In one of nature's remarkable flukes, scientists in 1991 discovered a protein in frog eggs that proved to be a potent killer of cancer cells. With this finding, we can also begin to think about tailoring proteins to work more effectively against specific forms of cancer. Raines' research questions begin with the 1991 discovery that a ribonuclease protein in the Northern leopard frog possesses anti-cancer properties. Delivered to patients intravenously, Onconase has shown promising results in treating malignant mesothelioma, an asbestos-related cancer. Raines found the answer by comparing the molecular structure of the protein produced by frogs with a similar ribonuclease protein in cows.
Bovine ribonuclease is very similar to the human form.
But Onconase does not bind effectively with this inhibitor, which makes it free to seek out and kill other cells. Raines says it is not entirely clear why the ribonuclease attacks only cancer cells, yet is otherwise gentle to healthy human cells. One possibility is there are unique receptors on the outside of cancer cells that bind more tightly to ribonucleases. The researchers were then able to create, with a bovine form of ribonuclease, two variant strains of the protein that did not bind tightly to the inhibitor. Those variants that evade RI were proven in laboratory tests to be lethal to cancer cells.