Annual Report 2008

The figures on the cover are projections into the plane

of n-dimensional hypercubes (aka n-cubes), as n var-
ies from zero to eight – eight to coincide with the year
of the annual report, 2008. The projections are orthog-
onal projections chosen in such a way that the convex
hull of the n-cube projection is a regular 2n-gon in the
plane, called the Petrie polygon of the projection. Since
the n-cube is a face of the (n+1)-cube, the projections
are linked in a natural way: the vertices that make up
each projection's convex hull can be seen in the pro-
jection of the next higher-dimensional cube. Thus, the
red polygon highlighted in each figure is the image of
the Petrie polygon of the next lower-dimensional cube,
helping the viewer to grasp the relationships between
the n-cubes.
Contents
2 President’s Message
4 Math & Science
14 SFARI
26 Financials
30 Simons Staff
32 Simons Grants
2 Simons Foundation Annual Report 2008 { President's Message }

Letter from the President

“Collaboration can lead to new ways of looking
at old problems; partnerships can lead to a synthesis
of ideas; teamwork can help us build something
greater than ourselves.”

In today’s complex, deeply specialized, and vast world of research possibilities, how
does the Simons Foundation envision having an impact? We see our potential to
advance research through grantmaking that encourages collaborations, makes con-
nections, and builds bridges. We seek to fund studies that will heighten interchanges
between institutions, across fields, and among scientists to facilitate the exchange of
new ideas. A few examples of grants made this fiscal year will illustrate our funding
strategies and goals.

Modern theoretical physics and the geometric aspects of mathematics have had
increasingly fruitful interactions in the past 30 years, illuminating and advancing both
fields. We have every reason to expect that this approach will continue to be produc-
tive. To this end, the Simons Foundation is funding the Simons Center for Geometry
and Physics in order to bring together mathematicians and physicists investigating
the fundamental shape and structure of the universe.

The application of quantitative methods to biology has been progressively more

productive over the past several decades. The use of statistical methods and large-
scale data analyses, for example, is in the process of revolutionizing modern genet-
ics. The applications of both math and physics have been critical to neurobiology.
Bringing together mathematicians and biologists, the Simons Foundation supports
a Biology Colloquium at the Mathematical Sciences Research Institute (MSRI), a
systems biology program at the Institute for Advanced Study (IAS), and a newly
established biology program at the Institut des Hautes Études Scientifiques (IHÉS).
Through these interdisciplinary programs, the foundation hopes to stimulate col-
laborations that will further advance research in the life sciences.
 3

Connecting investigators and facilitating their joint efforts to build a repository of

blood samples and a collection of psychological assessment data is the goal of
the Simons Simplex Collection (SSC). This project, involving over 100 people work-
ing in research teams at 13 outstanding institutions, is compiling a large sample of
genotypic and phenotypic information to be made available for research worldwide.
By coming together to assure a uniform standard of excellence, it is hoped that
scientists will further our understanding of the fundamental roots of autism.

These grants are important representatives of our key strategy of building

bridges. Collaboration can lead to new ways of looking at old problems; partner-
ships can lead to a synthesis of ideas; teamwork can help us build something
greater than ourselves. By working together we anticipate exciting developments
in the years ahead.

The Foundation is pleased to support many excellent projects. I hope you will enjoy
reading about our work.

Sincerely,

Marilyn Simons
President
Simons Foundation
4 Simons Foundation Annual Report 2008 { Math & Science }

Progress through
Math and Science
 5

The Flower of Maths

What is a mathematician?
Not a scientist
Not an artist
But caught between the two
In a world of structures and truths
Creating the seeds
But proving the flowers
And vaguely hoping
That their scent will save the world

– Wendy Lowen
6 Simons Foundation Annual Report 2008 { Math & Science }

Simons Center for

Geometry and Physics
“The Simons Center will give mathematicians and physicists the opportunity
to work in an environment and architecture designed to enhance collaboration.”
– Jim Simons

From the work of Archimedes on the center of mass to present mathematicians with a remarkable opportu-
that of Einstein on the shape of the universe, there has nity to develop new mathematics. Environments that
been crucial interdependence between theoretical phys- encourage younger generations of mathematicians to
ics and the geometric side of mathematics. Recent devel- become aware of this physical intuition and these poten-
opments in cosmology, string theory and quantum field tial worlds of mathematics are welcome and timely.”
theory, together with important progress in topology and
differential geometry, have caused these fields to become The Simons Center will give mathematicians and
increasingly intertwined, as developments on each side physicists the opportunity to work in an environment
stimulate and inform developments on the other. and architecture designed to enhance collaboration. In
addition to providing an attractive facility, the gift will be
At the Simons Center for Geometry and Physics at used to recruit and retain permanent faculty, provide
Stony Brook University, researchers will explore these enhanced training and support for graduate students,
interactions, hopefully deepening their understanding attract visiting scholars and post-docs – up to 30 at a
of each field in its own right and continuing to unravel time – and sponsor workshops and conferences.
their remarkable relationship to each other. The building
housing the center is scheduled to open in 2010. John Morgan, known for his contributions to topology
and geometry, and formerly chair of the Mathematics
“Mathematicians often develop their mathematical con- Department at Columbia University, will be the center’s
cepts based on internal consistency, elegance and first director. Among the permanent faculty members of
appropriate generality, independent of these physical the center will be internationally renowned string theorist
connections,” said Dennis Sullivan, professor of mathe- Michael R. Douglas. Dr. Douglas was instrumental in the
matics at Stony Brook, National Medal of Science recipi- development of the first solvable models of string theory
ent, and trustee of the new center. “Physical models and its relations to particle physics and mathematics.

Left: Rendering of the

new Simons Center for
Geometry and Physics.

Right: Dr. Morgan,

a mathematician known
for his contributions
to topology and geometry,
is the Simons Center's
first director.

www.scgp.stonybrook.edu
 7

Interview with John Morgan

Director of the Simons Center for Geometry and Physics

“What we are attempting to do here is to create an environment in which

geometers and physicists can exchange ideas in a way that enriches
both disciplines.”

Why is it important to have a center for both geom- level, we will be running workshops where the topics
etry and physics under the same roof? will be of interest to both geometers and physicists.

Around the world there are many centers for geometry What are some areas of research interest that the
and centers for physics. Sometimes, like for example center will focus on?
at the Institute for Advanced Study, they exist side by
side in the same place, but even when they exist in There are many topics that I could list, but I will list
the same place there is usually little organized interac- the topics of this year’s workshops. The titles of the
tion between the groups. What we are attempting to three workshops planned for the spring are ‘Derived
do here is to create an environment in which geom- Geometry’, ‘Kahler Geometry and Extemal Metrics’,
eters and physicists can exchange ideas in a way that and ‘String Field Theory’. As the first two names indi-
enriches both disciplines. The recent interaction has its cate, these topics fit squarely in the area of geometry,
origin in conversations between Jim Simons and C.N. but there is a modern twist in the topic inspired by
Yang, here at Stony Brook in the 1960s, concerning the physics, and in particular by string theory, which is
latest developments in physics, gauge theories, and the one of the most active areas in theoretic high-energy
corresponding mathematical context. But as physics of physics. In the study of string theory, the appropriate
gauge theories developed and string theory came along, geometry is not the classical geometry of Gauss and
the developments in physics outstripped the available Riemann alluded to before, but rather a more abstract
geometry. While these developments give hints about form of geometry ‘derived’ from these classical forms.
the nature of the geometry that would be needed, what Ideas from string theory have led to new insights into
is needed is far too vast, new and different to be devel- and new questions about these derived geometries and
oped full-blown out of the hints so far provided by phys- their relation to classical geometry. These insights have
ics. What the nature of this geometry is and how it will already produced a revolution in how we think about
be useful in physics are fundamental mysteries in both ‘classical geometry’, and there promises to be much
subjects. Progress toward their resolution will surely more to come. This geometric revolution is providing
have major impacts, some indication of which we can new impetus for progress in physics. The topic of the
already see. Studying these mysteries – from the math- last workshop this year is one that belongs more purely
ematical perspective, the physical perspective and the to physics: the study of modern string theory.
joint perspective – is the focus of the Simons Center for
Geometry and Physics. For interviews with John Morgan and Dennis Sullivan
visit www.simonsfoundation.org.
How will the center create an atmosphere where sci-
entists from both disciplines can collaborate?

We hope to create the collaborative atmosphere in sev-

eral ways. First of all, the building will have much open,
common space with blackboards, chairs and tables to
facilitate spontaneous, scientific conversations. As we
search for permanent members, post-docs and visitors,
we will put real emphasis on a desire for collaboration
across the math-physics divide. On the programmatic
8 Simons Foundation Annual Report 2008 { Math & Science }

Math for America

The program has recruited, trained and retained more than 200 skilled
mathematicians to work as teachers.

Zach Korzyk’s biggest challenge teaching math at a MƒA. After joining the program, MƒA sent him to Bard
New York City public school is keeping his students College for a master’s degree in teaching with a con-
motivated. centration in secondary mathematics.

“Some students don't like that I won't let them be pas- Korzyk is about halfway through his five-year commit-
sive in class and do poorly,” said Korzyk. “I make them ment to MƒA, and while it’s a tough job, he said he
take notes and answer questions. The upper-level loves his work.
students are grateful for challenging problems and
engaging conversations.” “I really enjoy coming up with interesting activities that
pleasantly surprise my students,” Korzyk said. “I like to
Korzyk, 24, has been teaching math since 2007 as encourage them and see them grow mathematically.”
a fellow in the Math for America (MƒA) program. He’s
one of about 200 teachers MƒA has recruited to help MƒA was launched in 2004 to address the deficit in
address a critical shortage of qualified math teachers. math education. To date, the program has recruited,
Nearly 40 percent of all public high-school math teach- trained and retained more than 200 skilled mathemati-
ers do not have a degree in math or a related field, cians to work as teachers in New York City’s public
according to one study. schools.

As an undergraduate at Boston College, Korzyk
majored in theatre arts and computer science, with a
minor in mathematics. He wanted to teach math but
wasn’t sure how he could get a job without a degree
in teaching. Then, he spotted an advertisement for
Building on this success, MƒA is expanding to other
cities around the country. The nonprofit has created
a national office while starting new programs in San
Diego, Los Angeles and Washington, DC.
 9

“The ultimate goal of MƒA programs is to convince people that our approach
to recruit and retain outstanding teachers works and our underlying principles
can dramatically improve mathematics education across the country.”
– John Ewing

To further its expansion, MƒA seeks partnerships with
state governments, educational institutions and foun-
dations. Leading the expansion is MƒA’s new presi-
dent, John Ewing, the former head of the American
Mathematical Society.
Exceptional high-school math teachers currently work-
ing in public schools are recruited into the four-year
Master Teacher program. Teachers receive annual
stipends and participate in professional development
and leadership opportunities.

“The ultimate goal of MƒA programs is to convince peo- For Korzyk, the experience of teaching with MƒA and
ple that our approach to recruit and retain outstanding being part of a corps of other math-savvy individuals
teachers works and our underlying principles can dra- has taught him lessons that he applies every day on
matically improve mathematics education across the the job.
country,” Ewing said.
“I’ve learned to maintain high but clear expectations for
For gifted mathematicians who are new to teaching, my students,” he said. “I am getting better at explaining
MƒA offers its five-year fellowship. Following a rigor- assignments in different ways so my students at every
ous selection process, fellows spend a year earning learning level know what to do.”
a master’s degree in mathematics education with a
partner college or university. Fellows then teach for four www.mathforamerica.org
years in New York City’s public schools. The fellowship
includes a full tuition scholarship with a stipend of
$100,000 over five years to supplement their teacher’s
salary. The program includes mentoring, leadership
opportunities and professional development services.
10 Simons Foundation Annual Report 2008 { Math & Science }

Institut des Hautes Études

Scientifiques
Gromov’s team hopes that the knowledge they will gain through their
investigation could help in discovering ways to prevent heart attacks.

Heart attacks, known to doctors as myocardial infarc-
tions, are a leading cause of death around the world.
At the Institut des Hautes Études Scientifiques (IHÉS), a
research team led by Mikhail Gromov is seeking to use
mathematics to better understand the cause of heart
attacks.
The Simons Foundation supports Gromov’s investiga-
tion of the heart as part of its 11-year record of contri-
butions to IHÉS. Half of a recent contribution from the
Simons Foundation will fund the Institute’s activities at
the interface of biology and mathematics.
IHÉS is one of the world’s premiere research institutions.
Located in Bures-sur-Yvette, France, IHÉS is dedicated
to fostering fundamental advances in mathematics,
physics and other related theory-based disciplines.
Founded in 1958, IHÉS has a small number of perma-
nent professors, appointed for life, and invites about
200 visitors a year for varying terms averaging three
months. It also has a small number of long-term visi-
tors. Research is not contracted or directed: it is left to
each individual researcher to pursue their own goals.
Permanent professors are only required to be in resi-
dence six months a year.

The investigation into the electrophysiological geometry www.ihes.fr

of the heart by Gromov continues the Institute’s tradi-
tion of fundamental research in the sciences. Gromov’s
team hopes that the knowledge they will gain through
their investigation will help in discovering ways to
prevent heart attacks.The objective is to identify a
metric that governs the propagation of electromagnetic
waves in the heart. The metric may prove useful in
characterizing normal and abnormal heart functions.

Left: Mikhail Gromov.

Right: Dennis Sullivan

and Mikhail Gromov.
 11

Top: Image of an
electrocardiogram.

Left: Maxim Kontsevich.

Right: Alain Connes.

12 Simons Foundation Annual Report 2008 { Math & Science }

American University of Beirut

“In the broad light of day mathematicians check their equations and their
proofs, leaving no stone unturned in their search for rigour. But, at night, under
the full moon, they dream, they float among the stars...”

Michael Atiyah is sometimes described as one of the mathematical modeling will be greatly enhanced with
greatest living mathematicians. He was the corecipient, leadership in this chair in the mathematical sciences,”
along with Isadore Singer, of the Abel Prize, an award Bitar said.
that is compared to the Nobel Prize. The prize was
awarded for their development of the Atiyah-Singer Atiyah has spoken passionately about the importance
Index Theorem that is used to count the number of of mathematics. During a speech at AUB, he described
independent solutions of many important differential mathematics as “an essential component of our world.
equations. In all the sciences, physical, biological or social, math-
ematics is increasingly important, and in recent years
In honor of Atiyah’s achievements, the Simons the business and financial community has also woken
Foundation has established the Michael Atiyah Chair up to this fact.” When he was awarded an honorary
in Mathematical Sciences at the American University doctorate from AUB in 2004, Atiyah described himself
of Beirut (AUB). as “a firm believer in the fundamental and central role
that mathematics plays in our modern technological
The gift will be used to attract top researchers and society, where it underpins everything from science
professors to the university. AUB’s Faculty of Arts and and engineering to finance and economics.”
Sciences Dean Khalil Bitar noted that the endowment
would bring new possibilities to the study of mathemat- The Simons Foundation hopes that the gift will help the
ics at the university. university excel in both academic research and out-
standing pedagogy.
“The recent surge in the use of mathematical tech-
niques via computer simulations in fields that tradition- “For many years AUB has been a beacon of scholarship
ally have not made use of mathematical analysis and/or and tolerance in an embattled part of the world,” said
Jim Simons. “We are pleased to think that our contribu-
tion will help and strengthen the university in continuing
to fulfill this important mission.”

www.aub.edu.lb

College Hall, the main

building at the American
University of Beirut.
 13

Memorial Sloan-Kettering
Cancer Center
Scientists are trying to create therapies that target cancer cells and the
abnormal signaling pathways needed to maintain them.

Of the hundred of types of cancers that can afflict the to kill cancer cells, specifically block cell proliferation,
human body, brain cancer poses some of the toughest inhibit development of specific stem cells and prevent
treatment challenges. Getting drugs into the brain can cancer cell survival.
be difficult because a barrier physically shields the brain
from chemicals circulating in the body. Medications that “These machines can screen compounds thousands of
do enter the brain may cause serious side effects. times faster than we could in the past,” said Hakim
Djaballah, the director of the high-throughput screening
Memorial Sloan-Kettering Cancer Center’s new Brain core facility.
Tumor Center (BTC) is working to overcome these
obstacles using recently revealed insights into the BTC director Dr. Eric Holland has developed a prom-
molecular and cellular properties of tumors. Scientists ising new system for glioma modeling. Holland’s col-
are trying to create therapies that target cancer cells league, neurosurgeon Philip Gutin, and Shahin Rafii,
and the abnormal signaling pathways needed to main- a hematologist at Weill Cornell Medical College, are
tain them. seeking to treat tumors by cutting off their blood supply.
The team is studying the use of blood supply-produc-
The Simons Foundation supports this important work ing cells derived from bone marrow.
by underwriting preclinical studies of new therapies for
the type of tumors called gliomas to confirm that they Research into brain tumors may also be useful in
produce their desired effect in animal models. There understanding autism. Of the several candidate genes
currently exists no drug pipeline developed specifically that enhance the risk for autism uncovered so far,
for gliomas, and such preclinical work is an essential three – PTEN, TSC1 and TSC2 – are part of biochemi-
step in the design of new therapies for use in humans. cal pathways that suppress the formation of tumors.
Disabling these genes in mice produces signs and
The BTC is undertaking both basic scientific investiga- symptoms that are relevant to autism in humans.
tions into brain tumors and translational research in
which potential new targets and therapies make the “Putting Memorial Sloan-Kettering’s basic science peo-
transition from animal experiments to humans. ple together with neurosurgeons and medical oncolo-
gists and radiation oncologists – everyone who treats
One major goal at BTC is to find chemicals that can brain tumors – facilitates the exchange of ideas among
be used in glioma treatment. In a gleaming room in investigators with conjoined interests,” said Dr. Holland.
Memorial Sloan-Kettering’s new research tower on
Manhattan’s Upper East Side, the arms of a robotic www.mskcc.org
laboratory click and whirr. Machines are testing
250,000 compounds to see if they might be useful in
killing tumor cells. The screening machines have found
several compounds that enhance the ability of radiation
14 Simons Foundation Annual Report 2008 { SFARI }

SFARI: Simons
Foundation Autism
Research Initiative
 15

“We are not alone in the effort to

understand autism. This effort goes
to the core of the human condition,
so one can expect that real advances
will take the combined efforts of a
world wide community of scientists
of all stripes.”

– Gerald D. Fischbach
16 Simons Foundation Annual Report 2008 { SFARI }

From the SFARI Director

“To deal with the massive amounts of phenotypic
and genetic data, we have created an interactive
database called SFARI Base that will allow
sophisticated queries of the data, and hopefully
uncover new correlations.”

An important goal of SFARI is to create tools that scientists can use to enhance our
understanding of autism. Last fall, we released the first set of phenotype data and
DNA from the SFARI Simplex Collection (SSC). The SSC is a tool of fundamental
importance that will facilitate the identification of autism genetic risk factors. Studying
alterations in gene structure and function is a crucial first step toward understand-
ing underlying molecular mechanisms. This information will, in turn, lead us to new
therapeutics and to a better understanding of environmental influences on the devel-
oping nervous system.

The SSC aims to establish a repository of genetic samples and phenotypic data from
simplex families, where one child is diagnosed with an Autism Spectrum Disorder
while both parents and other siblings are unaffected. Our initial goal is to identify de
novo copy number variants (chromosomal deletions or duplications) in probands
from 2,000 families.

To deal with the massive amounts of phenotypic and genetic data, we have created
an interactive database called SFARI Base that will allow sophisticated queries of the
data, and hopefully uncover new correlations.

We recently unveiled SFARI Gene, a new online autism gene database that appears
on our website at http://gene.sfari.org. SFARI Gene collects information on genes
linked to Autism Spectrum Disorders from the published scientific literature. This
publicly available database will be expanded by addition of new, interactive modules
that incorporate genetic structural alterations as well as biochemical, physiological
and anatomic data.
 17

 critically important “tool” is an interactive community of scholars dedicated to shar-

A
ing information, research reagents, animals, and most important, ideas to enhance
autism research. To build this community, we have organized a series of workshops
at the Simons Foundation and many discussions with individuals and small groups,
and we are looking forward to our first Annual Science Meeting in New Orleans in
April 2009. We will expand the number of workshops in the coming year as collabo-
rations expand and questions become better defined. Our website will serve as an
important resource for Simons Investigators and for all other scientists with interests
in related areas.

At the present time, we fund research in three areas: gene discovery, molecular
mechanisms, and cognition and behavior. Our hope is to blur the distinctions, tech-
nical hurdles and strategic barriers that keep these approaches too far apart. A list of
Simons Investigators can be found at http://sfari.org/simons-investigators.

 e are not alone in the effort to understand autism. This effort goes to the core of
W
the human condition, so one can expect that real advances will take the combined
efforts of a worldwide community of scientists of all stripes. We look forward to
building partnerships in the coming years.

Gerald D. Fischbach
SFARI Director
 18 Simons Foundation Annual Report 2008 { SFARI }

John Constantino

“ How is it that you can have part of the syndrome, but not all of it?”

From the very beginning of his medical training, John iors – are not independent of each other. “It seems that
Constantino has coupled rigorous clinical research with they’re very tightly connected to each other and that
teaching social workers, educators and parents about some underlying cause may produce symptoms in all
children’s mental health. three domains of autism at the same time,” he says.

In 1999, he helped develop the first scale of traits of The SRS has also allowed Constantino to quantitatively
people on the autism spectrum that is quick and easy study the ‘broader autism phenotype’ – milder behav-
enough for general practitioners and school teachers ioral, neurobiological or anatomical traits in the siblings
to use. and parents of children with autism – and to increase
the statistical power of traditional linkage studies.
Since its commercial release in 2005, the test, the Social
Responsiveness Scale (SRS), has been published in “How is it that some individuals have subtle autistic
seven languages and is set to be available in eight more. social impairments that fall below the level of severity
Clinicians say it’s one of the most reliable measures of seen in fully affected children?” he asks. “Understanding
autism, and has a 70% correlation with scores on the this can provide insight into the confluence of factors
ADI-R – the gold standard of autism diagnoses. that give rise to the full autistic syndrome.”

The SRS’s 65-item questionnaire focuses on reciprocal

social behavior, such as the ability to understand and
respond to emotional cues from others, and takes just
15 to 20 minutes to complete.

On the basis of the first sets of SRS data, Constantino

found that the three domains of autism – social impair-
ment, language impairment and repetitive behav-
 19

Guoping Feng

“Our goal now is to look at how the genes [causing] synaptic  

defects in the striatum are related to autism.”

People on the autism spectrum tend to exhibit repeti- “Many steps can affect circuitry function, but the syn-
tive behaviors – a characteristic that’s also seen in those apse is definitely one of the key places where some-
with obsessive-compulsive disorder (OCD). thing can go wrong,” Feng says.

Neurobiologist Guoping Feng is searching for the The synapse is likely to prove equally important in
genetic basis of repetitive behaviors by unraveling the autism, Feng says. SAPAP3 interacts directly with
mechanisms at work in OCD. another synaptic protein, SHANK3, mutations in which
have been associated with autism.
In August 2007, Feng and his colleagues at the Duke
University Medical Center published the first well- SAPAP3 and SHANK3 are expressed highly in syn-
described mouse model of OCD, a disorder defined apses located in the striatum – the deep, central brain
by recurrent, unwanted thoughts and aimless rituals. region that is known to undergo changes in people with
The researchers focused on SAPAP3, a protein that OCD. Some studies have also found abnormally large
provides scaffolding at the synapse, the junction at striatal volumes in people on the autism spectrum.
which nerve cells communicate. By deleting the gene
for SAPAP3, the researchers were able to turn healthy “We think that compulsive behavior in OCD and autism
mice into compulsive, round-the-clock groomers that may have a common circuitry mechanism,” Feng says.
scratched the hair right off their faces. “Our goal now is to look at how the genes [causing]
synaptic defects in the striatum are related to autism.”
Using up to 400 samples from the Simons Simplex
Collection, a gene bank of children on the autism spec-
trum and their families, Feng’s team plans to look for
mutations in SAPAP3 and about 20 other genes that
encode synaptic proteins.

Feng’s team reported in a January 2009 paper that

they had found rare mutations in the SAPAP3 gene in
4.2 percent of people with OCD, compared with 1.1
percent in a control group without OCD.
 20 Simons Foundation Annual Report 2008 { SFARI }

Dan Geschwind

“ Nowhere has there been more progress in genetics in any  

complex disease than in autism.”

In August 2001, neurogeneticist Daniel Geschwind males. In November 2008, the researchers linked
and other researchers affiliated with the nonprofit Cure CNTNAP2 to families with specific language impair-
Autism Now created the Autism Genetic Resource ment, another childhood development disorder.
Exchange (AGRE), a gene bank of more than 4,500
samples from families in which at least two children Geschwind, whose first career was strategic business
have autism. consulting, says “you’d need a crystal ball” to know
where the rapidly growing autism field is headed, par-
Since then, using the AGRE samples, Geschwind has ticularly because it comprises such a diverse spectrum
led many of the largest high-resolution genome scans of behavioral and genetic characteristics.
intended to pinpoint the chromosomal anomalies in
people on the autism spectrum. “What we’ve learned most is that autism is far more
heterogeneous than any of us expected,” he says.
At the University of California, Los Angeles, Geschwind’s “But on the other hand, nowhere has there been more
lab studies brain asymmetry, fronto-temporal dementia progress in genetics in any complex neuropsychiatric
and other neurological diseases. But its main focus is the disease than in autism.”
genetics of autism. In particular, Geschwind is seeking
genetic similarities among people with autism who share
endophenotypes – quantifiable markers of disease – such
as sex, language ability and social impairment.

For instance, his team found in January 2008 that a

gene thought to be involved in nerve cell communica-
tion, contactin-associated protein-like 2 or CNTNAP2,
is associated with autism and language deficits in
 21

Rebecca Saxe

“ The answers are not going to be at the level of the biology,  

the answers are going to be at the level of the systems.”

‘Theory of mind’ – the ability to sense what other people Saxe plans other autism-related experiments, including
want, believe or intend – has fascinated philosophers brain scans of people on the spectrum making moral
and psychologists for centuries. But it wasn’t until judgments, and a comprehensive survey of how spe-
2003 that Rebecca Saxe, then a graduate student, cific brain regions develop in babies at risk of develop-
identified a precise region in the brain, a part of the ing autism and in healthy controls.
temporo-parietal junction, that's active when we try to
divine others’ thoughts. “My gut instinct about the mind – and I don’t know about
autism, but I’m trying what I know – is that the answers
Now an assistant professor at the Massachusetts are not going to be at the level of the biology,” she
Institute of Technology’s Department of Brain and says. “The answers are going to be at the level of the
Cognitive Sciences, Saxe is using functional magnetic systems.”
resonance imaging to study social cognition in people
on the autism spectrum, who often have trouble grasp-
ing what others are thinking.

In one experiment, for instance, Saxe uses a new pro-

cedure in which live video displays brain activity during
real-time, back-and-forth social interaction – a measure
that she predicts will be strikingly different in people
with autism.
22 Simons Foundation Annual Report 2008 { SFARI }
Michael Wigler Q&A
“We were discovering new mutations – things that occur spontaneously
in the parental germ line.”
The Simons Simplex Collection (SSC) aims to collect
DNA and phenotypic information from 2,000 ‘simplex’
families, in which one child has autism but siblings
and parents are unaffected. The SSC is a collabora-
tion of 13 university-affiliated research clinics across
the United States and Canada, under the guidance of
the University of Michigan Autism & Communication
Disorders Center. The clinics follow meticulous phe-
notype protocols, and this information is paired with
genetic data from the blood samples.
Using different technologies, groups led by Michael
Wigler, of Cold Spring Harbor Laboratory, and Matthew
State, of Yale University, are analyzing the samples to
detect copy number variations – chunks of DNA that
are duplicated or deleted.
Here, Dr. Wigler discusses the evolution of the SSC.
How did the idea for the SSC come about?
We had preliminary results that de novo (spontaneous
or new) copy number variations are present at a higher
rate in kids with autism than in unaffected children, but
we only saw this as a significant difference in the so-
called ‘simplex’ families, families with only one child on
the spectrum. This effect was not significant in families
with multiple children on the spectrum (the ‘multiplex’
families). We were discovering new mutations – things
that occur spontaneously in the parental germ line. So
you wouldn’t expect two kids in the multiplex family to
have them. Previous autism collections were devoted to
multiplex families. We decided that it would be very use-
ful to have a collection devoted to the simplex families.
What's the status of the collection?
We’ve been getting samples since March 2008, and
we’ve only [genotyped] the first 250 families. But the
results that we saw previously are holding up. There’s
also a strong genomic asymmetry in boys and girls.
Why use two methods to genotype the data?
Why do you have two lungs? In case one of them fails.
There’s a little bit more information of one type that
Left: Close-up of a syringe
injecting buffer fluid into
a sequencer gel. The gel
will then be loaded into
a sequencer, which
will automatically analyze
the DNA molecules.
Right: Dr. Michael Wigler,
a researcher at Cold Spring
Harbor Laboratory.
 23

“The real goal is to find the genes that are causing autism, so that we can
formulate a neurophysiologic hypothesis for why a child is on the spectrum.”

you can get from the Yale method, and a little bit more Another goal is to see if there are common polymor-
resolution that you can get from our method. The two phisms [common genetic variations in the general pop-
platforms search for copy number variations using dif- ulation] that are associated with autism. So far, there’s
ferent strategies. no evidence that these things exist. They would be
very important to find. For instance, why are girls less
What are your genotyping goals for the end of 2009? likely to be on the spectrum? It’s got to be something
genetic ultimately. It would be an enormously useful
We’d like to identify several hundred loci [the area on clue if we could see something like that.
a chromosome where a particular gene is located].
Hopefully some of these will be recurrent. That is, they
will be independently occurring events that tell us this
region is important. The real goal is to find the genes
that are causing autism, so that we can formulate a
neurophysiologic hypothesis for why a child is on the
spectrum. We should be further along in 2009, by at
least threefold more families than we have now.

Left: Electrophoresis gel.

Right: Fluorescence
microscopy of
chromosomes.
24 Simons Foundation Annual Report 2008 { SFARI }

How the SSC Works

The primary goal of the Simons Simplex Collection is to establish a permanent
repository of genetic samples from 2,000 families, each of which has one
child affected with an autism spectrum disorder (ASD) and parents unaffected
with ASD. Each genetic sample will have an associated collection of data that
provides a precise characterization of the individual (phenotype). Rigorous
phenotyping will maximize the value of the resource for a wide variety of future
research into the causes and mechanisms of autism.

Visit http://sfari.org/ssc

Families Phenotype
recruited data and
blood samples
collected

Families with one child on the spectrum are recruited

into the collection at 13 sites across North America.
Site staff members screen each family to ensure they
meet study criteria.

Participating family members complete an extensive Blood samples

testing protocol, including questionnaires, behavioral sent to central
assessment, cognitive testing, physical exam and blood repository
sample collection.

Blood from each family member is sent to the Rutgers

University Cell and DNA Repository (RUCDR) for pro-
cessing. The RUCDR runs screening tests, whole-blood
DNA extraction and cell line creation.
 25

Centralized Final phenotype

review of key data published
phenotype in SFARI Base
data data repository

Data are reviewed and validated by a panel. The review

includes diagnoses, behavioral assessment and medi-
cal history. Data are made anonymous.

Researchers
request access
and submit
findings

Approved researchers can access phenotype data

directly from SFARI Base. Shipments of biological sam-
ples are coordinated through the RUCDR.

Data from researchers is submitted to SFARI Base,

continuing to add to the richness of the information.
26 Simons Foundation Annual Report 2008 { Financials }

Financials
 27

Desintegration d'un kaon

positif (meson K+) en vol.
© CERN Copyright

This image is taken from

one of CERN's bubble
chambers and shows the
decay of a positive kaon in
flight. The decay products
of this kaon can be seen
spiraling in the magnetic field
of the chamber. The invention
of bubble chambers in 1952
revolutionized the field of
particle physics, allowing real
tracks left by particles to be
seen and photographed by
expanding liquid that has
been heated to boiling point.
28 Simons Foundation Annual Report 2008 { Financials }

Balance Sheet

ASSETS June 30, 2008 June 30, 2007

Cash and Cash Equivalents $27,861,666 $815,022
Investment Portfolio 1,064,269,117 693,764,890
Property and Equipment, Net 16,094,323 514,561
Prepaid Excise Taxes 182,146 0
Other 93,749 886,350
Total 1,108,501,001 695,980,823

LIABILITIES
Grants Payable 129,546,444 76,690,635
Taxes Payable 0 2,245,374
Deferred Excise Tax Liability 8,659,983 7,071,983
Other 0 265,548
Total 138,206,427 86,273,540

NET ASSETS
UNRESTRICTED NET ASSETS $970,294,574 $609,707,283
 29

Income Statement

REVENUE June 30, 2008 June 30, 2007

Contributions $180,480,577 $70,923,570
Investment Income 290,467,232 182,565,644
Total 470,947,809 253,489,214

EXPENSES
Grants Paid 47,660,532 32,607,522
Change in Grants Payable 52,855,809 47,349,034
General and Administrative 1,649,880 817,816
Program 5,287,127 1,102,637
Depreciation and Amortization 222,199 164,939
Federal Excise Taxes 2,908,800 3,633,092
Other 0 89,000
Total 110,584,347 85,764,040

NET INCOME $360,363,462 $167,725,174

Proportions of Expenses ($’s in Thousands)

30 Simons Foundation Annual Report 2008 { Simons Staff }

Trustees

Marilyn H. Simons, Ph.D.

President
Marilyn Hawrys Simons has worked primarily in the nonprofit sector as a volunteer
for the past 20 years, focusing on education. She has served as president of the
Simons Foundation since 1994. Ms. Simons is currently president of the board of
LearningSpring School, a school for children diagnosed with autism spectrum disor-
ders, and is a member of the board of trustees of the East Harlem Tutorial Program.
Ms. Simons is also a trustee of the Cold Spring Harbor Laboratory. She received a
B.A. and a Ph.D. in economics from the State University of New York at Stony Brook.

Mark Silber, J.D., M.B.A.

Vice President
Mark Silber, J.D., M.B.A., is vice president and general counsel at Renaissance
Technologies, where he has held responsibility for finance, administration and
compliance since joining the firm in 1983. Prior to joining Renaissance, he was a
Certified Public Accountant with the accounting firm of Seidman & Seidman, now
BDO Seidman. Mr. Silber holds a bachelor’s degree from Brooklyn College, a J.D.
and L.L.M. in tax law from the New York University School of Law, and an M.B.A. in
finance from the New York University Graduate School of Business Administration.

James H. Simons, Ph.D.

Secretary and Treasurer
James H. Simons, Ph.D., is secretary and treasurer of the Simons Foundation. Dr.
Simons is president and founder of Renaissance Technologies. Prior to his finan-
cial career, Dr. Simons served as chairman of the Mathematics Department at the
State University of New York at Stony Brook, taught mathematics at Massachusetts
Institute of Technology and Harvard University, and was a cryptanalyst at the Institute
of Defense Analyses in Princeton, N.J. Dr. Simons’ scientific work was in the area
of geometry and topology, and his most influential work involved the discovery and
application of certain measurements, now called Chern-Simons invariants, which
have had wide use, particularly in theoretical physics. Dr. Simons holds a B.S.
from the Massachusetts Institute of Technology and a Ph.D. from the University
of California, Berkeley, and won the American Mathematical Society’s Veblen Prize
for his work in geometry in 1975. He is a former chairman of the Stony Brook
Foundation and is currently a trustee of Rockefeller University, Massachusetts
Institute of Technology, Brookhaven National Laboratory, the Mathematical Sciences
Research Institute and the Institute for Advanced Study.
 31

Simons Foundation Staff

Marilyn Simons, Ph.D. Adrienne Greenberg, B.S.

President Business Manager

James H. Simons, Ph.D. Marion Greenup, M.P.H., M.Ed.

Secretary and Treasurer Vice President, Administration

Maria Adler, M.B.A. Stephen Johnson, Ph.D.

Vice President, Finance Informatics Director

Marta Benedetti, Ph.D. Apoorva Mandavilli, M.S., M.A.

Associate Director for Research Executive Editor

Sascha Brodsky, M.S., M.I.A. Alan Packer, Ph.D.

Director of Communications Associate Director for Research (not pictured)

Meghan Criswell Amy Pasquariello, B.A.

Administrative Assistant Project Manager, SFARI

Gerald D. Fischbach, M.D. Lauren Rath, B.A.

Scientific Director Grants Associate

Chris Fleisch, B.S. John Spiro, Ph.D.

Programmer/Analyst Senior Associate Director for Research

Andrea Gallego, B.A. Patricia Weisenfeld, M.P.A.

Executive Assistant Director of Family Giving
32 Simons Foundation Annual Report 2008 { Simons Grants }

Connect and Collaborate

33
34 Simons Foundation Annual Report 2008 { Simons Grants }

The Simons Foundation supports outstanding individual researchers and

institutions seeking funding for advanced work in the basic sciences
and mathematics, with a focus on innovative scientific projects where our
involvement will play an essential role. In the course of this support,
the foundation is interested in partnering with other entities, or providing
matching support where appropriate.

Historically, the Simons Foundation has accepted only solicited grant

proposals. All grant decisions are made by the trustees of the foundation and
the foundation staff. The foundation does not make awards to individuals,
except through their institutions.

Simons Investigators

Ralph Adolphs Michael D. Ehlers

California Institute of Technology Duke University
John M. Allman Guoping Feng
California Institute of Technology Duke University
Mark Bear Gordon J. Fishell
Massachusetts Institute of Technology New York University School of Medicine
Arthur Beaudet Eric Fombonne
Baylor College of Medicine McGill University
Raphael Bernier John Gabrieli
University of Washington Massachusetts Institute of Technology
Joseph Buxbaum Daniel Geschwind
Mount Sinai School of Medicine University of California, Los Angeles
Brian Chait Jay Gingrich
The Rockefeller University Research Foundation for Mental Hygiene, Inc.,
New York State Psychiatric Institute
Aravinda Chakravarti
Johns Hopkins University School of Medicine Joseph Gogos
Columbia University
Andrew Chess
Massachusetts General Hospital Ann Graybiel
Massachusetts Institute of Technology
John Constantino
Washington University Paul Greengard
The Rockefeller University
Edwin Cook, Jr.
University of Illinois at Chicago James F. Gusella
Massachusetts General Hospital
Eric Courchesne
University of California, San Diego Nathaniel Heintz
The Rockefeller University
Mark Daly
Massachusetts General Hospital Barbara Hempstead
Weill Medical College of Cornell University
Ted M. Dawson
Johns Hopkins University School of Medicine Z. Josh Huang
Cold Spring Harbor Laboratory
Curtis Deutsch
University of Massachusetts Medical School
 35

Eric R. Kandel Vijaya Ramesh

Columbia University Massachusetts General Hospital
Ami Klin Louis Reichardt
Yale University University of California, San Francisco
Richard Krauzlis Bernardo Sabatini
Salk Institute for Biological Studies Harvard Medical School
Abba Krieger Joshua Sanes
University of Pennsylvania Harvard University
Louis Kunkel Rebecca Saxe
Children's Hospital Boston Massachusetts Institute of Technology
David Ledbetter Morgan Sheng
Emory University Massachusetts Institute of Technology
Arnold J. Levine Maggie Shiffrar
Institute for Advanced Study Rutgers, The State University of New Jersey
Pat Levitt Pawan Sinha
Vanderbilt University Massachusetts Institute of Technology
Dan Littman Hazel Sive
New York University School of Medicine Whitehead Institute for Biomedical Research
Catherine Lord Matthew State
University of Michigan Yale University
Christa Lese Martin Thomas Südhof
Emory University Stanford University
Steven McKnight David Sulzer
University of Texas Southwestern Medical Center Columbia University
Judith Miles Mriganka Sur
University of Missouri Massachusetts Institute of Technology
Alea Mills James Sutcliffe
Cold Spring Harbor Laboratory Vanderbilt University
Anthony Monaco Susumu Tonegawa
University of Oxford Massachusetts Institute of Technology
Daniel Notterman Li-Huei Tsai
Princeton University Massachusetts Institute of Technology
Opal Ousley Richard Tsien
Emory University Stanford University
Luis Parada Michael Ullman
University of Texas Southwestern Medical Center Georgetown University
Karen Parker Christopher Walsh
Stanford University Beth Israel Deaconess Medical Center
Paul Patterson Stephen Warren
California Institute of Technology Emory University
Kevin Pelphrey Zachary Warren
Yale University Vanderbilt University
Bradley Peterson Michael Wigler
Columbia University Cold Spring Harbor Laboratory
Judith Piggot Huda Zoghbi
University of California, Los Angeles Baylor College of Medicine
Joseph Piven
University of North Carolina at Chapel Hill
36 Simons Foundation Annual Report 2008 { Simons Grants }

Grants to Institutions

Math and Physical Science Memorial Sloan-Kettering Cancer Center

New York, New York
American University of Beirut
Beirut, Lebanon The Rockefeller University
New York, New York
Friends of the Institut des Hautes Études Scientifiques
New York, New York
Harvard University Autism
Cambridge, Massachusetts Baylor College of Medicine
Massachusetts Institute of Technology Houston, Texas
Cambridge, Massachusetts Beth Israel Deaconess Medical Center
Mathematical Sciences Research Institute Boston, Massachusetts
Berkeley, California California Institute of Technology
Science Festival Foundation Pasadena, California
New York, New York Children’s Hospital Boston
S. S. Chern Foundation for Mathematical Research Boston, Massachusetts
Beijing, China Children’s Hospital Philadelphia
Stony Brook University Philadelphia, Pennsylvania
Stony Brook, New York Cold Spring Harbor Laboratory
Tsinghua Education Foundation Cold Spring Harbor, New York
Beijing, China Columbia University
University of California, Berkeley New York, New York
Berkeley, California Cornell University
New York, New York

Math and Science Education Duke University

Durham, North Carolina
Aquarium of the Pacific
Long Beach, California Emory University
Atlanta, Georgia
Fannie & John Hertz Foundation
Livermore, California Georgetown University
Washington, District of Columbia
Math for America
New York, New York Harvard Medical School
Boston, Massachusetts
New England Aquarium
Boston, Massachusetts Johns Hopkins University
Baltimore, Maryland
Ohio State University
Columbus, Ohio Massachusetts General Hospital
Boston, Massachusetts
Massachusetts Institute of Technology
Life Sciences Cambridge, Massachusetts
Beth Israel Deaconess Medical Center McGill University
Boston, Massachusetts Montreal, Canada
Cold Spring Harbor Laboratory Mount Sinai School of Medicine
Cold Spring Harbor, New York New York, New York
Institute for Advanced Study New York University School of Medicine
Princeton, New Jersey New York, New York

Princeton University
Princeton, New Jersey
Research Foundation for Mental Hygiene, Inc.,
at New York State Psychiatric Institute
New York, New York
Rockefeller University
New York, New York
Rutgers, The State University of New Jersey
New Brunswick, New Jersey
Salk Institute for Biological Studies
La Jolla, California
Stanford University
Menlo Park, California
University of California, Los Angeles
Los Angeles, California
University of California, San Diego
San Diego, California
University of California, San Francisco
San Francisco, California
University of Illinois at Chicago
Chicago, Illinois
University of Massachusetts Medical School
Worcester, Massachusetts
University of Michigan
Ann Arbor, Michigan
SFARI Scientific Advisory Board
Dennis W. Choi, M.D., Ph.D.
Emory University
Wendy Chung, M.D., Ph.D.
Columbia University Medical Center
Thomas M. Jessell, Ph.D.
Columbia University
Nancy Kanwisher, Ph.D.
Massachusetts Institute of Technology
37
University of Missouri
Columbia, Missouri
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina
University of Oxford
Oxford, England
University of Pennsylvania
Philadelphia, Pennsylvania
University of Texas Southwestern Medical Center
Dallas, Texas
University of Washington
Seattle, Washington
Vanderbilt University
Nashville, Tennessee
Washington University in St. Louis
St. Louis, Missouri
Whitehead Institute for Biomedical Research
Cambridge, Massachusetts
Yale University
New Haven, Connecticut
Richard P. Lifton, M.D., Ph.D.
Yale University
Catherine E. Lord, Ph.D.
University of Michigan Autism
and Communication Disorders Center
J. Anthony Movshon, Ph.D.
New York University School of Medicine
Martin Raff, M.D.
University College London
38 Simons Foundation Annual Report 2008 { Contact }

For more information on the

Simons Foundation and SFARI,
please visit our websites:

simonsfoundation.org
sfari.org
The Flower of Maths
was quoted on page 5
with permission from “The
Unravelers: Mathematical
Snapshots,” AK Peters
Ltd, 2008.

All photos on the bottom

of pages 10 and 11 are courtesy
of IHÉS and appear in the book,
“The Unravelers: Mathematical
Snapshots,” © Copyright
Jean-François Dars, AK Peters
Ltd, 2008.

Michael Atiyah was quoted

on page 12 with permission
from “The Unravelers:
Mathematical Snapshots,”
AK Peters Ltd, 2008.
101 Fifth Avenue 5th Floor
New York, NY 10003
646 654 0066
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