Dr. Elazer R. Edelman, director of the Harvard-MIT Biomedical Engineering Center, is an electrical engineer who became a cardiologist and went on to do path-breaking work on the use of stents, small mesh tubes placed in narrowed or weakened arteries for the treatment of heart disease.
Of necessity, he and his colleagues had to develop skills in fields such as metallurgy, materials science, tissue kinetics, vascular biology, polymer chemistry, and computer modeling. Such interdisciplinary work has become the norm on the frontiers of translational research in the biomedical sciences. So when Edelman talks about the forces driving biomedical innovation, as he did at a recent AAAS-organized lecture on Capitol Hill, he does so from personal experience.
Edelman is concerned that what he calls the “Big Bang” in medicine and engineering—the explosion of new knowledge in diverse fields—could actually hurt innovation and slow scientific progress.
Researchers who once might have been able to encompass knowledge across many fields are in danger of being overwhelmed. As a discipline grows in mass, Edelman said, the practitioners at the core tend to lose sight of developments on the periphery. Those on the edge lose sight lines to the core. And practitioners in each discipline, in turn, lose view of the developments in adjacent disciplines.
By analogy, he argued, the disciplines are growing apart as the universe of knowledge expands, much as the galaxies diverge in an expanding cosmos. The challenge of the future, Edelman said, is to master the connections that bind disciplines together, just as dark matter binds the galaxies.
“It becomes harder and harder to bridge disciplines once you let them slip away,” Edelman said in a wide-ranging 17 April talk sponsored by AAAS and the journal Science Translational Medicine, which is published by AAAS and for which Edelman is co-chief scientific advisor.
“The argument that one must focus on mastering only a single field is a slander on human capacity, bound to isolate and separate rather than coalesce and advance science,” Edelman said. Science pursued in isolation is, by its nature, a selfish pursuit, he said. Without community goals and ambitions, he argued, the exercise ultimately is sterile.
“There is a moral obligation to science,” Edelman said, and the realization of that obligation takes practical form through the discipline of engineering. He noted the Webster’s Third New International Dictionary definition of engineering, described as the “application of science and mathematics by which the properties of matter and the sources of energy in nature are made useful to people.”
Recalling his own efforts to make science useful to people, Edelman described his introduction to the world of biomedical research as a young electrical engineer with an interest in cardiology. Morris Karnovsky, an eminent Harvard University pathologist who was to become one of his mentors, warned that “the dumbest blood vessel is smarter than the smartest vascular biologist.”
Undeterred, Edelman pressed on and eventually undertook fundamental studies on the design and performance of cardiac stents, which are snaked into heart arteries via soft, thin tubes called catheters inserted into blood vessels. One of the risks is that scar tissue will grow in the area of the stent, narrowing the artery once again. Edelman and his colleagues helped perfect a drug-coated stent that delivers time-released medication that can limit the growth of scar tissue.
Dr. Elazer R. Edelman [Credit: AAAS]
Such drug-eluting stents, as they are called, are now widely used, have low failure rates, and, according to Edelman, should be considered on a par with antibiotics and the perfection of anesthesia as one of the most transformative innovations in medicine.
A key to the success has been the team’s use of sophisticated computer models to predict the performance of different kinds of stents under a variety of conditions. “We can actually marry our understanding of tissue binding with computational modeling,” Edelman said, in order to target “where we want the drug to go and how many receptors are bound so we can get very high local concentrations or more uniform concentrations” of the drug.
The stent designs are made to exacting tolerances by industrial firms and permit delivery of just the right amount of drug deep into the artery. Successful innovation, Edelman said, depends on such collaboration by those who envision new scientific approaches and those who can implement them for practical benefit.
He cited some historical examples, including Wilhelm Konrad von Röntgen, credited with discovering X-rays in 1895. He selflessly refused to patent his finding, maintaining that his discovery should be free for the benefit of humankind. Others followed through with commercialization of devices such as inventor Thomas Edison’s fluoroscope, which made X-ray use widely available.
Academic-industrial collaboration “rather than being seen as a conflict, needs to be celebrated in this country,” Edelman said.
In pursuing new innovations, he said, there must be a balance between the need to protect patients from unnecessary risk (the traditional medical dictum to “First, do no harm’) and the pressure, as in the field of oncology, to rush to treat critically ill patients with new devices and treatments that inevitably carry risks. Edelman proposed his own guiding principle: “Above all, seek to understand.”
That inevitably means an interdisciplinary approach, Edelman argued. Even some of the historical figures who are celebrated as lone wolves were multidimensional thinkers who borrowed from many disciplines, he said, including Ernest Rutherford, the father of nuclear physics, and Albert Einstein, who published multiple breakthrough papers in a single year—1905—on Brownian motion, the photoelectric effect, and special relativity.
The trick, Edelman said, is to nurture researchers who are able to incorporate the best ideas from multiple disciplines in their work. It is more important for a biologist to have a knack for learning how to use science and engineering on specific problems, he argued, than to have multiple doctorates in different fields.
Asked whether he had any policy recommendations to support his call for such multidisciplinary thinking, Edelman urged more attention to funding of individual scientists who show promise for such thinking rather than funding of large research institutes through senior investigators with proven track records. “We need to identify investigators whose careers we want to foster,” Edelman said.
Edelman also reiterated his support for university-industry collaboration. “The best way to get technology into the clinic is to let industry get involved,” Edelman said. And if academic scientists start companies based on advances funded by federal agencies such as the National Institute of Health, he said, both the researcher and the funding agency should benefit. “The NIH should get back something for what they did,” he said.
Edelman also said that, in a time of tight budgets, the challenge for lawmakers is not just to provide more funding for biomedical research. “We need to re-evaluate what we fund, how we fund it, and how people use the funds we give them.” That includes an ethical obligation on the part of researchers to make sure they are using funds properly, he said. “It’s an obligation I have to my patient,” he said, for the time he is taking away from his clinical practice to do research.