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George Daley: individualising stem-cell research
Paper of the Year Shortlist
Profile George Daley: individualising stem-cell research I became committed to the goal of developing diseasespecific, patient-derived stem cells many years ago”, says George Daley. From high-school, he found the discovery involved in science “thrilling, like the risk-taking explorers of yesteryear”. This year, Daley’s team published in Cell the first report of the induction of patient-specific pluripotent stem-cell lines, derived from somatic cells of ten patients with disorders ranging from severe combined immunodeficiency to Down’s syndrome. The research and clinical implications are enormous. What started Daley, associate professor at the Children’s Hospital Boston, on his scientific explorations, and what keeps him going, is an interest in treating children with genetic blood disorders. He joined the laboratory of Nobel Prize winner David Baltimore in the late 1980s on a joint scholarship to Harvard University and the Massachusetts Institute of Technology. During his PhD, Daley made a mouse model of human chronic myelogenous leukaemia, proving that the oncogene BCR/ABL can cause the disease. Now, Daley’s own laboratory aims to translate research into treatments for haematological disorders. He envisions the use of induced pluripotent stem cells for “rejectionproof” gene and cell therapy. “We want to make stem cells from children with immune deficiency or sickle cell disease, do precise gene repair on their cells, direct those cells to differentiate into blood cells, and provide a transplant. This could address any of dozens of bone marrow disorders.” Daley is confident that his team will achieve this goal. “It’s just a matter of time.” Previously, Daley pursued techniques such as nuclear transfer and parthenogenesis to make disease-specific stem-cell lines. He also discovered that parthenogenesis— which starts from an unfertilised egg—was the actual mechanism behind the retracted South Korean claims of human cloning and genetically matched human cell lines. “That was a bitter-sweet contribution”, he recalls. Eventually, he turned to viral vectors to introduce transcription factors into adult cells, including fibroblasts, using a technique pioneered by Shinya Yamanaka, from Kyoto University, Japan. Now, says Daley, “we can take skin cells of any patient and by introducing three or four genes, create versatile, pluripotent stem cells”. The Cell paper describes this procedure in ten patients with different disorders, some single gene defects and some of complex inheritance. An inexhaustible supply of cells that can induce any tissue type is a valuable tool to model diseases. Sean Morrison, director of the University of Michigan’s Center for Stem Cell Biology, explains that this research “will open up new possibilities for better understanding the origin of inherited human disease and for developing www.thelancet.com Vol 372 December 20/27, 2008
safer and more effective new therapies by making it possible to screen for new drugs using differentiated human cells that carry the exact genetic defects that cause disease in patients.” Only the twelfth person to graduate from a Harvard MD summa cum laude (with highest praise), Daley is keen to acknowledge the huge contribution of others, especially In-Hyun Park, first author of the Cell paper “who did 90% of the work”, according to Daley. He also credits the contributions of his “inspiring” mentors, especially Baltimore: “His intellectual rigour, and the collaborative community he inspired, was brilliant” and gave Daley “a standard to emulate”, he says. Baltimore recalls that Daley “was a remarkable student, clearly maturing toward greatness when he joined me to do his thesis. But he never coasted on his abilities: he worked hard and effectively”. Going on to complete his medical training, Baltimore remembers that Daley’s work on human chronic myelogenous leukaemia “was so well known that he kept being invited to meetings to describe it long after he had completed it. He was so smart and followed the field so carefully that I am sure they wanted his intelligence and good humour to spice up the meeting”. Daley has recently been involved in drafting the new International Society on Stem Cell Research (ISSCR) guidelines on clinical translation of research. Daley was last year’s ISSCR president and “an outstanding leader” in the field, according to Morrison, who notes that “almost nobody is as effective” as Daley. “The field would not be where it is today without him, in multiple ways. On top of all that, it’s a real pleasure to work with him”, Morrison adds, saying that Daley makes the field “more exciting and more fun to be part of”. Daley keeps his priorities clear. “It is a gift to do clinical medicine and teach incredible students at Harvard, and work in a research field that is exploding with excitement. We have fun in the lab and there’s a lot of productivity.” In private, Daley enjoys sports with his two sons and cooking with his wife, a Harvard business professor. He is amused to recall that they once discovered they were going to meetings at the same resort the night before they left. At once, “we switched reservations and booked a romantic dinner”, says Daley. In public, he has been outspoken and testified to Congress on the value of stem-cell research for several years, and hopes that president-elect Barack Obama will reverse the current restrictive US policy “as one of the first acts of his presidency”.
See Comment page 2096 Park IH, Arora N, Huo H, et al. Disease-specific induced pluripotent stem cells. Cell 2008; 134: 877–86.
To vote for this paper as The Lancet’s 2008 Paper of the Year see http://www.thelancet.com
Kelly Morris [email protected]
2107
Profile George Daley: individualising stem-cell research I became committed to the goal of developing diseasespecific, patient-derived stem cells many years ago”, says George Daley. From high-school, he found the discovery involved in science “thrilling, like the risk-taking explorers of yesteryear”. This year, Daley’s team published in Cell the first report of the induction of patient-specific pluripotent stem-cell lines, derived from somatic cells of ten patients with disorders ranging from severe combined immunodeficiency to Down’s syndrome. The research and clinical implications are enormous. What started Daley, associate professor at the Children’s Hospital Boston, on his scientific explorations, and what keeps him going, is an interest in treating children with genetic blood disorders. He joined the laboratory of Nobel Prize winner David Baltimore in the late 1980s on a joint scholarship to Harvard University and the Massachusetts Institute of Technology. During his PhD, Daley made a mouse model of human chronic myelogenous leukaemia, proving that the oncogene BCR/ABL can cause the disease. Now, Daley’s own laboratory aims to translate research into treatments for haematological disorders. He envisions the use of induced pluripotent stem cells for “rejectionproof” gene and cell therapy. “We want to make stem cells from children with immune deficiency or sickle cell disease, do precise gene repair on their cells, direct those cells to differentiate into blood cells, and provide a transplant. This could address any of dozens of bone marrow disorders.” Daley is confident that his team will achieve this goal. “It’s just a matter of time.” Previously, Daley pursued techniques such as nuclear transfer and parthenogenesis to make disease-specific stem-cell lines. He also discovered that parthenogenesis— which starts from an unfertilised egg—was the actual mechanism behind the retracted South Korean claims of human cloning and genetically matched human cell lines. “That was a bitter-sweet contribution”, he recalls. Eventually, he turned to viral vectors to introduce transcription factors into adult cells, including fibroblasts, using a technique pioneered by Shinya Yamanaka, from Kyoto University, Japan. Now, says Daley, “we can take skin cells of any patient and by introducing three or four genes, create versatile, pluripotent stem cells”. The Cell paper describes this procedure in ten patients with different disorders, some single gene defects and some of complex inheritance. An inexhaustible supply of cells that can induce any tissue type is a valuable tool to model diseases. Sean Morrison, director of the University of Michigan’s Center for Stem Cell Biology, explains that this research “will open up new possibilities for better understanding the origin of inherited human disease and for developing www.thelancet.com Vol 372 December 20/27, 2008
safer and more effective new therapies by making it possible to screen for new drugs using differentiated human cells that carry the exact genetic defects that cause disease in patients.” Only the twelfth person to graduate from a Harvard MD summa cum laude (with highest praise), Daley is keen to acknowledge the huge contribution of others, especially In-Hyun Park, first author of the Cell paper “who did 90% of the work”, according to Daley. He also credits the contributions of his “inspiring” mentors, especially Baltimore: “His intellectual rigour, and the collaborative community he inspired, was brilliant” and gave Daley “a standard to emulate”, he says. Baltimore recalls that Daley “was a remarkable student, clearly maturing toward greatness when he joined me to do his thesis. But he never coasted on his abilities: he worked hard and effectively”. Going on to complete his medical training, Baltimore remembers that Daley’s work on human chronic myelogenous leukaemia “was so well known that he kept being invited to meetings to describe it long after he had completed it. He was so smart and followed the field so carefully that I am sure they wanted his intelligence and good humour to spice up the meeting”. Daley has recently been involved in drafting the new International Society on Stem Cell Research (ISSCR) guidelines on clinical translation of research. Daley was last year’s ISSCR president and “an outstanding leader” in the field, according to Morrison, who notes that “almost nobody is as effective” as Daley. “The field would not be where it is today without him, in multiple ways. On top of all that, it’s a real pleasure to work with him”, Morrison adds, saying that Daley makes the field “more exciting and more fun to be part of”. Daley keeps his priorities clear. “It is a gift to do clinical medicine and teach incredible students at Harvard, and work in a research field that is exploding with excitement. We have fun in the lab and there’s a lot of productivity.” In private, Daley enjoys sports with his two sons and cooking with his wife, a Harvard business professor. He is amused to recall that they once discovered they were going to meetings at the same resort the night before they left. At once, “we switched reservations and booked a romantic dinner”, says Daley. In public, he has been outspoken and testified to Congress on the value of stem-cell research for several years, and hopes that president-elect Barack Obama will reverse the current restrictive US policy “as one of the first acts of his presidency”.
See Comment page 2096 Park IH, Arora N, Huo H, et al. Disease-specific induced pluripotent stem cells. Cell 2008; 134: 877–86.
To vote for this paper as The Lancet’s 2008 Paper of the Year see http://www.thelancet.com
Kelly Morris [email protected]
2107