Father of PNI reflects on the field's growth

Robert Ader finds the rise in popularity of psychoneuro-immunology gratifying and frightening.

Robert Ader--the father of psychoneuroimmunology (PNI)--is proud of the basic research that has grown out of key studies he and several other pioneers conducted in the 1970s.

But he fears the term he coined will be undermined by "so-called-friends"--clinicians and researchers who embrace the idea of holistic or alternative medicine too zealously and use PNI data to legitimize claims for all types of alternative therapies.

PNI, as Ader defines it, is the study of the connection between the brain and the immune system. The theoretical consequence of that link is that psychological experiences, such as stress and anxiety, can influence immune function, which in turn may have an effect on disease course. There are data to show that psychosocial factors influence susceptibility to disease, and studies have begun to show a link between the mind and the immune system, but there is no definitive evidence that psychosocial factors influence disease via changes in the immune system, says Ader, director of the Center for Psychoneuroimmunology Research in the department of psychiatry at the University of Rochester Medical Center.

And while he is dismayed at some premature claims that the mind can cure cancer and other diseases, he bristles at the mention that many medical researchers continue to deny a connection between the brain and the immune system, despite many replicated studies that find such a link. The problem, critics contend, is that researchers have yet to find a biological mechanism linking the two systems.

Not having found a mechanism doesn't bother Ader, he says, because "there are many psychological phenomena, and medical phenomena for that matter, for which we have not yet defined the precise mechanisms. It doesn't mean it's not a real phenomenon."

Ader himself was "forced" to recognize the connection between the brain and the immune system--and eventually coin the word psychoneuroimmunology--by his data. It was the early 1970s and he was studying taste aversion learning in rats: When he paired a saccharin-flavored drink with the transient stomach upset caused by a dose of the drug cyclophosphamide, animals learned in one trial to avoid saccharin-flavored drinks. The drink was the conditioned stimulus and the taste aversion was the conditioned response.

Ader and his colleagues found that the volume of saccharin consumed before the animals were injected with the drug predicted the strength of the conditioned response. It also predicted how long it took for the animals to lose the conditioned response and begin drinking saccharin-flavored drinks again. And, the more saccharin an animal consumed on the one conditioning trial, the stronger its aversion to saccharin and the longer it took to extinguish the aversion (by giving the animal a saccharin-flavored drink without an injection of the drug).

A troublesome finding was that over the course of the extinction trials, some animals began to die. In fact, death, like the strength of the animals' taste aversion, varied directly with the volume of saccharin consumed during conditioning.

To explain this orderly relationship, Ader hypothesized that along with conditioning the animal to avoid saccharin, he was also conditioning a suppression of the animals' immune systems--an effect of cyclophosphamide. So every time the animals were re-exposed to the saccharin solution, their immune systems would be suppressed, leaving them more susceptible to any germs that may exist in the laboratory. And the stronger the taste aversion and the more exposures it took to extinguish the aversion, the more susceptible the animals would be to infection, he theorized.

The potential was enormous--if they could modify immune responses through environmental stimulation, they might have the potential to activate the immune system against disease, including cancer.

"People listened politely," recalls Ader in a recent book chapter, "but I did not have much luck in generating any interest in this hypothesis."

At least not until he met Nicholas Cohen, PhD, an immunologist with the techniques required to test Ader's theory.

In 1975, they published "Behaviorally conditioned immunosuppression" (Psychosomatic Medicine, Vol. 37, No. 4, p. 333_340), in which they presented evidence that immune responses could be modified by classical conditioning. Then, a study that set out to prove them wrong replicated the finding.

Other researchers before Ader and even more so after have found equally consistent evidence for a link between the brain and the immune system. And that work has led to the now booming field of PNI. Several prominent research journals publish PNI studies and the U.S. Public Health Service is funding hundreds of research grants in the area. The rise in PNI's popularity is both gratifying and frightening for Ader.

"The basic research isn't a fad," he says. "But the way some people are using the term could turn it into a fad. Some of our biggest followers and fans are trashing it" by claiming that every type of psychosocial therapy and relaxation technique can boost the immune system.

"If you're an immunologist and you read a lay magazine about how psychoneuroimmunology means you can boost your immune system and make you healthy, wealthy and wise, you're not going to want any part of it," says Ader, who will present the Neal Miller lecture at this year's APA Annual Convention. "In the long run, the rush to apply the findings of psychoneuroimmunology could be doing the field a disservice."

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