May
13,
2005
Mr.
Tim
Oppelt
Acting
Assistant
Administrator
Office
of
Research
and
Development
US
EPA
Washington,
DC
20460
Dr.
Robert
Kavlock
Director
National
Center
for
Computational
Toxicology
US
EPA
Research
Triangle
Park,
NC
27711
RE:
National
Center
for
Computational
Toxicology
Dear
Mr.
Oppelt
and
Dr.
Kavlock:

This
is
a
letter
report
from
the
Board
of
Scientific
Counselors
(
BOSC)
reviewing
the
progress
of
the
new
National
Center
for
Computational
Toxicology
(
NCCT).
Dr.
Kavlock
and
his
staff
at
the
NCCT
presented
an
overview
of
the
Center's
structure,
activities,
goals
and
progress
on
April
25­
26,
2005,
to
a
subcommittee
of
the
BOSC.
The
subcommittee
consists
of
George
Daston,
Chair,
and
James
Clark,
Richard
DiGiulio,
Michael
Clegg,
and
Ken
Ramos.
Dr.
Clegg
was
unable
to
attend
the
briefing,
and
Dr.
Ramos
recused
himself
because
of
a
potential
conflict
of
interest.

Because
the
NCCT
is
so
new,
becoming
operational
in
February
2005,
this
report
is
a
prospective
one,
and
is
intended
to
be
the
first
of
several
consultative
reviews
of
the
Center's
progress.
In
particular,
we
concentrate
on
NCCT's
strategic
goals;
its
collaborations
and
connectedness
to
the
rest
of
the
Agency
and
to
outside
scientists;
its
staffing
plan;
and
its
thematic
choices.
We
addressed
a
number
of
charge
questions
intended
to
focus
on
each
of
these
areas.
Those
charge
questions
and
the
subcommittee's
responses
are
listed
below,
following
some
general
comments
about
the
Center.

The
subcommittee
was
extremely
impressed
with
the
progress
NCCT
has
made
in
the
few
short
months
of
existence.
NCCT's
mission
is
to
serve
as
a
focal
point
for
EPA
in
the
application
of
mathematical
and
computational
tools
to
all
facets
of
the
risk
assessment
process.
To
be
successful
at
this,
the
NCCT
must
1)
provide
a
critical
mass
of
expertise
in
computational,
mathematical
and
statistical
modeling;
2)
develop
research
collaborations
and
partnerships
with
a
large
number
of
groups
within
and
outside
the
Agency;
and
3)
have
a
clear
understanding
of
and
regular
interactions
with
its
customers
in
the
rest
of
ORD,
the
Program
Offices,
and
Regions.
The
Center
has
already
made
considerable
progress
on
all
three
fronts.

Because
its
staffing
is
limited,
the
NCCT
has
made
the
appropriate
choice
of
concentrating
on
gathering
staff
with
biological,
chemical
and
statistical
modeling
expertise
rather
than
on
a
particular
biological
or
chemistry
specialty.
This
is
an
appropriate
choice,
as
the
staff
is
strongly
aligned
to
the
mission
of
the
NCCT.
The
composition
of
the
staff
is
impressive;
it
includes
some
of
EPA's
most
accomplished
biological
modelers,
chemists
and
statisticians.
Most
of
these
individuals
have
strong
track
records
of
collaboration
with
multiple
laboratories
and
are
already
sought
after
as
research
partners.
This
choice
of
personnel
automatically
leverages
NCCT's
potential
well
beyond
what
would
normally
be
expected
of
a
group
of
19.
Housing
these
people
together
allows
them
to
synergize
and
form
ad
hoc
groups
to
make
progress
on
multiple
fronts
simultaneously.

The
Center
already
has
collaborations
and
programmatic
augmentations
via
internal
and
STAR
grants.
These
partnerships
cover
a
large
number
of
areas
of
modern
biology
and
chemistry
that
require
high­
powered
computational
and/
or
modeling
expertise,
such
as
genomics,
proteomics
and
metabonomics,
with
coverage
of
mammalian
toxicology,
ecotoxicology,
microbiology,
exposure
assessment
and
quantitative
risk
assessment.
The
NCCT
has
a
steering
committee
 
NCIST
 
that
represents
ORD
laboratories,
Program
Offices
and
Regions.
The
role
of
NCIST
is
still
evolving
and
it
will
be
an
important
avenue
for
communication
and
identifier
of
possible
partnerships.

Charge
Questions
and
Responses:

For
the
Center
as
a
whole:

1.
Success
of
the
NCCT
will
depend
upon
establishing
effective
collaborations
with
the
other
ORD
Laboratories
and
Centers.
What
advice
can
you
provide
to
ensure
that
operations
remain
integrated
with
the
other
labs
and
centers
within
ORD?

We
believe
that
NCCT
has
been
set
up
in
an
optimal
way
to
maximize
interactions,
by
concentrating
expertise
in
modeling
within
the
Center,
rather
than
the
toxicologists,
risk
assessment
specialists,
etc.
who
populate
the
other
labs
and
centers.
This
provides
a
natural
focus
area
with
which
the
other
labs
will
seek
collaboration.
Furthermore,
most
of
the
staff
at
the
Center
are
highly
experienced
and
have
a
long
history
of
successful
collaborations,
including
a
number
of
active
collaborations
that
they
bring
with
them.
They
are
a
natural
magnet
for
collaborations.

One
challenge
will
be
to
transition
the
Center
from
a
collection
of
experts
in
various
fields
to
a
center
of
excellence
in
applying
the
broad
tools
of
computational
toxicology
to
address
the
human
health
and
environmental
health
issues
under
the
purview
of
the
EPA.
Experts
will
need
to
develop
procedures
to
capture
the
essence
of
thought
processes
and
computational
tools
that
can
be
applied
to
the
diversity
of
challenges
the
Agency
addresses.
The
Center
will
have
to
find
a
way
to
ensure
that
the
staff
is
looking
out
and
up,
and
not
in
and
down
as
they
work
to
find
computational
solutions
to
agency
questions.

Not
all
the
modeling
expertise
within
EPA
resides
within
NCCT,
let
alone
the
disciplines
that
rely
on
computational
toxicology.
The
Center
should
consider
forming
an
informal
"
community
of
practice"
within
EPA
that
can
serve
a
networking
function
for
interested
scientists.
This
community
of
practice
would
not
be
an
administrative
unit,
but
a
virtual
professional
society
within
the
Agency.
Most
of
its
business
can
be
conducted
via
electronic
media,
with
occasional
meetings.
The
subcommittee
endorses
the
Center's
concept
of
trying
to
develop
various
personnel
alignments
and
management
tools
(
e.
g.
appointing
agency/
federal/
academic
scientists
as
adjunct
or
associate
faculty
of
the
Center)
to
help
recruit
or
gain
input
from
a
broader
number
of
scientists.
Those
individuals
with
technical
expertise
aligned
with
the
Center's
activities
can
be
encouraged
to
contribute
to
Center
activities
while
being
housed
in
another
organization
within
ORD,
EPA
or
outside
of
EPA;
they
will
form
the
nucleus
of
the
"
community
of
practice".

The
NCIST
should
be
explicitly
tasked
with
identifying
possible
partnerships
and
collaborations
(
and
of
prioritizing
them,
if
need
be).
ORD
should
continue
to
hold
regular
meetings
of
its
lab
and
center
directors,
at
which
partnerships
among
centers,
including
NCCT,
can
be
explored.

The
internal
grant
program
that
supports
many
of
the
NCCT
collaborations
is
important
and
likely
to
be
highly
successful.
Future
grant
programs
should
provide
a
preference
for
projects
that
collaborate
with
the
Center.

Finally,
NCCT
should
develop
a
communications
plan
to
share
its
accomplishments
and
capabilities
with
the
rest
of
EPA.

2.
In
terms
of
anticipated
staffing,
are
there
particular
areas
that
should
receive
greater
or
lesser
attention?

Efforts
to
add
expertise
to
the
Center
staff
should
include
a
plan
to
locate
leading
scientists
in
the
field
of
ecological
modeling.
Targeted
competencies
could
include
fields
such
as
modeling
large­
scale
ecological
processes;
population
and
community
dynamics;
tissue
dynamics
in
ecological
receptors
(
PB/
PK,
bioaccumulation
processes,
and
lethal/
adverse
effects
of
body
burdens);
and
environmental
fate
and
effects
of
chemicals
(
including
microbial
biodegradation
and
bioavailability).
During
the
review,
the
Center
staff
demonstrated
the
importance
of
obtaining
insight
from
social
scientists
in
developing
technically
sound
and
meaningful
studies.
This
area
of
expertise
should
be
included
among
the
core
competencies
of
the
center.

NCCT
may
wish
to
consider
one
or
two
staff
in
bioinformatics.
The
planned
grant
for
an
external
bioinformatics
center
will
cover
most
of
the
Center's
needs
in
this
area,
but
having
some
internal
expertise
would
complement
the
external
bioinformatics
efforts
and
provide
a
natural
point
of
contact
between
the
external
group
and
NCCT.
NCCT
should
also
consider
whether
there
are
social
science
applications
to
computational
toxicology,
and
if
so,
whether
there
is
an
expertise
here
that
should
be
represented
on
the
staff.
3.
As
we
find
ourselves
in
the
post­
genome
era,
science
is
progressing
at
a
rapid
pace.
This
makes
it
difficult
to
stay
abreast
with
the
current
state
of
the
science.
Clearly,
being
cognizant
of
and
understanding
the
technologies
and
advanced
methods
in
the
areas
of
the
omics,
modeling,
and
statistics
is
a
considerable
vested
interest
to
the
NCCT
for
several
reasons,
such
as
being
able
to
make
decisions
about
which
technologies
are
best
for
the
Center
to
pursue
and
most
beneficial
to
the
Agency.
Can
the
BOSC
provide
any
suggestions
on
how
best
to
keep
apace
with
new
technologies
and
methodologies?

This
is
a
problem
that
we
all
face,
but
is
perhaps
more
severe
for
an
integrating
group
such
as
NCCT.
Partnerships
with
other
organizations
with
similar/
complementary
interests
may
be
the
best
way
to
facilitate
keeping
current.
Active
collaborations,
which
is
already
the
stock­
in­
trade
for
the
Center,
publication
and
participation
in
professional
meetings,
will
keep
the
Center
staff
fresh
and
well
informed.
It
will
also
serve
to
attract
the
brightest
students
and
post­
doctoral
fellows,
who
will
bring
with
them
the
latest
technologies.

For
the
areas
of
emphasis,
or
"
Concept
Topics":

4.
Has
the
Center
articulated
a
clear
rationale
for
each
topic
area,
and
has
it
provided
evidence
that
the
contemplated
approaches
will
be
able
to
address
the
major
goals
stated
in
A
Framework
for
a
Computational
Toxicology
Research
Program?

The
subcommittee
believes
that
NCCT
is
on
track.
It
will
be
important
for
the
Center
to
prepare
a
synthesized
set
of
goals/
milestones
for
the
numerous
projects
in
which
the
Center
is
involved,
explaining
how
each
fulfills
a
need,
and
how
each
topic
area
will
provide
tools
for
the
Agency.
The
prioritization
process
that
the
Center
leadership
has
developed
is
a
good
one,
that
works
well
in
selecting
program
areas
that
are
consistent
with
the
Center's
mission.

5.
To
be
successful
in
addressing
the
Concept
Topics,
can
you
help
identify
potentially
fruitful
partnerships
with
others
outside
the
Agency?

The
review
provided
plenty
of
evidence
that
the
Center
is
reaching
out
to
find
potential
collaborators
among
a
diverse
set
of
US
government
and
private
institutions.
Many
of
the
collaborations
discussed
should
be
formalized
in
MOU,
IAGs
and
other
formal
commitments
to
demonstrate
the
degree
of
cooperation,
leverage,
and
interest
generated
with
other
partners.
Also,
the
Center
will
need
to
have
opportunities
to
work
with
scientists
and
regulatory
authorities
from
countries
around
the
world,
as
Computational
Toxicology
is
an
area
of
evolving
science
with
expertise
in
Europe,
Canada,
Asia,
perhaps
Russia,
as
well
as
the
US.

One
approach
to
broaden
international
contacts
would
be
to
consider
development
of
ties
with
US­
based
academic
centers
and
institutions
that
have
liaisons
with
international
scientists
and
organizations.
Also,
management
may
want
to
specifically
reserve
some
travel
allocations
to
allow
attendance
at
conferences,
workshops
or
technical
exchanges
and
site
visits
at
leading
international
sites
and
organizations
around
the
world.
A
world­
class
center
will
need
worldwide
perspectives
in
computational
toxicology.

NCCT
is
already
doing
a
good
job
of
establishing
liaisons
with
other
organizations
involved
in
aspects
of
computational
toxicology,
such
as
the
National
Center
for
Toxicogenomics
at
NIEHS.
Efforts
should
be
continued
to
partner
with
private
industry
in
areas
of
mutual
interest.

6.
Given
the
mission,
staffing,
and
resources
of
the
Center,
what
is
your
view
of
the
depth
and
breadth
of
the
areas
currently
selected
for
emphasis?
Are
there
additional
areas
that
should
be
considered?

The
subcommittee
believes
that
the
Center
is
doing
a
good
job
of
maintaining
broad
coverage,
through
its
collaborations
with
multiple
labs.
Depth
will
come
from
the
other
labs
and
programs
with
which
NCCT
collaborates.

The
Center's
goal
to
take
advantage
of
opportunities
to
broaden
and
generalize
the
technical
approaches
to
the
diverse
scope
of
Agency
issues
is
an
admirable
goal,
and
one
that
will
require
a
disciplined
approach
among
the
technical
and
managerial
team
to
implement.
The
review
panel
realizes
that
the
Endocrine
Disrupter
studies
offer
many
concrete
examples
of
the
kind
of
molecular
and
cellular
work
the
Computational
Toxicology
Center
can
provide
in
the
future.
It
will
be
important
that
the
Center
quickly
provide
similar
services
and
value
to
EPA
programs
that
can
benefit
from
these
tools
applied
to
non­
endocrine
disruption
issues.
Plans
to
broaden
program
office
representation
in
the
CTISC
should
quickly
bring
these
opportunities
to
the
forefront.
Discussions
should
proceed
with
agency
programs
and
offices
dealing
with
waste
management
and
issues
surrounding
remediation
of
contaminated
sites;
applications
of
environmental
models
to
TMDLs;
environmental
health
monitoring
programs
such
as
EMAP,
various
regional
Bay
programs
(
Chesapeake
Bay,
Great
Lakes
Program,
Florida
Everglades),
as
well
as
the
air
and
water
monitoring
programs
conducted
by
the
states
with
federal
assistance.
Understanding
the
chemical
and
biological
stressors
encountered
in
these
environmental
health
studies
will
broaden
the
types
of
contaminants
and
thus
computational
tools
that
must
be
considered
by
the
Computational
Toxicology
Center.
It
will
also
challenge
applications
of
the
Center's
tools
to
issues
with
a
broad
temporal
and
spatial
scale
and
provide
opportunities
to
assess
some
dynamic
aspects
of
human
and
animal
populations.

In
conclusion,
the
BOSC
subcommittee
believes
that
NCCT
has
made
great
progress
and
is
on
the
right
track
to
deliver
against
its
mission.
We
are
pleased
to
provide
advice
on
this
important
Center
and
look
forward
to
our
continuing
oversight
of
the
NCCT.

Sincerely,

etc
