Powering Diabetes Research
Timely support puts scientists on the path to breakthroughs
Science is hard—and not just because it involves lots of math. No, the real challenge, scientists will tell you, is getting someone to pay for your research. And the funding situation isn't getting any better. In 2011, the National Institutes of Health (NIH), which is the country's largest source of research funding, reported that only 18 percent of grant applications were successful, compared with 31 percent in 1998.
A university will pay a tenured professor's salary even without government grants and often provide a little start-up money to a newly hired researcher. But grants allow a researcher to purchase laboratory equipment, employ support staff and students, and buy any other supplies that are necessary to carry out groundbreaking studies. Getting grant money from the government—as opposed to big business—allows scientists to do work that may benefit humankind regardless of whether it's likely to be profitable.
Winning grant money from the NIH is particularly difficult these days for young researchers. In 1980, the average age for getting a first big NIH grant was 35. Today, it's 42. Grants seem to beget more grants, so getting that first award is a critical challenge. "The competition for research funding at NIH has become brutal," says Robert Ratner, MD, FACP, FACE, chief scientific and medical officer at the American Diabetes Association (ADA).
That's why nongovernmental organizations, such as the ADA, are important alternate sources of grants (the ADA provided a total of $34.6 million in 2012 alone), some of which exclusively target and nurture young researchers. "The greatest creativity and innovation usually come from young minds," says Orville Kolterman, MD, chair of the ADA Research Foundation. "So we need to be attracting young investigators into the field of diabetes."
Here are the stories of five scientists, three just starting out and two with distinguished careers, who received awards from the ADA at critical moments and now work each day to improve the lives of people with diabetes.
ADA Research Grant Program: Emerging Talent
Hubert Tse, PhD (photograph by Jason Wallis)
Assistant professor, Department of Microbiology, University of Alabama–Birmingham School of Medicine
I've always been drawn to science, says Tse. "I really like making discoveries." Tse has taken a circuitous route in his scientific interests, starting out studying microbiology as a graduate student at the University of Colorado in Denver. He moved to Colorado State for a postdoctoral fellowship. A postdoc is a kind of junior associate in the academic world, somewhere between being a student and a professor.
|Pathway to Stop Diabetes: Big Bucks, Bold Ideas|
|Hypothesis: Brilliant young scientists with radical new approaches can bring us breakthroughs. "If someone has an idea that's off the wall but bright, intelligent, well thought out, and plausible," that's something the American Diabetes Association research portfolio is now poised to invest in, says Orville Kolterman, MD, chair of the ADA Research Foundation.
Catalyst: The ADA's new grant program, Pathway to Stop Diabetes, launched in 2013 with founding support of $20 million from Eli Lilly & Co., Novo Nordisk, and Sanofi. The program is set to ignite an explosion of research talent. Winners of the grant will receive up to $1.625 million. This tops the prestigious $1.5 million Howard Hughes Medical Institute awards for early career scientists in biomedical research.
Results: "Pathway will fund investigators rather than projects in order to give these scientists the independence to pursue their visions free from the distractions of writing other grants," says Robert Ratner, MD, FACP, FACE, ADA chief scientific and medical officer. The projected outcome? Significant innovations in treating, preventing, and curing diabetes.
Postdoc pay isn't great, especially considering these are doctors we're talking about—the NIH set the minimum salary for postdocs with no experience at $39,264 for fiscal year 2012. A fresh PhD entering the private sector can expect to make considerably more. But a postdoc salary is enough to live on and often includes good benefits, and it's a stepping-stone to the dream that drives many a young scientist: a tenured professorship. The postdoc's life in the lab includes some independence, but a supervising professor still provides the lab space and funding, though some postdocs get their own small grants. Today, most science PhDs do multiple postdocs—so this phase can last five years or more—before landing an assistant professorship.
At Colorado State, Tse began studying the body's immune-system response to disease-causing organisms (pathogens). That brought him one step closer to investigating type 1 diabetes, which is a disorder of the immune system. A couple of years later, a friend who studied type 1 at the University of Pittsburgh offered him a postdoc in his laboratory. "That's when I fell in love with type 1 diabetes research," Tse says. At that time, he received an ADA grant. "I was lucky to get a Junior Faculty Award from the ADA right at the end of my postdoc," he says. That put him on track to do sustained diabetes research.
Tse is back to studying pathogens, in the context of how viruses may trigger an autoimmune response that causes type 1 diabetes. He also is looking into the connection between oxidative stress on the body's cells and the immune response that kills the insulin-producing beta cells of the pancreas. "The fact you can really help kids born with the disease is very gratifying," says Tse. "I hope in my lifetime we find a cure. The amount of knowledge we've gained from the first day I started is incredible."
Ling Qi, PhD (photograph by Brady Dillsworth)
Assistant professor, Division of Nutritional Sciences, Cornell University
As a child in China, Qi began to imagine a future in science. "I was always fascinated by science as a little boy," he says. Qi started out his research career studying viruses, bacteria, and other sometimes dangerous critters. "I didn't get interested in diabetes until way later," he says. In graduate school, he started researching the body's immune response and continued along those lines in his postdoctoral fellowship, studying how tumors can trigger an immune-system reaction. But in 2003, near the end of that postdoc, Qi thought it was time to move in another direction.
"After being in the United States for six years," he says, "I started to become very fascinated with obesity. How does obesity occur, and how does [type 2] diabetes occur?" He decided after his first postdoc to spend time in a diabetes lab. "I felt like I'd seen the future in the diabetes field," he says. After a few years, he landed an assistant professorship at Cornell. In his first year there, he applied for an ADA Junior Faculty Award and received it. "These funding sources are critical," he says. "They give us a lot of time to do the things we want to do and get enough data to apply for NIH grants. Nowadays, with funding being so low, a lot of people get frustrated. If you don't have a lot of preliminary data, it won't go well with NIH funding. Funding from ADA or other smaller agencies becomes critical to survive."
Qi began studying the emerging science of how protein folding influences the way cells function. Proteins are long strings of chemicals that must fold up into a three-dimensional structure, something like origami, to work properly. Qi discovered a protein that is made by fat cells and appears to help a wide range of other proteins to fold up correctly. In diabetes, there is less of this helper protein, which leads to misfolded proteins and broken fat cells. These dysfunctional fat cells lose their ability to respond to insulin, which is a hallmark of type 2 diabetes. "It was totally unknown how folding and misfolding controls insulin sensitivity," says Qi. He hopes that his research in protein folding will offer new opportunities to prevent insulin resistance and type 2 diabetes.
Norma Frizzell, PhD (photograph by Jeff Amberg)
Assistant professor, Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina School of Medicine
Why did she want to be a scientist? "I've always been curious," says Frizzell, who is 34 and a new mother. She studies how excess nutrients may alter certain biological molecules, particularly those in fat cells, and how this process affects the health of people with diabetes.
Frizzell's very first project, which she undertook while attending university in her native Ireland, was related to diabetes. "I got a six-week internship at a hospital on diabetic retinopathy. I had not been in a lab before," she says. "I ended up doing my PhD in that lab."
Frizzell then came to the United States to learn a new technique as a visiting scientist at the University of South Carolina. She liked it so much that she stayed to do a postdoc. After her first postdoc, Frizzell returned to Ireland to do a second one, until she was offered a position as a research scientist back in South Carolina.
This was a crossroads in Frizzell's career, because unlike a tenure-track position, the research scientist job wouldn't allow her to run her own lab, with job security, her own students, and a good salary. She applied for and received an ADA Junior Faculty Award, which provides support for postdoctoral fellows or scientists just starting out. This grant gave her the resources to start gathering data to publish in peer-reviewed journals, establishing her as a scientist with potential and helping her successfully apply for a tenure-track position.
In these research papers, Frizzell describes a process called succination, in which succinate—a byproduct of metabolism—gets stuck to important protein molecules, gumming up the works. "This modification is interesting because, unlike other modifications, this one is permanent," she says. "Nothing can take it off, so it accumulates at high levels and may cause damage." Succination seems to occur more frequently in the context of diabetes, and this abnormal reaction, Frizzell hypothesizes, may be responsible for certain diabetes complications.
The ADA grant "has been invaluable for my career," Frizzell says. These types of awards show that you stood out from a bunch of other people. "People have faith that you are going to continue to succeed." Frizzell hopes the studies this grant supports will give her enough experience to apply for and win NIH grants.
ADA Research Grant Program: Proven Producers
Robert Henry, MD
Professor, Division of Endocrinology and Metabolism, University of California–San Diego School of Medicine
Henry started as a physician treating patients but began doing research in endocrinology soon after medical school. Before the 1970s, "we didn't know anything about [diabetes]. There wasn't a lot of information," he says. "In the beginning, I did a lot of nutrition and dietary therapy and looked at how lifestyle makes a difference."
Early in his career, he won a Research Award from the ADA, so he could start studying diabetes on a deeper level. "I'm not sure I would have been able to continue as a researcher without the grant of the ADA. … That gave me a real big springboard," he says. "Without grant money, you can't do research." Henry went on to receive a series of important NIH grants.
In his long career, which has included serving as the ADA's president for medicine and science, Henry has made many significant contributions to the diabetes field. "I'm very interested in what comes out of muscle and what comes out of fat," he says. These molecules act as signals for the rest of the body, he says; some may be harmful and some may be good. "We have discovered hundreds of hormones that are released," he says. "The big question is which are important." He continues to seek new answers.
George King, MD
Professor of Medicine, Harvard Medical School
"I've been involved in research projects ever since high school," says King, when he got a summer fellowship and studied an enzyme involved in heart attacks. While in medical school, King spent a year doing basic research on gout, a metabolic disease. During his residency, King switched his focus to diabetes and never looked back. He applied for and received an ADA grant when he was 31 years old. "Getting the grant was huge. From that, we collected preliminary data," he says, "and then got an NIH grant a year later." King, who is director of research at the Joslin Diabetes Center, has had NIH funding ever since.
Some of King's research involves studying people who are complication-free after living with type 1 diabetes for 50 or more years. "Then we can compare people who develop eye and kidney disease with those who don't," he says. He hopes to find biological molecules that can protect people with diabetes from developing complications and use that information to help create new medications.
Though he's been studying diabetes for decades, King still has a special place in his heart for the kind of ADA grant that launched his career. "It entices people to go into diabetes research," King says. "If you can turn that into additional grants, then you can stay in diabetes research." And the more smart people there are in diabetes research, the sooner they can find a cure.