Arrel D. Toews and Helga Jurevics

University of North Carolina (UNC) Neuroscience Center, CB# 7250, Chapel Hill, NC  27599-7250, USA
email: atoews@med.unc.edu

Published online: 19 May, 2004  | Article readership
Copyright © 2004 A D Toews and H Jurevics, Licensee Neurobiology of Lipids

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PIERRE MORELL SELECTED PICTURES SELECTED PUBLICATIONS OF PIERRE MORELL

Pierre Morell, Professor of Biochemistry and Biophysics at the University of North Carolina-Chapel Hill, passed away on July 15, 2003 after a brief illness.  Pierre was educated at the Bronx High School of Science, Columbia University, and The Albert Einstein College of Medicine, doing post-doctoral research with Norm Radin at the University of Michigan-Ann Arbor.  Pierre was a leader in the field of myelin metabolism, in particular the synthesis and turnover of myelin lipids (glycosphingo-lipids, phospholipids, cholesterol).  A re-curring theme was use of altered states (e.g., mutant or genetically engineered mice, toxicants, altered nutritional states) to examine myelin metabolism and function.  He was a tireless supporter of various scientific societies, including the International Society for Neurochemistry, and he provided wise counsel and advice to several generations of neuroscientists throughout the world. His premature passing has left a void that will be difficult to fill.  A memorial fund at UNC has been established.

The neuroscience community lost one of its most valued members, and a great many neuroscientists lost a treasured friend and colleague, when Pierre Morell passed away on July 15, 2003 following a brief yet valiant fight against brain cancer. Pierre was a brilliant scientist, a distinguished and highly respected university professor, a tireless supporter of numerous scientific endeavors outside his own lab, but most importantly, a very kind, generous, and caring human being.  We are honored and humbled by the request to provide a memorial tribute to Pierre.  Because of our close association and daily interactions with Pierre for a good many years, this will perhaps have a rather personal tone, but one we feel is appropriate given the nature of the man we now remember.

Our reflections on Pierre’s life fittingly begin with his parents, who were very important to him from the moment of his birth until his last breath.  In the late 1930s, the newlywed Anatol and Halina (Leszczynska) Mosewicki escaped the pre-war horrors of Nazi-occupied Poland, crossing the vast frozen Siberian spaces of Stalin’s Russia and gaining ship’s passage to Japan.  After a brief stay in Japan and passage through the United States, they eventually arrived at the Sosua refugee community in the Dominican Republic where, on 10 December 1941, Pierre was born.  After several years, the young family realized their dream of coming to the United States, settling in New York City, where Anatol soon began his long and successful career as an academic research scientist in the Biochemistry Department of the Albert Einstein College of Medicine.  Anatol’s collaborative efforts with Gilbert Ashwell on hepatic glycoprotein receptors and their role in clearing circulating glycoproteins represent some of the early seminal work demonstrating the importance of carbohydrate moieties on glycoproteins in defining biological functions and metabolism.  Pierre’s mother, Helena, enjoyed two successful careers, first as a biochemist and then as a social worker.  Both are now retired to Stoney Brook, NY, adjacent to the Stoney Brook campus where they remain in the midst of a caring community of scholars and thinkers.

The young Pierre attended PS6 elementary school in Manhattan and then the prestigious Bronx High School of Science.  He attended Columbia University, majoring in Chemistry and competing on the varsity swim team.  Following graduation in 1963, Pierre began his graduate studies in the Biochemistry Department at Einstein, working in the laboratory of Julius Marmur on early studies of RNA sequences in bacteria.  The first of his many publications appeared in P.N.A.S. in 1965.

Following his graduate studies, Pierre accepted a post-doc in Norm Radin’s lab at the University of Michigan in Ann Arbor.  His early work on sphingolipid biosynthesis began the path that led to his long and distinguished research career examining various aspects of myelin metabolism.  He quickly corrected the established but incorrect pathway for synthesis of cerebroside, an early indicator of his uncanny ability to zero in on problems and weaknesses and attack them with a vengeance, a trait he retained throughout his life.  Peter Braun was also in the Radin lab at this time, with Joyce Benjamins across the hall in Bernie Agranoff’s lab, and these three young scientists quickly became valued colleagues and close friends.

In 1968, Robert Katzman, Chair of Neurology at Einstein, gave Pierre his first faculty job.  He provided Pierre with 300 sq. ft. of lab space and some initial research support, but noted his expectation that Pierre would “soon apply for your own grant to meet your continuing research needs.”  Pierre of course did exactly that – his initial NIH grant on “Assembly and Maintenance of the Myelin Sheath” was in its 33rd year of continuous funding at the time of his death.  Bill Norton, Kuni Suziki, Bob Ledeen, and countless others became his valued mentors, colleagues, and lifelong friends during his years at Einstein. Pierre continued his studies on cerebroside biosynthesis, with Elvira Costantino-Ceccarini as his first postdoc. Their work included the synthesis of brain sphingolipids and their relation to myelination, the earliest studies of this important relationship.  He was involved in very early studies characterizing ceramide galactosyltransferase, the enzyme responsible for synthesizing cerebroside, and many years later, in collaboration with Brian Popko, in cloning and genomic studies of this enzyme as well.  Pierre was among the first to realize the potential of mutant mice, well before the transgenic and gene knockout era, to show how alterations in a specific gene can compromise myelin function and metabolism, and he remained active in this area until his death.

In 1973, Pierre moved to the University of North Carolina at Chapel Hill (UNC), where he remained for the rest of his life.  Early work at UNC involved a very productive collaboration with Joyce Benjamins examining kinetics of synthesis and assembly of individual lipid and protein components into myelin. A recurring theme in Pierre’s work was the use of neurotoxicants and other perturbed systems as models to learn more about both normal and abnormal metabolism in myelin.  Notable among these studies was elucidation of the underlying metabolic defect in tellurium-induced demyelinating neuropathy (with Maria Wagner, Jean Harry, Arrel Toews, and Tom Bouldin as collaborators). Under Pierre’s guidance, his lab was able to determine that tellurium’s action involves a specific inhibition of squalene epoxidase, an enzyme in the cholesterol biosynthetic pathway.  The resulting block in cholesterol synthesis causes a cholesterol deficit and a massive accumulation of squalene in sciatic nerve.  Lack of cholesterol required for continued accumulation and maintenance of myelin results in the demyelination and its associated neuropathy.

The source of the vast quantity of cholesterol required for normal myelin formation in the peripheral nervous system (de novo synthesis, from circulating serum lipoproteins, or both) was also determined by Pierre’s lab (Helga Jurevics and Arrel Toews were major collaborators).  Using an experimental approach pioneered by John Dietschy, John Andersen, Stephen Turley, and their colleagues, Pierre’s lab used tritiated water as a cholesterol precursor to determine the absolute in vivo synthesis rates and absolute amounts of accumulation of cholesterol in sciatic nerve during development and during remyelination following demyelinating insult.  In both situations, all cholesterol required for myelin formation was synthesized locally, not imported from blood.  The same was shown to be true for the cholesterol required for myelin formation in the CNS.

This experimental approach was also utilized in Pierre’s lab to determine absolute in vivo synthesis rates and accumulation of the “myelin-specific” lipid, cerebroside, and its sulfated derivative, sulfatide.  Synthesis and accumulation of these glycosphingolipids in brain track closely the accumulation of myelin, making them sensitive and reliable markers for quantitating myelin formation.  Most recently, in studies on Cuprizone-induced demyelination and subsequent remyelination in the CNS (in collaboration with Glenn Matsushima, Jeffrey Mason, and others mentioned above), in vivo synthesis rates for myelin glycosphingolipids were used to quantitate the degree of remyelination following the Cuprizone-induced demyelinating insult.  This methodology allows determination of in vivo synthesis rates of myelin over a relatively short time period (several hours), making it potentially very useful for determining, in a living animal, the efficacy of various drugs or growth factors that might promote remyelination.

Pierre was also active in the field of axonal transport, particularly with respect to the deposition and transfer of axonally transported membrane lipids (phospholipids, cholesterol), as well as the mitochondria-specific cardiolipin; Regina Armstrong, Jeffry Goodrum, Bill Blaker, and Arrel Toews, among others, were significantly involved.

Numerous post-docs (Sheldon Miller and Richard Wiggins were the first at UNC, one of the authors (AT) the third) and countless graduate students all benefited from their interactions with Pierre in the lab and in the world outside the lab as well.  Pierre assembled and edited the first edition of his “Myelin” book in 1977 when only 35 years old, and for many years, this and a subsequent edition were the definitive references on myelin for both beginners and established investigators.  This accomplishment showed not only his precocious development as a neuroscientist, but also his organizational skills and underlying drive to get things done right and done well, traits he put to good use in many areas of science and academia.

Pierre was very active in many aspects of the neuroscience and general academic community, both at UNC and on national and international levels as well.  For 10 years, he was Director of the UNC Curriculum in Neurobiology, the second oldest neuroscience training program in the US; he presided over unprecedented growth in neuroscience graduate training and established UNC as a leader in this field.  Not only students, but also post-docs, junior faculty, staff, and many others benefited from his leadership and guidance, because their development and professional growth were always important priorities for Pierre.  He was a wise mentor and counselor to more than a generation of neuroscientists, and his willingness to share his knowledge, advice, and guidance extended far beyond the boundaries of his University.  This, even more than his considerable scientific accomplishments, will perhaps be his most lasting legacy.

Pierre was an early, tireless, and perpetual supporter of the International Society for Neurochemistry (ISN) and the American Society of Neurochemistry (ASN), as well as the Society for Neuroscience (SFN).  He cared deeply about their stability and future, and worked hard behind the scenes to make them successful.  He served on the Councils of both the ASN and ISN, on countless committees, and as Program Chair for the Charleston 1979 ASN and Portugal 1989 ISN meetings.  A great many readers of this tribute will also have encountered the pointed thoughts and not-always-welcome advice of Pierre regarding submitted manuscripts and grants.  He was the joy of journal editors and Executive Secretaries, and the bane of submitting authors and grant applicants, further demonstrations of his uncompromising insistence on excellence and integrity in scientific research.  He served on numerous NIH and National Multiple Sclerosis Society study sections, as well as on the editorial boards of numerous journals, including the Journal of Neurochemistry and Brain Research.  He was a frequent reviewer for a host of other journals, including Lipids and The Journal of Lipid Research.

Despite his seemingly constant attention to scientific and academic matters, Pierre was also a loving and devoted husband and father.  Married to Bonnie Jean Brown, whom he met during a summer school interlude at UC-Berkeley (Pierre from Columbia, Bonnie from Cornell), theirs was a happy and lasting relationship blessed with two children, Sharon and David.  Those of you who knew Pierre may have difficulty visualizing him as a doting grandfather, but he was exactly that.  His granddaughter Katy, born in 2002, brought him great joy and happiness during his final year.

A realistic review of the life and times of Pierre Morell cannot ignore a very important aspect of his life outside the lab (but not outside the realm of science!).  Pierre was an avid scuba diver, and his budding love for this activity in the early 1990s quickly (and typically) evolved into a role as distinguished teacher.  Quickly becoming certified at all levels of instruction, he taught several wildly popular courses in scuba diving at UNC and was locally famous for taking his students to the Florida Keys for their final checkout/certification dives.  His appointment as Adjunct Professor of Physical Education and Exercise Sport Science was among his proudest accomplishments, and his energy, enthusiasm, and guidance will be sorely missed there as well.

Pierre’s premature passing has left a void in the neuroscience community and in many lives that will be difficult to fill.  His sharp wit, his lively and enthusiastic approach to science and to life in general, his incisive (and often wildly inappropriate) remarks about all aspects of life, and his generous assistance and advice will all be sorely missed.  Although we will all miss Pierre very much, we are also all better for our associations with this truly remarkable and cherished colleague, teacher, and friend.

A memorial fund has been established and contributions may be made to the address given below: “Pierre Morell Memorial Fund” The Medical Foundation of North Carolina, Inc., 880 Airport Road, Chapel Hill, NC 27514.
 

SELECTED PICTURES OF PIERRE MORELL  Note: you may need to resize your browser window for better picture view (To see other pictures of Pierre Morell please view the Acrobat .PDF reprint of this article, available at this link) A, Pierre at work in his office (rejecting a submitted mss); B, Director, UNC Curriculum in Neurobiology (1978-1988); C, Pierre with his parents, Helena and Anatol (Stoney Brook, NY, 2002); D, Pierre, Maurice Rapport, Norm Radin & Dave Bowen (Ann Arbor, MI, 1972); E, Bernard Droz, Arrel Toews, Pierre and Ephraim Yavin (Phospholipids Satellite Meeting, Harrison Hot Springs, BC, after ISN, Vancouver meeting); F, Pierre and Bonnie (Capri, Italy, 1996, Smith-Lemli-Opitz meeting); G, Pierre, Professor of Scuba and Underwater Science, 2002. To see more pictures please open Acrobat .PDF reprint of this article.

1. Dubnau D, Smith I, Morell P, Marmur J. Gene conservation in Bacillus species 1. Conserved genetic and nucleic acid base sequence homologies.  Proc Natl Acad Sci (USA). 54, 491-8 (1965) [ PubMed ][ Back2Text ].

2. Morell P, Smith I, Dubnau J, Marmur J. Isolation and characterization of low molecular weight ribonucleic acid species from Bacillus subtilis. Biochemistry. 6, 258-65 (1967) [ PubMed ][ Back2Text ].

3. Morell P, Radin N. Synthesis of cerebroside by brain from uridine diphosphate galactose and ceramide containing hydroxy fatty acids.  Biochemistry. 8, 506-12 (1969) [ PubMed ][ Back2Text ].

4. Braun PE, Morell P, Radin N. Synthesis of C18- and C20- dihydrosphingosines, ketodihydrosphingosines and ceramides by microsomal preparations from mouse brain. J Biol Chem. 245, 335-41 (1970) [ PubMed ][ Back2Text ].

5. Costantino-Ceccarini E and Morell P. Quaking mouse: In vitro studies of brain sphingolipid biosynthesis. Brain Res. 29, 75-84 (1971) [ PubMed ][ Back2Text ].

6. Morell P and Braun P. Review.  Biosynthesis and metabolic degradation of sphingolipids not containing sialic acid. J Lipid Res. 13, 293-310 (1972) [ PubMed ][ Back2Text ].

7. Constantino-Ceccarini E and Morell P. Biosynthesis of brain sphingolipids and myelin accumulation in the mouse. Lipids. 7, 656-9 (1972) [ PubMed ][ Back2Text ].

8. Benjamins JA, Miller S, Morell P. Metabolic relationships between myelin subfractions:  entry of galactolipids and phospholipids. J Neurochem. 27, 565-70 (1976) [ PubMed ][ Back2Text ].

9. Morell P. (Ed) Myelin. 2nd Edition. New York: Plenum Press, 545 pages, Sept 1984, ISBN 0-306-41540-2 [ Find this book at: Kluwer | Bookfinder.com | Alibris ][ Back2Text ].

10. Miller SL, Benjamins JA, Morell P. Metabolism of glycerophospholipids of myelin and microsomes in rat brain. Reutilization of precursors. J Biol Chem. 252, 4025-37 (1977) [ PubMed ][ Back2Text ].

11. Morell P and Norton WT. Myelin. Scientific American. 242, 74-89 (1980) [ PubMed ][ Back2Text ].

12. Toews AD, Saunders BF, Blaker WD, Morell P. Differences in the kinetics of axonal transport for individual lipid classes in rat sciatic nerve. J Neurochem. 40, 555-68 (1983) [ PubMed ][ Back2Text ].

13. Armstrong R, Toews AD, Ray RB, Morell P. Retrograde axonal transport of endogenous phospholipids in rat sciatic nerve. J Neurosci. 5, 965-9 (1985) [ PubMed ][ Back2Text ].

14. Toews AD, Armstrong R, Ray R, Gould RM, Morell P. Deposition and transfer of axonally transported phospholipids in rat sciatic nerve. J Neurosci. 8, 593-601 (1988) [ PubMed ][ Back2Text ].

15. Toews AD, Lee S, Popko B, Morell P. Tellurium-induced neuropathy:  a model for reversible reductions in myelin protein gene expression. J Neurosci Res. 26, 501-07 (1990) [ PubMed ][ Back2Text ].

16. Ousley AH and Morell P. Individual molecular species of phosphatidylcholine and phosphatidyl-ethanolamine in myelin turn over at different rates. J Biol Chem. 267, 10362-69 (1992) [ PubMed ][ Back2Text ].

17. Toews AD, Griffiths IR, Kyriakides E, Goodrum JF, Eckermann C, Morell P, Thomson CE. Primary demyelination induced by exposure to tellurium alters Schwann-cell gene expression: A model for intracellular targeting of NGF receptor. J Neurosci. 12, 3676-87 (1992) [ PubMed ][ Back2Text ].

18. Jurevics H and Morell P. Sources of cholesterol for kidney and nerve during development. J Lipid Res. 35, 112-20 (1994) [ PubMed ][ Back2Text ]

19. Stahl N, Jurevics H, Morell P, Suzuki K, Popko B. Isolation, characterization, and expression of cDNA clones that encode UDP-galactose: ceramide galactosyl-transferase. J Neurosci Res. 38, 234-42 (1994) [ PubMed ][ Back2Text ].

20. Jurevics H. and Morell P. Cholesterol for synthesis of myelin is made locally, not imported into brain. J Neurochem. 64, 895-901 (1995) [ PubMed ][ Back2Text ].

21. Wagner M, Toews A, Morell P. Tellurite specifically affects squalene epoxidase: Investigations examining the mechanism of tellurium-induced neuropathy. J Neurochem. 64, 2169-76 (1995) [ PubMed ][ Back2Text ].

22. Toews AD, Jurevics H, Hostettler J, Roe EB, Morell P. Tissue-specific coordinate regulation of enzymes of cholesterol biosynthesis:  Sciatic nerve vs liver. J Lipid Res. 37, 2502-9 (1996) [ PubMed ][ Back2Text ].

23. Jurevics H, Kidwai FZ, Morell P. Sources of cholesterol during development of the rat fetus and fetal organs. J Lipid Res. 38, 723-33 (1997) [ PubMed ][ Back2Text ].

24. Jurevics H, Bouldin TW, Toews AD, Morell P. Regenerating sciatic nerve does not utilize circulating cholesterol. Neurochem Res. 23, 401-6 (1998) [ PubMed ][ Back2Text ].

25. Muse ED, Jurevics H, Toews AD, Matsushima GK, Morell P. Parameters related to lipid metabolism as markers of myelination in mouse brain. J Neurochem.76, 77-86 (2001) [ PubMed ][ Back2Text ].

26. Jurevics H, Hostettler J, Muse ED, Sammond DW, Matsushima GK, Toews AD, Morell P. Cerebroside synthesis as a measure of the rate of remyelination following Cuprizone-induced demyelination in brain. J Neurochem. 77, 1067-76 (2001) [ PubMed ][ Back2Text ].

27. Matsushima GK and Morell P. The neurotoxicant, Cuprizone, as a model to study demyelination and remyelination in the central nervous system. Brain Pathology.11, 107-16 (2001) [ PubMed ][ Back2Text ].

28. Jurevics H, Largent C, Hostettler J, Sammond DW, Matsushima GK, Kleindienst A, Toews AD, Morell P. Alterations in metabolism and gene expression in brain regions during Cuprizone-induced demyelination and remyelination. J Neurochem.82, 126-36 (2002) [ PubMed ][ Back2Text ].

29. Jurevics H, Hostettler J, Sammond DW, Nave K-A, Toews AD, Morell P. Normal metabolism but different physical properties of myelin from mice deficient in proteolipid protein. J Neurosci Res. 71, 826-34 (2003) [ PubMed ][ Back2Text ].

30. Mason JL, Toews A, Hostettler JD, Morell P, Suzuki K, Goldman JE, Matsushima GK. Oligodendrocytes and progenitors become progressively depleted within chronically demyelinated lesions. Am J Pathol. 164, 1673-82 (2004) [ PubMed ][ Back2Text ].
 

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This article should be cited in the following way: Toews AD and Jurevics H. Pierre Morell tribute for neurobiology of lipids. Neurobiol. Lipids  Vol.3, 3 (2004), Published online May 19, 2004, Available at: http://neurobiologyoflipids.org/content/3/3/ Please note: Because Neurobiology of Lipids is published online only,  the articles are identified with an article number rather than with traditional (printed) page numbers. Adobe Acrobat (.PDF) reprint, however, allows citation with page numbers, and serves the algorithmic needs of tenure committees to count published print pages.