The Twenty-First Century, The First Century of NeuroImmune Pharmacology
A History of SNIP

The idea for forming the Society on NeuroImmune Pharmacology (SNIP) was fostered by a group of scientists with interests in understanding the impact of drugs of abuse on immune function and infectious disease. This article is meant to provide a historical sketch of the history of, and the impetus for founding SNIP as relates to the evolution of the science, events and people involved. A good place to assimilate a reasonably up-to-date overview of the scientific background that drove the formation of SNIP can be found in a special review-issue of the Journal of Neuroimmunology (Vol. 83, March 15, 1998) dedicated to expositions on “Pharmaconeuroimmunology, AIDS and Other Diseases”.

Sporadic studies over the past century showed that opiates can alter various immune functional parameters. The very first truly scientific publication in this area came in 1898, from the laboratory of Elie Metchnikoff, Nobel Laureate and acclaimed ‘father’ of cell-mediated immunology. This work, by Cantacuzene, showed that morphine could interfere with leukocyte trafficking and phagocytic activities. Clinical observations over the next ½ century consistently showed that heroin addicts were abnormally susceptible to various types of infections. During this time, also, a smattering of basic studies extended the documentation that opiates affect immune process. However, the basic data had little if any impact on clinical thinking regarding the propensity of addicts to infection. The prevalent if not universal clinical view was that poor health practices of addicts, especially as connected to intravenous drug use and needle-sharing, fostered conditions whereby adventitious infectious agents gained easy access.

By the mid-1940s and early 1950s, speculation began to appear that injection drug use (IDU) may be immunocompromising due to the drug itself. Nonetheless, this notion had little if any known influence on clinicians treating addicts. By the late 1960s, however, public awareness of these circumstances grew as the nation’s blood supply was threatened by the spread of hepatitis-B. When IDUs were singled out as the primary source of the problem, guidelines for collecting blood were improved. However, this situation also afforded the scientific community an opportunity to focus on the role of IDU in infectious disease and to re-question whether opiates had direct immune effects.

Renewed public and scientific interest in the influence of opiates on infection came at a propitious time because scientific knowledge was accumulating that fostered a meaningful and appropriate scientific reaction. Unlike circumstances when this issue arose in the 1950s and prior, the 1970s were witness to an emerging understanding of how opiates affected physiologic change. Scientists were now able to view the drug abuse/infection connection in new light. As a consequence the ‘floodgates’ began to slowly open.

Disparate interests in the impact of abused substances on host physiology began to merge. Pharmacologists first identified specific cell surface receptors to opiates on neuronal tissues. Then, endogenous ligands for opiate receptors (enkephalins and endorphins) were discovered. Several studies showed that opiates alter various measures of immune status in street addicts; and that cytogenetic damage accumulates in T-lymphocytes from heroin addicts. Other abused substances like alcohol and cannabinoids, the main psychoactive ingredient in marijuana, were also being reported to have immune modulating properties--adding to an ever-growing list.

By the end of the decade, in 1979, Joseph Wybran and colleagues showed that both endogenous (met-enkephalin) and exogenous (morphine) opioids could change E-rosetting characteristics of T-lymphocytes, in vitro. Moreover, and most importantly, they showed that these opioid effects were reversible with the use of naloxone, a mu-opioid receptor antagonist. Contemporaneously, a similar observation was made by McDonough, Madden and Falek, et al., with T-cells from heroin addicts--a report that led to the National Institute on Drug Abuse (NIDA) funding its first grant (to Dr. Arthur Falek) in this area of research. During this same time, Lopker reported the first classical pharmacological evidence, by use of opiate-binding technology, that leukocytes themselves had opiate-receptor like binding sites.

These discoveries were especially important because they provided a direct conceptual link between neuronal and immune function. The Wybran study reported in the Journal of Immunology, in particular, had enormous impact. According to Current Contents, for 5 years running after it's publication, the Wybran report was the most cited biomedical scientific research article in publication. No longer was it controversial to link the interworkings of two disparate systems. It was soon thereafter that the term, neuroimmune, entered the scientific lexicon. Truly, the &8216;floodgates’ were fully ajar.

Thus, these were the beginnings of the study of neural-immune pharmacology. Many investigators internationally have devoted entire careers to pursuing studies in this area. In the early- and mid-1980s, various scientific conferences and symposia sprang-up around the theme of neuroimmune function, and its modulation and consequences. Various perspectives evolved with emphasis on psychological phenomena, psychiatric phenomena, neurological phenomena, hormonal phenomena, and pharmacological phenomena. Society formation around interconnected disciplines also occurred—The International Society of Neuroimmunomodulation (ISNIM), the Psynhoneuroimmunological Research Society (PNIRS) being two currently active prominent examples. In addition, the Gordon Conferences held a symposium where this topic was prominent in 1986, in Santa Barbara, CA. Drs. Herb Spector and Stanislaus Jankovic organized several of the earliest conferences in the field (1984, 1986); and the Gordon Conference, in Santa Barbara, CA, in 1988, devoted a significant portion of their program to this topic.

The advent of the AIDS era, in 1982, also spurred considerable interest in this field when IDUs were identified as a main risk group for contracting AIDS. Indeed, to this day the controversy still swells as to whether drugs themselves influence progression of AIDS and HIV-1 expression--a situation totally reminiscent of the circumstances in the late 1960s when IDUs and hepatitis infection raised the concern of public health officials.

In 1983, in response to the AIDS crisis, the NIDA held several technical reviews that specifically explored the influence of drug abuse on infectious diseases and immune processes--the first in October, in Rockville, Maryland; the second, a month later, in Boston. Recent evidence has drawn focus on the idea that neurological complications of AIDS are exacerbated by drug abuse. This situation has led to mergers of neurobiological, neuroanantomical and psychiatric interests with the drug-abuse/AIDS/immunology area. Many recent conferences have featured topics directed at this concern.

One of the oldest scientific groups with strong interests in the pharmacology of abused substances and their neuroimmune effects is the Committee (now College) on Problems of Drug Dependence (CPDD), [which started as a working committee of the National Institute of Medicine in 1928 and which was the forerunner of the National Institute on Drug Abuse (NIDA), formed out of this committee in 1974]. The CPDD was the first society to repeatedly hold symposia on this topic at their annual meetings. During the CPDD meeting in 1986 at Lake Tahoe interest in this field was increasingly apparent. Following a 30 minute talk on “Opiate Receptor-Mediated Regulation of the Immune Response in Vivo” by Rick Weber, Dr. Keith Killian suggested that a symposium on the subject should be organized for the meeting next year when CPDD met on Cape Cod. Arthur Falek spearheaded this effort, organizing the first CPPD symposium on drugs of abuse and the immune system. Speakers were Mary Jean Kreek, Robert Donahoe, Eric Smith and Richard Weber. In subsequent years, Dr. Martin Adler, the executive secretary of CPDD and several of its board members, Dr. Arthur Falek and Dr. Mary Jeanne Kreek, spearheaded development of these symposia, aided by Drs. Monique Braude and Charles Sharp of the NIDA, and CPDD members, Drs. Richard Weber and Robert Donahoe. Drs. Herman Friedman, Thomas Klein and Steven Spector from the University of South Florida organized the first conferences dedicated specifically to exploration of the the role of drugs of abuse in modulating immune function, in 1989 and 1992, in Clearwater, Florida. They also directed publication of compendia of findings reported at these meetings by Academic Press, in the journal, Advances in Experimental Medicine and Biology--the first of their kind.

When the annual CPDD meeting was held in Keystone CO, in 1992, not one, but two separate symposia were dedicated to the issue of drug abuse immunology. Many colleagues who had met and interacted at CPDD meetings, as well as the many other conferences referenced above had long spoken of the need for more targeted coverage for this expanding field. At the Colorado meeting, Drs. Martin Adler, Barbara Bayer, Jean Bidlack, Robert Donahoe, Toby Eisenstein, Nicholas Hall, John Madden, Thomas Rogers, Paul Shapshak, and Burt Sharp convened a meeting at John Madden’s condo to discuss holding a satellite conference to the CPDD the following year. This meeting led to formation of a working group of conference organizers. An R13 Conference Grant proposal evolved from this effort, generated by Drs. Madden and Sharp to promote and fund the meeting. This grant was funded by the NIDA and led to the first conference in neuroimmune pharmacology, held following the CPDD meeting in Toronto Canada, in 1993.

Subsequent meetings were organized by the working group, headed by Drs. Madden and Sharp. They convened, mainly, as satellites with the CPDD, but, also, at other venues as specified: Palm Beach, FL (1994); San Diego, CA (1995--with The Society for Neuroscience); San Juan, PR (1996); Nashville, TN (1997); Scottsdale, AZ (1998); NIH, Bethesda, MD (1999--independent meeting); and in 2001 at Emory University in Atlanta, GA. These conferences were attracting around 70—120 participants per meeting. At each meeting, it became increasingly evident that there was a general interest in forming a society. In both the Scottsdale and Bethesda meetings, a working group met to discuss this idea. It was felt that a society would be helpful in sponsoring future meetings and otherwise promoting the interests of the group of scientists that had coalesced around the common theme of neuorimmune-pharmacology.

At the behest of the working group that convened in Bethesda in 1999, Drs. Donahoe and Burt Sharp set up an organizing convention to launch a society. The initial organizing meeting was held in Dr. Sharp’s offices at the department of Pharmacology, at the University of Tennessee, Memphis, in March 2000, Drs., Madden, Sharp, Weber and Donahoe in attendance. This group was in contact with other working-group members who could not attend. Ideas were passed back and forth on how to structure a society, and a rough draft of by-laws was made. The organizational structure of officers, councilors and members for major committees were laid out for review by the working-group.

Various names for the society were discussed at the organizational meeting, with the idea that they be concise, catching and informative, and, of course, best represent the purposes of the society. These names were proffered to the working group. Several group members came back with suggestions of their own. In the end there were 4 major names that had relatively large pockets of support. These were voted on by the working-group and the final, nearly unanimous choice in an elimination process was The Society On NeuroImmune Pharmacology, abbreviated as SNIP.

The officers that formed the Executive Committee were: Dr. Burt Sharp, President; Dr. Jean Bidlack, President Elect; Dr. Thomas Klein, Secretary; and Dr. Robert Donahoe, Treasurer. The board of councilors chosen were: Dr. Sulie Chang, Dr. Toby Eisenstein,Dr. John Madden, Dr. Phil Peterson, Dr. Tom Rogers, Dr. George Sefano, and Dr. Richard Weber. Several key working committees were also staffed: Dr. Madden—grant and meeting committee; Dr. Sulie Chang—web-site and Communications Committee; Dr. Thomas Rogers--Membership committee. This governing body was elected unanimously by the participants at the 8th conference in Atlanta. At this conference, also, Dr. John Madden received the recognition of the society for his unrelenting efforts in helping to found the society. The President, Dr. Sharp, bestowed on him the society's first and only Presidential Founders Award.

The by-laws were also discussed by attendees of the Emory SNIP meeting. Officer terms, and nomination and election procedures were decided. The secretary, Dr. Klein, assumed the task of formalizing the SNIP by-laws, working interactively with members of the Executive Committee. He also generated the logo now used in SNIP advertising and documents. Dr. Donahoe, as treasurer, filed the necessary papers to incorporate the society in the State of Georgia, its current home-base, receiving an entity identification number to formalize this status. Tax exempt status from the IRS has recently been filed for. Its pro forma approval is expected soon. Drs. Donahoe and Sharp also led the recruitment of Charter Members to underpin the society. Various colleagues who had worked in making previous conferences a success and who had expressed interest in launching a society were recruited.

Forty individuals subsequently joined SNIP as Charter Members, each generously contributing from $150 to $500 to help launch the society. Seton Hall University also contributed an especially generous grant of $5,000, derived by the efforts of Dr. Sulie Chang on behalf of the organizing committee. And, Aventis Pharmaceuticals was recruited by Dr. Phillip Peterson and joined as a Corporate Partner, contributing $2,500. The donations received from these efforts have built the treasury to a level where SNIP is able to provide fiscal support to attain its goals. Drs. John Madden and Burt Sharp have submitted our most recent grant proposal, the first directly from the SNIP society, to help fund the 2002-meeting, scheduled for Clearwater Beach, FL, this October (2nd-6th). Gratefully, we can announce that this grant has just recently been approved by NIDA for funding.

A final epilogue to the evolution of our society and its interdisciplinary interests relates to the special role of Dr. Joe Wybran. We mentioned, above, his key scientific contributions to SNIP. Unfortunately, Joe Wybran came to an extremely untimely end at the hand of presumed terrorists. He was murdered, shot to death in his car, in the parking lot at his work, October 3, 1989, in Brussels. His active role in the Jewish community is why his wife and other friends believe he became a target. He was a world-renowned immunologist, physician, who made several important seminal discoveries during his too brief career. He trained and worked in the U.S.A. for a good part of his early career. He was recognized by his colleagues as supremely energetic and thoughtful, and, by many, as a good friend. Many of the SNIP organizers and members knew and worked with Joe. For these reasons, the working-group founders of SNIP were proud to institute an achievement award, called the Wybran Award, that has been given to figures in our group who have made consistent, long-term, key organizational and scientific contributions to the field. Presently, the winners of the Wybran Award, plus the President of SNIP comprise the selection committee for future awardees. The award is not annual, per se, and is made at the discretion of this committee.

The first recipient of the Wybran Award was Dr. Charles Sharp of the National Institutes on Drug Abuse (1995, San Diego,). He has been a stalwart of support for the goals of the society before, during and after its formation. The second recipient was Dr. Herman Friedman of the University of South Florida (1997, Nashville). He was instrumental in organizing the first two conferences on neuroimmune pharmacology and has been a constant and early scientific contributor in the field. The third recipient was Dr. Phillip Peterson, of the University of Minnesota (1999, Bethesda). He has been the most highly published author in our field over the past two decades. His work has opened new vistas about the role of abused substances in progression of infectious diseases, especially HIV1 and its neural manifestations. The most recent and fourth recipient was Dr. Martin Adler (2001, Atlanta). His organizational and scientific contributions have been and continue to be at the forefront of our field.

One of the main goals of our meetings has been to foster growth and bring new young talent to the field. At every annual meeting we have supported young investigators, financially; and recognized, by special award, several whose research poster presentations were judged outstanding. We look forward to continuing this tradition as we move forward as a society. We think, too, that it is time to bring new interests to the field. There are many neuroimmunologically active substances. They are endogenous as well as exogenous, and they are NOT all abused substances. There is a better than good chance that some of these substances or their congeners will, someday, be useful therapeutically. We want to have people with wide interests in such matters, whether basic or applied, join us and help drive our growth as a society.

Our next conference is planned for October, 2-6, 2002 in Clearwater, FL. You’ll be hearing more about this in our advertisements, on our web-site, and from this newsletter over the next several months. Please join us in Clearwater. It promises to be an exciting meeting at a relaxing venue.

One final codicil. The authors of this article have tried to be as accurate and inclusive as possible in reviewing the history of our society and of our field. Certainly, there is much more to this history than this brief outline permits. Also, we recognize that our recollections of events are inevitably parochial. If the reader feels that important facts on this topic have been overlooked, or are in error, please send your comments to the editor of the SNIP newsletter,

Dr. Richard Weber (rick@uic.edu). We would appreciate your insights and we will be glad to publish letters in reply as appropriate.

(Reported by Bob Donahoe and Rick Weber, June, 2001