By Asu Erden
“Don’t stay here, go to the U.S. if you can.” I heard my fair share of invaluable insight into the world of scientific research during my time at the Pasteur Institute in Paris, but this one really stuck with me. “The difference between Europe and the United States is that, if there are about ten hypotheses you can formulate to address a specific question, in France we have to choose the three or four more likely ones to test. In the U.S., they can test all ten in a heartbeat without worrying about funding.” This romanticized view of scientific research in the U.S. held some truth to it when I heard it back in 2005. But while the U.S. seemed to be the Eden of scientific funding in the early 2000s, funding cuts have had a tremendous impact on the state of research in the natural sciences on this side of the pond too.
A historical overview of public science funding
The National Institutes of Health (NIH) is the United States government’s medical research agency and the largest source of funding for medical research in the world. However over the last decade, it has not been able to fund as many projects as it used to. The funding for research project grants by the NIH – including the much coveted R01 grants which determine a lot of the tenure track positions in the natural sciences – increased steadily between 1995 and 2003, but has decreased by over 20% since 2004. “With shrinking government funding (or flat-lined, which is the same as shrinking), labs have to look for alternative sources, it’s just a fact of the situation,” admitted Dr. Heather Marshall, a former postdoctoral researcher in the Immunobiology Department at Yale University.
The percentage of successful research grant applications to the NIH was of 26.8% in 1995, reached 32.0% in 1999, before decreasing to 17.5% by 2013. “The state of funding most definitely shifted during my postdoc and it was most evident when discussing with PIs [ED: principal investigators], successful ones at that. The attitude was depressing and demoralizing. The funding percentiles of postdoctoral fellowships went down each year I was a postdoc and it became evident that attaining a fellowship was mostly out of your control,” shared Dr. Marshall. The success rate for new applications, which new faculty members rely on to start up their labs and research, has fluctuated between 18.6% in 1995, reached approximately 22% by 1999, before plummeting to 13.4% in 2013. According to the latest numbers, this means that investigators are 37.8% less likely to obtain an R01 or equivalent award today than they were in 2003. This decrease is partially explained by the NIH budget being cut by over one fifth of what it was in 1995.
Most of the time, it is the task of PIs – i.e. the professors running labs – to write grants lauding the importance of the research carried out in their laboratories in order to ensure the future of their line of research and that of their trainees. Graduate students and postdoctoral researchers also apply for fellowships and grants but the pecuniary benefits at stake only really affect their own work, not that of the lab overall. With the success rates for grants – new or continued – decreasing over the last decade and a half, grant applications have become particularly stressful endeavors. While PIs usually serve as a protective shield from this reality, it seems to be increasingly hard to cut the stress out…”I’ve been in research since 2003. PIs are communicating their stress more,” said Dr. Smita Gopinath, a postdoctoral researcher immunology at Yale University. The situation is not as dire in Ivy League or top tier universities. But for those PIs that do not work for private universities, loss in funding means laying off personnel or closing their lab altogether. This hinders research and in the long run biomedical advances.
With this decrease in funding for research in the natural sciences comes a sense of lack of job security for the extremely skilled highly educated workers that scientific researchers are. “Funding directly impacts the number of jobs available, so in that sense the state of funding absolutely played a major role in my decision to leave academia,” said Dr. Marshall. “In addition to that, I was worried that I wouldn’t get enough grants to fund the projects I wanted to take on, which would also impact my ability to train students and postdocs. That caused a lot of anxiety and I didn’t even have a job yet!”
The budget fluctuations in the NIH and other science funding agencies accompany political changes in the White House, the Senate, and the Congress. During the Bush presidency, the NIH funding initially increased between 2001 and 2003 but suffered a big decrease from then onwards. Entire fields of research were completely defunded such as stem cell research. In 2009, Obama refunded these fields but the NIH has not seen an increase in budget to match inflation. Over the last few years, Republicans have increasingly criticized a number of national agencies such as the National Science Foundation (NSF) and the NIH for the type of research they fund. “Sometimes these dollars they go to projects having little or nothing to do with the public good. Things like fruit fly research in Paris, France. I kid you not!” exclaimed McCain’s running buddy, ever-entertaining Sarah Palin, during the 2008 presidential campaign.
The importance of funding basic sciences
You may argue that basic research does not always lead to biomedical advances that can be translated to the treatment, cure, or prevention of infectious or non-infectious diseases in humans. “It’s like the mosquito bed net problem. I have so many friends that work on malaria but stop and think, “My stipend can buy 200 bed nets, what am I doing with my life when I could save people directly?” This is the eternal struggle,” shared Dr. Gopinath. “Why fund basic science? Because at some point bed nets will not be effective enough.” There lies the central problem of basic science funding. It can take years between the research and its putative application for humans. This time lag has affected the mentality of the funding agencies. There is a growing gap between what the NSF, which has traditionally funded more basic research in the natural sciences, and the NIH fund, which now funds more translatable research endeavors.
But you never know where the next thing is going to come from. The nature of basic research is that while fuelled first by scientific curiosity, it also aims to develop our understanding of the world surrounding us in order to potentially make translational contributions. Let’s take Sarah Palin’s insightful comments on fruit fly research. In 1933, Dr. Thomas Hunt Morgan received the Nobel Prize for his research on the inheritance of physical traits. His animal model? The fruit fly. Since then, fruit fly research has led to the identification of genes as the unit of biological inheritance, to understanding how organismal ontology works, and to the now growing field of epigenetics. Working on fruit flies, scientists have also been able to identify key components of the immune system, which in the long run increased our power to medically reduce human suffering. Drosophila melanogaster – one of the more studied fruit fly species – has provided much insight into the role of genes in neurological behavior including human genes involved in autism. The irony…I kid you not Mrs. Palin!
Many of the drugs and treatments we use today are derived from such discoveries in the basic natural sciences. 40% of the medical drugs we use target a protein family known as G protein-coupled receptors (GPCRs), which translate signals external to the cell into intracellular signaling. Hormones, neurotransmitters in the brain, and even light can activate these receptors leading to biological processes such as vision, taste, smell, mood regulation, and that of the immune system. Drs. Brian Kobilka and Robert Lefkowitz won the Nobel Prize in Chemistry – not Physiology and Medicine – for solving the crystal structure of this class of transmembrane proteins. Their work focused on the chemical structure of GPCRs. This had immense ramifications in understanding how these receptors transduce signal from outside the cell by interacting with components inside the cell. Eventually, it led to the better understanding of the cellular and physiological processes these receptors are involved in which allowed the scientific community to recognize their central importance in drug targeting. From crystals we reached therapy.
Other examples of basic science research leading to translational advances abound. Dr. Jennifer Doudna moved to the University of California Berkeley in 2002 where she started studying how bacteria can defend themselves against viruses that infect them, also known as bacteriophages. In particular, she was interested in the clustered regularly interspaced short palindromic repeats – CRISPR – in bacterial genomes that enable these microbes to kill off bacteriophages that previously infected them. With help from collaborators, Dr. Doudna was able to identify Cas9 as the protein allowing for this viral DNA editing. Thus was born the CRISPR-Cas9 system. Since its discovery in 2012, this system has allowed the genome editing of multiple cell lines commonly used in research, but also organ-specific genetic editing in mice. The method allows scientists to make mouse lines with permanent gene silencing – also known as knock-outs – in a matter of a few weeks where it previously took them years to breed the gene of interest out. Moreover, CRISPR-Cas9 allows researchers to delete genes of interest in fully developed mice, as opposed to embryonic deletions of genes, which can prove fatal if they are required during development. The technique is set to allow for great medical advances especially if applied to the genome editing of hematopoietic cells to cure blood disorders such as sickle cell anemia, primary immunodeficiencies (such as AIDS), and cancer. When Dr. Doudna’s research was funded, no one knew the implications it would have. It took over ten years to go from better understanding bacterial defenses against viruses to developing an incredibly potent tool that will potentiate the cure of many human woes.
Better tailored funding for the natural sciences involves better communication
There is a mismatch between the public’s understanding of the importance their taxes play in funding fundamental scientific advances and scientists pleading for politicians not to further cut their funding. As Dr. Marshall pointed out “We can’t really expect all government officials to have strong science backgrounds if they are also expected to have strong backgrounds in law, history, economics etc., but we absolutely need to have our representatives surrounded by scientists. So from that perspective, [better science funding] does start with the general public.” The nature of scientific funding, as with all funding, is that it is limited. “We can’t rely on our achievements alone. We need to put it out there and communicate the importance of scientific research,” shared Dr. Gopinath. “We need to be managers and communicators. We do get training to collaborate with other scientists and communicate on that level. Communicating science to non-scientists is not at all on our radar!”
It is usually the University Office, which is in charge of what gets or does not get communicated about the scientific research carried out on campuses. While the impetus should not be on scientists to carry out science communication by themselves, additional training of PhD students, postdoctoral fellows, and PIs is required. When a journalist picks up the phone to talk about the latest advance in stem cell research, she should not face a public relations wall. Perhaps unbeknownst to the public, researchers have to meet an astounding number of training requirements annually to be able to continue carrying out their research: radiation safety, animal care and use, biosafety, laboratory chemical safety, medical surveillance for animal handlers, blood-borne pathogens and so on and so forth. To these requirements we should add science communication. The ramifications are countless!