DMF

The movie Fantastic Voyage , the story of a miniaturized team of doctors traveling through blood vessels to make lifesaving repairs in a patient’s brain, was pure science fiction when it came out in 1966. By the time Hollywood remade the film in 1987 as Innerspace , a comedy, real-world engineers had already begun building prototypes of pill-size robots that could voyage through a patient’s gastrointestinal tract on a doctor’s behalf. Patients began swallowing the first commercially built pill cameras in 2000, and since then doctors have used the capsules to get unprecedented views of places, such as the inner folds of the small intestine, that are otherwise difficult to reach without surgery.

One important aspect of Fantastic Voyage that has remained fantasy is the notion that such tiny pill cameras could maneuver under their own power, swimming toward a tumor to get a biopsy, checking out inflammation in the small intestine, or even administering drug treatments to an ulcer. In recent years, however, researchers have made great strides in converting the basic elements of a passive camera pill into an active miniature robot. Advanced prototypes, now being tested in animals, have legs, pro­pellers, sophisticated imaging lenses and wireless guidance systems. Soon these tiny robots may be ready for clinical trials. Right now they are testing the limits of miniaturized robotics.

As a favor to friends in my academic department, I have frequently been a guinea pig in the functional magnetic resonance imaging (fMRI) scanner. In most of these cases, I fight valiantly against slumber as the stimuli flash on the small screen in front of me and the hypnotic, high-pitched beeps of the scanner reverberate all around. This time, though, it was different. Martin Monti, a fellow neuroscientist at the MRC Cognition and Brain Sciences Unit in Cambridge, England, was going to read my mind. As the bed I lay on slid robotically into the giant doughnut-shaped scanner, I had a strange sensation that I was about to be seen naked--mentally, at least.

The task was simple: Monti would ask me questions--did I have any siblings, did I think England was going to win the soccer match that night, and so on. If I wanted to answer “yes,” then I would imagine myself playing tennis, activating a known set of motor regions in my brain by doing so. If I wanted to answer “no,” then I was to imagine navigating around the rooms of my home, activating an entirely different set of areas involved in scene perception. Given that each scan--and thus each of my yes or no answers--took five minutes, the conversation was not the most riveting I had ever had, but when Monti accurately guessed my response every time, it was nonetheless thrilling and unnerving in equal measure.

In a head-to-head competition held 10 years ago, scientists at the National Institutes of Health tested two promising new types of vaccine to see which might offer the strongest protection against one of the deadliest viruses on earth, the human immunodeficiency virus (HIV) that causes AIDS. One vaccine consisted of DNA rings called plasmids, each carrying a gene for one of five HIV proteins. Its goal was to get the recipient’s own cells to make the viral proteins in the hope they would provoke protective reactions by immune cells. Instead of plasmids, the second vaccine used another virus called an adenovirus as a carrier for a single HIV gene encoding a viral protein. The rationale for this combination was to employ a “safe” virus to catch the attention of immune cells while getting them to direct their responses against the HIV protein.

One of us (Weiner) had already been working on DNA vaccines for eight years and was hoping for a major demonstration of the plasmids’ ability to induce immunity against a dreaded pathogen. Instead the test results dealt a major blow to believers in this first generation of DNA vaccines. The DNA recipients displayed only weak immune responses to the five HIV proteins or no response at all, whereas recipients of the adenovirus-based vaccine had robust reactions. To academic and pharmaceutical company researchers, adenoviruses clearly looked like the stronger candidates to take forward in developing HIV vaccines.