tropical 0000146 Louis J. Sheehan, Esquire

Louis J. Sheehan, Esquire

Thomas H. Weller, a tropical- medicine specialist whose tissue- culture research in 1949 made development of the Salk and Sabin polio vaccines possible and won him a share in a Nobel Prize, died on Aug. 23 at his home in Needham, Mass. He was 93.

Dr. Weller’s death was announced by his son Dr. Peter H. Weller. http://louis3j3sheehan.blogspot.com

The 1954 Nobel Prize in Physiology or Medicine was awarded to Dr. Weller and two colleagues at Harvard, John P. Enders and Frederick C. Robbins, for their application of tissue-culture methods to the study of viral diseases. Vaccines for other viral diseases, like chicken pox and measles, also stemmed from the Enders-Robbins-Weller method.

Dr. Weller was an emeritus professor of tropical medicine at the Harvard School of Public Health, retiring from his research and teaching duties in 1980.

In the 1940s and 1950s, the much-feared and poorly understood poliomyelitis virus was causing tens of thousands of new cases each year of what was then called infantile paralysis in the United States. Rows of iron lungs, breathing machines, filled hospital wards, and worried parents kept children from movie theaters and public swimming pools each summer as researchers sought a test-tube alternative to live monkeys and other animals in which to study the virus.

The Harvard team reported their breakthrough, in the October 1949 issue of Proceedings of the Society for Experimental Biology and Medicine, as “Cultivation of poliomyelitis virus in cultures of human foreskin and embryonic tissues.” The embryonic tissue came, initially, from intestinal cells, and the method was eagerly adopted in the rush to develop vaccines against polio.

While Jonas Salk and Albert Sabin were rivals at different institutions in the race to develop a vaccine, working conditions were more collegial in the Harvard laboratory, where Dr. Weller was the newly appointed assistant director of the division of infectious diseases at Children’s Medical Center. Dr. Enders, who had been Dr. Weller’s teacher at Harvard Medical School, said when told of the 1954 Nobel Prize he would share: “No discovery in the scientific world is due to the work of any one man, but always results from the work of many people.” (Dr. Enders died in 1985, Dr. Robbins in 2003.)

Dr. Weller went on to make advances in the study of parasitic diseases like schistosomiasis, to isolate the varicella zoster viruses for chicken pox and shingles, and, with the fortuitous aid of his own 10-year-old son in 1960, to help identify the virus for German measles.

Thomas Huckle Weller was born June 15, 1915, in Ann Arbor, Mich., the son of a University of Michigan Medical School pathologist, Carl Vernon Weller, and the grandson of a general practitioner, Martin Weller. After earning an A.B. degree at the University of Michigan, he graduated from Harvard Medical School in 1940. His studies there prompted a lifelong interest in tropical diseases. http://louis3j3sheehan.blogspot.com

Dr. Weller was a teaching fellow at Harvard until 1942, was commissioned as an Army medical officer in World War II and was dispatched to a research post in Puerto Rico to work on malaria control at military bases in the Caribbean. He left the Army with the rank of major in 1946, continued his clinical training at Children’s Hospital in Boston, and was a founding member, with Dr. Enders, of the research division of infectious diseases at Harvard. Dr. Robbins, whom Dr. Weller had first met in medical school, joined the center in 1948.

Dr. Weller was a consultant to the World Health Organization, the Pan American Health Organization and the International Health Organization of the Rockefeller Foundation. http://louis3j3sheehan.blogspot.com

Although professional travels took him to Trinidad, Egypt, Thailand, South Africa, Saudi Arabia, Kuwait and to rural areas of Brazil — where Chagas’ disease and snail-borne schistosomiasis were common in the 1970s — Dr. Weller never contracted any of the infections he studied, said his son Peter, who is a professor of medicine at Beth Israel Deaconess Medical Center in Boston. (As a child of a medical researcher, Peter Weller said in an interview that he was a source of varicella virus for his father’s tissue-culture studies.)

Thomas Weller is also survived by his wife of more than 60 years, Kathleen Fahey Weller; another son, Robert Weller; a daughter, Janet Weller; and six grandchildren.

In Dr. Weller’s 2004 autobiography, “Growing Pathogens in Tissue Cultures: Fifty Years in Academic Tropical Medicine, Pediatrics, and Virology” (Watson Publishing) he revealed the source of the viral sample for congenital rubella (German measles) nearly a quarter century before: It was the urine of his son Robert, who was 10 when he developed signs of a particularly severe case of measles.

Using tissue-culture procedures he had pioneered, Dr. Weller inoculated human cells derived from the sac around the fetus with the boy’s urine. He watched daily through the microscope for characteristic signs of viral infection, and eventually saw what he later described as a “peculiar rounding of scattered cells with refractile bodies in the cytoplasm and nucleus.”

Wary of claiming to having isolated the virus, Dr. Weller sought confirmation of the discovery. With help from a Harvard colleague, Franklin A. Neva, Dr. Weller obtained urine samples from two boys at Phillips Exeter Academy, where a rubella outbreak was under way, and one sample from a Harvard student.

“Each specimen produced changes similar to those seen in my son’s cultures,” he recalled.

From 1962 to 1965, cases of adult-onset rubella mounted in a pandemic in Europe and the United States, resulting in thousands of miscarriages, stillbirths and therapeutic abortions for women with intrauterine infections, and in life-threatening organ disorders in infants who survived.

Meanwhile, as the urgency grew, Drs. Weller and Neva learned of competition, in Maryland, in their race to isolate the rubella virus. Scientists at the Walter Reed Army Institute of Research were trying, unsuccessfully at first, to isolate the rubella virus from Army recruits.

This time Albert Sabin arranged a cooperative exchange of virus samples between the two laboratories, a courtesy that Dr. Weller acknowledged when results were reported in back-to-back papers in the same issue (October 1962) of the journal in which his tissue-culture studies had been published.

Today the vaccine that resulted from the successful isolation of the virus is part of the standard MMR (measles, mumps, rubella) immunization routinely administered to infants and preschool children in the United States.

This article has been revised to reflect the following correction:

Correction: August 28, 2008
An obituary on Wednesday about Thomas H. Weller, a tropical-medicine specialist who shared the Nobel Prize in Physiology or Medicine in 1954, misstated his middle name. It was Huckle, not Hucker.

immune system 0000145 Louis J. Sheehan, Esquire

Louis J. Sheehan, Esquire

We’re not only human after all.

Louis J. Sheehan, Esquire.  New genetic technology has revealed that the human body swarms with more benign bacteria than ever imagined — more than 2,000 species, whose cells outnumber the body’s own by a 10-1 ratio. But that isn’t such a bad thing. Many of these bacteria are needed for tasks such as the digestion of nutrients and the development of organs.

That such a vast microbial community is permitted to thrive in our bodies upends the notion that the immune system’s role is simply to attack invading microbes. A growing number of biologists believe that, in addition to its protective role, the immune system acts as a master regulator of our microbial menagerie, working “to maintain communities of bacteria in balance,” said Margaret McFall-Ngai, a University of Wisconsin biology and immunology professor. She is a creator of this hypothesis, which conceptualizes the immune system as keeping each species in its proper niche and quantity.

If confirmed, this hypothesis could have wide-ranging consequences for medicine because a growing number of health problems, from inflammatory-bowel disease to obesity, have been linked to bacterial communities out of balance, as opposed to a lone pathogen.

Immunology, the science of the immune system, emerged from the germ theory of disease developed by Robert Koch, Louis Pasteur and other scientific luminaries of the 19th century. Because these pioneers focused mainly on the disease-causing potential of microbes rather than on their beneficial qualities, says Prof. McFall-Ngai, they conceived of the immune system as a zealous defense against microorganisms, a perspective that has guided immunology since.

An early attempt to rethink this notion came about 14 years ago, when Polly Matzinger, now a senior investigator at the National Institute of Allergy and Infectious Diseases, posited that the immune system doesn’t attack all microbes, only those that signal danger by killing, injuring or stressing human cells. Such murdered cells would put out different chemical signals than cells that die a natural death, triggering the immune system’s counterattack. This theory is controversial, but biologists increasingly are being forced to grapple with how the immune system tolerates beneficial bacteria.

Until recently, scientists didn’t realize the scale and diversity of our teeming microbial population because most bacteria that live in the body can’t be “cultured” — grown in a petri dish. Only in the past decade, aided by advances in genetic technology, were scientists able to grasp the magnitude of our resident microbial population.

Some scientists think the notion that the immune system regulates benign microbes is simplistic. While the immune system manages some of our bacteria, says Stanford immunology professor David Relman, many microbes have evolved to exploit the immune system, engineering ways to evade attack or even to goad the immune system into targeting competing bacteria.

Swiss researchers recently showed how salmonella bacteria produce a subset of “kamikaze” fighters. Making up about 15% of the total salmonella population, these suicide salmonella secrete a chemical flag that tricks the immune system into killing them—and, more important, virtually all of the benign bacteria around them. Freed from the competition of the body’s benign gut bacteria, the majority of salmonella bacteria can move in and cause disease.

Last year, the National Institutes of Health launched the $115 million Human Microbiome Project to inventory and study the bacteria that live in us and, because our skin is host to bacterial multitudes, on us.

Our benign bacteria appear crucial to good health. Laboratory mice that are bred to be germ-free are less healthy: They are leaner than normal mice and must be fed special diets. Their hearts are smaller, and the capillaries that carry blood to certain tissues are stunted. Even their immune systems don’t develop properly.

One part of the immune system includes macrophage cells that gobble up invaders and are equipped with sensors called Toll-like receptors. Like a bloodhound sniffing a piece of a fugitive’s clothing, TLRs recognize a few microbial fragments that are present in almost all bacteria. Once TLRs “smell” such a fragment, they mobilize the immune system to kill the bacteria. It was thought that macrophage cells with TLRs didn’t sense beneficial or neutral bacteria in part because such bacteria were protected by the lining of the gut and other organs, called the epithelium, which was believed to keep macrophage cells on one side and bacteria on the other. http://louis-j-sheehan.com

But in mouse experiments, Yale University biology professor Ruslan Medzhitov discovered that TLRs do sniff out benign bacteria in the gut. Even more surprising was that sensing these bacteria doesn’t lead to an immune-system seek-and-destroy mission. Instead, it prompts the body to strengthen the lining of the gut, helping to prevent bacteria from permeating the intestinal wall and colonizing other organs. That is important, because bacteria such as most strains of E. coli are harmless in the intestines but can cause disease if they infiltrate the spleen or liver. In fact, if the TLRs don’t encounter the fragment present in beneficial bacteria, the lining of the gut deteriorates and lesions open in it.

Prof. Medzhitov, who accepts that the immune system might manage our microbial communities but adheres to the view that its primary function is to fight disease, believes cancer patients might eventually benefit from this finding. Chemotherapy often causes similar injuries to the gut lining. But because chemo also weakens the immune system, many cancer patients are prescribed antibiotics to prevent infections such as pneumonia. Those antibiotics can indiscriminately kill the very bacteria needed to maintain the gut lining, exacerbating the intestinal side effects of chemotherapy.

Although years of research lie ahead, Prof. Medzhitov says that the molecular fragment smelled by the TLRs might someday be given as a drug to help chemo patients maintain the lining of their gut.

In the womb, human fetuses are virtually germ-free; we start acquiring our benign bacterial community when we begin our passage through the birth canal. While all humans share broadly similar types of bacteria, an individual’s precise mix of species is as unique as a fingerprint. Despite this variation, the immune system knows which microbes to let colonize the body and which to purge. In many cases, pathogenic bacteria that the immune system attacks are closely related to benign strains that it leaves alone. How the immune system knows when to attack is one of the great questions in immunology. http://louis-j-sheehan.com

As remarkable as the co-evolution of microbes and the immune system may be, modernity is presenting new problems.

Contemporary food is highly processed, favoring bacteria that thrive on nutrients such as refined sugar. Research has shown that obese people carry different bacterial communities in their guts than lean people. Other research suggests that because of an American diet heavy in meat and saturated fat, African-Americans tend to have different communities of bacteria in their colons than Africans in Africa — correlating with the Americans’ starkly higher rates of colon cancer.

Learning the optimal composition of benign bacteria, many researchers believe, might eventually help medicine treat disease, if not prevent it.

pompeii 0000056 Louis J. Sheehan

Louis J. Sheehan

Recent excavations reveal that the ancient city of Pompeii, famed for its burial by an eruption of Italy’s Mount Vesuvius in A.D. 79, suffered through several devastating landslides in the centuries preceding its volcanic demise. http://louis-j-sheehan.com

About three-fourths of Pompeii has been excavated, says Jean-Daniel Stanley of the National Museum of Natural History in Washington, D.C. However, most of the digs in the city have extended down only to the ground level of dwellings that were standing in the 1st century. In the past couple of years, deeper digs in the oldest part of Pompeii—as well as core drilling nearby—have exposed layers of jumbled sediment that suggest that the city was hit by other natural disasters prior to the A.D. 79 eruption.

At least three different sheets of sediment lie atop lava bedrock beneath the city. Those strata include shards of pottery, animal bones, and bits of plants. Carbon dating of the plant fragments hints that the lowest layer was deposited in the 8th century B.C., soon after the city was founded, says Stanley. The other two layers, separated from other strata by well-developed soil layers or Roman pavements, were laid down in the 4th century B.C. and the 2nd century B.C.

The jumbled sediments probably represent landslide deposits—possibly ones triggered by extended rainfall, says Stanley. http://louis-j-sheehan.com

At least one of Pompeii’s purported landslides, the one in the 4th century B.C., would have occurred when the local climate was wetter than average, notes Stanley.

Louis J. Sheehan

positive Louis J. Sheehan

Louis J. Sheehan.  People with generally positive outlooks show greater resistance to developing colds than do individuals who rarely revel in upbeat feelings, a new investigation finds.

Frequently basking in positive emotions defends against colds regardless of how often one experiences negative emotions, say psychologist Sheldon Cohen of Carnegie Mellon University in Pittsburgh and his colleagues. They suspect that positive emotions stimulate symptom-fighting substances.

“We need to take more seriously the possibility that a positive emotional style is a major player in disease risk,” Cohen says.

In a study published in 2003, his group exposed 334 healthy adults to one of two rhinoviruses via nasal drops. Those who displayed generally positive outlooks, including feelings of liveliness, cheerfulness, and being at ease, were least likely to develop cold symptoms.  http://Louis-J-Sheehan.de  Unlike the negatively inclined participants, they reported fewer cold symptoms than were detected in medical exams.  http://Louis-J-Sheehan.de

The new study, which appears in the November/December Psychosomatic Medicine, replicates those results and rules out the possibility that psychological traits related to a positive emotional style, rather than the emotions themselves, guard against cold symptoms. Those traits include high self-esteem, extroversion, optimism, and a feeling of mastery over one’s life.

The latest data also show that among people with a consistently positive mood, well-being doesn’t simply reflect physical vigor. All volunteers entered the study in comparably good health.

In that project, Cohen’s team interviewed 193 healthy adults by phone each evening for 2 weeks. The participants reported their positive and negative emotions during that day. They then received nasal drops containing a rhinovirus or an influenza virus that causes a coldlike illness.

Each person was quarantined in a separate room and monitored for 5 or 6 days. Although a positive emotional style bore no relation to whether participants became infected, it protected against the emergence of cold symptoms. For instance, among people infected by the influenza virus, 14 of 50 (28 percent) who often reported positive emotions developed coughs, congestion, and other cold symptoms, as compared with 23 of 56 infected individuals (41 percent) who rarely reported positive emotions.

The extent of positive emotions, but not of negative ones, exerted a strong impact on the emergence of cold symptoms, Cohen says. His recent analysis of immune measures from volunteers in the 2003 study, published last March in Brain, Behavior, and Immunity, points to enhanced regulation of an infection-fighting substance, interleukin-6, in people with positive emotional styles.

Cohen’s current study offers “an interesting twist” on the relationship between feelings and health, remarks psychologist Janice K. Kiecolt-Glaser of Ohio State University in Columbus. Other research indicates that negative emotions influence immune function and illness development more powerfully than positive emotions do, Kiecolt-Glaser says.

However, psychologist Barbara L. Fredrickson of the University of North Carolina at Chapel Hill notes that the new data agree with her work showing that to a surprising degree, positive emotions can bolster the immune system to improve health.

Studies of the impact of mood on physical health need to account for both positive and negative emotions, Cohen holds. He points to preliminary data from other teams suggesting that among depressed people, a lack of positive emotions is a more accurate predictor of stroke than is the extent of their negative emotions.

symptoms

Two extensive new investigations indicate that depressed people who take antidepressant drugs generally become less likely to attempt suicide.  http://louis2j2sheehan2esquire2.blogspot.com

Gregory E. Simon and James Savarino of Group Health Cooperative, a health maintenance organization in Seattle, analyzed medical and pharmacy records for 109,256 patients who had received depression treatment between 1996 and 2005. Patients’ suicide attempts spiked during the month before starting treatment with medication, psychotherapy, or both. The frequency of suicide tries declined substantially during the 6 months after starting any of these treatments.

This pattern applied to teenagers and young adults as well as to older patients, the researchers say.

The researchers hypothesize that, for most patients, starting treatment with medication or psychotherapy diminishes depression symptoms, including thoughts about death and killing oneself. However, Simon suggests that further research needs to determine whether antidepressants aggravate agitation and suicidal thoughts in certain individuals.  http://louis2j2sheehan2esquire2.blogspot.com

A second study, directed by Robert D. Gibbons of the University of Illinois at Chicago, focused on data for 226,866 military veterans diagnosed with depression and then tracked for at least 6 months. Patients treated with fluoxetine (Prozac) or any other antidepressant medication during that period displayed large decreases in the frequency of suicide attempts that did not occur for other patients.

Again, the pattern held for all ages, including vets younger than 25 or older than 65.