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Dr. Michael J. Selgelid: So, again, I'm Michael Selgelid.
I'm the deputy director of the Center for Human Bioethics
at Monash University in Melbourne.
And I'm co-moderating this panel with Dr. Dave Franz who's
a NSABB member based in Frederick, Maryland.
And this panel is on "Discussion of science and security issues
utilizing an article on a SARS-like virus
as a case study."
And the panel will begin with a presentation by --
Dr. Dave Franz: We'll call the panelists up.
Dr. Michael J. Selgelid: Yeah.
The panel will begin with a presentation
by Dr. Mark Denison.
And we have panelists -- and Dr. Denison is at --
based at Vanderbilt University in Tennessee.
We'll have panelists Dr. Murray Cohen, who's an NSABB member and
the president and chairman of Frontline Healthcare Workers
Safety Foundation in Atlanta, Georgia; Dr. Za Hussein Reed,
who's based at the Regional Emerging Diseases Intervention
Center in Singapore; Dr. Herawati Sudoyo, who's the
deputy director of the Eijkman Institute for Molecular Biology
in Jakarta, Indonesia, and the president of the Indonesian
Biorisk Association; Dr. Jeffery Miller, who's an NSABB member
based out of the University of California, Los Angeles;
and Dr. Masayuki Saijo, who's the director of the
Department of Virology, National Institute of Infectious Diseases
in Tokyo, Japan.
Dr. Dave Franz: And with that, I think let's start with the
presentation by Dr. Denison.
Welcome.
Dr. Mark Denison: Thank you.
I very much appreciate the opportunity to be here.
I want to thank the organizers and the moderators for this
particular honor to be present.
I also want to thank all my co-investigators, particularly
the students and post-docs who performed this -- Dr. Becker,
Dr. Graham, and Dr. Donaldson, along with my chief collaborator
ad senior co-author, Ralph Baric at UNC Chapel Hill.
It's a pleasure and honor to be here and to talk about our
research and the important questions that were the focus
of this research.
Well, really the question -- the overarching goals of the
workshop are really precisely those that we incorporated into
our design, implementation and communication of our work.
As a -- coming from Music City, U.S.A., as a humble country
virologist, I'm also a little daunted by this, sort of the
environment, but I'll do my best to try to be cogent and also
brief or to abjure what Pascal said, which was "I have made
this letter longer than usual because I lack the time
to make it shorter."
So I will do my best to really be concise in this.
First of all, why do we pursue this path?
I think philosophy has a little
bit to do with our discussion, actually.
I think pursuing this initially was because of my initial
background and training as a pediatrician and specialist in
infectious diseases and with my earliest actually independent
work being in Kenya in a hospital there
in a resource-limited environment where I was
profoundly influenced by my exposure to children with
vaccine-presentable diseases that were still prevalent,
and whooping cough, tetanus, measles, as well as endemic
diseases like malaria and TB.
Now, those may not be the topics here, but they really informed
my concept of what happened in terms of trying to understand
and control these.
And the commitment to the career then was predicated on really
the capacity to try to understand,
diagnose and treat these diseases.
And my immediate concerns, both during my training and
subsequently as a specialist in this area, is really the things
that we don't know and we can't learn because we don't have the
capacity to grow them or to understand them.
So the very, very, very fundamental biology associated
with that and going in to a parent in this day and age,
even now, and saying to someone with an encephalitis or some
other cause, "I don't know, I don't have an answer,
it's not known, I can't do anything,"
is particularly galling and feels
like 1900s of medicine for me.
And that was a particularly frustrating environment, and
it's continued to be that way.
And I rail and push against that particular frustration.
In that context, I've always believed with many others that
perhaps one of the most seminal and transformative scientific
discoveries of the 20th century was, well, potentially dual use.
So, let me quote in part, and I'll extract or redact the name
of the virus.
Most of you will know what this is, of course.
The isolation and typing of blank virus for man has been
in past a laborious and time-consuming procedure since
it depended on the intracerebral inoculation of monkeys.
Therefore, we sought to determine whether the agent
could be recovered from feces or suspension of spinal cord.
The presence of a cytopathic agent was revealed by
differences in pH that occurred in these tissue cultures
as compared with control.
Subsequently, the antigenic type of the agent
was isolated and determined.
Indeed, when large amounts of virus are present, it has been
possible by simultaneously carrying out both steps in the
system to demonstrate the virus in feces within 48 hours.
Well, if I ask you all to tell me what that was, you would tell
me that that was a quote from the Nobel acceptance speech
of John Enders, Frederick Robbins, and Tom Weller
in December of 1954 and their discovery of the
use of tissue culture to grow polio.
In that seminal presentation, they also described that they
had discovered at the same time that those same cultures were --
could be used grow mumps.
They could be used to grow varicella virus.
They could be used to grow other viruses as well.
And so -- and they make some fascinating comments about that
at the end.
So, I couldn't help but think in that context that this could
be concerned to something that suddenly had changed the
trans-species potential of many different viruses and the
ability to grow them.
And so I put that in the context of what we're interested in and
what we're discussing here because I think that
fundamentally changed really the history of vaccinology, the
history of infectious disease and our capacity to really be
sitting here and even having these conversations today.
And so, what we rail against is, in some sense, is the unknown
as we try to investigate these things.
And so, I want to quote another luminary who said, "There are
knowns and there are things that we know.
We also know that there are unknowns.
And we know that there are things that we don't know.
And finally, there are unknown unknowns.
There are things that we don't know that we don't know."
And, of course, you all know that that was stated eloquently
by Donald Rumsfeld.
And, but where I might differ for a moment in my English major
background -- I think I favor it from a scientific background
in the sense of it's the -- it's areas that we can't really
understand until we are in a position to try
and investigate them.
So I'd like to put that in the context of our discussion.
So, I guess I want to then really tell you why we came
to what we did and where we went from there.
First of all, as I said, our commitment to -- my overall
commitment to understanding these complicated questions
of when there's an agent that we can't study.
And coronaviruses were pretty good at that, because human
coronaviruses that cause respiratory infections are
notoriously difficult to culture and require extensive passage.
And once you're working with them, you're not really working
with a primary agent anymore because it's been
modified so much.
I was, at the time this happened, I worked with
coronavirus for 20 years as the SARS epidemic came out with
its fairly innocuous low-grade humble virus family that
suddenly had a violent rogue serial killer lurking
in the background.
And so, to try and to really understand what had happened --
now, fortunately SARS grew in culture, but what couldn't be
answered from those kinds of questions was the issues
of where did it come from, how did it make
a transition and become
a human virus, how did it interact with human cells and
copy itself inside those cells; so how did it replicate, why did
it cause more severeness in adults, how did it have such a
significant ability to spread in certain populations.
So, trying to understand that predicated trying to understand
where it came from.
And where it came from was based on two excellent articles in
Science, suggested strongly that it came from bats,
from a bat background.
So, the issue, however, with that, with many coronaviruses
and with many, many other important viruses I'll -- to
name a few such as the human noroviruses, which are a very,
very important virus group, are very,
very difficult to propagate and culture.
And parenthetically, I wonder if these discussions or concerns
would be raised if it were about the capacity and ability to
robustly and easily have grown hepatitis C early on in its
epidemic stages.
So, we wanted to understand these things and we wanted to
try to understand prospectively rather than in some kind of a
viral archeology or back-gazing how a virus could have come from
a bat and come into humans.
So we could have tried to look backwards and try to maybe make
sense of mutations, or we proposed that it was important
to potentially try to look forward and see if we could have
a platform for recovering a non-cultivatable virus and
thereby using that to test the steps by which
a virus might move forward.
So, that question, I believe, is a -- and still believe --
is a fundamental question with any zoonosis.
Zoonoses, as we all know, are increasing in their frequency.
So that was the rationale for conducting this virus.
So what has then informed us?
And I want to talk now just very briefly about the science,
and then a minute about the communication of the science.
First about the science -- what did we do?
Well, we had the capacity already for making these viruses
by reverse genetics, segmented -- it's non-segmented virus, but
we segmented the cDNA pieces, put them together.
This was the exceptional work of Boyd Yount
and Ralph Baric's lab.
It's, I believe, brilliant.
And we -- that was already in place.
So when the sequences were published on bat viruses,
basically from sequencing of bat feces and other secretions,
no viruses were available.
No RNA was available.
They were impossible to study.
We looked at those sequences and through a group consensus came
up with a mechanism for identifying a consensus gene
sequence that then we could have synthetically made.
It was not SARS.
It was a different bat virus but likely related to the
virus that caused SARS.
And so then we had those pieces synthesized.
And those synthetic pieces then we could ligate together as
cDNAs, generate an RNA genome, electroporated that into cells
and hopefully recover virus.
So, in that context then were many, many steps.
How did we -- how and why did we start?
Well, I had the advantage of history and the advantage
of reading Dr. Ramshaw's work and other work and seeing the
kinds of positive and challenging
things that it had engendered.
And thus we were in a position to think about this.
I was also chair of the Vanderbilt Biosafety Committee
at the time.
So we basically engaged in communication and identified who
were the stakeholders and who would care.
So who, at the outset, would be interested
in being informed in this?
Certainly, NIH Program, certainly our own institutions
from the level, all the way from the level of biosafety through
the -- through our communications officers, and
once that happened, through the vice chancellor and the
chancellor [laughs] were interested.
As working during the SARS epidemic with different
organizations such as the Defense Threat Reduction Agency
and the WHO, we're also aware of their general interest and
surprisingly their general willingness to try to understand
complicated questions and to try to help engage.
And so we communicated with friends at the time who were
engaged at the CDC and the Respiratory Diseases Branch to
inform them.
We differentiated always between who we felt we needed to inform
and who we needed to ask permission or to get input from,
so, NIH Program, CDC Respiratory Branch.
We convened a group of our dual biosafety committees
at UNC and Vanderbilt.
We ask for input also from a Policy, Ethics and Law Core at
Duke, that was established as part of one of the Regional
Centers of Excellence.
And as projects were going forward, we made time points in
terms of when we'd communicate with NIH Program or with the CDC
or with anybody if we felt that we were -- if there was
a surprise or we felt that something was getting
out of hand.
We also maintained conditions that were absolutely required
for -- that we would use for SARS.
So there was -- and we made -- we didn't change security issues
at that point because we felt the bio -- at that level,
the biosafety that we were using for SARS also represented the
best security for what we were doing.
So, I won't go on in any other detail that will come to a
conclusion on this, but we also finally had a -- we convened a
session at the time the manuscript was submitted.
Where the manuscript was submitted, then we convened a
group of all of these interested individuals.
We asked for involvement from NIH who appropriately demurred
and said, "We do not believe it's appropriate for us to be
involved in the decision making, but we would like to be informed
of any decision that you come to and what the process is.
And then, we established some guidelines that we would use
in terms of response for publication at different levels.
So if we were told we couldn't, if we were told we shouldn't,
if we were told that other organizations needed
to be involved, how we would escalate
and what additional information we would ask for.
Surprisingly, in that process, there was great consensus and
unanimity about the value and importance of the research and
how these processes that were in place were
appropriate for managing.
Was there anything we did not publish?
Well, there was one thing.
And that was -- we published the sequence of the virus,
but we didn't the sequence of the primer termini
of the plasmids because we felt that that is
information that any credible investigator would want to get
from us anyway, and we would need to help them with
the art as well as the science of reproducing this work.
So, would it prevent reproduction?
No.
Would it make it so that there would have to be due diligence
or it would be harder?
Yes.
So that kind of gives you the kind of the framework of what
we're working on.
We believe that this kind of work is important.
I think it's a legacy and building on the shoulders
of giants, the concept of growing
and cultivating these viruses,
so the fundamental principles in place and the capacity to study
viruses and their movement from other species to humans, we
believe is a fundamental important principle.
And with that, I will stop.
And thank you all for your attention.
Thank you.
[applause]
Dr. Dave Franz: Thank you, Mark, for that nice summary.
The paper that he was discussing was published in PNAS, the
Proceedings of the National Academy of Science
in 2008, I believe.
Let's go to the panel and discuss some of the issues that
might fall out of this case study.
The first would be what role should an institutional
biosafety committee or reviewing body, a consultative group, have
in evaluating research with
potential biosafety, biosecurity concerns?
Dr. Sudoyo, would you have thoughts or comments on that?
Dr. Herawati Sudoyo: Thank you, yes.
I think the role of the institution on biosafety
or biorisk committee is very, very important.
But whether it is -- the institution is actually prepared
to do some evaluation from the biosafety point of view because
the concept of biosecurity is new.
Biological safety concept is -- has been recognized widely,
although I could say that it might not be implemented fully.
But biosecurity concept is definitely new in the country.
So, we have to actually -- the concept has to be introduced
first to the community.
The dual use research of concern also should be evaluated.
So I think, if you ask me, the role, the role is actually they
play important role, but we have to give them, the community
knowledge on the biosecurity and dual use research
of concern, of course.
Thank you.
Just an added question.
Dr. Dave Franz: Thank you.
How do you feel the scientists would -- would they accept this
kind of a role for the biosafety committee easily?
Dr. Herawati Sudoyo: They accept the biosafety because biosafety
is kind of actually protected the human being and environment.
But concept of biosecurity, well, it's some -- majority do
not accept that, frankly.
Dr. Dave Franz: Thank you.
Dr. Reed, do you have any further thoughts on this, or?
Dr. Za Hussein Reed: Thank you.
I guess I can just add on a little bit more because
I couldn't agree more with Dr. Sudoyo that maybe one model
-- I think Dr. Selgelid mentioned it earlier too,
is when we consider the time it's taken to get us to be more
sensitized to human subject research and the lessons that
we learned and the effort that's gone into formation
of institutional review boards and ethical review committees.
And that was not something that happened overnight, clearly.
And it's taken -- there are lots of events and historical events
that have happened that has helped to form that.
And it's formed in one country or in one situation.
And in order to percolate that to the biosafety committees
or other committees that take on oversight or review of research,
I think you do need to have this educational component or
sensitization component.
Those of us who have had the privilege of being on ethical
review committees, and reviewing science, I think that the review
of science, issues of concern, the quality of science, it's
probably better to put the dual use concerns embedded into that
as a paradigm versus to have that completely separate if
you're trying to reach out to scientists and researchers,
actually conceptualizing and principle investigators who are
conducting such research.
So I -- that would be my suggestion.
Dr. Dave Franz: Thank you for that, Za.
I think your point about human use and being in an analogous
situation reminds me of the Animal Welfare Act when that
was implemented in the U.S.
It was very much the same situation.
And in all of these situations, I think the importance of
leadership in our laboratories comes to the fore, leadership at
the top as well as leadership at the departmental level and so on
in implementing and underscoring the importance and the relevance
of these kinds of new situations.
Dr. Michael J. Selgelid: So I think Dr. Reed's
comments lead perfectly to our
next question, which is how prepared are institutional
biosafety committees to make determinations of dual use
research of concern and to provide guidance for research,
design and evaluation?
Dr. Saijo?
Dr. Masayuki Saijo: Thank you.
To -- let me introduce the situation on the issue of dual
use research concerning Japan to all of you.
In Japan, biosafety and biosecurity issues are well
recognized among the scientists, especially in the field
of medical and infectious disease scientists.
But the issue of dual use research concern is still not --
is not well recognized as important issues.
So, to tell -- if -- in our institute, we are publishing --
it's a paper -- Japanese Journal of Infectious Diseases.
But at this moment, we do not have a criteria for the
publication or rejection of the paper based on the dual use
research of concern.
And also, our institute, NIID, has strict regulations on the
biosafety and biosecurity issues that the discussion on the dual
use research of concern is the right, than the issue of the
biosafety and biosecurity issues.
I want to promote the importance and importance to recognize the
dual use research concern to the public, to the society of the
Japanese scientific peers.
And what I want to emphasize is that the research activities,
especially for the medical and radionuclear issues, chemicals,
must be conducted based on the public trust.
We never forget this fact.
So, I think that the balance of -- between the scientific
interest and the benefit and harm to the public
should always be considered.
For these purposes, I think that each institute or universities
must establish the committees to evaluate the dual use research
concern problems on the research works.
And finally, I want to emphasize the importance of the education
of the young generation who will become the scientist in the
future, not only for the technical or ethical issues or
scientific interest, but also we have to educate the young
generations on the issue of the ethical problems, including the
dual use research of concern.
Thank you.
Dr. Mark Denison: May I make a brief comment on that?
I was, as I mentioned, the chair of the Vanderbilt Institutional
Biosafety Committee at the time all this was going on, so
obviously I had to recuse myself
from their direct considerations.
But we had an exceptionally good community involvement,
and we had a committee that had worked together for many years
and actually enjoyed it, believe it or not.
And so they stayed together.
But the issue was they felt that this -- the concept of
evaluating security in a prospective fashion, there are
two aspects of it.
One is issue of security, physical security, right, of
something you're actually doing.
And the second one is security implications, which is outside
the venue of almost everyone, including myself, because it's,
again, I don't know what I don't know.
In other words, I don't know what the security implications
are because I'm not in a clearance mechanism to have
information related to what they might be.
So it's difficult for me to predict them
and to understand them.
And so, but from the position of the committee, they were
profoundly interested in issues of safety.
And our education is around the concept that increased safety
equals increased security but increased security does not
necessarily indicate increased safety.
And so, as a primary goal, I think the Spanish word for this,
"bioseguridad," which incorporates both terms,
is a more integrative term that I think reflects how we try
to approach it as part of our committee.
So they felt not good about that.
That's why we got a consultative role of people, particularly
from the PELC, the Policy, Ethics and Law Core
and from other individuals.
We invited anyone who wanted to participate in that process
to help with the committee.
And also we used terminology which was I think more helpful
to the committee, like what scares the hell out
of you about this research.
Okay, what scares you and why?
What would you -- what is it that you think that
we should do differently?
Why are you scared?
What movie have you seen?
What is it that's scaring you?
What are you acting on?
What information do you have?
What information do we need for you to make
a more informed decision?
So the process of evaluating our research was actually the actual
process of educating the committee in terms
of being able to do this.
So I would never participate in their determinations, but I did
participate in their discussions and in the process to try to use
this as a case to actually go through the educational process.
And I think it almost requires that, because these things being
discussed philosophically or ex vacuo are just really, really,
really difficult to get your minds around as a group.
Dr. Michael J. Selgelid: Thank you for that, Mark.
The next question I have is what systems have been established
in countries in the region to regulate biosafety
and biosecurity issues?
How is the potential for dual use in research evaluated?
We've covered some of those points, but do you have anything
to add to that, Dr. Saijo?
Dr. Masayuki Saijo: Yeah.
At this moment, as I mentioned, the dual use research of concern
is not well recognized in Japan.
But recently, we have started to discuss to implement
the regulations based on the dual
use research of concern among
the biodefense committees funded by the Ministry of Education,
Science and Technology.
And we have -- I think that we will declare the code of conduct
based for the dual use research of concern from the Japanese
Societies for Biology or Japanese Society for Vaccinology
or Microbiology or Academy of Science.
So, in Japan, I think that we promote this issue,
dual use research of concern to the public or to the scientist
working in the field of microbiology or other medical
sciences.
Thank you.
Dr. Michael J. Selgelid: Thank you.
Any other comments from the panel, either on that question
or on Dr. Denison's -- follow-on to Dr. Denison's?
Yes.
Dr. Masayuki Saijo: I have, frankly, another practical
question to Dr. Denison.
The recombinant virus produced from a Bat-SARS-like coronavirus
was -- is biosafety two or three or four pathogens?
How high the biosafety level for the recombinant virus?
Dr. Mark Denison: So, a couple comments.
One is, you know, SARS-like is a nom de guerre, right.
It's sort of a pseudonym.
It's not SARS.
It's a Bat coronavirus.
Now I'm not questioning your question.
I'm saying this is what we've dealt with.
This was a virus that lived in the closely related -- very
closely related family and allowed us to do this work,
which we were very fortunate at.
So, we established, even though there was absolutely zero
evidence that this was transmissible to humans, that we
would maintain it to BSL3 under all conditions, that if there
was any evidence in culture that it had increased virulence
compared to SARS, that we would stop the work until we had had
further consultations with NIH Program and other individuals
who might be -- we might consider stakeholders.
So we set up -- we established time points along the way to see
if this was -- if this was maintaining itself
in a good way.
We also -- what we did is we also, as I mentioned, this
algorithm, that infection does not equal transmission, does not
equal transmissibility, does not equal maintenance
in another population.
We often view infection as a high jump.
We use that term unfortunately -- "jump" -- and probably a much
more valid term would be 440 hurdles, right,
where someone is falling down at every hurdle.
The virus has to get over a lot of obstacles.
And so, we established the guidelines in terms
of incrementally trying to look at this and seeing
if at any stage
we were seeing a change that indicated to us that this
indicated that we might have evolved something that could
represent a human pathogen.
And so, that's -- we -- it was a single process initially in
terms of establishing at BSL3.
We will not come out at BSL3 with this virus.
On the other hand, we also set positive time posts that said,
at this point, we will stop and reconsider our work
independently before moving forward with it if we feel like
this direction is changing.
And so we're continually evaluating it.
It was sort of open source communication in a long way
and partly because we were
-- we had a lot of hubris and we said
we could do this and no one else can beat us to it, so we felt
comfortable with moving ahead with our work.
But that wasn't the reason we did it, but we felt that we
could move forward with the work in any case.
Dr. Michael J. Selgelid: So, dual use research
of concern raises
issues of publication.
In light of this case study, what is the best way to approach
journals about a publication based on research of potential
dual use research of concern?
This question is open to anyone on the panel.
Jeff?
Dr. Jeffery Miller: Mark, it seems as you were describing
your experience and the decisions and the consultations
you held about publishing and how much and when and where and
whatnot, that to some extent you would be chastised for not
having expected the unexpected, yet that belies the very nature
of scientific research.
I mean, we -- that's what makes it challenging.
That's what makes it fun.
And of course we expect the unexpected.
That's research.
I'm wondering -- you know, the question specifically is about
at the end stage, but when you're going through the
research itself and you're having hopefully the "Aha!"
moments and hopefully not too many of the "Oh no!"
moments, beginning to formulate where this might really be going
and what you might be publishing and how many pieces this might
turn out to be, you know, and that sort of thing.
Where in that thinking process, as you're discovering, as you're
making sense out of your data and planning your next steps,
just as you're thinking about when is the time to engage NIH
or research sponsors or colleagues, as your experience
was, is that parallel to -- is that a first and then subsequent
to the notion of the publication part?
Or is that all one basic consideration on your
part as research?
Dr. Mark Denison: I think they're absolutely continuum,
and I think of the nature of this kind of research that that
engagement is -- I don't see what the disadvantage
to that engagement is.
We ask for review and comments all along the way.
We set up guidelines at the level of publication,
so when we finally submitted for publication, we did review, but
I felt the -- I felt the peer review was absolutely, you know,
sine qua non.
It was essential and we had to maintain the integrity of it.
So I informed NIH that this had been submitted for peer review.
I informed them that if they wanted additional information
or the manuscript, I would call the
-- I would contact the journal
and ask their permission and tell them NIH had requested this
and we would submit it to them.
But at that point, the journal had dominance, I felt like, over
other possibilities of review if we had done them ahead of time.
So we established -- and I wrote a long letter to the program
officer to talk about here's the way that I would do this.
Here's the mechanism and pathways
I would use to handle this.
If you have concerns about this or feel this needs
to be elevated to a different level,
please inform me immediately.
If a group tells me that they feel that this should be
non-published, I would require an explanation.
And ultimately, then, if I couldn't publish my work,
I'd like to publish -- I would like to publish an article that
discussed the mechanism by which redaction or loss of ability
to publish the work was done.
That, I think, is the balance between academic freedom,
the importance of novel research that can't necessarily predict
it in a positive way and the requirements for excellent peer
review and our ability to say that we're willing to forego
something if it's really in the public interest, okay.
So those things are all -- those are all balanced.
But it was a continuum.
And so, at the time of publication, of submission,
we -- I informed.
We wrote a letter to the journal.
We told them of these concerns.
I recommended that if they wanted to write an editorial,
I thought that would be cool and that here's some names
of people, including several people are on the NSABB.
I said call these people, write them, and if you need to share
the manuscript with them, that's certainly -- you have
my permission to do that.
If they feel like a cooperative editorial is good,
that would be great.
And so, I encourage that process because I thought
it would be cool.
Plus, you know, I like the idea of a further and more detailed
discussion of the implications of the work.
Dr. Murray Cohen: Well, if I may, let me ask about
superimposing that process and experience on what our
colleagues from Asia Pacific have described as challenges,
and Dr. Sudoyo, your word was frustrations,
in your own research communities.
Dr. Sudoyo, you said in fact the majority of the researchers
wouldn't even accept this kind of looking over the shoulder,
meddling with, you know, individual researchers'
data and conclusions prior to publications.
What would we need to do?
How could we foster a greater acceptance or at least a paying
attention to lessons learned from the process that
Dr. Denison just described to make it less ominous or less
intrusive to your own researchers
in Asia Pacific countries?
Is there something peculiar, unusual or special culturally or
otherwise in terms of government regulation or whatnot in the
Asia Pacific region that would either block this kind of lesson
learned or perhaps facilitate it?
Dr. Herawati Sudoyo: Yeah, we have conducted a road show
on biosafety, biosecurity and code of conduct.
And before we could actually introduce the code of conduct
on biosecurity to the audience, we introduced the concept
of biosafety and biosecurity and also dual use.
To be able to get people know about dual use,
then we used actually some study cases.
So, when we introduced them, people don't think that they
actually do it -- well, they don't expect that dual use
research of concern as being part of their work.
So it is very difficult, actually, from my experience
in that three road show, to have the concept of that dual use.
I have to introduce them, that some study or the weaponization,
the so-called, I could say that kind of things, because the
concept is not there.
The biosecurity is new.
So you have to actually get people know, all of the life
scientists, all of the researchers about the
biosecurity first, in my opinion at that time, and then introduce
dual use research of concern before we could develop
code of conduct.
That my experience.
Dr. Michael J. Selgelid: Did you have another comment?
Yes, please.
Dr. Masayuki Saijo: I think that dual use research concern issues
should be recognized internationally,
not only in each countries.
So, for these purposes, we have to promote some discussion
issues of the dual use research concern under the international
organizations like -- such as WHO or United Nations.
We have a framework of the Global Health Security Action
Group in developed countries, G7 countries, including Mexico.
And we also discussing about the issue of the dual
use research of concern.
So definition of the dual use is very, very difficult --
important to evaluate the risk of the dual use
for each research project.
So I recommend to promote discussions on the issue of the
dual use research concern internationally or in the Asian
Pacific regional countries or United States
or finally internationally.
Thank you.
Dr. Dave Franz: Thank you.
Those are both excellent comments.
Dr. Miller, if you have a comment with regard to that,
let's go there.
And then I think we have time for one question from the
audience before we wrap up this section.
Dr. Jeffery Miller: I'll be very brief.
There's a lot of discussion about institutional biosafety
committees and the role they might play, but I think what's
particularly instructive about what we heard from Dr. Denison
is that the very thorough and thoughtful process that was
conducted to look at this, the research you described was
instigated and organized by the investigators
and their colleagues.
And I hope that that's sort of a paradigm that we can all move
forward with as a partnership, certainly with regulatory
agencies, et cetera, but also coming from the grassroots,
from the investigators themselves.
Dr. Mark Denison: I don't know -- if I could just comment.
I have found that to be incredibly educational for me.
I mean, I found that the people from the communities, from the
defense community to the analysis community, like DIA,
DTRA, CDC, WHO -- actually, once they understood the details and
why and what the motivations were, were more interested in
being helpful and in trying to understand this.
And it also altered their perception of real risk
associated with this, rather than just presenting the concept
that now we have a virus that grew in one species of cells and
now can grow in the other as opposed to a dichotomous view
that gradations were seen.
So it was educational all around, and it felt like
a collaborative process that involved not just scientists but
involved people who might have had the tendency or the desire
to top-regulate, they rather became sort of more partners.
I'm sound a little "Polyanna" maybe, but it was really the
experience that we ended up having.
Dr. Dave Franz: These are excellent comments, and I think
sort of lessons learned or observed from this scenario.
And again, your last comments, Mark, underscore the importance
of communication, vertically and horizontally and globally with
regard to these issues.
I think it's just so important that we keep talking.
So do we have any questions from the audience?
Yes.
Please identify yourself and --
Janet Peterson: I'm Janet Peterson from the
University of Maryland College Park in the U.S.A.
And I just wanted to say that it would be helpful to the IBCs
to be given tools to be able to review and evaluate dual
use research of concern.
Many scientists, at least that I've spoken with, equate dual
use research with either not being able to do their research
or not being able to publish.
And the IBC does not want to be the ones to tell
them they can't do that.
The IBC supports research and we work with the researchers
to do it safely.
And if you'd give us the tools or give these researchers and
the scientists the education, the information, these road
shows that you're talking about, which actually are a little
reminiscent, I believe, of when the early days
of recombinant DNA research.
And NIH, I believe, sponsored programs and there were a group
of researchers, Dr. Emmett Barkley and Dr. Don Vesley,
among others, who went to different locations and
described this and provided the education.
And I think that would be really very helpful to the IBCs.
Dr. Michael J. Selgelid: So we'll take one more question
from the audience and
then turn to the panel.
Dr. Dennis Dixon: So this is Dennis Dixon from the NIH, and
I'd like to engage Dr. Denison in a response to something we
actually did together through the intermediary of the program
officer, and that is in response to the question about what about
tools, is when Dr. Denison first contacted his program officer, I
suggested that the reference be made to the NSABB tools posted
on the website at the NIH.
And there was an excellent communication tool with a risk
analysis that walks you through the process.
And so, I'd like to ask Dr. Denison if he could comment
on the utility of that tool and how that worked.
Dr. Mark Denison: It was very helpful to us in terms
of identifying what the criteria were that we met.
We made it an active determination to use those
criteria for our determination of potential dual use
of concern, although in parallel in my heart of hearts I think
that it wasn't -- did I necessarily agree that those
really represented a level of risk for our virus,
I don't really think I did.
But nevertheless, we felt that those were established as
guidelines, that we should use those as a mechanism to move
forward with our work.
And so I think they are very helpful.
Another thing that's actually helpful and educational is the
Policy, Ethics, and Law Core from SERCEB, on that site, has
an excellent educational tool as well that
I recommend to anybody.
I'm using it for my students and for people that do RCR.
It's very easy to do.
It's very helpful and very useful.
I'd like to comment also briefly on the issue of tools
for the IBCs.
I find that one ounce of example is worth about
a hundred pounds of road shows.
So, in other words, if there's a case or a case study
or a mechanism to do something that would be even an unknown,
then they're in a position to make judgments.
And finally, I don't believe -- I might be heretical here
-- I don't believe IBCs should be put in the position
of telling someone they can't publish their research.
There shouldn't be a blockade.
IBCs, as we all know, they're funky in the sense that there
are actually guidelines that sort of semi have the
qualifications of regulations in the BMBL.
So it's -- so I think that giving them the potential to
give their input and insight, ask for additional help and
consultation, make recommendations, and make
recommendations that it's out of their league
as well is important.
Because I had a very informed and educated IBC, and they were
profoundly uncomfortable with anything that was at the level
of trying to determine an issue of biorisk and potential
biosecurity implications going forward.
So I think if we can relieve them of that burden and give
them tools that this is a consultation and advisory
capacity and they're not in a position to actually block
research, rather to facilitate the investigators' ability to
achieve their goals, then it becomes a collaborative process.
And that's kind of how I like to view it and would hope going
forward educationally we could do.
Dr. Michael J. Selgelid: Thank you for that.
We probably have time for a quick question
and a really quick answer.
Allan Shipp: This is just a quick comment.
I wanted to also mention there are some educational resources
available on the website of the NIH Office of Biotechnology
Activities, including an educational video and a brochure
that we disseminate to institutions, associations,
that they in turn can disseminate to the investigator
community just to raise awareness about the issue.
Dr. Michael J. Selgelid: Excellent.
I think this last five minutes has pointed out the need and the
value, the need for and the value of guidelines and of
principles and then maybe of even in-the-weeds tools to help
manage the whole process of science and publication
of that science.
So, with that, I would like to thank the panel,
thank in particular Dr. Denison for presenting
this particular case study.
And we are going to take a short break.
And we will return at five minutes after the hour.
Thank you very much.