The Rochester Review, University of Rochester, Rochester, New York, USA

The Mind-BODY Connection:
Granny Was Right, After All

Benefiting, he says, "simply from being in the right field at the right time," MacArthur "genius grant" winner David Felten has become one of the leading researchers in the emerging field of mind-body medicine.

If you color outside the lines, you'll have a lot of people trying to break your Crayolas. When you're the first with something, it's not easy getting other people to take you seriously."

Sporting a jaunty seasonal tie (Warner Brothers 'toons) and seated on his office sofa alongside a companionable (and life-sized) stuffed wolf, neurobiologist David Felten is talking about his work.

"Our grandmothers knew all along that our minds and our bodies were connected, even if the scientific community didn't. We've simply provided irrefutable data showing that it's true."

Blame it on Descartes that the scientific community has for centuries been contradicting Granny on the matter of an anatomical link between the physical and the psychological.

One morning, so the story goes, the 17th-century philosopher/scientist awoke from a dream, inspired to pursue the study of metaphysics. The culmination of this study was his conclusion that body and mind were separate entities. At that point he and the Roman Catholic Church struck a deal: As a man of science, Descartes would restrict himself to the study of human anatomy, leaving the mind and soul to the care of the church.

From that time on, studies of mind and body have for the most part remained two distinct and separate fields. Scientists endeavored to stay within the realm of the observable and strictly quantifiable. Meanwhile, those in the religious life lifted thought, reason, and emotion out of the body, into the realms of the spiritual.

We lay folk, however, living oxymorons of heavenly thoughts and mundane ills, have always acknowledged a link between our minds and our bodies. Literature and folklore are rife with aphorisms and anecdotes that attest to the bond.

Writing near the time of the birth of Christ, the Stoic Lucius Seneca allowed that "it is part of the cure to wish to be cured." Stories of miracles, confessional fuel for our spirituality, are thematically connected by tales of illnesses and cures. Visitors continue to flock every year to Lourdes, with enough claims of spontaneous cures to keep the shrine's 24-member International Medical Committee fully busy reviewing them.

The mind isn't restricted to curing, however; we have always sensed that human thoughts can kill as well as mend. Harvard physiologist Walter Cannon, for instance, in investigating deaths by voodoo in the 1940s concluded that humans could indeed die from "the fatal power of the imagination working through unmitigated terror."

It was not until the 1970s, however, that documented evidence of a physiological link between the mind and body was firmly established. One of the earliest such came from a study of rodents in labs at the University Medical Center, and led to the development of a new, hybrid field of study now known as psychoneuroimmunology, generally (and mercifully) shortened to "PNI."

PNI is now a highly rated specialty of the Department of Neurobiology and Anatomy at Rochester, the department headed since 1995 by David Felten. Felten, who also holds the Kilian J. and Caroline F. Schmitt Professorship, is recognized as one of the leading researchers in the field. The recipient of a MacArthur Foundation "genius grant," he is the unassuming wearer of numerous other laurels, including--in addition to a dozen or so teaching awards ("Teaching is my passion," he says)--two nominations for the Albert Lasker Award for Medical Research (sometimes the precursor to a Nobel), and, most recently, the Norman Cousins Award in Mind-Body Health given by the Fetzer Foundation.

He arrived at this work via the enthusiasms of a professor of neuroanatomy at M.I.T., where he did his undergraduate study before going on to earn both an M.D. and a Ph.D. at the University of Pennsylvania. "Everybody has to have a hero, and that M.I.T. professor, Walle Nauta, is mine," Felten says. "He invited me to take graduate courses in neuroanatomy, where I fell in love with the nervous system. And I learned that in the biosciences all fields are intrinsically fascinating. It's only our ignorance of them that gets in the way of the fascination."

Felten's office is deep within the Medical Center's warren of offices and research labs. The reception area's cinder-block walls are covered with prints of wolves, bears, and soaring hawks. Almost every available flat space has been claimed by a teddy bear, and a dusky brown stuffed monkey straddles a cubicle divider. A case of bottled diet cola is tucked in a corner on the floor.

If the plush menagerie doesn't make it clear that this is no traditional medical area, a sign on Felten's office door does. It reads: "I am lost. I have gone to look for myself. If I should get back before I return, please ask me to wait."

The door opens on airy blue walls that feel like sky on the eyes; large windows from this fifth-floor room look out on Crittenden Boulevard and more sky, a gift on this dark winter day. A desk and office paraphernalia are positioned to take advantage of the view. More wildlife prints and another herd of stuffed animals (from bear and monkey to buffalo) complete the picture. Should you ask about the wildlife decor, you get the idea that the professor just happens to like it that way, and that he'd much rather discuss what excites him about the emerging field of PNI research.

"If you don't have surprises happening, you're not being bold enough," he says. Felten's own big surprise happened in1981, at Indiana University School of Medicine, where he was then on the faculty. That was the day he and his team of researchers discovered a hard-wire connection between the body's immune system and the central nervous system under control of the brain.

When he first looked through the microscope that day, as he later told a reporter, "My initial response was 'Oh my God, what did I do wrong?'" At first he thought maybe he wasn't looking at the right slides. It turned out that he was, but they were telling him something that had not been observed before.

Using special fluorescent stains to trace nerves to various bodily locations, including bone marrow, lymph nodes, and the spleen, the Felten team had discovered a network of nerves leading to blood vessels as well as cells of the immune system. The researchers also found nerves in the thymus and spleen terminating near clusters of lymphocytes, macrophages, and mast cells, all of which help control immune function.

There it was, the mind-body connection--clear evidence that the brain has the ability to send signals to immune-system cells. Granny was right, after all.

The Felten team's breakthrough studies used existing Rochester research as a fundamental building block, he is quick to point out. The earlier findings came from the laboratory of Professor Robert Ader, who--literally--wrote the book on the new field (Psychoneuroimmunology, the standard text, which he edited with Felten and colleague Nicholas Cohen, an immunologist). "Bob Ader's work should win him a Nobel Prize some day," Felten asserts.

In 1974, Ader, an experimental psychologist, made what most consider to be one of the central discoveries of mind-body research. It, too, happened as a surprise. In the course
of investigating conditioned response (Pavlov's drooling-dog-and-bell concept), he was testing to see how long such a trained response might last in some laboratory rats. Using a combination of saccharine-laced water and the nausea-inducing drug Cytoxan, he had trained the rodents to associate the sweet stuff with a bad bellyache. Afterwards, while giving them saccharine-water without the accompanying Cytoxan, Ader watched to see how long it might take for them to forget the association between the two.

Unexpectedly, during the second month, the rats began to fall prey to disease and to die off. In investigating this unforeseen result, Ader checked into the properties of the nausea-inducing drug he had used and found that one of its side effects was as an immune suppressant. The rats had been conditioned, it developed, not only to associate sweet water with nausea, but also with an immune shutdown. The conclusion was obvious: Their minds were controlling their immune systems.

This was a critical discovery, Felten points out: The fact of the mind-immune system connection had been made clear. What remained was the central question of just how they were connected.

This was where Felten--benefiting, he says, "simply from being in the right field at the right time"--entered the picture. When on that day in 1981 he looked at a tissue sample from the spleen and there saw nerve fibers from the central nervous system (the wiring that leads to the brain), together with white blood cells (key players in the immune system), the "how" became clearer.

Now there were hard data to prove the mind-body connection. "Once you've reduced the concept to the level of cellular biology this way, mainstream science can put it in the context of physiology and begin to accept it," he says.

Standard medical research looks at each part of the body separately, in "anatomical slices," assigning them to separate disciplines, he explains. Investigators in these disparate fields frequently use different medical terminologies, and in preference to adopting each other's languages, "they'd rather use each other's toothbrushes." With such clear demarcation of scientific turf, it is not surprising that connections among fields of study went so long unrecognized.

"When we first started presenting our findings, people laughed at us. Mainstream scientists, who have a tendency to look at anything new as kooky alternative medicine, wondered why we couldn't just stick with traditional research."

On the other hand, although one might think that the legions of alternative-medicine proponents would embrace PNI as proof of the mind-body connection--a central tenet to therapies outside the medical mainstream--this wasn't happening either. The cohort that Felten calls "the white robe and crystal set" was put off also, but for different reasons. "The alternative medicine folks don't want to be bothered with all the scientific rigmarole of testing; they just want to promulgate their beliefs.

"But what we had finally given both factions was absolute, one hundred percent quantifiable results, showing that the immune system and the central nervous system are indeed connected."

It was shortly after this discovery that Felten received his MacArthur fellowship ("such a gratifying vote of confidence," he admits) and moved from Indiana to join the PNI investigators at the University Medical Center.

Further research by the Rochester group has since documented the ways in which the brain sends signals to the immune system--by finding receptors on the surface of immune-system cells that act as keyholes to accept chemical neurotransmitters released by the nervous system, as well as identifying new "keys," neurotransmitters that would talk to cells of the immune system. A stimulus such as emotional stress can trigger the release of the nerve-fiber chemicals, which then tell the immune-system cells what to do.

The Rochester scientists also have found that the reverse occurs: Chemicals released by immune-system cells have an effect on the brain, causing, for example, drowsiness and an elevated temperature when the body needs to fight illness.

Felten says that other systems in the body are undoubtedly also connected in this way--that there are countless "players," as he calls them, in the human body, together creating a virtual telephone network of transmitters and receptors.

In current research, the Rochester group is now looking at the ways in which aging affects the action of the immune and nervous systems. "Older animals lose sympathetic nerves in the spleen and lymph nodes," Felten says. "We are working on finding ways to get those nerves to grow back." Low doses of a drug called deprenyl stimulate the nerve growth and encourage increased function of the immune system.

In a related area, Medical Center researchers have teamed up with River Campus chemical engineer David Wu, who has created a three-dimensional bone-marrow culture that allows the researchers to grow "cells" and test responses to various drug dosages. "In the case of AIDS, for example," Felten says, "they might be able to stimulate more cell production."

"The entire understanding of the disease process is changing," says Ader. "Diseases that have always been defined by the system they belong to are no longer defined that way." Ader cites diabetes, traditionally considered to be a disease of the endocrine system and now looked at as an autoimmune disorder-- an immune system attacking itself.

Continued immune system/central nervous system research has profound implications for diseases such as AIDS and cancer, with potential effects on Parkinson's disease, multiple sclerosis, lupus, asthma, arthritis, or indeed any immune disorder or nervous-system condition, say both Felten and Ader. Enhancing immune function in a patient by behavioral means can lower the drug doses needed to manage some of the diseases, or can give the patient a longer time drug free before needing chemical treatment.

PNI has become more mainstream in the 16 years since Felten's discovery, and the popular media are picking up on it. Felten and Ader were, for instance, featured in a Bill Moyers PBS special, Healing and the Mind, and have been cited and featured in stories by such as Time magazine and The New York Times. The Times, in a January 1993 article on the National Institutes of Health's new Office of Alternative Medicine, cites Felten's research as an example of an idea "initially scorned by the mainstream medical community" that has "since been proved through rigorous studies to have scientific merit."

"The University Medical Center is now viewed by many as the primary site for the study of brain behavior and immunology," Felten says. "And not only are we in the forefront of research, but we teach our doctors and nurses to treat patients as human beings, not just as slices of anatomy. I never heard the word 'healing' the whole time I was a medical student; here we don't just dismiss it that way.

"I've been lucky," he concludes, in his self-deprecating way. "I have the chance to make a difference in a major way.

"When I was still battling the perception of this research as being a little wacky, I received encouragement from Jonas Salk," Felten says. He then recites it from memory, obviously touched by the advice from one of this century's greatest scientists: "This research area could turn out to be one of the truly great areas of biology in medicine. You'll meet some opposition. Continue to swim upstream."

"We probably still only know 10 percent of the molecules in the brain," Felten says. "There are so many we haven't even thought of. We just keep working to find building blocks for more work.

"There is so much left to find out--we are nowhere near identifying all the players. And we have no idea," he says, in zestful anticipation of surprises yet to come, "what might be out there lying around the next corner."

Kathy Quinn Thomas wrote about epilepsy research at the Medical Center in the Spring-Summer 1995 Rochester Review.