Two months ago, Professor Frederick Sachs from SUNY Buffalo came to visit me. We talked about the science going on in our labs and what we hoped to accomplish. Then he told me about his own funding problems, problems caused entirely by the sequester, which now threatened his lab's incredibly promising work. I have been thinking ever since about Fred, his lab's work, and the lost opportunities they represent.
But then just as I finished writing about these thoughts, Fred called with a "happy" ending. But before I can explain how his work was rescued, I must explain how Fred's problem arose—and how American scientific research came to such a wasteful and dangerous state. The details of Fred's experience can serve as an example to Congress of what the funding changes are doing to American science. His trials give us a horrifying glimpse of what the ever-tightening National Institutes of Health (NIH) budget is doing to many investigators and their projects.
Fred studies how cells sense and react to mechanical signals, what happens to them when they touch other cells or are pushed or stretched. Often cells are thought of only as small chemical factories, but we know that mechanical signals can regulate what cells do. For example, normal cells stop moving and growing when they contact other cells, but cancer cells, which can be thought of as mechanically defective cells, do not.
Fred has pioneered the study of how cells detect mechanical signals. Several years ago, he discovered a molecule in tarantula spider venom that blocks mechanical sensing in normal human cells. After studying the effects of the molecule on normal cells and finding that it does not kill cells or turn them into cancer cells, Fred started thinking about whether any human diseases might be helped if mechanical signaling were reduced. This way of thinking about human disease was unprecedented, but the results of Fred's groundbreaking work are amazing. Fred and others have found evidence that suggests this molecule may help atrial fibrillation (affecting 2.3 million people each year in the United States1), muscular dystrophy (1 in 3,500 male births each year; muscular dystrophy mainly affects young boys2), and sickle cell anemia (1 in 500 African-American births and 1 in 1,000–1,400 Hispanic-American births each year3). I want to caution that what Fred and others have found are tantalizing hints, not cures or treatments. No clinical trials have been started. Nonetheless, the Food and Drug Administration recently classified the peptide as an orphan drug for muscular dystrophy, a necessary step in establishing a clinical trial. I am sure other human diseases that are affected by mechanical signaling will also come to light as the research continues.
Fred has a small lab and relies mainly on two senior scientists who have worked with him for many years. He has a grant from the NIH that funds the salaries of these coworkers. He recently heard that the competitive renewal of his grant received a score in the ninth percentile, which means that after thorough peer review his proposal was deemed better than 91% of the proposals reviewed by NIH, an "A" grade in an honors class. Unfortunately, Fred was told that because of the sequester, only proposals in the sixth percentile or better could be funded. As a consequence, he would not able to keep the two scientists he needs to continue his research. More importantly, their loss and the imminent end of his research program would not be easily reversed. His senior colleagues, who have developed their expertise with this work over many years, would have to move on and could not easily be replaced. The wealth of experience and knowledge that Fred and his group have acquired over the years, as well as Fred's enthusiasm and dedication to the project, would be irretrievably lost.
To me, Fred's story was heartbreaking because it is a story of how basic research, the type of research that is never supported by industry, can offer novel insights into and possible treatments for devastating human diseases. Without funding, that research and those crucial discoveries disappear. This is also a story of how the sequester has derailed research that has been years in the making, an action that is both penny and pound foolish; it throws away years of previous NIH investment. In addition, those of us who are teaching the next generation of scientists are hearing our students, postdoctoral fellows, and even our junior faculty colleagues say that the current funding troubles are convincing them to leave scientific research. Countries like China, India, and Brazil are enthusiastically building up their research commitment, while in the United States, the sequester is effectively destroying American science. Since NIH supports 430,000 jobs, the 5.7% reduction mandated by the sequester will cause the loss of approximately 25,000 jobs in scientific research.
Listening to the news, one would think that the worst consequence of the sequester was air travel delays. But these problems are nothing compared to the delays that the sequester and further cuts in research funding will produce in the discovery of new medicines, new treatments, and the new knowledge that enables even more breakthroughs in biomedical science. Or as Fred told me, "As the lab decays, I am terribly saddened by the loss of my creative partners, and I can't help but think of the kids with muscular dystrophy."
And then came the "happy ending" call from Fred: the NIH payline had been changed to the eleventh percentile. His research and his lab will not be stopped. I am happy for Fred, but the real problem extends far beyond his work. Moving the payline just a bit helped him, but imagine all the promising projects just across the payline, projects that will be abandoned or never begun.
Photos of Martin Chalfie © Eileen Barroso/Columbia University