When Dr. James Baker returned from the first Gulf War in 1991, his University of Michigan colleagues must have assumed the medical researcher's head had sustained a direct Scud missile hit. The good doctor came home with some pretty wacky ideas.

Here was one of them: Instead of using live viruses to destroy diseased cells, why not send in man-made, nanoscale molecules with tiny tendrils that scientists could engineer to battle specific types of cancers?

Remember, this was the early '90s. Few had even heard of the internet, much less "nanotechnology," which was then firmly the domain of futurists, and certainly not on the radar of respectable beaker slingers.

"In fact, there was a lot of derision at NIH (National Institutes of Health) that this was not real science," Baker recalls. "But as it became clear that gene therapy was not going anywhere without different approaches, I think the reality of, the necessity of, bioengineering in this process became clear."

Today, the National Cancer Institute is on its way to becoming a Nano Cancer Institute as it prepares to spend $144.3 million over five years on the engineered nanoparticles "approach" that Baker and just a few others had championed more than a decade ago. As for Baker, he's doing rather well in his corner office at the Center for Biologic Nanotechnology with a panoramic view of downtown Ann Arbor, Michigan.

Baker had been involved in the Army's first attempts at DNA delivery of the adeno vaccine to combat acute respiratory illness among the troops. He found that not only was the body's immune system fighting off the viral-based vaccine, but the entire works were coming to "hard stops" at 150 nanometers. Things just did not get into cells very effectively beyond that.

It seemed clear to Baker that engineered nanoparticles would have to become part of the solution if they wanted to really chase after the bad guys in the body. "If we now want to fix the dysfunction of cells that lead to most of the diseases that we're currently fighting, we have to engineer at the same scale as the cells," Baker says.

That's the problem that was swirling around in Baker's head after the Gulf War. He wasn't the only scientist working on it, but he did have one advantage. He's located just 100 miles south of a nanotech pioneer: former Dow chemist Donald Tomalia, who had invented a type of particle called dendrimers. Tomalia realized – unfortunately about two decades before the rest of the world – that his man-made, tendriled molecule could be used in targeted drug delivery.

Tomalia saw that Baker was one of the few scientists at the time who also saw the possibilities within these sticky little nanothings. "He was a medical guy who could understand this," Tomalia says. "I think he very quickly began to realize the important implications that dendrimers would have."

All through the mid- and late '90s, Baker and Tomalia quietly experimented with these particles. A synthetic chemist and a medical researcher made for an odd couple at the time.

Lack of cooperation and understanding between the scientific disciplines is one of the toughest challenges facing nanotech researchers. Cooperation may sound simple to those outside the academic world, but cross-disciplinary collaboration is not the way universities have traditionally been organized.

U.S. National Nanotechnology Initiative officials often talk about "converging technologies," that is, connecting all the sciences – physics, chemistry, biology, information technology – and making connections as all these disciplines converge at the nanoscale.

That's the thinking behind the University of Michigan's new Nanotechnology Institute for Medicine and the Biological Sciences, which Baker will head. "I think any university that doesn't develop collaborative centers like this is going to be frozen out," he says.

The convergence of the sciences at Michigan has led to dramatic success of late. Baker's lab recently received a $6.3 million Gates Foundation grant to develop hepatitis B vaccines that can be delivered through the nose, rather than by needle. They will be able to survive outside a refrigerator, making them easier to use in developing nations. And a breakthrough announced in late June heralded a new kind of cancer therapy that acts as a kind of "Trojan horse," infiltrating cancer-cell receptors then turning the cancer against itself.

"I think one of the things that's really important is we actually can, for the first time, show that something injected not only gets into the cancer tumor, but actually gets into the cancer cells themselves," Baker says. "This is very important for both diagnosis and therapy."

The next challenge is getting any of this through the FDA, which is at once under pressure to speed up new drug approvals for an aging population, and to slow down the process in light of recent scandals involving bad side effects.

"Celebrex, Vioxx, all of these drugs that popped up here recently with problems, are whole-body administered – they go everywhere," Tomalia says. "They think they know where they have gone in all minute detail, and they think they know every enzyme and every receptor site, but you never really quite know."

The best-case scenario, Baker says, is nanotech-enabled cancer therapy in your doctors' office within five years. But that's assuming an accelerated approval process, being pushed by nanotech advocates, which is by no means a foregone conclusion. Left to the normal FDA process, it could be a decade or more.

The ultimate goal: The extinction of cancer through early detection. Baker is optimistic.

"We've all got relatives or friends who have died from this," he says. "The therapy is almost worse than the disease." If nothing else, perhaps the end of painful chemotherapy is in sight. "If we can make the therapy nontoxic ... then that's much more practical."

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