Floyd Bloom: Building a bridge to the future

Floyd Bloom and the transformation of brain research

Editor’s Note:  This profile of Floyd Bloom, written in 2003, has been updated.

Lisa A. DuBois
Published: November, 2003

In the late 1960s, Floyd Bloom was so frustrated by his administrative and teaching responsibilities at Yale University Medical Center that he asked if he could resign his position as assistant professor and become a post-doctoral research fellow again. Such a request was unheard of in the venerable halls of the Ivy League.

But Bloom was serious. Over his chairman’s objections, he left Yale and returned to his familiar training grounds at the National Institute of Mental Health (NIMH) in Bethesda, Md. There in a laboratory in St. Elizabeth’s Hospital, surrounded by patients with profound mental illness, many of whom had spent 20, 30, or 40 years hospitalized with schizophrenia, depression or debilitating psychoses, he resumed his true passion -- trying to decipher the biochemical reactions that lead to both normal and abnormal brain function.

Bloom is ardently devoted to basic science, a man willing to jump disciplines in order to test a theory or reach a solution, a firm believer in the integration of ideas. As a physician, he is equally dedicated to moving discoveries rapidly from the laboratory “bench” to the “bedsides” of patients.

“Floyd has this huge ‘super’ vision,” says Lee Limbird, Ph.D., former chair of Pharmacology at Vanderbilt University Medical Center. “He conceptualizes problems at a 30,000-foot level, but then he drops down to the ground to make those problems tractable to experiments.”

Over the course of his career, Bloom has identified new neurotransmitters and neuromodulators that led to the mapping out of the brain’s chemical pathways; he has spearheaded breakthroughs in the neurophysiology of drug addiction, alcoholism, degenerative diseases, and AIDS-related dementia; and he has ascended to a leadership role as an activist, calling for a national policy review that would jumpstart a complete restructuring of the American health care system.

“To me, he’s the Carl Sagan of neurobiology,” Limbird adds. “One of the things that Carl Sagan did was to help lay people put words not only to the science, but to the excitement and the importance of what was discovered. Floyd has that same contagious enthusiasm. Yet even though he has one of the most extraordinary and gifted minds, he’s totally unpretentious. There’s no feigned humility. He’s just a passionate human being.”

Married since 1980 to Jody Corey-Bloom, M.D., Ph.D., clinical professor of Neuroscience at the University of California, San Diego, he is the father of two and the grandfather of four. Sitting in his office at the biotech neuroinformatics company, Neurome, which he co-founded three years ago, he speaks with energy and he smiles often. And, most strikingly, he listens. Intently.

Born in 1936 in Minneapolis, Bloom has vivid early memories of sitting by the family radio listening to reports about World War II. His father Jack, who was a pharmacist, had dreamed of going to medical school, but had been turned down because of the pervasive quota system that thwarted many Jewish applicants.

His son would not have to suffer the same indignity. Following a younger sibling who told him, “Jewish boys can get a break in Texas,” Jack Bloom sold his Midwestern pharmacies and, in 1945, moved his family to Dallas.

Bloom graduated from high school in Texas, attended Southern Methodist University, where he majored in German literature, and, at his father’s directive, applied to medical school at Washington University Medical School in St. Louis. He had been a brilliant student in a variety of subjects – except for calculus. Calculus proved to be his nemesis in medical school as well, when he needed it to understand physiology.

Bloom (second from left in the first row) with colleagues in the Laboratory of Neuropharmacology at St. Elizabeth's Hospital in Washington, D.C., in 1974.
Courtesy of Floyd Bloom
Despite his less-than-stellar performance in that subject, his physiology professor, Gordon Schoepfle, was sure that Bloom had the capacity to master the course if he could study it in context. Schoepfle invited the medical student to spend a summer in his lab on a student fellowship at the National Institutes of Health, where he could learn physiology through bench research.

Doctors were still being drafted in the early 1960s in response to Cold War tensions, and Bloom decided to meet his service requirements by working at the NIH. After traveling to Bethesda for the interviews, however, he was told his research position had fallen through at the last minute. A jobless medical resident, he was suddenly a prime target for the draft and pictured himself being shipped off to Germany or serving on a Coast Guard cutter off the coast of Alaska.

Thrill of discovery

Frantically, he called the director of the research associates program, Dr. Robert Berliner (whom he would later know as the Dean of Yale Medical School), and begged him to find him another spot in their program. At Berliner’s suggestion, Bloom interviewed at one of the oldest government-run psychiatric hospitals in the country, St. Elizabeth’s Hospital in southeast Washington, D.C. He was accepted into the lab of Dr. Giancarlo Salmoiraghi, but he had no idea what he was being hired to do.

“That was a brain laboratory, not a peripheral nerve lab,” he says. “I’d done all my biophysical work on the sciatic nerve of a frog. And now I was working with the brains of cats. It was neurosurgery, physiology, and pharmacology all in one. It was terribly exciting – one of the neatest times of my life. We were doing things that no one had ever been able to do before. We were discovering stuff that had just been lying there waiting to be discovered.” Hooked, Bloom never returned to St. Louis to complete his residency.

Using multi-barreled microelectrodes, the NIMH investigators would supply very small amounts of chemicals to various parts of the animal’s brain and record the activity of nerve cells, trying to examine the action of the neurotransmitters.

Bloom demonstrates stereotaxic injection techniques for studying brain function to postdoctoral fellows (left to right) Leonard Koda, James Nathanson and David Taylor at St. Elizabeth's Hospital in 1974.
Courtesy of Floyd Bloom
One of Salmoiraghi’s colleagues, Dr. Erminio Costa, helped mentor the young physician-scientist.

“In those days there were only one or two known neurotransmitters, and the NIMH labs assisted in the discovery of 20 or more additional ones. There was an explosion in known neurotransmitters,” says Costa, scientific director of the Psychiatric Institute at the University of Illinois at Chicago. “At the time nobody believed a chemical substance would be important for brain function. Everything in the brain would be electrical and neurotransmitters would be like part of a machine.

“During that period we began to discover that electrical impulses were stimulated by chemical substances.”

Bloom realized that in order to study a cat or rabbit’s brain, scientists had to anesthetize the animal. He stepped back and asked a question: “Is the response I’m seeing in the anesthetized animal predictive of what the response would have been if the anesthesia wasn’t there?” To answer that question, he and his colleagues developed methods for surgically isolating the brain.

“We found that some neurotransmitters totally changed the quality of what they did in the absence of anesthesia from what we would have predicted. Whereas others were absolutely consistent,” he says. “I think this was the first time that kind of insight had been obtained – that the actual act of studying the brain was confused by the use of the anesthetic.”

Propelled by this new paradigm, in 1964 Bloom accepted another post-doctoral fellowship at Yale, so he could learn histochemistry, using tissue sections to understand the chemical basis of brain function and define where neurotransmitters and their receptors are located. Bloom and others were sowing some revolutionary seeds: If certain brain diseases arise from chemical imbalances, perhaps those imbalances could be corrected with new medications that avoided the serious side effects of the older psychotropic drugs, and without having to use electroconvulsive shock therapy.

Bloom measures how long it takes the drug naloxone to reverse the effect of opioids in an experimental rat model at the Salk Institute in 1977.
Courtesy of Floyd Bloom
Although Bloom was gaining prestige for his research, over time he began to feel too squeezed by the demands of his job to pursue it as effectively as he wanted. He asked his Yale superiors to demote him back to the position of post-doc. Instead, they promoted him to associate professor. Throwing up his hands, he returned to the NIMH where he could spend more time in the lab. Within a year he was named chief of the laboratory of neuropharmacology at St. Elizabeth’s Hospital.

George Siggins, Ph.D., professor at The Scripps Research Institute, was one of Bloom’s first postdoctoral fellows at the NIMH and the two have continued their collaboration for 35 years. “St. Elizabeth’s Hospital was where the federal government put all the worst psychiatric cases that they did not know what to do with,” Siggins recalls. “The hospital was a former 'snake pit' wherein I believe they once had used all kinds of questionable 'therapies' (lobotomy, hydrotherapy, etc.), and it was kind of grim in an ‘Addams Family’ kind of way.

“The setting thus added to the plight of the patients, who ran the gamut of serious psychiatric problems. Since many of them were allowed to roam the grounds pretty much, we saw them on a daily basis when we entered or left the building, or went to lunch, and occasionally we would find one rifling through our desk drawers or file cabinets. We got to know them and their afflictions pretty well. But the daily encounters greatly reinforced our sense of duty, that we had a mission to improve their lives and conquer these disorders by our research.”

Pedals of the piano

Bloom was particularly intrigued by norepinephrine, a neurotransmitter related to adrenaline that causes blood to vessels to constrict and the heart to beat more forcefully and rapidly, and he began what he calls a career-long “obsession” with that neurotransmitter.

Initially focusing on the cerebral cortex, the center of higher mental functions in the brain, Bloom and his associates mapped out the pathway of norepinephrine-associated nerve fibers, and discovered that the origin of the fibers came from an area of the brainstem called the locus coeruleus. The researchers found that while other neurotransmitters directly affected the “excitability” of this small group of cells, norepinephrine worked by modulating other signals.

“It was a completely novel action, not predictable by anything that was previously known,” Bloom says. “Along with others, we were then able to extend that action to the hippocampus and other areas of the brain. (The finding) told us that norepinephrine does not convey specific information, but is more like the foot pedals on a piano. It changes the harmonics of the other information that’s going on. People like to call it a modulator instead of a transmitter. It is transmitting modulatory information. It’s enhancing, or in its absence, diminishing, the effectiveness of other inputs.”

At the electron microscope at the Scripps Research Institute in 1987.
Courtesy of Floyd Bloom
With a better grasp of these novel chemical pathways, investigators began relating synaptic information to behavioral responses, such as depression, and then biochemically lacing those responses with epinephrine, dopamine and serotonin. Those experiments, in turn, ultimately led to the development of such antidepressant drugs as Prozac. Citing other seminal work that he and Bloom completed together, Siggins says they were the first to dissect the neurophysiological effects of prostaglandins in the brain, the first to describe the actions of beta-endorphin in the brain, and the first to report a novel mechanism of action of brain endorphin and other opiate peptides, termed “disinhibition,” that could cause epilepsy-like effects.

Building on discoveries in the “norepinephrine days,” Bloom’s lab members were open to the notion that the brain has adapted many unusual ways of sending messages, which inspired them to search for other possible novel ways neurons communicate. “It put us in the right frame of mind to study brain peptides, for example,” Siggins says. “What we ultimately found with opiate peptides and virtually every other peptide we studied much later is that they all had their own unusual signature or fingerprint of action very different from the fast, rapidly-conducting classical pathways. And Floyd had this intuition early on that the peptides were the wave of the future.”

Bloom was so energized by the concept of neuropeptides that while he was being recruited to join the Salk Institute in La Jolla, Calif., he persuaded the Salk researchers to share their compounds. His coat pockets loaded with little vials of endorphin, enkephalin and other opioids, Bloom flew back to his lab in Washington, D.C., to test their action on brain neurons.

George Koob, Ph.D., a behavioral neuroscientist, joined Bloom’s lab in the mid-1970s, when Bloom moved his group to the Salk Institute. “I think we both always believed that the brain was the key to behavior -- in fact, that behavior was the ultimate expression of the brain’s function,” Koob says. They began to explore the relationship between the action of certain neuropeptides and observable physical behavior. The focus on neuropeptides was Bloom’s idea. Recalls Koob, “He said his mustache whiskers were twitching, so he knew we were on to something.

“Another corner we turned,” Koob continues, “was our work on alcohol where Floyd insisted -- and he was right -- that alcohol MUST act on neurons to (create) its intoxicating- and dependence-inducing effects.

“That work has been confirmed, and our Alcohol Research Center (which Floyd started and directed for almost 20 years) is well on the way to determining what changes in the brain lead to alcohol dependence, alcoholism.”

There is evidence, for example, that norephinephrine may play a role in the motivational aspects of opiate and alcohol dependence. “It is very exciting to return to norepinephrine,” Koob says. “It speaks to the point that science, like a good wine, can age with time, and observations that made little sense 20 years ago can then fit into the puzzle later on to clarify the picture.”

Cinnamon stick

In the early fall of 1979, Bloom was running a meeting of scientists at Woods Hole, Mass. He was a widower and had two teenaged children. A second-year post-doctoral fellow, Jody Corey, was working in a lab at Woods Hole, and she sneaked downstairs to listen to some of the lectures.

She noticed that he would jump up and comment after every talk, drawing parallels and contrasts to previous talks, explaining their relevance to each other. “It was pretty fascinating to listen to him synthesize what we just heard and to tell the audience why what we had just heard was so interesting and important,” she says. “I was very taken by his ability to do that, actually. It was a very attractive feature of him, I thought.”

Bloom recalls his future wife introducing herself to him after the session when she offered him “a cup of coffee she had made with a cinnamon stick.” A year later they married. With a Ph.D. in anatomy in hand, she then went on to medical school at the University of California, San Diego, graduating in 1986, and now specializes in the clinical care of patients with cognitive and degenerative problems like Alzheimer’s and Huntington’s diseases.

Bloom moved his labs to The Scripps Research Institute in 1983, where he chaired the Department of Neuropharmacology for 14 years before retiring in 2005.

He is a member of the National Academy of Sciences, the Institute of Medicine and a foreign member of the Royal Swedish Academy of Sciences. He served on the Science Advisory Board of the MacArthur Foundation and has received an abundance of awards, including the Janssen Award in the Basic Sciences and the Pasarow Award in Neuropsychiatry.

George Siggins (left) and George Koob (right) share memories of their long-time collaboration with Floyd Bloom at the Scripps Research Institute.
“Floyd has an ability to bridge different disciplines in neuroscience,” Corey-Bloom says, citing as an example the large center grant he was awarded to attack the problem of AIDS-associated dementia. “Only someone like my husband could have brought it all together, because he saw the pathology, the pharmacology, the chemistry and the neurochemistry. There are few sub-fields in neuroscience that he hasn’t touched in some way.”

The mapping of the human genome has led to some of the most exciting possibilities for neuroscience, Bloom says. The next great challenge is to understand how modest mutations in several different genes can make a person vulnerable – but not necessarily certain – to develop a psychiatric disease.

“It’s an inheritability to vulnerability,” Bloom explains. “You can have two identical twins with exactly the same genomes, experiencing the same life.

One of them gets schizophrenia and one of them doesn’t. One of them gets depression and one of them doesn’t. One of them becomes an alcoholic and one of them doesn’t.

“Whatever the history of your life is, you have the same genes you start with, but you’re following slightly different trajectories. So, where is it that the brain fails to adapt to those demands of the environment? And what is it about the twin who didn’t get the disease that I can draw from?”

In the 1990s, Bloom began assuming editorial positions at some of the most esteemed scientific journals, most notably, as editor-in-chief of Science from 1995-2000. During that period he made some radical changes, such as moving Science—which is published by the American Association for the Advancement of Science—onto the Internet, greatly expanding its reach.

Fixing health care

After he retired as editor, and while he was president of AAAS, he stood before his constituency at its annual meeting and delivered a clarion call about the wretched state of the American system of health care. His cry, repeated in an essay in the June 13, 2003, issue of Science, called for a complete overhaul of the way American medicine is taught, delivered and financed. Specifically, he demanded that a new breed of physician, one responsible for translating bench research into patient protocol, be introduced into academic institutions.

The speech shook the venerable scientific community to its core. AAAS is an esteemed organization dominated by basic scientists, who have made tremendous contributions to the body of medical knowledge. Suddenly a physician who hadn’t been involved in clinical care in 40 years was putting it all on the line -- the American medical system is failing not scientists, but patients, he claimed, because the fruits of the AAAS are not being applied to the needs of the public.

“I think what he said is tremendously important,” says Alan Leshner, Ph.D., executive publisher of Science and CEO of AAAS. “It brings to bear a new pressure in understanding that health care won’t be able to take advantage of advances that are coming and it adds urgency to our need for fixing the health care system.”

Bloom used the AAAS as his bully pulpit because he had continued to listen. He observed his wife battling with HMOs and insurance agencies over treatment for her patients with dementia and severe degenerative diseases. He knew that layers of bureaucracy were being added, almost daily, layers that waylaid the delivery of new discoveries and the delivery of appropriate care.

“Floyd knows that it’s becoming increasingly frustrating because we are no longer in control of what our patients can and cannot have – even when new discoveries become available,” says Corey-Bloom. “What he’s seeing now, at the time that you’d expect fruition in the setting of the Human Genome Project, is that many of the decisions about treatment and patient care are being taken out of the hands of people who were trained to make those decisions. And he’s aghast at it.”

In 2000, when Bloom was at an age when many academic physicians begin winding down their careers and settling into emeritus status, he joined with colleagues John Morrison, Ph.D., and Warren Young, Ph.D., to form the biotech firm, Neurome, Inc.

The company is developing standardized, quantitative databases that can integrate gene expression patterns within the brain and correlate that data with the rapidly growing store of information on brain structure and function. The goal, says Bloom, is to aid the discovery and development of new ways to diagnose, treat and prevent brain disorders such as Alzheimer’s disease.

“Do you treat the disease when it’s so bad that nothing your body does will bring it back into health? Or do you try to detect the first point at which you veered off the normal healthy track and get a medication that will keep you healthy?” he asks. “The right time to treat Alzheimer’s patients might be when they’re 30 years of age.”

Therein lies the root of the problem with American health care: There is no room for what Bloom calls “medical engineers,” scientists and physicians who could design and implement earlier treatments or even ways of preventing the most debilitating diseases. “We have chemical engineers, we have civil engineers,” he says. “They take the rules of physics and bend them to the needs of society. We need somebody who can make the transistors that can make medicine.”

Bloom raises his arms for emphasis. “I want to be able to be in this big, bubbling vat of new information, and this clamoring throng of patients in need,” he says, “and make soup that will feed the hungry.”

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