|
|
Yale-created Lyme
vaccine hits the market
LYMErix, a vaccine
against Lyme disease based on Yale research licensed to SmithKline
Beecham Pharmaceuticals, received Food and Drug Administration
approval in December for prescription use. Yale served as a major
study center during clinical trials of the compound, which is
the first vaccine approved for the disease.
The vaccine,
which became available to patients in January, was derived from
basic research performed at the School of Medicine by a team
including Richard A. Flavell, Ph.D., Fred S. Kantor, M.D., Erol
Fikrig, M.D., and Stephen W. Barthold, D.V.M., Ph.D.
The FDA approval
restricted its use to people between 15 and 70 years old pending
the outcome of further testing. “There are currently studies
in progress to evaluate the vaccine in children,” said Robert
T. Schoen, M.D., clinical professor of medicine and director
of the Lyme Disease Clinic at the medical school. In addition,
researchers will track the need for booster shots beyond the
three initial injections. Given over the course of a year, the
three doses of the vaccine were found in clinical trials to provide
78 percent protection against Lyme disease.
Schoen cautioned
that other measures, such as protective clothing and insect repellent,
should be taken with use of the vaccine. “The vaccine is
not 100 percent protective,” he said. “Other tick-transmitted
infections could also occur. It is important that the vaccine
be part of an overall prevention program.” |
|
|
|
“First
aid” for medical students
Yale’s
student editors weigh in with advice for the boards
Every spring
second-year medical students across the country prepare for the
first of three exams collectively known as “the boards,”
with a great deal riding on the outcome. At most medical schools,
students must pass Step 1, the first of the three tests that
comprise the United States Medical Licensing Exam, before they
can proceed to their clinical training in the third and fourth
years. And board scores are a yardstick by which applications
to residencies are measured. “If you do poorly on this exam,
it can make it difficult to get into the residency program you
want,” said Antony Chu, one of several Yale medical students
who played a role in publishing this year’s edition of the
leading guidebook to the exam. “Basically, it can have a
major impact on your career.”
Chu, a senior
student co-editor of the book, spent hundreds of hours last year
shaping and writing First Aid for the USMLE Step 1. Published
in January by Appleton and Lange, it is a student-written guide
that helps medical students focus their preparation for the boards.
Divided into three parts, it offers a description of the exam,
“high-yield” facts that apply to a variety of exam
topics and a guide to resources for study. “Essentially
every medical student in the country who is taking the exam will
have this book,” said Chu.
The 1999 edition
counted on the work not only of Chu, but several other writers,
editors and reviewers affiliated with Yale. Medical student co-editor
Esther Choo revised sections of the book and contributors included
M. Vaughn Emerson, Ronald Yap and Amy Nuernberg. William Stewart,
Ph.D., associate professor of surgery, was one of several faculty
reviewers. Tao T. Le, M.D., a third-year resident in internal
medicine at Yale, was one of the book’s three primary authors.
Because the
exam this year is being offered via computer at educational testing
centers instead of lecture halls, the book has changed some of
its advice, said Le. “The exam is no longer a pencil and
paper exam,” Le said. “The guide is now computer-oriented;
students need to know what buttons to push, how to navigate in
Windows.”
When the guide
emerged in 1990 as a 100-page book that sold for $12, it was
written and self-published by students at the University of California
at San Francisco. In 1992, Appleton and Lange picked it up, expecting
to sell 12,000 copies over three years. It sold 9,000 in its
first year alone, said Jessica Hirshon, an associate editor at
Appleton and Lange, adding that the book now sells about 30,000
copies a year.
For the Step
1 guide, Chu and Choo supervised the work of seven student contributors
and seven other students who reviewed material. The students’
incentive, Chu said, was not money. “They got a small stipend,
but in terms of the hours they put in, it’s nothing,”
he said. “The spirit of this book is a reflection of the
Yale System. It’s about students helping each other grow.” |
|
|
|
NCI
renews Cancer Center’s comprehensive designation
The Yale Cancer
Center, which is marking its 25th year in 1999, has again earned
designation from the National Cancer Institute as one of the
nation’s comprehensive cancer centers. It is one of 37 such
centers in the United States and the only one in southern New
England.
The center first
received NCI designation in 1974. Last August the NCI renewed
the center’s five-year Cancer Center Support Grant, which
supports research administration for the center’s 14 research
programs, shared resources and developmental activities. Redesignation
as a comprehensive cancer center followed in December.
To attain comprehensive
recognition, an institution must pass a peer review and perform
basic research, clinical research and cancer prevention, control
and population-based research. The NCI designation indicates
that Yale is a center of unusual excellence in research and clinical
care and an important community resource for education, information
and outreach. |
|
|
|
Graduate
students celebrate common ground at research symposium
Toiling away
in a highly specialized branch of scientific research, a graduate
student may feel isolated at times, however well the work is
going. But across the University, there is a larger community
of scholars, many working on similar problems. To enhance communication,
some 200 Yale graduate students in the biological and biomedical
sciences gathered in early February to exchange ideas across
department lines.
The fourth annual
Graduate Student Research Symposium brought together students
from the 12 core bioscience departments at Yale to discuss their
work. “We are all in related fields,” said Helen A.
Seow, a doctoral candidate in pharmacology and one of the symposium
organizers, “but once you get into a department you are
very separate. There are people who do things very similar to
what I do, but they’re across campus.”
During the conference,
11 students presented talks on their research in progress. In
addition, representatives of pharmaceutical and biotechnology
firms were present at a career forum and on panels discussing
topics such as Where Do You Go After Yale? and What
Else Can You Do With Your Ph.D.? Other speakers included
Susan Hockfield, Ph.D., dean of the Graduate School of Arts and
Sciences and professor of neurobiology at the medical school,
and Eric S. Lander, D.Phil., professor of biology at the Massachusetts
Institute of Technology and director of the Whitehead Institute/MIT
Center for Genome Research. A panel on careers in science communications
included Douglas Starr, co-director of the science journalism
program at Boston University, and Peter Brown, Ph.D., editor
of The Sciences magazine, published by the New York Academy
of Sciences.
Since the first
conference in 1996, graduate students have found many new vehicles
for communication, including the Combined Program in the Biological
and Biomedical Sciences, which this year met its goal of linking
all the relevant Yale departments. The greater sense of community
has been noticeable, said Elizabeth Doherty, a Ph.D. candidate
in the Department of Molecular Biophysics and Biochemistry and
chair of this year’s gathering. “Students find there
has been a lot more integration around campus,” she said. |
|
|
|
In
Macedonia refugee camp, students serve as volunteers
As the exodus
of ethnic Albanians from Kosovo continued this spring, a team
of student emissaries left for neighboring Macedonia on April
22 to work in a refugee camp served by the medical relief organization
Doctors of the World. Margaret Bourdeaux, Seth Goldbarg, Vivian
Lombillo, Sharon Chekijian, Aaron Covey and Anya Szeglin were
accompanied by their preceptor, Pamela Perry, M.D., assistant
professor of surgery (emergency medicine), and by Emine Alijaj,
R.N., P.A.-C., a physician associate in the Emergency Department
at Yale-New Haven Hospital who was born in Kosovo and speaks
Albanian.
The students
traveled as volunteers and made themselves available to distribute
blankets and oral rehydration fluids, set up tents, dig ditches
and change bandages. Before their departure, the group consulted
with faculty on medical and psychological issues, as well as
the culture shock they can expect to encounter in the camp and
upon their return. The students planned to stay in Macedonia
for four weeks before returning to New Haven. |
|
|
|
Elective
C-sections found to reduce HIV transmission to infants
An international
study has found that elective caesarean sections, coupled with
anti-retroviral therapy, can reduce the incidence of HIV transmission
from mother to infant to 2 percent, a nearly 10-fold decrease
compared to mothers who received neither treatment. The study,
in which a team from Yale participated, was published in April
in the New England Journal of Medicine. The principal
investigator for the Yale team, Warren A. Andiman, M.D., professor
of pediatrics and epidemiology, said the study by the International
Perinatal HIV Group could change approaches to delivery of infants
of HIV-positive mothers.
“My feeling
is that the usual practice in the United States will be to do
a C-section,” Andiman said. “Obstetricians will have
to think of compelling reasons not to provide caesarean sections
for their patients with HIV.”
Physicians were
already using elective C-sections to prevent transmission of
other infectious diseases, such as herpes simplex. “It has
been long held that being born vaginally poses a risk,”
said B. Joyce Simpson, R.N., M.P.H., pediatric HIV coordinator
at the Pediatric AIDS Care Program, and co-leader of the Yale
study. But when it came to vertical transmission of HIV, no single
study, either in the United States or in Europe, included a sample
large enough to provide statistically significant results. Moreover,
most data did not distinguish between controlled, elective C-sections
and emergency C-sections, which are almost as likely as vaginal
delivery to result in HIV infection in the infant. To prevent
transmission of HIV, the C-section must be done before labor
has begun and membranes have ruptured, Andiman said.
The National
Institute of Child Health and Human Development organized the
international study, which included mother-child pairs who were
studied prospectively, some beginning in 1982. It was comprised
of 15 study sites in the United States and Western Europe, including
Yale’s Prospective Longitudinal Cohort Study. More than
8,500 cases were reviewed to ensure that all data conformed to
the study’s strict guidelines. They found that elective
C-section, without anti-retroviral therapy, reduced the incidence
of HIV transmission from 19 percent to 10 percent. Elective C-sections
combined with anti-retroviral therapy, including AZT given during
pregnancy and at delivery, reduced the rate of transmission to
2 percent. |
|
|
|
Outlook
for Y2K: partly cloudy but no hurricanes in sight
The medical
school’s computer infrastructure and processor-controlled
medical devices are largely in good shape for the turn of the
millennium, according to an analysis by the school’s Year
2000 Steering Committee. While the school’s Information
Technology Services division (ITS-Med) has overseen the inventory
and risk assessment phase of planning for problems that could
occur on January 1, 2000, the individual owners of equipment
and systems are primarily responsible for their own testing and
troubleshooting. An extensive web site [http://info.med.yale.edu/computing/year2000/]
contains up-to-the-minute information as well as tools that allow
users to test their own hardware and software. Testing experts
for biomedical equipment and other Y2K resources are also available
through ITS-Med. The school has hired PricewaterhouseCoopers
to assist with business continuity planning. The dire predictions
associated with the millennium bug are for the most part exaggerated,
said the division’s associate director, Susan Grajek. “The
impact will be neither a big nothing nor a catastrophe, but more
likely a number of localized breakdowns,” she said. “That’s
why it’s important for people to assess and plan ahead now.” |
|
|
|
Digital
imaging center comes to library
Students, residents
and faculty members can now create presentation graphics, put
videotapes of lectures online and design their own web sites
at a new Digital Imaging Center located in the medical library.
Judy Spak, instructional technology coordinator at the library,
said students are also using the equipment to prepare graphics
for their theses. The new center, comprised of three state-of-the-art
computers in the Computer Resource Laboratory, a digital camera,
color printer, color scanner, and a full suite of imaging and
graphics software, was the gift of Martin E. Gordon, M.D. ’46,
and his wife, Evelyn Gordon. Gordon, who heads the Associates
of the Cushing/Whitney Medical Library, demonstrated the new
equipment at a reception in November. |
|
|
|
Apoptosis
gene suggests new target for chemotherapy
Yale scientists
who identified a gene that enables cancer cells to evade one
of the body’s mechanisms for weeding out mutations have
refined their understanding of the gene and suggested potential
new avenues for cancer treatment.
Their findings,
published in a December cover story in the journal Nature,
show that the gene, called survivin, is concentrated on the mitotic
spindle, a cell component that is central to the process of cell
division. “Survivin was absolutely undetectable in normal
tissues, but we found it over-expressed in all the most common
human cancers,” said Dario C. Altieri, M.D., associate professor
of pathology and leader of the study. Survivin inhibits apoptosis,
the programmed death of cells, thereby allowing mutated cells
to survive.
Because it is
present at mitosis, the gene may also be the link between two
processes researchers have long believed were connected, apoptosis
and cell cycle regulation. In normal tissue, survivin is expressed
only during embryogenesis and fetal development, where it is
believed to play a role in controlling apoptosis to maintain
homeostasis and organ and tissue development.
In its recent
findings the team built on its 1997 discovery and cloning of
survivin. “We are providing some mechanistic implications
for why cancer cells might have selected this particular gene
for survival,” said Altieri, who collaborated on the project
with Pier C. Marchisio, M.D., Ph.D., of the S. Raffaele Scientific
Institute in Milan. The next step, Altieri said, is to identify
survivin antagonists that would increase the effectiveness of
chemotherapy by removing survivin’s protective function
on the mitotic apparatus. |
|
|
|
Unveiling
of protein structure could yield tumor-starving drugs
In a finding
that could result in more effective angiogenesis blockers, biochemists
at Yale and Cornell have discovered the three-dimensional structure
of a protein linked to blood vessel growth. Researchers believe
the protein, MetAP-2, enables endothelial cells in the lining
of blood vessels to respond to growth factors. When the drug
TNP-470 blocked the activity of the protein in tumor-bearing
mice, new blood vessels failed to grow, thereby starving the
tumor.
In the Nov.
13 issue of Science, Craig M. Crews, Ph.D., assistant
professor of molecular, cellular, and developmental biology,
and his colleagues published a “snapshot” of human
MetAP-2, both alone and bound to fumagillin, the parent compound
of TNP-470. “If we can get a snapshot of how one drug binds
to a particular protein, we will know to what part of a protein
a drug must bind,” said Crews. With such knowledge, he adds,
pharmaceutical companies can more easily find drugs that might
inhibit MetAP-2 by a similar mechanism. “Knowing how the
drug binds to its target is an important step in tweaking the
chemical structure, like carving a key to mesh with a lock, in
order to make future versions of fumagillin-based drugs even
more effective.” |
|
|
|
Salmonella
vector overcomes an obstacle
A year ago,
scientists at Yale and Vion Pharmaceuticals reported success
in experiments that used a modified salmonella bacterium as a
vector to attack tumors in mice. Now the researchers have found
a way to reduce the risk of potentially fatal septic shock in
humans, making the mutated salmonella a candidate for cancer
therapy. “You can eliminate the main culprit that induces
septic shock from bacteria,” said David Bermudes, Ph.D.,
assistant professor (adjunct) of medicine and associate director
of biology at Vion, which is funding the research. Bermudes,
K. Brooks Low, Ph.D., and John M. Pawelek, Ph.D., who have collaborated
on the salmonella experiments, removed from the bacterium a gene
essential to the biosynthesis of lipid A, or endotoxin, which
induces septic shock.Their findings were published in the January
issue of Nature Biotechnology.
The mutated
salmonella, tested in mice and pigs for safety, has been shown
to reduce tumor growth in mice by more than 90 percent. Injected
directly into the blood stream, the bacterium suppresses, but
does not completely eliminate, tumors through a process the scientists
have yet to decipher. Phase I clinical trials are expected to
begin this year. |
|
|
|
Researchers
discover odor receptor genes in fruit flies
In a finding
with profound implications for controlling insect pests that
spread disease and cause crop blights, scientists at Yale have
identified 16 odor receptor genes in fruit flies. Although researchers
had searched for at least 15 years, this is the first time anyone
identified those genes in insects. “The reason people have
looked so long is that insect olfaction is tremendously important
in the real world,” said John R. Carlson, Ph.D., associate
professor of molecular, cellular, and developmental biology at
Yale, and leader of the study. The finding, reported in the February
issue of Neuron, could help scientists develop agents
that would disrupt insects’ ability to smell, making it
harder for them to mate or target human, animal or plant hosts.
Carlson’s laboratory is further exploring its discovery
by breeding fruit flies with the odor receptor genes either missing
or misexpressed.
Also important,
Carlson said, was the method used to search for the genes. Junhyong
Kim, Ph.D., assistant professor of ecology and evolutionary biology,
developed a computer program that used a search algorithm to
scour the Berkeley Drosophila Genome Project for putative odor
receptor genes. “It identified a large number of candidate
genes that were likely to encode proteins with transmembrane
domains,” Carlson said. Previous research had led them to
believe odor receptor genes would contain seven transmembrane
domains. The algorithm, which can be adapted to identify channels,
transporters and other membrane proteins needed for the normal
function of a cell, can be used for other projects, Carlson said. |
|
|
|
A
simple test to predict presence of Alzheimer’s
Dementia often
goes unrecognized in elderly people because tests for it are
difficult and time-consuming. Yale geriatricians have devised
a fast and simple screening method to identify those at risk
for dementia who might be candidates for more elaborate testing.
In the “time
and change” test, developed by a team led by Sharon Inouye,
M.D., associate professor of medicine, patients have two tries
in 60 seconds to tell the time on a clock face set to 11:10 and
two tries in three minutes to extract one dollar in change from
a selection of three quarters, seven dimes and seven nickels.
“The test is not designed to replace standard tests,”
said Inouye, “but to be used as an initial screening to
identify people who should be evaluated more thoroughly with
more sensitive tests.” A study of the test was published
in the Journal of the American Geriatrics Society in December.
“Based on our results, the test could reduce the percentage
of patients with unrecognized dementia from 44 to 19 percent,”
said Inouye. |
|
|
|
“What’s
in your Medicine Cabinet?” gives the public an inside look
at drug discovery
During the past
150 years, scientists and physicians first discovered that germs,
bacteria and viruses caused disease, then found agents that could
destroy, thwart and obstruct the pathogens. Disease and its treatments
were the topic this winter of a five-part public lecture series
sponsored by the Office of Postgraduate and Continuing Medical
Education. This year’s series was titled What’s
In Your Medicine Cabinet?
“The past
few decades have seen remarkable advances in pharmacology and
the management of a large number of common diseases,” said
James D. Kenney, M.D., associate dean for postgraduate and continuing
medical education and the course organizer. “The effectiveness
of frequently prescribed drugs, as well as their costs and interactions,
are matters of public concern.” The Patrick and Catherine
Weldon Donaghue Medical Research Foundation, based in Hartford,
Conn., provided support for the series, which attracted 44 people
from New Haven and surrounding towns.
While scientists
today explore the genetic and molecular underpinnings of disease
and treatment, early chemists and physicians found medications
in unlikely sources. Toxic waste generated in the manufacture
of coke yielded synthetic indigo, from which German chemists
derived sulfa drugs that stymie the production of bacterial DNA.
Arsenic, a heavy metal, became a remedy for syphilis. Scientists
developed gramicidin as they exploited bacteria found in soil
to control other bacteria.
Speakers for
the lecture series included Frank J. Bia, M.D., professor of
medicine (infectious diseases), who discussed How We Pick
and Choose Antibiotics; Silvio E. Inzucchi, M.D., assistant
professor of medicine, Diabetes Treatment in 1998: Something
Old, Something New; Karl L. Insogna, M.D., associate professor
of medicine, Osteoporosis and Paget’s Disease of the
Bone; John F. Setaro, M.D., associate professor of medicine,
The Management of Hypertension; and Elena Citkowitz, M.D.,
assistant clinical professor of medicine, Treatment of Cholesterol
and other Lipid Disorders. |
