DOCSLIB.ORG

The Lasting Legacy of Donald Metcalf Brty Ku Samson

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Lasting Legacy of Donald Metcalf Brty Ku Samson 14 The Lasting Legacy of Donald Metcalf BRTY KU Samson onald Metcalf, Among the many hon- MD, considered ors and awards he received “the father of were the Albert Lasker oncology-times.com modern hematol- Award for Clinical Medical • Dogy,” died Dec. 15, at age 85, Research, the Gairdner surrounded by his family, in Foundation International Melbourne, Australia. Award, the Royal Medal Professor Emeritus at the of the Royal Society, the University of Melbourne Victoria Prize, and the and the Cancer Council Lifetime Achievement Victoria’s Carden Fellow in Award from American the Division of Cancer and Association for Cancer February 10, 2015 Hematology at the Walter Research in 2007. • and Eliza Hall Institute of “As an experimental pa- Medical Research, he was thologist, I have studied the the first to discover colony- manner in which mature stimulating factors (CSFs), blood cells are formed by hormones that control white ancestral cells in the bone blood cell production to marrow. This required the bolster recovery after cancer development of clonal cul- treatment. ture systems, allowing the Metcalf worked at the progeny of individual cells Oncology Times Walter and Eliza Hall to be analyzed,” Metcalf Institute for 60 years, from wrote for a biographi- 1954 to 2014. After he devel- and Eliza Hall Institute Walter cal sketch for the National oped pancreatic cancer this DONALD W. METCALF, MD (1929-2014) Academy of Sciences at the past August, he continued time of his election as a his research at home until member in 1987. October, when he conducted his final weakened by chemotherapy. This led “The four CSFs were purified and experiment, his colleague, Douglas to development and eventual ap- can now be mass produced in re- Hilton, PhD, the Institute’s Director proval of the drug G-CSF (filgrastim, combinant form. The CSFs are now and a molecular biologist, said in an Neupogen). widely used clinically to stimulate interview. blood cell formation, particularly in Metcalf’s pioneering research fo- patients undergoing chemotherapy cused on the control of blood cell for- Revolutionized Stem Cell where the treatment damages bone mation and, specifically, leukemic cells. Transplantation marrow cells. We are currently gen- In 1965 he co-developed a series of spe- As well as boosting the immune system erating mice with homozygous inac- “He made the cialized culture techniques that allowed in chemotherapy patients and in other blood cell system scientists to grow various types of blood immune deficiencies, CSFs revolution- cells, after which he discovered colony- ized blood stem cell transplantation. It For more than the ‘poster stimulating factors, which control the was later found that CSFs also contrib- formation of white blood cells that re- ute to such diseases as rheumatoid ar- 50 years he child’ of medical sist infection. thritis, and medications that block CSF pursued his research and He and his colleagues next discovered function are currently entering clinical the effectiveness of two primary white trials. understanding shone a light into blood cell regulators—granulocyte- Metcalf later investigated stem cells, macrophage colony-stimulating factors CSF receptors, cell survival, and sup- of CSFs, and the darkness for and granulocyte colony-stimulating pressors of cell signaling. He was in- helped lead those who followed factors—to speed regrowth of blood volved in discovering a multiple-action cells after chemotherapy and bone growth factor, the leukemia inhibitory researchers him to work on marrow and peripheral blood factor. transplants. to identify and understanding other His early studies on white blood purify four tissues such as the cell regulators led him to hypoth- José Carreras esize that there was some hormonal Among the first patients in the world separate breast, skin, and process involved in controlling their to receive treatment with a colony- production—substances he called col- stimulating factor was opera tenor stimulating factors. colon.” ony stimulating factors. For more than José Carreras when he developed acute 50 years he pursued his understanding lymphoblastic leukemia that failed to of CSFs, and helped lead researchers respond to initial treatment. He re- tivation of genes encoding blood cell to identify and purify four separate ceived CSF therapy in 1987, recovered, regulatory factors or their receptors stimulating factors. He and his team and today continues to raise money to to establish the precise functions were also among the first researchers help leukemia patients and advance re- attributable to each factor. Parallel in the world to discover the genes for search through the establishment of the studies are using mutagenized recep- CSFs. José Carreras International Leukemia tors to establish the domains in each A leading researcher in interna- Foundation. receptor chain initiating each of the tional clinical trials of CSFs in the During the course of Metcalf’s ca- variety of signaling cascades required 1980s, Metcalf came to better un- reer, he mentored hundreds of research to mediate the pleiotropic actions derstand how and why these factors students and authored 700+ papers on each regulator has on responding boost immune cell numbers in cancer his findings; he also holds 21 patents. cells.” patients whose immune systems were continued on page 15 15 Oncology Times FDA Approves Gazyva Combo Treatment for CLL he U.S. Food and Drug in combination with chlorambucil received Gazyva plus chlorambucil 8.8% of the patients who received TAdministration has approved a compared with use of rituximab plus or rituximab plus chlorambucil. The rituximab combination; and supplemental biologics license ap- chlorambucil and compared with use first stage of that trial included 589 • At two years, the rate of death plication for Gazyva (obinutuzumab) of chlorambucil alone. patients with previously untreated for patients receiving Gazyva plus in combination with chlorambucil for That latest data is from Stage 2 of CLL, which compared use of Gazyva chlorambucil was 9% compared with the treatment of patients with previ- a Phase III, multicenter, open-label, plus chlorambucil with Gazyva alone. 20% for those who received chloram- • ously untreated chronic lymphocytic The results showed: bucil alone. (Median overall survival February 10, 2015 leukemia (CLL). Gazyva, made by • Patients has not yet been reached.) Genentech, is a monoclonal antibody who received Gazyva that attaches to CD20 and attacks plus chlorambucil had Side effects for Gazyva include: cells directly and with the body’s im- a median progression- hepatitis B reactivation, progressive mune system. free survival of 26.7 multifocal leukoencephalopathy, in- In 2013, the drug became the first months compared fusion reactions, tumor lysis syn- drug to be approved by the FDA with 14.9 months for drome, infections, and low white that had been granted Breakthrough the patients receiv- blood cell counts. The most com- • Therapy Designation (OT 12/10/13 ing the rituximab mon side effects are infusion reac- oncology-times.com issue). The latest approval is based randomized study (CLL11), which in- combination; tions, low white blood cell counts, on data that found significant im- cluded 663 previously untreated pa- • 26.1% of the patients receiv- low platelet counts, low red blood provements across multiple clinical tients with CLL who had co-existing ing the Gazyva combination had a cell counts, fever, cough, nausea, O endpoints when the drug was used medical conditions. Those patients complete response compared with and diarrhea. T DONALD METCALF Metcalf char- Continued from page 14 acterized blood stem cells and Millions of their daughter Patients Helped cells, which pro- “Over the past 20 years, more than 20 duce multiple million cancer patients have been treated types of white with CSFs and, as a result, have been given blood cells that the best possible chance of beating their fight infection cancer,” Hilton said. “There can be no and prevent greater legacy for a medical researcher.” bleeding. In a tribute, he along with “In doing Professors Warren Alexander, PhD, so he made the and Nicos Nicola, PhD, Heads of the blood cell sys- Division of Cancer and Hematology tem the ‘poster A stamp was created in his honor in 2002 as part of at the Institute, wrote the following: child’ of medi- the Australian Legends series, which commemorate “‘Don,’ to most everyone with whom cal research and Australians “who have made lifetime contributions he worked, was a Colossus of science shone a light to the development of the Commonwealth’s national who, working at the Walter and Eliza into the dark- identity and character.” Hall Institute and supported by the ness for those Cancer Council of Victoria from 1954 who followed Nevertheless, Don knew he needed to 2014, stood astride the world of he- him to work on understanding other tis- collaborators who would take him out matology for 60 years. sues such as the breast, skin, and colon,” his comfort zone and help him fulfill “In 1964, studying leukemia, he and Hilton, Alexander, and Nicola wrote. his ambition of delivering health ben- Ray Bradley, from The University of “Despite Don’s profound funda- efits from his discoveries and so he Melbourne, discovered it was possible mental discoveries, which shaped our assembled a team of researchers who worked with him for 40 years. “Don’s ability to identify a glimmer of talent in younger researchers and mold “Decades ahead of its time, his model them into a cohesive, loyal, and vibrant of collaborative, multidisciplinary science team, that consistently came up with ground-breaking discoveries, was re- is now seen as almost mandatory if big markable. Decades ahead of its time, his model of collaborative, multidisciplinary problems are to be tackled and science shaped the culture of the Walter significant breakthroughs are to and Eliza Hall Institute and is now seen as almost mandatory if big problems are to be made in medical science.” be tackled and significant breakthroughs are to be made in medical science.” He is survived by his wife, to grow bone marrow cells in plates of basic understanding of how blood cells Josephine, four daughters, and six partly set agar jelly.
Load more

Recommended publications
  • 2010-2011 Annual Report
    Annual Report 2010-2011 Mastery of disease through discovery | www.wehi.edu.au Contents 1 About the institute 3 Director’s and Chairman’s report 5 Discovery 8 Cancer and Haematology 10 Stem Cells and Cancer 12 Molecular Genetics of Cancer 14 Chemical Biology 16 Molecular Medicine 18 Structural Biology 20 Bioinformatics 22 Infection and Immunity 24 Immunology The Walter and Eliza Hall Institute 26 Autoimmunity and Transplantation of Medical Research 28 Cell Signalling and Cell Death 1G Royal Parade 30 Inflammation Parkville Victoria 3052 Australia Telephone: (+61 3) 9345 2555 32 Molecular Immunology Facsimile: (+61 3) 9347 0852 34 Publications WEHI Biotechnology Centre 36 Awards 4 Research Avenue 37 Translation La Trobe R&D Park Bundoora Victoria 3086 Australia Translating our research 38 Telephone: (+61 3) 9345 2200 40 Developing our research Facsimile: (+61 3) 9345 2211 42 Patents www.wehi.edu.au www.facebook.com/WEHIresearch 43 Education www.twitter.com/WEHI_research 46 2010-11 graduates ABN 12 004 251 423 47 Seminars Acknowledgements 48 Institute awards Produced by the institute’s Community Relations department 49 Engagement Managing editor: Penny Fannin Editor: Liz Williams 51 Strategic partners Writers: Liz Williams, Vanessa Solomon and Julie Tester 52 Scientific and medical community Design and production: Simon Taplin Photography: Czesia Markiewicz and Cameron Wells 54 Public engagement 57 Engagement with schools Cover image 58 Donor and bequestor engagement Art in Science finalist 2010 Vessel webs 59 Sustainability Dr Leigh Coultas, Cancer and Haematology division 60 The Board This image shows the delicate intricacy in the developing eye of a transient population of web-like blood vessels.
    [Show full text]
  • M. Moore: Introduction for Donald Metcalf
    Haematology and Blood Transfusion Vol. 31 Modern Trends in Human Leukemia VII Edited by Neth, Gallo, Greaves, and Kabisch © Springer-Verlag Berlin Heidelberg 1987 Introduction for Donald Metcalf M. Moore 1 It is a personal pleasure to introduce my understand the environment, the man, and friend and former colleague, Donald Met­ the interplay of chance and the prepared calf. He is best recognized as one of the mind. In 1965 the Nobel Laureate, Sir Mac­ founding fathers of modern experimental farlane Burnet, retired as Director of the hematology, but we should not forget his Walter and Eliza Hall Institute for Medical pioneering work on the thymus. From 1956 Research (WEHI), appointing as his suc­ and the decade thereafter, Don undertook a cessors his two proteges, Gus Nossal as Di­ series of elegant studies on thymic cell kin­ rector and Don Metcalf as Assistant Direc­ etics and was one of the first to analyze the tor and Head of the Cancer Research Unit. impact of thymectomy and thymic grafting This was a wise decision, since Don re­ on lymphopoiesis. Indeed, he should be con­ mained relatively unburdened by adminis­ sidered the first to demonstrate the effects of trative responsibilities, which he naturally thymectomy on lymphoid tissue and the au­ finds irksome, and was able to pursue his sci­ tonomous control of lymphocyte prolifer­ entific interests. The "golden age of immu­ ation within the thymus. In addition, his nology" can be considered to have begun in analysis of leukemogenesis in AKR mice is the mid-1960s and the Hall Institute was still considered definitive, revealing his abil­ very much at the forefront.
    [Show full text]
  • Cytokine Receptors and Hematopoietic Differentiation
    Oncogene (2007) 26, 6715–6723 & 2007 Nature Publishing Group All rights reserved 0950-9232/07 $30.00 www.nature.com/onc REVIEW Cytokine receptors and hematopoietic differentiation LRobb The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Colony-stimulating factors and other cytokines signal via finely tuned regulatory pathways that control both basal their cognate receptors to regulate hematopoiesis. In and emergency hematopoiesis are mediated largely by many developmental systems, inductive signalling deter- cytokines and their cognate receptors. Cytokines are a mines cell fate and, by analogy with this, it has been large family of specific extracellular ligands that can postulated that cytokines, signalling via their cognate stimulate biological responses in diverse cell types by receptors, may play an instructive role in lineage binding to, and activating, a family of structurally and specification in hematopoiesis. An alternative to this functionally conserved cytokine receptors. instructive hypothesis is the stochastic or permissive Cytokines of the hematopoietic system include inter- hypothesis. The latter proposes that commitment to a leukins (ILs), colony-stimulating factors (CSFs), inter- particular hematopoietic lineage is an event that occurs ferons, erythropoietin (EPO) and thrombopoietin independently of extrinsic signals. It predicts that the role (TPO). They bind to a family of cytokine receptors that of cytokines is to provide nonspecific survival and share a number of features. The receptors can be proliferation signals. In this review, we look at the role composed of dimers of a single receptor (granulocyte of cytokine receptor signalling in hematopoiesis and (G)-CSF receptor (R), EPO receptor (EPOR), TPO consider the evidence for both hypotheses.
    [Show full text]
  • Donald Metcalf: the Father of Modern Hematology Jerry M
    RETROSPECTIVE Donald Metcalf: The father of modern hematology Jerry M. Adams1 and Suzanne Cory Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia On December 15, 2014, the hematology and founded each colony and for the previously leukemia research communities lost one of unknown extracellular cytokines required for their greatest leaders to pancreatic cancer. their survival and proliferation, which Don Through a remarkable 60-year research ca- termed “colony-stimulating factors” (CSFs). reer, Donald Metcalf led the discovery and Over time, Don’s team and others devised characterization of the regulators of blood similarclonalassaysfortheprogenitorsof cell production. The legacy of his work is not other white blood cell types, eventually reveal- only that blood cells have become the best- ing the complete genealogical “tree” from the understood complex biological system, but multipotential blood stem cell to the diverse also that the clinical applications of its reg- mature cell types. Furthermore, Don’sper- ulators have already benefited over 20 million ceptive analysis revealed that their leukemic cancer patients. counterparts had acquired self-renewal hall- Metcalf—Dontoallwhoknewhim—was marks of stem cells while losing features of born in 1929 in Mittagong, a small Australian terminal differentiation. The insights gained countrytowninNewSouthWales.Hisfirst on the multifaceted blood cell system made it scientific work, on ectromelia virus, came du- a paradigm for the normal and neoplastic de- ring medical training at the University of Syd- velopment of many other tissue types. ney. In 1954, Don moved to Melbourne’s From the outset, Don had the bold vision Walter and Eliza Hall Institute of Medical that if the CSFs could be purified in sufficient Research (WEHI), which became his perma- amounts, they could become new medicines Donald Metcalf.
    [Show full text]
  • 2014 WEHI Annual Report
    ANNUAL REPORT JULY–DECEMBER 2014 CANCER | IMMUNE DISORDERS | INFECTIOUS DISEASE CONTENTS 1 About the institute The Walter and Eliza Hall Institute of Medical Research 2 President’s report 3 Director’s report Parkville campus 1G Royal Parade 4 The board Parkville Victoria 3052 Australia 5 Vale Professor Donald Metcalf Telephone: +61 3 9345 2555 6 Research highlights Bundoora campus 4 Research Avenue 13 Chief operating officer’s report La Trobe R&D Park 14 Our supporters Bundoora Victoria 3086 Australia Telephone: +61 3 9345 2200 16 Members of the institute www.wehi.edu.au 17 Institute organisation www.facebook.com/WEHIresearch www.twitter.com/WEHI_research 18 Statistical summary www.youtube.com/WEHImovies 19 The period at a glance ABN 12 004 251 423 20 Supporting our research © The Walter and Eliza Hall Institute of Medical Research 2015 Produced by the Walter and Eliza Hall Institute’s Communications and Marketing department Cover image Director Art of Science finalist 2014 Douglas J Hilton BSc Mon BSc(Hons) PhD Melb FAA FTSE FAHMS A merging of worlds by Dr Lachlan Whitehead, Systems Biology and Personalised Medicine division, and Mr Caleb Dawson, Assistant Director Molecular Medicine division. David Vaux MB BS BMedSc PhD Melb FAA Platelets are cells that make your blood clot when you get a cut, stopping the bleeding. Understanding how platelets form and the role they play in human Chief Operating Officer development and growth may help us develop Samantha Ludolf treatments for diseases in which someone has too BA(Hons) Lincoln MEnterp Melb few or too many platelets. This image shows partially analysed data that is normally buried by the computer Chief Financial Officer as it converts images of blood samples into numbers.
    [Show full text]
  • August 17, 2016 Oversight Committee Peer Reviewer Recommendations
    Recommendations for Scientific Research Peer Review Panels Steve Altschuler, Ph.D. Paul A. Bunn, M.D. Arion Chatziioannou, Ph.D. Michael A. Hollingsworth, Ph.D. David A. Mankoff, M.D., Ph.D. Alexander Meissner, Ph.D. Carolyn D. Runowicz, M.D. Kristin R. Swanson, Ph.D. Cameron Turtle, M.D., Ph.D. Eliezer M. Van Allen, M.D. Henry VanBrocklin, Ph.D. Lani Wu, Ph.D. Recommendation for Prevention Peer Review Panels Bob Riter Recommendations for Product Development Peer Review Panels C. Glenn Begley, Ph.D. Renzo Canetta, M.D. Terence Porter, Ph.D. Sandra Silberman, M.D., Ph.D. 6-0 6-00 OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FIVE PAGES. NAME: Altschuler, Steven J. eRA COMMONS USER NAME (credential, e.g., agency login): SALTSC POSITION TITLE: Professor EDUCATION/TRAINING DEGREE Completion (if Date FIELD OF STUDY INSTITUTION AND LOCATION applicable) MM/YYYY University of Pennsylvania B.A. 06/85 Mathematics University of California, San Diego MA 06/86 Mathematics University of California, San Diego PhD 06/90 Mathematics A. Personal Statement Over the past decade, my laboratory, in collaboration with the laboratory of Dr. Lani Wu, has pioneered multiple approaches for quantifying and interpreting cancer heterogeneity in normal and diseased tissues. Traditionally, this phenotypic heterogeneity, whether arising from microenvironment, epigenetic or genetic sources, has been viewed as an impediment to understanding and treating cancer. We were therefore very surprised by our ability to identify biological and clinical information hidden within patterns of heterogeneity.
    [Show full text]
  • Mastering Disease Through Discovery
    Mastering Disease Through Discovery CELEBRATING THE ACHIEVEMENTS OF PROFESSOR DONALD METCALF ON HIS 80TH BIRTHDAY 080730 booklet.indd 1 12/03/09 9:59 AM THE WORLD OF 1929 …and the Jazz Age hits dizzy heights. …while the harbour is bridged in Sydney… The illustrious Donald Bradman hits a six… Chaos on Wall Street in late 1929, with the stock market crash and the onset of the Great Depression. Meanwhile, the infant Donald Metcalf A view of prosperous Bourke Street, Melbourne, in enjoys Australian country life. early 1929, looking east towards Parliament House. 080730 booklet.indd 2 12/03/09 9:59 AM CAUSE FOR CELEBRATION: A WEHI AND AUSTRALIAN LEGEND AT 80 A personal reflection by Professor Suzanne Cory A CauseHow does one capture in just a few forparagraphs the essence of an 80-year old icon? I shall begin with his remarkable scientific achievements. Known the world over as ‘the father of modern haematology’, Don Metcalf’s 44-year quest to understand how blood cells are generated by the body led to the identification and purification of the CSFs, hormone-like proteins essential for white blood cell production. CSFs have now been used to treat over 8 million cancer patients, in order to replenish the vital blood cells destroyed by their chemotherapy. Don has garnered almost every major international science prize, including the Bristol-Myer Prize for Distinguished Cancer Research Professor Suzanne Cory (1987); Robert Koch Prize (1988); Alfred P Sloan Prize of the General CMotors Cancere Researchl Foundationebrat (1989); Albert Lasker Award for Clinical Medical Research (1993); Gairdner Foundation International Award (1994); Royal Medal of the Royal Society (1995) and the AACR Lifetime Achievement Award (2007).
    [Show full text]
  • Contents Research Illuminating the Interplay of Cancer and the Immune System December 2013 Volume 1 Issue 6
    Cancer Immunology Contents Research Illuminating the Interplay of Cancer and the Immune System December 2013 Volume 1 Issue 6 MASTERS OF IMMUNOLOGY PRIORITY BRIEFS 351 The Colony-Stimulating Factors and 378 Inverse Association between Cancer Programmed Death Ligand 1 and Genes Donald Metcalf in the VEGF Pathway in Primary Clear Cell Renal Cell Carcinoma Richard W. Joseph, Mansi Parasramka, CANCER IMMUNOLOGY AT THE Jeanette E. Eckel-Passow, Dan Serie, Kevin Wu, CROSSROADS: PUBLIC/PRIVATE Liuyan Jiang, Krishna Kalari, R. Houston Thompson, Thai Huu Ho, Erik P. Castle, PARTNERSHIP John Cheville, Eugene D. Kwon, E. Aubrey Thompson, and Alexander Parker 357 The Melanoma Research Alliance: The Power of Patient Advocacy to Accelerate Synopsis: In a retrospective, nested, case–control Research and Novel Therapies study of 98 primary clear cell renal cell carcinoma Debra Black and Laura Brockway-Lunardi tumors, Joseph and colleagues demonstrate an inverse correlation between genes in the VEGF pathway and PD-L1 expression, providing further MILESTONES IN CANCER IMMUNOLOGY support of the immunosuppressive role of VEGF on the tumor microenvironment. 362 The 2013 William B. Coley Award for Distinguished Research in Basic and 386 mTOR Inhibition Improves Antitumor Tumor Immunology Effects of Vaccination with Antigen- Encoding RNA Mustafa Diken, Sebastian Kreiter, Fulvia Vascotto, Abderraouf Selmi, Sebastian Attig, Jan Diekmann, CANCER IMMUNOLOGY MINIATURES Christoph Huber, Ozlem€ Tureci,€ and Ugur Sahin 365 An Abscopal Response to Radiation and Synopsis: Diken, Kreiter, and colleagues report that Ipilimumab in a Patient with Metastatic treatment of mice in the B16 melanoma model with Non–Small Cell Lung Cancer rapamycin at the effector-to-memory transition Encouse B.
    [Show full text]