In Memoriam of
Andrzej W. Lipkowski
by Aleksandra Misicka and Daniel Carr)
In Memoriam of
Dr. Avram Goldstein
Brian Cox, Charles Chavkin, Lakshmi Devi & Ray Dingledine)
In Memoriam of Dr. K.
Stephen LaForge (from
MySpace page of band member)
In Memoriam of Edna Leong (submitted
by Dr. Eric Simon)
In Memoriam of Dr.
Tom Burks (from
In Memoriam of Dr. Akira Takemori (submitted
by Dr. Sandra Roerig)
In Memoriam of Dr. Sydney Archer (submitted
by Dr. Eric Simon)
In Memoriam of Dr. Hans Kosterlitz (submitted
by Dr. R. Alan North)
DR. EDDIE WAY CELEBRATES HIS 100-YEAR BIRTHDAY!
Thanks to Professional Event Photography by Frank Jang for these pictures.
(click on picture
image to see full size, hit 'BACK' button to return here)
everyone who came for the great Chinese ‘lunch’
faculty who were there back in the day and others who worked in the department
Eddie’s great smile, seated with his brother Jimmy Way
Barry Berkowitz, Bill Schmidt, Eddie, Edgar and Paul Fisher
Walter Dixon, Eddie and Harvey Kupferberg
John Holaday, Eddie, and Adron Harris
John Holaday, Fred Craves, Bob Hitzmann
Barry Berkowitz and Eddie
Andrzej W. Lipkowski
December 19, 2014)
With profound regret and
sadness we write to inform you of the sudden death of Andrzej W.
Lipkowski, a visionary scientist, a great man and a caring mentor and
friend to many of us.
Andrzej W. Lipkowski, a native of Poland, received his Ph.D. (1976) and
D.Sc. (1987) in chemistry from the University of Warsaw. He started his
career in Professor Stefania Drabarek’s group in the Chemistry
Department working on oxytocin analogues. His first scientific adventure
was during his PhD studies, when he spent a year (1973-74) isolating
proteins from the Antarctic krill in the Polish Antarctic Station "Arctowski"
as a member of 3rd Antarctic Expedition of Polish Biologists. He did his
postdoctoral work (1977-78) at Northwestern University (Chicago, USA)
with Professor George Flouret working on iodo analogs of LHRH and
oxytocin. After returning to Poland, Andrzej started his research on the
structure-activity relationships of opioid peptides at the Department of
Chemistry of Warsaw University. Following the then-recent discovery of
the enkephalins (1975) this field was progressing rapidly at that time.
Andrzej, from the beginning of his research in the opioid field, was
committed to searching for new molecules, particularly peptides, that
could be employed in the clinic as analgesics with fewer adverse effects
and liabilities compared with traditional opioid alkaloids. His goal
remains timely today. To achieve this, he was the first in Poland who
gathered chemists, pharmacologists and anesthesiologists to discuss
problems associated with pain, especially neuropathic pain, in order to
develop new and better painkillers. In order to better understand the
problems associated with opioid pharmacology Andrzej joined for a few
months, in 1983, Albert Herz’s group at the Max Planck Institute for
Psychiatry (Munich, Germany). After returning from Germany Andrzej
designed and synthesized a simple molecule (a dimeric enkephalin
analogue connected by a hydrazide bridge), which is 1000 times more
potent than morphine when administrated intrathecally. He named his
molecule “biphalin”. Numerous subsequent studies in many laboratories
over the world confirmed that biphalin is an extremely potent analgesic
compound with substantially lower addictive potential than traditional
opioids. Unfortunately, the lack of patent protection of this compound
removed any commercial incentive for the pharmaceutical industry to
develop biphalin. The reason for the lack of patent protection was
political, not scientific or clinical. At the time that Andrzej
developed biphalin in Poland, it was not possible to patent a novel
molecular entity (Poland was behind the iron curtain then, with
different patent laws than the democratic West).
In the 1980s like millions of Poles, Andrzej was involved in the
Solidarity movement. He remained active in Solidarity even when the
authoritarian government of general Jaruzelski in Poland, in an attempt
to crush political opposition in Poland, introduced martial law on
December 13th 1981, starting a difficult chapter for Poles and Polish
Andrzej later obtained a research fellowship position (1986-88) at the
University of Minnesota with Professor Philip Portoghese (Minneapolis,
USA), where he designed a kappa agonist based on Robert Schwyzer’s
concept of message-address components in biologically active compounds.
While working in Portoghese’s lab, Andrzej synthesized the famous
norbinaltorphimine (norNBI), a κ-selective antagonist used in most
laboratories involved in opioid research to the present day.
In 1988 Andrzej joined the laboratory of Professor Victor J. Hruby at
University of Arizona (Tucson, USA), starting a long-term collaboration
that also encompassed Frank Porreca’s and Frank Yamamura’s laboratories
there. From the outset, Andrzej suggested that it would be more rational
to design multivalent drugs instead of devising receptor-selective
compounds, which was the dogma at that time. Now this concept has been
widely adopted, and many laboratories are now involved in the search for
multivalent drugs. Andrzej stayed at the University of Arizona for
longer or shorter periods of time over the years 1988-2005. This
fruitful collaboration resulted in many publications and new ideas in
opioid research. The joint research results have strongly indicated a
great potential for the use of peptide analogues or peptidomimetics for
therapeutic application, an idea that still remains to be embraced
vigorously by big pharma.
Through the connection of Stanislaw Szyfelbein, then Chief of Anesthesia
at the Harvard-affiliated Shriners Burns Institute in Boston, Andrzej
developed a fruitful collaboration with several Boston laboratories.
Starting in 1989, he extended the Shriners’ preclinical pharmacological
studies (initiated by the late Patricia Osgood, Ph.D.) to investigate
the role of biphalin and numerous other peptide analogs in a variety of
preclinical pain models. In this laboratory, and later the
Anesthesiology Laboratory at Tufts-New England Medical Center, he helped
nurture the careers of young scientists and clinicians being trained in
laboratory research at Harvard University and the Massachusetts General
Hospital. These clinician-scientists became investigators in their own
right, some returning to their home countries throughout the world.
Characteristically for Andrzej, while in Boston he maintained his
established collaborations outside Boston and developed new ones with
other Boston laboratories (e.g., Dan Carr and Richard Kream at Tufts’
Anesthesiology Laboratory Donald Wise at Northeastern University). These
fruitful efforts are reflected in multiple PhD students’ theses and
dozens of patents for novel molecules and delivery systems such as
engineered release from polymers. The Tufts interaction, that included
co-sponsorship of several Poland-US scientific conferences, continued
well into the 2000s.
In 1991 Andrzej was appointed as Assistant Professor in the Medical
Research Centre of Polish Academy of Poland in Warsaw (Poland) and Head
of the Department of Neuropeptides. Within a few years, Andrzej created
an interdisciplinary group gathering biologists, chemists and medical
doctors doing complementary work on structure-activity relationships of
peptides with the objective of developing a new generation of
analgesics. The roles of neuropeptides in pain transmission and
modulation, and translation of this knowledge into new methods of pain
control were the major themes of his scientific activities. For his
achievements Andrzej was appointed as a full Professor of Medical
Science in 2001. As one of the leaders in the Medical Research Centre of
the Polish Academy of Sciences, he was highly successful in gathering
scientists from different areas to collaborate on bigger projects, for
example in the European Grant “Normolife - Development of New
Therapeutic Substances and Strategies for Treatment of Pain in Patients
with Advanced Stages of Cancer”. This comprehensive program was
coordinated by Andrzej, with nine partners from seven countries
including i.a. Dirk Tourwe (Vrije Universiteit Brussels, Belgium), Geza
Toth (Biological Research Center, Szeged, Hungary), Iro Georgoussi
(National Centre for Scientific Research "Demokritos" Athens, Greece),
Giuseppe Ronsisvalle (University of Catania, Catania, Italy) and others.
In the years 1993-2010 Andrzej served also as the Head of the
Biotechnology Department at the Industrial Chemistry Research Institute
in Warsaw (Poland). The interdisciplinary group that he created there
worked on bioactive peptides derived from natural proteins, preparation
of porcine spinal cord enzymatic hydrolyzates for therapeutic
applications, on the development of antimicrobial peptides, and of
biofuel production technologies.
In 2010 Andrzej was elected as a Director of the Mossakowski Medical
Research Centre of the Polish Academy of Science in Warsaw. During the
last four years the Medical Research Centre blossomed under his
leadership, was continuously funded by grants from multiple sources, and
became one of the foremost scientific institutions in Poland. Andrzej
had also initiated steps to organize the legal framework for
commercialization of research results and development activities. He
always dreamed of making a “real drug” available for patients.
Andrzej was always open to cooperation, generously sharing his
scientific ideas, enjoying discussing study results and planning new
experiments. Among many long-term collaborators was Professor Masaaki
Yoshikawa from Kyoto University (Kyoto, Japan). They collaborated on
bioactive peptides derived from natural proteins and together published
many papers on opioid, anti-opioid, and vasoactive peptides which they
discovered. The project was selected as a topic of Polish-Japanese Joint
Research under the title “Drugs from Natural Products” from 1999 to
2008. Andrzej stayed twice at Kyoto University as a visiting professor
(2000–2001 and 2007). His collaboration with Professor Yoshikawa was
Andrzej also has collaborated for years with Giuseppe Ronsisvalle, his
former colleague from the Portoghese laboratory, who later became a
professor of pharmaceutical and toxicological chemistry at the
University of Catania (Catania, Italy). In 1999, with Giuseppe and Geza
Toth from Szeged (Hungary) Andrzej proposed to the Pharmaceutical
Societies of Italy, Hungary and Poland the organization of a joint
meeting on medicinal chemistry in order to strengthen relations between
scientists from eastern and western European countries. The first
meeting took place in 1999 in Taormina (Italy). The success of this
event was so evident that the Joint Meeting now links the scientists of
eight countries and is a great opportunity for launching collaboration
especially for young researchers. In 2003 Andrzej was awarded the Marie
Curie Visiting Professorship, which he spent with Giuseppe in Catania
working on the synthesis of new opioid compounds.
Professor Lipkowski was a co-author of over 250 publications (articles,
proceedings and book chapters) and over 50 patents concerning new drug
candidates for the treatment of pain, multiple sclerosis, and
Andrzej had extensive knowledge of chemistry, pharmacology and medicine.
Additionally he had great ability to integrate information from various
fields, allowing him to synthesize experimental findings that others
would find difficult to consolidate.
Andrzej was an extremely kind and modest person with an outstanding
mind. He had a rare ability to visualize molecules from different points
of view and was always full of ideas, many of which are still unfolding.
His loss is a tragedy for all of us who knew him and benefited from his
unique way of thinking. He will be sorely missed by all of his friends
and coworkers, in addition to his family.
Aleksandra Misicka, PhD, DSc,
Department of Chemistry, University of Warsaw and
Department of Neuropeptides, Mossakowski Medical Research Centre Polish
Academy of Science, Warsaw,
Daniel Carr MD
Departments of Anesthesiology, Medicine, and Molecular Physiology and
Tufts University School of Medicine
Dr. Avram Goldstein - AN
Avram Goldstein, one of the founders of INRC and an
icon in the world of pharmacology, died on 1 June 2012. He played a
major role in strengthening the scientific basis of the discipline of
pharmacology in the middle years of the last century. He was very
influential in improving the rigor of research approaches to
understanding drug addiction at both the pre-clinical and clinical
levels, and in persuading politicians and administrators that treatments
and policies in the area of drug abuse should be based on rational
scientific principles and experimental evidence whenever this was
Avram was born in New York City in 1919, the son of a
prominent New York rabbi and a mother who he described as a ‘feminist,
socialist and free-thinker” (1,2). His mother ensured that he was
sent not to a strict religious school but to Walden, a progressive private
school. This unusual background exposed him to the rigors of traditional
Jewish intellectual life, but tempered by the drive to challenge all
authority that could not survive the test of experimental confirmation or
demonstration. He was something of a child prodigy, admitted to Harvard at
age 15, but deferring entry for another year while he traveled in Europe and
worked at a kibbutz in what was then known as Palestine. After majoring in
chemistry, he entered Harvard Medical School where he became interested in
pharmacology, graduating in 1943 at the height of the Second World War.
After a brief internship at Mt. Sinai Hospital, he entered the US Army and
was assigned to Camp Carson, Colorado; his major role was to treat frostbite
and trench foot. After the war he returned to Harvard, first as a Post-Doc
then as Assistant Professor of Pharmacology, and in 1947 married Dora
Benedict, known affectionately to all as Dody, who was then a medical
student at Harvard. Dody went on to have her own independent research
program, becoming well-known for her contributions to alcohol research, and
a professor of pharmacology at Stanford once the anti-neoptism rules that
had blocked the advancement of many women scientists were rescinded. The
marriage lasted for more than 60 years, until Dody’s death in October 2011.
In 1955, while still an Assistant Professor at Harvard,
he was invited to take the chair of pharmacology at Stanford University,
which was at that time moving its medical school from San Francisco to the
main university campus in Palo Alto. At Stanford, Avram was instrumental in
dramatically increasing the size of the medical school faculty and
recruiting many very talented younger scientists to Stanford, including
Arthur Kornberg as chair of biochemistry. Avram went on to play a major role
in developing the educational and research programs at Stanford (1,2).
He also at this time founded the journal, Molecular Pharmacology, for
ASPET, and he cajoled his Stanford faculty colleagues Lewis Aronow and
Sumner Kalman to write a new text, Principles of Drug Action, that
emphasized the scientific foundations of pharmacology, in contrast to most
other pharmacology textbooks of the time that were essentially annotated
lists of drugs in the style of materia medica.
Avram’s initial research studies in pharmacology were
on enzyme kinetics, where he analyzed the mechanisms of actions of
inhibitors of cholinesterases, and explored enzyme kinetics (3) and
the binding of drugs to proteins, but he soon became fascinated with new
developments in biochemistry and for a while his lab was focused on enzyme
mechanisms and the role of RNA in bacteria. At the same time, however, he
was conducting studies of the effects of caffeine in human subjects, using
Stanford students and their spouses as subjects in a project that was
initially a class exercise on how to conduct clinical research but
eventually became a series of published research studies demonstrating the
extent to which adaptations in the effects of the drug occurred in some
individuals after chronic use (4). He also at this time developed a
method for quantifying the kinetics of opioid tolerance development in a
mouse model5, that opened the way for quantitative correlations
between behavioral and biochemical actions.
He states in his autobiographical
that his interest in drug addiction was provoked by a lecture delivered at
Stanford in 1970 by Vincent Dole, a biochemist and professor at Rockefeller
University, on the use of methadone in a novel treatment of heroin
addiction, but the chronology of his publications indicates that he was
already shifting his focus in this direction. Nevertheless, the novel
concept of a safe legal maintenance therapy for heroin addiction that was
presented by Dole fascinated Avram and he saw here an opportunity to combine
fundamental research on very poorly understood facets of opiate drug
pharmacology - the extreme tolerance that could developed to opiate drugs
and the closely related development of physical dependence - with his desire
to utilize his medical training to impact a significant social phenomenon,
the escalation in the use of drugs of abuse in Western societies. He now
directed the work of his lab, and of his long-time assistant Louise Lowney
in particular, to identification of the receptor target for morphine, noting
that the stereo-specificity of opiate drug action pointed to a way of
identifying the critical fraction of opiate drug present that was actually
bound to functional receptor, although this was small relative to the much
larger amount of drug bound by “non-specific” tissue proteins6.
To address the clinical problem of heroin addiction, he started a
research-based methadone treatment program serving the hitherto neglected
Latino community in nearby San Jose, gaining the trust of the leaders of
this community. With Barbara Judson, Priscilla Grevert, Bob Dent and
others, he began to conduct experimental studies on opiate actions in human
It was at about this time that Avram joined with Hans
Kosterlitz, Eric Simon, Harry Collier and Sydney Archer in founding the
International Narcotics Research Club (later Conference). As described by
Syd Archer in his history of INRC, on the INRC web site(7), the
initial meeting of this distinguished group was held at the Hotel Euler in
Basel during the 1969 International Union of Pharmacology (IUPHAR) Meeting,
and at this meeting they planned for a full symposium on opiates to be
presented in 1971 in Aberdeen, Scotland during a meeting of the British
Pharmacological Society. Avram then hosted the next INRC meeting in San
Francisco, again during an IUPHAR meeting (1972), and he became the
Secretary (the position was later named President) for the next few meetings
of INRC. At this time, the Secretary was by far the most important person in
the Club; he arranged the venue, secured funding and developed the program.
While the other Founders played very important roles in building INRC as the
critical place to present novel research on the actions of opiate drugs, it
was the administrative skill and organizational drive of Avram that kept the
Club going during its early years.
Avram’s research group expanded substantially at this
time. He brought a number of foreign scientists to his lab, including Harry
Collier (for a brief sabbatical), Rudiger and Karin Schulz, Hans-Jörg
Teschemacher, Brian Cox, Shinro Tachibana, Walter Fischli, and Ji-Sheng Han,
recruited gifted graduate students at Stanford, including Ray Dingledine,
Charles Chavkin, Maureen Ross and Carl Romano, and post-doctoral fellows
from a number of disciplines, including Kent Opheim, Lakshmi Devi, Francis
Leslie, Vartan Ghazarossian, Tsung-Ping Su, Susan Gentleman, Gene Baizman,
Ian James, Barbara Herman, Charles Weitz and Guo-Xi Xie. This expansion was
funded by the newly created National Institute on Drug Abuse, and required
more space than he was able to obtain in the Stanford Medical School
building1. The solution was a typical Goldstein solution; he
would create a new non-profit organization to support his research, the
Addiction Research Foundation, and locate this in beautiful purpose-built
laboratories on the Stanford business park in Palo Alto, where the walls of
the new laboratory were painted in all colors of the spectrum and the room
numbers were dictated by the wavelength of wall color. He brought one
component of his clinical heroin addiction treatment program to the Palo
Alto campus and began an evaluation of a methadone analog, LAAM. LAAM
initially appeared to offer a number of advantages over methadone, until it
was later withdrawn because of unanticipated hepatic toxicity. To maintain
the scientific vigor of the Foundation, Avram also recruited a world- class
scientific advisory board, including Jerry Jaffe (the first White House Drug
Tsar), Floyd Bloom, Arnie Mandell, Harold Kalant and others. Those working
there then still remember the interesting and entertaining scientific
discussions when this group visited the lab.
Avram’s contributions to opiate drug research are
many. His strategy for identification of opiate receptors6
provided the approach that was later exploited by the Snyder, Terenius and
Simon groups to demonstrate the presence of opioid receptor in brain. Avram
had used a 14C-labeled opiate reasoning that the apparent
affinity of the major opiate drugs for the opiate receptor was about 1 µM.
We now know that in the absence of sodium the affinity of many opiates is
close to 1 nM. The Snyder, Terenius and Simon groups used very
high-specific activity tritium-labeled opiate drugs, enabling them to
identify opioid receptors despite their low tissue concentration, and to
demonstrate that this binding was stereo-specific. Avram was one of the
first to recognize that an endogenous ligand for opiate drug receptors was
likely to be a small peptide, and his laboratory first demonstrated the
presence of opioid activity in extracts of the pituitary gland, describing
different pituitary extracts that displaying the opiate-like properties of
what are now known as b-endorphin (8)
and dynorphin (9). This was when he posted copies of the sheet
music for Handel’s “He shall Purify” from the Messiah on the lab walls to
exhort the group to greater productivity (2). He quickly recognized
that b-endorphin had
already been isolated by Cho Hao Li in San Francisco in his work on ACTH and
related peptides, but that its opioid activity had not previously been
appreciated (10). Purification of dynorphin took a long time
because of its very high receptor affinity and its extraordinary stickiness
at surfaces of all kinds, but it was eventually achieved (11).
The lab had some interesting discussions on the
differing properties of the receptors mediating the actions of dynorphin and
morphine. In 1975, Hans Kosterlitz and colleagues had published studies
suggesting that the receptors mediating enkephalin effects in guinea pig and
mouse vas deferens were different. Avram was initially opposed to the
proposal that there was more than one type opioid receptor, largely on the
grounds that the concept offended Occam’s razor. However, repeated exposure
during lab meetings (held during the summer around the swimming pool of the
Goldstein home on the Stanford campus) to data from studies on receptors in
different peripheral tissues eventually persuaded him that one receptor
could not explain the data and he became an enthusiastic advocate for
multiple opioid receptor types. With Charles Chavkin, he demonstrated
convincingly that dynorphin was an endogenous ligand with high selectivity
for the kappa opioid receptor (12).
In the clinical arena, the careful quantitative
evaluation of the effectiveness of methadone and LAAM treatment programs
provided some of the best evidence that these programs were a very
cost-effective way to address the growing problem of heroin addiction. He
also contributed significantly to the development of science policy. He
advised Jerry Jaffe, then working in Nixon’s White House, on how to bring
the troops home at the conclusion of the Vietnam War without introducing a
major heroin abuse epidemic to the USA. The solution was a reliable device
for detecting the presence of opiate drugs in the urine of all troops before
they were repatriated; those whose urine sample did not pass the test were
not permitted to return until they could provide a clean urine sample1.
He was a very strong advocate for the establishment of methadone maintenance
programs at public expense in all communities where heroin addiction was
rampant. He served on NIDA Council and was consulted often by NIDA
Directors. With Harald Kalant he began to think about national policies
that would reduce illicit drug use (13), and this eventually
developed into a book seeking to explain drug addictions to a national
audience (14). His reputation in this area resulted in his being
invited to offer a primer on drug addiction biology and treatment approaches
to General Barry McCaffrey, Bill Clinton’s Director of National Drug Control
Avram could be intimidating to some and loved to debate
weighty topical issues with those up to the challenge. He acquired something
of a reputation of being difficult to work with, and he did not hesitate to
use his height and impressive intellect to achieve his goals. He frequently
expressed his disdain for committees (1). However, for those who had
the pleasure of working closely with him (after surviving his initial
probing for intellectual weakness), Avram could be the most instructive,
friendly and supportive of mentors. He used his very considerable ability to
charm to great effect, whether it was to persuade a post-doc to try once
more to solve an intractable problem (always with a novel approach offered
by Avram), or in his approaches to potential private donors for the
Addiction Research Foundation, or in his interviews with reporters, or in
his persuasion of politicians that it was in their best interests to treat
drug addiction as a disease rather than a punishable offence, because the
former approach might be effective but the latter had been a proven failure.
Avram had many interests inside and out of science. He
came to be good friends with Ji-Sheng Han at a time when relations with
China were more difficult than today. A prominent plaque resides on the wall
outside the Neuroscience Research Institute of Peking University
memorializing Avram’s donation, upon his retirement from laboratory
research, of a substantial amount of lab equipment and furnishings to the
new Institute. To help teach pharmacology to medical students he wrote a
book on biostatistics in 1964. Although titled “an introductory text”, it
was anything but. The beautiful arguments and logic that characterize this
book can best be appreciated after years of routine use of statistics in the
lab, and they contrast starkly with the more contemporaneous “how-to”
menu-driven books on the subject. Avram dug deeply into the subjects that
interested him. Flying his own plane gave him great satisfaction and he used
this frequently to travel to meetings on the west coast for many years. Not
content with simply learning to fly, he became a certified flight instructor
and then an instrument flight instructor, publishing three lengthy teaching
manuals in the process.
INRC owes Avram a debt of gratitude for his insistence
on the highest scientific standards at the initial meetings of the Club,
establishing a tradition that has continued as the club became a
Conference. Under his leadership it became in the late 1970s the critical
place to present new data relating to the actions of opiate drugs and opioid
peptides, and the tradition of frank discussion has continued under the
succeeding leadership. The success of the Conference today can be
attributed to the strength of Avram’s leadership in the initial years. We
remember him with gratitude and affection.
Brian Cox, Charles Chavkin, Lakshmi Devi & Ray
The biographical details here are taken from Avram’s wonderful
autobiographic reminiscences: Goldstein A, A rewarding research pathway,
Annu. Rev. Pharmacol. Toxicol. 37: 1-28, 1997.
More biographical details can be found on the Stanford University web
Goldstein A. The mechanism of enzyme-inhibitor-substrate reactions
illustrated by the cholinesterase-physostigmine-acetylcholine system. J. Gen
Physiol 27: 529-580, 1944.
Goldstein A, Warren R, Kaizer S. Psychotropic effects of caffeine in
man. I. Individual differences in sensitivity to caffeine-induced
wakefulness. J. Pharmacol. Exp. Ther. 149: 156-159, 1965.
Goldstein A. and Sheehan P. Tolerance to opioid narcotics. I.
Tolerance to the “running fit” caused by levorphanol in mice. J. Pharmacol.
Exp. Ther. 169: 175, 1969.
Goldstein A, Lowney LI, and Pal BK. Stereospecific and non-specific
interactions of the morphine congener levorphanol in subcellular fractions
of mouse brain Proc Natl Acad Sci USA 68: 1742-47, 1971.
Archer S. The early history of the INRC (1969-1975).
Teschemacher, H.-J., Opheim, K., Cox, B.M. and Goldstein, A. A
peptide-like sub-tance from pituitary that acts like morphine. 1. Isolation.
Life Sci. 16:1771-1776, 1975.
Cox, B.M., Opheim, K., Teschemacher, H.-J. and Goldstein, A. A
peptide-like substance from pituitary that acts like morphine. 2.
Purification and properties. Life Sci. 16:1777-1782, 1975.
10. Cox, B.M., Goldstein, A., & Li,
C.H. Opioid activity of a peptide, β-lipotropin-(61-91), derived from β-lipotropin.
Proc. Natl. Acad. Sci USA 73: 1821-1823, 1976.
11. Goldstein, A, Fischli W, Lowney
LI, Hunkapiller M, Hood L. Porcine pituitary dynorphin: complete amino acid
sequence of the biologically active heptadecapeptide. Proc. Natl. Acad.
Sci. USA 78:7219–23, 1981.
Chavkin C, James IF, Goldstein A. Dynorphin is a specific endogenous
ligand of the k
opioid receptor. Science 215:413–15, 1982.
Goldstein A, Kalant H. Drug policy: striking the right balance.
Science 249:1513–21, 1990.
Goldstein A. ADDICTION: From Biology to Drug Policy. New
York: Freeman. 321 pp., 1994.
(Karl) Stephen LaForge
Last night in Las
Vegas, the Toasters dedicated their set at the International Ska Circus
to the memory of Steve Hex aka Karl Steven Laforge. Although it was not
possible to get the band back to NYC mid-tour we did have the
opportunity to bring KSL out here with us. Steve was a massive
influence. Not only as a co-founder of the group but also as a key-
thinker, industrious, positive and astute. The early sound of the band
was largely built around his keyboard stylings before we upsized to the
horn-driven sound that characterizes the band today. Along with our gang
of fellow miscreants, Vicky Rose and Gary Eye, and then shortly
thereafter Messrs Grinnell, Dugan, Reginato and the Unity 2, we managed
to create a Frankenstein's monster that rampaged out from the crucible
of the lower east side to take over the world. And in fact is still
doing it. Steve's contributions to the band are innumerable. In the dark
hours of tours most foul his caustic sense of humour and pragmatism were
often what kept us going. Steve's chapter in the Toaster's history will
be a long and colourful one. But most of all what made KSL stand apart
was the man himself. There are few people that I personally rate as
being my friends. Steve was one of those. Whenever we saw each other –Steve
had the ability to just show up when you least expected him – it was
if time had stood still and we simply took up where we left off. That's
a rare gift, but Steve was a master at it. Acerbic wit, a black sense of
humour drier than the Sahara, and a lot of heart. The world needs more
Laforges, not less of them. So here's to you KSL. Wherever you are I'm
sure somebody is getting a zinger right about now.
(from band members of
the Toasters, a Ska musical group Stephen co-founded)
Ms. Edna Leoung
It is with great sadness that we report to all INRC members the recent death
of Ms Edna Leong. Edna, the sister-in-law of Dr. E. Leong (Eddie) Way, was well
known to all INRC regulars. During Eddie Way’s 10 years as Treasurer of INRC,
Edna attended every meeting. She was the one who spent much of the week gathering
receipts from all of the recipients of NIDA travel awards and made sure that
checks were mailed to them in a timely fashion. She always had a smile for everyone.
It was obvious that she enjoyed her work for INRC immensely, including the opportunity
to make friends from all over the world and to have even a small role in the
development of young scientists. Edna kept the INRC books for the entire period
during which Eddie was treasurer and did a fine job. Edna was the wife of the
late John Way Leong, the loving mother of 5 children, grandmother of 8 grandchildren
and great-grandmother of two. She will be missed very much by her family and
by all who knew her.
Mary Jeanne Kreek, President/Secretary Eric J. Simon Vice President/Treasurer
Please reply to: email@example.com
Dr. Tom Burk
The INRC is diminished by the loss of Dr. Tom Burks who died March 2nd from
a heart attack. Tom was a friend and mentor for many of us. His
interests in opioid pharmacology, neuropeptide actions, and gastrointestinal
function made him a frequent contributor to the INRC.
Tom contributed to the vitality of this organization in many ways and served
as program chairman for the Copper Mountain INRC-1991 meeting that was held
jointly with FASEB. Most recently, Tom was executive vice president for research
and academic affairs at The University of Texas Health Science Center at Houston
and a professor of pharmacology at the university's Medical School.
Additional information can be obtained at the following University of Texas
A Tribute to Dr. Akira E. Takemori
Members of the INRC were shocked
by the untimely death of Akira Takemori on March 12, 1998 while battling with
cancer. His passing was particularly tragic because he had only recently retired
from his position as Professor in the Department of Pharmacology at the University
of Minnesota and had been planning numerous activities for his retirement years.
Through his pioneering work with opioid receptor antagonists, he had made lasting
contributions to our understanding of the mechanisms of opioid action.
Dr. Takemori was born in Stockton,
CA and received his B.A. degree in Physiology from the University of California
-Berkley. He then earned the M.S. degree in Comparative Pharmacology and Toxicology
from the Universtiy of California Medical Center in San Francisco. Later, he
moved to Wisconsin and earned his Ph.D. degree in Pharmacology at the University
of Wisconsin, Madison in 1958, working with Dr. Gilbert Mannering. Dr. Takemori
stayed in Madison for his postdoctoral studies at the Institute for Enzyme Research
in the laboratory of Dr. Henry Lardy.
Dr. Takemori's first academic
appointment was at the State University of New York, Upatate Medical Center
in Syracuse, New York, where he was an Instructor, then an Assistant Professor
in the Department of Pharmacology. In 1963, he joined the Department of Pharmacology
at the University of Minnesota where he was promoted to Professor in 1969. He
remained in this Department until his retirement in 1994. During this time,
he was also a Visiting Professor in the Departments of Pharmacology at Keio
University School of Medicine in Tokyo, Japan (March-September 1971) and at
the University of California Medical Center in San Francisco (June 1973).
During his tenure at the University
of Minnesota Dr. Takemori trained eighteen Ph.D. graduate students and twenty
post-doctoral fellows as well as providing a research environment for six visiting
scientists. Those who trained in his laboratory have continued their successful
scientific careers in academic as well as industrial positions in the United
States and around the world. Dr. Takemori also served as the Department of Pharmacology
Director of Graduate Studies from 1987 until his retirement, when two faculty
members were then required to fill this position. His committment to education
of young scientists was also shown by his service on numerous graduate education
committees at the University as well as by serving as Program Director for the
Medical School Minority High School Student Research Apprentice Program. He
also received teaching awards including Teacher of the Year Award from the University
of Minnesota Dental School.
On the national/international
scene, Dr. Takemori was active in a number of professional societies, including
the INRC and the American Society for Pharmacology and Experimental Therapeutics
(ASPET) He served on the Executive Committee of INRC from 1973-1974 and from
1979-1982. He was also the INRC Program Chairman for the 1982 INCR meeting.
His major contributions to ASPET included serving as President (1992), Councillor
(1978-1981) and IUPHAR Delegate (1991-1995). He also served on numerous ASPET
committees including the Program Committee and the Committee for Graduate Recruitment
in Pharmacology among others. He was on editorial boards for several journals
including the Journal for Pharmacology and Experimental Therapeutics and the
Annual Review of Pharmacology and Toxicology. In addition, he was a member of
Study Sections for the National Insititues of Health (Pharmacology Section),
the National Insititues on Drug Abuse and the National Science Foundation. He
also was a scientific consultant for other academic and industrial organizations
in the United States and other countries.
Of particular importance to
the INRC are Dr. Takemori's numerous contributions to our understanding of opioid
actions. His first publication on opioids was a Journal of Pharmacology and
Experimental Therapeutics paper on metabolic demethylation of morphine and morphinan-type
analgesics in 1958. Some of his more 200 publications (manuscripts, reviews
and book chapters) on opioids resulted from his work with Dr. Philip Portoghese,
a collaboration that produced the irreversible µ-selective opioid receptor antagonist
beta-funaltrexamine (b-FNA). Use of b-FNA as well as other opioid receptor subtype-selective
antagonists characterized by Dr. Takemori, has greatly advanced the study of
opioids and these drugs are widely used today in opioid research. For his many
scientific contributions, he received the Nathan B. Eddy Award in 1991 from
the College on Problems of Drug Dependence (CPDD).
Even though he was a very productive
scientist, Arky (a nickname used by his friends) found time to participate in
and excel in multiple sports, including golf, handball, skiing, judo and tennis.
For many years, he and his lifelong colleague and friend Dr. James Fujimoto
competed annually for a golf trophy. He would regularly challenge his graduate
students to a game of handball - and win. He also found time to coach baseball
and manage his son's ice hockey league.
After he retired from the University,
Dr. Takemori moved to California and began a new life, finally having enough
time to devote to his many non-academic interests. Even then, he could be available
to provide advice and support when necessary. His loss leaves a large void in
the community of scientific thought. But most of all, we will miss Arky for
his spirit. He was often the life of the party, able to entertain his friends
with many humerous stories. Even though he was a well-known, busy scientist,
he always had time to speak with and encourage his students and junior colleagues.
He served as an excellent role model and mentor. We trusted his counsel. He
will live on in our collective memories, fondly and respectfully.
Sandra Roerig, Ph.D.
Department of Pharmacology
Lousiana State University
A Tribute to Dr.
Dr. Sydney Archer, one of the founders of INRC, an outstanding
scientist and wonderful friend to many of us, passed away on August 22, 1996.
Syd was one of a handful of scientists who met in Basel at the International
Congress of Pharmacology in 1969 and conceived the formation of what has become
the INRC. He served as its second Secretary, immediately following Avram Goldstein.
He continued to be active and just a few weeks ago at our meeting on the Queen
Mary, Syd offered to host the 1999 INRC in Saratoga, NY, --what better way to
illustrate his positive outlook on life! In fact, he had already begun work
on it by appointing a program committee and meeting with people from the Saratoga
Convention Center. At this years INRC meeting, a few of Eddy Way's friends
organized a surprise dinner for him at a Chinese restaurant in honor of his
80th birthday. At the dinner Syd Archer served as M.C. He was in great form,
charming and funny.
As a scientist, Sydney was one of the outstanding medicinal
chemists of our time. He attacked 3 of mankinds major scourges, drug abuse,
cancer and schistosomiasis with equal vigor, creativity and enthusiasm. In the
area of drug abuse he made numerous contributions, many more than I can touch
on here. He synthesized many compounds of both theoretical and practical interest.
His best known compound pentazocine (Talwin) is still in clinical use as an
analgesic. He synthesized numerous affinity ligands and other useful compounds
and participated in many basic research projects. Most recently, in collaboration
with Dr. Jean Bidlack at the University of Rochester, he developed a sensitive
fluorometric assay for opioid receptor binding and was hard at work on a promising
approach to the treatment of cocaine addiction. He played a crucial role in
the creation of the New York State Capital District Center for Drug Abuse Research
During the many years (1943-1973) Syd spent at Sterling-Winthrop
Research Institute, he rose to the rank of Vice President for Research. He returned
to Academia in 1973, namely, to the Rensselaer Polytechnic Institute (RPI),
where he remained as Professor of Chemistry until his death. He also served
as Dean of the RPI School of Science from 1980 to 1985. How well-liked and highly
regarded Syd was at RPI, was shown by the overflow crowd that filled the RPI
chapel at a recent memorial service for him.
Dr. Archer received many awards, among them the Medicinal
Chemistry Award from the American Chemical Society in 1968 and the Inventor
of the Year Award from the Eastern Patent Law Association. He was the holder
of well over 100 patents as well as the author of numerous publications in prestigious
NIDA utilized Syds talents in many ways. He served
on Study Sections, the Editorial Advisory Board, the Board of Advisors of the
Addiction Research Center and on the Directors External Advisory Committee.
He was active in CPDD and served on its Board of Directors. He also served on
an Advisory Committee on Schistosomiasis of WHO, for which he did a considerable
amount of work and traveling.
On a personal level, I was privileged to interact with Syd
in many ways and we became close friends. We served on many committees together,
planned meetings for INRC (it was he who persuaded me to succeed him as Secretary)
and published a half dozen papers together. I shall always remember his generous
introduction at the occasion of my Nathan B. Eddy Award in Lexington, Kentucky.
Irene and I spent an unforgettable week end at Teddie and
Sydneys house with many laughs, excellent food, great discussions and
forays to concerts at Tanglewood and the Saratoga Performing Arts Center (SPAC).
Sydney often came to New York and we always had lunch together on these occasions.
Lunch at Bouley, New Yorks number 1 restaurant at the time, was a gourmet
experience. As many of you know, Sydney was well known as a real gourmet among
his myriad of interests.
Dr. Sydney Archer will be mourned and remembered by his family
and by many friends and admirers throughout the world.
Dr. Eric J. Simon
A Tribute to Dr.
The following obituary was written by Dr. R. Alan North of
Glaxo Geneva Biomedical Research Institute, a former student and colleague of
Hans Walter Kosterlitz was born in Berlin on 27 April 1903.
He was the son of a physician, and he himself studied medicine in Berlin. Upon
graduation in 1928 he became an assistant in the First Department of Medicine
at the University of Berlin, working both in clinical radiology and in biochemical
research in the area of carbohydrate metabolism and particularly galactosemia.
Kosterlitz arrived in Aberdeen in March 1934; he took a research
assistantship with Professor J J R MacLeod. MacLeod, who shared the 1923 Nobel
prize in Physiology and Medicine for the discovery of insulin, had returned
to Scotland from Toronto in 1929 to the chair of Physiology. At first Kosterlitz
worked on the relationship between blood pressure and blood sugar concentration;
but MacLeod died in 1935, and Kosterlitz then returned to his earlier interest
in why patients with liver failure had galactosemia. This led to the isolation
of galactose-1-phosphate, the first step in the conversion of galactose to glucose;
the absence of the converting enzyme underlies familial galactosemia. He became
medically qualified in Britain, and received the PhD (1936) and DSc (1944) from
the University of Aberdeen. In 1939 he was appointed Lecturer in the Department
of Physiology and remained on the faculty thereafter (Senior Lecturer, 1945
- 1955; Reader, 1955 - 1968; Professor and Head of Pharmacology Department,
1968 - 1973; Professor Emeritus and Director of the Unit for Research on Addictive
Drugs, 1973 - 1996).
During the war he sought more direct application for his
research and entered the area of nutrition. This led him to try to determine
how diet affected the amount of sympathin (now noradrenaline) released from
hepatic sympathetic nerves. The interest in the autonomic nervous system developed
further during a visit to Otto Krayers laboratory at Harvard in 1953,
in which he studied the actions of veratrum alkaloids on the heart. At about
that time, Kosterlitz read a paper by Paul Trendelenburg which had been published
in 1917; this described that low concentrations of opium alkaloids inhibited
the peristaltic reflex on the guinea pig. It was the pursuit and elaboration
of this finding which set the stage for much of his subsequent work.
He showed that morphine inhibited the release of neurotransmitters
from several autonomic neuroeffector junctions, that the effect was greatest
at low frequencies of stimulation, and did not result from local anesthetic
action. He determined the dissociation equilibrium constant for naloxone as
an antagonist of morphine in the guinea pig ileum. In a blind experiment
with compounds supplied by Maurice Seevers of Michigan he showed that the action
of various opiates to inhibit acetylcholine release in the guinea pig ileum
correlated very well with their effects in monkey and man. Much of this work
was carried out together with Cairnie, Gyang, Lees, Lydon, Thompson, Wallis,
Watt and Waterfield.
At the age of 65, Hans Kosterlitz became Professor when the
new department of pharmacology was created. One of his appointees as lecturer
was John Hughes, a neuropharmacologist with particular expertise in the release
of noradrenaline. John Hughes joined Hans Kosterlitz when, obliged by age limitations
to retire in 1973, he established the Unit for Research on Addictive
Drugs. Several features of the actions of morphine in man and isolated animal
tissues (but particularly the marked selectivity of enantiomers), led them to
reason that it mimicked the actions of substances that occurred naturally in
the body as hormones or neurotransmitters. As it happened, Graeme Henderson
(a PhD student with Hughes and Kosterlitz) had just found a further example
of a morphine-sensitive neuroeffector junction in the mouse vas deferens and
this was used as the principal bioassay for the isolation of the enkephalins.
Such is serendipity -- the guinea pig ileum preparation probably would not have
worked to follow the isolation and purification because it has too much enkephalinase
The second element of serendipity, and a prepared mind, is
better known. Howard Morris, who had collaborated with Kosterlitz and Hughes
to identify enkephalin definitively by mass spectrometry, heard a lecture by
Derek Smyth on the subject of the pituitary prohormone b-lipotropin. He noticed
that the C fragment of b-lipotropin (now known as b-endorphin) began with the
pentapeptide sequence of Met-enkephalin. Thus was initiated the search for all
the opioid peptide precursor proteins. The discovery of the enkephalins catalyzed
major new fields of research endeavour in neuroscience, physiology, pharmacology
The Unit for Research on Addictive Drugs remained at the
forefront of opioid research for the next 10 - 15 years, supported by the Medical
Research Council of Great Britain and the National Institute on Drug Abuse of
the United States. The main contributions during this time were the first distinctions
between m (morphine) and d (vas deferens) receptors, elucidations of the factors
determining the binding of ligands to m, d and k receptors, and studies on the
release of enkephalin from nerves and its degradation in biological tissues.
During these years, Kosterlitz received many awards, prizes, and lectureships.
They included the Schmiedeberg Plakette of the German Pharmacological Society,
the Wellcome Gold Medal of the British Pharmacological Society, the Royal medal
of the Royal Society of London and the Albert Lasker award. He was an honorary
member of the British Pharmacological Society and the Physiological Society,
a Fellow of the Royal Society of London, and a foreign member of the U.S. National
Academy of Sciences.
Hans Kosterlitz died on 26th October 1996 at the age of 93.
All those who met him learned that science was tough but science was fun. Tough
meant rigorous; it meant not discussing things that you did not understand.
Tough meant hard work; Kosterlitz was a man of long hours. Tough meant argumentative,
when an intellectual point was to be made. Fun for Hans was good company, travel,
food and wine. Fun showed itself in his wry humour and the twinkle in the eye.
Fun was embodied in his constant admonition to "work harder but play harder".
He is survived by Hannah, indefatigable wife of almost 60 years, and beloved
of the opioid research community worldwide. Hans and Hannah have one son, Michael,
who is a theoretical physicist at Brown University in Providence, Rhode Island.
They have three grandchildren Karin, Jonathan and Elizabeth.
Kosterlitzs legacy is not only enkephalin; it is the
INRC. At the Fourth International Pharmacology Congress in Basle in 1969, Hans
Kosterlitz and Harry Collier organised a small satellite session of opiates;
thus began the International Narcotics Research Club (now Conference).
The history of the development of the INRC is chronicled
elsewhere, but its future will be a lasting testimony to a man who not only
did science well, but loved science well, and loved the fun of communicating
Dr. R. Alan North