well welcome everyone this is rick
woychik the director of NIEHS and i want
to welcome
everyone to the 162nd meeting of the
national advisory environmental health
sciences council
so i will have my virtual gavel
and i have just started the meeting so i
also want to say that pursuant to the
government in the sunshine act
all aspects of this meeting are open to
the public except the review
discussion and evaluation of grant
applications
and related information so
with that introduction pat i think i'm
turning over the
the virtual platform to you
all right thank you rick um welcome
everyone
as rick i said glad to have you here um
we want to start as we always do by
going around the virtual table and uh in
letting the council members and our
senior leadership members um
introduce themselves i will call your
name and then i will ask you to you know
say who you are and what your
affiliation is so starting with council
members
jose can you introduce yourself please
good morning i'm jose cordeiro
from the university of georgia thank you
uh lynn good morning i am lynn goldman
and i am
dean at the milken institute school of
public health at the george washington
university hi everyone
thanks um irva i think i saw you on are
you with us
yes i am ah there you are hi herba herze
picciotto university of california davis
i direct the environmental health
sciences center
and shook me home are you available yes
i am
mae hall university of arkansas for
medical sciences
thank you um terry
terry cavanaugh university of washington
and director of our edge
edge center terrific uh katrina
katrina korffmacher i'm the community
engagement core director at the
environmental health sciences center at
the university of rochester
thank you eva i'm edith parker i'm dean
of the
college of public health at the
university of iowa
marla marla perez logo professor of
environmental sociology at
the university of puerto rico mayaguez
and now visiting professor at macalester
college
thank you um trevor trevor penning from
the university of pennsylvania i direct
our p30 environmental health sciences
call center
okay thank you brad brad we're set
washington university school of medicine
okay um sue
dr shenz hi sue schatz
uh beckman institute for advanced
science and technology at the university
of illinois at urbana champaign
thank you um andy she
hi andy sure autism speaks thank you
um uh patrick simon patrick sung
i'm a professor of biochemistry and
structural biology
at the university of texas health
science center san antonio
thank you robin robin tangway oregon
state university
um jalon good morning jalon white news
some founder of empowering a green
environment and economy
llc thank you and bob
bob wright chair of environmental
medicine mount sinai school of medicine
terrific thank you and now our ex
official members bill
good morning it's bill cebulas i serve
ex officio representing cdc
and atsdr and
um suzanne suzanne fitzpatrick
u.s food and drug administration thank
you and do we have andy geller on
not yet okay terrific thank you and now
um
i would like to uh the senior leadership
to introduce itself gwen are you
with us good morning glenn coleman
acting deputy director at iehs
and daryl i am daryl zelden scientific
director dir
thank you uh brian hi i'm brian barrage
i'm the scientific director for the
division of the national toxicology
program
and do we have jan on
okay um and then chris
long was here a minute ago
that jan should be on i
hope if she if she's on just on mute and
you can introduce yourself
okay i'm not seeing her on the list but
i did see chris
are you there chris i just had to step
off
um anybody from senior leadership oh
gary i'm sorry yes
dr allison sorry good morning everyone
i'm gary ellison i'm acting director of
the division of extramural research and
training
in iehs all right have i called everyone
who's on senior leadership
don't miss anyone terrific okay well
thank you everyone
um rick i'm going to turn it back over
you for a special introduction
great thanks pat so i would like to
introduce bill elwood
who is a health science administrator in
the office of behavioral and social
sciences research obssr
so he facilitates nih's basic behavioral
and social science opportunity network
so
bill are you on the zoo
yes sir thanks rick happy to be with you
terrific great to have you with us okay
so pat do we go around the table and and
others who are on uh introduce himself
or do we move on
we move on um you're now up to the um
the next step here i understand that
there are some
retiring members of council so i'd like
to acknowledge the service of dr jose
cordeiro
shook me ho suzanne shenz
andy she and patrick sung so thank you
all
for your dedicated service to council
over the course of the last uh four
years
uh it seems like yesterday but we were
just welcoming you on council
so because of the transition of course
uh your your certificates will be
mailed to you at a later date so uh
just i want to express my appreciation
for the time the effort that you put
into helping us on council so
okay pat back to you
sorry just a few housekeeping things
here um
first i want to remind everyone that um
we will be having a working lunch today
because
of the fact that we're spread out coast
to coast and
um finding an appropriate lunch period
was difficult
what we will do is we'll take a
15-minute break um in the middle of
the meeting today give you a chance to
go grab your sandwich or salad whatever
and bring it back and we will
have like i say the working lunch um so
we will
be back within 15 minutes of you
um i would typically at this point be
telling you like where the cafeteria is
for me it's right over here uh the
restrooms well whatever
um just a reminder of some of the uh
virtual meeting etiquette while you're
not speaking
please mute your microphone and turn
your video off try to save bandwidth
if you want to speak you can raise your
hand virtually or literally
um or you can put a note in the chat
saying um that you would like to speak
um but if force comes to worst if you
don't get called on just go ahead and
talk
i would rather that you have be heard
than us be too polite
i should let you know that we remind you
that this is a public meeting we're
being webcast and so the public
will be hearing us members of the public
who want to express views
regarding anything we're talking about
can do so uh
via a the email that is on our niehs
webpage
we will have one vote today for a
concept that will be conducted
electronically via the council book like
we did during the closed session
the next step for us is to is
consideration of the september 2020
meeting um council meeting minutes these
meetings
excuse me these minutes are available on
the uh
nae hs council webpage and council
members also have them in their ecb
so hopefully you have time to review
them
at this point i need a motion to approve
the minutes from last
council meeting if i can have a council
member
make that motion please and i can't see
you so move so
moved okay thank you um
and i said got a second and got any
second any discussions
no if not um liz i believe they can vote
on this through the council book is that
right
i can't see you on the on the zoom list
so you'll have to but there you are i
can't see you all right
we're just waiting for everyone to vote
and liz you'll let me know when the
voting is complete
you're muted
okay so voting is complete okay i'll
take that as it is thank you all
um the next thing i'll just mention in
the
information we sent you are the future
uh
council meetings our next one is june
1st uh and second
at this point it will at this point it
will be a virtual meeting
um the september council meeting the
fourth and 14th and 15th of september
um a decision hasn't been made about
whether that will be virtual or
face-to-face moving and with that
um i will finish up the business
part of this and rick i guess i will
introduce our first our next which is
the uh
concept um we have
okay we have sri natador who will be
speaking now
um when we have um new programs or
programs that we're looking to review
every five years or so we have the
program officer come to council
and present um and uh ask for a present
the concept
and we'll ask for your approval at the
end so shari will make his presentation
at the end of that time i'll call for a
vote
so sri if you're ready um and john can
you
get us going yeah um thanks pat
um good morning um thank you for the
opportunity to share with you
this concept to promote fundamental
research
in support of the transcendent
countermeasures against chemical threat
agents program which we abbreviate as
counter
act program sometimes my counteract
pronunciation will be
sounding like a contract excuse me it is
the counter act program
this concept did i get the
opportunity to move this lives
sheree we're getting some notes here
that they can't see your slides
so i can see the slides i can see them
too i see them
i've seen them okay i see them too
so i um so david i'm not sure what's
happening on your end
sri did you click on the on your slide
single click twice in a row
there you go there you go yeah
okay okay um
the concept i'm going to share with you
today is a joint effort
with the national eye institute on
national histology and infectious
diseases
um aroused from the ni
nei and dave young from and
ir are available on zoom if you have any
specific questions
on during the discussion session um
jackie merger who recently joined our
group
from the intramural research program
will be supporting this program
in this presentation i will provide you
a
high level overview on the efforts
at the federal government to address the
public health emergency
medical countermeasures and what's the
role
nih plays in this process and
that is exclusively focused on chemical
countermeasures
chemical threats research program and
i'll provide you
what are the current opportunities
available for
funding through this program and we'll
provide some examples from the existing
research efforts within the
pulmonary portfolio share with you some
success stories and then what are the
ongoing efforts within this program
supporter
at NIEHS and will then provide them
what what the gaps and needs we
identified and
how this opportunity may contribute to
address those
gaps and needs and on the end i will
want to share with you
of information about the couple of
upcoming meetings
and that may be of interest to all of
you
so the events of the september 11 2001
exposed the vulnerability of the united
states to acts of terrorism
that could employ unconventional weapons
and tactics such as chemical biological
radiological or nuclear
agents against the civilian population
so to prepare the country to handle such
potential high consequences and public
health emergency scenarios the
department of
health and human services from the
public health
enterprise medical public health
emergency medical council
measures enterprise to coordinate
activities across
multiple federal agencies such as the
department of homeland security
department of defense
usda veteran of fives
the this program is
led by the assistant secretary for a
preparedness and response
with the core members of from
the director of the cent cdc director of
naid and the commissioner of
food and drug administration serving as
core members advising the
assistant secretary for the preparedness
and response
the NIEHS place the
foundational and essential role
by supporting the early stage research
towards medical countermeasures
development
as part of this emergency preparedness
within nih the
office of the biodefense research and
security located in
and infectious diseases who oversees
this program
under the umbrella of chemical
countermeasures research program
there are three major components within
the countermeasure
the ccrp program one is the counteract
extramural researching program with the
participation of six different ics based
on the
threat agents of interest and the target
organ for example
the ocular toxicity program is run by
national high institute similarly the
neurological effects
by ninds and dermal effect toxicity by
niams and for the pulmonary research
program
NIEHS is the lead the other components of
the
ccrp are one is an interagency agreement
program
with the department of defense which
supports
a vibrant research program at the u.s
medical
army research institute and also
in this program we have a
contract mechanism to support
for advanced development efforts such as
synthesis of the target compounds or
synthesis
of um are carrying out pharmacokinetics
of toxicokinetic studies for the
lead candidates identified within this
program
in essential this is a um
collaborative program where nih plays
the
role in supporting the fundamental
research whereas
and border plays a support in advanced
therapeutic developments so the success
of the program
is the transition of the lead candidates
of for countermeasures identified
through the nih program
to the border nih also plays a critical
role
in in this process by facilitating
meetings between the nih grantees
with the boredom of scientists
the mission of the chemical
countermeasures research program or ccrp
is to accelerate development of medical
countermeasures
and in support of stockpiling these by
border
for any emergency use we
it was initially targeted only for a
deliberate
effort of exposure to toxic chemicals
and in 2005 we also included the
any accidental public health emergency
situations such as what we faced in them
planet will chlorine exposure
how the threat agents are identified for
this program
are the from the
efforts by the department of homeland
security
where chemical threats risk assessment
program identified about 200 chemicals
of concern and these are the chemicals
that can target cellular respiration
eye skin pulmonary or neurological
systems
the research priorities for this program
are
identification of multiples of acute
toxicity
and identification of potential
biomarkers
and facilitating screening assays to
identify
novel or improved candidates for medical
countermeasure
demonstration of a target or appropriate
biological
activity for the candidate therapeutics
and development use of animal models to
demonstrate primary proof of principle
currently this program is heavily
focused on the
demonstration of target and then proof
of principle studies with the
animal models
the ccrp program has an annual budget of
about 50 million dollars which is a
congressionally mandated program
and this pie chart shows you the
distribution of
funds across different target agents and
different
and in last year alone for the pulmonary
program
we invested about 20 12 million dollars
so currently the contract research
program
is supported through the funding
opportunity
four funding opportunity mechanisms that
are available
one is for this forming research centers
of excellence
and identification of lead compounds
optimization of lead compounds
or in a text exploratory research
program
for example in the explanatory
parent r21 program we support the
exploration of therapeutic approaches
or in the once you have identified a
potential lead
foreign and through the mechanistic
understanding the parent
uo one will support initial
field relevant delivery proof of
principle efficacy for example
the program insists on having a
therapeutic
method that can be applied in the field
situation
of an emergency for example something
like an ap pen that can be applied
by intramuscular route and
the other mechanism the uo and what we
have
for the optimization of lead compounds
is this will support iterative
structural activity relationship studies
or effectiveness of bio
increase the biological availability or
absorption
or reduce the toxicity the u54
centers of excellence program make have
a combination
of either identification of your lead
compound
or optimization of the lead compound the
the final goal of all these programs is
how the leads identified and optimized
in this program
can transition to advanced development
through border
the hallmark of this program is
how many i leads identified by the nih
efforts
can lead towards advanced development
supported by bada
currently within the pulmonary and
ocular portfolio
we have about 10 toxic atoms being
studied
the ones i marked here with astric are
the ones that are common
across pulmonary and ocular portfolio
for example sulfur mustard
acrylene on or silicons whereas
chloropicrin is the only compound
currently
in the ocular portfolio or the pulmonary
portfolio is also dominated with the
chlorine bromine phosgene and
other gaseous agents
so this is a very small set of chemical
toxic agents being pursued in this
program currently
let me share with you some one success
story
that transitions from the nih to the
boredom
um sulfur mustard or the mustard gas is
a vesican
and it's the most utilized chemical
weapon over the last hundred years
it is in large amounts of um sulfur
mustard is still
stockpiled in many countries
with them unstable leadership
and the for the sulfur mustard the
in inhalation is the route of exposure
though
respiratory tract is the primary target
we have
in eyes and skin are also greatly
affected
i'm going to share with you what has
been accomplished by
the u-54 center funded at the university
of denver colorado led by
carl white and libya so
based on the autopsy of the iran iraq
war victims
sulfur mustard poisoning demonstrated
airway occlusions are formed with the
fibrin clots the in the
death is mostly due to the or these
fibrin clots
and inability to breathe so
claw call white and then
livium can simulate the similar
occlusion of the airways with the fibrin
clots in their
sulfur mustard and morphology rat model
and demonstrated sub fibrin clots
both in the major highways and in the
dependent highways
arrays as you see here with the
cash scores so
they explored whether tissue plastinogen
actor
activator or tpa which is a potent
fibrolytic agent currently
fda approved for intravascular clot
lysis
in stroke and heart attack as a under
emergency youth also
emergency use authorization so
when they explored the by introductively
administering the tpa to these threats
they could see a hundred percent survive
of the
sulfur mustard exposed rats in 48 hours
this program is now currently
in advanced development by evaluating
the feather similar vibrant cross can be
hydrolyzed with the tpa administration
in a large animal model
in collaboration with genetic tech
there are two other compound elites
identified within the
pulmonary program supported by NIEHS have
also
transitioned to the body one is
within trip four in channel blocker it
is currently on advanced development
by border support in collaboration with
gs game
and another all and an
agent for the bifunctional nitric oxide
donor
agent developed by the radical
therapeutics
also for chlorine induced injuries
over the period about eight of the leads
compound
have been transitioned from this program
three for the new rule
one for ocular and the rest for the
pulmonary portfolio
[Music]
i want to share with you the couple of
um
studies within this program um
i'm sure many of you remember
the one of the worst industrial
disasters happened in 1984
in bhopal india where
a huge quantities of methyl isocyanate
was accidentally exposed
that led to almost 11 000 mortality
acute mortalities above and still half a
million people
suffering from different diseases
associated with exposure to
methyl isocyanate carl white's group
again at the university of denver
colorado center
are exploring two hypotheses
to find a countermeasure for methyl
isocyanate poisoning
when the methyl isocyanate exposure
leads to cellular depletion of thial
groups
due to carbon myelation of thiols and
also they found the inhibition of the
thyroid active
thyoroxin reductase and the another
observation they made is
a delayed fiber analysis or elevate due
to the elevation of anti-pharmaceutical
agent or a plasmid activator
inhibitor one so
can an antioxidant therapy
or a promotion of fibronym
fibre analysis can be a
counter measure for methyl isocyanate
exposure
use the graph i am showing here is after
a series of trials with different
anti-accident agents they had some
promising results from
mesnorm which is a
used currently and in adjuvant cancer
therap chemotherapy to protect the
toxicity from the cyclophosphamide
or other chemotherapy agents if by
administering the messner in this methyl
isocyanate
mortality model they could see about 40
percent survival
by 24 hours when they had a combination
therapy of both
mesna and the tpa
it they could improve the survival to
about
65 percent so this is one of the
promising lead candidate that can be
explored further through this program or
eventually through border support
another observation i want to share with
you is
and within the program we support
couple of projects on bromine induced
acute lung injury
um the what i am going sharing here you
with you
is the work from sadie madeline's group
at university of alabama
where they observed that probing on
brominated lipids
can lead cause the degradation
of the high molecular weight hyaluron
and then the degraded small hyaluron are
pro-inflammatory
and they can interf and cause in
pulmonary inflammation
and link injury so is providing
a native or high molecular weight
hyaluron can rescue these animals they
tried
a com with an earbud which is
a hyaluronan solution available for a
nebulization
marketed in europe and using the airboat
they could demonstrate
that it can thereby can reduce the
bromine
induced hyper airway hyper
responsiveness
pulmonary inflammation and also could
they absorb about
45 percent survival in the bromine
acute um mortality
model so this is another promising lead
candidate
who that will be pursued further by
sadist
group at uab i'm
listing here some other ongoing projects
within the portfolio
for example uh sven
george group a duke who earlier tried
with the trap for inhibitor
are now exploring the third generation
trap a1 inhibitor as a counter measure
for a chlorine induced acute lung injury
or drunk
bo or bronchiolitis obliterans in the
mouse and a big modern another center
that is supported through the nih's
program
is the one focused on arsenicals led by
of the atar ahmed at university of
alabama
where they are looking at the skin lung
and kidney toxicity
is the how the arsenicals are modulated
causing the toxicity through epigenetic
modulation
that leads to information tissue damage
and
transcriptional regulation the project
in this is also looking both at acute
and delayed lung injury
from skin exposure to arsenicals and
drivers small molecule inhibitors of
bromo domain signaling
are being explored in this program
um another one i want to touch upon
is how the delayed effects of the
exposure to hydrochloric acid as a model
for chlorine exposure
being pursued by john katrawa such world
dominion university
where he is exploring the heat shock
protein inhibitor
which is currently in trials as an
anti-cancer agent
whether that will rescue the heat shock
19 mediated other
signals for fibronectic signals
so from the so far what i shared with
you you can easily guess
that there are very limited number of
chemicals being
investigated currently in this program
and also the funding opportunities
currently available
are more targeted towards translation to
border i mean more looking at the target
identification of a target and
optimization of the target as a
potential
so the these programs also have other
restrictions because
most of them are um cooperative
agreement mechanisms so
these eu ones are milestone driven and
there's a limited opportunity
for discovery research
and as i mentioned in current portfolio
has only limited number of chemicals
explored and majority of them are known
for
chemical warfare agents as i showed
earlier there are about 200 chemicals
identified by
the chemical threats risk assessment
program at
department of homeland security that
includes
industrial and agricultural chemicals
these chemicals are produced and
transported across the country so there
is a potential for any accidental
exposures like what happened with
chlorine
and there are about 50 of these known
these among the 1 200 chemicals are
pulmonary
and ocular toxicants and majority of
them
understudy what we know is about the
ld50 or lc50
and we have limited understanding on the
pathophysiology of these chemicals
for example i listed here sorry for this
busy slide
the only reason i wanted to show here is
that these are all the chemicals
that are in the citroen that we don't
have much information
about their pathogens of physiological
mechanisms
for examples ammonia is produced in as
fertilizers or a cleaning agent on
boron trichloride is produced
in used in pharmaceuticals and in
electrical work
carbo fueron for example is a
multi-use pesticide and agrochemical
ethylene dioxide
italian oxide you know as an insecticide
as a sterling
sterilizing agent and phosphorous strike
chloride is
used as a chemical warfare agents also
but as a pesticide
and used in the production of plastics
so what we know about these chemicals
is very limited on
excuse me
understanding and getting fundamental
mechanisms of injury for these chemicals
is critical if you want to have any
identification of a target to rescue
on exposure to these chemicals
so any research on the mcm development
for these toxicants in the citra
is difficult at this stage
so what we want to do is in this new
funding opportunity mechanism
to support a development of
pathophysiological
knowledge base for these understudied
chemicals within the center
to support fundamental molecular
cellular
and physiological pathways involved in
acute toxicity
of these chemicals proof of principle
efforts using combination of in vitro
and in vivo models
and support high throughput screening
approaches to identify common mechanisms
of
injury that may lead to some potential
shared therapeutic targets and systemic
toxic effects on inhalational exposure
for example how the delayed and
acute and delayed effects in other
organs
role of susceptibility and co-morbidity
factors
and identification of biomarkers of
exposure
so what we hope
is that this kind of an
investigation into gaining understanding
on the
fundamental mechanisms will serve as a
launch pad towards identification of
targets
for example as i showed earlier the
current programs are all more targeted
on identification of a target
for a confirmation so this will come up
front
as a fundamental research feed into the
existing programs so by gaining
fundamental understanding through this
mechanism
you may the investigators maybe position
themselves
to target and
particular mechanism or particular
candidate
gene as a target for a therapeutic
approach as a counter measure here and
then later through advanced development
by border
and i want to share with you the la
couple of the last couple of slides
about the
uh upcoming meetings and so they are
assessing the current
state of the research on acute lung
injury
and ards irrespective of the origin
and i we can identify common mechanisms
across these
and those mechanisms and the already
existing
approaches to treat those aila and ards
may be useful for the chemical induced
lung injury
so this will open an opportunity for in
interacting with the critical care
physicians on
the toxicologists who are pursuing
pulmonary toxicity mechanisms for
mechanisms for acute lung injury
and we have we are look
excited to host these meetings hopefully
covet permitting
in october at the roadville auditorium
and
i hope many of you join in this meeting
on another aspect of the contract
program is we
host an annual meeting every year and
this year's annual meeting will be
hosted by
atops group at uab and the meeting will
be held on in the month of december
hopefully
kobe permitting at new orleans and
the grant is funded through this new
funding opportunity will also be
participating in the future annual
meetings to share their
research i'll stop there
here now and terry kavanagh and trevor
penning are
the reviewers for the concept lead the
discussion
and thank you for your attention
[Music]
thank you sheree um terry or trevor
whichever you
would like to go first yeah this is
trevor i'm gonna be going
first um i think there was a decision
between
terry and i that i would go first
because uh
i'm most familiar with the uh counteract
program
i have been on the external advisory
board of the u-54 center at rutgers
whose focus has been on
sulfur mustard and i thank srifa he's a
nice presentation because i think he's
identified
some gaps that need attention it's very
it's very clear that uh from the u-54
program
that there are only a number of these
centers of excellence and
uh they're focused on single agents and
although they're doing
great work in terms of understanding
mechanism
identifying of of molecular targets
and also identifying agents that
can be used as counter measures
they can't do it all and i think that
the program that sri
is presenting provides an opportunity to
do a lot more
on a broader range of agents
the things i that do come to mind that
perhaps
need some attention are as follows
sri identified 200 chemicals
that have been identified by the
chemical
terrorism risk assessment and i'd like
to know
more about how they did that risk
assessment to come up with those 200
chemicals
but assuming they've done it right they
then come up with 50 chemicals
that sri identified as being
of potential uh pulmonary threats
and uh as you saw in his presentation
uh we know very little about many of
these chemicals uh he indicated that so
we have the ld50s but not much else and
i think one thing
that actually may not be a component of
what he proposes but does
bring to mind and that is what is the
margin of exposure what's the margin of
safety here do we know
the knowers and the lowest from animal
studies that we can extrapolate
safe human exposures i think that's an
important component to consider
if we are going to have the protective
of human health
i'd also like to think that if we have
50 chemicals
there may have to be some for into price
rising
which chemicals we might actually want
to
think about investing uh funds into
uh understanding more about mechanism
the rfa that would probably come out of
this ultimately
would could be of two types it could be
an rfa where it's just going to take
the best the best applications or there
could be some prioritization in the rfa
of the chemicals of most concern and i
think that perhaps
that needs some attention a broader
aspect of this whole program of course
is the opportunity to expand it into
occupational exposures and hazmat
workers as well as the
disaster response component of nahs
as well which spoke to the accidents i
think that sri was referring to
so knowing that there are 50 chemicals
at least that we want to uh focus on
one has to wonder whether 12 million
dollars is going to do the job
and so you know this could be a tiered
program whereby we start off small
and then actually develop a increased
funding stream for it
based on metrics of success
and that brings me to what the metrics
of success are going to be
and i think this has to be spelled out
in the rfa
that might go with this and uh i think
i think they're self-evident but i think
they need to be emphasized
and clearly they would be identification
of a new mode of action for
a toxicon in terms of this pulmonary
pathophysiology uh wherever or not
a a lead compound has been identified or
whether we can repurpose an existing
drug
to uh tackle that target and
and whether or not something is ready
for transition either to the eu
mechanism or to barda
i think those are things that should be
uh
should be considered uh as we move
forward
i like the concept also that he raised
that
many of these agents might have a common
mechanism of action meaning that we
might be able to have
a counter measure that might actually
deal with pulmonary pathophysiology
that might be applicable to more than
one uh toxicant exposure
but overall i'm supportive of this
concept i i just wonder
whether or not some effort has to be put
into prioritizing chemicals
and how much money we wish to invest in
this program
very important topic
shari did you want to respond to those
questions or do you wanna hear from
terry nixon
um and i had earlier discussions with
both
teddy and trevor on that i took some of
the points and then
definitely the
i mentioned to both terry and trevor at
the time
uh it's unfortunate i cannot share what
are the chemicals in the list i
used some here as an example but the
investigators who are invest
interested may have to contact us so
whether the chemicals they would like to
explore is
a part of the citron and we can provide
that information
and as um trevor mentioned our goal is
um when we write the rfa we are going to
make all those points very clear
the um if a center
if a grantee is interested in high
throughput screening for three or four
bank
chemicals that may lead to
identification of a common mechanism
or common mode of action or common
target for a
counter measure development so um all
those
um are very nice points we will
definitely consider
in that while we're writing the rfa
okay hi terry you wanna sure uh so
um i i fully agree with the sentiments
of trevor and
and uh uh agree with uh the
answers that that sri has given as being
uh important uh responses
one of the things that i thought would
also be important to highlight
in the rfa would be chemical
in silicon modeling if there's a common
mechanism for instance that's identified
across
multiple agents then perhaps
in the rfa that that the um
that the institute's open to uh that
kind of approach
uh because i think those kinds of things
can also help to accelerate
discovery uh of course you're going to
need both in vitro and vipo
verification but still i think that the
in silico modeling
has come a long way and that can that
can add to this
the other thing we identified as
potential issue here has to do with
engaging pharmaceutical firms as
partners in some of the research
and perceived markets and all of those
issues
the idea that a lot of this would be
especially subcontracting for
for some of the more expensive aspects
of the research
would would i think allay some of those
fears but still this is a
has been as my understanding is a little
bit of an issue um
to engage pharmaceutical partners
especially repurposing some of their
existing pharmaceuticals so they also
have a lot of the industry has a lot of
things that
you know they've not um taken all the
way through phase three clinical trials
but still might have
um and may have failed in those droughts
but still may have
a lot of application in emergency
situations that could be
uh could be pursued i agree that the
uh prioritization is a is a huge issue
and so obviously it's going to be
important in the rfa that
that applicants are encouraged to
contact a program officer to determine
whether or not
what they're interested in uh is is
likely to be impactful
one thing also we talked about that is a
is potentially an impediment for
investigators
is the idea that some of these things
are likely to be
to require a security clearance do you
work on them
and we um you know again wonder how
that's going to be handled in an rfa
uh because there could be issues for
certain groups to be able to apply for
the work if in fact
they can't get a security clearance and
there's obviously bureaucratic
hurdles and hassles associated with that
finally
extremely important is that the rfa
include information
on chemical safety plans for
laboratories that are working with these
agents
and especially in the context of their
university regulations
and any federal regulations that come
from working with
select agents
with regard to that question it depends
on the how much
amount of the toxic chemicals you are
going to
hold at in your laboratory at a time
if it is a smaller amounts we don't may
have to go through
all the bureaucratic process of getting
the security clearance
but again it depends on the amount and
the type of the compound
we try to help the grantees to go
through that process as much as possible
but it is then
mostly handled by the academic
institutions
so sri this was a concern that terry and
i did have about the biohazard safety
because if the
target is pulmonary pathophysiology or
pulmonary damage
then one can imagine that whole animal
studies this would be an inhalation
uh paradigm and so i think i think i
would endorse what terry said and that
is we do need
in the rfa some explicit language about
biohazards
yeah definitely that will be and also
um and also um may not
all the institutions be ready to do
an expo inhalation or a nose only even a
nose only explode inhalation exposure of
these chemicals
and the
rfa will be written such a way that if
there are any
investigator initiated but maybe would
like to use a contract facility
to support that kind of an animal
exposure studies but they can do
other mechanistic studies on the in the
laboratory we may have to
include that also as part of the rfa
one other thing i had in my notes which
i forgot to mention
was the issue of acute toxicity
versus delayed lung injury uh
you know fibrosis for example can be a
a very uh delayed response to a toxicant
exposure so i think
we want to indicate in the rfa that
we're interested not only
in acute toxicity but delayed injury as
well
yeah definitely we have a few uh
council members queued up here who want
to ask some questions i think dr goldman
i believe you were
next in line well i wanted to start out
with just saying wow
i think this is a really great program
and it's one of these things that you
know i just want to go why didn't i
think of that
i mean you know that we have for so many
years not just
you know seeing these as potential
homeland security threats
but also many of these chemicals
regularly
exposed workers have exposed communities
that have releases
and to not have developed specific
agents for their treatment and and when
you look at the progress that's been
that's being made already i'm just so
impressed by this program
so there were a couple of things i just
wanted to say about that and
one is that you know to i hope
you know those of you involved from the
um nia
ehs side are making sure that it's very
clear
when some of these countermeasures may
be useful in occupational medicine
or in pulmonary medicine and
and could be applicable on many levels
not just in the case of warfare
that you know there that the information
about these countermeasures isn't buried
you know
under um you know in classified systems
that people can't access
i mean and so you know i just really
want to urge
uh to have that information out in the
open where p
you know physicians and public health um
people can
can access it um anywhere in the world
you know
because these releases happen everywhere
the
um the other thing i i wanted to say is
that
i think you might be able to get actual
support from the chemical industry
the people who make these chemicals they
want to be responsible stewards
they themselves um have situations where
they want to be responsive if they have
a train load
of one of these things that um that
spills in a community and people are
exposed
and i i would not be at all um
embarrassed about seeking you know their
actual financial support unlike
it's it's a little different than what
you might go to the pharmaceutical
industry for but
i mean they actually could be involved
in that in doing research in their own
labs but they
i could see they're being willing to do
cooperative research some kind of public
private
around some of it just to show that
they're being responsible
um in terms of these agents and
and last but not least i just know of
course that the occupational medicine
and pulmonary medicine community will be
really excited about this and i hope
that
the outreach plans for this program will
include at some point in time
you know doing sessions at their
meetings and
um and and informing them of some of
this
it it's just so exciting uh to think
about the availability these treatments
obviously i'm all about prevention
but realistically um these things happen
and
it's it's great uh to be um developing
these counter measures
thank you thank you i mean we have been
trying at the
american thoracic society meeting there
is um
within the environmental health of
occupational health group
we have a smaller group on a disaster
management
and then at all the annual meetings we
are making our efforts to bring
the attention of the physicians to this
pro
physicians and other scientists to this
program so there's a whole group of
people over the years who've been
involved in developing the eagles
um you know and they would be very
interested in this as well
thank you our next question then is from
dr
white newsome hey where
all right okay just a second oh yeah dr
sri thank you so much
um and my question kind of touches on
our question or comment kind of touches
on a point that dr penny brought up
more so about the prioritization of
agents
and i just remember working in several
chemical facilities with
large amounts of bad stuff particularly
anhydrous ammonia
and while that was 15 years ago my hope
is there
that there is a more heightened sense of
responsibility around
the chemical industry but again i don't
think that plays out
all times in all places particularly in
facilities where they're in low-income
communities and communities of color
and so i'm interested in really
understanding um as you think about this
rfa
are there any what are some of the
criteria of prioritization that you're
looking at
uh is it who's living around these
stockpiles even some of the smaller
amounts of
really bad stuff um are there certain
folks that continue to be more at risk
and exposed either through occupation or
again
just the places that they live and then
thinking about some of the accidents
that continue to happen
particularly in some of these deep
chemical corridors in houston and
louisiana
um you know should this be a part of
again your criteria of prioritization
um again i'm not sure you know if this
type of research of those questions have
been
asked um particularly around
environmental justice and equity and
who's being exposed but i think if there
is an opportunity
um through the work that you're
proposing to make that a part of the
criteria
in some way um that will be super useful
not only from an environmental justice
standpoint but an equity standpoint
uh from prevention as well as in
response
so um thanks so much for what you shared
and
whatever you can share will be great
thank you i mean the
currently the way the program has been
designed
is to focus on the therapy promoting the
development of countermeasures
so that we are in a more in at least a
preparedness mode
and the priority chemicals are
annually assessed by the in consultation
with department of homeland security
and also with border border will come
with a list of chemicals
that have been indicated to them as
priority chemicals
for which the countermeasures need to be
on the pipeline at least so we work with
both the agencies
in them prioritizing those and
definitely once the
this program evolves a little bit more i
will be glad to
in have interactions with them within
our
community outreach program at NIEHS and
with the environmental justice to see
how this information can be disseminated
to those communities for sure
thank you for that thank you and and dr
wright i will give you a
next to last question um
a great presentation and a very
interesting program so
i wanted to provide a clinical
perspective i'm actually a pediatric er
physician and i did a medical toxicology
fellowship so your presentation brought
back some
fond memories from 25 years ago when i
was training
it's pretty much the same agents but um
having said that it seems like one of
the big research
gaps is actually in diagnostics
um very few physicians would recognize
mustard gas poisoning very few
physicians would
know what chlorine does or what bromine
does
and how to treat it and i think there
should be some research i would argue in
that area
you know there may be diagnostic tests
maybe using untargeted methods
but also ambient sensors could be used a
lot of these agents stick to the clothes
and there's actually been cases that
people
working in the emergency room have been
had had secondary poisons
and also i think that would address
jalon's question to some extent because
if these are in uh waste sites you know
ambient sensors could help to alert
whether or not you know they're being
released so i
i would really urge the program to think
about diagnostics as well
i know it's too late for this particular
rfa
the through the dvod program we have
an efforts going on for a sense of
development for
assessing the exposure levels and
also some of the biomarkers some of the
biomarkers develop through our program
also for example chlorinated lipids
um that can stay in your system for
longer periods
as one of the markets for exposure to
chlorine
it's in developed by uh rakesh patel and
others
uab and it's still in the developmental
stages of some that is something
promising as a measure of exposure
on as a biomarker of exposure and
we definitely we have this interaction
with
all the agencies but um we have to do a
lot
more on the diagnostic things as you
suggested and we'll definitely take that
into consideration
thank you okay thank you um and our last
question is from dr
geller thank you uh thank you pat
and thank you sheree for that
presentation i just wanted to check or
offer um potential interaction with the
environmental protection agency we've
got a homeland security research program
and i'm sure you know our responsibility
is for for cleaning up
and remediating um for bio rad
uh chemical um uh
and nuclear materials um we do
look at contaminant characterization and
assessment so in terms of of identifying
those situations and the situations that
we've
put together and actually the
simulations that our homeland security
research program
runs may be really very very fertile
ground for thinking about
the the uh the medical and biomedical
responses that you're thinking of
we really think mostly in terms of our
physical responses
and cleanup responses um working
and and drawing in these biomedical
approaches would be a i think a great uh
a great opportunity so thank you and
look forward to working with you
yeah definitely i'll be in touch with
you andy
and sure you have a question from doctor
from shipment hoe in that oh and it just
went away
um about open where did it go well open
tip burning
exposure be included if you can give us
a quick answer that then we can kind of
move on to our vote
um i may not be in this program because
this is more focused on the
chemicals identified through them
[Music]
etc
okay um i'm looking at the uh
i'm gonna in the interest of time i'm
gonna go ahead and move us to a vote i
would suggest that people look on the
the chat especially dr young has
provided some explanation about the uh
from the toxicity availability and such
and so
um at this point i want to thank um
doctors kavanaugh and penny and i will
ask
for a and tell people if they have more
questions they can contact sheree
directly or put them in the chat and
shriek and respond that way
i'm going to ask for a motion to approve
this concept to go forward
i've got a motion they'll have a second
they've got a second any discussion for
the discussion or
debate if not i will ask you to
go into your electronic council book and
vote
for this concept
and liz you will let me know when we
have
achieved our goal
okay
okay okay looks like we're there and i
assume that
that was approved is we have our voting
approval okay congratulations shari
thank you very much
and thank you all for a um for a very
nice discussion there again
i recommend that people go into the chat
uh and and look we have a question from
dr
tangway too that shri you may want to
address that
as well i will look into the chat
thanks sir um we're now um
scheduled for a quick 15 minute grab
your lunch and come back break
um why don't we try to get back here at
1205
give us our full 15 minutes at which
time dr woychik will will give his um
his report of the director followed by
um
some interesting um an interesting
presentation from our division of
national tax ecology program um dr
watson did you say anything before we
take our break no i just thank everyone
for the morning session
and let's get back here in 15 minutes