Maine man of the world
Chuck Hewett's wide-ranging experience and travels come to bear in his work at the Laboratory.
A scientific paper critical of the use of mice in human sepsis, burns and trauma research provoked widespread reaction in the scientific community when The New York Times reported on it Feb. 12. From the paper's narrow focus, the article made broad statements implying that mice provide limited value to biomedical research.
The Laboratory's president and CEO, Dr. Edison Liu, and two physician-scientist colleagues, Dr. David Valle of The Johns Hopkins School of Medicine and Dr. Robert Darnell of The Rockefeller University, responded. The following is a summary of that response:
The article "Mice Fall Short as Test Subjects for Humans' Deadly Ills" is misleading by minimizing the importance of laboratory mice in biomedical research. In fact, experimental mice remain the best proxy we have for ethically studying diseases, testing response to drugs, and making predictions about human disease. Oversimplification of the complexity of mouse genetics and outdated experimental designs led to the misinterpretations in the report that were carried through in the article.
All the studies in the report used only one kind of mouse, BL6, to generate information generalized to all human beings. This is akin to making clothes sized for one person and attempting to sell these to the rest of the population. Moreover, experimental conditions for sepsis and trauma do not represent what human beings face in clinical settings.
Most of what we learn by studying mice is relevant to human studies, some of it not. The differences are as enlightening as the similarities.
The cover story in the March 23 edition of Science News provides an in-depth look at new mouse models that mimic the human immune system and are revolutionizing approaches to cancer, infectious disease and other conditions. Reporter Susan Gaidos interviewed Jackson Laboratory Professor Leonard Shultz, Ph.D., who developed the premier "humanized" mouse model known as NSG, as well as Shultz's longtime collaborator Dale Greiner, Ph.D., of the University of Massachusetts Medical School and other researchers.
When Superstorm Sandy hit the mid-Atlantic coast in October 2012, New York University's Langone Medical Center suffered major damage. Power loss and flooding led to the evacuation of patients and destruction of research laboratories, including the loss of thousands of research mice. An Associated Press article by Malcolm Ritter describes NYU's rebuilding effort, including The Jackson Laboratory's program to provide the university with more than 200 varieties of research mice. The story was published in hundreds of media outlets including the Wall Street Journal and Washington Post websites.
More than 300 people gathered at the future site of The Jackson Laboratory for Genomic Medicine in Farmington, Conn., on Jan. 17 for a noontime ceremony marking the start of the facility's construction.
At an open house earlier in the day, Jackson staff, scientists and guests mingled in JAX Genomic Medicine's temporary quarters on the UConn Health Center campus. The event included a scientific poster session and opportunities to learn about the specific work being done by researchers in Connecticut. After the groundbreaking ceremony and a luncheon, guests heard an afternoon academic seminar by genomicist Charles Lee, Ph.D., of Brigham and Women's Hospital and Harvard Medical School. A reception and professional networking opportunity wrapped up the day's activities.
"We will make you proud, Connecticut," Jackson President and CEO Edison T. Liu, M.D., promised a standing-room-only crowd gathered under a tent on the 17-acre construction site. "Genomics is comprehensive and precise. The comprehensiveness gives us speed in the discovery of preventions and cures. The precision allows us to personalize these treatments to best suit each patient. Ultimately, the goal of our science is to transform medicine toward improving care, lowering costs and increasing both life span and health span."
Connecticut Gov. Dannel P. Malloy, who has championed bioresearch as the cornerstone of economic development in Connecticut, said, "What we are doing in bioscience is critical. We are positioning the state to be a hub of bioscience activity— activity that connects health care, engineering, science, institutions of higher education and technology."
He underscored his support by announcing the proposed creation of a new $200 million fund to support biomedical research over 10 years. The new research fund, he added, "will strengthen our capacity to innovate and create the investment tools necessary to attract business and grow good jobs."
The Fireside Science program, a series of free talks by Laboratory scientists and executives, has attracted a few hundred people to the Bar Harbor campus in recent months. The talks provide the local community an opportunity to hear how the Laboratory is impacting science, human health and the regional economy.
President and CEO Edison T. Liu, M.D., launched the series on Jan. 31 by recounting his education and career path and what it has taught him about life. Later events included Assistant Professor Gareth Howell, Ph.D., and Senior Research Scientist Ron Korstanje, Ph.D., who discussed their research on diseases of aging, and Executive Vice President and Chief Operating Officer Charles Hewett, Ph.D., and Senior Director of Facilities Services John Fitzpatrick, who spoke about the Laboratory's economic impact.
Jackson Laboratory researchers led by Associate Professor Zhongwei Zhang, Ph.D., have provided direct evidence that a specific neurotransmitter receptor is vital to the process of pruning synapses in the brains of newborn mammals. Faulty pruning at this early developmental stage is implicated in autism-spectrum disorders and schizophrenia.
Soon after birth, mammals' brains undergo significant development and change. Initially, large numbers of synapses form between neurons. Then, in response to stimuli, the synaptic connections are refined— some synapses are strengthened and others eliminated, or pruned.
The definitive evidence for N-methyl-D-aspartate receptor (NMDAR) in pruning has eluded researchers until now, but in research published in the Proceedings of the National Academy of Sciences, Zhang's lab had serendipitous help in the form of a mouse model containing brain cells lacking NMDAR side by side with cells containing the receptor.
Zhang and colleagues showed that the refinement process was disrupted in the absence of NMDARs. At the same time, neighboring neurons with the receptors proceeded through normal synaptic strengthening and pruning, clearly establishing the necessity of NMDARs in postsynaptic neurons for synaptic refinement.
"Whenever I give a talk or meet colleagues," Zhang says, "the first question that comes up is whether the receptor is important. It's good that this is now settled definitively."
The Glaucoma Research Foundation awarded Jackson Laboratory Assistant Professor Gareth Howell, Ph.D., with the 2013 Shaffer Prize for Innovative Glaucoma Research.
Howell received the award from Thomas M. Brunner, president and CEO of the Glaucoma Research Foundation, at the annual Catalyst for a Cure Benefit Gala at the Palace Hotel in San Francisco on Jan. 31.
The Shaffer Prize, presented annually by the Glaucoma Research Foundation, recognizes the researcher whose project best exemplifies the pursuit of innovative ideas in the quest to better understand glaucoma. Howell was recognized for his study investigating the mechanism by which a spontaneous mutation prevents retinal ganglion cell death in glaucoma.
Glaucoma is a complex disease characterized by the loss of the nerve cells in the retina known as retinal ganglion cells, Howell explains. While working as a research scientist in the laboratory of Professor Simon W.M. John, Ph.D., Howell and Research Assistant Katharine Harmon investigated the multiple events that occur prior to the demise of these cells.
"Using funds kindly provided by the Glaucoma Research Foundation, we have adopted a new strategy using a mouse model of glaucoma that has been genetically modified to prevent loss of nerve cells," Howell says. To develop improved and new therapies for human glaucoma, Howell notes, "it will be important to boost beneficial responses and lessen or inhibit damaging events."
Now a principal investigator with his own lab, Howell is continuing to explore the fundamental processes involved in the initiation and early propagation of glaucoma, as well as those of other age related neurodegenerative diseases including Alzheimer's disease
The Jackson Laboratory for Genomic Medicine in Connecticut has appointed Stanford University computational biologist Zhengqing Ouyang, Ph.D., as assistant professor.
Ouyang received Ph.D. training at Stanford University in the laboratory of Wing Hung Wong. Since 2010, Ouyang carried out postdoctoral training in the laboratories of Michael Snyder and Howard Chang at Stanford's School of Medicine. Snyder made news last year as perhaps the world's most analyzed person, leading proof-ofconcept research that integrated his own genomic sequence with RNA, protein, metabolic and auto-antibody profiles. Interestingly, Snyder's genome showed a genetic predisposition to type 2 diabetes, which he developed following a viral infection. He managed the disease through early and significant lifestyle changes.
At JAX Genomic Medicine, Ouyang will develop statistical methods for analysis of data from novel technologies to reveal new layers of biology. He will also develop predictive models for integrative analysis of high-throughput sequencing and functional genomics data. He aims to facilitate the understanding of the global gene regulatory network in cellular processes and human diseases.