Over the past months, a team of scientists had reviewed Wilson\u2019s proposal for the NIH and scored its scientific merit and likelihood of success. The score waiting in Wilson\u2019s inbox would tell him if the NIH would fund his work for the next five years, bringing science that much closer to a cure. Heady stuff, but there was also something personal at stake for Wilson. Although he had earned grant money before, winning an R01 would mean that he would finally become, as Kotton says, \u201ca card-carrying, bona fide independent researcher.\u201d He took another deep breath, then he went to the NIH website for his score.<\/p>\n
\u201cIt\u2019s actually one of the most tense, defining moments in a scientific career,\u201d says Kotton, a founding director of BU\u2019s Center for Regenerative Medicine<\/a>(CReM), a MED professor of medicine and pathology, and an attending physician in pulmonary and critical care medicine at Boston Medical Center<\/a>. \u201cThere are very few crystal clear moments in science, but that\u2019s one of them. You know when you click on that button that you\u2019re either going to see a score in a percentile that makes you happy, or you\u2019re going to see the dreaded ND\u2014not discussed.\u201d ND means your grant has been \u201ctriaged,\u201d sent packing without discussion and formal comments. \u201cThat\u2019s hard to recover from, statistically,\u201d says Kotton. \u201cYou really want a good score.\u201d<\/p>\n These are tough times to be a scientist relying on NIH money. The NIH is the major source of federal funding for biomedical research in the United States, supporting over 300,000 scientists working at more than 2,500 universities, hospitals, and research institutions, according to a report<\/a> from the Congressional Research Service. Although researchers find money elsewhere\u2014scientists in Kotton\u2019s lab have secured funds<\/a> from theMassachusetts Life Sciences Center<\/a>, theAmerican Lung Association<\/a>, and theAlpha-1 Foundation<\/a>, among others\u2014the NIH is the big enchilada, distributing about $30 billion in FY 2014. But that $30 billion figure has barely risen since 2003, and has actually declined in constant dollars. Researchers use words like \u201cfrustrating,\u201d \u201cgrim,\u201d and \u201cpainful\u201d to describe the current funding situation. \u201cThe resulting strains have diminished the attraction of our profession for many scientists\u2014novice and experienced alike,\u201d notes a gloomy 2014 article<\/a> in the journal PNAS<\/em><\/a>, coauthored by formerNational Cancer Institute<\/a> leader Harold Varmus. \u201cEven the most promising trainees are increasingly pessimistic about the future of their chosen career.\u201d<\/p>\n Except, it seems, for Darrell Kotton and his posse of scientists. Like a cluster of hardy cacti, they have managed to bloom in the desert. Kotton runs CReM with cofounders and codirectors Gustavo Mostoslavsky<\/a> and George Murphy<\/a>, both MED assistant professors of medicine, and their center is home to 34 scientists at multiple levels, from students to postdocs to faculty. Within CReM, Kotton, Wilson, and another scientist, Laertis Ikonomou, a MED assistant professor of medicine and a College of Engineering assistant professor of biomedical engineering, have created an unusual three-headed lab group they informally call KIWI<\/a>, for Kotton, Ikonomou, and Wilson. \u201cWe always worked closely together, and just decided it was a good model,\u201d says Ikonomou, who trained under Kotton. \u201cIt\u2019s much more efficient.\u201d For instance, he says, if one of Kotton\u2019s technicians finds a new recipe for growing stem cells, he or she shares it with the group. \u201cThen I don\u2019t have to make the recipe from scratch,\u201d he says. \u201cIt saves a lot of time and effort.\u201d<\/p>\n All three scientists are principal investigators\u2014PIs in science lingo\u2014who raise their own money, but they hold joint lab meetings, share ideas and equipment, and pool all their grants and resources. \u201cThat way the science isn\u2019t so disproportionately influenced by the waxing and waning funding of any individual PI,\u201d says Kotton. At the moment, though, and for the foreseeable future, the K of KIWI is the group\u2019s biggest rainmaker. Since fiscal year 2005, Kotton alone has received $9,692,409 in direct NIH funding, as well as $406,550 in NIH \u201cflow-through\u201d funding\u2014money given to other researchers who subcontract to Kotton and his scientists. That\u2019s in addition to the millions he\u2019s pulled in from foundations and other sources. No wonder he seems perpetually upbeat. \u201cI think we\u2019re the happiest guys in the world,\u201d he says often\u2014and means it. Visitors to his lab wonder what he\u2019s been drinking and where they might get some.<\/p>\n \u201cHe\u2019s just a glass-half-full kind of person,\u201d says Linda Hyman<\/a>, associate provost for the Division of Graduate Medical Sciences<\/a> at MED. \u201cI\u2019m sure he has his moments, but his upbeat nature is infectious and people want to work with him.\u201d When Hyman needed someone to speak to potential graduate students thinking of coming to BU, Kotton was the obvious choice. \u201cWe wanted to put our best face forward, and he was just awesome,\u201d says Hyman. \u201cI think half the people who came to BU came because of Darrell\u2019s talk.\u201d<\/p>\n His optimism spills over to the younger scientists in his lab. \u201cI think whining is harmful,\u201d says Kotton. \u201cWe\u2019re really trying to protect the young\u2014meaning our graduate students and younger scientists\u2014from a kind of negative thinking. We have to train them in the scientific method and put them in the most fertile soil so they can thrive. That isn\u2019t a soil contaminated with a lot of whining.\u201d<\/p>\n Finn Hawkins, a MED assistant professor of medicine and a junior member of Team KIWI, is a case in point. A physician, Hawkins came to Boston for a pulmonology fellowship in Kotton\u2019s lab. But he was so inspired by Kotton and captivated by the science that he never left. \u201cMy mind was totally blown,\u201d he says. \u201cI had no idea what I had been missing.\u201d Still, the choice of science as a career sometimes gives him pause. \u201cI\u2019ve seen some talented researchers really struggle,\u201d he says. \u201cBut I\u2019m in the best possible situation\u2014I have a great mentor, there\u2019s good science, and I\u2019m working as hard as I can. When you\u2019re a young researcher, there\u2019s so much gloom and doom around. You have to stay optimistic.\u201d<\/p>\n Of course, optimism alone doesn\u2019t bring in the grants. Kotton\u2019s team is full of gifted scientists, working in two fields\u2014stem cells and regenerative medicine\u2014that Hyman describes as very sexy. The KIWI group combines physician-scientists and straight PhDs, and Kotton says this mixture helps them envision clinical applications for their work\u2014the bench-to-bedside payoff that many funders now demand. This is evident is Kotton\u2019s overall research goal: to cure inherited lung diseases like alpha-1 and cystic fibrosis using induced pluripotent stem (iPS) cells\u2014adult skin cells that scientists reprogram, giving them the ability to grow into almost any type of tissue. In the near term, iPS cells may serve as surrogates for a patient, allowing doctors and scientists to test a battery of drugs on a patient\u2019s cells before trying them on the actual patient. That\u2019s the promise of personalized medicine, another field high on the \u201cvery sexy\u201d scale.<\/p>\n Within Kotton\u2019s KIWI crew, Ikonomou focuses on the biochemistry of the primordial progenitors, the 100 or so undifferentiated stem cells that eventually lead to all lung cells. Wilson works from a disease angle, studying how stem cells from patients with alpha-1 grow into abnormal liver cells, while those from healthy people develop normally. That, broadly, was the subject of his NIH grant proposal, the one with the score still sitting in his inbox.<\/p>\n Wilson clicked on the NIH website for his score: it was an 11. That means his grant ranked in the top 11th percentile. But in today\u2019s dismal funding environment, even an outstanding score like 11 is no guarantee of funding. Scientists have to hit the payline, the cold cutoff above which no money will be offered. These days, around 10 percent of NIH grant proposals are funded, says William Cruikshank<\/a>, director of the MED Graduate Program in Molecular and Translational Medicine<\/a> and a MED professor of medicine, pathology, and laboratory medicine. In the heady days of high funding, that number approached 20 percent; the lowest he\u2019s seen has been 5 to 6 percent. \u201cThe economy went down and NIH funding went down with it,\u201d Cruikshank says. At the same time, the cost of biomedical research, from fancy freezers to mouse models, has increased, leaving many scientists queasy over funding. \u201cThe real frustration is that you put in one grant and it\u2019s bare-bones\u2014just what you need to accomplish your minimum goals and nothing else,\u201d he says. \u201cThen that may get cut programmatically, and your bare-bones budget gets even smaller.\u201d The result is that most scientists cannot survive on one large NIH grant, as was traditionally the case. Instead, it\u2019s a constant scramble to write the papers and generate the data to create more strong proposals asking for yet more money. \u201cIt\u2019s truly a rat race to survive,\u201d he says.<\/p>\n That\u2019s why Kotton\u2019s system of pooling resources is so beneficial, Cruikshank says. But there\u2019s another, critical benefit: the collaboration improves the science. \u201cKotton has assembled a team with a lot of different expertise, and they fit together like a jigsaw puzzle,\u201d he says. \u201cEverybody\u2019s coming at the same problem from different directions. This lets you ask the broad questions that make science exciting. If everyone\u2019s inbred, it doesn\u2019t really go anywhere.\u201d<\/p>\n \u201cWe want to collaborate with as many people as we can. The constant, free exchange of ideas really helps the science,\u201d says Ikonomou. \u201cBeing well-funded is just a side benefit.\u201d It\u2019s a talent that\u2019s critical for grant writing, and one that Kotton takes pains to pass on to younger scientists. He had carefully coached Wilson through the long process of writing, and rewriting, his NIH proposal. Wilson had asked the NIH for $1.25 million over five years\u2014the standard R01 award\u2014to study alpha 1 in liver cells. Here\u2019s how he explains the proposal: \u201cWe think the cells are surrogates for the patient. That\u2019s widely believed to be the case, but it hasn\u2019t actually been proven. So for this grant we teamed up with a clinical trial in Pittsburgh of patients with alpha-1 and liver disease. There\u2019s a seizure medicine that has a side effect, which happens to help the liver cells deal with the abnormal alpha-1 antitrypsin protein inside them. It works in mouse models, and so in Pittsburgh they\u2019re giving these patients this drug for a year, and they\u2019re doing liver biopsies before and after. So we\u2019re making iPS cells from the patients who are in the trial, and basically trying to run the trial in a dish.\u201d<\/p>\n Kotten nods at his prot\u00e9g\u00e9, smiling at the perfectly executed pitch. \u201cIt\u2019s good stuff, isn\u2019t it? It totally makes sense.\u201d<\/p>\n It is good stuff. The NIH agreed. When Wilson saw his score was in the 11th percentile, he knew it was good. But was it good enough to hit the payline? He took a screenshot of the website and e-mailed it to Kotton. \u201cI thought I knew what it meant,\u201d he says, \u201cbut I just needed someone else to look at it and confirm what I was seeing, so I could believe it was real.\u201d Kotton called him moments later\u2014that year\u2019s payline was 13. The grant would be funded.<\/p>\n And if it hadn\u2019t been? \u201cOne of the hallmarks of people who are successful in science these days is a willingness to persist in the face of failure and rejection,\u201d says Wilson. \u201cAnd so I would have kept trying.\u201d<\/p>\n The feeling is echoed by younger Kotton mentee Hawkins, who says his biggest strength is not creativity or intelligence, but \u201can enormous capacity for failure.\u201d<\/p>\n \u201cMaybe if we actually paused and thought about the statistics for a moment, we\u2019d realize we\u2019re crazy and stop doing science,\u201d says Kotton. \u201cBut we\u2019re getting paid to be children. We play in the science lab, we do experiments, we try to figure out how nature works. I work with really smart young people, and mentor them, and really enjoy their success and emergence. It\u2019s really an amazing career. I wouldn\u2019t trade it for anything.\u201d<\/p>\n This <\/em>BU Today<\/a> story was written by Barbara Moran. She can be reached at\u00a0bmoran@bu.edu<\/a>.<\/em><\/p>\n","protected":false},"excerpt":{"rendered":" Amid science funding’s grim realities, one group is making it work Andrew Wilson read the e-mail. He took a few deep breaths. He read it again. It was a couple of days earlier than expected, but there it was, sitting in his inbox. Four months earlier, Wilson, a School of Medicine assistant professor of medicine, […]<\/p>\n","protected":false},"author":7398,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[90],"tags":[153],"_links":{"self":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/6214"}],"collection":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/users\/7398"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/comments?post=6214"}],"version-history":[{"count":0,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/6214\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/media?parent=6214"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/categories?post=6214"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/tags?post=6214"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}![\"The](\"\/camed\/files\/2015\/04\/NIH-appropriations.jpg\")
<\/a>The rainmaker<\/h3>\n
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\u201cI think whining is harmful,\u201d says Kotton. \u201cWe\u2019re really trying to protect the young\u2014meaning our graduate students and younger scientists\u2014from a kind of negative thinking.\u201d<\/span><\/h6>\n<\/blockquote>\n
An enormous capacity for failure<\/h3>\n
![\"Three](\"\/camed\/files\/2015\/04\/web_15-8713-KOTTON-006.jpg\")
<\/a>
\nKotton also has the rare gift of knowing how to explain the science. \u201cHe can communicate the excitement and relevance of what he does to scientists, the public, and investors,\u201d says Hyman. \u201cIt\u2019s a talent. He can tell the story.\u201d<\/p>\n\n
\u201cOne of the hallmarks of people who are successful in science these days is a willingness to persist in the face of failure and rejection,\u201d says Wilson.<\/span><\/h6>\n<\/blockquote>\n