Getting large – or, for that matter, small – numbers of academics to collaborate has been compared by some to herding cats.
The National Institute of General Medical Sciences, a unit of the National Institutes of Health (NIH; Bethesda), has decided that a good way to herd cats is to glue them together. The institute makes available large-scale collaborative grants, called “glue grants,” with the goal of encouraging independently funded investigators to collaborate on major biomedical research problems. The money is meant to glue together geographically dispersed scientists.
In some areas at least, the approach seems to be working. In the March 29 issue of the Proceedings of the National Academy of Sciences, a multidisciplinary glue-grant funded research program on “Inflammation and the Host Response to Injury” reported on the analysis of gene expression changes in white blood cells response to trauma-induced inflammation.
The current study’s lead author, J. Perren Cobb, hails from Washington University Medical School (St. Louis), where he is associate professor of surgery and genetics.
“Trauma is the fifth-leading cause of death in this country, and the No.1 cause between the ages of 2 and 40,” Cobb told Medical Device Daily’s sister publication, BioWorld Today. The scientists specifically studied gene expression changes after an inflammatory response to trauma, a condition known as systemic inflammatory response syndrome, or SIRS.
“It’s really a wastebasket name for anything that causes activation of the inflammatory response and the loss of the host ability to control that inflammatory response,” Cobb said. “We use trauma as a model, as one type of insult that can cause SIRS. But we believe that this information will ultimately be of interest to a broad range of clinicians.”
In recent years inflammatory processes have been found in an extremely wide variety of diseases, including acute conditions like sepsis, trauma and pancreatitis, but also more chronic diseases such as cancer, rheumatoid arthritis and Alzheimer’s disease.
Cobb said the current publication “represents our report to the medical community that this can be done, despite the fact that microarrays are exquisitely sensitive to the details of sample collection.”
Standardized protocols enabled data collection in such a way that the differences between trauma and control patients could be seen over the variance generated by the analytical procedures and the fact that the research was conducted by more than 70 investigators at 20 institutions across the continental U.S.
Developing those protocols took 2-1/2 years. Once they were done, however, the researchers were able to show that despite the fact that trauma patients had greater variability in gene expression than controls, it was possible to detect changes in a number of genes. They also found that changes in gene expression were different in different types of blood cells; neutrophils, monocytes and T cells all showed distinct changes in gene expression.
The long-term goal of the program is to identify the physiological processes behind SIRS, and from there, develop a diagnostic and therapeutic arsenal to combat the condition.
Cobb said the consortium has been collecting longitudinal data from trauma patients and that a report on gene-expression changes of patients as they go through the stages of inflammation in response to trauma is planned.
“We hope to figure out the difference between individuals who survive and those who die, given what looks to be the same level of injury,” he said. “We hypothesize that there is a huge genetic component to this, and that is what we are testing now.”
While the study of gene-expression changes already is part of determining treatment options in diseases like cancer, the response to injury occurs over a considerably shorter time period, putting extra demands on its use there.
Nevertheless, Cobb hopes that once the researchers identify gene-expression changes involved in SIRS, “our partners in industry will create tools that allow us to take advantage of this knowledge.” He said that it will ultimately be possible to use gene-expression changes to help guide treatment even in such a time-critical environment as the ER.
The research program has no industrial collaborators, but Cobb noted that lead investigator Ronald Tompkins from Massachusetts General Hospital (Boston) is in discussions regarding collaborations and intellectual property issues. However, while Cobb expects the project to lead to commercial products, he noted that another goal of glue grants is to make information from large-scale collaborations freely available to benefit the larger scientific community – which the project is doing by publishing both papers and their protocols.
“Since we spent millions of dollars validating this, no one, at least in the short term, should have to do it again. All of our protocols are available for free,” he said.
“That is also one of the reasons we chose to publish in the Proceedings of the National Academy of Sciences, and why we chose open-access publication. Given the money we’d spent on the research, it was really a no-brainer.”