Protomag

Call for Short Story Submissions

2012-01-24T15:25:37-06:00

We at Time Inc. publish Proto, a quarterly biomedical magazine, on behalf of Massachusetts General Hospital. Though we’re sponsored by MGH, we cover the entire world of basic and clinical research, medical technology and policy. Our readers include physicians, researchers, industry executives and policymakers.

We at Proto would like to explore some new territory: short stories.

We’re not looking for ER thrillers or science fiction. Rather, we seek something thoughtful and beautifully composed, a piece that illuminates an aspect of medicine (whether it be clinical care, research or even policy) in ways we can’t elsewhere in the magazine.

We’ve achieved this occasionally by excerpting full-length pieces of fiction. Though an excerpt is naturally different from a short story, I’d like to point to several examples for the quality of writing and what they impart: about cheating in research (Allegra Goodman’s Intuition), about the meaning of “care” (Abraham Verghese’s Cutting for Stone), and about doctors living up to high expectations (Samuel Shem’s The Spirit of the Place).

We’re looking for very short stories: 2,000 to 2,500 words, and we’re seeking submissions by Monday, February 27. We’ll pay upon publication ($2,000), but I’d be glad to discuss your idea before you begin.

Sarah Alger
Senior Editor
sarah underscore alger at timeinc dot com

Video: Back to the Beginning

2011-12-09T15:52:55-06:00

Unveiling the Brain's Architecture

2011-12-08T10:51:36-06:00

Using a new technology called diffusion spectrum imaging, scientists are able to see for the first time—and in stunning detail—how neural fibers crisscross the brain and connect its regions. The imaging technique, developed at Massachusetts General Hospital, greatly increases the power of conventional scanners and uses mega-magnets to map the way water molecules move in the brain’s gray matter, delineating in real time which neurons are activated and in which direction they are sending impulses.

The following images by MGH’s Randy Buckner, director of the Psychiatric Neuroimaging Research Program, and Bruce Rosen, director of the Athinoula A. Martinos Center for Biomedical Imaging, depict the connecting architecture, known as white matter, of one person’s brain. The colors in the images, which were taken at various angles and show different brain subsections, allow scientists to track the fibers’ multiple pathways. But less than 1% of the white matter is revealed here; capturing too much of the dense neural pathways would obscure the brain’s underlying structure.

Two ambitious new initiatives directed by Buckner and Rosen—the Superstruct Project and the Human Connectome Project, which also involves collaborators at the University of California, Los Angeles—are collecting images like these showing the white matter architecture of thousands of adults. Their goal is to understand what makes the human brain different from the brains of other animals and why some people are at risk for mental illness. Neuroscientists believe that diseases such as schizophrenia, bipolar disease and autism may be caused by subtle disruptions to the brain’s wiring. In compiling and comparing brain images of so many healthy and mentally ill people, scientists hope to see how connections go awry in disease so that they can develop early interventions and therapy targets.

Courtesy of Randy Buckner and Bruce Rosen of the Massachusetts General Hospital and the Visualization group, Laboratory of Neuro Imaging

MGH: The Research Engine

2011-12-08T12:48:51-06:00

23
Approximate area, in acres, dedicated to biomedical research at Massachusetts General Hospital

30
Approximate number of departments and centers that conduct research, including five Thematic Centers, which take an interdisciplinary approach to regenerative medicine, computational and integrative biology, systems biology, photomedicine and genetics

2,100
Approximate number of researchers, many of whom are also working physicians

3,600
Approximate number of staff who support these researchers

No. 1
Among independent U.S. hospitals, MGH’s rank in terms of National Institutes of Health funding

73
MGH-created products—including diagnostics, medical devices, medical imaging, research and screening tools, software and therapeutics—on the market in 2010

$750,000,000
Approximate amount of NIH funding, operational hospital support and philanthropy that MGH devotes annually to biomedical research—more than any other U.S. hospital

4
MGH researchers who figure among the approximately 330 Howard Hughes Medical Institute investigators, who direct laboratories at more than 70 universities and other research organizations in the United States

4,200
Approximate number of scientific papers by MGH researchers published in peer-reviewed scientific journals in 2010

182
U.S. patents filed by MGH in 2011

85
U.S. patents issued to MGH in 2011

93.2
Millions of dollars in licensing income in 2011

$360,000,000
Amount granted to MGH by the NIH in fiscal year 2011

26
Products under development in 2010

14
Startup companies based on MGH technology that launched in 2011

96
Startups since 1979

Ether: Anesthesia’s Maiden Voyage

2011-12-08T13:27:13-06:00

In December 1846, a steamer docked at Liverpool bearing extraordinary news from Boston. In its hold was a letter from Jacob Bigelow, an American physician, to his British colleague Francis Boott. Bigelow reported, “Limbs and breasts have been amputated, arteries tied, tumors extirpated, and many hundreds of teeth extracted without any consciousness of the least pain.”

Some two months before, Bigelow had been part of the crowd watching as dentist William T. G. Morton and surgeon John Collins Warren set in motion a chain of events that culminated in the birth of a new medical discipline. Using an apparatus that consisted of a rounded glass vessel, a glass tube and a metal mouthpiece with two valves, Morton administered a dose of vaporized ether to a 20-year-old patient. Thus sedated, the young man scarcely let out a sound as Warren made an incision on the left side of his face and removed a tumor on his jaw. The operation, the patient claimed later, caused no pain, only the sensation of a “blunt instrument passed roughly across his neck.”

This first public demonstration of ether during surgery (depicted above) so impressed the local community that the Massachusetts General Hospital building where it took place—an amphitheater with a copper-clad cupola—became known as the Ether Dome.

Apic/Getty Images

Boott passed along the news to a colleague, dentist James Robinson, and on Dec. 28, 1846, the physician John Snow observed as Robinson used ether while extracting teeth. Snow, who had already tried using ether to treat respiratory disorders, was thus inspired to investigate the effects of temperature on ether vapor, to develop better inhalers for administering the gas (such as the one shown at left), and to write more than 80 articles, letters, speeches and books that helped shape anesthesia into a science.

Snow’s awareness of how gases such as ether affect the respiratory system also proved critical during London’s 1848 cholera epidemic. Most believed the disease spread through miasma, or foul air, in places like slaughterhouses. But if this were true, Snow realized, slaughterhouse workers would have been most susceptible, and they weren’t. The insight spurred him to collect data showing that cholera was spread by contaminated water.

In 1853 Snow’s name was so synonymous with anesthesia that he provided it at a royal labor. For Queen Victoria, Prince Leopold’s birth was “soothing”; among physicians, the event sparked debate over the drug’s safety. By the time Snow repeated the feat at the birth of Princess Beatrice, in 1857, labor anesthesia had become more accepted—thanks partly to its very public sanction.

MGH and the Nobel Prize

2011-12-08T13:58:42-06:00

Hulton Archive/Getty Images

GEORGE R. MINOT (1934)

Minot shared the prize for helping to formulate a liver extract that became the standard treatment for pernicious anemia. (In 1948 it was replaced by the current therapy, injections of vitamin B12, the active component of Minot’s extract.) Minot said it was based on ideas that came to him as early as 1912, when he was a house officer at MGH. This seminal work identified the nutritional causes of anemia.

Fox Photos/Hulton Archive/Getty Images

CARL F. CORI (1947)

Cori shared the award for shedding light on how the body converts glycogen into blood sugar. He came to MGH in 1966 to head the hospital’s Enzyme Research Laboratory, and later helped establish the genetic foundation of the relationship between mutations of an enzyme, glucose-6-phosphatase, and metabolic deficiencies. Cori’s work led to a more complete understanding of human energy metabolism.

Keystone-France/Getty Images

FRITZ A. LIPMANN (1953)

Lipmann shared the prize for work that has had significant implications for the understanding of diabetes, mitochondrial disorders and lipid metabolism. He was director of MGH’s Biochemical Research Laboratory in the mid-1940s when he isolated coenzyme A, which was eventually determined to be an essential component in all living cells for metabolizing carbohydrates, fats and certain amino acids.

Bettmann/CORBIS

GERALD M. EDELMAN (1972)

Edelman, who interned at MGH, shared the prize for discoveries related to chemical structures in antibodies, the body’s defense against bacteria and harmful viruses. He constructed a complete model of the antibody molecule, a giant protein made up of more than 1,300 amino acids. Antibodies have since revolutionized medical practice in such diverse areas as oncology, transplantation and rheumatology.

Bettman/Corbis

MICHAEL S. BROWN AND JOSEPH L. GOLDSTEIN (1985)

Brown and Goldstein, who became friends as MGH interns in 1966 and both moved on to the University of Texas Southwestern Medical Center in Dallas, shared the prize for determining how human cells regulate cholesterol. Their discovery of cellular receptors for low-density lipoprotein helped revolutionize the treatment of high cholesterol.

AP-Photo/stf/Paul Sakuma

J. MICHAEL BISHOP (1989)

A research fellow in pathology at MGH in the 1960s, Bishop was at the University of California School of Medicine in San Francisco when he shared the prize for revealing that normal cells contain potential cancer genes—paving the way for other discoveries about how DNA damage and mutations convert normal genes into cancer genes in humans—and for the field of personalized cancer therapy.

Paul S. Howell/Getty Images

FERID MURAD (1998)

Once a resident at MGH, Murad was at the University of Texas Medical School when he shared the prize for discovering how the nitric oxide (NO) molecule—used (in nitroglycerin) to treat heart patients—relaxes smooth muscle and increases the diameter of blood vessels. Murad’s work laid the basis for another discovery at MGH: that NO gas could lower the pressure in a blue baby’s lungs and save its life.

Denise Bosco for Proto

JACK W. SZOSTAK (2009)

Szostak, of the MGH Department of Molecular Biology, shared the prize for discovering telomerase, the enzyme that builds and maintains telomeres, protective caps at the tips of chromosomes. Subsequent studies have shown that telomerase plays crucial roles in both cancer and aging-related ailments. “I’m hopeful that telomere research will lead to therapeutic benefits in the near future,” says Szostak.

Dimitrios Kambouris/Getty Images

RALPH STEINMAN (2011)

Steinman shared the prize for shedding light on how the immune system works. After training at MGH, he moved to New York’s Rockefeller University. There, in 1973, Steinman discovered dendritic cells, which he speculated could be important to the immune system. He went on to prove that dendritic cells have a unique ability to set off a cascade of immune reactions. The discovery opened new lines of research into treating common diseases, from infections to cancer.

MGH: Two Centuries of Discovery

2011-12-08T16:45:59-06:00

Click on infographic for a larger PDF version.

reverse chronological order: malte gather/andy yun; sunitha nagrath; david w. corson/camerique inc./classicstock; antagain/istock; albert mollon/getty images; pasieka/getty images; science photo library/getty images; fritz goro/time life pictures/getty images; courtesy of mgh (2)

Human Cell: From Micro to Macro

2011-12-07T13:24:23-06:00

Molecular biologists at MGH study the intricate machinery of the cell, from the tightly coiled DNA in its nucleus to the labyrinthine, bumpy endoplasmic reticulum where proteins are made and folded, to the sugars, lipids and other waste products the cell excretes. The ultimate goal: to deepen understanding of how these complex components work to maintain or disrupt human health. With this knowledge, therapies can be developed to treat diseases at the cellular level.

Click on infographic for a larger PDF version.

Flying Chilli

Genetics: Crunching the Data Within

2011-12-07T14:02:45-06:00

The human genetic makeup can seem almost unfathomably complex. Yet, for at least 150 years, since Charles Darwin detailed his theory of natural selection, scientists have been peeling back layer upon layer of the mystery. From Darwin and Gregor Mendel in the 19th century to landmark discoveries in the 1950s involving deoxyribonucleic acid (DNA), genes and chromosomes, and the completion of the Human Genome Project in 2003—a watershed accomplishment that determined the sequence of the 3 billion chemical base pairs on DNA’s double helix—knowledge has expanded geometrically. But with each advance, making sense of what we’ve learned has become ever more daunting. For several decades, Massachusetts General Hospital researchers have been deciphering crucial parts of this science, and the hospital’s newly formed Analytic and Translational Genetics Unit (ATGU) will play a leading role in managing and interpreting this widening sea of genetic information.

During the early 1980s, a team led by James Gusella, now director of the Center for Human Genetic Research at MGH, pioneered a twist on a traditional genetic strategy called linkage analysis—the analysis of traits such as hair color or blood type that, when inherited together, are caused by genes located near one another on the same chromosomes. By modifying the technique to look at inherited variations in DNA, they mapped the position of the gene responsible for Huntington’s disease, a devastating adult-onset neurodegenerative disease that causes loss of motor control, altered personality, and psychiatric and cognitive symptoms. Gusella’s finding opened the route to what became the widely used strategy of positional cloning, which involves cloning genes based on their location in the genome.

“At the time I came into the field, there were only about 30 traditional genetic markers,” Gusella says, “and none of them was associated with Huntington’s, so we knew the gene wasn’t located near any of them.” Instead, he and his team looked for variations in the DNA sequences themselves (on average, about 1 in 1,000 base pairs of DNA differs in any two individuals). “By tracking the inheritance of sequence variation within the families we studied, who carried the Huntington’s disease mutation, we could actually use the sequence differences as the markers to find the chromosome,” he says. “It was just a matter of finding enough sequence variations and testing them until we hit one that traveled with Huntington’s disease.”

By 1983, Gusella and his team had narrowed down the location of the gene for Huntington’s disease to chromosome 4, and 10 years later they found the gene itself. During the following decade, this same basic strategy, refined as scientists made more detailed maps of the human genome, was repeated in family linkage studies conducted for many single-gene disorders, including cystic fibrosis.

“The strategy was very successful,” says David Altshuler, a faculty member of the Center for Human Genetic Research at MGH and director of the Program in Medical and Population Genetics at the Broad Institute of Harvard and MIT. “But for the more common diseases that are caused by many genes, it didn’t work.” Such disorders include type 2 diabetes, heart disease and psychiatric conditions, including anxiety, autism and schizophrenia. So, by the early 2000s, researchers had moved on to studying which sequence variations in the genome were associated with a particular disease by comparing research subjects with the disease to those without it—a strategy called genome-wide association—and the search was aided by rapid developments in sequencing technology. In its wake, Altshuler and Mark Daly, chief of ATGU, have helped lead three major genomic mapping efforts—the International HapMap Project, the SNP Consortium and the 1000 Genomes Project. MGH has been an active collaborator in all three, in partnership with the Whitehead Institute and now the Broad Institute, and researchers at the hospital have used genome-wide association studies to investigate type 2 diabetes, Crohn’s disease, blood lipids, anxiety and more.

According to Altshuler, that research has led to the discovery of roughly 1,000 genetic contributors to common diseases (only about 10 were known a decade ago). “Now, we’re embarking on an era in which the continued acceleration of sequencing technology—which makes it possible to sequence the entire genomes of many patients in research studies or even in the clinic—is generating the highest-resolution map of our genes that you could possibly imagine,” Altshuler says. “You can know every letter of DNA in a research subject.”

The cost and time required to do whole-genome sequencing have decreased dramatically—leading to a proliferation of genetic information that ATGU will attempt to organize and interpret. “When we run sequences with the new technologies, we find millions and millions of places in the genome that differ between two individuals,” Daly says. “We only understand the function of the genetic variations for a very small handful of those differences.” Now Daly wants to elucidate the function of those gene variations by conducting large-scale studies.

“It’s hard to explain to people that, just because we have this machine that can sequence your genome, doesn’t mean we can actually tell you all of these exciting things about your medical past and future,” he says. “We need to go through a period of using the technology in a research setting to learn where in the genome the most interesting bits of information are, as well as what the genes are telling us about the causes of disease and how we can reverse that. That’s now our focus.”

Heart Disease: An Inerited Quirk

2011-12-07T14:07:07-06:00

“People with a strong family history of heart disease have two to three times the normal risk of heart attack,” says Sekar Kathiresan, director of preventive cardiology at MGH. Seeking to discover the genetic underpinnings of that heightened vulnerability, Kathiresan and his colleagues looked at 38 members of one family across three generations. But this particular clan didn’t have an elevated risk of heart disease. On the contrary, family members shared a quirk that reduced their risk—abnormally scant levels of low-density lipoproteins (LDL).

When LDL is high, so is the risk of heart disease. By looking for a gene that might explain this family’s unusually low levels, Kathiresan hoped to uncover a way to push down LDL in other people. For each family member, the researchers sequenced the exome, the portion of the genome that provides the genetic code for forming proteins. They discovered “nonsense mutations”—changes in the normal DNA sequence that hindered production of the angiopoietin-like 3 (ANGPTL3) protein. Family members who had one copy of the mutated gene had lower than normal levels of ANGPTL3, but those who had two copies made virtually none of the protein—and had the lowest levels of LDL.

Knowing that ANGPTL3 raises LDL levels in humans will help lead scientists to a very specific avenue for reducing LDL in people at risk of heart disease, says Kathiresan. “We’re now in a position to systematically apply a genomic approach to find out why some people are protected from heart disease.”