Serendipity Science: From Treating Cancer to Mapping Genes
Ravi Pandey was trying to determine if carbon nanotubes could be a weapon in the fight against cancer when he discovered something quirky about DNA that could revolutionize gene-sequencing technology.
Nanotubes have major potential as part of a drug-delivery system. Chemotherapy is a tried and true cancer therapy, but for many patients, the drugs are so toxic that the cure is worse than the disease. So, rather than dosing the entire person with healing poisons, scientists want to deliver those drugs directly to the tumor, with carbon nanotubes serving as the shuttle.
First, however, they want to make sure they aren't making things worse. Nanotubes are, as their name suggests, incredibly tiny, not much bigger than a strand of DNA. Common prudence would suggest that, before injecting them into human tissue, you would want to make sure they don't cause more problems than they solve.
In particular, Pandey, chair of Tech's physics department, PhD student Sankara Gowtham and postdoctoral fellow Ralph Scheicher were studying whether or not carbon nanotubes react with the constituent bases of DNA—adenine, cytosine, guanine and thymine, or ACGT for short. If those bases are not reactive, then carbon nanotubes are probably safe. If A, C, G and T are reactive, then the nanotubes might cause problems ranging from birth defects to cancer and should probably be crossed off the list of chemotherapy delivery tools.
When physicists test a substance for reactivity, they go down to the sub-molecular level, to the cloud of electrons that hovers around each nucleus. When molecules and atoms get close to each other, they deform that electron cloud. Some deform more than others, a quality known as polarizability.
If the polarizability is really significant, the substance tends to bind strongly to the given material. When Pandey's group calculated the polarizability of A, C, G and T vis a vis carbon nanotubes, however, he got good news: low binding, meaning that carbon nanotubes had crossed one bridge on the path to a safer, more effective way to deliver chemotherapy drugs.
But he noticed something else. With respect to the carbon nanotube, a subtle variation in the polarizability of each of DNA's ACGT constituent bases was predicted.
"They are subtle, but there are differences in the binding energy that come from polarizability," said Pandey. "At one of our conferences, we sat down at dinner one evening and asked, 'Could we apply these differences somehow?'"
The answer was an emphatic maybe. Maybe you could sequence DNA by somehow measuring the binding energy of each of the ACGT bases, one after another. "It was a little hunch, a napkin decision," he said.
Back at the University, Pandey, PhD student Haiying He and postdoctoral fellow Ralph Scheicher began to turn the back-of-the-napkin maybe into a yes, with collaboration with Trinity College, the Army Research Lab and Uppsala University.
Using computer modeling, they developed a new way to sequence DNA that could be far easier and cheaper than current methods.
"You just pull strands of DNA through a carbon nanotube membrane with an electric current going through it," Pandey said. It's a little more complicated than that, but tiny changes in the voltage signal which base is which, in perfect order, along the famous double helix.
Present sequencing methods are expensive and time consuming, and Pandey hopes that their breakthrough might someday revolutionize the technology.
Now, they are working with Lanrong Bi, an assistant professor in Michigan Tech's chemistry department, to develop a prototype of their model.
"This is only possible because the scale of materials has gone down to the nano-level," said Pandey. "We're using quantum mechanics to understand biological processes. It's the fusion of biology and physics, a whole new world."