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5 Pioneers Are Awarded Lasker Medical Prizes.(National Desk).Lawrence K. Altman. The New York Times (Sept 18, 2005): pA18(L). (868 words)

The 2005 Lasker Awards for medical research are going to scientists who discovered stem cells, invented genetic fingerprinting and developed a powerful technology that played a crucial role in mapping the human genome.

And a nonscientist, Nancy Brinker, is the winner of the Lasker Public Service Award for creating the Susan G. Komen Breast Cancer Foundation, which has helped transform a disease once rarely mentioned in polite conversation into an international issue.

The awards, widely considered the United States' most prestigious medical prizes, are being announced today by the Albert and Mary Lasker Foundation. The two scientific awards each carry a $50,000 prize, split between the winners; the public service award has no monetary prize.

Starting with $200, Ms. Brinker created the Komen foundation in 1982 to fulfill a promise to her sister, Susan Komen, who had died of breast cancer two years earlier, at age 36.

Among other things, Ms. Brinker started the Komen Race for the Cure, a series of five-kilometer running and walking races around the country that have helped the foundation raise more than $750 million to support breast cancer research, education, screening and treatment.

Ms. Brinker started and ''nurtured the grass-roots breast cancer advocacy movement,'' the Lasker Foundation said. Now 58, Ms. Brinker is also a breast cancer survivor.

Mary Lasker created the awards in 1946 as a birthday gift to her husband, Albert, in hopes of curing cancer in 10 years.

The research award for stem cell work is going to Drs. Ernest A. McCulloch and James E. Till, emeritus professors at the University of Toronto and the Ontario Cancer Institute.

Scientists had long theorized that the body contained cells that could renew themselves, mature and specialize in various ways. But no one had found them until Dr. McCulloch, now 79, and Dr. Till, 74, proved their existence in the blood-forming system.

Their work started in the late 1950's, when scientists were trying to understand when and how radiation therapy stopped cancer and the military was seeking ways to treat personnel exposed to radiation from nuclear weapons.

Working with mice, Dr. McCulloch and Dr. Till designed a system to measure the sensitivity of bone marrow cells to radiation. With rigorous experiments that relied on principles from microbiology, they showed that the spleen contained cells that divided into the three main types of blood cells -- red, white and platelets.

The findings led to a system for studying the factors that send the stem cells down different developmental paths, and helped transform the study of blood cells from an observational science to a more experimental one. Dr. McCulloch and Dr. Till found that molecules both within and outside a cell can determine its fate.

Their work also helped scientists learn how and why bone marrow transplants replenish blood cells,

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thereby improving a procedure that can prolong the lives of people with leukemia and other blood-cell cancers.

Sir Edwin Southern of the University of Oxford and Sir Alec J. Jeffreys of the University of Leicester in England received the Lasker Award for developing two powerful technologies, Southern blotting and DNA fingerprinting, that, the foundation said, ''together revolutionized human genetics and forensic diagnostics.''

Working in Edinburgh in the 1970's, Dr. Southern, now 79, developed the technique now known by his name that allowed detection of a single gene in a complex genome and that eventually enabled the rapid sequencing of entire genomes.

Suddenly, scientists had a new way to search for gene sequences of particular interest and to detect subtle DNA differences among individuals.

Scientists used the technique, for example, to pinpoint mutations linked to inherited diseases. Detection of such mutations has led to tests for prenatal detection of diseases like sickle cell anemia and thalassemia.

Southern blotting also led to the second breakthrough, genetic fingerprinting. The method provides a way to distinguish every person from every other person, except an identical twin.

Genetic fingerprinting has changed the way law enforcement agencies have solved new and old crimes like murder and rape, and has absolved the innocent, settled paternity and immigration disputes, helped improve techniques for transplanting organs and tissues, led to tests to detect and better understand inherited diseases, and helped establish human origins and migrations.

Dr. Jeffreys, now 55, was interested in uncovering genetic variation in different populations. He used the Southern blot technique to study certain DNA segments present in all humans. In 1984, he noticed in one Southern blot that the pattern of these segments varied from person to person, creating a unique genetic ''fingerprint'' of an individual.

He also found that parents passed the patterns on to their offspring, with each child carrying half of each parent's fingerprint. Dr. Jeffreys's ''predictions about the utility of the method not only have been borne out, but have been surpassed,'' the Lasker Foundation said.

Although the discoveries were made decades ago, the awards are being given this year because newer research has shown their broad potential, said Dr. Joseph L. Goldstein, chairman of the Lasker jury. Dr. Goldstein, a Nobel laureate from the University of Texas Southwestern Medical Center in Dallas, said that because it can take years to appreciate a discovery's significance, awards are often given long after the discovery is made.

Source Citation: Altman, Lawrence K. "5 Pioneers Are Awarded Lasker Medical Prizes.(National Desk)." The New York Times (Sept 18, 2005): A18(L). General OneFile . Gale. UNIVERSITY OF TORONTO. 9 Aug. 2008 .

Gale Document Number: A136301715

Disclaimer: This information is not a tool for self-diagnosis or a substitute for professional care.

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Canadian Institutes of Health Research Biographies of Honourees

[ Press Release 2005-46 ]

Date: October 17th, 2005 at 6:30 p.m. Location: The Fairmont Royal York Hotel, Toronto (Imperial Ballroom)

Dr. Ernest McCulloch

Senior Scientist, Ontario Cancer Institute, Princess Margaret Hospital University Professor Emeritus, University of Toronto

E. A. McCulloch was born in Toronto in 1926. He was educated at Upper Canada College and the University of Toronto. He received his MD degree in 1948; he then spent a year at the Lister Institute in London, England, where he began his education in research. After completing clinical training at the Toronto General Hospital and Sunnybrook Hospital, he spent a further period as a research fellow under the direction of Professor K. J. R. Wightman. He then was appointed to the scientific staff of the newly-formed Ontario Cancer Institute. There he began his research with contributions to the viral etiology of cancer.

However, his major work has been concentrated on normal and malignant blood formation. With his colleague Dr. James Till, he devised the first functional assay (the spleen colony assay) for primitive blood cell precursors (pluripotent stem cells of CFU-S). Dr. Till and Dr. McCulloch exploited their assay to characterize murine hemopoietic stem cells, using physical, radiological, physiological, and genetic parameters. The discovery of the spleen colony assay for stem cells and its exploitation were major stimuli for the development of the field of experimental haematology. Since 1970, he has concentrated on the malignant cells characteristic of acute leukemia in man. He has developed assays for their growth properties and determined many of the factors regulating their behaviour, including their responses to chemotherapeutic drugs.

In collaboration with clinical colleagues, he has emphasized associations between laboratory and clinical parameters of disease. He has stressed the training of medical scientists; many graduates of his laboratory now hold important positions in universities and research institutes in Canada and around the world. Often in collaboration with his colleagues and students, Dr. McCulloch has reported his findings in over 275 published papers. He has been an invited speaker throughout North America, Europe, the Middle East, and Asia.

In parallel with this research program, Dr. McCulloch has held a number of senior posts. He was Director of the Institute of Medical Science in the School of Graduate Studies at the University of Toronto for four years. He then served as Assistant Dean of the School for three years. In this capacity, Dr. McCulloch was responsible for the research centres and institutes affiliated with the School of Graduate Studies. From 1982-1989, he was Head of the Division of Biological research of the Ontario Cancer Institute at Princess Margaret Hospital.

After that time, he continued his research in leukemia as a Senior Scientist Emeritus.

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From 1991-1993, Dr. McCulloch was a Visiting Professor of Laboratory Medicine and pathology at the University of Texas, MD Anderson Cancer Center; after his return to Toronto, he retained his affiliation with UTMDACC as a Consultant and Professor.

Dr. McCulloch has served on a number of provincial, national, and international medical and scientific bodies. He was President of the Academy of Science in the Royal Society of Canada and Vice-President of the Society from 1987-1990. For over 20 years, he was an Editor of the Journal of Cellular Physiology and served on many other editorial boards or advisory committees.

Dr. McCulloch's work has been recognized by a number of awards, including the Gairdner Foundation International Award in 1969, the Thomas W. Eadie Medal in 1991 (both shared with Dr. James Till), and the Stratton Lectureship of the American Society of Hematology. The University of Toronto recognized Dr. McCulloch's achievements by making him a University Professor in 1982 and awarding him an honorary doctor of science degree in 2004.

In 1998, Dr. McCulloch was appointed Officer of the Order of Canada, and he was elected a fellow of the Royal Society of London. In 2004, Dr. McCulloch and Dr. Till were inducted into the Canadian Medical Hall of Fame, and in 2005, they received the Albert Lasker Award for Basic Medical Research -considered the most prestigious medical science award in the United States.

Dr. McCulloch is married to Ona Moranty. They have five children and six grandchildren.

Dr. James Till

Senior Scientist, Ontario Cancer Institute, Princess Margaret Hospital University Professor Emeritus, University of Toronto

Born in Lloydminster, Saskatchewan, James Edgar Till completed his Ph.D. in biophysics at Yale University in 1957. He then relocated to Toronto and focused his studies on cell biology and the radiation sensitivity of mammalian cells. Resulting from this research was a 1961 original paper published in Radiation Research on the radiation sensitivity of normal mouse bone marrow cells. The publication, produced jointly with colleague Dr. Ernest A. McCulloch, was a groundbreaking paper in stem cell biology, because it established for the first time a quantitative method to study individual stem cells in adult bone marrow.

Over the next decade, Dr. Till and Dr. McCulloch made many contributions to the understanding of normal and abnormal blood cell development. They also established the concept of stem cells and set the framework in which stem cells are studied today. This work continues to influence the research of investigators worldwide in many fields of study.

Since the 1980s, Dr. Till's sphere of research has expanded to include quality of life research, clinical and epidemiological studies, and research ethics. Currently, he investigates decision-making behaviours of cancer patients and those at high risk of cancer, and the influence of the Internet as a source for information, support, and advocacy.

Besides his research accomplishments, Dr. Till has served on many national and international committees and in numerous leadership positions, including ones at the Ontario Cancer Institute, affiliated with Princess Margaret Hospital (now part of the University Health Network), the University of Toronto, and the National Cancer Institute of Canada. In 1969 he was awarded the Gairdner Foundation International Award and in 1991 he won the Thomas W. Eadie Medal, Royal Society of Canada (both with E. A. McCulloch). In 1993, he was awarded the Robert L. Noble Prize (for outstanding achievements in cancer research, National Cancer Institute of Canada & Eli Lilly Canada).

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In 1994, he became an Officer of the Order of Canada. The University of Toronto recognized his achievements by making him a University Professor in 1984, and awarding him an honorary doctor of science degree in 2004. Dr. Till is a Fellow of the Royal Society of Canada and the Royal Society of London (UK). In 2004, Dr. Till and Dr. McCulloch were inducted into the Canadian Medical Hall of Fame. In 2005, they received the Albert Lasker Award for Basic Medical Research - considered the most prestigious medical science award in the United States.

Dr. Tak Mak

Director, Campbell Family Institute, Princess Margaret Hospital University Professor, Department of Medical Biophysics and Department of Immunology, University of Toronto.

He was trained at the University of Wisconsin in Madison, the University of Alberta and the Ontario Cancer Institute. His research interests center on immune recognition and regulation as well as cell survival and cell death in normal and malignant cells. He is best known as the leading the group that first cloned the genes of the human T cell antigen receptor.

His more recent work includes the creation of a series of genetically altered mice that have proved critical to unraveling intracellular programs governing the development and function of the immune system, and the dissection of signal transduction cascades in various cell survival and apoptotic pathways. Dr. Mak holds Honorary Doctoral Degrees from universities in North America and Europe, is an Officer of the Order of Canada, and has been elected a Foreign Associate of the National Academy of Sciences (USA) as well as a Fellow of the Royal Society of London (UK). Dr. Mak has won international recognition in the forms of the Emil von Behring Prize, the King Faisal Prize for Medicine, the Gairdner Foundation International Award, the Sloan Prize of the General Motors Cancer Foundation, the Novartis Prize in Immunology and the Paul Ehrlich Prize and Ludwig Darmstaedter Prize of Germany.

Dr. Tony Pawson

Director of Research, Samuel Lunenfeld Research Institute, Mount Sinai Hospital; Professor, Department of Molecular Medical Genetics, University of Toronto

Tony Pawson received an MA in Biochemistry from the University of Cambridge, England. He did his graduate training at the Imperial Cancer Research Fund, London, working with Alan Smith on the expression of retroviral gene products, and received his Ph.D. in 1976 from King's College, University of London. From 1976-1980 he pursued postdoctoral work at the University of California at Berkeley, with Peter Duesberg and Steven Martin, investigating the biochemical functions of retroviral oncogenes and their role in neoplastic cell transformation. In 1981, he took up a position as an Assistant Professor at the University of British Columbia, and in 1985 moved to the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto. Currently, Dr. Pawson is the Director of Research, Samuel Lunenfeld Research Institute of Mount Sinai Hospital. He is a Professor in the Department of Molecular and Medical Genetics at the University of Toronto, and a University Professor of the University of Toronto. Dr. Pawson is a Distinguished Scientist of the Canadian Institutes for Health Research, holds the Apotex Chair in Molecular Oncology, and is an International Research Scholar of the Howard Hughes Medical Institute. He has received a number of awards, including the Gairdner Foundation International Award (1994), the Robert L. Noble Prize from the National Cancer Institute of Canada (1995), the George Drummond Memorial Award (1996), the Boehringer-Mannheim Prize (1997), the Henry Friesen Award (1998), the AACR-Pezcoller International Award for Cancer Research (1998), the Dr. H.P. Heineken Prize for Biochemistry and Biophysics from the Royal Netherlands Academy of Arts and Sciences (1998), the Killam Prize for Medicine (2000), the J. Allyn Taylor International Prize in Medicine (2000), the Prix Galien Canada (2002), the Michael Smith Prize in Health Research (2002), the Premier's Platinum Medal for Research Excellence (2002), elected Associate Member, EMBO (2003),

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Poulsson Medal from the Norwegian Society of Pharmacology and Toxicology (2004), elected Foreign Associate of the National Academy of Sciences ( US) (2004), elected Foreign Member of the American Academy of Arts and Sciences (2004), elected Fellow, American Academy of Microbiology (2004), the Ernst W. Bertner Memorial Award from the MD Anderson Cancer Center (2004), Louisa Gross Horwitz Prize (2004), Special Achievement Award from the University of Miami (2005), Wolf Prize in Medicine (2005), The Royal Medal from The Royal Society of London (2005). He is a Fellow of the Royal Societies of London and Canada, and a recipient of the Order of Canada.

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Canadian Institutes of Health Research Canadian cancer researchers win prestigious award for their stem cell research -- Government of Canada congratulates Drs. Till and McCulloch

For immediate release -- 2005-36

OTTAWA (September 19, 2005) --The Honourable Ujjal Dosanjh, Minister of Health, the Honourable David L. Emerson, Minister of Industry and Dr. Alan Bernstein, President of the Canadian Institutes of Health Research (CIHR), offered their congratulations to Drs. James Till and Ernest McCulloch for receiving the 2005 Albert Lasker Award. The award is considered to be 'America's Nobel Prize,' and is one of the most distinguished scientific honours given for outstanding contributions to health research and public service.

"The Albert Lasker Award recognizes world-leading scientists who have made an exceptional contribution to the understanding, diagnosis, prevention and treatment of diseases," said Minister Dosanjh. "I send my congratulations to Drs. Till and McCulloch, and thank them on behalf of all Canadians."

"The Government of Canada has made significant investments in R&D to generate knowledge, train highly qualified personnel and encourage commercialization," said Minister Emerson. "This prestigious award highlights the great work of both scientists and recognizes Canada's contribution to the international scientific community."

Drs. Till and McCulloch are being honoured for their groundbreaking discovery demonstrating the existence of stem cells in the blood-forming system. In the early 1960s, their discovery laid the foundation for human bone marrow transplantation for patients with leukemia and other cancers.

"Drs. Till and McCulloch motivated me as a young scientist - and continue to influence an entire generation of Canadian health researchers," says Dr. Bernstein, a former student of Dr. Till at the University of Toronto and the Ontario Cancer Institute.

The award will be presented to Drs. Till and McCulloch at a prestigious ceremony on Friday, September 23 at the Pierre Hotel in New York City, NY.

"The pioneering stem cell discovery made by Drs. Till and McCulloch opened up the entire stem cell field. The Lasker Foundation's recognition of their pioneering research almost 40 years after the research was carried out, is a measure of just how far ahead of their time they were, " said Dr. Bernstein. "It is so appropriate that this announcement take place on the 25th anniversary of Terry Fox's Marathon of Hope, for their groundbreaking research has truly been one of the most important advances in cancer research."

About CIHR: The Canadian Institutes of Health Research is the Government of Canada's agency for health research. Its objective is to excel, according to internationally accepted standards of scientific excellence, in the creation of new knowledge and its translation into improved health for Canadians, more effective health services and products and a strengthened Canadian health care system. Composed of 13 Institutes, CIHR provides leadership and support to close to 10,000 health researchers and trainees in every province of Canada. http://www.cihr-irsc.gc.ca/

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For further information:

Marie-France Poirier CIHR Media Relations Tel.: (613) 941-4563 [email protected]

Adèle Blanchard Office of Minister Dosanjh (613) 957-0200

Christiane Fox Office of Minister Emerson (613) 995-9001

Printed from: http://www.cihr-irsc.gc.ca/e/29092.html

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Proﬁle Ernest McCulloch: father of experimental haematology

Ernest McCulloch was attracted to medicine because of the Till, a biophysicist, volunteered to help McCulloch with his independence the profession offered, and his colleagues research. They began by injecting varying amounts of bone say his independent nature—along with a flourishing marrow cells into mice after the animals were given a lethal scientific imagination—were key to his co-discovery of dose of radiation. “We found that the more marrow cells stem cells. “One of his characteristics is that he just doesn’t you gave, the higher percentage of animals survived”, Till accept dogma, he really actively resists it in fact”, said recalled. To figure out how the transplants saved the animals, James Till, who shared the 2005 Lasker Award for Basic they began a series of careful observations of the blood- Medical Research with McCulloch for their 1960 discovery. forming tissues of mice after injections of bone marrow cells. “He would ask awkward questions all the time and insist on In the course of these experiments, McCulloch observed odd getting an answer.” bumps in the spleens of some of the animals.

The idea of stem cells arose in the early 20th century, but McCulloch wasn’t the first person to see these sort of AP for 60 years, no one had actually seen one. McCulloch and bumps, Till notes, but he was the first to grasp their Till were able to make their discovery, both agree, because importance. “Both of us had experience in cell culture—we they began thinking in terms of how stem cells might immediately thought colony”, Till recalls. With the help of function and how they could be quantified. To McCulloch, graduate students Andy Becker and Charles Ford, Till and who speaks with a measured, deliberate voice, this McCulloch showed that the strange bumps were indeed paradigm shift was their most important contribution. “As colonies of a sort—they were clumps of clones somehow a result of our work, the whole science of experimental derived from the transplanted bone marrow. “We knew haematology developed and has grown”, he said. “There’s then that we were in business and that we had something now a Society for Experimental Haematology, there are that was a candidate for this stem cell concept”, Till says. several journals devoted to experimental haematology, and They developed a definition of stem cells that holds true all of these are based on the notion of cells’ functioning and today: they are self-renewing, able to give rise to differenti- usually depend on some method for counting cells.” ated descendants, and capable of extensive proliferation. McCulloch, the Shakespeare-quoting son of a Toronto McCulloch, Till, and their colleagues then showed that physician, and Till, a more down-to-earth man from a a single stem cell could produce any type of adult blood little town in western Canada, made an odd couple. But cell. With Elizabeth Shull Russell and Sheldon E Bernstein, their research collaboration lasted for decades. Both of the Jackson Laboratory in Bar Harbor, ME, USA, they men were among the original faculty of the Ontario identified genes within stem cells essential for their Cancer Institute at Princess Margaret Hospital, Toronto, function, as well as an external gene that provides the ON, Canada. The well funded institute had a relaxed milieu essential for the cell’s survival. atmosphere: formal meetings were rare, administration Despite having helped to create the foundations for didn’t meddle, and scientists went curling together. It research into stem cells, McCulloch has no interest in “was a perfect place for scientists to grow up”, recalls weighing in on the current ethical debate about the use Lou Siminovich, another early recruit. “No one told us we of embryonic stem cells. “These are ethical questions and should be multidisciplinary, we just were multidisciplinary.” as a scientist I have ethical views, but they’re no more McCulloch was always willing to share his many ideas, important than the ethical views of anybody else. As remembers Siminovich, now Director of Research Emeritus scientists, we must always obey the laws of the land.” at the Samuel Lunenfeld Research Institute and University As Senior Scientist at the Division of Stem Cell and Professor Emeritus at the University of Toronto, Toronto. Developmental Biology, McCulloch is now semi-retired, but “He is a very imaginative scientist.” his scientific imagination is still active and engaged with cur- Fresh from his medical training and research work in rent issues. He serves on the advisory panel of the Atomic pathology and on the genetics of the blood, McCulloch Energy Corporation of Canada, with the goal of developing planned to study the sensitivity of mammalian cells to nuclear power stations as a clean alternative to fossil fuels. radiation. “There was considerable fear of an atomic bomb “Nuclear power makes electricity and you can use electricity and we were greatly interested in ways of protecting against to make hydrogen, and I can see in the future an economy that and bone marrow infusion seemed to be one hopeful which is not based on petroleum but is based on hydrogen avenue of exploration”, he explained. Other puzzles of the and that that will solve many of our problems of pollution.” time included why radiation was helpful in treating some cancers, and how the new technique of bone marrow Anne Harding transplantation was able to restore blood system cells. [email protected]