessment, biological containment, physical
containment, and those sorts of things, again, are themes,
and even security, are themes that were mentioned
in the early days.
Now some other important considerations, I think it's
real important to test and to confirm for therapeutic efficacy
of agents, and so again, here you would want to make sure that
any virus that might emerge is tested for sensitivity
to antivirals as well as for its antigenicity.
Training and competency of scientists is very, very
important, not only must they be well trained but they must
demonstrate competency in the laboratory.
And furthermore, education of scientists in general, education
of students in general, is an important function.
You know, we all talk about the need to get the public onboard
in supporting our research and I really think this is something
we need to promote, is the value of the work we do.
And I think the more we train young people and students about
biosafety, biosecurity and dual use -- research of concern,
you'll have a much more well engaged public.
Occupational health programs are critical.
These should include vaccinations as well as Health
Watch protocols, understanding that a Health Watch protocols
wherein someone who exhibits symptoms of any illness, whether
or not they've had a known exposure, gets channeled into
the occupational health program.
This is really important.
Culture of responsibility at the local level is really important.
The PI has to demonstrate leadership, has to have direct
involvement with the research, and shouldn't just
be managing this from afar.
I also believe that there should be an institutional person,
a responsible person at an institution, who, in addition
to the IBC and the PI has an opportunity to comment
and oversee the research.
Again, as I said, IBC review at the local level, national review
in terms of regulation or guidelines are important,
but international harmonization is very, very important.
And obviously, I'm not going to spend a lot of time talking
about physical and IT security, but this is another element that
is mentioned in a number of these various guidelines
and is a very important consideration.
So with that I'll stop and move it along.
Thank you.
>> Dr. Zarifah Reed: Thank you.
Our next speaker is Dr. Gene Matthews, who's a senior fellow
at the North Carolina Institute for Public Health,
at the Gillings School of Public Health
at the University of North Carolina, Chapel Hill.
>> Dr. Gene Matthews: Thank you very much, Dr. Reed.
In a -- I'm one of the two recovering lawyers
on the program these two days.
In a prior incarnation long ago and far away I served
for 25 years as chief legal counsel
at Centers for Disease Control.
Part of that job was pattern recognition transference
of lessons learned, so I guess I'll try to respond quickly.
The two questions A and B I can dispose of fairly quickly.
Changes in current requirements, the GOF framework
is an add on to the existing matters.
Robbin just spoke about select agents and Kevin Wolf will talk
in a minute about import export,
double use I think has been covered.
One point I would make regarding the WHO Pandemic Influeza
Preparedness Framework is that that framework
is based upon transparency.
And there was a question from the floor about that yesterday.
I think it's important as we look at the issues relating
to closed cells of information as to how that might impact
the PIP framework that WHO is trying to move ahead on.
And, of course, this adds another layer to the other
layers listed on 1A.
I'll get to come back in a minute to the question that
certainly Dr. Fineberg was familiar with in the swine flu
affair report of how do you scale back down
after you scale up?
Very quickly, on other models, not a lot exists but go back
and look at the smallpox virus destruction protocol.
In the 1990s it was worked on, and a parallel to that, which
WHO still has a playbook on, I assume, is polio virus
destruction planning that was worked on six to eight years ago
before polio broke back out again.
Those bear some analogies here for dangerous agents and how
to deal with them, though those were in a contracting field
of research and this GOF is in an expanding field of research,
so it is not exactly the same.
The other analogy though, is the protocols that were put -- that
I was personally involved in putting into place in 1989 for
the Ebola-Reston virus that was discovered about 20 miles from
here in the animal shipment facility at Dulles Airport,
and so there were limitations quickly put in on the transport
and movement of three types of non-human primates
and how that played out.
That was more of a reactive function, which is what this is.
So, in my last two minutes, let me talk about three pattern
recognition principles that apply here: Guns of August,
windows of opportunity, and one way ratchet.
Guns of August, that's what this is about.
Barbara Tuchman's book about the start of World War I in 1914
goes into very interesting insight into what happens when
technology leaps ahead of strategy and doctrine.
That's what's been happening for the past year in this field,
and we are scrambling to put strategy doctrine and procedures
in place to deal with the technology that's
sort of the analog to machine guns and long range artillery
that World War I had to deal with.
Second is windows of opportunity.
We are moving along sort of at a linear pace.
But be prepared, a window of opportunity, both politically
and public education, a teaching moment, can open up whenever,
whenever there's another big event of some type.
So be prepared to move this agenda along
when the next big event happens.
The next big event will most certainly happen, and you see
the analogy in this morning's paper about the tragedy
in Connecticut and possible opportunities to do something
in this country about gun control.
So just draw your analogies and recognize your patterns.
And in the last is the principle of the one way ratchet,
which my predecessor, *** Riseberg, taught me well.
It's easy to put in place a restrictive protocol.
The hard part is how do you back down on it?
So Dr. Fineberg and his colleague, Richard Neustadt
wrote eloquently on that with respect
to the 1976 swine flu affair.
We had to deal with the same matter at other times.
So, the question in my last three seconds is who is watching
the dashboard for when you need to ratchet this down?
It becomes a risk averse decision maker's nightmare
to say we have this protocol that we've not created
and put in place.
How do we back out of it knowing that eventually there will be
some mistake downstream and you don't want to be the elected
official or the political appointee
that released the ratchet on it?
Liability and Q-and-A's, I don't think that's -- I don't have
time, I mean, I'll respond in discussion
if anybody wants to talk about liability.
Thank you.
>> Dr. Zarifah Reed: Thank you, Dr. Matthews.
Our next speaker is Dr. Anna Lönnroth Sjödén, who's a deputy
head of unit, infectious disease and public health
at the DG's Research and Innovation
at the European Commission, Brussels.
>> Dr. Anna Lönnroth Sjödén: Thank you very much for
inviting the European Commission here.
We've very pleased to be involved because we are one
of the really greatest funder of influenza research in Europe.
We have, in the last decade, invested over 150 million into
influenza research, funding some 80 projects that involves over
300 institutions in 60 countries,
going beyond Europe as you can hear.
So that's the baseline, and I'd like to -- in my presentation
here give an overview of how it works in the commission,
and the commission's position on these issues for the moment,
and the little -- longer term perspective.
And the emphasis will be question 1A and B here.
So anyone who is applying for a research grant
in the European Commission has to declare
that they comply fully
with national EU safety, ethics, legislation, and guidelines.
So all research proposals that have passed scientific scrutiny
are also screened for any ethical safety or dual-use
issues that may come up, and applications are actually asked
also to make a self-assessment for potential dual-use
implications of their work.
But even if that is the case and they haven't declared it
this will get picked up anyway.
Now, for those proposals where there are issues, they go on to
a scrutinized specialized ethics and biosecurity review board,
and then the recommendations are, of course,
on the case by case situation.
So the first point I'd like to make here is the European
Commission, regarding the legal framework that we have in
Europe, the national law and EU law, we consider for the moment
that that is adequate and that no change is necessary
on the legal side regarding this type of research.
However, we can become much better when it comes to being
vigilant about the operations being more aware of what's
actually going on in the projects, and while we fully
subscribe to what's being said here in this workshop, many
times the training of scientists is absolutely crucial,
raising awareness.
We do believe that the sort of softer approach rather
than regulation is a much more productive way forward, because
we find it very difficult to write some regulation
or law that would exactly determine what is dangerous
and what is safe.
You can't predict that, you will always be behind.
So we think it's better to address directly the scientists
that are actually working in the lab to raise their
awareness about these issues.
Now, having said that, then within the projects, the
international collaborations we are funding, we would like
to have a better than today system for looking after the --
not only scientific progress that we're looking at today
but also the biosafety and biosecurity potential dual-use
issues, where that is relevant.
So, that is -- those are things we're looking at for the future.
In the longer term perspective, it is to be recognized
so we're not only talking about influenza, H5N1, we're looking
at all sorts of pathogens, existing ones and those
that are yet to be discovered.
So we would like -- whatever we install, we'd like to have
something which is solid and works and can also
anticipate the unforeseen.
And we need to recognize that there could be actually far more
dangerous experiments than those that we've been looking
at in this workshop.
Secondly we have come a very long way in building up trust
in the international level, and we would not like to see this
jeopardized by, let's say, stifling of very important
research that needs to be done, or the dissemination of results
that are actually very important
for public health and protection.
And so that leads actually to the conclusion,
which is we don't really have in our hands today the solution
how all of these matters are to be solved.
But we do believe strongly that continue dialogue with all
of you and others who are in this field is the way forward,
so that we can come up with something which is in harmonized
approach that would work, and be sustainable and not running
ahead -- sorry, running behind the evolution of events.
We find it's a very difficult challenge to understand
who is going to police, so to speak, the activities within
the projects unless we have a specialized board and
a continued dialogue and full awareness of the scientists
who are working on this.
So we are very much looking forward to continue this.
We don't see this as sort of the end of anything and we don't
have ready, let's say, new proposals for you other than our
position of today, as I said, is we don't see the need
today to change the existing EU legislation.
But I cannot speak on behalf of all my colleagues, maybe the
continued dialogue will actually lead to change in this;
this is something which is beyond my control.
Thank you.
>> Dr. Zarifah Reed: Thank you very much.
Our next speaker is Dr. Kevin Wolf.
He's the assistant secretary of commerce for Export
Administration, the Bureau of Industry and Security,
the U.S. Department of Commerce.
>> Dr. Kevin Wolf: I have a five minute to five hour
and a five day version of this talk.
I'll stick to the five minute version.
My name is Kevin Wolf.
My bureau is responsible for regulating dual-use items
of concern; it's the export administration regulations.
My colleagues at the State Department under
the international traffic and arms regulations have
similar degrees of controls over the export of sensitive
technology items, hardware, software, and services.
Under our regulations, the Export Administration
regulations, a license permit from the United States
government responsible for that is the Commerce Department,
is required to release to foreign persons pretty much
all the technology that's at issue in this conference,
and a long list of other types of technologies that are set out
in our commerce control list, which is, again,
part of the Export Administration regulations.
And these controls extend not only to the physical release
of particular items outside of the United States, but also
the release of control technology to foreign persons
within the United States.
The type of technology here doesn't really have any
exceptions available to for nationals of particular
countries, even to nationals of Canada.
A license would be required from the Commerce Department
to release it.
These regulations have been in place for several decades.
They're there largely as a result of various international
agreements that the United States has agreed to
and administered by something called the Australia Group,
which is a multilateral organization.
When someone submits an application to release
to foreign persons, or to export outside of the United States
control technology, that's reviewed by our counterparts
at the Departments of State, and Defense, and also Energy in some
cases, and they review it with respect to whether it's released
to foreign persons or outside of the United States would be
a national security or foreign policy issue, and if so, whether
there should be any conditions or whether the license should be
denied or if it should be granted,
whether the approval should be conditioned.
The primary exception that most in this room think about with
respect to the scope of these controls and these regulatory
requirements, which by the way, have both civil and criminal
penalties attached to them, in the sense that if you
deliberately violate the regulations, then they're
enforceable by substantial monetary penalties
or incarceration, and we do so regularly.
But the primary carve out to these regulations that this
group is interested in, perhaps, are what are known as the
fundamental research carve outs or published information
or public domain exceptions, and that is that information,
regardless of content -- and we're speaking only of
unclassified information in this context, which is in the public
domain, it's intended to be made freely and available without
restriction or government limitation, or without
conditions such as published in journals.
As a result of the First Amendment, doesn't fall within
the scope of these two sets of export control regulations.
Similarly, the results of fundamental research, research
done with the intent of having it promulgated and used in basic
science and research is also not within the scope
of these carve outs.
There's also another limited carve out with respect
to information that's released in a curriculum course
at a university, and the difficulty becomes, in analyzing
whether any particular fact pattern that you're dealing
with A, is within the scope of the control technology
that we're dealing with for the production and development
of a virus, for example, that's listed, and then B,
whether that technology is within the scope
of the various definitions of public domain
or published information or fundamental research.
With respect to this topic -- so, those are the conditions
to respond to the topic of the assignment,
under which research has to be conducted.
The commerce department is working with the other parts
of the U.S. government,
NIH and HHS, and working out a way in which
to work with these regulations as part of conditions that
the U.S. government would impose upon funding for this type
of research to make more flexible and clear the scope
of these conditions.
That is, when fundamental research would apply or not,
or when a license from the commerce department and reviewed
by the other parts of the U.S. government
would be permitted.
So that's my five minute version.
I'll come in a little bit short and then leave it
for questions later.
>> Dr. Zarifah Reed: Thank you.
Our next speaker is Dr. Celia Alpuche-Aranda.
She is the director of Research, Center for Infectious Diseases
at the National Public Health Institute in Mexico.
>> Dr. Celia Alpuche-Aranda: Well, good morning.
First I want to thank the organizers that gave me
the opportunity to be here.
It's a great meeting.
The good part to participate at almost the end of the meeting
and the panel is that I have listened to, the discussion
of many experts, and that's feeding my participation,
but the bad part is that most of my discussion points
have been addressed before.
So I'll do my best and I'm going to try to focus
on the experience that we had in the Latin American region,
mostly in Mexico.
In regards of the first question of the common principles,
biosafety and biosecurity,
I would like to emphasize just few things.
That no matter the objectives of biosafety and biosecurity are
different, they are mutually complementary because they also
share common concepts or components that have been
mentioned before, such as risk assessment and the others.
But, in fact, it's a total culture of work linked
to responsibility lying in bioethical principles.
But sometimes, some of these procedures may be conflicting
between biosafety and biosecurity, and there's one
example that you all know.
The open and transparent signing of the type of hazards
of microorganisms that they are being addressed
in specific laboratories.
It's a rule for biosafety and it's a problem for biosecurity.
So, and I would like to extend these sort of -- extrapolate
these to the example of the gain-of-function,
H5N1 research discussed here.
And I'm not talking about a specific biosafety, biosecurity
issues in laboratory.
I'm talking about security and safety in public health.
There is a concern here that has driven to classify,
or even limited, the gain-of-function H5N1 research
because of security issues, but at the same time, this condition
will have a negative balance to obtain scientific evidence
that may help better preparedness and response
for a possible pandemic
with a highly pathogenic microorganisms such as H5N1.
So if we talk about the second question, do we need to extend
biosafety, biosecurity, it has been addressed many times
and I just want to mention that it's obvious that those expert
laboratories doing research in H5N1 here, that they are here,
discussing all these issues, they fulfill all the basic
requirements for security of biological materials.
But it is also true there is a lack of harmonized standard
for exactly definition of BSL-3 enhanced outside,
out there in the world.
And I'm talking about my own experience coming from
developing country with a very recent history of biosafety,
biosecurity program up to BCL3, BCL3 enhanced.
We do not have BCL4s, and we are not doing a specific research
in H5N1, only surveillance.
We use a lot of help from our partners from CDC and National
Microbiology Laboratory, Public Health Agency of Canada,
to increase our infrastructure.
But we need to be practical and know that it's not only
a responsibility of international organizations
to do more in these regards, in depends on each country.
It depends of each institution to do more.
They are many guidelines, programs try to harmonize
standards, WHO, CDC, NIH, European Commission.
We've been listening in all that.
And programs, so biological convention, dual-use research
concern, IHR, there are biosafety international
associations now, there are in-countries biosafety
associations, and I want to be optimistic that --
and I think this culture of work is getting much better.
But -- so you know much better than me, but it seems that it
doesn't need to extend the biosafety, biosecurity
requirements, but we need to emphasize the harmonization of
standards for BCL3 enhance it, and to make it not ambiguous,
needs to be very clear for everybody out there.
In terms of other programs to oversight, the research
legalizing highly pathogenic agents, I just want to emphasize
that and look very carefully in the Latin American countries,
and I couldn't find a formal official document to do these.
There's some mentions in the bioethic and the ethic, and
security committees coming from IRBs and other research
committees, but now then we need to work in that.
It has been also mentioned many times that the concern is not
regarding the well-known experts working in H5N1 research.
The concern is in those who may be using the information to do,
or to start doing, research or for misuse.
And in my own experience in my country, this happens during
the 2009 H1N1 pandemic.
And in the confusion, in the beginning part of the pandemic,
when we did have very limited knowledge of about the virus,
several researchers, with no experience in influenza,
suddenly became experts.
And it's very hard to control that, so we really need to have
in place the elements, the procedures, to control that,
to help to control that.
But again, it's not humanly feasible to control each one or
the possible misuse of these, so we all need to work together to
push and to reinforce these.
I will not add more about these different programs because they
have been mentioned before.
To finalize my participation, I would like to mention that our
own experience in Mexico to develop infrastructure and human
resources to work highly pathogenic microorganisms
to become part of CDC laboratory response network.
[unintelligible] also helped us to have a much better prepare
for H5N1 surveillance, to define much better BCL3 enhanced,
and now we're working to harmonize these
with the animal surveillance part.
And I'm pretty sure that some of these strategies in coming out
of this meeting, to make highly pathogenic avian influenza,
H5N1, gain-of-function research better, will have a positive
impact to oversight other models for highly pathogenic
microorganisms' research in general.
In conclusion, my personal opinion is that scientific
evidence produced by gain-of-function, highly
pathogenic avian influenza H5N1, may be important for a better
preparedness and response, and for a pandemic influenza,
as a highly pathogenicities [phonetic sp].
And always, and maybe it's a much better, and in fact,
if it's based in rationalized science, then nothing.
Thank you.
>> Dr. Zarifah Reed: Thank you very much.
Our next speaker is Dr. David Harper.
He is the special advisor to the office of the assistant director
general -- at the Office of the Assistant Director General of
Health Security and Environment
at the World Health Organization in Geneva.
>> Dr. David Harper: Thank you, chair,
and good morning, everyone.
I'd like to thank the organizers for their kind invitation to
the World Health Organization to participate in this discussion.
It's very important and it's always a real pleasure to look
around the room and see old friends and colleagues,
some of whom I've not met for some considerable time.
I thoroughly enjoyed the discussion yesterday.
I found it very interesting.
And what I thought I would do is just start by saying
a little bit about the World Health Organization.
I'm sure that all of you, or most of you, are aware
of what the World Health Organization is.
The World Health Organization is its countries,
its member states.
Sometimes there is the perception that the people
sitting in Geneva, or at a regional level or indeed
at a country level, are the World Health Organization.
I should point out before we get into the post-panel presentation
discussion, that in fact that's the secretariat to the World
Health Organization, so there's an important distinction there
that might become apparent and important later.
The organization and the secretariat, the assembly
and the governing bodies, is the directing and coordinating
authority for health within the United Nation's system.
It's responsible for providing leadership on global health
matters, for shaping the health research agenda.
Importantly, for setting norms and standards, for articulating
evidence based policy options, and particularly for providing
technical help and support to countries and for monitoring
and assessing health trends.
And right the way back to the 1948, to the constitution of the
World Health Organization, at the heart of the constitution
is this statement of the need to attain, for all people,
the highest possible levels of health.
I'd like to use my few minutes to talk briefly about the first
part of question one that we have on the screen, not
venturing, for the time being, into A and B, but really just
what is going on around the world, and in particular,
what have WHO done and what are we currently doing.
And this is building on what my distinguished co-panelists have
already said, of course.
As far back as 1983, the World Health Organization published
its laboratory biosafety manual, and a couple of people have
already mentioned that this morning and indeed yesterday.
And this encouraged countries to accept and implement basic
concepts in biosafety, and to develop national codes of
practice for the safe handling of pathogenic microorganisms
within their geographical borders.
Second edition was produced about 10 years later in 1993.
And the third, in the extent edition, which I'm sure many of
you in the room will recognize, the so-called "red book,"
was produced in 2004.
And this edition also recognizes
and introduces biosecurity concepts.
You all know that biosecurity in this context means the
protection of microbiological assets from theft, loss,
or interesting word, "diversion."
I'm not quite sure what that means, but diversion anyway,
which could lead to the inappropriate use of agents,
and to cause public health harm.
Unsurprisingly, in many ways, as ideas and thinking developed,
there was a general feeling within the international
community that something more was needed.
And one important step amongst others, around the world, to try
to address this need, was taken in 2008 by CEN, the European
Committee on Standardization.
When it produced its workshop agreement 15793 for those
aficionados amongst you, and a number of countries,
non-European countries and indeed the World Health
Organization played a role
in the workshop agreement development.
This focused far more on a management systems approach
built on the concept of continual improvement through
a cycle of planning, implementing, reviewing,
and improving the processes and actions
that an organization undertakes to meet its goals.
And this is a relatively well known approach.
It's an approach that international standards
organizations have taken for many years, ISO and the likes.
So, it's a well-tried and tested approach.
This agreement was renewed in 2011, and I think it gives an
indication of one of the key directions of travel
in this important area.
As colleagues have said this morning, it's very much a risk
assessment and then risk management based approach.
Now, you heard talk yesterday of international agreements,
and very brief mention of the international health
regulations, so I thought I should just say a little bit
about the international health regulations, which form a vital
plank in our approach to dealing with many of these international
infectious disease and toxicological and radiological
hazards, and way beyond that.
What are they?
Well, they were adopted in 2005.
They're one of the very few international legal instruments
that's binding in the -- in all of the 194 member countries
of the World Health Organization.
The aim is to help the international community prevent
and respond to acute public health risks that have the
potential to cross borders and to threaten people worldwide,
pandemic influenza causes is an excellent example of that sort
of public health event.
They entered into force on the 15 of June, 2007 and countries
are in the process of implementing.
A lot of discussion of the World Health Assembly last May about
how far countries had got in terms of the implementation
of these important regulations.
That was the deadline for full implementation in a number of
countries for a very good reason, understandable reasons
have requested a two year extension to the time
that they would take for full implementation.
The regulations define the rights and the obligations
of countries to report public health events.
And this is very important in the context of some of what
was mentioned yesterday around surveillance, the need
for good systems to be in place.
They also establish a number of procedures that the World Health
Organization must follow in its work
to uphold global public health security.
I can say more about that hopefully in the discussion
session that follows the panel presentations if people would
like to, or in fact, happy to pick things up in the margins
of the main discussion.
In the context of the international health
regulations, I'd just like to say something about our
laboratory bio risk management.
And, in January this year, the strategy, the action plan, the
framework for action has been applicable, and under the
regulations all state parties have made this legally binding
commitment to assess, develop, and maintain their national core
capacities for surveillance assessment and response.
Appropriate laboratory capacities are essential
for all the obvious reasons and I won't go into them now.
I know I'm running short of time, but they're essential
to identify, confirm the agents involved
in these public health events.
And to meet IHR requirements, every state party, every country
needs to access laboratory services, domestically
or internationally.
So the aim of our strategic framework is towards the
development of sustainable global, regional, and national
plans, where we have that link to have laboratory bio risk
management in the right place, as far as possible.
The vision, which is easy to say and in typical civil service
understatement very challenging to achieve, it's -- the vision
is to have safe and secure environments in and around
every laboratory in the world.
So, I just leave that thought with you as a concept.
There is a mission that goes along with this.
I won't take the time this morning to talk about that.
So we feel that without such strategic planning, bio risk
management runs the danger of failing to meet this vision,
the objective of delivering solutions that allow countries
to build standalone capacity and capability, so in this context
I'm using the word capability as a combination of capacity
and competence just to be clear.
I hope it gives you a flavor, in general terms, in broad terms,
not just focused on the H5N1 situation that we're discussing
in this meeting, but in a broader sense of what WHO has
done and, indeed, are doing in the area
of biosafety and biosecurity.
It's very much a dynamic situation and a continuous,
continuously improving situation.
Very happy to pick up other issues in discussion where
I'm able to, although there are other experts on the panel who
I think are very well placed to pick up those different areas.
And I'd just like to finish by saying how much we're looking
forward to hosting the forthcoming meeting in Geneva
that we're organizing at the end of February.
A number of you in this room are invited to the meeting
or will be invited very shortly.
This will build on the meeting held in February of this year,
which focused on the two research studies that we've
heard so much about in recent times.
But it will address the broader concerns about dual-use research
of concern, and it'll provide an international forum where the
perspectives, a wide range of stakeholders across governments
and society, whole of society approach after all, can be
exchanged, including health, security, defense, academia,
scientific and technical associations, societies,
journals, ethics, biotechnology,
and, of course, private sector stakeholders.
So, absolutely finally, just to say that the World Health
Organization is very pleased to participate in this continuing
dialogue with all of you.
Thank you very much.
>> Dr. Zarifah Reed: Thank you, Dr. Harper.
Our final speaker is Dr. Gary Kobinger, who's the head of
vector design and immunotherapy special pathogens
at the National Microbiology Laboratory,
the Public Health Agency in Canada.
>> Dr. Gary Kobinger: Thank you and I just briefly want
to repeat that my opinion and position is not necessarily
reflecting the one of my agency and the government of Canada.
I have been again more focusing on the questions,
and on the first question about common principle,
I think there is common principle
in biosafety and biosecurity,
and these include answering questions of importance
locally, nationally, internationally regarding
if the agent is endemic, preventable,
treatable, fatality rate, associated to it.
Extra, -- but overall, this may need to have
different answer for, to the same questions.
And, an example I'll give you is CCHF, which is a level 4 agent
and counted as Crimean-Congo hemorrhagic fever virus.
This virus is a level 3 agent in South Africa, and this is
to recognize that there's a possibility to have, again,
the same answer -- different answer for the same question,
but it's to recognize that each location should be assessed
in a case by case basis for each proposed project,
and to recognize the future and the strength of each location.
I think in this regards, there is -- a problematic associated
with trying to harmonize everything, and to say that all
the level three should be -- they could meet the minimum
requirement, but the example I like to give you is a facility
in Madison which I have not visited but I've seen pictures,
and in many features of that location, has a specificity that
goes beyond what normally is expected, to my knowledge,
of a biosafety level -- biosafety three lab,
and at least the one I've worked in,
in Canada and here in the U.S.
So to try to harmonize and bring the bar to, for example,
this location, the same level, it will be basically impossible
for a lot of other location, which are still appropriate
to do a lot of work on
and answer different scientific questions.
I think what could be improved is the development
of a continuous link between biosafety, biosecurity.
The dual-use work, and scientist, and maybe here,
involved -- we thought about communication yesterday,
but maybe involve what we call community liaison but it could
also -- may be called public liaison
to favor transparency, basically.
At all level of the process, from -- even from evaluation
of proposal to acceptance of proposal and to -- and it's hard
for me to decide how this should work, but as a suggestion,
I think this will optimize the process.
Right now, there's more -- it's more groups that have specific
input, but there's not this continuity in the process.
I think that one thing I wanted to mention, it's something that
I heard and I've been thinking about it, and I thought that it
makes a lot of sense, is to not fall in the trap of relying only
on biosafety, biosecurity, and legal groups to make decisions,
and to involve -- this could be seen in my view as relying
on the other scientists to self-regulate themselves,
aside from the conflict of interest problem.
But I think everybody will agree that their job, and,
by definition, biosafety, biosecurity, and legal people
are risk adverse.
And for them to not do the experiment is what's safe,
and is what has no risk attached to it.
But, but from another angle, as was said also yesterday,
to not do the experiment, not do the work and not advance the
knowledge has a big risk attached to it, which is that,
again, these things are being done in nature, and reacting
is always less efficient than preventing.
So an assessment with the comprehensive approach involving
all sites should be optimal and, finally, the assessment should
be considered to a more dangerous version of the agent
is something I wanted to mention also.
So if the initial agent is going -- features are going to be
knocked out -- well, this is where it starts.
If an agent is thought to be acquiring some features,
then the final possible agent is what should be
the point of discussion.
And, again, the goal is to predict and prevent natural
infectious event, and stop reacting all the time where we
spend a lot of time identifying the agent and then focusing
on diagnostic, and then, after weeks of work, trying
to find solution with vaccine and treatment.
Thank you.
>> Dr. Zarifah Reed: Thank you very much.
That ends our session with the panelist presentations.
We'll now move into the moderated panel discussion,
and for this I turn over to my co-moderator Kirsten.
>> Dr. Kirsten Jacobsen: And actually I'd like to just turn
to our meeting co-moderators to see if you have any comments
or questions following the panel discussion,
or, panel presentations.
>> Dr. Harvey Fineberg: I would just raise one question.
Today, particularly and up in the discussion yesterday, there
was a lot of consideration about biosafety level that's
appropriate for managing this organism: 3-enhanced, 4,
those have been the debates back and forth.
A number of you have offered your -- your views on this.
If you were to persuade or to offer the evidence for someone
who did not have experience in understanding exactly what each
level entailed, how would you describe the appropriate level
of safety in the facilities that manage this research that ought
to be the core requirement wherever it is conducted?
>> Dr. Kirsten Jacobsen: So see, we could turn to -- we've
had a few opinions on this today; so maybe we can actually
start with you, Dr. Kobinger.
>> Dr. Gary Kobinger: This is an also very difficult question,
but I think there is ways to do this.
I think it goes down to -- to communicate, efficiently.
The feature of each of those environment and how they address
the agent that is being -- that is being worked with,
and I mean, I think it needs a little time
to come up with the right wording and the right images,
and I don't have the -- I think the --
I'm not going to go and tell you that I know about this,
but I think really, you know, these lives are a box in a box
and they are, in that view, maybe easy to explain
and some have showers, some don't have showers.
And I think there is images that can be developed.
There is a strategy; there is a communication strategy that can
be developed to really explain why an agent is being worked
with in this environment and what it entails, what it means
for somebody to go in to work and to get out
with simple images.
So I think it's possible and I think it would be very useful
as a matter of fact.
And probably lacking right now.
>> Dr. Kirsten Jacobsen: How about Dr. Kanabrocki, would you?
>> Dr. Joseph Kanabrocki: All right, so, when I think
of BSL-3 enhanced,
I think about respiratory protection full time.
I think about a really strong occupational health program
wherein any illness is reported through occupational medicine.
One of the things I didn't mention earlier is, and I think
is very critical, is to establish a code of conduct
for this work, such that each person
is their brother's keeper, if you will.
I think we're all in this together in that situation
and I think it's critical that if there are people who are not
abiding by the established standards, that be reported
in a way that is not punitive but corrective, if you will.
So these are some of the elements that I think contribute
to a good biosafety program in general, but in this context
these are the elements of, you know, above standard BSL-3
that I think are important.
>> Dr. Kirsten Jacobsen: How about Dr. Anna Lönnroth Sjödén,
would you like to add to that, or Dr. Alpuche-Aranda?
Dr. Anna Lönnroth Sjödén: No, I don't think so.
Dr. Celia Alpuche-Aranda: No.
>> Dr. Kirsten Jacobsen: No, nothing to add?
Okay, all right, thank you.
One of the things that a number of people touched on
was biosafety risk assessment, biosecurity risk assessment,
and one of the questions that I have is, what is the role
that you see, the regulator or the highest level of advisor,
playing in biosafety risk assessment and biosecurity risk
assessment, and then what's the role of the institution
or the individual in that?
>> Dr. Robbin Weyant: Well, thank you, actually, I think
it's important to differentiate the role of regulator
from role of advisor.
The regulator is the individual or the component that's
responsible to ensure that an institution is operating
in compliance with laws and regulations, and I think that's
a very different role than an advisor would be.
The regulator has to make judgments and, as our colleague
from the Department of Commerce indicated, there could be civil,
monetary penalties, potentially even criminal penalties
in association with regulatory issues.
That being said, speaking from the regulator perspective, I
think it's critical that we have science-based, evidence-based
regulatory standards that we work off of
and that we apply them in a fair and equitable way
with respect to the United States select agent regulations,
there are sort of fundamental
programs that are required to be in place at an institution that
possesses, uses, or transfers any select agent
to the United States.
And Dr. Kanabrocki touched upon some of these programs.
It's important that these institutions have biosafety,
biosecurity, and incident response plans that are designed
in response to the risk and are trained and are drilled
on an annual basis.
And I think in the area of these flu viruses, incident responses
is an area that is really critical.
The possessors of dangerous influenza viruses that are
regulated in the United States must have effective incidence
response plans, and they must demonstrate to us that the folks
that use these agents understand what their plans are
and that the plans are drilled.
And the plans usually have to involve interactions
with the surrounding community.
So that the community has a role in the event that something
adverse has happened, and there's a -- sort of a teamwork
atmosphere around these facilities.
>> Dr. Kirsten Jacobsen: [affirmative], do you have some
other input on that?
Would you like to comment?
Yeah?
Dr. Cecilia Alpuche-Aranda: So, I would like to add something.
I mean, for us, in Mexico, to implement the biosafety,
biosecurity plan, not just for the high contingency
laboratories BCL3, we try to match whatever we had coming
from the CDC LRN going down to the World Health Organization
program for biosafety, biosecurity,
so we include all the BCL2s.
It took us four years to actually make it to work and
to include all the people and to have the new culture of work.
So for these specific pathogens I think -- when we started doing
the pandemic, that it was not H5N1, it was just H1N1.
We just, together with the CDC personnel and the NML personnel
that we had in Mexico, we sit down, we viewed the risk
assessment that we have for influenza virus.
We didn't have much information for that virus in the beginning,
so we basically took whatever was there and we did a list of
things that there were, minimum requirements to try to set up
a safe environment for us.
And all of those researchers wanted to do something.
We used the same format to try to evaluate them, to see
if it was possible to share samples or isolates or so on.
So that was for the critical moment, and now we used that
to keep growing, and how to set up the minimal standards,
at least for the BCL3 labs that are around in Mexico.
So and to have a program to educate the scientists and all
the universities and so on, so we're using the WHO program,
with the help of CDC and some Public Health Agency of Canada
personnel to do this training, so that's what we're doing.
>> Dr. Kirsten Jacobsen: Yes.
>> Dr. Joseph Kanabrocki: So think the role, obviously,
of the regulator is to set the boundaries, and to determine
what specific elements should be addressed.
As Rob mentioned, incident response, biosafety,
biosecurity, these are components of a program
that are established, or need to be established.
The role at the local level though is to consider the local
culture, the local environment, and, in fact,
obviously involve the local community.
And the good news in the biosafety realm
is that the regulatory and the guidelines are --
these are performance based, and so it really does provide
an institution at the local level, a fair degree of latitude
in how they meet a particular goal.
And I think that's critical to have that flexibility, and to
have all of this be risk based and not driven by a checklist.
So I think there's a very important collaboration
that has to happen between the local oversight entity
with the federal oversight entity.
Dr. Kirsten Jacobsen: Yes, Dr. Harper.
Thank you, Dr. Kanabrocki.
>> Dr. David Harper: Yes, thank you.
Well, I think it's a very good question, of course, and I think
this link between the regulator and the advisor
are very important, not to confuse them.
I think sometimes there is a risk that --
that they're confused.
But what Robbin and Joseph have already said, I think, gets
to the heart of the regulatory side, and there are many, many
laws in many, many countries that make very clear
what the role of the regulator is.
I think the advisor is less well defined.
It applies at the institutional level right the way through to
the global level, and the case of the World Health
Organization, as I said, a little earlier,
we're an organization responsible for norms
and standards amongst other parts of our core activities.
It's important, I think, to recognize the words norms
and standards don't necessarily have the power of law.
In a court of law, or at least looking at many countries'
national laws, there has to be a very, very powerful reason
why those norms and standards, the advisory elements, the
appropriate advisory elements are not taken into account.
So if an organization, an institution chooses not to take
account of the advice in the context in which I'm using
the word advice, from the appropriate authority,
then in a court of law
that would be challenged quite carefully,
and I think that has to be an overwhelming -- be interesting
in my legal colleagues' view on that, that has to be a very
persuasive reason as to why a norm or a standard, whether
national or international, has not been taken into account
or why an institution has decided to go down
a different course of action.
So I think the WHO is very keen to help facilitate
the discussions, particularly looking at some sort of
harmonization, if that is what member countries are asking for,
and particularly to do what is necessary to avoid divergence.
I think these are some pretty key elements of that issue
prompted by the role of the advisor vis-à-vis the regulator.
Thank you.
>> Dr. Anna Lönnroth Sjödén: Thank you.
Yes.
So I mentioned in the beginning of my presentation that we are
actually engaging with about 60 countries, which is far more
than the member states of the European Union, and the funding
that we provide is actually in collaborative research
that involves at least three countries.
There are members of the European Union, or associated,
and very often we ask for involvement also
in the projects, in the research projects, of countries
from the member countries.
So that means that within the projects that we are funding
there is some internal control of standards of the laboratories
from the developing countries that are participating.
I think this is a nice opportunity to foster training
and to share good practice in research.
And I really take that back to my colleagues for reflection,
how we could better use this tool.
>> Dr. Kirsten Jacobsen: Thank you.
Dr. Matthews.
>> Dr. Gene Matthews: Just to follow up very, very briefly
on David's invitation.
The conformance with whatever the applicable, generally
accepted safety security standards are becomes a matter
of great advantage after an event occurs.
There's always a post mortem and the mandatory floggings that
will have to, you know, be inflicted by the body politic
as well as courts.
And so having conformed with those, whatever the appropriate
standards were, it is in the enlightened self interest
whether you happen to fall under the scope of, you know, HHS
funding or if you were doing it with some other methodology.
So it certainly is -- makes good sense to do that from a number
of different dimensions.
I don't need to rub that in.
I think you got it.
>> Dr. Kirsten Jacobsen: Thank you.
No further points on that discussion line.
So one of the other things that was mentioned a number of times
was the importance of education, engaging scientists
and establishing a culture of safety.
I'm just, you know, if you could offer somebody guidance
on how you could use the culture of safety in education just
fundamental engagement as one of the other models
other than regulation.
What would that look like?
Dr. Anna Lönnroth Sjödén: Maybe I can start that.
We've had some discussions about this in relation to some of the
bigger projects that are looking at the influence of research
and there is some best practice under development, I should say,
under discussion, under scrutiny, under development,
which is based on setting up some, what do you call it,
ethics liaison within collaborate research project
engaging maybe 15 partners or so.
And this ethics liaison will deal with all types of ethics
issues but also safety and security.
So that would be a point where you could go to consult on
anything which is in the ethics and safety and security domain.
Anything ranging from patient data to clinical trials
involving children, to all these things
as well as what we're talking about here.
So that's a nice model that we're looking at then, how that
could be implemented best and filled with content of course.
And I think this is maybe an area
where we're a little bit weak, in general though.
We don't have a lot expertise who will provide the contents.
We can set up the structure.
That's fine.
But to provide the actual, meaningful advice there is maybe
an area that we need to become better
and to foster that better.
>> Dr. Kirsten Jacobsen: Thank you very much.
Yes, Dr. Kanabrocki.
>> Dr. Joseph Kanabrocki: So absolutely agree.
I think it's in the realm of ethics training
for young scientists.
That this is a perfect opportunity to engage
young scientists in the ethics of safety and security
and actually after five years of trying we finally managed at my
institution to have that, have biosafety and dual-use research
of concern added to the mandatory ethics training
that our students are required to take.
And in my brief experience with this program, so far, I must say
the dual-use research of concern topic is one that young
scientists really engage directly with very, very well,
a lot of great discussion on those topics.
So this goes back to what I said in my earlier comments about
educating the public about the importance of our work
and the steps we take to manage our risks.
I think it's important that that be understood.
>> Dr. Kirsten Jacobsen: Thank you very much.
Dr. Matthews?
>> Dr. Gene Matthews: In education then the finer piece
of that is who is your target audience.
I think the target audience for the researchers is by far
the easiest of the layer of target audience.
Standing in the middle of the room here is a little elephant
wagging his tail that says 60-day moratorium.
Well it's been a year.
That elephant is a year old now.
So at some point the moratorium will be rolled back and
an organization certainly as sophisticated as NIH and HHS
will have thought through the education for those
other target audiences.
So Dr. Fineberg's question was very important about how do you
explain biolevel-3-enhanced to a lay audience.
And the lay audiences are sort of at least three layers.
The first one would be the press.
Okay?
So you're going to have to have
a one paragraph, three- or four-sentence paragraph
to talk about what Gary just explained,
what BSL-3-enhanced.
And then you'll need to be able to explain it to the various
organizational administrators and managers and apparatchniks
that will be looking over your, you know, your shoulder.
And you have to be able to explain this to the public,
regardless, again, whether this is under the scope of, you know,
HHS federal funding or done internationally.
It's the same problem and same issue.
So, you know, anticipate, it's not hard to figure out what's
coming and it's just important to be prepared.
>> Dr. Kristen Jacobsen: Thanks.
Thank you, Dr. Matthews.
>> Dr. David Harper: Thank you.
So the issue of education and awareness-raising for scientists
and others, I think, there's a lot of good stuff that's being
done, lots of models, whether in undergraduate training,
postgraduate training, ethics; I think we've been making
progress, maybe not in a particularly visible way,
but still progress over a period of years.
If I think back to my undergraduate days this was not
something that was a feature at all, and I think in the past
decade probably we've begun to address
some of those key issues.
How to do it will always be an issue.
It needs good communicators.
There are, you know, some great communicators,
looking around this room.
Scientists themselves, I think, need to demonstrate
that scientific leadership.
I think there is, there are professional societies
around the world.
There are lots of vehicles through which this can be
facilitated through continuing professional development
schemes, through revalidation
in professional qualification terms.
But I'm quite sure that this is, at least in part, if not
in large part, an issue of scientific leadership,
and what I'll call responsible stewardship.
>> Dr. Kirsten Jacobsen: Thank you very much.
Anything to add to that?
So one, question two is one that's maybe a bit technical
in nature about the experimental design as one of the risk
mitigation measures.
I was wondering if anybody could speak to that a little bit more.
I mean, Dr. Kobinger, you have spoken a little bit about, you
know, that it can be done safely but I wonder if you can talk
about the controls themselves that would mitigate the risks
associated with this type of work.
>> Dr. Gary Kobinger: I mean there's always room
for improvement, I think.
That being said I think these experiments were very well
designed and very well -- the oversight was very good.
The environment worked very good.
So it's a little bit difficult, in my view.
But one thing that I mentioned that I think could be improved
again is clear communication to the public is -- instead of them
seeing the result of the study and sometimes with an angle
that is not the intended goal of the study.
Maybe at the beginning even before the work is being done,
maybe during, while the work is being done this could be
something to consider.
And, again, I think it's important to emphasize that each
site needs to be evaluated in regards to the specific project
that is proposed, and that some sites have specifications that
are, that could be more valuable for a type of work and other
sites that could be valuable for another type of work.
And these two sites could be different.
And each location and each project, you know, needs to be,
to be evaluated in -- with those angles, and to realize that at
the end of the day each country will decide themselves what they
think is appropriate, although, of course, this is where having
international regulations helps sometimes as guidelines
to guide those decisions.
>> Dr. Kirsten Jacobsen: Yes Dr. Weyant, thank you.
>> Dr. Robbin Weyant: In terms of experimental design
as an assessor or regulator I'm always more comfortable with
experiments that are highly defined, that start off
with a good understanding of what your starting material is.
And especially with the technology and tools available
today at the molecular level, what you're working with and
precisely what you want to do at the molecular level.
It makes it a lot easier, I think, to assess issues
such as consequence.
What I'm less comfortable with are experiments
that are sort of prone to serendipity.
You know, let's just passage something in a system for awhile
and see what happens, and then once we have this product let's
study it and see if we can understand it better.
I think those types of protocols are more difficult to assess.
>> Dr. Kirsten Jacobsen: Yes.
Thank you very much.
>> Dr. Gary Kobinger: I don't know to what extent this was --
and I think, again, like the experiment that were done that
were the subject of this meeting.
They were well-designed.
But I wonder now if there should be maybe more in phases on
thinking about okay, so if we get this, what's the appropriate
environment for this agent now with added feature.
And are we going to have a good vaccine, are we going to have
good drugs, so I'm not saying that it was not done but I think
that in the light of all the reflections that have been
going on I think this could be emphasized in the future.
>> Dr. Kirsten Jacobson: Thank you, doctor.
>> Dr. Gary Kobinger: But this is going to be hard because then
you also get into the unknown and a little bit speculative
part of the thought process.
>> Dr. Kirsten Jacobsen: Thanks, Dr. Kobinger.
Yes, doctor.
>> Dr. Anna Lönnroth Sjödén: I just want to raise an issue
to which I'm not at all expert myself, but came up yesterday
in the discussion.
I think this could be work picking a bit on your brains
here while you're still here because first to this question,
and the issue is really the attenuating mutations,
attenuation of pathogenicity that could be relevant
in some of the experiments to increase safety.
Maybe -- sorry to take over from you but if somebody
has some views on that?
>> Dr. Kirsten Jacobsen: Yes that would be good.
Dr. Kanabrocki?
>> Dr. Joseph Kanabrocki: Yes.
So again I think, you know, to always consider biological
containment, some element of biological containment when
possible and to use attenuated strains for the initial
experiments if that is scientifically sound.
Ultimately you have to do the ultimate experiment, I think.
But maybe you don't have to do or maybe that's the last
experiment you do and so some of the, you know, some of the basic
information that can be gathered in backgrounds
that are perhaps not so risky.
>> Dr. Kirsten Jacobsen: Thank you.
Anything further?
>> Dr. Gary Kobinger: I agree.
Actually, this also could open the door
to more testing on vaccine.
For example, with a virus that is not what you ultimately want
to be working with but as a first step.
I agree.
>> Dr. Kirsten Jacobsen: So we're doing well for time.
I just wanted to ask the panel if they had any other things
that they would like to add to fill up this discussion.
>> Dr. Joseph Kanabrocki: Just briefly, again, I think one
thing I touched upon earlier and we haven't really talked a lot
about but code of conduct I think, this is something that
has been mentioned yesterday and I've really observed that for
our select agent program we have a written code of conduct that
our scientists sign and I had a number of them visit with me
in my office to talk about it before they were willing
to put their names on the dotted line, so to speak.
But I really believe that pushing it to that level
establishes a level of commitment that maybe you don't
get if there isn't a signature required.
So code of conduct and establishment of code of conduct
here I think is very important.
>> Dr. Kevin Wolf: I'll put in a summary plug with respect to the
core question of what conditions the research should be conducted
under, which is to summarize what I said earlier, a license
to release the type of technology that we're speaking
about here to foreign persons or outside the United States
is required from the Commerce Department unless that
technology is published or intended to be published, widely
available without publication limitations, is the result of
fundamental research, which has the same intent to make widely
available without restriction concept to it; or is otherwise
within the scope of whatever government funding conditions
exist with respect to the creation of that research.
And if you have questions -- it's a very -- the way I've just
laid it out, in a long sentence, is rather straightforward
but there are lots of details behind it.
We have a significant amount of outreach and education and are
willing to speak with anybody that would like about how to
better comply with the existing regulations, which again
are there as a matter of law and international agreement,
and our website is www.bis.doc.gov,
or my email address is Kevin.wolf.@bis.doc.gov,
so if any of you want to follow up further
on the scope of U.S. export control laws
don't hesitate to give us a call
and we'd be happy to speak with you.
>> Dr. Kirsten Jacobsen: Thank you very much.
Any last points?
In that case I will turn it back over to Dr. Reed
to lead the audience discussion.
>> Dr. Zarifah Reed: All right.
Thank you, Kirsten.
Okay, so I guess we're on to the final session for this morning,
and that gives you an opportunity
to ask our panel your questions.
And just like yesterday if you could just introduce yourself
and then a question, thank you, or comment.
>> Dr. Peter Hale: Peter Hale, Foundation for Vaccine Research.
On the issue of whether future gain-of-function studies
with H5N1 should be conducted and enhance BSL-3 or BSL-4
laboratories, my understanding was that the, and Nancy, please
correct me if I'm wrong -- my understanding was that
the proposal that was on the table -- the HHS/CDC proposal
that was on the table was that for the purposes of experiments
that would increase the transmissibility of H5N1
that H5N1 should be classified as a tier one agent that would
require that those studies be conducted in a BSL-4 laboratory.
Nancy -- am I right or am I wrong?
Isn't that the proposal that's on the table?
>> Dr. Joseph Kanabrocki: I can speak to that.
No, that's not true.
There are tier-one agents -- all of the bacterial pathogens
that are on the tier-one list are BL-3 agents.
>> Dr. Robbin Weyant: Yeah, there isn't a specific link
between the tier-one requirements
and biosafety level four.
>> Dr. Joseph Kanabrocki: Tier one is a -- think of tier one
is security-driven, not biosafety.
>> Dr. Peter Hale: Okay.
Thank you.
>> Dr. Zarifah Reed: Yes?
>> Dr. Dawn Wooley: Dawn Wooley, Wright State University.
Okay, if novel variants are being created that have never
before been seen in nature and then on top of that you're
passing this through animal models, where there could be
further mutations that are unknown, then one cannot say
that there are effective treatments
because that's simply not known.
So rather than try to move these potentially dangerous variants
that are resistant to therapy to a higher level after the fact,
wouldn't it be more prudent from a public health standpoint to
test them at a higher level, and then if they're found to have
effective treatments, then allow them to be studied
at a lower containment level?
>> Dr. Joseph Kanabrocki: I'd like to speak to that, if I may.
As far as I know, none of the studies we've been discussing
are really targeting the neuraminidase here,
and so I don't think there's a reason to anticipate
that something that might emerge
might not be sensitive to the drug.
But the point of all this research is, in fact, to develop
antivirals and therapeutics and I'm -- it's a balancing act
between making sure this work gets done in a timely fashion
or not, and I really am worried that pushing it to level four
is going to slow down the advancement of drugs
and therapeutics and vaccines that are necessary to mitigate
the threat from nature, and that is not under our control.
So, again, there's not a perfect answer here, but I think that if
you -- as long as you do your testing early on as these
viruses emerge and if you identify something that is
in fact resistant, now you move into level four.
This is, I think, a reasonable approach.
>> Dr. Zarifah Reed: Any other opinions from the panel?
>> Dr. Gary Kobinger: I would agree.
I could add also that you know all the level four agents could
be safely handled in an NS level three
like it was done in this case.
There is a lot of added feature in a level four because there's
work being done but, as a matter of fact, if you take Marburg
virus, initially it was working level two just with a mask,
so I agree with you.
>> Dr. Zarifah Reed: Yes, sir.
>> Dr. Gary Munk: Gary Munk from Hackensack.
So the issue that I have and am watching is for
the gain-of-function, if you are truly going to embrace biosafety
and go back and work with code of conducts, what are you giving
as what I tend to feel is the right to know to the laboratory
personnel who are going to be working with these agents
because you want to start off
with a common understanding of the agent.
So there is, as Dawn said, there's great variability.
You're going to start with a select agent or a characteristic
but you're going to be adding this gain-of-function.
So how often do you review with your workers the right to know
the information as it's becoming available through data on maybe
the need to go back to codes of conduct or practices?
I might agree that collapsing from a four to a three, you're
going to be prudent in managing the questions that might arise.
But people are learning real time.
They're not coming in fully versed.
Some -- you're doing extreme training, but you really don't
know enough about the agents.
So as I said, you're changing the characteristic of the agent.
So I'd just like to address this transparency in the right
to know from going back and educate.
>> Dr. Joseph Kanabrocki: Again it's about communication and
opportunities for discussion of the results and the implications
of those results and, again, what we do is we have monthly
meetings with all of our staff wherein we talk
about these issues.
This is happening monthly.
So it's all about reinforcing what we know, reinforcing what
we don't know, and making sure that everyone is understanding
what their role and what the procedures are in the event
of an untoward occurrence.
In terms of the formal re-attestation, if you will,
of the code of conduct, that's again,
that's an annual event for us.
So this is an ongoing dialogue.
It's not a snapshot in time.
>> Dr. Zarifah Reed: Do any of the other members of the panel
have anything to contribute to that in terms of experience
or other sort of frameworks of monitoring or oversight over
the, I guess, yes,
whether there's adherence or following up.
Yes.
>> Dr. Robbin Weyant: Well, with respect to the select agent
arena part of the regulatory responsibility of a facility
working with select agents is if any of the work results
in a significant change
to the risk profile or their biosafety plan,
they need to adjust their biosafety plan accordingly
and they need to provide their regulator with an updated
biosafety plan and an amendment of the regulations.
So within the regulated space
there are some oversight requirements.
A lot of these, probably a lot of these advances come in little
steps, so I would concur with my colleague here that it's
important that on the ground at the local level that there be
routine updates on where the work is going, so that whenever
a significant change in the risk or characteristics of the work
in a lab occurs that they can adjust their biosafety,
their security plans and then notify the regulator.
>> Dr. Zarifah Reed: Any other thoughts on that?
Okay, next question?
>> Dr. Dennis Dixon: Thank you.
Dennis Dixon from NIH NIAID, and I have a question
for Dr. Lönnroth.
So Anna, in your comments where you were speaking as an
individual associated with the European Commission and funding
decisions for a large number of countries in the European Union
and beyond, you made a comment something along the lines
that you wouldn't want to see publications
and research stifled.
So that's certainly an admirable goal.
I noticed you were keenly observing the discussions
yesterday and this morning, so would you be willing to give
a comparative statement on where you think the stringency
level is in the European area versus United States relative
to the tone of the discussions we've had here where --
on some of the experiments and case studies
that we went through yesterday, for example?
Dr. Anna Lönnroth Sjödén: Okay.
Well as I said we're working not only with the EU countries
in the projects and everyone is aware of the fact
that some countries are less well-equipped.
So part of the objectives in the projects that we're funding is,
let's say, to raise the capacity and also on the safety
and security issues.
It goes without saying, in a way, because in these
collaborative projects everyone is obliged to follow
the national EU legislation and it's not -- it doesn't work like
because we have a developing country then we can sort of
use maybe less stringent rules in another country
to conduct experiments.
It's absolutely out of the question.
So that is -- we're very, very keen on that aspect.
I mentioned the fact that we need, of course, in whatever
measures we take, to make sure that we don't stifle
or suffocate research, which is absolutely necessary
for public health.
It was mentioned many times yesterday as well.
That is a general statement, of course.
It's not that -- it's not to be interpreted that everything
can be published at any price no matter what it contains.
Of course, there could be situations where you have
really, let's say, delicate information
that should not be published.
And we have to -- I think that's part of this very difficult
exercise to better understand what mechanisms we actually have
to put in place so that we can reach a system, let's say
a control system that actually works in practice, that doesn't
harm very legitimate research; that actually needs to be done
at the same time as it provides security.
It's a very difficult issue, and I haven't heard, to be very
honest, I haven't heard from anybody here really a good idea.
And I think we're all confronted with this big challenge, and
we're trying to kind of throw a hot potato between us here.
It was in all the panels yesterday as well as here.
I think I talk to people bilaterally and in the field
and the press as well have the feeling well, this is something
that is so hard no one can actually give a good answer
to how we can solve this.
So I don't have a good answer to you, Dennis.
I'm sorry.
But I think we are fighting with the same problem.
I wish that we -- I hope we see it also in the same way.
What I said also was that we're looking at EU law as it is now.
There are basically five different components.
I didn't have the time to go into what they are because
I wouldn't have had time to explain the system, but there's
national law and there's EU law, and national law cannot
contradict EU law, but that package together, when looking
at that, is good enough, we consider good enough for what
we have confronted today.
I can't guarantee, though, that it will be good enough
for all possible situations in the future.
And that's something we'll have to look at.
>> Dr. Dennis Dixon: A simpler question.
>> Dr. Anna Lönnroth Sjödén: Pardon me?
>> Dr. Dennis Dixon: I have a simpler follow-up question.
Dr. Anna Lönnroth Sjödén: Okay.
>> Dr. Dennis Dixon: Have there been projects that passed peer
review in the European Union that were not funded
because of DURC concerns?
Dr. Anna Lönnroth Sjödén: There is a possibility that products
that power scientific review will be stopped, blocked
definitely, not funded for whatever ethical -- if you take
the broad definition of ethics here,
including say security, dual-use.
There is a theoretic possibility that that can happen.
To my knowledge it hasn't happened because we tend
to enter into a dialogue with the applicants to find
a good way out, and I have not seen an example
where such a dialogue has not been able to produce a result
that everyone can live with.
Maybe it's happened.
We have a lot of projects out there in other areas
but to my knowledge it hasn't happened.
But I'll be very happy, Dennis, to discuss further and compare
our protocols and how we work because I think this is a good
way forward, to learn from each other what worked
and what didn't work.
>> Dr. Zarifah Reed: Thank you.
Yes, next question, sir.
>> Dr. Harold Jaffe: Thank you.
Harold Jaffe from CDC.
There was a question asked yesterday that I wonder if this
panel could re-explore, and the question involved breaches
of biosafety and biosecurity.
We were reassured that in laboratories that handled
tier-one select agents these were reportable.
So I wonder, number one, if Rob Weyant can tell us
what actually is reportable.
Number two, is that the case in other laboratories.
And third, to add to the length of the question,
is this something the public has the right to know?
In other words if I'm John Q.
Public and my money supports as BSL-3+ or 4 laboratory and there
is something dangerous that goes on there, do I have the right
to know that or not?
>> Dr. Robbin Weyant: Harold, I'll start off with the easy
part of your question.
Yeah, there is a system in the regulations,
there's a reporting requirement.
It's called the theft, loss, and release reporting requirement.
And we interpreted that --
we interpret that regulation fairly liberally.
We instruct regulated entities that if they have any incident
where there's any concern at all that there may have been
even a potential theft, loss, or release,
that they report that to us.
And the regulated community has been very receptive to this.
In the last -- since 2003 we've gotten a little over 700
of these reports.
The vast majority of them turn out to be incidents of minor
consequence that are easily contained by the plans that are
already in place at these entities, but there is, yeah,
there is in the regulated community a formalized reporting
program and we also have follow-up activities
that we do in response to these.
>> Dr. Harold Jaffe: Does that include the exposure
of laboratory staff to pathogens?
>> Dr. Robbin Weyant: Yes, sir.
It most certainly does.
Any even anticipated exposure, if you're working
in a laboratory and someone drops a vial,
even if there's thought to be very little chance
that someone may have been infected,
we strongly encourage, and some would say we require,
that to be reported to us and then we do the follow up.
>> Dr. Gene Matthews: As general matter the transparency
and the sunshine is better over the long haul
for the credibility of any kind of publicly funded research
or any private entity as well.
The limitations in the non-public sector, you know,
is sort of the trade secret in that issue.
The limitation in the public sector is the privacy of the
individual, so if I drop the beaker I don't know that --
and my family had to be tested and whatever the results
of the testing came out, then you get into some kind
of HIPAA-type privacy issues.
But, in general, not only is it smart science, it's good
politics, and I think it's good biosafety because if those --
that information is publicly available then that makes
the organization much more attuned to react to
and head off and prevent future occurrences
because it's in the public domain.
>> Dr. Zarifah Reed: Any additional perspectives on this?
>> Dr. Joseph Kanabrocki: So again I would just add that yes,
the -- you know, we do require this reporting and it is
something that from my experience we get, whether it's
a real genuine exposure or a potential exposure,
this does come to us.
We, in turn, review this during our monthly meetings with all
of our staff, so it's reported throughout the laboratory
at that level.
It's also discussed at IDC meeting and our laboratory
is located on the campus of a national laboratory and I attend
a weekly meeting, a safety meeting, with the staff of the
national laboratory and we report any of our incidents
in that environment as well.
I also am aware that I know of one national lab, level-four
laboratory that actually posts their exposures
on their website.
So I do agree.
This is a public right to know.
I think it's part of, again, educating the public about our
capabilities and how we respond to these things and, in fact,
the genuine biosafety risk associated with it.
>> Dr. Zarifah Reed: Thank you.
Yes, sir, next question.
>> Dr. Richard Henkel: Yeah.
My name is Richard Henkel.
I'm with the CDC Select Agent Program, and I have a question.
We are really talking here when we talk about BSL-4 and Ag-3
and enhanced-3 about biosafety, and those really, that really
addresses unintended releases.
That's accidents is the concern there.
That's what you'll get by moving potentially up or down for some
reason, but I'm not sure that's the solution.
Has any thought -- but there's the intentional release
component, which is not directly related to the biosafety level.
It's more like someone said related to the tiering.
Has there been any consideration to possibly upgrading security
issues with this particular subset of the H5?
>> Dr. Zarifah Reed: [unintelligible].
>> Dr. Joseph Kanabrocki: So again, what we've found is
the code of conduct is immensely helpful here because part of the
code of conduct is that everyone is responsible for reporting
any suspicious behavior, any security breach, any spill,
any safety incident, whether it happened to them
or not directly.
And on top of that we do have CCTV and this is something that
all the investigators are aware of, and so I think that really
kind of supports the idea that you better report it
if something happened.
So we've had incidents persons, investigators, have come to me
with concerns about behavior of certain individuals in
the laboratory and we've, on a number of occasions,
had to sit down with individuals.
You know, some of these things are, in an isolated incident,
as an isolated incident are relatively minor, but when you
see a number of things over a period of time and it's always
the same person you have a problem.
So in order to keep, even just to keep morale high,
I think it's important that the institution respond.
So we've actually -- we've for those, those lack of cooperation
I guess you would say, we've actually removed a person
from our select agent program.
There was no obviously, you know, any obvious problem.
It was really a question of not rowing in the same direction
as the rest of the team.
And it was really hurting the whole program.
And so we removed that individual from that program.
So it's not perfect.
You know, the insider threat is very, very difficult to
mitigate, in particular with an organism that replicates,
and so it is not perfect.
As you know with the select agent program we also have
inventory requirements, so I think those things help, but --
so we try, and I think so far, so good.
But we've certainly given it a great deal of thought.
>> Dr. Zarifah Reed: Yes, sir.
>> Dr. John Parker: Good morning.
My name's John Parker.
I'm from Science Applications International Corporation,
but in my previous life I commanded Fort Detrick.
So I'd like to make a comment and then ask a question.
There's been some discussion about community need to know,
and I agree that that's very important for the community to
know what you're doing and how you mitigate
and how you keep them safe.
But it can't be a single message because communities change and
my experience at Fort Detrick is that I've worked
with a community that has lived with bio-containment and very
interesting research for years and years and years but you
can't depend on going out once and explaining what's going on
because the reaction in the community comes and goes,
year to year.
One or two years you're the biggest employer in the
community and the next year they sort of want you gone.
So working with your community is very, very important, but
don't think it's a one-time thing and make sure you have --
I say it needs to be intense.
Never let it fall off the shelf.
That's my comment.
Now the question is that as I listen over the past two days
as we debate, you know, the biosafety and surety and where
gain-of-function research should go, and terms like BSL-3
enhanced and everything, are we dipping our toe in the water on
the road to saying that there's no need of BSL-4 anymore?
>> Dr. Zarifah Reed: Any of the panelists
would like to take that?
Dr. Kobinger? [laughs]
>> Dr. Gary Kobinger: That would be me without a job.
So, I mean, what am I going to say?
I -- no, I there is a need for them and maybe there'll be a
condition found even with H5N1 that will, you know, directly
lead to the decision that it should be done in level four.
Right now in Canada it's a level-4 agent as is 1918.
So, no, I think the need is definitely there and thankfully
we have attained that level as a step up if there's a need
from work that is being done in level three.
But at the same time there is this tendency sometimes to push
everything in four just because it's safer, and I think this
is not necessarily the right approach because, again,
it slows down a lot of the work that can be done.
The community that can -- that have access to those labs is
very small and if the work can be safely done in three or in
two, then it should be done in three or in two so that there's
more people, more brain, more hands into solving problems.
But, I mean, the day we close it and we put the key in the door
I'll be happy because it means that all these viruses will
have, in my view, treatment and preventive measure
and all this, but in the meantime...
>> Dr. Zarifah Reed: Dr. Harper?
>> Dr. David Harper: Yes.
Thank you.
Just a brief response on the dipping a toe in the water.
I think it's not an issue of dipping a toe in the water.
I think on this one, as colleagues have said,
it's a very reasonable risk-based approach.
It's a risk assessment and then whatever appropriate
and importantly proportionate risk-management measures need
to be put in place -- that's the decision that needs to be taken.
So that was just a brief comment.
But a comment on your comment on the community issue, if I might.
And I fully agree.
I like your -- the way you described -- you moved I think
from communicating a message to the community into working with
the community, which I think is absolutely
the way that we see things.
I'm really pleased to say that it's long since passed the time
where so-called risk communicators felt that somehow
if you find the right words it's an on/off switch
and you can communicate.
Well, we all know that that is not the case.
This is an ongoing dialogue, a relationship.
It needs to be the right environment in which to have
that working relationship or communication relationship,
and I think the point that you make
is absolutely at the heart
of how we, as scientists, as public health professionals,
engage with the community and having community-centered
public-health policies is absolutely where we should be.
Thank you.
>> Dr. John Parker: With your permission,
may I say one more thing?
>> Dr. Zarifah Reed: Yes, go ahead.
>> Dr. John Parker: If we're not dipping our toe in the water,
and I agree, we probably are but we haven't dipped it yet,
and your comment, Gary, was very good that we have judged this
on the basis of the risk of the experimentation
and the risk of the result.
But outside of this room there's a lot of people that when you go
to the Internet, which most people will go to and they'll
type in BSL-4 and they'll see a definition, okay?
Or BSL-3, and the discussion of the risk of the work is absent.
So I think we have some work to do, that if we're going to look
at our individual experiments and what we're doing and placing
them properly in a biosafety atmosphere, we need to do
a better education about what is risk assessment and how risk
assessment defines level.
>> Dr. Zarifah Reed: Thank you very much for the comments.
>> Dr. Gary Kobinger: I completely agree and I think
this is why the comments are very important that were
mentioned to come up with strategies and ways to clearly
express what is the environment and why it was selected
as a correct environment for a specific work.
I think this is a ...
>> Dr. Zarifah Reed: Next question.
>> Veronique Kiermer: Veronique Kiermer,
with Nature Publishing Group.
My question is going to focus on biosafety, and I appreciate that
this discussion here is really happening at the level of
funding, which is exactly where this discussion should happen.
But you've been talking about communication.
There has been concern expressed saying that it's not necessarily
the work, the biosafety conditions in the work that is
done by the world leaders that is of concern, but perhaps when
the same type of work is being repeated in circumstances where
actually necessity is driving the research.
I was wondering if you see a role for journals in increasing
the transparency about biosafety, and I'm thinking that
when the Kawaoka paper was published there was a fairly
detailed statement in the methods section detailing
some of bare safety measures.
Some of them were BSL-3;
some of them were what was making BSL-3 enhanced.
And we've been wondering whether this should become the norm
for this kind of research and perhaps other kind of research.
But in the spirit of doing a risk-benefit assessment, I think
I realize this is an approach that really has limitations.
We're talking about a few paragraphs.
We're not talking about a 20-page paper.
We're talking about something where standards are not defined,
and so is there a risk that we would be focusing attention
on a subset of issues that may not be the most important?
Is there a risk that in areas where biosafety regulation
is not as well defined, we would be sending investigator
on a goose chase that would stifle publication?
I would really welcome your opinion about the benefit
or the risk of such an approach.
>> Dr. Zarifah Reed: Somebody would like to address that?
>> Dr. Joseph Kanabrocki: I support it.
I think it's very important.
One of the -- during the NSABB review of one of the two
manuscripts one of the requests made was that information about
biosafety measures and biosecurity measures
be included in the manuscript.
I think you cannot communicate that enough.
But I also think we have to communicate the value
and the importance of the work.
And we don't do that well enough.
And so I very definitely would welcome more sunshine,
if you will, on those aspects of our work.
Thank you, yeah.
>> Dr. Zarifah Reed: Yes.
Next question?
I'm sorry.
Dr. Weyant, did you have something that --
>> Dr. Robbin Weyant: Yeah.
I just had a brief comment in thinking about how this issue
relates to the larger issue that we've been talking about
in terms of building a better culture,
a culture of safety and security.
I think that there would probably be tremendous benefits
if the norm of a journal article had in its subject or materials
and methods section a section devoted to what was put in place
to insure that the work was done safely.
That way every graduate student that's working on their
dissertation and going through their bibliography would be
exposed time and time again to this concept.
I think it has certain merit.
>> Dr. Zarifah Reed: Okay.
>> Dr. Daniel Perez: Yeah.
Daniel Perez, University of Maryland.
Mine is more like a comment regarding some of the, what I
see sometimes a misconception, on safety in BSL -- comparing
BSL-3 enhanced with BSL-4.
I mean, somehow there is this misconception that BSL-3
enhanced is less safe than BSL-4, and that's not true.
I mean, that's part of the risk assessment that we do and BSL-3
enhanced, there is tremendous amount of engineering in the
air-handling systems that make it very, very safe to handle
the agents based on the risk analysis that we made.
But somehow in the general public there is this notion
that BSL-3 enhanced is less safe than BSL-4.
And that's a complete misconception, and I think
that's why I think we're having this discussion here on the
safety containment that we should have, because there
is a misconception in terms of the safety
that BSL-3 enhanced provides.
And I think we need to make the message very clear
that the work done under the conditions
that we've been doing it so far is safe.
Another issue is regarding with personnel
and how we control the personnel.
I mean, all of us working with these agents go
through a tremendous amount of effort
training the personnel that works.
There is a tremendous amount of training before people
are allowed to work in BSL-3 by themselves.
In our facility we have a buddy system so no single person can
work by himself or herself.
There has to be always someone in there.
So there are a lot of things that go into this.
There's a lot of thinking that goes into this to train people
to do the right thing.
In addition, you know, in the United States these personnel
have to have FBI clearance before they are allowed to work
and to be in this type of conditions.
So I think we do our homework in terms of who finally ends up
working in there, and the conditions that these pathogens
are being handled, BSL-3 enhanced is really very safe.
There is nothing that BSL-4 would offer
that would make it safer, really.
I mean, if the idea is to protect the environment, BSL-3
enhanced is all we need.
If the idea is to protect the person working with it, I mean,
just having a hose hooked up to the outside air doesn't make it
any safer than a PAPR, okay?
Because that, the hose hooked up to the outside air,
can also fail.
So for the type of pathogen that we use, the H5N1 highly
pathogenic, BSL-3 enhanced is all we need.
We don't need anything safer than that.
>> Dr. Zarifah Reed: Thank you for your comment.
We have time for two questions.
Yes.
Perfect.
Please go ahead.
>> Dr. Rob Webster: I think you all know me and how long
I've been in this business.
Worked from Plum Island to influenza H5N1
and I fully understand H5N1.
I just want to comment on the --
and complement the panel this morning.
This is a fantastic discussion because the comments
from Gene Matthews are so important.
We have got to educate the public on the difference
between BL-3 advanced and BL-3 Ag, and BL-4.
The agent we're talking about, high path AI H5N1
gain-of-function can safely be handled in BL-3 advanced.
On my life's work I can assure you of that.
But we've got to assure the public about this, and we're not
doing a particularly good job outside this room.
And the other thing is that we must put into perspective
the incidents that are occurring in BL-3 and BL-4.
We mustn't terrify the public.
We're being extremely responsible in reporting
every tiny incident.
Let's put it into perspective and not use those incidents
to scare the public.
So this kind of communication is absolutely essential.
Thank you.
>> Dr. Zarifah Reed: Thank you.
Yes, of course, Dr. Matthews.
>> Dr. Gene Matthews: I appreciate your comments.
I would just say that, you know my observation of public health
is that we are almost bipolar in how we communicate over the
whole arc of public health.
So I think we're really being very intentional on how we're
communicating in the scientific community.
But there are plenty of other examples where over the arc
of public health we have been spectacularly inept at
communicating to the public what it is is public health -- duh --
or how it is that a healthy community
is an economically viable community.
We're dealing with at least the two areas.
So this is simply part of the challenge of our DNA in public
health, cultural DNA in public health.
We tend to have blind spots in how we communicate.
And so I appreciate your endorsement that we need
to really be thinking out ahead.
Certainly Harold Jaffe and I were trained by one of the best
intuitive communicators, former CDC public affairs officer Don
Berreth, about how do you explain this, you know,
to his father in North Dakota, what we're doing.
And we've got to continue to discipline ourselves, to pick
our heads back up, recognize the patterns, have our situational
awareness, and how do we communicate to the public,
how do we communicate to the press, how do we communicate
to our administrators and folks doing so.
So thank you very much.
>> Dr. Zarifah Reed: Thank you.
Yes.
Our final question.
>> Dr. David Swayne: Great being last.
Great to be last, I think.
David Swayne, U.S. Department of Agriculture.
I had just a couple of comments to kind of flesh out
some of the other comments, so maybe people who don't work
in high-containment labs will have a better understanding.
First thing, we've talked about BSL-3, BSL-3 Ag,
BSL-3 enhanced, and BSL-4.
And BSL-4, BSL-3 are well-defined as BSL-3 Ag.
The BSL-3 enhanced is essentially BSL-3 with certain
enhancements, and those are either facility enhancements,
or they can be safety equipment enhancements, or they can be
procedural enhancements, and those are decided based upon
risk assessment -- which ones are needed to meet the level
of the experimentation and the agent that are used.
So they're essentially driven by the science to maintain
a certain safety level based on risk.
The second comment, which is about select agent approvals,
and if you are working with high-path AI it's a select agent
and you have to have a select-agent approval
for your facility.
And your personnel have to go through personnel suitability
determinations to be able to work on the agent
in that facility.
But part of the plan that you have to have as a select
agent-approved facility is you have to have
a biosafety-biosecurity plan, and in that plan it has
a requirement for an educational component.
So you have to have a component in education for your employees
who work in that particular facility.
If you make changes to, for example, the agents
as far as transmission or pathogenicity or procedural
changes you have to go back and reeducate those employees.
So that's all part of the mechanism of being a laboratory
that has that select agent approval.
And the final comment and then I'll have a question
is the comment about incidences.
And just so you'll know that if you do have an incidence no
matter how minor you're required by law to report that, and it's
not just a matter of reporting the incident since you have to
do an investigation of what happened, why it happened, how
it happened, and then you have to develop a mitigation plan to
prevent it from happening again,
and then you have to reeducate the employees.
So this is a process that is ingrained in the whole system
of being a select agent and a research lab to make sure you do
science safely and that if you do have a problem or an incident
that occurs that you investigate that and that you develop
mitigation strategies to prevent it from happening again and that
you reeducate your employees and say what do we, as a group,
need to do differently so that does not happen again.
My final is a question to the panel: In talking about
the gain-of-function studies,
and it seems that in the conversation
the biggest issue with these compared to non-gain-of-function
H5 studies would be a change in both the education
of the employees and possibly the occupational health.
So as a panel what would you see would be needed, or necessary,
at that level as far as education or as in the case
of occupational health?
>> Dr. Zarifah Reed: Anyone want to take that one on?
>> Dr. Robbin Weyant: I guess I'll start.
I think in terms of occupational health, I think that folks
involved in this work need to be constantly aware of advances
and changes in availability of therapeutics and drugs that may
be available to be of use.
I think institutions need to make some fundamental decisions
and establish policies based on what's available
and how they'll make it available to their staff.
Those policies may need to be reviewed and changed
as work progresses.
But I think that there definitely needs to be
an awareness of what's going on in terms of the toolbox for
occupational health and that institutions doing this work
need to stay current and up to date on what's available
and make sure that their workers are informed
of what their options are in this area.
You know, I think the policy of requiring vaccination for
seasonal flu is extremely wise.
You know, one of the things that I think should be a concern of
any institution working with these more advanced viruses
is one of their workers showing up in an emergency room
with the sniffles.
And if vaccinating them against the routinely circulating
viruses each year can reduce that, not only it's good for
that person, obviously, but it has greater ramifications
based on the work that they do.
So that's sort of a first cut at your question.
>> Dr. Joseph Kanabrocki: We would probably do the same
things whether we're doing a gain-of-function or not.
I mean, if there was an exposure incident you'd want to test
the strain to be sure it was sensitive to drug and obviously
the importance of that would be heightened in this scenario.
But in terms of standard operating procedures
I think we're already there.
I don't know that it would
change the picture substantially.
Obviously an awareness that there's a potential, that
sensitivity has changed is part of the communication piece.
But in terms of -- your question is about how would you change
your occupational health program and I agree with Rob.
I think seasonal flu vaccine is critical for this type of work,
and I think that's -- period.
Whatever influenza work you're doing I think that's important.
Sorry to be so vague, but I can't really think of a profound
change in our occupational health program
for this specific work.
>> Dr. Zarifah Reed: Thank you very much.
I'd like to just thank all our panelists as well
as the audience for their participation,
and with that I'm going to turn it back to our über moderator,
as Amy's described him.
>> Dr. Robbert Dijkgraaf: Well I think you all join me
in thanking indeed the panelists and the moderators.
[applause]
You set a high bar yesterday but I think you jumped
over it very elegantly and, in fact, you have a rather daunting
job, because within an hour we will be back here.
You will have to summarize this discussion.
We are now breaking, on the program is called an early
lunch, a late coffee break.
Before we do that, three practical messages: First,
again, just as mentioned yesterday the lunch options
include a cafeteria here in the building directly
up to the stairs.
There is a convenience store in front of the cafeteria and you
can also go across the street to the cafeteria
in the National Library of Medicine.
Secondly, if any of you need a taxi, be sure to sign up at
the register desk, registration desk here just outside the hall.
And finally, and this is for all the moderators and presenters
and panelists, so basically everyone who appeared here
on the podium.
We want to get a group photo and so please gather just directly
now at the staircase at the right if you exit the hall
direct -- at the right for a group photo.
And then I'll suggest we all be back here at 12:25
for the final session.
Thank you.