A duo of university initiatives seeks to significantly
alter the medical landscape in terms of
disease research and patient treatment by combining the
latest in genetic science with good old-fashioned Johns
Hopkins know-how.
Discovery grants seeded both initiatives. A program in
computational genomics has already
blossomed into a center, while an effort to pioneer
individualized medicine has firmly taken root and
spawned a steering committee.
The programs were among the 11 inaugural grant winners
out of 74 proposals submitted to the
Framework for the Future's Discovery Working Group. Each of
the 11 selected initiatives received
startup funding of up to $200,000 per year for up to three
years. The university hopes that these
Discovery grants will ignite new areas and strengthen
existing ones where crossdisciplinary
interactions make a major difference.
The Discovery Working Group is one part of Framework
for the Future, a strategic planning
process that then Provost Kristina Johnson and President
William R. Brody initiated in May 2008. The
other two are Ways and Means, and People.
From their Discovery grant proposal "Nucleating a
Discipline: Creating Leadership in
Bioinformatics and Computational Biology," faculty from the
schools of Arts and Sciences, Engineering,
Medicine and Public Health have recently organized the
Johns Hopkins Center for Computational
Genomics, which will officially launch its work next
month.
The new center looks to extend the work of the
university's Genome Café — a genome biometry
laboratory housed in the School of Public Health's
Department of
Biostatistics — and the Genomic
Integration Across N Technologies (GIANT) working group,
which facilitates interactions among
people trained in statistics, bioinformatics, computer
science, biostatistics and medicine.
Sarah Wheelan, assistant professor of oncology
biostatistics and
bioinformatics at the School
of Medicine and the center's initiating principal
investigator, said that high-throughput technologies
such as microarrays generate unprecedented amounts of
highly interconnected biological and clinical
data, whose interpretation requires pioneering and
multidisciplinary approaches. The emergence of
these new technologies has made it seemingly impossible,
she said, for a single person to conceive,
direct, perform and interpret a modern large-scale
experiment.
The center looks to bring together the expertise
needed to take advantage of these new data
sets that promise breakthroughs in disease research.
Through training and by facilitating
collaboration, the center seeks to enable an investigator
to correctly interpret and make use of a
much larger fraction of his or her data. Prominent
bioinformaticians estimate that out of any given
biological or clinical experiment, only a fraction of the
potential biological discoveries are made when
the data are analyzed with standard techniques by a
nonspecialist.
"The average biologist can't make a dent analyzing all
this complicated information, and the
average statistician doesn't have the biological intuition
to follow up on leads presented by the
results," said Wheelan, who has a joint appointment in
Biostatistics in the School of Public Health.
"There are not enough people who have both biological and
statistical knowledge to direct these
experiments and clinical trials. The center will provide
this hybrid training and foster collaboration
that will allow us to more effectively attack biological
problems using statistical and computational
approaches."
The Johns Hopkins Center for Computational Genomics
will encompass three interacting
entities: a research center, a graduate education program
and a program in skills development for
professionals. The core staff are Wheelan; Rafael Irizarry,
a professor of
biostatistics at the School
of Public Health; Luigi Marchionni, an instructor of
oncology at the School of Medicine; and Jonathan
Pevsner, an associate professor at the Kennedy Krieger
Institute and of
neuroscience at the School of
Medicine.
It will be housed in the Preclinical Teaching Building
on the East Baltimore campus. The center's
Web site,
genomics.jhu.edu, is currently under construction.
A three-year grant also dealing with genetics was
given to a proposal in individualized medicine
submitted by faculty and staff from the Applied Physics
Laboratory, the
Berman
Institute of
Bioethics and the schools of Arts and Sciences,
Medicine and Public
Health.
David Valle, director of the
McKusick-Nathans Institute of Genetic Medicine at Johns
Hopkins
and a principal member of the newly founded Johns Hopkins
Individualized Medicine Program, looks to
shake up the one-size-fits-all approach to medicine and
usher in a new era where physicians treat a
person based on his or her genome and environmental
factors.
"Since the earliest days of medicine, physicians have
been educated in terms of generalities. In
a sense, standard medicine is average medicine; not to say
it's mediocre, but that it's based on a law of
averages," Valle said. "You'll learn here is what happens
with a patient with pneumonia. But once you get
into practice, you don't see generalities; you see a
specific person with pneumonia. When you talk with
experienced physicians, very often you come to the
realization that no two patients are exactly alike."
While the genomes of any two people are 99 percent
identical, the minute genetic variations in
the 3 billion DNA letters can make the difference between a
person who needs five times the average
amount of a certain drug to someone for whom the average
dose would be unsafe.
The Johns Hopkins Individualized Medicine Program
looks to take advantage of recent advances
in genetics, fueled by the completion of the Human Genome
Project in 2003 and the HapMap Project, a
multicountry effort to identify and catalog genetic
similarities and differences in human beings. To
date, HapMap has identified up to 90 percent of the common
genetic variation in humans.
Valle said that the evolution of genotype technology
has made the process cheaper and the
prospect of individualized medicine more practical.
"All of a sudden we can see right before us the
possibility of assessing each patient based on
his or her genetic individuality," Valle said. "By the same
token, there is an emerging field of exposure
biology aimed at understating environmental-experience
histories. We have the means to see the
differences and similarities among all patients."
Valle said that JHIMP will help measure and interpret
those differences.
"That is a big challenge, but one can certainly argue
that the future of health care will be in
individualized medicine," he said. "We have a strong
clinical-rich tradition here at Johns Hopkins. We
should be the leaders in this area. We should set the
pace."
JHIMP's initial aim will be to select a small pilot
group of patients, collect DNA samples from
each, give each an environmental questionnaire, and begin
to assess and develop a framework of
utilizing genetic and environmental variants in each
patient.
Researchers will develop a set of criteria of how and
when to use such information. Valle said he
realizes that major issues need to be confronted, such as
building a secure computational
infrastructure for storing and sharing this sensitive
information.
"For it to be practical, the information needs to be
instantly accessible so that a physician can
use it following a diagnosis, but we need to store it in a
way that protects the patient's privacy," he
said. "The transformation from average medicine to
individualized medicine will not happen overnight.
It will be an evolving process."
Valle said that the program will initially target 10
biological systems and develop research tools
to make use of the genetic information gathered from the
pilot group. As part of this effort, the
program will partner with the Johns Hopkins Center for
Computational Genomics.
"Sarah's group will be crucial to our activities,"
Valle said.
To date, a 16-member JHIMP steering committee, from
across JHU divisions, has been formed.
Its principals include Kathy Hudson, director of the Genetics and Public
Policy Center; Stephanie Reel,
the university's chief information officer; and Alex
Szalay, Alumni Centennial Professor in the Krieger
School's
Department of Physics and Astronomy.
"Alex is familiar with big-computations issues, so
that is where he comes in. What we're doing
also has enormous ethical aspects, and Kathy Hudson will
play a vital role so that we can avoid
pitfalls," he said.
Scott Zeger, acting provost and senior vice president
for academic affairs, said that important
scientific questions often require interdisciplinary teams
for significant discovery.
"I am encouraged and pleased to see outstanding Johns
Hopkins faculty, like these, working
across disciplines, departments and schools to use the new
biological measurements to advance our
understanding of biologic processes and ultimately to
promote health and treat disease," Zeger said.