Dr Andrzej W. Lipkowski
(posted 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 science.
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 ongoing.
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 Alzheimer’s disease.
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 Pharmacology
Tufts University School of Medicine