Here, Larry Dossey speculates on the possible parallels between subatomic particles—which spin in the same direction at the same moment in time, even after they are separated—and separated identical twins, whose lives manifest eerie concordances.

The Strength of Small

A Nobel Laureate research scientist wonders whether nanotechnology can kill his cancer.

by Jill Neimark

SEPTEMBER/OCTOBER 2001—“Am I living in the last generation to die of cancer or the first generation to be saved by nanotechnology?” asks Nobel Prize winner Richard Smalley, director of the Center for Nanoscale Science and Technology at Rice University in Houston. Nano-medicine is still more science fiction than science but in the next few decades, it promises to usher in a miraculous new era of medicine.

Imagine smart molecules able to enter our bodies and do everything from seek out and kill cancer cells to replace defective genes. In a sense, we will be able to swallow our own surgeons and healers: A molecular nanobot could go inside a blood vessel, look around, find a faulty vessel, take out a chemical knife, and repair it. “I don’t know if we can do it in the next nineteen years,” says Richard Klausner, director of the National Cancer Institute, “but I’m absolutely convinced that we need it. And when we achieve it, we’ll look back and recognize that there has been a revolution.”

Smalley’s own life hangs on that vision: A few years ago, he almost died of a massive strep infection, recovering only to discover he was suffering from non-Hodgkin’s lymphoma. A brutal round of chemotherapy put the disease into remission, but shortly before being interviewed for this article, Smalley had suffered a recurrence and undergone a series of much gentler treatments with a designer molecule, a monoclonal antibody. Though it may put his cancer in remission once again, it’s unlikely to cure it.

“Is Mr. Nano going to die without nanotechnology?” Smalley wonders. “Cancers like mine are completely disseminated through the body, so there’s no way to cure them by cutting them out. The only way is for billions of little agents to nestle up against each and every cell and sense somehow whether that cell is good or bad, and if it’s bad, tell it somehow to gently commit suicide.

“My only hope is nanomedicine, and I find that kind of poetic.”

Smalley is one of the heroes of the burgeoning field of nanotechnology in part because he’s one of the few individuals to have accomplished something tangible. In 1996, he and his colleagues won the Nobel Prize for finding a new form of a pure element. Smalley discovered a cluster of carbon molecules with a beautiful geometric shape, and he nicknamed them buckyballs—after Buckminster Fuller, the designer of the geodesic dome. Buckyballs were the first in a family of carbon molecules known as fullerenes. These structures have now been fashioned into tubes that have the potential to be the world’s strongest wire or fiber, and they can serve as insulation or as a semiconductor.

Smalley likes to divide nanotechnology into two categories, the wet and the dry. Dry nanotech can do things like conduct electricity and store enormous amounts of information in incredibly small spaces. In a 1995 address at the University of Dallas, Smalley stated emphatically that the problems facing our world, such as the population explosion and global warming, could be remedied only by dry nano: “We need it urgently to get through these next fifty years,” he said.

In contrast, wet nanotechnology was originally engineered by nature herself and is the domain of the new medicine. “To me, the most stunning examples of wet nano are provided by enzymes,” Smalley says, “each of which is a whole chemical factory on a nanometer scale. Such molecular nanomachines are what enable life to work, not only in us but also in every plant and bird, in everything you ever thought about that ever crawled on the surface of the earth. This wet nanotechnology is incredibly powerful.”

How does Smalley imagine nanomedicine might save his life? Right now, he points out, chemotherapy may knock back cancer cells, but then you wait for the survivors to multiply. “The population that multiplies is the one that survived your last treatment. So you tend to set up a circumstance where you are intensely breeding this thing that you can’t treat at all.” It’s quite an experience to go to the cancer wards to be treated, Smalley says. “People are being hosed with almost lethal drugs. They’re being taken next to death, and then brought back again. These are very brutal, coarse weapons that we have right now.”

The monoclonal antibody Smalley is receiving is a step in a kinder, gentler direction: It binds to a molecule on particular lymphocytes called b-cells and turns on his body’s immune response. “Luckily, in my case, this molecule is gloriously expressed on my cancer cells,” Smalley says. However, some of the mutant children of his cancer cells will have less of that surface molecule, and they may survive.

It seems we’re undergoing a fundamental change of perspective, where we literally look inward for life’s answers and not out at the mysterious heavens. There, in the minutiae of the cell, lives a fusion of biology and physics that has its own vast majesty.

“That antibody doesn’t guarantee the death of the cell. Now suppose you could attach a buckyball to that antibody, and inside it was a radioactive nucleus. Or if you want to be really snazzy, attach something to the buckyball that the cancer cell wants. So it brings the buckyball into the cell and then—bang—this little nuclear weapon goes off and kills that one cell.”

Sound far-fetched? Smalley’s colleague, Michael Rosenblum, of the University of Texas M.D. Anderson Cancer Center in Houston, thinks he may just have the nanomolecule that could save Smalley. Rosenblum’s department has engineered a product that is one part growth factor, one part protein. The growth factor binds to the blood vessel lining of tumor cells and kills them; because tumors need new blood vessels to grow, this halts cancer’s progression. The plant protein is lethal.

“There was this horrifically toxic plant protein that the KGB used to kill a diplomat. It’s toxic at tiny doses you can’t even see,” Rosenblum says. In fact, the material was too dangerous to handle in a lab.

Rosenblum says he and his colleagues searched until they found a plant that produced a very similar protein that lacked the ability to enter and kill every cell it brushed against: “We purified the protein and have hooked it with antibodies and fused it to the growth factor that kills cells.” The potential to develop this nanomachine to attack many different diseases—from arthritis to cancer—is enormous. Currently, it’s in clinical trials at Anderson for leukemia. “We’re really excited. It’s the first of a new generation of products that have this one killer protein at its core,” Rosenblum says.

Robert A. Freitas, Jr., a research scientist at Zyvex Corporation, a nanotechnology firm, says, “The good thing about these kind of immunotoxins is that we can build them now, and deploy them clinically now. During the next five years, they are going to have a big impact. The first fullerene-based drug (an anti-HIV medicine) is already in the FDA approval process. I’ve also heard about a C-60 (fullerene) based molecule that, when irradiated by light, induces tumor necrosis without any damage to the overlying normal tissue. This stuff is in the labs today. It is not science fiction.”

As we aspire to greater and greater achievements, our salvation might lie in the most humble and tiny—a micron is one millionth of a meter, and a nanometer is a millionth of a micron. It seems we’re undergoing a fundamental change of perspective, where we literally look inward for life’s answers and not out at the mysterious heavens. There, in the minutiae of the cell, lives a fusion of biology and physics that has its own vast majesty. Genomes are just the beginning: We now have proteomes (proteins) and have just coined a new buzzword—metabolome—to describe how the pumps and engines within proteomes turn molecules into a living cell.

In his classic 1959 speech There’s Plenty of Room at the Bottom, physicist Richard Feynman envisioned the universe of nanotechnology: “A biological system can be exceedingly small. … Consider the possibility that we too can make a thing very small which does what we want—that we can manufacture an object that maneuvers at that level!”

Smalley says: “This nanometer is about as far down in size as it is sensible to go, because from one side of the nanometer to the other, there are only about three to five atoms. Although there are tinier things in the universe than atoms, these are not the sort of things you can put in a bottle.”

And small is very much on Smalley’s mind these days. “Though I’ve had a ridiculously fulfilling life, I have a four-year-old baby boy. And he needs his daddy, and that is just an unresolvable, agonizing fact.”

Originally published in Science & Spirit magazine.