Dr. Molecool

Quantum Iconoclast Randell Mills's Grand Visions of Microscopic Medicine

Randell Mills is a doctor better known for stirring up trouble in quantum physics than for giving flu shots. But now he's injecting new vigor into medical projects he claims will spur breakthroughs in fighting cancer and AIDS, as well as scanning the human body in three dimensions, in real time.

"You'll go in to see your doctor and he'll check you out with my scanner," Mills predicts. "If he finds cancer, you'll be treated for it as an outpatient with my therapy. If he finds something else—hypertension, an infection, arthritis—almost any medicine that he'll use will be more efficacious when he uses my drug-delivery molecule."

Mills is the founder of BlackLight Power Inc., based near Princeton, New Jersey. The company promises limitless clean energy and fantastic compounds, based on a "grand unified theory" that is hotly derided by luminaries in theoretical physics (see "Quantum Leap," Voice, December 28). Meanwhile, in a smaller laboratory down the hallway from those activities, Mills is quietly exploring medical innovations that no one seems to be calling nutty.

Mills says he plans to fold his medical ventures into BlackLight Power after that company has its initial public offering of stock, anticipated this year. Profits would then be plowed into his medical pursuits, he adds. "To me it's all the same; it's all engineering," says Mills.

Mills conceived many of his ideas while a student at Harvard Medical School or shortly after he graduated in 1986. Now 42, he acknowledges that it might seem odd that he backburnered early successes in medicine. He says he wanted to milk his brain while it was young and most nimble without the distractions of business or university politics. Today, he's ready to implement his designs.

In December 1988, Mills proposed in the peer-reviewed journal Nature how cancer might be destroyed with such little radiation that it could be treated on an outpatient basis. He says he was moved to improve cancer treatment when, as a student, he witnessed the private hopelessness of doctors caring for an otherwise healthy woman who was being slowly ravaged by tumors.

Currently, patients are carpet bombed with radiation in the hope that normal cells adjacent to cancer cells will be able to recover and reproduce, while malfunctioning cancer cells won't. Patients suffer terribly and injuries from repeated radiation can accumulate to a point where the cure itself threatens to become a killer. What Mills tested in mice were essentially the world's smallest smart bombs.

Dr. Greg Gagnon, assistant professor of radiation medicine at Georgetown University Medical Center, has investigated Mills's radiation technique, called Mossbauer Isotopic Resonant Absorption of Gamma Emission, or MIRAGE. Gagnon says Mills found a molecule to carry iron into a cell and plant it flush against DNA, the control center. Then comes the detonation.

The patient is given a tiny dose of gamma radiation, far less than a standard X ray. The gamma ray photons and iron atoms are tuned to react with each other in something called the Mossbauer isotope. When an iron nucleus absorbs a photon, it becomes unstable and releases a small burst of energy that knocks an electron out of its proper orbit, which then bumps outer electrons astray. What follows is an Auger cascade, a kind of microscopically localized electron explosion, Gagnon explains. "The electrons are shooting off, breaking things all over the place, and then the iron becomes attached to the DNA fragments. There's no way a cell can repair so much damage."

Healthy cells tear apart the transport molecule and the iron drifts safely off.

"It's just an amazingly clever idea. Randy is probably the most intelligent person I've met," remarks Gagnon.

Dr. John Humm, a medical physicist now at Memorial Sloan-Kettering Cancer Center who critiqued MIRAGE in Nature, argues that because such mild gamma rays wouldn't likely penetrate deep into tissue, "there would be severe limitations on clinical use. But having said that, this is nothing to sneeze at. The elegance of the idea is impressive. I know of no other way of so selectively inactivating sections of DNA." Scientists might instead embrace MIRAGE as a laboratory-setting microscopic cellular probe, Humm says.

Mills counters that while MIRAGE may not work for every cancer, in the years since the Naturearticle, he's found other Mossbauer isotopes that can work at deeper levels. In addition, he says, the radiation used in his original tests was so negligible that he could increase it by a factor of 1000 without any resulting discomfort to the patient.

Back then, Mills took a stab at bringingMIRAGE to hospitals, but researchers at would-be partner Bristol-Myers Squibb reported that test results weren't clear enough to pursue, according to M. Dianne DeFuria, senior director of business development.

DeFuria doesn't remember details, but adds that another factor could have been that the radiation therapy "may have involved equipment beyond the scope of a pharmaceutical company, meaning that we couldn't take it further alone."

Mills says he's since sharpened his technique to use ultrasound or magnetic scanners to take aim at malignant growths, and then destroy them with gamma rays pixel by pixel on a computer screen. Beyond that, he adds, "you should really think of this as a microscopic scalpel" good for cleaning out arteries and reducing swollen prostates, among other applications.

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