Prashant Nair

Second act: Drug repurposing gets a boost as academic researchers join the search for novel uses of existing drugs.

In February 2011, the British drug company AstraZeneca shelved its experimental drug zibotentan, intended for the treatment of nonmetastatic prostate cancer in men who do not respond to hormonal treatments. Despite early promise, the drug failed to improve patients’ survival in trials. But more than a year later, the drug might get a second wind, this time as a potential treatment for Alzheimer’s disease, thanks to a partnership between industry and academia. With AstraZeneca crowdsourcing the search for potential new applications for its drugs in the academic community, the partnership could lead to treatments not apparent during the original development of the drug.

Brain–machine interface

In a world awash in technology, the line between humans and machines has begun to blur, our thoughts and actions increasingly shaped and substantiated by machines. Perhaps nowhere is the blurring more evident than in a scientific endeavor called “neural interfacing,” a term for technology aimed at bridging the workings of machines and the human brain. Brain–machine interfaces operate at the nexus of thought and action, using the brain’s electrical signals to maneuver external devices such as prosthetic limbs, among other applications. (Noninvasive imaging techniques such as electroencephalography and functional MRI are also examples of brain–machine interfaces.) The …

Brown and Goldstein: the cholesterol chronicles.

When his parents took three-year-old John Despota to his primary care physician in Chicago in 1964, orange-tinted fat-laden bumps lined the skin on the back of his lower legs. Eruptions caused by excess cholesterol, the bumps spread across Despota’s body, mirroring a total blood cholesterol level that hovered above six-times the normal range. By age 12, Despota experienced shortness of breath upon slight exertions, frequent fatigue, and chest pain: cardinal signs of a cardiac illness called angina, caused by a short supply of oxygen-rich blood to the heart muscles. “Compared with normal kids, I would get tired too soon playing baseball and hockey,” recalls Despota. Fig. 1. LDL in FH: A comparative look. Courtesy of Brown and Goldstein. Fig. 2. Partners for life: Brown and Goldstein circa 1975. Courtesy of Brown and Goldstein. Fig. 3. Electron micrographs of normal human skin cells ( A ) showing labeled LDL particles and the LDL receptor clustered in cell membrane pockets called coated pits. In Despota’s skin cells ( B ), however, most of the LDL receptor was found to be remote from the coated pits and randomly scattered across the membrane. Reprinted by permission of Macmillian Publishers, Ltd: Nature (3), copyright 1977. Under cardiologist Neil Stone’s care at a lipid clinic at the now-renamed Lurie Children’s Hospital of Chicago, Despota received a diagnosis of familial hypercholesterolemia (FH), a metabolic disorder marked by high blood levels of cholesterol, artery-clogging plaques, and premature heart attacks. “When John first came to the clinic, his local cardiologist had given him a year to live,” says Stone. At 51, Despota leads a quiet life of early retirement in Tarpon Springs, a coastal town near Florida’s Tampa Bay, his ailment held in abeyance by an array of drugs and medical procedures. Described in the early 1960s as a disease that manifests in one of two genetic forms, FH …

Foreign minds, fenceless imagination: The 2013 Vilcek Foundation Prizes

Every year, the White House announces the winners of the National Medal of Science and the National Medal of Technology and Innovation. Awarded during a special ceremony by the president, these medals represent the highest honors bestowed by the United States government on scientists and engineers. In his address during the White House awards ceremony in the fall of 2011, President Obama noted that nine of the 12 honorees were born outside of the U.S. (1). The winners came to the U.S., he said, because “America is the best place in the world to do the work they do.” At a time when immigration counts as an issue of pressing political currency, the importance of foreign-born scientists to the U.S. biomedical research enterprise bears repeating: the proportion of foreign-born researchers among recipients of high honors bestowed on American scientists typically exceeds the percentage of foreign-born people living in the U.S., which—including undocumented aliens—hovers around 13% of the general population (2). In fact, at least one in three scientists honored with the Nobel Prize in Physiology or Medicine for work done in the U.S. during the past century was born outside of the country (3). The United States is a nation of immigrants, and most Americans are proud of their ancestral roots. Nevertheless, a significant portion of the populace subscribes to the view that new immigrants are a burden on the country’s economy. To raise public awareness of the invaluable contribution of immigrants to science in America, the Vilcek Foundation initiated an annual program of prizes to recognize accomplished foreign-born biomedical scientists who are widely regarded as leaders in their fields (Table 1). Currently, each of these prizes includes a cash award of

Woese and Fox: Life, rearranged

100,000 (3–5). To recognize a younger generation of distinguished immigrant scientists, the Vilcek Foundation established annual Prizes for Creative Promise in 2009; to be eligible, applicants must be 38 years of age or younger (4–5). In 2013, three winners of the Prize for Creative Promise in Biomedical Science were selected, and each winner was awarded a cash prize of

QnAs with Eric S. Lander

35,000 (Table 2). Similarly, the Vilcek Foundation (5) confers annual prizes on prominent, foreign-born artists for outstanding achievement in various artistic endeavors. This year, the Vilcek Prize in Biomedical Science is shared by immunologists Richard Flavell and Ruslan Medzhitov, both Howard Hughes Medical Institute Investigators in the Department of Immunobiology at Yale University.

Sequencing ancient DNA

(A) Carl Woese examining film on which ribosomal signatures are displayed (2003). (Photo by Jason Lindley; used with permission of the College of Liberal Arts and Sciences, University of Illinois at Urbana–Champaign.) (B) George Fox (1999). (Used with permission of the Department of Biology and Biochemistry at the University of Houston.)

Conservation genomics

T his year marks the 10th anniversary of the sequencing of the human genome. More than two decades after the launch of the Human Genome Project, researchers have made remarkable inroads into unraveling human biology, evolution, and disease. As the tools of genome sequencing and analysis grow more sophisticated, insights into the human genome will slowly shift the terrain in the treatment of disease. To be sure, the shift has already begun. Eric Lander, founding director of the Broad Institute of Harvard and Massachusetts Institute of Technology and a member of the National Academy of Sciences, offers PNAS readers his perspectives on the role of genome sequencing in the transformation of medicine.

Gems from Distant Shores: The 2012 Vilcek Foundation Prizes

The well-preserved mummy of an old man (Upper) is displayed in an exhibition in Denmark’s National Museum. The mummy was removed, as displayed, from an excavation in 1875 at Borum Eshoj, near Aarhus, Denmark. Carpenter and colleagues used hair samples from the mummy to isolate ancient DNA and validate the technique. (Lower) Valdiosera isolates ancient DNA from a different sample in a clean room—a highly sanitized laboratory—in the archaeology department at La Trobe University, Melbourne. Images courtesy of Kristian Kristiansen and Cristina Valdiosera.

QnAs with Cynthia Kenyon

A female northern white rhinoceros, Ceratotherium simum cottoni, one of only seven remaining individuals of a form of African rhinoceros on the verge of extinction. Image courtesy of San Diego Zoo Global.