Of Drugs and Diseases:
GCRC Provides Site for Clinical Studies
By Mika Ono
Hairy cell leukemia, a rare form of chronic leukemia, can
be fatal. But thanks to research conducted by investigators
of The Scripps Research Institute (TSRI) in its General Clinical
Research Center (GCRC), a seven-day course of 2CdA, an intravenous
medication with remarkably few side effects, now cures or
produces many years of freedom from disease in almost all
those receiving treatment.
The GCRCs role in bringing 2CdAmarketed under
the name cladribine (Leustatin) by Ortho Biotech, Inc., an
affiliate of Johnson&Johnsonfrom bench to bedside throughout
the 80s and 90s is perhaps the most dramatic example
of the GCRCs success. But it is by no means the only
The GCRC enables researchers to test the clinical
utility of discoveries made in the lab, says Program
Director Francis Chisari, who has himself conducted research
at the facility with the goal of developing therapeutic vaccines
to terminate chronic hepatitis B and C virus infections. "The
GCRC provides a forum to study the underlying mechanisms of
illnessessuch as thrombotic and cardiovascular diseases,
alcoholism, infectious diseases, sleep disorders, allergic
and autoimmune diseases, neurogenerative diseases, and canceras
well as to test the safety and efficacy of potential small-molecule
Located in a wing of the Scripps Green Hospital (although
still part of TSRI), the GCRC provides investigators with:
- a seven bed inpatient unit, including a sleep lab;
- an adjacent outpatient suite;
- nursing staff specially trained to provide both excellent
patient care and rigorous research data collection;
- a core laboratory staffed and equipped to perform specialized
research assays and provide specimen preparation and storage;
- a computer center, staffed with a biostatistician and
a systems manager, to help investigators design studies
and perform sophisticated genetic and clinical data management
In addition, the GCRC runs a forward-looking normal blood
donor program, which ensures that the blood used in laboratory
experiments is properly drawn, screened, and categorized.
"We have a health care professional who draws blood from a
pool of 200 to 300 donors," says the GCRCs Administrative
Manager Beth Bieger. "We are able to provide a medically controlled
environment for the procedure, protect the anonymity of donors,
and screen the blood for disease. This is a valuable servicea
much better alternative than having a post-doc roll up his
or her sleeve every time blood is needed in the lab."
The GCRC is funded by a competitively renewed grant from
the National Institutes of Health (NIH) and supplemented by
founding donations from the William Black family and continuing
support from the Stein Endowment Fund.
"The GCRCs NIH grant will support the clinical aspects
of an investigators researcheven if his or her
research grant does not have a clinical budget," Chisari notes.
"The GCRC can pick up the tab for things like documenting
a disease state or monitoring clinical parameters that may
be relevant to the fundamental question under investigation.
It also provides a licensed hospital environment for research
subjects to be monitored, for tissue and body fluids to be
collected, and for observational and interventional studies
to be performed in an outpatient setting."
Any researcher who wishes to conduct a study at the GCRC
must submit a protocol to the Human Subjects Committee (independent
of the GCRC), which reviews the safety, ethical, and human-protection
aspects of the study. If the protocol passes, the study is
then reviewed by the GCRC Scientific Advisory Committee, which
evaluates the proposal for scientific merit before granting
access to the facility. There are currently some 80 active
protocols at the GCRC, all of which have passed this rigorous
In addition to supporting studies by TSRI investigators,
the GCRC is open to clinicians in The Scripps Hospital and
Medical Group interested in conducting research. When studies
are sponsored by a for-profit entity, such as a pharmaceutical
company, the cost to the GCRC is reimbursed in full.
Ernest Beutler, professor and chair of the Molecular and
Experimental Medicine Department, is a TSRI investigator who
has made ample use of the facility during his 21 years at
the institute. Beutler initiated the initial 2CdA studies
on leukemia and lymphomaand subsequent studies that
showed the compound effective in the treatment of multiple
sclerosis. Most recently, he conducted research there showing
that the cost of effectively treating Gauchers disease
could be reduced from $500,000 to $80,000 per year by using
a lower dose of the recommended drug.
"When I first came to TSRI the economic situation in health
care was not as desperate as it is today," Beutler comments.
"It was still possible to carry out studies in a hospital
without paying a prohibitive amount for a bed. Today, the
GCRC is the only way TSRI researchers can carry out independent
clinical studies. The GCRC is absolutely key."
Registered Nurses Janine Kampleman (left)
and Kristen Greiner process patients specimens in the
Core Laboratory located on the GCRC nursing unit in the Green
Registered Nurses Helen Darnley (left)
and Susan Dastrup perform the daily calibration of the pulmonary
function equipment, used to measure the lung capacity of patients
participating in any of several allergy studies.