Cytometry Part AVolume 97, Issue 12 p. 1202-1208 In MemoriamFree Access In Memoriam: Mortimer L. Mendelsohn (1 December, 1925–8 January, 2020) First published: 28 September 2020 https://doi.org/10.1002/cyto.a.24231AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL The scientific community, and ISAC in particular, were greatly saddened by the passing of Mort Mendelsohn on January 10, 2020 at the age of 94. It was his vision and leadership that created the Society for Analytical Cytology, as ISAC was originally named, and our Journal, Cytometry. Like all great scientists, Mort was driven by curiosity and the refusal to accept the status quo. Throughout his career, he strove to understand human cancers—their epidemiology, pathogenesis, and susceptibility to treatment. He was convinced that the secret to understanding and treating human cancers lay in analyzing individually the cells comprising the cancer population. To do this, he applied the tools of statistics and mathematical modeling to data extracted from individual cells. And in order to obtain such data, he recognized the necessity to devise and construct new instruments and techniques for analyzing cells and their chromosomal complement. These themes resonated throughout his long and illustrious career. Mort was a native of New York City. He graduated from Harvard Medical School cum laude in 1948 and continued his medical training in oncology as a Damon Runyon Research Fellow. From 1953 to 1955, he served as a Captain in the US Army at the Walter Reed Medical Center. Already, he was active in scientific research, particularly examining the effects of radiation on animals and tissues (1-7). He was awarded a British/American exchange fellowship and obtained his PhD from Cambridge University in 1958. His thesis on tumor cells required him to construct a two-wavelength micro-spectrophotometer, his first foray into instrumentation (8-12). He then joined the Department of Radiology at the University of Pennsylvania, where he created the Radiobiology Section. His research into oncology had him leading the way in use of tritiated thymidine and DNA quantification to analyze the cell cycle and tumor growth (13-24). The insight he gained from these studies lead to his examination of the efficacy of radiologic methods and of radiotherapy (20, 21, 24-28). He realized the potential of using cell cycle specific treatments, both radiologic and chemotherapeutic, to enhance therapy by increasing selective damage to the tumor cells, thereby sparing normal tissues (24, 25). Recognizing that this would require careful quantitative analysis, Mort championed mathematical modeling of the cell cycle (23, 29). While at the University of Pennsylvania, Mort was awarded the NIH/Airborne Instruments CYDAC project, which used either flying spot or Nipkow disk scanning methods to create photometrically accurate digital microscope images. He and his colleagues created novel approaches to the processing and analysis of digital images. They applied the techniques to the quantification of blood cells, tumor cells, and spermatozoa. Possibly the most important cytometric contribution was the quantification of the DNA content of the individual human chromosomes (26, 27, 30-38). These were the most precise measurements achieved up to that time and rank even today among some of the most accurate ever made. They revealed for the first time the existence of significant DNA content polymorphisms among individuals. During 1960s, several groups were using flow systems to count and analyze cells in suspension. Of particular relevance were the contributions of Marv Van Dilla (fluorescent Feulgen to quantify DNA) and Mack Fulwyler (cell sorting) at the Los Alamos National Laboratory, Len and Lee Herzenberg at Stanford (Fluorescence Activated Cell Sorting), Lou Kaminsky (Cytofluorograph, fluorescent DNA Analysis), and Wolfgang Göhde (Fluorescent Cell Sorting). Mort immediately appreciated the importance and future potential of making measurements on individual cells, rather than the classical “grind and find” approach of biochemistry. He was so eloquent about this vision that he persuaded the US Atomic Energy Committee to fund the transfer in 1972 of his group (including Bart Gledhill, Brian Mayall, and Dan Moore) to the Livermore National Laboratory, to be joined by Marv Van Dilla, Phil Dean, Tony Carrano and Joe Gray. He became the Associate Director for BioMedical and Enviromental Sciences. The group rapidly expanded and became a leading center for cytometric research and application, attracting scientists from around the world and making many seminal advances in the field. At this time, the Engineering Foundation was sponsoring conferences on Analytical Cytology. Mort organized the 1973 meeting at Asilomar and had the proceedings published in the Journal of Histochemistry and Cytochemistry; participants sensed that they now were part of a new discipline. Mort consolidated this development by spearheading the formation of the Society for Analytical Cytology (SAC) at the meeting in Schloss Elmau, Germany, in 1978. At the same time, he supported the founding of Cytometry as the official journal for the SAC and provided space and financial support for an editorial office. The first issue of Cytometry appeared in July 1980 and contained mainly papers from the second SAC conference. (Incidentally, Mort thought that the cytometry community was too technology-oriented and would last only about 20 years!). Mort was acutely aware of the potential importance of advances in quantitative biology being made by his group at Livermore, especially as they related to cancer treatment, quantitative cytogenetics and assessment of persistent radiation induced biological damage. He championed the development of quantitative tools for cell cycle analysis (29, 39), chromosome analysis and sorting (28, 40) and immortalization by cloning (41). The latter led to the development of the National Laboratory Gene Library Project at Livermore and Los Alamos, which produced and distributed chromosome libraries world-wide (42). The availability of chromosome-specific libraries led directly to the development of fluorescence in situ hybridization (FISH) techniques to analyze DNA in chromosomes and cells (43, 44). FISH was initially conceived of as way to speed translocation detection as a measure of radiation damage; indeed it is still used for this purpose at the Radiation Effects Research foundation (45, 46). However, medical applications soon eclipsed radiation dosimetry in importance (47-49). Characteristically, Mort never added his name as an author to the many papers coming from his group unless he himself had actively participated in the scientific conduct of the work. Based on these advances in chromosome sorting and analysis and the success of the National Laboratory Gene Library, Mort proposed the Human Genome Project as a feasible mega-project for the US Department of Energy. Mort was always seeking ways to improve cancer risk analysis by applying the many advances in cytogenetics and in detection of mutagenesis being made by the scientists at Livermore. His skill in cancer epidemiology was important in his studies of workers at the Lawrence Livermore National Laboratory (50-52), Chernobyl clean-up workers (53, 54), atomic bomb survivors in Japan (55, 56) and carcinogenesis in general (57-62). Throughout his career, Mort was an active participant in many scientific and advisory committees. He was appointed as an American Director of the Radiation Effects Research Foundation (RERF), the joint US/Japan program to follow the epidemiology of the Hiroshima and Nagasaki atomic bomb survivors. He and Marian (his wife) moved to Japan for 3 years. For his work with RERF, he was awarded the Third Order of the Sacred Treasure, which is Japan's Highest Civilian Honor. Mort refused to retire and continued to make significant contributions for many years after normal retirement, until the passage of years finally took its toll. He was a mentor and inspiration to innumerable people by virtue of his intellect, insight, character, and towering presence, physical and otherwise. His capacity of persuasion was prodigious, yet when he encountered resistance to his exhortations, he did not hesitate to utilize his official status to secure the desired outcome. Thus, in paying tribute at Mort's passing, we acknowledge all of the remarkable personal and professional attributes of a unique individual. Personal Memories I started working with Mort in 1964 at the University of Pennsylvania and was with him as my mentor and colleague for the next 34 years. Initially, with his support, I completed construction of a semi automatic two wavelength microspectrophotometer. This instrument was designed by Mort as a more sophisticated version of the instrument he created at Cambridge University while working on his thesis. It used servo devices to solve the two wavelength equations in real time. It measured the DNA content of individual cells permitting sophisticated cell cycle analysis for his studies of the cellular effects of radiation. Shortly after, I became lead of the CYDAC project in which microscope images were quantitatively digitized. Mort originated image processing techniques that allowed us to explore not only the manner in which cancer cells differed from normal cells but also to quantify the DNA content of human chromosomes (26, 27, 34-38). Mort was always meticulous in defining both the power and the intrinsic errors and limitations of any instrument or technique. When Mort heard a presentation by Marv Van Dilla, he immediately recognized the potential of flow systems and arranged a visit to Los Alamos. The Los Alamos culture includes much outdoor activity, and so the visit found Mort on skis, although he had never skied before. The next day, he came back for more, even though he sported some magnificent bruises. This was typical of Mort; he was always willing to try something new but would persevere until it was mastered. Armed with his insight into the potential of flow systems, he approached the Atomic Energy Commission with a proposal to create a cell analysis center at the Lawrence Livermore Laboratory. Our group from the University of Pennsylvania would be joined by Marv, bringing his flow expertise. In 1972, the upheaval of the move to Livermore was tempered by finding a home that shared a private tennis court; bliss for Mort and Marian, although they were concerned lest their neighbors did not play to their standard! At Livermore, he was the Associate Director for Bio-Medical and Environmental Sciences and created a unique environment for advancing Analytical Cytology. New instruments and techniques were developed in the collegial spirit he fostered. Scientists from around the world came to study and to work. As the discipline evolved, Mort was the visionary who felt the need to define it by organizing the Engineering Foundation Conferences on Automated Cytology and by enabling the proceedings to be published. At the Pensacola conference in 1976, Mort proposed the organization of a society. At the 1978 Schloss Elmau conference, this led to the formal creation of the Society for Analytical Cytology and of Cytometry, its publication. While Mort was a visionary, he also was exacting in the standards he set for himself and for others. He created a remarkable collegial environment. He was a demanding but genuinely modest leader; an inspiring colleague, mentor, companion, and friend. Brian Mayall, Founding Editor, Cytometry Fresh out of graduate school at UC Berkeley, I had two job options. One was a faculty position in Biostatistics at the University of Michigan; the other was a research job at the University of Pennsylvania with Mort's group: a standard university-track versus government-funded research position, subject to renewal. It turned out to be an easy choice. I could immediately tell that Mort had a keen appreciation for the work I had done and could see the importance of statistics in improving the measurement of chromosomes and understanding their relationship to cancer and disease. In my first publication with Mort, we created a mathematical framework for assessing cancer treatments taking into account probabilities of tumor ablation and complications as a function of dose (28). Mort suggested using ROC curves to determine whether more aggressive treatment of cancer could increase the chance of a meaningful benefit. He insisted that I present our results at a large gathering of radiotherapists at their annual meeting in Boston. I was terrified, having never previously lectured before such an esteemed collection of clinical researchers, but Mort gave me confidence and good advice on delivering the talk. (Keep your sentences short.) Early work with Mort and Brian Mayall was based on measurement of DNA in chromosomes by cytometry and the relative amounts of DNA in the long and short arms of chromosomes. Our goal was to use such measurements to link specific chromosomal abnormalities with disease, particularly cancers. This was several years before DNA sequencing was a technology. Later, Mort asked me to apply statistical methods to summarize information from a large IARC/WHO database of results from different bio-assays to try to predict carcinogenicity. The system, inspired by Mort's ideas, provided stable carcinogenicity rankings of a wide variety of chemicals. For nearly all chemicals, there was some evidence of mutagenicity and so we realized that mutagenicity is a continuous, rather than a dichotomous, quality. This work, published as three papers (59-61), again demonstrate Mort's broad interest in using statistical methods to organize and better understand research by use of fundamental principles. I shared with Mort his enthusiasm for puzzles. I remember several late Friday afternoon sessions working together on Cryptic puzzles, which are similar to English-style crosswords. He was also an avid tennis player and had a collection of pinball machines that he kept in working order. For many years we shared, along with Brian Mayall, a season series of San Francisco Opera tickets. He was a founding member of the Del Valle Fine Arts that brought classical music performances in Livermore. Dan Moore (Lawrence Livermore National Laboratory) We met Mort Mendelsohn for the first time during the early 70s after he had instituted the American Engineering Foundation Conferences on Analytical Cytology. Mort had the foresight at the onset of these conferences to attract scientists from the international community interested in instrumentation and the underlying cell biological phenomena. We had become very interested in flow cytometry during our postdoctoral time in the Biochemistry Department at Stanford Medical School, where Len Herzenberg of the Department of Genetics was pioneering the use of flow cytometry. We initiated our own development of a computer-controlled cell sorter with multiple laser excitations at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany in 1971, and presented our first results at the 1973 Asilomar conference. Mort exerted a strong influence on the participants and we had inspiring conversations with numerous individuals— including Mack Fulwyler, inventor of the cell sorter at Los Alamos—who went on to be close collaborators, friends, and visitors to our lab. In fact, by the fifth conference in Pensacola it was clear that we all wanted to create an independent structure for organizing the conferences. One of us (Tom) assumed that role for the next meeting, which in 1978 took place in the unique setting of Schloss Elmau, located in Bavaria, Germany. Thus, Tom became the first “past” president of the Society for Analytical Cytology, as it was called upon its creation at Elmau. This and later conferences, for example, one organized by Donna at Cambridge University in 1987, reinforced our strong ties to the Los Alamos Scientific Laboratory, the Lawrence Livermore Laboratory and many other SAC-member groups. During the ensuing years, the reciprocal exchange of postdoctoral students and visiting scientists enriched the research activities in both directions. Mort's open-mindedness and strong commitment to excellent science promoted strong partnerships and discouraged negative competition. We remember him with great fondness, admiration, and gratitude. Donna Arndt-Jovin, ISAC President 1985–1987 Tom Jovin, SAC Honorary Past-President 1978 I first met Mort in Livermore the summer of 1972 during a recruitment interview organized by Marv Van Dilla. That was the start of a decades-long interaction that fundamentally shaped my career. Mort taught me the power of multidisciplinary science as a way of approaching otherwise intractably large projects. Mort built the Biomedical Division program at Livermore by attracting individuals with expertise in biology and medicine, chemistry, statistics, engineering, mathematics, and computer science. My own research programs build on that model. He also instilled in me his interests in genetics, cancer and mathematical modeling—all of which I pursue today. Mort had a remarkably good working knowledge of these many disciplines. Indeed, I was frequently amazed to find that Mort had a better grasp of the scientific projects that I was working on than I did. He was both challenging and supportive. I learned a lot from his mentoring—a good part of which came on the tennis court during changeovers. I rarely won at tennis but the discussions were worth the beatings. Indeed, my work on the cell cycle and cancer and on work that led to FISH and other genome analysis approaches was inspired by Mort's interest in quantifying radiation damage and quantitative cytogenetics. I continue these studies even today, participating in the NCI Cancer Systems Biology Consortium and the NCI Human Tumor Atlas Network. Our work on FISH got a particularly large boost when Mort took Dan Pinkel and me—both neophytes in nucleic acid chemistry and cytogenetics—to the US Department of Energy headquarters and encouraged us to pitch the idea of chromosome painting using FISH for aberration detection. The result was immediate, long-term funding and support from Mort that gave us the opportunity to “learn the field” and pursue several false starts that were needed to develop a reliable technique. One of the first applications of FISH was in analysis of radiation-induced chromosome aberrations in the A-bomb survivors in Hiroshima and Nagasaki by the Radiation Effects Research Foundation (RERF). Mort introduced me to the RERF—a connection I maintain to this day—and administered several educational beatings on the clay tennis courts at the RERF headquarters in Hiroshima. Mort was a leader, mentor, supporter, friend and amazingly insightful scientist. I cannot overstate the impact he had on my career and my life. Joe Gray, ISAC President 1998–2000 For a fast neutron physicist, I had pleasing cross-disciplinary interactions with Mort, and they led to big things. Soon after Joe Gray joined Livermore, we found ourselves playing handball together. When he described what he was doing with flow cytometry, it sounded to me a lot like neutron time-of-flight. Pretty quickly I grabbed a crate of nuclear electronics from our spectrometer and wandered over to see if he and I could make improvements in signal to noise and time resolution in his spectrometer. With little effort, we were delighted to see that we could. As this was in the years before equipment controls and inventory, I suspect the electronics remained there. Joe was happy, I was happy, and the hunt across lines was stimulated. A decade and a half later, I was bringing up the facility that became the Center for Accelerator Mass Spectrometry. One of its purposes was ultrasensitive detection of C14 for archeology and the earth sciences. I mentioned to Bart Gledhill that we now had a capability to detect an isotope that the biosciences routinely used, but with a sensitivity a million times higher. Surely there must be some interesting experiments to be done with that? Bart set up a meeting with Mort, Ken Turteltaub, and Jim Felton with John Vogel and me. Things went very fast thereafter. The Lab tossed in discretionary money and we soon had a wonderful response curve for carcinogen metabolite binding to mouse DNA. We thought the paper grand, but were not prepared for editorial rejection. The paper was rejected by both Science and Nature. I remember Ken's justified rage at one reviewer's remark: “This is wonderful work, but I don't believe it.” My major Professor, Heinz Barschall, bailed us out and we published in PNAS, which then required a Member's sponsorship to publish. From that grew a rich program, including re-measuring the Hiroshima neutron dosimetry, a subject near and dear to Mort. Finally, Mort got to see the start of my most exciting technical mission. I was sitting in his office on a Friday morning in June of 1991 discussing future experiments and program possibilities when his phone rang and he handed it to me. He said with a puzzled expression on his face “Lab Security is looking for you.” It was DOE calling to ask whether I could be in Washington by Tuesday to join the second UN Nuclear Inspection of Iraq. I excused myself and hurried home to explain to Mary a few things about my job that she was unaware of. I spent the weekend putting my gear together. We never resumed the discussion, but younger and faster folks carried on just fine without our direction. Jay Davis, Associate Director, Lawrence Livermore National Laboratory In moving to LLNL in 1972 to become the head of the lab's Bio-Medical Division, Mort arrived carrying a singular and much deserved reputation. He had played an important role in bringing the NIH/NCI to insist on defensible rigor in research funded by the NIH in cancer biology and clinical practice. Importantly, this included not just statistical rigor in how data were analyzed, but also ensuring that study designs had the statistical power needed to answer the questions posed. It should then not have surprised me, though it did, to witness Mort's also singular behavior during scientific talks, whether by invited guests or his own staff. He would invariably sit in the front and pay very close attention, particularly to any quantitative data presented, whether in tables or graphs. And it stunned me how often he found problems—to put the matter softly. He was never harsh, but his actions said plainly, “this is not a ‘make nice’ social exercise; this is science, and the experimental observations, all the points on a graph, literally matter; they are in fact everything.” This was as inspirational, and as educational, to me, as it was not at all what I was accustomed to nor had expected. It was, in a beneath-consciousness way, a deliverance for me. But the high point for me in my experience of the consequences of Mort's respect for the literal truth in science came during the so-called “Alta Summit” meeting in 1984 (see, e.g. https://web.ornl.gov/sci/techresources/Human_Genome/project/alta.shtml). That meeting was sponsored by the DOE and is credited as being significantly responsible for launching the human genome project launched by the DOE; (see http://arep.med.harvard.edu/gmc/HGP.html). The meeting was conceived by Mort and David Smith (then of OHER/DOE), and was designed to ask “… those working on the front lines of DNA analytical methods to address a specific technical question: could new methods permit direct detection of mutations, and more specifically could any increase in the mutation rate among survivors of the Hiroshima and Nagasaki bombings be detected (in them or in their children)?” This was in part motivated by the fact that the study of those survivors, which had sought to measure the frequency of new heritable mutations present in the survivor's children, was just then concluding, and with a largely null result. This very large and very expensive study, on which Mort had served as vice chairman, had been undertaken jointly by Japan and the United States, and it was highly consequential, both socially and politically. During that meeting, it was reported that ionizing radiation was dramatically less efficient than had been presumed in producing single-amino-acid substitution mutations, the only kind the survivor study could detect. The conclusion, grasped immediately by Mort, was that the survivor study did not come close to having the statistical power needed to measure the incidence of the most frequent and most relevant mutations; this implied that it had been a wasted effort, one based on a overly facile and incorrect assumptions about mutations. Mort was shocked and very concerned. And he knew that coming out with this surprise revelation would likely have “terrible” political and social consequences (not excluding pretty harsh ones for himself personally). After a bit of intense, but very brief, soul searching, he immediately set out to do the right thing and moreover did so in a way that got the science right while minimizing the social and personal costs to others. But there again, in that high stakes, high altitude, Alta moment, was Mort. Still “sitting in the front row.” Still paying fierce attention to the data, to the sacred numbers, striving to grasp their implication. And at the same time holding to the core obligation of the scientist (of the citizen?) to face whatever truth the facts reveal, and to do that truth's bidding without fear or favor. To that high but sadly rare office, we might all aspire. Elbert Branscomb, Human Genome Project, Lawrence Livermore National Laboratory In 1984 Mort, along with Dave Smith of the Department of Energy's Office of Health and Environmental Research (OHER), initiated a meeting aimed in part at assessing methods for measuring the rates of heritable mutations in humans. It attracted a Who's Who in human genetics. Mort's report on the meeting was clear and bold and seemed to chart important new directions for the OHER radiation biology programs. I immediately called Mort. That conversation, during which we discussed DNA mapping and sequencing, lasted no more than 15 min, but I cannot recall ever learning so much so quickly. It was not that Mort conveyed information—which he did, and remarkably well—it was his uncanny ability to ask the right questions. And those particular questions, which led me to think through issues I had not previously considered, were tightly linked to the Santa Fe workshop and the proposal to sequence the human genome. It was the first of several fruitful question-driven educational exchanges I had with Mort. He led our advisory committee with a keen intellect and a light hand. He was a towering figure in the DOE's Health and Environmental Research programs, but his impact on science goes beyond the Department. He will not soon be forgotten. Charles DeLisi, Boston University While Dr. Mendelsohn was serving as the associate director of Lawrence Livermore National Laboratory, he was nominated as science councilor to the Radiation Effects Research Foundation (RERF) in 1981. He served as the councilor until 1992 when he was elected director of RERF in 1992. Dr. Mendelsohn was then appointed as the vice chair of the institute in 1993, serving until 1995. With his wide range of knowledge in advanced science, he was best fit for management and operation of RERF. The time period of his leadership at the RERF, 1981–1995, overlapped with the era of birth and advancement of molecular biology, which was ignited by the discovery of Src oncogene in 1977. Indeed, he urged the institute to keep up with the expansion of biology to life science by incorporating advanced tools, such as the FACS cell sorting system. In addition to a wide coverage in science, Dr. Mendelsohn had personal connection to many scientists and scientific organizations which helped him safeguard the bi-nationality of RERF and overcome the crisis brought about by the drastic change of the yen/dollar ratio. With the great accomplishments at RERF and for Japanese science, Dr. Mendelsohn was liked by many at RERF for his gentle personality. He was decorated with the Third Order of Merit with the Order of the Sacred Treasure on November 3, 1994, for his scientific accomplishments and contributions to advancement of Japanese science. It is interesting to note that Dr. Mendelsohn succeeded Dr. Schull for the directorship, but also for the honor since Dr. Schull was also decorated with the same medal in 1992. In addition to great accomplishment and the honor, Dr. Mendelsohn, together with his wife, Marian, enjoyed their days in Hiroshima, exploring Japanese culture and Japanese life. Ohtsura Niwa, Radiation Effects Research Foundation, Hiroshima Mortimer L. Mendelsohn: Selected Bibliography 1Mendelsohn ML, Bodansky O. The value of liver-function tests in the diagnosis of intrahepatic metastases in the nonicteric cancer patient. Cancer 1952; 5: 1– 8. 2Mendelsohn ML, Caceres E. Effect of x-ray to the kidney on the renal function of the dog. Am J Physiol 1953; 173: 351– 354. 3Mendelsohn ML, Szutu C. Relationship of renal function to blood pressure during ganglionic blockade in the anesthetized dog. Am J Physiol 1953; 173: 355– 358. 4Farr LE, Sweet WH, Robertson JS, Foster CG, Locksley HB, Sutherland DL, Mendelsohn