This morning, the Lasker Foundation handed out its 2009 Awards (the webmaster recycled the 2008 banner but, trust me, it's 2009). The prizes honor three categories of work: basic biomedical research, applied clinical research, and public health, and those who are cited in one of the first two categories have a tendency to go on to win a Nobel Prize, which has lead to the Laskers picking up the nickname "America's Nobels." This year, the awards go to two highly significant areas of research: the development of techniques to reprogram adult cells to a stem-cell-like fate, and the development of a therapy for chronic myeloid leukemia (CML) that was based on our biochemical and genetic understanding of the underlying cause. The award for public health went to a figure who's widely recognized, but not generally for his contributions in this area: New York City's Mayor, Mike Bloomberg.
Stem cells on demand
The stem cell award does a brilliant job of recognizing the deep history of most major scientific developments. In this case, one of the two honorees, Cambridge's John Gurdon, is being cited for work he did back in the 1950s. Gurdon used eggs and cells from a frog, Xenopus laevis, to show that transplanting the nucleus (and the DNA within) from adult cells to an egg was sufficient to reprogram the DNA and enable it to undergo embryonic development. Prior to that, it was thought that adult cells might commit to specific roles by losing part of their DNA, leaving them incapable of adopting alternate fates.
Gurdon's work made clear that (for most cells, at least) their current activity is largely controlled by factors external to the DNA itself. For decades, that knowledge primarily influenced the field of developmental biology, which focused on identifying the processes and factors that compel cells to adopt specific fates and perform specialized functions.
Shinya Yamanaka, who has appointments at both Kyoto University and San Francisco's Gladstone Institute, is cited for applying the logical consequences of Gurdon's findings to stem cells. If the environment of an egg is sufficient to reprogram the genetic material to a stem cell like fate, Yamanaka reasoned, then it should be possible to identify the factors within this environment that do so. Starting with 24 genes that had been implicated in controlling stem cell fate, Yamanaka and his colleagues patiently whittled the list down to just four—expression of these genes in adult cells would cause them to adopt stem cell properties.
It's hard to overstate the excitement that greeted this finding and the promise it holds. By using patient-specific stem cells, researchers can avoid genetic incompatibilities that could lead to immune rejection of stem cell based therapies. Researchers have also used this to produce stem cells that carry mutations associated with specific genetic diseases, enabling more detailed studies of these disorders—in a couple cases, scientists have shown that it's possible to correct the genetic defect in the stem cells. It may be years before these developments reach the clinic, but in the few short years since Yamanaka's paper, there has been an explosion of follow on work.
Cancer as a manageable disease
Chronic myeloid leukemia (CML) is one of the great success stories of modern biomedicine, but it also has a deep history. As far back as 1960, researchers recognized that it was frequently associated with a specific abnormality in the chromosomes, and it was eventually determined that the changes caused the fusion of two genes, BCR and ABL. The fusion of the two genes is what spurs the uncontrolled and ultimately fatal proliferation of immune cells.
ABL encodes a cell signaling protein called a kinase, and the fight against CML has represented a new approach to cancer: instead of generally attacking dividing cells, researchers generated chemicals that specifically targeted the ABL kinase. Nicholas Lydon is being honored for his work at Ciba-Geigy, where he was involved with the development of compounds that specifically targeted ABL as part of a larger effort to develop inhibitors specific to a variety of kinases implicated in cancer. He set up a collaboration with Brian Druker, who was at Dana-Farber and later the Oregon Health & Science University to demonstrate one compound's effectiveness in cell culture and mice.
The two paired with Charles Sawyers (among others), then at UCLA, to start clinical trials. The compound, now sold under the brand name Gleevec, had dramatic effect, with roughly 90 percent of the patients in the trials responding; the FDA approved it for sale on the expedited schedule of three years. Sawyers received the award in part because of his further work at Memorial Sloan-Kettering, where he's helped develop further drugs to target versions of ABL that pick up additional mutations that make the protein resistant to Gleevec.
The drug doesn't "cure" cancer in the traditional sense—potentially cancerous cells are still present in those treated—but it prevents them from proliferating out of control, essentially turning this form of cancer into a disease that's managed in much the same way high blood pressure is. The promise of disease-specific biochemical therapies hasn't seen as many success stories as most would like, as Gleevec remains a bit of an exception. Nevertheless, it is extremely significant in that it represents the promise of modern biomedicine, where therapies are based on a deep understanding of the underlying biological causes of a disease.
Enhancing public health to the Big Apple
The final citation, the Mary Woodard Lasker Award for Public Service, goes to New York City's mayor, Michael Bloomberg. Most of the country is probably aware of him for his role in leading the city in the years following the 9/11 attacks, a narrative that has tended to focus on economic revitalization and public safety. But public health initiatives have been a cornerstone of his administration from the start, and he has matched this public commitment with private philanthropy.
Over nearly overwhelming opposition from local businesses, Bloomberg instituted a smoking ban in restaurants and bars as a matter of occupational safety for the workers there, an approach that has been adopted internationally. He coupled that with a series of aggressive advertising campaigns, increased tobacco taxes, and public access to smoking cessation programs. The end result has been a plunge in smoking rates, with teen smoking now below half the national average.
Similar efforts have eliminated trans-fats from the city's restaurants, and posted calorie counts for all food served to the public. These have focused on areas where consumers have had little choice in how their food was prepared, or were simply left in the dark about its nutritional content; it's one thing to know a blueberry muffin is an an indulgence, another thing entirely to realize it has nearly 20 percent of the recommended daily calories for an adult. One recognition of his administration's achievements has been the naming of the city's former Health Commissioner to run the US' Centers for Disease Control.
Bloomberg's public focus on health issues has been matched by private donations, which have lead Johns Hopkins to rename one of its institutions the Bloomberg School of Public Health.
Overall, this year's awards not only recognize a significant collection of research, but they do an important job of emphasizing the incremental nature and rich history of scientific discovery. Basic research may take decades or more to impact medicine, and seemingly obscure findings from species like frogs can ultimately have a significance far beyond initial appearances.