brdgt | Science Tuesday - Neurosurgery, Neuroscience, Chronic Fatigue, and Antarctica

Inside Neurosurgery’s Rise
By RANDI HUTTER EPSTEIN, M.D., The New York Times, August 23, 2010

NEW HAVEN — Two floors below the main level of Yale’s medical school library is a room full of brains. No, not the students. These brains, more than 500 of them, are in glass jars. They are part of an extraordinary collection that might never have come to light if not for a curious medical student and an encouraging and persistent doctor.

The cancerous brains were collected by Dr. Harvey Cushing, who was one of America’s first neurosurgeons. They were donated to Yale on his death in 1939 — along with meticulous medical records, before-and-after photographs of patients, and anatomical illustrations. (Dr. Cushing was also an accomplished artist.) His belongings, a treasure trove of medical history, became a jumble of cracked jars and dusty records shoved in various crannies at the hospital and medical school.

Until now. In June 2010, after a colossal effort to clean and organize the material — 500 of 650 jars have been restored — the brains found their final resting place behind glass cases around the perimeter of the Cushing Center, a room designed solely for them.

These chunks of brains floating in formaldehyde bring to life a dramatic chapter in American medical history. They exemplify the rise of neurosurgery and the evolution of 20th-century American medicine — from a slipshod trial-and-error trade to a prominent, highly organized profession.

These patients had operations during the early days of brain surgery, when doctors had no imaging tools to locate a tumor or proper lighting to illuminate the surgical field; when anesthesia was rudimentary and sometimes not used at all; when antibiotics did not exist to fend off potential infections. Some patients survived the procedure — more often if Dr. Cushing was by their side.

Most of the jars contain a single brain; a few hold slices of brains from several patients. Some postoperative photographs next to the jars show patients with tumors bulging from their heads. When Dr. Cushing could not remove a tumor, he would remove a piece of the skull so the tumor would grow outward rather than compress the brain. It was not a cure, but it relieved the patient of many symptoms.

Dr. Cushing, born in Cleveland in 1869, was an undergraduate at Yale and finished his career here as a professor of history of medicine. In between, he went to Harvard for medical school, did his early surgical training at Johns Hopkins and became a surgical professor there, and then spent most of his career as chief of neurosurgery, a new specialty, at Peter Bent Brigham Hospital at Harvard (now Brigham and Women’s).

When he began operating in the late 19th century, a few other doctors were also venturing into the brain, but for the most part the patients did not survive the procedure.

“In the first decade of the 20th century, Harvey Cushing became the father of effective neurosurgery,” the medical historian Michael Bliss wrote in “Harvey Cushing: A Life in Surgery” (Oxford, 2005). “Ineffective neurosurgery had many fathers.

“Cushing became the first surgeon in history who could open what he referred to as ‘the closed box’ of the skull of living patients with a reasonable certainty that his operations would do more good than harm.”

Sometimes doctors went into the brain and could not find the tumor. Sometimes they talked to patients during surgery. Dr. Cushing, for one, often used only the local anesthetic Novocain. (The brain itself does not have pain receptors, but having one’s skull cut open must have been agonizing.) Mr. Bliss writes that in 1910, midway through a 10-hour operation on the renowned physician and Army Gen. Leonard Wood, Cushing wanted to stop operating and continue another day, but General Wood — fully alert — begged him to continue.

Dr. Dennis Spencer, the chairman of neurosurgery at Yale and the Harvey and Kate Cushing professor of neurosurgery, said Dr. Cushing’s major accomplishment was “his meticulous operative technique.”

“Whatever approach he was going to use to get to a tumor,” Dr. Spencer said, “he had this incredibly good judgment in terms of where the tumor was, getting there without harming the brain and then getting out.”

Brain surgeons in those days were medical sleuths, relying largely on patients’ accounts of their symptoms to figure out where the tumor was. Dr. Cushing popularized an eye exam that took advantage of the specific ways in which different tumors can distort vision — a strategy used into the 1970s, when M.R.I.’s and other imaging tools replaced it. Even today, many tumors in the pituitary gland, which straddles the optic nerves, are initially detected because patients have trouble seeing.

Dr. Cushing also discovered that pituitary tumors could lead to vast changes in the body. Cushing’s disease and Cushing’s syndrome — two illnesses linked to hormones gone awry — are named for his discoveries.

Indeed, comparatively little progress has been made since Dr. Cushing’s time in actually prolonging life in brain-cancer patients. “It is fascinating how far we’ve come in terms of technology but not really in terms of progress for most malignancies,” Dr. Spencer said. “Everything we’ve done in the last 100 years has changed the progress for malignant brain tumors very little, extending life maybe eight months to two years.”

He added, though, that “in many tumors we are getting closer to the genetic understanding, and I’m optimistic in the next 10 years we will make a lot more progress.”

In addition to his medical achievements, Dr. Cushing won a Pulitzer Prize in 1928 for his biography of his mentor, Dr. William Osler. He devoted his life to his work, leaving little time to his five children. His three daughters gained notoriety for their marriages — one to James Roosevelt, a son of President Franklin D. Roosevelt, whom she divorced, later marrying the publishing plutocrat John Hay Whitney; one to William Vincent Astor, heir to a $200 million fortune, whom she divorced, later marrying the painter James Whitney Fosburgh; and the youngest to the Standard Oil heir Stanley Mortimer Jr., whom she divorced, later marrying the CBS founder William S. Paley.

The collection expanded while he moved from Johns Hopkins to Harvard and eventually Yale, where they ended up in dusty storage bins before their recent $1.4 million restoration, partly paid for by money from a former patient’s family. The brains and their records were a “complete mess,” recalled Dr. Gil Solitaire, a professor of neuropathology at Yale in the 1960s who once shared an office with some of the Cushing paraphernalia. “Some were totally dehydrated, and the jars were cracked.”

In 1979, the specimens were moved from the bowels of the hospital to the basement of the medical school’s dorms. It was there that the students in the 1990s started a Brain Society — with membership extended to anyone who had the nerve to sneak into the dank basement, walk through the cluttered hall of brains and sign a poster, which now hangs in the Cushing Center.

“It was a rite of passage,” said Dr. Tara Bruce, now an obstetrician-gynecologist in Houston, who became a society member during her first year of medical school in 1994. “Everyone went to see the brains. It was surreal. I had just got to Yale and I remember thinking, ‘I guess Yale has so much great stuff that they can just shove a bunch of brains in the basement.’ ”

Dr. Christopher J. Wahl, an assistant professor of orthopedics and sports medicine at the University of Washington, wrote his thesis about the brains when he was a Yale medical student, stirring an interest in the restoration.

“The most incredible thing is that it’s not just the physical documentation of the founding days of neurosurgery but a social document,” Dr. Wahl said. “The bravery of these patients that really had nowhere to turn and this guy who was — cowboy is the wrong word, but an incredible innovator who was doing things at the right time and place.”

The Cushing collection in the Cushing/Whitney Medical Library at Yale University at 333 Cedar Street, New Haven, is open to the public Monday through Friday, 8 a.m. to 8 p.m.; Saturday, 10 a.m. to 8 p.m.; and Sunday, 9:30 a.m. to 8 p.m. (203) 785-5352.

Peeling Away Theories on Gender and the Brain
By KATHERINE BOUTON, The New York Times, August 23, 2010

“Delusions of Gender” takes on that tricky question, Why exactly are men from Mars and women from Venus?, and eviscerates both the neuroscientists who claim to have found the answers and the popularizers who take their findings and run with them.

The author, Cordelia Fine, who has a Ph.D. in cognitive neuroscience from University College London, is an acerbic critic, mincing no words when it comes to those she disagrees with. But her sharp tongue is tempered with humor and linguistic playfulness, as the title itself suggests. Academics like Simon Baron-Cohen and Dr. Louann Brizendine will want to come to this volume well armed. So would Norman Geschwind if he were still alive. Popular authors like John Gray (“Men are from Mars”), Michael Gurian (“What Could He Be Thinking?”) and Dr. Leonard Sax (“Why Gender Matters”) may want to read something else.

Sometimes all it takes is their own words, as in this example from Dr. Brizendine’s 2007 book “The Female Brain”: “Maneuvering like an F-15, Sarah’s female brain is a high-performance emotion machine — geared to tracking, moment by moment, the nonverbal signals of the innermost feelings of others.” Is Sarah some kind of psychic? Dr. Fine clarifies: “She is simply a woman who enjoys the extraordinary gift of mind reading that, apparently, is bestowed on all owners of a female brain.”

Experts used to attribute gender inequality to the “delicacy of the brain fibers” in women ; then to the smaller dimensions of the female brain (the “missing five ounces,” the Victorians called it); then to the ratio of skull length to skull breadth. In 1915 the neurologist Dr. Charles L. Dana wrote in this newspaper that because a woman’s upper spinal cord is smaller than a man’s it affects women’s “efficiency” in the evaluation of “political initiative or of judicial authority in a community’s organization” — and thus compromises their ability to vote.

These days gender inequality is commonly explained by neurological differences, most popularly the notion that the surge of testosterone that occurs in the eighth week of fetal development affects the relative size of the right and left hemispheres of the brain, and of the corpus callosum, the bundle of neurons that connects the two. In the 1980s Norman Geschwind proposed that the surge results in a smaller left hemisphere for males, leaving them with greater potential for right-hemisphere development, which, as he put it, results in “superior right-hemisphere talents, such as artistic, musical, or mathematical talent.” In female brains the hemispheres are more collaborative, explaining women’s superior verbalizing skills.

There are two problems here, Dr. Fine says. First is that several studies have found no difference in hemispheric size in neonates. The supposedly larger female corpus callosum is also in dispute. But even if size difference does exist (as it does in rats), she says, “getting from brain to behavior has proved a challenge.” Given that there may be sex differences in the brain, “what do they actually mean for differences in the mind?”

Dr. Baron-Cohen builds on this theory, suggesting that low levels of testosterone result in a female, “E type” brain (for empathy); medium levels yield a balanced brain; and high levels a male, “S type” brain (for systemizing). Medium levels account for the fact that some girls are systemizers and some boys are empathizers.

Dr. Baron-Cohen’s lab conducted research on infants who averaged a day and a half old, before any unconscious parental gender priming. Jennifer Connellan, one of Dr. Baron-Cohen’s graduate students, who conducted the study, showed mobiles and then her own face to the infants. The results showed that among the newborns the boys tended to look longer at mobiles, the girls at faces.

Dr. Fine dismantles the study, citing, among other design flaws, the fact that Ms. Connellan knew the sex of some of the babies. Because it was her face they were looking at and she was holding up the mobile, Dr. Fine says, she may have “inadvertently moved the mobile more when she held it up for boys, or looked more directly, or with wider eyes, for the girls.”

The study could be redone to eliminate these flaws, of course. And the results might be the same. But, Dr. Fine asks, “Why think that what a newborn prefers to look at provides any kind of window, however grimy, into their future abilities and interests?”

Summarizing the research, she writes, “Nonexistent sex differences in language lateralization, mediated by nonexistent sex differences in corpus callosum structure, are widely believed to explain nonexistent sex differences in language skills.”

What all this adds up to, she says, is neurosexism. It’s all in the brain.

But Dr. Fine persuasively argues that it is, in fact, all in the mind. Jan Morris, the historian, travel writer and male-to-female transsexual, saw this implicit stereotyping firsthand: “The more I was treated as a woman, the more woman I became. ”

Dr. Fine’s research is well documented, with 82 pages of footnotes. Surely Dr. Baron-Cohen can marshal a spirited defense of his position, as well might Ms. Connellan. I’d like to hear their response. The closest we get is Dr. Fine’s quotation of Dr. Baron-Cohen cautioning that we should be “careful not to overstate what can be concluded” from these studies.

It’s too late to tell that to Dr. Sax, a proponent of single-sex education, who cited the Connellan study as evidence that “girls are born prewired to be interested in faces while boys are prewired to be more interested in moving objects.”

But it’s not too late to read this book and see how complex and fascinating the whole issue is. It’s really not just a few steps from looking longer at moving objects to aptitude in math, from gazing at faces to mind reading.

Study Links Chronic Fatigue to Virus Class
By DAVID TULLER, The New York Times, August 23, 2010

When the journal Science published an attention-grabbing study last fall linking chronic fatigue syndrome to a recently discovered retrovirus, many experts remained skeptical — especially after four other studies found no such association.

Now a second research team has reported a link between the fatigue syndrome and the same class of virus, a category known as MRV-related viruses. In a paper published Monday by The Proceedings of the National Academy of Sciences, scientists found gene sequences from several MRV-related viruses in blood cells from 32 out of 37 chronic-fatigue patients but only 3 of 44 healthy ones.

The researchers did not find XMRV, the specific retrovirus identified in patients last fall. But by confirming the presence of a cluster of genetically similar viruses, the new study represents a significant advance, experts and advocates say.

“I think it settles the issue of whether the initial report was real or not,” said K. Kimberly McCleary, president of the CFIDS Association of America, the leading organization for people with chronic fatigue syndrome.

Leonard A. Jason, a professor of psychology at DePaul University and a leading researcher on the syndrome, agreed. “This class of retroviruses is probably going to be an important piece of the puzzle,” he said.

Chronic fatigue syndrome, estimated to afflict at least one million Americans, has no known cause and no accepted diagnostic tests, although patients show signs of immunological, neurological and endocrinological abnormalities. Besides profound exhaustion, symptoms include sleep disorders, cognitive problems, muscle and joint pain, sore throat and headaches.

The new paper, by researchers from the National Institutes of Health, the Food and Drug Administration and Harvard Medical School, was accepted for publication in May. Social networks and online communities soon learned the general findings and were eagerly awaiting the paper.

But in July, researchers from another federal agency, the Centers for Disease Control and Prevention, published a study finding no XMRV or other MRV-related viruses in patients with the syndrome. News of the conflicting findings had led the Proceedings editors and the authors of the new paper to delay publication for further review, and some patients expressed alarm that important scientific information might be suppressed.

People with a diagnosis of chronic fatigue syndrome are used to hearing scientists, doctors, employers, friends and family members dismiss the condition as psychosomatic or related to stress or trauma, despite evidence that it is often touched off by an acute viral illness. Many were ecstatic at news that the second study was being published.

“We’re really hoping this will blow the lid off,” said Mary Schweitzer, a historian who has written and spoken about having the illness. “Patients are hopeful that now the disease itself might be treated seriously, that they’ll be treated seriously, and that there might be some solution.”

The senior author of the new paper, Dr. Harvey J. Alter, an infectious-disease expert at the National Institutes of Health, said he was well aware of the intense interest in his findings but had been unable to respond publicly.

“I was sympathetic to the desire of people to know, and it was difficult because we didn’t feel we could communicate with the patient community directly until the paper was published,” he said.

Retroviruses, including H.I.V., store their genetic code as RNA, convert it to DNA and integrate themselves into the host cell’s genome to replicate. At least three antiretroviral drugs used against H.I.V. have been shown in laboratory studies to inhibit XMRV, which has also been associated with prostate cancer.

Some chronic fatigue patients are already trying H.I.V. medications prescribed “off label.” One patient, Dr. Jamie Deckoff-Jones, a physician in Santa Fe, N.M., has been keeping a popular blog about her improving health while taking antiretrovirals prescribed by her doctor. “I think the sickest patients have the right to try the drugs,” she commented in an e-mail.

Dr. Alter was quick to note that “it’s not at all proven” that a retrovirus causes chronic fatigue syndrome. Instead, such an infection could result from underlying problems with the immune system.

Moreover, it remains unclear why only two research teams found evidence of retroviruses. One reason could be that different groups used varying testing and detecting methods; federal health officials have organized an effort to standardize the process.

The studies also used different methods of sampling chronic fatigue patients. Many experts and researchers argue that the C.D.C.’s strategy leads to overdiagnosis because it fails to fully distinguish the disease from psychiatric disorders like depression.

Officials with the agency say their methods are sound. William M. Switzer, a microbiologist who was the lead author of the agency’s paper, said of the new research, “These are very intriguing findings that need to be confirmed.”

The findings are sure to raise concerns about the safety of the blood supply. AABB, formerly known as the American Association of Blood Banks, recommended in June that people with the illness be discouraged from donating, pending further study.

“The possibility that these agents might be blood-transmitted and pathogenic in blood recipients warrants extensive research investigations,” Dr. Alter and his co-authors wrote in the new study.

Judy A. Mikovits, the senior author of the Science paper, said she hoped to organize clinical trials of antiretrovirals by the end of the year, noting that they could lead to answers about whether a retrovirus causes the disease as well as to effective treatments. (Dr. Mikovits is director of research at the Whittemore Peterson Institute for Neuro-Immune Disease at the University of Nevada, Reno, which collaborated on the XMRV study with the National Cancer Institute and the Cleveland Clinic.)

Cara Miller, a spokeswoman for Gilead, which makes one of the H.I.V. drugs tested against XMRV, said the company was interested but proceeding cautiously. “We are tracking this evolving field,” she wrote in an e-mail, “and will continue to evaluate future research possibilities.”

Scientist at Work - Notes From the Field: 50 Years Ago: Photographs of an Antarctic Odyssey
By THOMAS LIN, The New York Times, August 23, 2010

In 1959, when Robert A. McCabe ventured to Antarctica as a freelance photojournalist, there were no rules against handling penguins and seals. So when an emperor penguin wandered onto McMurdo Base, Mr. McCabe and his cohorts put the almost three-foot-tall bird on a bar for snapshots. At Cape Royds, he photographed a man holding a diminutive Adélie penguin under its wings as if it were a toddler. Another photograph shows a man about to pet a seal pup.

The military personnel running the base even killed seals to feed the sled dogs, Mr. McCabe said, adding, “Today that’s absolutely prohibited.”

For the 100th anniversary of Roald Amundsen’s and Robert Falcon Scott’s race to the South Pole, Mr. McCabe has published a book of photographs and journal entries called “DeepFreeze! A Photographer’s Antarctic Odyssey in the Year 1959.”

“At that time, the penguins seemed to be very curious beasts. This one that I photographed just appeared at the American base and made the rounds,” he said. “He wasn’t afraid of anyone or anything.”

Robert A. McCabe A Weddell seal pup. Slide Show

Mr. McCabe used a Contax with a Zeiss 35mm lens for his color photographs and a Rolleiflex for black and white exposures. The book’s publisher, however, decided to print everything in black and white.

If Mr. McCabe was out for more than 15 minutes, the shutter on the Contax froze so that only half the frame was exposed. The Rolleiflex, he said, never failed.

With the 24-hour days, Mr. McCabe said, he felt guilty putting away his camera to get some shut-eye. He marveled at the “wonderful raking angle” of the sunlight. “The light creates a wonderful texture in the ice that doesn’t look flat.”

In the race to the South Pole, Amundsen’s Norwegian team was first to arrive, on December 14, 1911, more than a month before Scott’s. Tragically, Scott and the other four members of his British team died on their return trip.

The American Museum of Natural History currently has an exhibit called “Race to the End of the Earth” open through Jan. 2.

Click here for a slide show of the photographs and journal entries from Mr. McCabe’s book.