Science Tuesday - Glass Organisms, Psychiatry, and Vaccines
In Pursuit of an Underwater Menagerie (and related slide show)
By C. DREW HARVELL, The New York Times, May 6, 2013
MAUNA LANI REEF, Hawaii - After a long, cold swim in the dark, we spotted it on the night reef with our dive lights: Octopus ornatus, the ornate octopus, a foot-long creature in an amber shade of orange with bright white spots and dashes along all its arms.
It sat stolidly in the light of the camera, 30 feet below the surface, unfazed by the attention. I reached out a finger and it touched me with its suctioned tentacles. When it scuttled in the other direction, I herded it between my cupped hands as it watched me attentively with searching golden eyes.
As if levitating, it smoothly lifted off and tried to jet over my head, but slowly enough that I could catch it gently in midair - like handling a large bird, albeit one with eight sticky tentacles. Holding it at eye level, I looked into its eyes. I felt connected, sort of an octopus whisperer.
Then a tentacle slapped the front of my mask. The octopus crawled up my arm and vanished into the night.
I’ve been a marine biologist my entire professional life, spending more than 25 years researching the health of corals and sustainability of reefs. I’m captivated by the magic of sessile invertebrates like corals, sponges and sea squirts - creatures vital to the ecosystem yet too often overlooked in favor of more visible animals like sharks and whales.
The filmmaker David O. Brown and I want to change that. To make a documentary, “Fragile Legacy,” we are on a quest to lure these elusive and delicate invertebrates in front of the camera lens.
Our inspiration springs from an unlikely source: a collection of 570 superbly wrought, anatomically perfect glass sculptures of marine creatures from the 19th century.
These delicate folds and strands of glass make up the Blaschka collection of glass invertebrates at Cornell, of which I am the curator - enchanting and impossibly rare jellyfishes of the open ocean; more common but equally beautiful octopus, squid, anemones and nudibranchs from British tide pools and Mediterranean shores.
They are the work of an extraordinary father-and-son team, Leopold and Rudolf Blaschka. Leopold Blaschka (1822-95) was a Czech immigrant to Dresden, in what is now Germany; on a trip to America in 1853, his ship was becalmed and he was enchanted by a spectacular display of bioluminescence from a type of jellyfish called a siphonophore.
He decided to study the jellyfish more closely and create their likenesses in glass. His first works were a set of anemones for the Dresden Natural History Museum in 1863, inspired by the naturalist Philip Henry Gosse’s “British Sea-Anemones and Corals.”
Leopold’s son, Rudolf (1857-1939), was a keen natural historian in his own right, and an ardent aquarist, or aquarium keeper. He followed his father’s lead, expanding in biodiversity to reach the edges of the animal kingdom. (And beyond: Later they created a comprehensive collection of flowers that is now on display at Harvard.)
To restore Cornell’s vast collection - bought from the Blaschkas themselves in 1885 - a glassworker, Elizabeth R. Brill, has painstakingly cleaned each piece and glued back fragmented gills and wayward tentacles. The collection is on view at several galleries and the Johnson Museum of Art on the Cornell campus, and restored pieces can be seen in an online gallery.
The marine biodiversity recreated by the Blaschkas is a phantasmagorical view of life in the oceans. For they were artists as well as keen natural historians, with an eye for the forms that would enchant in glass and that were too rare or fragile to be seen readily. They were also superb teachers, eager to share the wonders of nature with students.
Their favorite subjects were the ephemeral, translucent, bright forms of the Cnidaria (anemones, jellyfish, corals), unshelled mollusks (nudibranchs, octopus and squid) and brilliant tentacled worms. Some of their most brilliant creations are of the different species of cephalopods, like the ornate octopus.
David Brown and I came to Hawaii with the goal of making videos of as many Blaschka cephalopod look-alikes as we could find. (The ornate octopus we found was not an exact match with the Blaschkas’, but the common octopus was: Our glass counterpart still sits dusty and broken in its original shipping box, soon to be restored by Elizabeth.)
Our quest is also to use the Blaschka collection as a time capsule, to take a snapshot of change. How many of these creatures that were so common 150 years ago can still be found today?
The oceans are changing rapidly, with a 30 percent increase in acidity in the last 200 years, lethally stressful warming in many tropical seas, and significant coastal pollution and overfishing just about everywhere. If ever there was a time to compare the plentiful past with an ocean in jeopardy, that time would be now.
The chances of finding cephalopods are much improved while they are out foraging at night. So we did a series of night reef dives, followed by a “black water” dive three miles off the Kona coast.
That one put us in 1,000-foot-deep water, well after sunset, with the very real possibility of encountering tiger sharks and great white sharks. Floating in the current, the captain turned off all the boat’s lights, the better to see bioluminescent “black magic.”
We clipped onto our safety lines and slipped below the surface without lights, into darkness punctuated by bioluminescent splashes. We had to drift close to identify whether these splashes were from jellyfish, ctenophores, salps or squid. As we settled into our depth at 50 feet below the surface and turned on our dive lights, the sparkles of bioluminescence turned into a stream of tiny plankton floating by.
What I really hoped to see were siphonophores, the creatures that created the mid-Atlantic bioluminescence that so inspired Leopold Blaschka in 1853 and whose models are some of the most intricate in our collection.
For example, the glass model of Apolemia uvaria has the basic form of a siphonophore that I could see before me - the large swimming bell, its powerhouse for fast movement, and the long dangling tentacles - each capped with a deadly harpoon loaded with neurotoxin - that are death traps for all manner of small shrimp and fish.
And the siphonophores put on quite a show for us, even if they were small and wickedly hard to film. They stretched out those long tentacles, hauling them in rapidly when prey arrived.
And when they encountered danger, their nervous systems fired a signal to muscles that zipped up the tentacles and powered the swimming bell to high speed. A three-foot-long string of stinging tentacles contracted in a flash to a three-inch stream of jet propulsion. (Somehow, the term “jellyfish” doesn’t capture the extravagant evolution and biology at work here!)
Then I heard an underwater shout from David as he caught a picture of an exquisite tiny octopus zooming past.
The next stop in our quest is the Mediterranean, ground zero for Blaschka subjects. This month I head to Italy, to the Naples Marine Station, which supplied the glassmakers with many of their live animals.
Perhaps we’ll find exact matches for such spectacular invertebrates as the curly tentacled octopus (Eledone moschata) and the giant siphonophore Apolemia uvaria, which at 20 feet long can dominate a Mediterranean food web. At any rate, we hope to find out whether they are surviving in the sea as magnificently as they do in glass.
C. Drew Harvell is the associate director for environment at the Atkinson Center for a Sustainable Future at Cornell, and curator of the Cornell Collection of Blaschka Invertebrate Models.
Psychiatry’s Guide Is Out of Touch With Science, Experts Say
By PAM BELLUCK and BENEDICT CAREY, The New York Times, May 6, 2013
Just weeks before the long-awaited publication of a new edition of the so-called bible of mental disorders, the federal government’s most prominent psychiatric expert has said the book suffers from a scientific “lack of validity.”
The expert, Dr. Thomas R. Insel, director of the National Institute of Mental Health, said in an interview Monday that his goal was to reshape the direction of psychiatric research to focus on biology, genetics and neuroscience so that scientists can define disorders by their causes, rather than their symptoms.
While the Diagnostic and Statistical Manual of Mental Disorders, or D.S.M., is the best tool now available for clinicians treating patients and should not be tossed out, he said, it does not reflect the complexity of many disorders, and its way of categorizing mental illnesses should not guide research.
“As long as the research community takes the D.S.M. to be a bible, we’ll never make progress,” Dr. Insel said, adding, “People think that everything has to match D.S.M. criteria, but you know what? Biology never read that book.”
The revision, known as the D.S.M.-5 and the first since 1994, has stirred unprecedented questioning from the public, patient groups and, most fundamentally, senior figures in psychiatry who have challenged not only decisions about specific diagnoses but the scientific basis of the entire enterprise. Basic research into the biology of mental disorders and treatment has stalled, they say, confounded by the labyrinth of the brain.
Decades of spending on neuroscience have taught scientists mostly what they do not know, undermining some of their most elemental assumptions. Genetic glitches that appear to increase the risk of schizophrenia in one person may predispose others to autism-like symptoms, or bipolar disorder. The mechanisms of the field’s most commonly used drugs - antidepressants like Prozac, and antipsychosis medications like Zyprexa - have revealed nothing about the causes of those disorders. And major drugmakers have scaled back psychiatric drug development, having virtually no new biological “targets” to shoot for.
Dr. Insel is one of a growing number of scientists who think that the field needs an entirely new paradigm for understanding mental disorders, though neither he nor anyone else knows exactly what it will look like.
Even the chairman of the task force making revisions to the D.S.M., Dr. David J. Kupfer, a professor of psychiatry at the University of Pittsburgh, said the new manual was faced with doing the best it could with the scientific evidence available.
“The problem that we’ve had in dealing with the data that we’ve had over the five to 10 years since we began the revision process of D.S.M.-5 is a failure of our neuroscience and biology to give us the level of diagnostic criteria, a level of sensitivity and specificity that we would be able to introduce into the diagnostic manual,” Dr. Kupfer said.
The creators of the D.S.M. in the 1960s and ’70s “were real heroes at the time,” said Dr. Steven E. Hyman, a psychiatrist and neuroscientist at the Broad Institute and a former director at the National Institute of Mental Health. “They chose a model in which all psychiatric illnesses were represented as categories discontinuous with ‘normal.’ But this is totally wrong in a way they couldn’t have imagined. So in fact what they produced was an absolute scientific nightmare. Many people who get one diagnosis get five diagnoses, but they don’t have five diseases - they have one underlying condition.”
Dr. Hyman, Dr. Insel and other experts said they hoped that the science of psychiatry would follow the direction of cancer research, which is moving from classifying tumors by where they occur in the body to characterizing them by their genetic and molecular signatures.
About two years ago, to spur a move in that direction, Dr. Insel started a federal project called Research Domain Criteria, or RDoC, which he highlighted in a blog post last week. Dr. Insel said in the blog that the National Institute of Mental Health would be “reorienting its research away from D.S.M. categories” because “patients with mental disorders deserve better.” His commentary has created ripples throughout the mental health community.
Dr. Insel said in the interview that his motivation was not to disparage the D.S.M. as a clinical tool, but to encourage researchers and especially outside reviewers who screen proposals for financing from his agency to disregard its categories and investigate the biological underpinnings of disorders instead. He said he had heard from scientists whose proposals to study processes common to depression, schizophrenia and psychosis were rejected by grant reviewers because they cut across D.S.M. disease categories.
“They didn’t get it,” Dr. Insel said of the reviewers. “What we’re trying to do with RDoC is say actually this is a fresh way to think about it.” He added that he hoped researchers would also participate in projects funded through the Obama administration’s new brain initiative.
Dr. Michael First, a psychiatry professor at Columbia who edited the last edition of the manual, said, “RDoC is clearly the way of the future,” although it would take years to get results that could apply to patients. In the meantime, he said, “RDoC can’t do what the D.S.M. does. The D.S.M. is what clinicians use. Patients will always come into offices with symptoms.”
For at least a decade, Dr. First and others said, patients will continue to be diagnosed with D.S.M. categories as a guide, and insurance companies will reimburse with such diagnoses in mind.
Dr. Jeffrey Lieberman, the chairman of the psychiatry department at Columbia and president-elect of the American Psychiatric Association, which publishes the D.S.M., said that the new edition’s refinements were “based on research in the last 20 years that will improve the utility of this guide for practitioners, and improve, however incrementally, the care patients receive.”
He added: “The last thing we want to do is be defensive or apologetic about the state of our field. But at the same time, we’re not satisfied with it either. There’s nothing we’d like better than to have more scientific progress.”
Jeryl Lynn Hilleman with her sister, Kirsten, in 1966 as a doctor gave her the mumps vaccine developed by their father.
A Forgotten Pioneer of Vaccines
By RICHARD CONNIFF, The New York Times, May 6, 2013
We live in an epidemiological bubble and are for the most part blissfully unaware of it. Diseases that were routine hazards of childhood for many Americans living today now seem like ancient history. And while every mother could once identify measles in a heartbeat, now even the best hospitals have to call in their eldest staff members to ask: “Is this what we think it is?”
To a remarkable extent, we owe our well-being, and in many cases our lives, to the work of one man and to events that happened 50 years ago this spring.
At 1 a.m. on March 21, 1963, an intense, irascible but modest Merck scientist named Maurice R. Hilleman was asleep at his home in the Philadelphia suburb of Lafayette Hill when his 5-year-old daughter, Jeryl Lynn, woke him with a sore throat. Dr. Hilleman felt the side of her face and then the telltale swelling beneath the jaw indicating mumps. He tucked her back into bed, about the only treatment anyone could offer at the time.
For most children, mumps was a nuisance disease, nothing worse than a painful swelling of the salivary glands. But Dr. Hilleman knew that it could sometimes leave a child deaf or otherwise permanently impaired.
He quickly dressed and drove 20 minutes to pick up proper sampling equipment from his laboratory. Returning home, he woke Jeryl Lynn long enough to swab the back of her throat and immerse the specimen in a nutrient broth. Then he drove back to store it in the laboratory freezer.
The name Maurice Hilleman may not ring a bell. But today 95 percent of American children receive the M.M.R. - the vaccine for measles, mumps and rubella that Dr. Hilleman invented, starting with the mumps strain he collected that night from his daughter.
It was by no means his only contribution. At Dr. Hilleman’s death in 2005, other researchers credited him with having saved more lives than any other scientist in the 20th century. Over his career, he devised or substantially improved more than 25 vaccines, including 9 of the 14 now routinely recommended for children.
“One person did that!” said Dr. Anthony S. Fauci, a longtime friend of Dr. Hilleman’s and now director of the National Institute of Allergy and Infectious Diseases. “Truly amazing.”
As a young man in Montana, Maurice Hilleman had intended only to become a manager at the J. C. Penney store. He turned out not to have the perfect retail personality. (Asked later in life what he was proudest of in his career, he replied, “Being able to survive while being a bastard.”)
After getting a Ph.D. in microbiology at the University of Chicago, he went on to spend most of his career at Merck, but the corporate personality also eluded him. He had a sailor’s vocabulary, and his brand of peer review often included shipboard expletives (though he used them “in a constructive way,” Dr. Fauci said with a smile).
But everyone recognized Dr. Hilleman’s genius at discovering and perfecting vaccines, which he pursued, Dr. Fauci said, with a rare combination of “exquisite scientific knowledge” and an “amazingly practical get-it-done personality.”
Vaccines are tools for coaxing the immune system to resist a disease without producing the actual symptoms, and making them was as much an art as a science. “It’s not like there was a formula for this,” said Dr. Paul A. Offit, a Philadelphia pediatrician, vaccine developer and the author of “Vaccinated,” a 2007 biography of Dr. Hilleman.
The general practice was to isolate a disease organism, figure out how to keep it alive in the laboratory, then weaken or “attenuate” it by passing it over and over through a series of cells, typically from chicken embryos, until it could no longer reproduce in humans but could still elicit an immune response. Other steps followed, particularly for Dr. Hilleman, who was obsessed with safety and with stripping away unwanted side effects.
That spring of 1963, the Food and Drug Administration also granted the first license for a vaccine against measles. Much of the early work on the virus had been done in the laboratory of John F. Enders at Boston Children’s Hospital, but the vaccine still commonly produced rashes and fevers when Dr. Hilleman began to work on it.
Under pressure from public health officials to stop a disease then killing more than 500 American children every year, Dr. Hilleman and Dr. Joseph Stokes, a pediatrician, devised a way to minimize the side effects by giving a gamma globulin shot in one arm and the measles vaccine in the other. It was the beginning of the end of the disease in this country.
Dr. Hilleman then went on to refine the vaccine over the next four years, eventually producing the much safer Moraten strain that is still in use today. As always, he kept himself in the background: The name stands for “more attenuated enders.”
One other crucial event in the development of M.M.R. happened that spring of 1963: An epidemic of rubella began in Europe and quickly swept around the globe. In this country, the virus’s devastating effect on first-trimester pregnancies caused about 11,000 newborns to die, according to the Centers for Disease Control and Prevention. An additional 20,000 suffered birth defects, including deafness, heart disease and cataracts.
Dr. Hilleman was already testing his own vaccine as the epidemic ended in 1965. But he agreed to work instead with a vaccine being developed by federal regulators. It was, he later recalled, “toxic, toxic, toxic.” By 1969, he had cleaned it up enough to obtain F.D.A. approval and prevent another rubella epidemic. Finally, in 1971, he put his vaccines for measles, mumps and rubella together to make M.M.R., replacing a series of six shots with just two.
Or rather not finally. In 1978, having found a better rubella vaccine than his own, Dr. Hilleman asked its developer if he could use it in the M.M.R. The developer, Dr. Stanley Plotkin, then of the Wistar Institute in Philadelphia, was momentarily speechless. It was an expensive choice for Merck, and might have been a painful one for anyone other than Dr. Hilleman.
“It’s not that he didn’t have an ego. He certainly did,” Dr. Plotkin recalled in a recent interview. “But he valued excellence above that. Once he decided that this strain was better, he did what he had to do,” even if it meant sacrificing his own work.
Given Dr. Hilleman’s obsession with safety and effectiveness, it came as a bitter surprise toward the end of his life when his vaccine was at the center of what Dr. Offit called “a perfect storm of fear.” In 1998, The Lancet, a respected British medical journal, published an article alleging that M.M.R. had caused an epidemic of autism.
The lead author, Dr. Andrew Wakefield, became a media celebrity, and some parents began to balk at having their children immunized; the vaccine’s very success had made them forget just how devastating measles, mumps and rubella could be. Dr. Hilleman, who might reasonably have been expected to win a Nobel Prize, got hate mail and death threats instead.
Multiple independent studies would eventually demonstrate that there is no link between M.M.R. and autism, and Dr. Wakefield’s work has been widely discredited. In 2010, the British medical authorities stripped him of the right to practice medicine, and The Lancet retracted the 1998 article.
It came too late, not just for Dr. Hilleman, who by then had died of cancer, but also for many parents who mistakenly believed that avoiding the vaccine was the right way to protect their children. In 2011 alone, a measles outbreak in Europe sickened 26,000 people and killed 9. Because the disease is contagious enough to pick up from a traveler walking by in the airport, cases still also occur in this country among the unvaccinated.
But Dr. Hilleman would probably still find reason to be encouraged. The Measles and Rubella Initiative, a global campaign organized in 2001, has given the M.M.R. vaccine to a billion children in this century, preventing 9.6 million deaths from measles alone, for less than $2 a dose. According to Dr. Stephen L. Cochi, a global immunization adviser at the C.D.C., the initiative is “on the verge of setting a target date” to eradicate the disease.
In this country, the strain that Dr. Hilleman collected from his daughter that night in 1963 has reduced the incidence of mumps to fewer than 1,000 cases a year, from 186,000. Characteristically, he named it not for himself but for his daughter. Jeryl Lynn Hilleman, now a financial consultant to biotech start-ups in Silicon Valley, turns the credit back on her father.
He was driven, she said in an interview, “by a need to be of use - of use to people, of use to humanity.”
“All I did,” she added, “was get sick at the right time, with the right virus, with the right father.”
This article has been revised to reflect the following correction:
Correction: May 6, 2013
An earlier photo caption with this article misspelled the given name of one of Dr. Hilleman’s daughters. She is Jeryl Lynn, not Jeri Lynn.
This article has been revised to reflect the following correction:
Correction: May 6, 2013
An earlier version of a home page summary on this article misspelled the surname of the girls pictured. It is Hilleman, not Hillemann.
By C. DREW HARVELL, The New York Times, May 6, 2013
MAUNA LANI REEF, Hawaii - After a long, cold swim in the dark, we spotted it on the night reef with our dive lights: Octopus ornatus, the ornate octopus, a foot-long creature in an amber shade of orange with bright white spots and dashes along all its arms.
It sat stolidly in the light of the camera, 30 feet below the surface, unfazed by the attention. I reached out a finger and it touched me with its suctioned tentacles. When it scuttled in the other direction, I herded it between my cupped hands as it watched me attentively with searching golden eyes.
As if levitating, it smoothly lifted off and tried to jet over my head, but slowly enough that I could catch it gently in midair - like handling a large bird, albeit one with eight sticky tentacles. Holding it at eye level, I looked into its eyes. I felt connected, sort of an octopus whisperer.
Then a tentacle slapped the front of my mask. The octopus crawled up my arm and vanished into the night.
I’ve been a marine biologist my entire professional life, spending more than 25 years researching the health of corals and sustainability of reefs. I’m captivated by the magic of sessile invertebrates like corals, sponges and sea squirts - creatures vital to the ecosystem yet too often overlooked in favor of more visible animals like sharks and whales.
The filmmaker David O. Brown and I want to change that. To make a documentary, “Fragile Legacy,” we are on a quest to lure these elusive and delicate invertebrates in front of the camera lens.
Our inspiration springs from an unlikely source: a collection of 570 superbly wrought, anatomically perfect glass sculptures of marine creatures from the 19th century.
These delicate folds and strands of glass make up the Blaschka collection of glass invertebrates at Cornell, of which I am the curator - enchanting and impossibly rare jellyfishes of the open ocean; more common but equally beautiful octopus, squid, anemones and nudibranchs from British tide pools and Mediterranean shores.
They are the work of an extraordinary father-and-son team, Leopold and Rudolf Blaschka. Leopold Blaschka (1822-95) was a Czech immigrant to Dresden, in what is now Germany; on a trip to America in 1853, his ship was becalmed and he was enchanted by a spectacular display of bioluminescence from a type of jellyfish called a siphonophore.
He decided to study the jellyfish more closely and create their likenesses in glass. His first works were a set of anemones for the Dresden Natural History Museum in 1863, inspired by the naturalist Philip Henry Gosse’s “British Sea-Anemones and Corals.”
Leopold’s son, Rudolf (1857-1939), was a keen natural historian in his own right, and an ardent aquarist, or aquarium keeper. He followed his father’s lead, expanding in biodiversity to reach the edges of the animal kingdom. (And beyond: Later they created a comprehensive collection of flowers that is now on display at Harvard.)
To restore Cornell’s vast collection - bought from the Blaschkas themselves in 1885 - a glassworker, Elizabeth R. Brill, has painstakingly cleaned each piece and glued back fragmented gills and wayward tentacles. The collection is on view at several galleries and the Johnson Museum of Art on the Cornell campus, and restored pieces can be seen in an online gallery.
The marine biodiversity recreated by the Blaschkas is a phantasmagorical view of life in the oceans. For they were artists as well as keen natural historians, with an eye for the forms that would enchant in glass and that were too rare or fragile to be seen readily. They were also superb teachers, eager to share the wonders of nature with students.
Their favorite subjects were the ephemeral, translucent, bright forms of the Cnidaria (anemones, jellyfish, corals), unshelled mollusks (nudibranchs, octopus and squid) and brilliant tentacled worms. Some of their most brilliant creations are of the different species of cephalopods, like the ornate octopus.
David Brown and I came to Hawaii with the goal of making videos of as many Blaschka cephalopod look-alikes as we could find. (The ornate octopus we found was not an exact match with the Blaschkas’, but the common octopus was: Our glass counterpart still sits dusty and broken in its original shipping box, soon to be restored by Elizabeth.)
Our quest is also to use the Blaschka collection as a time capsule, to take a snapshot of change. How many of these creatures that were so common 150 years ago can still be found today?
The oceans are changing rapidly, with a 30 percent increase in acidity in the last 200 years, lethally stressful warming in many tropical seas, and significant coastal pollution and overfishing just about everywhere. If ever there was a time to compare the plentiful past with an ocean in jeopardy, that time would be now.
The chances of finding cephalopods are much improved while they are out foraging at night. So we did a series of night reef dives, followed by a “black water” dive three miles off the Kona coast.
That one put us in 1,000-foot-deep water, well after sunset, with the very real possibility of encountering tiger sharks and great white sharks. Floating in the current, the captain turned off all the boat’s lights, the better to see bioluminescent “black magic.”
We clipped onto our safety lines and slipped below the surface without lights, into darkness punctuated by bioluminescent splashes. We had to drift close to identify whether these splashes were from jellyfish, ctenophores, salps or squid. As we settled into our depth at 50 feet below the surface and turned on our dive lights, the sparkles of bioluminescence turned into a stream of tiny plankton floating by.
What I really hoped to see were siphonophores, the creatures that created the mid-Atlantic bioluminescence that so inspired Leopold Blaschka in 1853 and whose models are some of the most intricate in our collection.
For example, the glass model of Apolemia uvaria has the basic form of a siphonophore that I could see before me - the large swimming bell, its powerhouse for fast movement, and the long dangling tentacles - each capped with a deadly harpoon loaded with neurotoxin - that are death traps for all manner of small shrimp and fish.
And the siphonophores put on quite a show for us, even if they were small and wickedly hard to film. They stretched out those long tentacles, hauling them in rapidly when prey arrived.
And when they encountered danger, their nervous systems fired a signal to muscles that zipped up the tentacles and powered the swimming bell to high speed. A three-foot-long string of stinging tentacles contracted in a flash to a three-inch stream of jet propulsion. (Somehow, the term “jellyfish” doesn’t capture the extravagant evolution and biology at work here!)
Then I heard an underwater shout from David as he caught a picture of an exquisite tiny octopus zooming past.
The next stop in our quest is the Mediterranean, ground zero for Blaschka subjects. This month I head to Italy, to the Naples Marine Station, which supplied the glassmakers with many of their live animals.
Perhaps we’ll find exact matches for such spectacular invertebrates as the curly tentacled octopus (Eledone moschata) and the giant siphonophore Apolemia uvaria, which at 20 feet long can dominate a Mediterranean food web. At any rate, we hope to find out whether they are surviving in the sea as magnificently as they do in glass.
C. Drew Harvell is the associate director for environment at the Atkinson Center for a Sustainable Future at Cornell, and curator of the Cornell Collection of Blaschka Invertebrate Models.
Psychiatry’s Guide Is Out of Touch With Science, Experts Say
By PAM BELLUCK and BENEDICT CAREY, The New York Times, May 6, 2013
Just weeks before the long-awaited publication of a new edition of the so-called bible of mental disorders, the federal government’s most prominent psychiatric expert has said the book suffers from a scientific “lack of validity.”
The expert, Dr. Thomas R. Insel, director of the National Institute of Mental Health, said in an interview Monday that his goal was to reshape the direction of psychiatric research to focus on biology, genetics and neuroscience so that scientists can define disorders by their causes, rather than their symptoms.
While the Diagnostic and Statistical Manual of Mental Disorders, or D.S.M., is the best tool now available for clinicians treating patients and should not be tossed out, he said, it does not reflect the complexity of many disorders, and its way of categorizing mental illnesses should not guide research.
“As long as the research community takes the D.S.M. to be a bible, we’ll never make progress,” Dr. Insel said, adding, “People think that everything has to match D.S.M. criteria, but you know what? Biology never read that book.”
The revision, known as the D.S.M.-5 and the first since 1994, has stirred unprecedented questioning from the public, patient groups and, most fundamentally, senior figures in psychiatry who have challenged not only decisions about specific diagnoses but the scientific basis of the entire enterprise. Basic research into the biology of mental disorders and treatment has stalled, they say, confounded by the labyrinth of the brain.
Decades of spending on neuroscience have taught scientists mostly what they do not know, undermining some of their most elemental assumptions. Genetic glitches that appear to increase the risk of schizophrenia in one person may predispose others to autism-like symptoms, or bipolar disorder. The mechanisms of the field’s most commonly used drugs - antidepressants like Prozac, and antipsychosis medications like Zyprexa - have revealed nothing about the causes of those disorders. And major drugmakers have scaled back psychiatric drug development, having virtually no new biological “targets” to shoot for.
Dr. Insel is one of a growing number of scientists who think that the field needs an entirely new paradigm for understanding mental disorders, though neither he nor anyone else knows exactly what it will look like.
Even the chairman of the task force making revisions to the D.S.M., Dr. David J. Kupfer, a professor of psychiatry at the University of Pittsburgh, said the new manual was faced with doing the best it could with the scientific evidence available.
“The problem that we’ve had in dealing with the data that we’ve had over the five to 10 years since we began the revision process of D.S.M.-5 is a failure of our neuroscience and biology to give us the level of diagnostic criteria, a level of sensitivity and specificity that we would be able to introduce into the diagnostic manual,” Dr. Kupfer said.
The creators of the D.S.M. in the 1960s and ’70s “were real heroes at the time,” said Dr. Steven E. Hyman, a psychiatrist and neuroscientist at the Broad Institute and a former director at the National Institute of Mental Health. “They chose a model in which all psychiatric illnesses were represented as categories discontinuous with ‘normal.’ But this is totally wrong in a way they couldn’t have imagined. So in fact what they produced was an absolute scientific nightmare. Many people who get one diagnosis get five diagnoses, but they don’t have five diseases - they have one underlying condition.”
Dr. Hyman, Dr. Insel and other experts said they hoped that the science of psychiatry would follow the direction of cancer research, which is moving from classifying tumors by where they occur in the body to characterizing them by their genetic and molecular signatures.
About two years ago, to spur a move in that direction, Dr. Insel started a federal project called Research Domain Criteria, or RDoC, which he highlighted in a blog post last week. Dr. Insel said in the blog that the National Institute of Mental Health would be “reorienting its research away from D.S.M. categories” because “patients with mental disorders deserve better.” His commentary has created ripples throughout the mental health community.
Dr. Insel said in the interview that his motivation was not to disparage the D.S.M. as a clinical tool, but to encourage researchers and especially outside reviewers who screen proposals for financing from his agency to disregard its categories and investigate the biological underpinnings of disorders instead. He said he had heard from scientists whose proposals to study processes common to depression, schizophrenia and psychosis were rejected by grant reviewers because they cut across D.S.M. disease categories.
“They didn’t get it,” Dr. Insel said of the reviewers. “What we’re trying to do with RDoC is say actually this is a fresh way to think about it.” He added that he hoped researchers would also participate in projects funded through the Obama administration’s new brain initiative.
Dr. Michael First, a psychiatry professor at Columbia who edited the last edition of the manual, said, “RDoC is clearly the way of the future,” although it would take years to get results that could apply to patients. In the meantime, he said, “RDoC can’t do what the D.S.M. does. The D.S.M. is what clinicians use. Patients will always come into offices with symptoms.”
For at least a decade, Dr. First and others said, patients will continue to be diagnosed with D.S.M. categories as a guide, and insurance companies will reimburse with such diagnoses in mind.
Dr. Jeffrey Lieberman, the chairman of the psychiatry department at Columbia and president-elect of the American Psychiatric Association, which publishes the D.S.M., said that the new edition’s refinements were “based on research in the last 20 years that will improve the utility of this guide for practitioners, and improve, however incrementally, the care patients receive.”
He added: “The last thing we want to do is be defensive or apologetic about the state of our field. But at the same time, we’re not satisfied with it either. There’s nothing we’d like better than to have more scientific progress.”
Jeryl Lynn Hilleman with her sister, Kirsten, in 1966 as a doctor gave her the mumps vaccine developed by their father.
A Forgotten Pioneer of Vaccines
By RICHARD CONNIFF, The New York Times, May 6, 2013
We live in an epidemiological bubble and are for the most part blissfully unaware of it. Diseases that were routine hazards of childhood for many Americans living today now seem like ancient history. And while every mother could once identify measles in a heartbeat, now even the best hospitals have to call in their eldest staff members to ask: “Is this what we think it is?”
To a remarkable extent, we owe our well-being, and in many cases our lives, to the work of one man and to events that happened 50 years ago this spring.
At 1 a.m. on March 21, 1963, an intense, irascible but modest Merck scientist named Maurice R. Hilleman was asleep at his home in the Philadelphia suburb of Lafayette Hill when his 5-year-old daughter, Jeryl Lynn, woke him with a sore throat. Dr. Hilleman felt the side of her face and then the telltale swelling beneath the jaw indicating mumps. He tucked her back into bed, about the only treatment anyone could offer at the time.
For most children, mumps was a nuisance disease, nothing worse than a painful swelling of the salivary glands. But Dr. Hilleman knew that it could sometimes leave a child deaf or otherwise permanently impaired.
He quickly dressed and drove 20 minutes to pick up proper sampling equipment from his laboratory. Returning home, he woke Jeryl Lynn long enough to swab the back of her throat and immerse the specimen in a nutrient broth. Then he drove back to store it in the laboratory freezer.
The name Maurice Hilleman may not ring a bell. But today 95 percent of American children receive the M.M.R. - the vaccine for measles, mumps and rubella that Dr. Hilleman invented, starting with the mumps strain he collected that night from his daughter.
It was by no means his only contribution. At Dr. Hilleman’s death in 2005, other researchers credited him with having saved more lives than any other scientist in the 20th century. Over his career, he devised or substantially improved more than 25 vaccines, including 9 of the 14 now routinely recommended for children.
“One person did that!” said Dr. Anthony S. Fauci, a longtime friend of Dr. Hilleman’s and now director of the National Institute of Allergy and Infectious Diseases. “Truly amazing.”
As a young man in Montana, Maurice Hilleman had intended only to become a manager at the J. C. Penney store. He turned out not to have the perfect retail personality. (Asked later in life what he was proudest of in his career, he replied, “Being able to survive while being a bastard.”)
After getting a Ph.D. in microbiology at the University of Chicago, he went on to spend most of his career at Merck, but the corporate personality also eluded him. He had a sailor’s vocabulary, and his brand of peer review often included shipboard expletives (though he used them “in a constructive way,” Dr. Fauci said with a smile).
But everyone recognized Dr. Hilleman’s genius at discovering and perfecting vaccines, which he pursued, Dr. Fauci said, with a rare combination of “exquisite scientific knowledge” and an “amazingly practical get-it-done personality.”
Vaccines are tools for coaxing the immune system to resist a disease without producing the actual symptoms, and making them was as much an art as a science. “It’s not like there was a formula for this,” said Dr. Paul A. Offit, a Philadelphia pediatrician, vaccine developer and the author of “Vaccinated,” a 2007 biography of Dr. Hilleman.
The general practice was to isolate a disease organism, figure out how to keep it alive in the laboratory, then weaken or “attenuate” it by passing it over and over through a series of cells, typically from chicken embryos, until it could no longer reproduce in humans but could still elicit an immune response. Other steps followed, particularly for Dr. Hilleman, who was obsessed with safety and with stripping away unwanted side effects.
That spring of 1963, the Food and Drug Administration also granted the first license for a vaccine against measles. Much of the early work on the virus had been done in the laboratory of John F. Enders at Boston Children’s Hospital, but the vaccine still commonly produced rashes and fevers when Dr. Hilleman began to work on it.
Under pressure from public health officials to stop a disease then killing more than 500 American children every year, Dr. Hilleman and Dr. Joseph Stokes, a pediatrician, devised a way to minimize the side effects by giving a gamma globulin shot in one arm and the measles vaccine in the other. It was the beginning of the end of the disease in this country.
Dr. Hilleman then went on to refine the vaccine over the next four years, eventually producing the much safer Moraten strain that is still in use today. As always, he kept himself in the background: The name stands for “more attenuated enders.”
One other crucial event in the development of M.M.R. happened that spring of 1963: An epidemic of rubella began in Europe and quickly swept around the globe. In this country, the virus’s devastating effect on first-trimester pregnancies caused about 11,000 newborns to die, according to the Centers for Disease Control and Prevention. An additional 20,000 suffered birth defects, including deafness, heart disease and cataracts.
Dr. Hilleman was already testing his own vaccine as the epidemic ended in 1965. But he agreed to work instead with a vaccine being developed by federal regulators. It was, he later recalled, “toxic, toxic, toxic.” By 1969, he had cleaned it up enough to obtain F.D.A. approval and prevent another rubella epidemic. Finally, in 1971, he put his vaccines for measles, mumps and rubella together to make M.M.R., replacing a series of six shots with just two.
Or rather not finally. In 1978, having found a better rubella vaccine than his own, Dr. Hilleman asked its developer if he could use it in the M.M.R. The developer, Dr. Stanley Plotkin, then of the Wistar Institute in Philadelphia, was momentarily speechless. It was an expensive choice for Merck, and might have been a painful one for anyone other than Dr. Hilleman.
“It’s not that he didn’t have an ego. He certainly did,” Dr. Plotkin recalled in a recent interview. “But he valued excellence above that. Once he decided that this strain was better, he did what he had to do,” even if it meant sacrificing his own work.
Given Dr. Hilleman’s obsession with safety and effectiveness, it came as a bitter surprise toward the end of his life when his vaccine was at the center of what Dr. Offit called “a perfect storm of fear.” In 1998, The Lancet, a respected British medical journal, published an article alleging that M.M.R. had caused an epidemic of autism.
The lead author, Dr. Andrew Wakefield, became a media celebrity, and some parents began to balk at having their children immunized; the vaccine’s very success had made them forget just how devastating measles, mumps and rubella could be. Dr. Hilleman, who might reasonably have been expected to win a Nobel Prize, got hate mail and death threats instead.
Multiple independent studies would eventually demonstrate that there is no link between M.M.R. and autism, and Dr. Wakefield’s work has been widely discredited. In 2010, the British medical authorities stripped him of the right to practice medicine, and The Lancet retracted the 1998 article.
It came too late, not just for Dr. Hilleman, who by then had died of cancer, but also for many parents who mistakenly believed that avoiding the vaccine was the right way to protect their children. In 2011 alone, a measles outbreak in Europe sickened 26,000 people and killed 9. Because the disease is contagious enough to pick up from a traveler walking by in the airport, cases still also occur in this country among the unvaccinated.
But Dr. Hilleman would probably still find reason to be encouraged. The Measles and Rubella Initiative, a global campaign organized in 2001, has given the M.M.R. vaccine to a billion children in this century, preventing 9.6 million deaths from measles alone, for less than $2 a dose. According to Dr. Stephen L. Cochi, a global immunization adviser at the C.D.C., the initiative is “on the verge of setting a target date” to eradicate the disease.
In this country, the strain that Dr. Hilleman collected from his daughter that night in 1963 has reduced the incidence of mumps to fewer than 1,000 cases a year, from 186,000. Characteristically, he named it not for himself but for his daughter. Jeryl Lynn Hilleman, now a financial consultant to biotech start-ups in Silicon Valley, turns the credit back on her father.
He was driven, she said in an interview, “by a need to be of use - of use to people, of use to humanity.”
“All I did,” she added, “was get sick at the right time, with the right virus, with the right father.”
This article has been revised to reflect the following correction:
Correction: May 6, 2013
An earlier photo caption with this article misspelled the given name of one of Dr. Hilleman’s daughters. She is Jeryl Lynn, not Jeri Lynn.
This article has been revised to reflect the following correction:
Correction: May 6, 2013
An earlier version of a home page summary on this article misspelled the surname of the girls pictured. It is Hilleman, not Hillemann.