J Neural Transm (2015) 122:171–175 DOI 10.1007/s00702-014-1331-y
OBITUARY
Merton Sandler (March 1926–August 2014)
Ó Springer-Verlag Wien 2014
Merton Sandler was a pioneer of Psychopharmacology, and published influential scientific papers in the field for nearly 50 years. He formulated the monoamine hypothesis of depression in 1959. He, together with his friend and psychiatrist Mike Pare, confirmed that iproniazid acted as an antidepressant. It had already been reported that this drug acted to inhibit the enzyme monoamine oxidase. They, therefore, suggested that depression was caused by a deficiency of monoamines in the brain (Pare and Sandler 1959). This was at a time when most psychiatry was still quite psychoanalytic, and was part of the beginning of biological psychiatry. He remained interested in monoamine oxidase for the rest of his working life (Sandler 2004). He and his colleagues demonstrated that the enzyme had multiple forms, and that deprenyl, a selective inhibitor of monoamine oxidase B was helpful and safe in the treatment of Parkinson’s disease. In later years, he and colleagues discovered the endogenous monoamine oxidase inhibitory activity, which he named tribulin (after trials and
tribulations) and identified the selective B inhibitory component as isatin. In the early days he experimented on himself. He used to describe how he took reserpine and it made him, usually a very calm man, aggressive towards his wife Lorna. Luckily the effect soon wore off. He continued to encourage members of his lab to test things on themselves. In studies of the effects of wine in triggering migraine, we all drank cold red wine or an equivalent amount of vodka in lemonade in darkened bottles the first thing in the morning. The red wine certainly made many of us feel quite unwell. Some bottles of wine remained in the lab for a while, raising eyebrows in visitors. When we finally had to clear out the labs where he had worked for many decades we found an unlocked cupboard full of LSD, amphetamines, and many other banned substances. Men dressed in what looked like space suits came to clear it all out. The labs certainly did not look state of the art, In the 1990s they were used to make a black and white film of research in the 1930s. However, Merton was quick to appreciate and invest in new techniques and was an early user of mass spectrometry. As well as the well-trodden pathways of 5-HT, dopamine and noradrenaline he loved the more obscure byways of tyramine, phenylethylamine, isoquinolines and carbolines. He developed the tyramine test as a marker for depression, where the subject took a 100 mg capsule of tyramine and the level of tyramine sulphate conjugate excreted in the urine, was measured. This too was tested on members of the lab. A more recent interest was in the neurotrophins, and especially the role of BDNF in depression (Sandler 2001). When he started to be interested
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in this it seemed a really obscure topic, but current research has shown his foresight in this too. His extraordinary breadth of interest is shown by the range of topics of the books he wrote or edited. Their titles include Wine, Mental Illness in Pregnancy and the Puerperium, Psychopharmacology of Anticonvulsants, Psychopharmacology of Food, Design of Enzyme Inhibitors as Drugs, Migraine, 5-HT in Psychiatry, Sexual Behaviour: Pharmacology and Biochemistry, Psychopharmacology of Alcohol, Migraine: Pharmacology and Genetics, Progress in Catecholamine Research, Psychopharmacology of Aggression Parkinson’s Disease, as well as one on Medical Humour and Anecdotes. Merton spent most of his working life as Professor of Chemical Pathology at Queen Charlotte’s maternity hospital. He took the job originally as he had a theory about the role of 5-HT in preeclampsia. He disproved his own theory within 6 months and this gave him freedom to work on what he wanted for the rest of his life. His role in chemical pathology only took up a few days each year, as he had a good team working with him on this. However, although in general he lost interest in the science of maternity he organized the first meeting on mental illness in pregnancy and the puerperium and edited the first book on the subject. He also was instrumental in setting up the Association for Postnatal Illness. Merton loved to travel to conferences around the world. He and his wife Lorna were often to be seen by the pool. The ACNP meeting in Puerto Rico was a particular favourite. But he was always networking, talking, discussing new ideas, stimulating new avenues of research, and forging new collaborations and making connections for others. He was very funny too, and the best after-dinner speaker on the conference circuit. Merton had colleagues from the UK, many countries in Europe, Israel, USA, Russia, India, Japan, and Australia. All regarded him as their friend. He never said a bad word about anyone. He had especial links with Russia; Lorna is a translator and her languages include Russian. He was a great supporter of Russian Jews in the Soviet days and helped some such as Gregory Oxenkrug to leave; but he also maintained close contact with non-Jewish Russians, such as Alexei Medvedev, too. I worked with him for over 20 years. He made science fun. Vivette Glover
Merton Sandler: an appreciation I first met Merton Sandler in 1963 at the old Allan Memorial Institute, at McGill University, where he was visiting Theodore L Sourkes laboratory, where I was an
123
Obituary
M.Sc. Student. I always wanted to get back to England after finishing my Ph.D. with Sourkes, who suggested I should go to Merton Sandler’s laboratory for my postdoctoral. Indeed Merton accepted me and in 1966, I joined him and was with him until 1972. Besides the significant works we published, these were to be the most informative time of my scientific life, learning from Merton to write papers and how to give informative lectures. I came to Merton to continue my studies on monoamine oxidase (MAO) and its inhibitors, which I had started at McGill and where I had shown that MAO existed in two forms. I continued to work on rat brain MAO and was the first to study human brain MAO, which were provided by the city of London neuropathologist and psychiatrist Mike Pare. We showed that extrapyramidal region of human brain, unlike rat brain, had high activity for dopamine and benzylamine metabolism. We also received brains obtained from patients who had terminal diseases, but were treated with various MAO inhibitors for their depression. These inhibitors had differential effects on MAO activity in various brain regions and serotonin and noradrenaline metabolism. These were the first studies on human brain MAO and its multiple forms, which resulted in us receiving the International Anna Monika Prize. We continued to study MAO and tyramine metabolism in dietary migraine patients, who associated their headaches with certain foods such as cheese and chocolate. We discovered that they had low platelet MAO activity and had a defect in tyramine metabolism via MAO and conjugation. For these studies Merton and I were given the British Migraine Association Gold Medal. When I joined Merton one of the things he wanted me to study was the action of the anti-angina Hoechst drug, segontin, on catecholamine metabolism in man. It was thought that the drug had similar activity to reserpine. So, we started probably the craziest set of studies in volunteers, which included us and various members of the Merton’s laboratory. The study comprised of giving intravenous segontin and comparing it to intravenous reserpine and amphetamine and drinking one third bottle of vodka in 1 h. The idea being to collect urine for 24 h and examine urinary catecholamines and metabolites. If I recall correctly these were the first such studies in volunteers. It would not be allowed today, since in those days there was no Helsinki Committee. Intravenous amphetamine was great but had its down side. Reserpine was terrible, both Merton and I were reserpinized for a month and were paranoiac. He told me that Lorna constantly told him so. I will always be most grateful and indebted to Merton for receiving a position at Oxford University with David Grahame-Smith and introducing me to Peter Riederer in 1973. These two events were to completely alter my scientific life and direction.
Obituary
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Merton was always most generous and supportive to his colleagues. We travelled to numerous conferences and meetings before and after I left him. One of the delights was to hear Merton’s brilliant witty summary of the meetings and after-dinner speeches, for which he became world renowned. I well remember the first time he ever had to give an after-dinner talk. It was the 1972 New York Columbia University Serotonin Meeting, which his friend Ermino Costa had organized. Merton was asked to give after-dinner talk 2 days before the end of the meeting. He told me he was going to leave the meeting to prepare his talk, because he was nervous and never had given after-dinner talk. He came back 2 days later like Moses out of the desert. A changed man and gave a most unbelievably funny talk that had most of audience falling off their chairs. This started a new career for him and no conference would finish without Merton’s speech. Many of his speeches were recorded by Earl Usdin. No one could match him in this and there will not be another like him. He had an amazing command of the English language and he always learned new words to introduce in his scientific papers. There will not be one like him. He was sorely missed when he had to retire and will be, especially as a colleague and friend.
In October 1974, Moussa Youdim and I discussed this issue again in Vienna and I convinced him to use (–) deprenyl for the treatment of ON–OFF phases in PD. The beneficial effects of this clinical trial were published in 1975. In retrospect, this idea at Merton Sandler’s laboratory had wideranging consequences for the benefit of PD patients. Merton Sandler and I continued our collaboration especially when Gavin Reynolds joined the laboratory at the Department of Neurology, Lainz Hospital, Vienna, for about 2 years and concentrated his work on L-deprenyl’s effect on phenylethylamine and amphetamine. A final cooperation with Merton has been the detection of quinolinic acid in postmortem brain tissue of Alzheimer’s disease in 1989. We had continuous contact at meetings, conferences and congresses. And the song and dance at my 60th birthday party was an unforgettable event for everyone listening to Merton Sandler’s and Gerald Stern’s performance. The brilliance of their sketch and their ‘‘literally English’’ was a lot of fun for all attendees. Merton Sandler has been influential for my career and I will miss him as a wonderful friend.
Moussa B. H. Youdim
Memoirs on Merton Sandler
Merton Sandler: a personal appreciation I was one of those post-docs visiting Merton Sandler’s laboratory. In early November 1973, I started with Linda Fellows to develop a method for the proper detection of MHPG using gas chromatography. Merton Sandler’s laboratory was at that time the centre for GC and GC–MS. They had more than 15 GCs available with every useful methodological variation. Linda and I developed this sensitive assay and together with Merton Sandler published a paper in 1975. It was at this research visit that I told Merton Sandler about the problems with ON–OFF phases in PD and that we were looking for a MAO inhibitor without major side effects, for example, with no liver toxicity and blood pressure crisis. The reason for this idea was based on our own findings of diurnal fluctuations of MAO activity and the in principle beneficial use of various MAO inhibitors in the treatment of PD as shown in the early 60s by Walther Birkmayer/Oleh Hornykiewicz and Andre Barbeau and colleagues. Merton proposed to invite Moussa Youdim, who worked at that time at Grahame-Smith’s laboratory in Oxford, to visit Queen Charlottes and to discuss this idea but it was not pursued at this occasion.
Peter Riederer
I had always pleasant and enjoyable memoirs with Merton Sandler in discussing science and a wide range of topics, whenever I met him in many international conferences in USA, Europe, Israel, and Japan. Merton was a pioneering worker in chemical pathology and in psychopharmacology, mainly in the field of biogenic amines where I have been working. Merton and his colleagues presented many important discoveries which linked basic science to clinical science. One remarkable finding is that dopamine is the substrate of monoamine oxidase B in the human brain. This work leads to the present clinical use of (–) deprenyl (selegiline) in the treatment of Parkinson’s disease. Merton was a pioneer in introducing gas chromatography with mass spectrometry (GC–MS) for the analysis of biogenic amines. For the work in GC–MS he was invited to several international conferences including the mass spectrometry conference in Japan. Merton was a very kind and warm-hearted person and always helped young scientists internationally. He was always gentle and cheerful, and was also a great speaker. I was impressed by the memorable speeches in several international conferences by Merton Sandler and Gerald Stern. I clearly remember his great speech after dinner in the 4th International Catecholamine Symposium in USA in
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1978, adding much humour even presenting slides written in Japanese. When he was invited to Japan to present his special lecture in a mass spectrometry conference, he also kindly visited my laboratory at School of Medicine, Nagoya University. He presented an impressive lecture on GC–MS, and we had unforgettable pleasant time with my colleagues. When I visited Merton in London at the 12th International Symposium on Parkinson’s disease in 1997, he kindly invited me to his house. I was very grateful to Merton and his wife Lorna for their warm hospitality. I will miss Merton with my great admiration for him both in science and in his decent personality. Toshi Nagatsu
Merton Sandler There was so much that was memorable about Merton and his contributions that it is difficult to know where to start. As a scientist, his work was marked by a wide-ranging interests, enthusiasm and knowledge. He could never be accused of tunnel vision in his research life spent in examining the involvements of amines and their metabolism in diseases that ranged from depression, through migraine and schizophrenia to preeclampsia and jet lag. His enthusiastic divergent approach spawned a wide range of ideas and concepts, which have, and should continue to stimulate other researchers. His, early investigations on the effects of amine precursors on the lag in response to antidepressants and the development of the tyramine test for depression and other diseases were particularly influential. One should also mention his after-dinner speeches, latterly often illustrated by slide shows. These were witty accounts of the people and ideas arising from the meetings. They were always to the point but never unkind, I think that those who gave presentations would not have been offended by their becoming meeting highlights in their own right. In his biographical details published in Debrette’s People of Today he lists his recreations as reading, listening to music and lying in the sun. However, he was also concerned with, what are said to be, the usual male preoccupations with sex, drinking and fighting; having edited scholarly volumes on the pharmacology of sexual behaviour, wine and aggression. Merton will be missed as a stimulating scientist, raconteur and bon viveur and also for his kindness and generosity to others working in his fields. His influences will persist for many years to come. Keith Tipton
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Obituary
We remember Merton Merton Sandler was the most unforgettable person we have ever met. In fact, we knew a lot about him from his friend, Michael Pare, who came to NIH to work in the Laboratory of Clinical Science in the National Institute of Mental Health, in Bethesda, which was headed by Dr. Seymour Kety. Michael had served in the same unit during World War II and shared quarters. Mike remembered that Merton’s father sent Kosher Salami, because, at that time, Merton was an observant Jew. He regaled us with accounts of Merton’s ingenious observations and rare humour. When we came to England in 1964, Mike and Barbara invited Merton, Lorna and their first two children (more to come later) to their home and we met and it began as a wonderful friendship. Across the Atlantic and over many years, that friendship and common interests in science endured. On every visit to England, usually to attend symposia or the like, we always arranged to see the Pares and Merton and Lorna. We visited the Sandlers home in London, their summer cottage in Redlynch, and another home in Nice. On one occasion, Merton took us to Stonehenge, on another to his club, the Athenaeum, with Lorna, for dinner. In 1976, Merton became a Foreign Fellow of the American College of Psychopharmacology, which often met in San Juan, Puerto Rico. He gave a Key Note Address, which was outstanding not only for the Science but for the clarity and articulate delivery. He was sought after as a speaker at dinners, where his wit enraptured the audience, using references, in a slide show, to obscure papers in journals that most of us did not even know existed. He once told us that his ‘‘spontaneous remarks’’ were the result of hours of preparation! At the ACNP meetings, which Merton attended almost yearly (sometimes accompanied by Lorna), he would particularly enjoy the sun and strolling down to the pier overlooking the sea. Privately he would tell us about Lorna, his children and how lucky he was to have good friends and colleagues, especially Vivette Glover. When we learned that Merton was invited to lecture in Montreal, Rita told him to contact her mother. He did, had Friday Night Dinner at her home with all in the family. They were enchanted by Merton and very much enjoyed his visit. The next day, Phil, Rita’s brother, spent the day showing Merton the sites to be seen in Montreal. Irv was a speaker at the Festschrift honouring Merton at the Royal Society of Medicine in September of 1991 and co-honoree at a Monoamine Oxidase Workshop hosted by Keith Tipton in Galway, Ireland in August of the following year. We both attended the Norman Weiner Festschrift in Denver, Colorado in 1993. That year, we suspect that he
Obituary
and Mike Pare were instrumental in having Irv elected to Honorary Member of the Royal Society of Medicine. Merton travelled widely and we have photos of Merton in Kyoto, sitting next to Irv in front of a Geisha, with her chalk white-coated face. He asked Irv if he noted that she was pale! In a note to me in 1996, Merton wrote to me, regarding one of the ACNP meetings, ‘‘As I watch Irv complete his sixty-seventh length of the swimming pool, suddenly I realize how a butterfly, beating its wings in Tokyo, can cause a hurricane in the Caribbean. What we have to do, therefore, to make Puerto Rico safe, is to get rid of all those Japanese butterflies.’’ I also treasure an e-mail that Merton sent to me only a relatively short while ago (2012). Its contents are attached below. When Merton retired, he was offered several opportunities to continue his research in the US, but he refused, he told us ‘‘It was always about me, but now it’s Lorna’s turn and I want to support her as she did me for so many years.’’ That was our Merton! As a valued scientist-physician, brilliant speaker and humourist, kind, loving husband, father and grandfather and our very special endearing friend, he will be very much missed by all of us. E-mail from Merton Dear Irv and Rita, I think of you nearly every day but thanks to sloth and indolence, I never seem to get round to writing! What gave me a jolt was flicking through the ACNP Handbook and finding that my own e-mail address was out of date by 3 or 4 years! So that’s why the well is running dry—with respect to messages from American chums. I admit, too, that death might get in the way—but not very often!! So, I
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said to Lorna, ‘‘Let’s go to the ACNP meeting this year’’ but, alas, she vetoed the idea on the grounds that she only goes to places where they speak foreign languages: I am a sad man! Well! The years seep by—it’s almost time for my annual Haftorah Yonah. So far, we’ve had two bar—and one batmizvah out of eleven, with another barmitzvah in the new year. TG we are both well but we’ve quietened down on the foreign travel; indeed, we sold our French house last year—it was such a schlepp to get there! On the other hand, we had the builders in at Redlynch and increased the size of the house by 50 %—we cordially invite you both there, as long as you don’t mind sharing the bed with a few grandchildren. Well, now, do you think you can forgive the long silence? We’d love to hear how you are and that your family prospers. Tell all! Love, Merton Irwin and Rita Kopin
References Pare CM, Sandler M (1959) A clinical and biochemical study of a trial of iproniazid in the treatment of depression. J Neurol Neurosurg Psychiatry 22:247–251 Sandler M (2001) Neurotrophins: possible role in affective disorders. Hum Psychopharmacol 16(1):61–64 Sandler M (2004) My fifty years (almost) of monoamine oxidase. Neurotoxicology 25(1–2):5–10
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OBITUARY
Merton Sandler (March 1926–August 2014)
Ó Springer-Verlag Wien 2014
Merton Sandler was a pioneer of Psychopharmacology, and published influential scientific papers in the field for nearly 50 years. He formulated the monoamine hypothesis of depression in 1959. He, together with his friend and psychiatrist Mike Pare, confirmed that iproniazid acted as an antidepressant. It had already been reported that this drug acted to inhibit the enzyme monoamine oxidase. They, therefore, suggested that depression was caused by a deficiency of monoamines in the brain (Pare and Sandler 1959). This was at a time when most psychiatry was still quite psychoanalytic, and was part of the beginning of biological psychiatry. He remained interested in monoamine oxidase for the rest of his working life (Sandler 2004). He and his colleagues demonstrated that the enzyme had multiple forms, and that deprenyl, a selective inhibitor of monoamine oxidase B was helpful and safe in the treatment of Parkinson’s disease. In later years, he and colleagues discovered the endogenous monoamine oxidase inhibitory activity, which he named tribulin (after trials and
tribulations) and identified the selective B inhibitory component as isatin. In the early days he experimented on himself. He used to describe how he took reserpine and it made him, usually a very calm man, aggressive towards his wife Lorna. Luckily the effect soon wore off. He continued to encourage members of his lab to test things on themselves. In studies of the effects of wine in triggering migraine, we all drank cold red wine or an equivalent amount of vodka in lemonade in darkened bottles the first thing in the morning. The red wine certainly made many of us feel quite unwell. Some bottles of wine remained in the lab for a while, raising eyebrows in visitors. When we finally had to clear out the labs where he had worked for many decades we found an unlocked cupboard full of LSD, amphetamines, and many other banned substances. Men dressed in what looked like space suits came to clear it all out. The labs certainly did not look state of the art, In the 1990s they were used to make a black and white film of research in the 1930s. However, Merton was quick to appreciate and invest in new techniques and was an early user of mass spectrometry. As well as the well-trodden pathways of 5-HT, dopamine and noradrenaline he loved the more obscure byways of tyramine, phenylethylamine, isoquinolines and carbolines. He developed the tyramine test as a marker for depression, where the subject took a 100 mg capsule of tyramine and the level of tyramine sulphate conjugate excreted in the urine, was measured. This too was tested on members of the lab. A more recent interest was in the neurotrophins, and especially the role of BDNF in depression (Sandler 2001). When he started to be interested
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172
in this it seemed a really obscure topic, but current research has shown his foresight in this too. His extraordinary breadth of interest is shown by the range of topics of the books he wrote or edited. Their titles include Wine, Mental Illness in Pregnancy and the Puerperium, Psychopharmacology of Anticonvulsants, Psychopharmacology of Food, Design of Enzyme Inhibitors as Drugs, Migraine, 5-HT in Psychiatry, Sexual Behaviour: Pharmacology and Biochemistry, Psychopharmacology of Alcohol, Migraine: Pharmacology and Genetics, Progress in Catecholamine Research, Psychopharmacology of Aggression Parkinson’s Disease, as well as one on Medical Humour and Anecdotes. Merton spent most of his working life as Professor of Chemical Pathology at Queen Charlotte’s maternity hospital. He took the job originally as he had a theory about the role of 5-HT in preeclampsia. He disproved his own theory within 6 months and this gave him freedom to work on what he wanted for the rest of his life. His role in chemical pathology only took up a few days each year, as he had a good team working with him on this. However, although in general he lost interest in the science of maternity he organized the first meeting on mental illness in pregnancy and the puerperium and edited the first book on the subject. He also was instrumental in setting up the Association for Postnatal Illness. Merton loved to travel to conferences around the world. He and his wife Lorna were often to be seen by the pool. The ACNP meeting in Puerto Rico was a particular favourite. But he was always networking, talking, discussing new ideas, stimulating new avenues of research, and forging new collaborations and making connections for others. He was very funny too, and the best after-dinner speaker on the conference circuit. Merton had colleagues from the UK, many countries in Europe, Israel, USA, Russia, India, Japan, and Australia. All regarded him as their friend. He never said a bad word about anyone. He had especial links with Russia; Lorna is a translator and her languages include Russian. He was a great supporter of Russian Jews in the Soviet days and helped some such as Gregory Oxenkrug to leave; but he also maintained close contact with non-Jewish Russians, such as Alexei Medvedev, too. I worked with him for over 20 years. He made science fun. Vivette Glover
Merton Sandler: an appreciation I first met Merton Sandler in 1963 at the old Allan Memorial Institute, at McGill University, where he was visiting Theodore L Sourkes laboratory, where I was an
123
Obituary
M.Sc. Student. I always wanted to get back to England after finishing my Ph.D. with Sourkes, who suggested I should go to Merton Sandler’s laboratory for my postdoctoral. Indeed Merton accepted me and in 1966, I joined him and was with him until 1972. Besides the significant works we published, these were to be the most informative time of my scientific life, learning from Merton to write papers and how to give informative lectures. I came to Merton to continue my studies on monoamine oxidase (MAO) and its inhibitors, which I had started at McGill and where I had shown that MAO existed in two forms. I continued to work on rat brain MAO and was the first to study human brain MAO, which were provided by the city of London neuropathologist and psychiatrist Mike Pare. We showed that extrapyramidal region of human brain, unlike rat brain, had high activity for dopamine and benzylamine metabolism. We also received brains obtained from patients who had terminal diseases, but were treated with various MAO inhibitors for their depression. These inhibitors had differential effects on MAO activity in various brain regions and serotonin and noradrenaline metabolism. These were the first studies on human brain MAO and its multiple forms, which resulted in us receiving the International Anna Monika Prize. We continued to study MAO and tyramine metabolism in dietary migraine patients, who associated their headaches with certain foods such as cheese and chocolate. We discovered that they had low platelet MAO activity and had a defect in tyramine metabolism via MAO and conjugation. For these studies Merton and I were given the British Migraine Association Gold Medal. When I joined Merton one of the things he wanted me to study was the action of the anti-angina Hoechst drug, segontin, on catecholamine metabolism in man. It was thought that the drug had similar activity to reserpine. So, we started probably the craziest set of studies in volunteers, which included us and various members of the Merton’s laboratory. The study comprised of giving intravenous segontin and comparing it to intravenous reserpine and amphetamine and drinking one third bottle of vodka in 1 h. The idea being to collect urine for 24 h and examine urinary catecholamines and metabolites. If I recall correctly these were the first such studies in volunteers. It would not be allowed today, since in those days there was no Helsinki Committee. Intravenous amphetamine was great but had its down side. Reserpine was terrible, both Merton and I were reserpinized for a month and were paranoiac. He told me that Lorna constantly told him so. I will always be most grateful and indebted to Merton for receiving a position at Oxford University with David Grahame-Smith and introducing me to Peter Riederer in 1973. These two events were to completely alter my scientific life and direction.
Obituary
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Merton was always most generous and supportive to his colleagues. We travelled to numerous conferences and meetings before and after I left him. One of the delights was to hear Merton’s brilliant witty summary of the meetings and after-dinner speeches, for which he became world renowned. I well remember the first time he ever had to give an after-dinner talk. It was the 1972 New York Columbia University Serotonin Meeting, which his friend Ermino Costa had organized. Merton was asked to give after-dinner talk 2 days before the end of the meeting. He told me he was going to leave the meeting to prepare his talk, because he was nervous and never had given after-dinner talk. He came back 2 days later like Moses out of the desert. A changed man and gave a most unbelievably funny talk that had most of audience falling off their chairs. This started a new career for him and no conference would finish without Merton’s speech. Many of his speeches were recorded by Earl Usdin. No one could match him in this and there will not be another like him. He had an amazing command of the English language and he always learned new words to introduce in his scientific papers. There will not be one like him. He was sorely missed when he had to retire and will be, especially as a colleague and friend.
In October 1974, Moussa Youdim and I discussed this issue again in Vienna and I convinced him to use (–) deprenyl for the treatment of ON–OFF phases in PD. The beneficial effects of this clinical trial were published in 1975. In retrospect, this idea at Merton Sandler’s laboratory had wideranging consequences for the benefit of PD patients. Merton Sandler and I continued our collaboration especially when Gavin Reynolds joined the laboratory at the Department of Neurology, Lainz Hospital, Vienna, for about 2 years and concentrated his work on L-deprenyl’s effect on phenylethylamine and amphetamine. A final cooperation with Merton has been the detection of quinolinic acid in postmortem brain tissue of Alzheimer’s disease in 1989. We had continuous contact at meetings, conferences and congresses. And the song and dance at my 60th birthday party was an unforgettable event for everyone listening to Merton Sandler’s and Gerald Stern’s performance. The brilliance of their sketch and their ‘‘literally English’’ was a lot of fun for all attendees. Merton Sandler has been influential for my career and I will miss him as a wonderful friend.
Moussa B. H. Youdim
Memoirs on Merton Sandler
Merton Sandler: a personal appreciation I was one of those post-docs visiting Merton Sandler’s laboratory. In early November 1973, I started with Linda Fellows to develop a method for the proper detection of MHPG using gas chromatography. Merton Sandler’s laboratory was at that time the centre for GC and GC–MS. They had more than 15 GCs available with every useful methodological variation. Linda and I developed this sensitive assay and together with Merton Sandler published a paper in 1975. It was at this research visit that I told Merton Sandler about the problems with ON–OFF phases in PD and that we were looking for a MAO inhibitor without major side effects, for example, with no liver toxicity and blood pressure crisis. The reason for this idea was based on our own findings of diurnal fluctuations of MAO activity and the in principle beneficial use of various MAO inhibitors in the treatment of PD as shown in the early 60s by Walther Birkmayer/Oleh Hornykiewicz and Andre Barbeau and colleagues. Merton proposed to invite Moussa Youdim, who worked at that time at Grahame-Smith’s laboratory in Oxford, to visit Queen Charlottes and to discuss this idea but it was not pursued at this occasion.
Peter Riederer
I had always pleasant and enjoyable memoirs with Merton Sandler in discussing science and a wide range of topics, whenever I met him in many international conferences in USA, Europe, Israel, and Japan. Merton was a pioneering worker in chemical pathology and in psychopharmacology, mainly in the field of biogenic amines where I have been working. Merton and his colleagues presented many important discoveries which linked basic science to clinical science. One remarkable finding is that dopamine is the substrate of monoamine oxidase B in the human brain. This work leads to the present clinical use of (–) deprenyl (selegiline) in the treatment of Parkinson’s disease. Merton was a pioneer in introducing gas chromatography with mass spectrometry (GC–MS) for the analysis of biogenic amines. For the work in GC–MS he was invited to several international conferences including the mass spectrometry conference in Japan. Merton was a very kind and warm-hearted person and always helped young scientists internationally. He was always gentle and cheerful, and was also a great speaker. I was impressed by the memorable speeches in several international conferences by Merton Sandler and Gerald Stern. I clearly remember his great speech after dinner in the 4th International Catecholamine Symposium in USA in
123
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1978, adding much humour even presenting slides written in Japanese. When he was invited to Japan to present his special lecture in a mass spectrometry conference, he also kindly visited my laboratory at School of Medicine, Nagoya University. He presented an impressive lecture on GC–MS, and we had unforgettable pleasant time with my colleagues. When I visited Merton in London at the 12th International Symposium on Parkinson’s disease in 1997, he kindly invited me to his house. I was very grateful to Merton and his wife Lorna for their warm hospitality. I will miss Merton with my great admiration for him both in science and in his decent personality. Toshi Nagatsu
Merton Sandler There was so much that was memorable about Merton and his contributions that it is difficult to know where to start. As a scientist, his work was marked by a wide-ranging interests, enthusiasm and knowledge. He could never be accused of tunnel vision in his research life spent in examining the involvements of amines and their metabolism in diseases that ranged from depression, through migraine and schizophrenia to preeclampsia and jet lag. His enthusiastic divergent approach spawned a wide range of ideas and concepts, which have, and should continue to stimulate other researchers. His, early investigations on the effects of amine precursors on the lag in response to antidepressants and the development of the tyramine test for depression and other diseases were particularly influential. One should also mention his after-dinner speeches, latterly often illustrated by slide shows. These were witty accounts of the people and ideas arising from the meetings. They were always to the point but never unkind, I think that those who gave presentations would not have been offended by their becoming meeting highlights in their own right. In his biographical details published in Debrette’s People of Today he lists his recreations as reading, listening to music and lying in the sun. However, he was also concerned with, what are said to be, the usual male preoccupations with sex, drinking and fighting; having edited scholarly volumes on the pharmacology of sexual behaviour, wine and aggression. Merton will be missed as a stimulating scientist, raconteur and bon viveur and also for his kindness and generosity to others working in his fields. His influences will persist for many years to come. Keith Tipton
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We remember Merton Merton Sandler was the most unforgettable person we have ever met. In fact, we knew a lot about him from his friend, Michael Pare, who came to NIH to work in the Laboratory of Clinical Science in the National Institute of Mental Health, in Bethesda, which was headed by Dr. Seymour Kety. Michael had served in the same unit during World War II and shared quarters. Mike remembered that Merton’s father sent Kosher Salami, because, at that time, Merton was an observant Jew. He regaled us with accounts of Merton’s ingenious observations and rare humour. When we came to England in 1964, Mike and Barbara invited Merton, Lorna and their first two children (more to come later) to their home and we met and it began as a wonderful friendship. Across the Atlantic and over many years, that friendship and common interests in science endured. On every visit to England, usually to attend symposia or the like, we always arranged to see the Pares and Merton and Lorna. We visited the Sandlers home in London, their summer cottage in Redlynch, and another home in Nice. On one occasion, Merton took us to Stonehenge, on another to his club, the Athenaeum, with Lorna, for dinner. In 1976, Merton became a Foreign Fellow of the American College of Psychopharmacology, which often met in San Juan, Puerto Rico. He gave a Key Note Address, which was outstanding not only for the Science but for the clarity and articulate delivery. He was sought after as a speaker at dinners, where his wit enraptured the audience, using references, in a slide show, to obscure papers in journals that most of us did not even know existed. He once told us that his ‘‘spontaneous remarks’’ were the result of hours of preparation! At the ACNP meetings, which Merton attended almost yearly (sometimes accompanied by Lorna), he would particularly enjoy the sun and strolling down to the pier overlooking the sea. Privately he would tell us about Lorna, his children and how lucky he was to have good friends and colleagues, especially Vivette Glover. When we learned that Merton was invited to lecture in Montreal, Rita told him to contact her mother. He did, had Friday Night Dinner at her home with all in the family. They were enchanted by Merton and very much enjoyed his visit. The next day, Phil, Rita’s brother, spent the day showing Merton the sites to be seen in Montreal. Irv was a speaker at the Festschrift honouring Merton at the Royal Society of Medicine in September of 1991 and co-honoree at a Monoamine Oxidase Workshop hosted by Keith Tipton in Galway, Ireland in August of the following year. We both attended the Norman Weiner Festschrift in Denver, Colorado in 1993. That year, we suspect that he
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and Mike Pare were instrumental in having Irv elected to Honorary Member of the Royal Society of Medicine. Merton travelled widely and we have photos of Merton in Kyoto, sitting next to Irv in front of a Geisha, with her chalk white-coated face. He asked Irv if he noted that she was pale! In a note to me in 1996, Merton wrote to me, regarding one of the ACNP meetings, ‘‘As I watch Irv complete his sixty-seventh length of the swimming pool, suddenly I realize how a butterfly, beating its wings in Tokyo, can cause a hurricane in the Caribbean. What we have to do, therefore, to make Puerto Rico safe, is to get rid of all those Japanese butterflies.’’ I also treasure an e-mail that Merton sent to me only a relatively short while ago (2012). Its contents are attached below. When Merton retired, he was offered several opportunities to continue his research in the US, but he refused, he told us ‘‘It was always about me, but now it’s Lorna’s turn and I want to support her as she did me for so many years.’’ That was our Merton! As a valued scientist-physician, brilliant speaker and humourist, kind, loving husband, father and grandfather and our very special endearing friend, he will be very much missed by all of us. E-mail from Merton Dear Irv and Rita, I think of you nearly every day but thanks to sloth and indolence, I never seem to get round to writing! What gave me a jolt was flicking through the ACNP Handbook and finding that my own e-mail address was out of date by 3 or 4 years! So that’s why the well is running dry—with respect to messages from American chums. I admit, too, that death might get in the way—but not very often!! So, I
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said to Lorna, ‘‘Let’s go to the ACNP meeting this year’’ but, alas, she vetoed the idea on the grounds that she only goes to places where they speak foreign languages: I am a sad man! Well! The years seep by—it’s almost time for my annual Haftorah Yonah. So far, we’ve had two bar—and one batmizvah out of eleven, with another barmitzvah in the new year. TG we are both well but we’ve quietened down on the foreign travel; indeed, we sold our French house last year—it was such a schlepp to get there! On the other hand, we had the builders in at Redlynch and increased the size of the house by 50 %—we cordially invite you both there, as long as you don’t mind sharing the bed with a few grandchildren. Well, now, do you think you can forgive the long silence? We’d love to hear how you are and that your family prospers. Tell all! Love, Merton Irwin and Rita Kopin
References Pare CM, Sandler M (1959) A clinical and biochemical study of a trial of iproniazid in the treatment of depression. J Neurol Neurosurg Psychiatry 22:247–251 Sandler M (2001) Neurotrophins: possible role in affective disorders. Hum Psychopharmacol 16(1):61–64 Sandler M (2004) My fifty years (almost) of monoamine oxidase. Neurotoxicology 25(1–2):5–10
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