News From Harvard Medical, Dental, & Public Health Schools - March 21, 1997
Contents:
Dental Medicine
With much attention lavished on T cells these days, other members of the body's diverse army of defense cells are languishing in relative obscurity. Yet some of these cells may prove key to novel ways of fending off infection, says Richard Niederman, instructor in periodontology at the Harvard School of Dental Medicine.
Consider gum infections. One in five Americans over age 40 has severe periodontal disease, as do 2 percent of children and teenagers. Left untreated, this condition slowly erodes the bone around teeth, ultimately causing them to fall out. Hoping to hand dentists an alternative to antibiotics, Niederman and his colleagues are testing an experimental drug that for the first time would harness the ability of phagocytic white blood cells to eliminate bacteria around the beleaguered teeth.
At the annual meeting of the International Association for Dental Research in Orlando, Fla., on March 21, Niederman is presenting the results of two preclinical studies: one showing the drug can fight the type of bacteria that causes human periodontal disease, the other describing early work toward testing its ability to prevent the condition in children.
To be sure, the compound must clear more hurdles before it can enter dental practice, and it might disappoint in human trials. But if all goes well, it could, in a few years, herald "the beginning of a new era in treating infection," says Niederman. The drug already has passed muster in two initial clinical trials for a different use (see sidebar), and researchers at Harvard and elsewhere are studying its potential benefits in other applications.
For decades, antibiotics have been the mainstay of infection control. These drugs attack bacteria directly. The new compound takes a different tack, however. It attempts to boost the immune response by triggering particular types of white blood cell to divide and to ingest and kill bacteria.
Developed by Worcester-based Alpha-Beta Technology, Inc., the drug is PGG-glucan, a sugar molecule extracted from yeast. It is a purified component of earlier, cruder glucans, which are known to dampen infections. Yet crude glucans cannot be used in humans because they also unleash cytokines such as interleukin-1 and tumor necrosis factor. Secreted in inflammations around infection sites, these cytokines damage tissue, in this case causing bone degeneration around affected teeth. What makes PGG-glucan so appealing, says Niederman, is that it increases the phagocytes' appetite for bacteria while turning off or downregulating production of the cytokines.
The studies Niederman is presenting are the latest steps in his effort to improve nonsurgical treatment for periodontal disease. First, he and Philip Stashenko, associate clinical professor of oral biology and pathophysiology at Forsyth Dental Center, had asked whether PGG-glucan had any effect on oral infections, which involve multiple types of bacteria. With their coworkers, they reported in 1995 that PGG-glucan-treated rats had only half as much tissue destruction as did control rats. The model they used simulated the sort of throbbing dental infection unforgettable to anyone who has ever had to resort to a root canal to get rid of an infection.
Next, the researchers tested whether PGG-glucan treatment could work against the type of bacteria that causes periodontal disease in humans, Porphyromonas gingivalis. They implanted steel chambers under the skin of mice and infected the chambers with P. gingivalis. Again, PGG-treated mice were more resistant against the pathogen than control mice. Treated mice contained more phagocytes, which removed the bacteria more quickly.
Moreover, the mice's immune systems tended to attack only the pathogen while sparing benevolent bacteria in the mouth. This ability of PGG-activated phagocytes to tell good from bad microorganisms is why Niederman calls PGG-glucan a "smart" immunomodulator. This is important because using PGG-glucan is "ecological," he says. "We would like to shift the bacteria in the mouth from a pathogenic to a harmless population that prevents bad bugs from coming in," he adds.
Many children develop early-onset periodontal disease (EOP) associated with genetic defects in their white blood cells. When the researchers looked for animal models to study whether PGG-glucan might prevent gum disease in these children, serendipity helped them out. A collaboration of researchers at Harvard and MIT had just created a knockout mouse that became an instant candidate. Researchers led by Denisa Wagner, HMS associate professor of pathology at the Center for Blood Research, reported last year that mice lacking certain selectins--proteins that help phagocytes leave the bloodstream to reach infection sites--were especially susceptible to bacteria.
Together with these researchers, Niederman's group studied these mice and found that indeed, they develop early-onset periodontal disease. The mice suffer significantly more bone loss around their teeth than do normal mice, and they are infected with the same bacteria as are humans. Having found a good model to mimic EOP, the researchers are now beginning to treat these mice with PGG-glucan to see if it can slow disease progression.
It is too early to predict when human trials can start, says Niederman. But if the drug proves its worth, he hopes that it could become a "terrific preventive" that would reduce the need for painful and costly gum surgery.
--Gabrielle Strobel
To the Editor:
Dr. Joseph T. Coyle suggests in his letter to Focus (3/7/97), that I "apparently preferred to permit only those who share [my] opinions to be heard at Harvard." For the record, I would like to restate here what I wrote to Dr. Howard J. Shaffer in my letter (12/4/96) of resignation from the faculty of the Norman E. Zinberg Center for Addiction Studies:
I am surprised and troubled to learn that Dr. Coyle could believe that I would have any objection to controversy and the free expression of opinions, at Harvard or anywhere else.
Lester Grinspoon
HMS Associate Clinical Professor of Psychiatry,
Massachusetts Mental Health Center
"As you know from our phone conversations, I am distressed about your choice of General Barry McCaffrey as the recipient of the Norman E. Zinberg Award of the Division on Addictions of the Harvard Medical School. I am sure both of us want to be faithful to our understanding of what Norman stood for, but we have different ideas about how he would have viewed this decision.
In our conversations, you suggested that I was objecting to the award because of McCaffrey's controversial political positions. You pointed out that you had invited other controversial speakers, including Thomas Szasz and myself, and you told me that you had to defend these choices against critics. I agree with you that Norman would have had no objection to a controversial speaker, and the general has a right to speak in any forum that requests his presence. But in this case, he is not just giving a speech: He is receiving an award that implies scholarly achievement in a field in which he has no record of scholarship. He is not a scholar but a political appointee who commands great power, and in my view, has been using that power to do harm. If he is controversial, it is largely for two reasons: his rejection of medical marijuana, which he calls a 'hoax,' and his opposition to needle-exchange programs. By working to block access to medical marijuana and clean needles for addicts, he is exacerbating the problem he was appointed to solve. . . ."
Editor's Note: Gen. McCaffrey stated his current positions on medicinal marijuana and needle-exchange programs during a question period following his Zinberg Lecture. For coverage, see "Psychiatry".
As a wave of for-profit hospital takeovers sweeps across the country promising greater efficiency and lower costs, a new study by Harvard Medical School researchers suggests that for-profit takeovers may actually drive costs up while lowering efficiency.
"There has been a widely believed myth--which there's no data to support--that increasing the business orientation of the health-care system is going to make health care more efficient," says David Himmelstein. He and Steffie Woolhandler, both HMS associate professors of medicine at Cambridge Hospital, conducted the examination, which appears in the March 13 New England Journal of Medicine.
The researchers studied records from over 6,000 hospitals--for-profit, public, and nonprofit--for 1990 and 1994. They found that in 1994, for-profit hospitals spent 23 percent more than nonprofit hospitals and 34 percent more than public hospitals on administration. In addition, they found total costs per in-patient day averaged $1,403 in for-profit hospitals, compared with $1,040 at nonprofit and $895 at public hospitals.
In a dissenting editorial, Stuart H. Altman and David Schactman of Brandeis University write that other data show for-profits have actually reduced their cost per case relative to nonprofit and public hospitals. "Although timely research is lacking, there is anecdotal evidence that for-profit hospitals provide fewer money-losing community services," write the Brandeis authors.
How is the administration money spent? According to the HMS researchers, billing swallows a large chunk. Increased market competition also has meant that hospitals are hiring consultants to figure out how to cut costs. "They're hiring ten MBAs; they're firing 11 nurses. They're ahead. Only the patients are behind," says Woolhandler.
Despite the promise of efficiency, the researchers believe the cutting back of staff and increased administrative spending has led to a lowering of efficiency at for-profit hospitals.
The researchers are working with the 7,000-member Chicago-based Physicians for a National Health Program to reopen the health-care debate in this country. "We think medicine needs to be a universal public service and not a business--and administrative costs are really the costs of doing business," says Woolhandler.
--Misia Landau
For centuries, people have recounted the adventures of Robin Hood, the hero who pilfered from the rich and gave to the poor. That centuries-old story is taking on a new twist through a bevy of studies to be published in the coming months by researchers at the Harvard School of Public Health. They suggest that reducing the gap between wealthy and poor may, by strengthening social cohesion, lower the rate of mortality in a community.
In the new studies, the researchers, led by Bruce Kennedy and Ichiro Kawachi, surveyed 39 states with regard to their levels of "social capital." Social capital includes features of community life--civic participation, mutual trust, and respect--that promote cooperation among members of a group.
The researchers found that people in states with the smallest gap between rich and poor were richest in "social capital": They had the highest levels of civic participation, trust, and respect for minorities. People in these same states were shown in a previous study by the researchers to have the lowest overall death rates and, also, lowest rates of mortality from heart disease, stroke, and homicide.
Although preliminary, the findings begin to tell a story of their own about how economic inequalities can sabotage health. Gross disparities in income can breed hostility and distrust and, in general, deplete the social capital of a community, say the researchers. Communities with low levels of social capital may be less likely to invest in public services such as education, setting in motion a whole train of deleterious consequences for people in poor communities.
"They're not able to pull themselves together to get any outside resources. So they continue to live in a bad area--their schools suffer. Everything about their community is bad. It's got to have an impact on their health," says Kennedy, director of Public Health Practice at HSPH.
In addition, individuals within these poor communities may experience greater levels of anger, anxiety, and depression, which put them at greater risk for stress-related disease, says Kawachi, assistant professor of health and social behavior at HSPH. His previous research has shown that negative emotions increase a person's risk of heart attack.
He and Kennedy, who were just named 1996 recipients of the Robert Wood Johnson Foundation Investigator Awards in Health Policy, believe the moral of their research is clear. "We're the wealthiest nation on Earth and yet on many social and health indicators, we fall far behind other less wealthy industrialized nations," says Kennedy. "Economic policy needs to pay more attention to the distribution of wealth. So far it hasn't been taken seriously."
Although the notion that the "rich are getting richer" is not new, only in the last twenty years have researchers begun to explore the health consequences of income disparity. Until then, most studies had focused on the effects of poverty on individual health. In the 1970s, a seminal study showed that in developing countries communities taken as a whole could be equally dirt-poor, but those in which income was evenly distributed did remarkably well in terms of infant mortality rates and life expectancy.
Intrigued by that study--and encouraged by the late Sol Levine, who was a professor of health behavior at HSPH--Kawachi and Kennedy decided to explore the possibility that some states might be more or less healthy, depending on how income is distributed. As they and their colleagues reported in the April 1996 British Medical Journal, the bigger a state's gap between rich and poor, the higher the mortality rate.
Suspecting that a lack of social cohesion--due to depleted social capital--might be at fault in those states, the researchers looked at participation in a whole raft of associations--hobby groups, unions, sports clubs, and religious groups. They assessed levels of trust by looking at answers to questions such as: Do you think most people will take advantage of you?
"It turns out, there are quite enormous differences," says Kawachi. Louisiana and Alabama, where income inequality and mortality are highest, had the lowest levels of trust and participation in social groups. Iowa, a state with low income disparity and low mortality, had among the highest trust and participation rates.
In a follow-up study, the researchers looked at the level of respect for minorities by asking whether people thought African Americans do not get good jobs because of decreased inborn ability, motivation, and will power. Once again, they found striking correlations. People in states with high income inequality and high mortality showed the highest levels of prejudice. The high mortality rates in these states affected the poor white population as well as African Americans.
One of the researchers' immediate goals is to see who exactly is being most affected by the negative social factors that appear to accompany income inequality. Ultimately, they would like to see how large disparities in economic wealth lower not only the social capital but also the material, cultural, and political resources of a community. "Our big vision is to look at all these forms of capital and develop a theory about how they're related to health," says Kennedy.
--Misia Landau
To alleviate the pain of labor and delivery, many American women receive epidural anesthesia. But that relief may come at a price for the infant, according to a new study by researchers at Brigham and Women's Hospital. The study reveals that women who receive epidurals are more likely to develop fever. Consequently, their infants are more likely to be checked for infection and treated with antibiotics--even though the infants are not more likely to actually be infected.
"When a woman has a fever during labor, it is difficult for doctors to eliminate the possibility of infection. As a result, physicians are more likely to evaluate newborns to rule out infection," says Ellice Lieberman, associate professor of obstetrics, gynecology and reproductive biology at BWH and lead author of the March Pediatrics study.
She and her colleagues looked at 1,047 women who received an epidural and 610 women who did not. They found 14 percent of women in the epidural group developed fevers during the course of labor compared to only 1 percent of those who did not receive anesthesia. The researchers also observed that the longer women in the epidural group remained in labor, the greater the risk of developing fever. Without the epidural, the rate of fever remained low regardless of the length of labor.
Infants born to women in the epidural group were four times more likely to be evaluated for infection and treated with antibiotics--even though those infants were not more likely to have sepsis.
Antibiotic treatment can extend a newborn's neonatal stay. "Given the cost, risk, and discomfort to the infant due to sepsis evaluation and treatment, the possible consequences of fever resulting from epidural use should be discussed by women and their health-care providers when making the decision about the method of pain relief during labor," says Lieberman.
Each year, millions of Americans are diagnosed with coronary artery disease. Traditionally, patients either undergo bypass surgery to redirect blood flow or angioplasty to open blocked arteries. In both cases, the majority of arteries eventually become reblocked.
Now researchers at Beth Israel Deaconess Medical Center have treated cardiac patients with a growth factor they believe may grow new blood vessels in the heart, offering a more permanent solution for coronary artery disease.
"This has potential for revolutionizing the way we treat patients with blockages in their coronary arteries," says Michael Simons, assistant professor of medicine and principal investigator of the study.
He and his colleagues had previously conducted animal studies showing that a growth factor implanted in the hearts of pigs could promote angiogenesis, the growth of new blood vessels. In the human study, the researchers implanted capsules containing a small amount of basic fibroblast growth factor at or around the site of the blockage.
Three patients have undergone the treatment. These and others in the double-blind study will be followed for 12 months to determine the clinical risks and benefits of this approach. So far, there have been no side effects.
"If this treatment works, it will be the first permanent solution that we can offer for this devastating disease," says Roger Laham, an instructor in medicine in the study.
One of the big challenges in medical research has been to find a way to introduce foreign molecules through the plasma membrane of living cells. Many techniques currently in use can kill the cell or result in a loss of cell function.
HMS researchers have shown that an engineered, self-assembling, proteinaceous pore, called H5, does appear to make the plasma membrane reversibly permeable to small molecules. In other words, the pore acts as a small door that can both open and close. The team announces its findings in the March Nature Biotechnology.
"We were able to demonstrate a dose-dependent increase in the permeability of the membrane to marker molecules over two orders of magnitude, reducing influx and efflux times from hours to minutes," says Michael J. Russo, a graduate student in the Harvard-MIT Division of Health Sciences and Technology, and an author of the study. The other HMS author is Mehmet Toner, associate professor of surgery at MGH's Center for Engineering in Medicine. The pore was designed by Hagan Bayley, a researcher at Texas A&M and another of the study's authors.
Says Toner: "The ability of this engineered pore to perform as it was designed encourages us to further explore this technology."
I have a problem with the metaphor, 'war on drugs,'" said General Barry McCaffrey, breaking ranks with those who he said focus on drugs instead of the people who use them. As director of the White House Office of National Drug Control Policy, he advocated helping people involved with drugs through prevention, treatment, and a sensible national policy based on scientific data.
He delivered his remarks on March 7, beginning the 20th annual "Treating the Addictions" conference offered by the Department of Psychiatry at Cambridge Hospital and the Department of Continuing Medical Education at Harvard Medical School. As part of the conference, McCaffrey was a corecipient--along with Senator George McGovern--of the eighth annual Norman E. Zinberg Memorial Lecture Award, an honor that aims to celebrate intellectual debate and innovative leadership in the addiction field.
This year, the two-day conference focused on what works in treating addictions. According to McCaffrey, whose talk was entitled, "What Works on a National Level," the biggest problem the U.S. faces is its past "failure to require effective drug treatment programs." He said we only have half the treatment, prevention, and education capacity we need.
"There is no cheap way out," he said. "There isn't a trick, a jujitsu move that you can use on this problem." He suggested that legalization is not such a one-stroke remedy. "Almost nobody believes in the legalization of drugs," he said.
McCaffrey culminated his talk by reiterating, "We'll make science, not ideology, the basis of U.S. drug policy."
In answering questions from the audience, McCaffrey addressed two issues that had been swirling in the media: needle-exchange programs and the medicinal use of marijuana. He suggested he had no immediate problem with needle-exchange programs per se unless they undercut efforts to fund and implement treatment programs. On marijuana, he said we would learn from research whether smoking it is effective in treating people with prostate cancer, glaucoma, and other diseases. "It's not a political question," he said.
Another in the series of conference speakers, Reid Hester, research associate professor of psychology at the University of New Mexico and director of the Research Division at Behavior Therapy Associates in Albuquerque, focused the discussion on clinical practice. His presentation was called "What Works Best ... Is What We Do Least."
In a review of 250 studies, Hester and colleagues found that no single treatment approach to addictions is superior to all others. Instead, there is a range of techniques whose effectiveness is borne out by empirical data.
The one with the "greatest evidence of efficacy" is brief intervention, Hester said. This approach is based on personalized feedback, responsibility, advice, a menu of options, empathy, and self-efficacy.
Ironically, brief intervention is not among the most common treatment elements, he said. And some of the most common elements--the confrontational approach and general education--are shown by studies to be significantly less effective.
Why is it that what we do best is what we do least? Hester suggested the problem lies in the distance he sees between clinical researchers and drug counselors, a chasm he says that communication and training programs could begin to bridge.
--Robert Neal
* Harvard University and five HMS affiliates were ranked in the top 100 for total dollars awarded by the NIH in 1996. Harvard was eighth and the affiliates in the top 100 were Massachusetts General Hospital (21); Brigham and Women's Hospital (22); Dana-Farber Cancer Institute (50); Children's Hospital (68); and Beth Israel Hospital [Now Beth Israel Deaconess Medical Center] (77). The rankings were based on total dollars for research facilities, construction, repairs and renovation, libraries, international training in epidemiology, and general research grants.
* Ouzama Nicholson, HMS '98, has been selected as a 1997 Arthur Ashe Program in AIDS Care fellow. She is one of eight selected nationally for her potential to play an important role in HIV-related care and research. Nicholson will receive $6,000 for expenses incurred during a one-month rotation in October of 1997 at the Harvard AIDS Institute.
* Last December, Donald R. Kirks, radiologist in chief at Children's Hospital and the John A. Kirkpatrick Professor of Radiology, was selected to the board of directors of the Radiological Society of North America (RSNA). Kirks will serve as secretary-treasurer, then as chairman, and finally, in 2004, as president. He will be the first pediatric radiologist to be president at RSNA.
* The January 24 issue of Rutgers University Focus announced a new student award honoring Martin Yarmush, Helen Andrus Benedict Professor of Surgery and Bioengineering at HMS. Yarmush, formerly a Rutgers professor, was the founding director of the Rutgers-UMDNJ doctoral training program in biotechnology.
* Andrew Luster, assistant professor of medicine at HMS and MGH, has been named a 1997 Medical Scholar by the Charles E. Culpeper Foundation. The award will fund further research in the area of chemokines and their use as novel therapies for HIV and other diseases.
* First Lady Hillary Rodham Clinton has donated to Children's Hospital $29,000 in royalties from her best-seller, It Takes a Village. Children's is one of 15 children's hospitals throughout the nation chosen by Clinton to receive support.
* On February 21, 1997, Research to Prevent Blindness (RPB) presented awards to three Massachusetts Eye and Ear Infirmary researchers. Jarema Malicki, assistant professor of ophthalmology at HMS and MEEI, was granted a $160,000, four-year Career Development Award. Vadim Arshavsky, assistant professor of ophthalmology at HMS and MEEI, has been granted $100,000 in matching funds to help renovate laboratory space and purchase equipment. Evan Dreyer, director of the Glaucoma Service and associate professor of ophthalmology at HMS, was granted a $50,000 Lew R. Wasserman Merit Award.
* John Spengler, professor of environmental health in the School of Public Health, received the 1996 Jerome J. Wesolowski Award of the International Society of Exposure Analysis. The award, which recognizes Spengler's contributions to the field of exposure assessment and his leading role in education in his field, was presented at the 1996 annual meeting of the ISEA in December.
* Christopher Fletcher, chief of Surgical Pathology at Brigham and Women's Hospital and professor of pathology at HMS, is the recipient of the 1997 Young Investigator Award in pathology. The honor, given by the U.S./Canadian Academy of Pathology, recognizes a member of the academy under age 45 who has made significant contributions to the diagnosis and understanding of human disease.
* The Brain Imaging Center at McLean Hospital has been chosen as one of nine facilities worldwide to participate in a five-year, $5 million Human Brain Project. The NIH-funded project is also supported by more than a dozen U.S. government agencies and will center around the use of modern neuroimaging and statistical methodology to understand the structure and function of the human brain.
* Instructor in radiology Robert Boutin was awarded a Seed Grant Award to study MR imaging of early cartilage degradation. The Seed Grant Award is given by the Radiological Society of North America Research and Education Fund.
* The American Academy of Ophthalmology has chosen Elliot M. Finkelstein as its president-elect. Finkelstein, clinical instructor in ophthalmology at HMS, began his term January 1, 1997. Finkelstein has served as the academy's secretary for state affairs since 1992 and a member of the academy's State Affairs Committee since 1986.
* Edward Hundert, associate dean for student affairs at HMS, announced that on August 1, 1997, he will leave Harvard after seven years in this position. Hundert will become professor of psychiatry and medical humanities and the senior associate dean for Medical Education at the University of Rochester School of Medicine and Dentistry. In his new position he will assume leadership in a number of areas, including the MD program, residencies, and continuing medical education.
* Under a recently signed affiliation agreement, hospital-based ophthalmologists at Brigham and Women's Hospital have joined the staff at the Massachusetts Eye and Ear Infirmary. The expanded Massachusetts Eye and Ear Associates will provide ophthalmology services for the Brigham and its satellites. In addition, Leo T. Chylack, chief of Ophthalmology at BWH and professor of ophthalmology at HMS, will become the vice chairman for research in the Department of Ophthalmology at MEEI.
* Last month McLean Hospital announced plans to expand research facilities in Belmont. The site of construction is the Mailman Research Center, which houses one of three federally funded brain banks. The expansion includes updating existing laboratory space and construction of two floors of a 25,000 square-foot wing. More space will be added to the wing at a later date. The construction is possible in part through grants from the National Science Foundation, the Kresge Foundation, and the National Center for Research Resources.
* The Harvard International Office has a new Web site at the following address:
http://www.hio.harvard.edu.
The site will include the most current information on immigration law, traveling outside the U.S., procedures for obtaining employment authorization, and programs for spouses and family members.
* The William Randolph Hearst Fund has made available funding to members of the Faculty of Medicine whose research is in the area of prenatal and perinatal medicine with particular emphasis on the prevention of neuromotor disabilities. Preference will be given to junior and new investigators. The application deadline is May 1. Those interested should contact Liz Soares in Sponsored Programs at 432-1596.
* Partners HealthCare has named Hamilton (Chip) Moses III as interim vice president for Partners Mental Health Services. Moses will supervise the implementation of a mental health delivery system within Partners, including McLean, Brigham and Women's, Massachusetts General Hospital, and Spaulding Rehabilitation Center.
arvard's Center for Engineering in Medicine (CEM), has received a boost from the Whitaker Foundation. January 1 marked the start of the CEM's Development Award, presented to establish a center of excellence in biomedical-engineering education and research at Harvard. This honor, which includes a $1.8 million grant, has gone to only nine other institutions nationwide and carries the potential for additional funding up to a total of $5 million.
"The award to the CEM will help to raise the visibility of biomedical engineering at Harvard," says Martin Yarmush, Helen Andrus Benedict Professor of Surgery and Bioengineering at HMS and the director of the CEM. "The Whitaker Foundation has given our institution an extraordinary opportunity to create a model program, which emphasizes the dual role of biomedical engineers in an academic medical environment to develop tools for the advancement of patient care and to utilize the principles and tools of engineering science to answer fundamental questions in biology and medicine." The CEM, while based administratively at Massachusetts General Hospital, is a multi-institutional enterprise.
One of the CEM's educational programs is already up and running. The Biomedical Engineering Research and Education (BERE) program for physician fellows is a 2-year fellowship that integrates classroom study with laboratory training in biomedical engineering and molecular biology.
"We're setting out to create a new breed of biomedical-engineering practitioner," says Mehmet Toner, director of the BERE program. "We have incredible technology available to us today, and we need to ensure a steady stream of physician-engineers who are interested in and able to understand its potential."
One important recent spin-off from CEM activities is the newly formed Harvard Council on Biomedical Engineering (HCBE). Approved last November by the Faculty Council, the HCBE was formed by the senior faculty in the CEM to foster the career development of biomedical engineering practitioners. The HCBE offers help in mentoring younger fellows and faculty and serves the dean and department chairs in helping to evaluate promotions and appointments.
The Whitaker Award is also being used to fund a Biomedical Engineering Discovery Fund, a seed-grant program cosponsored by the HCBE and CEM. Last month, after competitive review, grants were awarded to six fellows and faculty who are involved with advanced research in biomedical engineering.
For more information, please contact Gregory Russo, programs administrator, phone: 617-374-5636; email: grusso@sbi.org.
Robert Geyer, professor emeritus of nutrition in the School of Public Health, died January 16, 1997. He was 78.
Geyer came to HSPH in 1946 as a research fellow in the department of nutrition. In 1971 he became a professor and assumed emeritus status in July of 1987.
His research focused on three areas of nutrition: lipid metabolism, parenteral nutrition, and the development of artificial blood substitute preparations. Geyer's work on fat emulsions for intravenous nutrition and artificial preparation for partial or total blood replacement is leading to clinical applications for humans.
Geyer served as secretary to the faculty and acting chairman of the Department of Nutrition. He also served on a number of other HSPH committees.
He leaves his wife, Beverly, one son, and one daughter.
For now, all Timothy Babineau can do is sit back and wait.
In 1992, the HMS assistant professor of surgery at Beth Israel Deaconess Medical Center began testing whether an unusual concoction that he jokingly calls "fancy sugar water" could do in people what it had proven to do well in animals: prevent infections after surgery.
Last month, the last of 1,246 patients enrolled in the phase-III clinical trial in this effort. The results of this double-blind, randomized trial--expected this June--will determine whether the company developing the drug can ask the FDA to approve it.
If the drug, PGG-glucan (see accompanying story) gets approved, "it could provide a dramatic benefit to patients of high-risk surgery," says Babineau, who led the 40-center trial. Ninety percent of all operations have a low infection rate, but for certain procedures--including liver or colorectal surgery--that risk reaches 25 to 40 percent, especially in vulnerable patients such as diabetics or the elderly.
While these complications are rarely lethal, common wound infections or pneumonia usually double the length of hospital stays and cost between $10,000 and $25,000 per infection. High-risk surgery therefore consumes a disproportionate share of hospital resources.
"This is a completely new way of trying to prevent infections," says Babineau.
Currently, patients routinely receive antibiotics before and after surgery, yet neither these drugs nor improvements in postoperative care have done enough to reduce infections in these patients. And the rise in antibiotic resistance "provides all the more reason why we need to take a different approach," says Babineau.
PGG-glucan enhances the body's resistance to infection. It primes phagocytosing white blood cells to multiply, migrate toward infections, and kill the offending organism. Since the drug leaves the task of recognizing the nature of the infection to the immune system, it is unlikely that microorganisms will become resistant, says Babineau.
Earlier trials have found that the drug is safe, causing only minor side effects. It does not prompt the immune system to make antibodies against it, as do many protein-based drugs. These trials, published in 1994, suggested that PGG-glucan reduces the rate and severity of postoperative infections in certain groups of patients but were too small to yield definitive data.
Despite all hopeful signs, it is good to keep in mind that clinical trials are notoriously fickle, capable of dealing last-minute blows to an apparently solid approach. While the data are being analyzed, Babineau points out that even a setback in this trial would not spell doom to the field of glucan immunotherapy, which is only just beginning to grow.
--Gabrielle Strobel
There was a time when scientists were perceived as mildly deranged and slightly obsessive people, single-mindedly engaged in quests rarely understood by more than a handful of their contemporaries. Gradually, scientific research turned from hobby to bona fide profession. (Incidentally, despite this change in social status, the public's perception of scientists may not have changed all that much since earlier times....)
When I started graduate school in '91, the only truly respectable scientific career was the academic one. The biotechnology boom was already in phase II--during which the industry was consolidating--and the pharmaceutical giants were confirming their confidence in its future by acquiring the most promising of the startup companies. And yet, considering a research career in the biotechnology industry as one's first choice was hardly conceivable in academic circles.
"The Industry," as it became known, was at best a fall-back plan, in case all university doors were to close in our faces. At fault were the allegedly low standards of scientific research there and the restricted freedom in the choice of questions to pursue. As to choosing a nonresearch career option, this was almost equivalent to a voluntary admission of failure.
In less time than it takes to produce a decent PhD dissertation, things have changed significantly. It may have been the mounting crisis in the academic job market or the threat of deep cuts in future science funding, but it became increasingly clear that postdocs and students were getting curious about alternatives to the academic track. For instance, I remember a seminar about three years ago in which two or three researchers from biotechnology companies presented their work at the Medical School. I wanted to attend, but when I opened the door of the seminar room, I found there wasn't even any standing room left.
The administration has been quick to perceive such signs and respond to the need. The words "alternative careers" can now be regularly spotted on announcement flyers around campus. This openness sometimes overshadows persistent resistance at various levels. Some faculty members admit that in view of the demand, they have simply sidelined--not overcome--their personal reluctance to advertise nonresearch career options to students. For some people, the line is drawn more strictly between academic and nonacademic research, and nonresearch careers are still discussed in disparaging terms.
Even among those who acknowledge the reality of the job and funding crises in our fields, some still argue that students graduating from top programs like Harvard's are unlikely to be affected. It would be very interesting to have a public debate around the issue of whether the job and funding situations justify diverting PhD-holders towards alternative career paths, and also, which nonresearch areas constitute a good use of a PhD degree and which don't.
To those of us graduate students or postdocs reaching decision time, the frequent opportunities we are now given to meet people who have taken their biology PhDs into various nonacademic professions are of enormous value. However, in my view, career forums are not sufficient in the long-run. They are adequate in describing the options, not in preparing for them. The scientific profession is currently going through a transition, and ultimately, a decision has to be made about appropriate diversification of the training process. There is no doubt in my mind that the reputed U.S. tradition in educating research scientists must continue, but variations on the rigid PhD theme need to be designed to integrate proficiency in selected skills with a solid scientific preparation.
The recent hype about cloning humans has brought back talk of the impending "Century of Genetics." Without putting it quite so dramatically, there is little doubt in my mind that the biological sciences will pervade more aspects of our world than we can presently foresee. In order to achieve a smooth integration, there is bound to be a high demand both inside and outside the laboratory for individuals allying advanced scientific capabilities with a keen understanding of the social, cultural, and economic context. Increasing numbers of biology PhDs will be following nonacademic tracks. We may well be the last members of this group for whom a nonresearch or nonacademic career choice could legitimately be referred to as "alternative."
--Diala Ezzeddine
Diala Ezzeddine is a PhD candidate in the Biological and Biomedical Sciences program at HMS.
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