Issue Date: March 28, 2005
Heart-lung machine. polarographic oxygen electrode. Synthetic blood substitute. Implantable glucose sensor. These are just a few of the dozens of inventions by biochemist Leland C. Clark Jr., whose propensity for designing medical devices has earned him numerous awards and accolades during his 60-year research career, including the nickname the "Edison of Medicine."
Clark's most recent award is one of engineering's highest honors: the National Academy of Engineering's 2005 Fritz J. & Dolores H. Russ Prize. It was given to him "for engineering membrane-based biosensors that benefit humankind in medical, food, and environmental applications." The $500,000 prize, established in 1999, is awarded every two years.
"My invention of the biosensor makes it easy now to monitor and control glucose, lactate, and dozens of other blood components," Clark says. He originally designed the electrode in 1962 to detect glucose, and it quickly became an essential tool in clinical studies of diabetes. The sensor uses glucose oxidase to oxidize glucose to gluconic acid and hydrogen peroxide, which can be detected electrochemically by oxidizing the peroxide to oxygen and water.
Although he is 86, Clark doesn't seem to have lost any of his inventiveness. "My latest patent, issued only four months ago, is a way to measure blood glucose from a tiny implant using a radio signal," he notes.
Clark received a B.S. degree in chemistry in 1941 from Antioch College, Yellow Springs, Ohio, and a Ph.D. degree in biochemistry and physiology in 1944 from the University of Rochester. He began his career as an assistant professor at Antioch, and he held concurrent research positions at Fels Research Institute, also in Yellow Springs, and at the University of Cincinnati College of Medicine.
He got started on the path to biosensors in 1949 when he created the prototype for the first heart-lung machine, Clark explains. He needed an easy way to measure blood oxygen levels, so he began tinkering with different electrode designs. In 1954, he came up with the membrane polarographic oxygen electrode, which allowed for real-time monitoring of a patient's blood oxygen level. The electrode works by reducing oxygen to hydrogen peroxide and water, he says, and its key feature is an oxygen-permeable plastic membrane that protects the electrode from becoming fouled by proteins.
The Clark electrode, as it is commonly called, became the standard for measuring blood gases and helped Clark and his colleagues perfect the design of the heart-lung machine. The Clark electrode also has become widely used to monitor oxygen levels in different media for industrial and environmental applications.
"The heart-lung machine saved more than a thousand lives over the years when I was in operating rooms--mainly children," Clark remembers. The device is "a symphony of chemistry," he adds, measuring blood oxygen and carbon dioxide concentrations, temperature, and other essential data. "Never a case of septicemia [blood infection], never a mechanical problem," he proudly notes.
Another of Clark's inventions, a synthetic blood substitute, began with a famous experiment in 1963 while he was on staff at the Medical College of Alabama, in Birmingham. Based on an earlier study on oxygenated saline solutions that he had read about, Clark submerged a white albino rat in oxygen-saturated silicone oil. Although the rat died a few days later from the toxic effects of the oil, it managed to "breathe" for 20 minutes while submerged. "I don't know who was more surprised," Clark once recalled in an interview, "myself or the rat!"
That experiment led to his recognizing the excellent gas solubility properties of perfluorocarbon (PFC) liquids. In 1965, Clark repeated his rodent-dunking experiment, but this time in perfluorobutyltetrahydrofuran. He showed that a mouse could breathe for several hours without any apparent harmful effects.?
Clark returned to Cincinnati in 1968 to work at the Children's Hospital Research Foundation and later rejoined the faculty at the University of Cincinnati and at Antioch. He became a driving force in the research and development of PFCs for biomedical applications, including liquid ventilation of the lungs of premature infants and retinal reattachment eye surgery. In 1991, he cofounded Synthetic Blood International, a company that is developing PFC formulations as oxygen carriers. The company also is developing Clark's implantable glucose sensor.
Clark's career hasn't been all smooth sailing. He gave up research with animals in 1995 because of harassment by some of the more extreme animal rights groups (C&EN, Jan. 22, 2001, page 45). But he hasn't been afraid to speak out about their tactics and how the groups can impede progress in biomedical research. "The worst thing that has happened, and very sadly is little known by most people, is the way in which well-financed animal rights organizations are destroying the scientific future for young researchers and taking away their inspiration for doing good," he observes.
Receiving the Russ Prize "surprised me and has brought me great joy," Clark concludes. "I think for someone like me it's even better than a Nobel Prize. At my age, it has lifted my spirits and motivates me to keep going as long as I possibly can. I hope my career will encourage young people to choose a life of science, discovery, and imagination."
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