Flipping through the chronicles of a Nobel Prize winner

"I want to share my time as a scientist by turning the pages in my scientific notebook", Oliver Smithies, 2007 Nobel Laureate for Medicine, said in front of a packed Love Auditorium in LSRC at Duke.

Oliver Smithies, a graduate of Oxford University, is the Excellence Professor of Pathology and Laboratory Medicine at University of North Carolina.

On Thursday, as part of The Duke MD-PhD Program Annual Symposium, Smithies delivered the keynote address "On Being a Scientist for 60 years."

"Science is a matter of chance, opportunity and planning. However, hardly anything ever happens as planned," Smithies noted. He said science has ups and downs. For example, his thesis paper for his PhD on the development of an extremely precise osmometer, "has the dubious distinction of never being cited by anyone."

"So what is, or what was, the point of all the work?" he asked. "It's how you learn how to do science."

Smithies has developed and pioneered numerous techniques in medicine and genetics over the past 60 years that are now universally used in all research work. Early in his career at the Connaught Medical Research Laboratory in Toronto, he developed a technique known as starch gel electrophoresis, which utilizes the properties of starch to act as a molecular sieve, allowing separation of proteins by size. Using this technique, he was able to isolate previously undiscovered protein components of the human serum.

"In my job at Toronto, I worked under David A. Scott, the first person to crystallize insulin. When I asked him 'what am I supposed to do here,' he acted like a true scientist and told me to do anything, as long as it was connected to insulin. That inevitably led to the development of starch gel electrophoresis. This was the chance- the chance invention."

In the mid-1980's , Smithies started to work on gene targeting, and he exploited the naturally occuring phenomenon of homologous recombination to introduce DNA at a defined position in the mammalian genome. "My opportunity here was the inherited differences in plasma proteins. The planning was to try and use the method of homologous recombination to modify the genes. It worked!" Smithies won the Nobel Prize for Medicine in 2007 for this seminal work.

Currently, even at the age of 83, Smithies continues to explore the field of medicine, and his lab at UNC currently focuses on the role of genetics in the development of high blood pressure.

Time is of the Essence

The models being used to predict and quantify the effects of environmental change fall short when it comes to understanding time, according to MacArthur award winner Alan Hastings, a professor of environmental science and policy at UC-Davis. He spoke Thursday at the French Family Science Center.

According to Hastings, time and space are essential to our understanding of ecological systems. However, “the classical approach to ecological models and theory ignores time scale issues,” he noted. “If we’re focusing on global change, we can’t ignore time scale issues.”

Another consideration is the relativity of time to living organisms. For instance, the last glaciation occurred 10,000 years ago. To a human, this represents a significant amount of time. However, to an organism such as a redwood tree, with a lifespan ranging from 500-2,000 years, that expanse of time is only a few generations.

Certainly, the earth works in mysterious ways. Hastings emphasized how even the most complex models cannot compensate for the natural complexity of ecosystems.

“Sudden changes may occur,” Hastings said. They don’t even have to be driven by external pressures. As a result, “complex behavior occurs even in very simple ecological models.”

The inherent unpredictability of earth processes can be frustrating. The key, Hastings said, is to know what can and cannot be predicted. Weather conditions for the next 1-5 days can be predicted with reasonable accuracy. However, any forecasting beyond that period becomes much more difficult. It’s just not possible to predict whether average rainfall or temperature for the next year will be above or below average, Hastings said.

Maybe we should cut the weatherman some slack.

Mercury Pollution in the Environment

If eight percent of women ages 18-49 -- child-bearing age -- have mercury levels exceeding federal health guidelines, how many children have potentially inherited high levels of mercury from their mothers?

“Tens to hundreds of thousands," says Helen Hsu-Kim, professor of civil and environmental engineering at Duke.

Hsu-Kim discussed all aspects of mercury pollution during a March 26 talk in Giles, a freshman dorm. Hers was the last of this year’s Chautauqua series, a program designed to facilitate discussion and give Duke freshmen greater access to accomplished faculty.

Seafood is perhaps the widest-known source of mercury exposure, Hsu-Kim said. However, additional sources include occupational inhalation, broken thermometers or compact fluorescent light bulbs, dental amalgam fillings, some flu vaccines, and transmission from mother to child through the placental barrier. Animals at the top of the food chain, such as humans, are most vulnerable to mercury accumulation because they eat large numbers of animals that have already accumulated mercury from their own diets.

Mercury poses the greatest threat to human health when it accumulates in the body. Elemental mercury is not accumulated, and is excreted by the body within days or weeks of consumption. Methyl mercury, on the other hand, can remain in the body for years if incorporated into the central nervous system. [More about the effects of mercury]

Overexposure to mercury can have dangerous repercussions. Typically, victims of mercury poisoning experience confusion, anxiety, depression, and impaired movement, speech, and vision.

The Mad Hatter, from Alice in Wonderland, is believed to have been inspired by mercury’s toxic effects, according to Hsu-Kim. Mercury used to be involved in the hat-making process, when it was applied for curing felt. Hatters could not avoid exposure as they worked, and many later suffered from significant neurological impairment. From this phenomenon, the phrase “mad as a hatter” emerged, and perhaps the inspiration for Lewis Carroll’s memorably “mad” character.

In some places, mercury exists naturally in the environment, and elemental mercury is occasionally released. However, the main releases of mercury are anthropogenic: coal power plants and artisanal gold mining. (In some parts of California, there are still high concentrations of mercury from the Gold Rush era!)

Mercury is a byproduct of coal combustion. It is released into the air via smokestacks, and also is present in fly ash. The controversy surrounding fly ash is that it is not treated as hazardous waste. Often, power plants will dump fly ash in large outdoor retention ponds-- there are around 1300 in the U.S. alone. However, what happens when this ash contaminates the surrounding environment?

Last Christmas, a retention pond in Tennessee gave way, releasing one billion gallons of coal ash sludge into a bordering river. People’s homes and backyards were inundated with a potentially toxic layer of muck. This material should be considered hazardous, according to Hsu-Kim, not stored in large pools that obviously are vulnerable to leaking or breakage.

And what about the mercury that coal plants release into the air? Unlike elemental mercury, which the body successfully excretes, the mercury from power plants is converted into methyl mercury-- the most dangerous kind. While the U.S. has reduced its coal-related mercury emissions by half over the past decade, developing countries are still highly reliant on coal for power production, and are responsible for an increasing percentage of mercury emissions.

Efforts have been undertaken to capture mercury before it leaves the smokestack. But this also creates an issue, according to Hsu-Kim: dispersed mercury in the air, or concentrated mercury in solid form? The latter still must be disposed of in some way.

“How do we balance energy security, waste management, and materials reuse?” Hsu-Kim said. It’s a question that largely remains to be answered.