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October 2, 2000

Humor: A Mind-body Connection

Will researchers and comedy legends demonstrate laughter's
therapeutic qualities?

By A.J.S. Rayl

A merry heart doeth good like a medicine, but a broken spirit dries the
--Proverbs 17:22

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Can humor cause a positive physiological impact? Could the gags, quips, and shtick of such legends as Charlie Chaplin, Bud Abbott and Lou Costello, and the Marx Brothers, or some of today's comedians, really be medicinal? During the last couple of decades--since the best-selling author Norman Cousins made headlines by laughing himself well--researchers have been working to uncover the physiological impact of laughter at the cellular and neurochemical level. By all indications, the eons-old notion is grinning and bearing out.

Cousins was diagnosed with ankylosing spondylitis, a degenerative
connective tissue disease. Bedridden and so weak he could barely raise his fingers, he was given a one-in-500 chance of complete recovery. He could sleep, he discovered, only after watching Marx Brothers comedies and Candid Camera episodes. It seemed to reduce his pain. Then, somehow, in the process of laughing, Cousins began to heal, eventually making an against-all-odds recovery.1,2

Now University of California, Los Angeles (UCLA), cancer researchers Margaret Stuber, professor of psychiatry and behavioral sciences, and Lonnie Zeltzer, director of the Pediatric Pain Program at Mattel Children's Hospital, have launched a five-year study--dubbed Rx Laughter--to investigate the impact of humor and laughter on the immune systems of dozens of healthy children and children confronting life-threatening diseases. The first physician-researchers to look at the impact of comedy on both healthy and sick children, Stuber and Zeltzer are calling on the talents of comedy's legendary heroes to help them out.

"We're not hypothesizing that humor will be curative or that it is going to take the place of any other kind of therapy, but we [believe]
that humor is going to have an additional benefit over and above simply removing or reducing stress," explains Stuber. "What I'm
hoping is that we'll actually be changing the level of arousal in the autonomic nervous system, so we'll get the children to relax at
that central level."

Adds Zeltzer: "If you're laughing, you feel better in general. And since it elevates your mood, it should do something physically in
your body to create that feeling of well-being. I think we're going to learn that exposing yourself to humor in life will not only change
mood and reduce stress hormones but also influence serotonin levels, which are involved in the pain-control system. That would
mean laughter could have an effect on chronic pain over time and enhance immunoreactivity, as well as help with depression and
sleep and anxiety disorders."

Stuber and Zeltzer will measure direct physiological responses of the autonomic nervous system. Initially, they will take
low-invasive measurements of the children's heart rates, blood pressure, and stress hormones. They plan to extend the tests,
adding blood surveys, among other things, to investigate the impact of humor on the immune system and on additional hormones,
neurotransmitters, and natural killer (NK) cells. The researchers will also try to differentiate which comedies work best for which
disorders or diseases and what types of individuals respond better to different types of humor.

The Rx Laughter study will add to the positive-thinking research that has been ongoing for the last 20 years at UCLA's Norman
Cousins Center for Psychoneuroimmunology, endowed by the renowned writer in the late 1970s. It will also expand on the basic
science investigations of Lee S. Berk, associate director at the Center for Neuroimmunology at Loma Linda University Medical
Center, also in southern California. Berk and colleagues have been at the forefront of investigating the concept of eustress, or good
stress paradigms, beginning in the 1970s with studies of exercise.

Actually, it was Cousins who set up Berk and colleagues with pilot study funds to begin investigating laughter as a "real eustress
metaphor," says Berk. With a small cohort of mostly medical students, they established the parameters of the study and took
blood samples via intravenous angiocatheters as the subjects watched a preselected, self-selected humor video, Over Your Head
by comedian Gallagher (Paramount Home Video) to measure impact on the neuroendocrine system.

They found that mirthful laughter--which Berk defines as "happy laughter as opposed to coping laughter or black humor or
derogatory humor"--reduces stress hormone levels.3 "The neuroendocrine responses produced were opposite to what is seen in
classical stress," he says. "We fell on the floor in disbelief that something from our own apothecary could actually have such an
impact. This silliness is really serious stuff. It's real biology."

The publication of those findings drew notable media attention, including a segment on CBS's 60 Minutes. Given that kind of notice
and the age-old adage, perhaps the most surprising thing is that more researchers didn't jump on the bandwagon. "To my surprise,
there are really minimal studies looking at the impact of humor on sick individuals, and nothing in children," says Zeltzer. In fact,
the amount of research into eustress and positive emotions has been minimal overall.

The reason, suggests Berk, "is because there were very few people who could bridge the gap across the borders of immunology,
behavioral sciences, and the technologies of psychoneuroimmunology." Of course, funding was also an issue. "If you turned in a grant request for a project that crossed multiple boundaries, as I often have, nobody knew what to do with it," he adds. Berk, however, continued to add slowly to the knowledge base with his small cohort studies.

marx.jpg (17633 bytes)
Bill Marx, Harpo Marx's son, makes a "Harpo" face for Justin Ybarra, a patient at the Mattel UCLA Children's Hospital during the RxLaughter advisory board tour in April.

It Came from Hollywood

If the scientific community at large was hesitating, the idea that laughter could help heal began emerging on other fronts. Rx Laughter actually came straight from Hollywood, the brainstorm of Sherry Dunay Hilber, a former ABC and CBS network programming executive who oversaw such hit sitcoms as Home Improvement, Roseanne, Coach, Who's the Boss?, and Cybill. The study even has its own Web site: www.rxlaughter.org. Hilber came up with the study idea about two years ago in the midst, she says, "of looking for some more meaningful way of using my abilities, something beyond worrying about the ratings of last night's show." She pitched her concept to Stuber and Zeltzer, who immediately came on board as the co-principal investigators and honed the study plan, and then enlisted the support of the offspring of comedy's legends. Included on Rx Laughter's Advisory Board: Josephine Chaplin, daughter of Charlie Chaplin; Chris Costello, daughter of Lou Costello; Ronald J. Fields, grandson of W.C. Fields; Melissa Talmadge Cox, the granddaughter of Buster Keaton; and Bill Marx, son of Harpo Marx of the Marx Brothers.

For a scientific investigation, it is a unique teaming. But the descendants of comedy's pioneers needed no convincing. Growing up in the whirlwind shadows of their famous forebears, they learned early that comedy was a potent and powerful force. "You grow up
with what you know, and I grew up with some wackos who taught me that when you have a sense of humor, you automatically have
an option in your view of life," says Marx. Fields agrees and adds, "Humor is nothing but extreme positive thinking."

With their support and assistance, Hilber secured all the necessary rights and permissions from the studios, free of any licensing
charges--something that almost seems unbelievable. But, as Chris Costello puts it: "There are some things you just can't put a
price tag on."

One reason Hilber, Stuber, and Zeltzer agreed on the works of Chaplin, Costello, Fields, Keaton, and the Marx Brothers was that
they had withstood the test of time. "We figured there's got to be a reason for that, and so we felt pretty safe going with those,"
explains Hilber.

"When I was a child, I never really understood the impact of what my father did, but I was watching The King in New York recently
and it is true: These films haven't gone out of date. And if they haven't gone out of date by now, they never will," says Josephine

The Rx Laughter team also figured that these movies and shorts would serve to establish a more objective reaction, because the
chances are good that most of the children have not seen many, if any, of them.

For funding, Hilber contacted Comedy Central, which several years ago had established its Comedy Rx program to promote the
positive effects of laughter. The cable network responded enthusiastically by putting up the initial $75,000.

'Who's on First?'

The impact of laughter on the immune systems of children has "just been waiting to be tested scientifically," says Zeltzer. "It
seems like such a no-brainer." The concept may be obvious enough, but designing the parameters of a study like this is most
certainly not a no-brainer. Comedy is highly subjective, while science strives to be objective beyond question. The levels of
complexity in a study like this are as numerous as they are intricate, and there are a lot of critical, basic questions to consider,

* How does one determine what will be viewed as funny across the board?

* Does it matter how much somebody laughs versus how funny they think something is? In other words, is the physical act of
laughter an operative factor?

* How does one test for differences across gender lines? Ethnicity lines? Age demographics?

In adult populations, says Berk, "We learned that there are a lot of potential pitfalls in selecting comedy. Self- selection of material
is important, because what is funny to one person is not necessarily funny to someone else. If you don't like slapstick, you will
experience a very different biology than I would."

Researchers investigating the impact of humor must also control for various other issues. "You have to be really pure when you do
this kind of research," says Berk, based on his previous studies. "Our subjects [had nothing to eat or drink] for six to eight hours
prior to beginning the study. They could not have exercised, or had coffee or any drugs or chocolate, and sex was not allowed." For
his research, whether the subject(s) had seen the video before was less of an issue. "I'm looking for the conditioned response," he
says. Actually, he found that the conditioned phenomenon is real. "In other words, we found positive effects from the anticipation."

Rx Laughter is a study of children, so theoretically, the researchers will be dealing with a less socially conditioned, less biased
population. Although the investigators are in the first phase of selecting the videos and finalizing study parameters, Stuber and
Zeltzer have already begun initial second-phase testing on healthy children to establish a baseline. In a third phase, they will look at
the impact of laughter on children with cancer, HIV, and other life-threatening diseases or disorders.

"In terms of selecting the comedy videos, part of what we have been going for are things that are consistently funny and things that
no parents are going to object to," says Stuber. That is actually harder than one may think. "We have to be careful, because today,
in the 21st century, we have different eyes for some of these things than people might have had originally."

On request from the researchers, the offspring of the legendary comedians made initial suggestions. Chaplin, for example,
suggested The Circus. "I thought it was the funniest one for this project, and that's the one we offered first," she says. Costello
recommended Abbott & Costello Meet Frankenstein, but then offered up all the duo's projects. Regardless of how parents might
view slapstick comedy, compared to today's humor there is, she suggests, "a certain purity of form" in these classics. "When you
watch any of these great legendary comics, the fun they poke is always brought back to themselves."

'Mikey Likes It'

"When we took a tour at the UCLA children's hospital, we discovered that many of these kids never had seen vintage comedy,"
says Costello. "Before they had turned the videos on, the room was quiet, with just the humming of machines, and then suddenly
the sound of laughter was everywhere. To watch those children sitting there and laughing over what was purely slapstick was so
wonderful. It kind of gets you choked up, because this is comedy that was done 50 years ago, before their parents were even born."

For now, the classics are producing the needed laughter, which, along with the internal physiological responses, is exactly what
the researchers are eager to investigate. "It's long been clear to me that people who are able to distance themselves have a sense
of humor, [and people] who have more perspective and who don't get so absorbed in all the tension of the moment, generally feel
better," says Stuber. "Now some of that obviously is psychological. But we know that most of the psychological feelings that we
have are actually biochemically based."

A few years ago, Peter Derks, now professor emeritus of psychology at the College of William and Mary, and colleagues used
21-electrode EEG topographical brain mapping to look at brain activity related to humor. He found that laughter affects substantial
and significantly unique electrical activity, and that the whole brain is involved.4 "Because there is substantial electrical activity in
the brain associated with laughter and humor, suppositionally, there must be appropriate neurochemical activity," contends Berk.
And that is exactly what he and his colleagues at Loma Linda have found.

Since 1990, Berk's lab has been investigating the impact of laughter on the immune system, acquiring cellular and neurochemical
samples via four measures: before, during, after, and the following day. They have documented and shown that mirthful laughter
increases the number of activated T lymphocytes and the number of T cells with helper/suppressor markers. They have also found
increases in NK cell activity, as well as increases in the actual numbers of NK cells, "very significant" in terms of

"The method we used to test this was to take blood samples from the experimental group before and after mirthful laughter," Berk
explains. "We literally put the peripheral mononuclear blood cells in test tubes with a type of tumor cell line .... It is astounding that
something as simple as mirthful laughter could in some manner modulate a significant immunological cell like NK cells." Berks
stops far short of suggesting that mirthful laughter is a panacea or that it will eradicate cancer. "The point is," he says, "mirthful
laughter modifies the physiology and the chemicals that affect natural cells and increases their numbers and activity."

Based on his research, Berk maintains that none of these changes would have occurred had there not been changes in
neuroendocrine components, and that the neuroendocrine components would not have been changed had they not been affected
from higher centers of the brain and central nervous system. "The fit is there relative to laughter and humor as a eustress state, and
that impinges on our psychophysiology as well as our psychoneuroimmunology."

Long-term Study

It will be about two years before preliminary results from Rx Laughter will be available, with definitive data due in about five years.
Meanwhile, initial test subjects are already laughing, and everyone is betting that positive biologic responses will be found.

Whatever the specifics of the scientific outcome, "Is there anything you could say [is] bad about making somebody laugh and feel
good?" wonders Bill Marx, who was part of his father's act for a number of years. "I don't think you can--and you can't say that
about a whole lot of things in the world. If anything, the Rx Laughter study will take the kids' minds off what they're there for and
offer them an option. Perhaps, too, it will help them realize somewhere down the line that humor and having a good attitude will help
strengthen them physically and mentally. If kids are taught the importance of laughter--and encouraged to laugh more--we'll have a
better world."

Berk concludes: "There is a very serious side to humor, and that is [that] what you wear on your face is what you have inside your
body. The question of what happens physiologically when we experience mirthful laughter forms the basis for a new frontier of
health care/medical research looking at positive emotional or eustress states and their consequence to health and disease."

Science is, however slowly, now producing the hard evidence that laughter is a powerful potion. Five years from now, says Rx
Laughter's co-principal investigator Zeltzer, "Maybe the prescription will include finding what the patient's favorite funny program is,
prescribing it, and then looking at the impact on both symptoms and physiology." Imagine a prescription that reads: One Abbott &
Costello, followed by doses of Charlie Chaplin, W.C. Fields, Buster Keaton. Wash down with Marx Brothers. Repeat as necessary.
Call me in the morning.

A.J.S. Rayl (ajsrayl@loop.com) is a freelance writer in Malibu, Calif.


1. N. Cousins, The Anatomy of an Illness, New York, Bantam Doubleday Dell, 1991.

2. N. Cousins, "The laughter connection," Head First: The Biology of Hope and the Healing Power of the Human Spirit, New York,
Penguin Books, 1989.

3. L.S. Berk et al., "Neuroendocrine and stress hormone changes during mirthful laughter," The American Journal of the Medical
Sciences, 298: 390-6, 1989.

4. P. Derks et al., "Laughter and electorencephalagraphic activity." Humor, 10:285-300, 1997.

5. L.S. Berk et al., "Eustress of mirthful laughter modifies natural killer cell activity," Clinical Research, 37:115A, 1989.



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