Dr. Molecool

Quantum Iconoclast Randell Mills's Grand Visions of Microscopic Medicine

"If Randy is now meeting with good success, I hope he will come back," DeFuria says. "His mind was certainly appreciated here."

Mills has also demonstrated what might be a better way to use existing drugs to attack AIDS, herpes, and hepatitis. One of the problems doctors have in fighting these diseases is that the drugs best able to halt viruses and bacteria from reproducing often have trouble getting past cell membranes. They can be modified for that purpose, but that usually means dumbing down the medicinal value or causing side effects. Also, toxic concentrations of drugs must sometimes be used in hope that enough will get through.

Mills has designed a type of nontoxic molecule to ferry unadulterated drugs into cells, says Dr. Jim A. Turpin, who manages a retrovirology lab at Serquest, a Southern Research Institute company.

In Mills's approach, a drug enters the body as part of a molecule with three segments. Once past the membrane, the molecule will more likely encounter oxygen-free radicals, created during respiration, which exist inside cells in far greater numbers than outside.

The radical excites the first section of the three-part molecule in a chemical reaction that should release a photon of light. But that light is instead channeled as bond-shattering disruptive energy running along the molecular carrier, which then falls away like the spent stage of a rocket. The drug is left alone to do its work, and the carrier is excreted as waste.

Mills calls his system the Luminide method, because the carrier "is a light-powered drug-release molecule based on a reaction analogous to that used by fireflies to glow," and "it just sounds cool."

Turpin tested the technique on HIV-infected white blood cells using the AIDS drug Foscarnet. With the Luminide carrier, "we measured a minimum ninefold enhancement of antiviral activity in tissue culture," Turpin says.

Mills says he and Turpin will submit apaper on their findings to The Journal of Medicinal Chemistryin February. Tests in mice with Dupont Corporation have been successful, Mills claims, and he plans further studies in animals and humans. He adds that the method could be used for a host of applications, from antidepressants to plant pesticides, but purifying the compounds is difficult.

The National Institutes of Health may be interested in getting behind that effort with its own manpower and resources. When presented with Luminide overview materials for an opinion, Dr. Nava Sarver, chief of NIH's targeted intervention branch in the Division of AIDS, was "a little more impressed than I thought I would be. There seems to be some real potential there."

Sarver explains that her program helps scientists develop cutting-edge technologies without taking any profits or making patent claims. Luminide molecules appear to be suitable for oral administration, Sarver says, and "anything that increases potency and decreases toxicity is a go."

Sarver cautions that many promising ideas stumble in the final steps of clinical testing.

For Luminide to be closer to an ideal approach to treating AIDS, Sarver says she'd like to "tweak" it with Mills to target only infected cells or systems. "Specificity is the missing link here."

Immunologist Dr. Gillian Woollett of Pharmaceutical Research and Manufacturers of America agrees that targeting will be important. "It's a neat idea and there will be a lot of companies keen to talk with him. But he has some hurdles ahead of him."

If clinical trials for one drug are positive, Woollett says, "Maybe the floodgates will open. And AIDS is not a bad place to start. This system seems especially good for use in blood, and oxygen-free radicals are used most by the immune system."

But AIDS and other infections aren't the most likely killers lurking in peoples' bodies, Mills points out.

"Let me tell you how you're going to die," he casually offers. "I'll say you're going to die of heart disease, cancer, or a stroke, and I'll be right 95 percent of the time."

That's why Mills has another project in the works at Harvard that he says could revolutionize diagnostic medical imaging.

"The guy is amazing," remarks Dr. Samuel Patz, an assistant professor at Harvard Medical School, with an appointment in the Department of Radiology at the university's Brigham and Women's Hospital in Boston.

"I've worked with him on his medical inventions and he's contributed some nontrivial creative ideas about a new imaging technique. It's very exciting and has some real possibilities," Patz says.

Today's scanners work best by giving doctors two-dimensional snapshots of the human body. Mills claims he's designing a scanner that may, for example, allow a surgeon to take a live-image virtual reality walking tour through a patient's beating heart (it could also be used to scan industrial materials).

Mills expounds. "The machine would work by distinguishing differences made in the magnetic field at a location by the material itself, like bone versus lung." Data would stream into a computer through parallel channels from up to a million points, providing far sharper relief than anything currently available.

And if a strongly magnetic substance like iron were added to the bloodstream, through an injection of Geritol for example, "the vascular system would light up." That would allow a doctor and patient to see blood vessels growing to feed a tumor, or clots and cholesterol, without any invasion.

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