Posted with permission from STAT

The Nobel Prize in chemistry was awarded on Wednesday to scientists based in the US, France, and the Netherlands for breakthroughs in designing molecular machines that can carry out tasks- and even mimic a four-wheel-drive car - when given a jolt of energy.

Winners J. Fraser Stoddart, Jean-Pierre Sauvage, and Bernard L. Feringa discovered how to build tiny motors - 1,000 times thinner than a strand of hair.

The machinery includes rings on axles, spinning blades, and even unimaginably small creations consisting of only a few molecules that can lift themselves off a surface like tiny robots rising on tip-toe. Those molecular robots can pluck, grasp, and connect individual amino acids. The machines can also be used as a novel mechanism of drug delivery.

And there's more to come: The Nobel committee said the molecular motor is about as advanced now as the electric motor was in the 1830s, "when researchers proudly displayed various spinning cranks and wheels in their laboratories without having any idea that they would lead to electric trains, washing machines, fans, and food processors."

The minuscule machinery honored Wednesday will likely be used in the future to build an array of sensors, energy storage systems, and even new material, the committee said.

Reached by phone by reporters in the Swedish Academy press room, Feringa was asked if he is concerned that nano-machines might one day escape the lab and run amok like a "gray goo" imaged by one of the pioneers of nanotechnology. "We have to think about how we can handle these things safely, but I'm not so worried about that," Feringa said. "We will have the opportunity to build in safety devices if that is needed."

Stoddart, a Scottish chemist, was knighted by Queen Elizabeth II in 2007 and now works at Northwestern University in Illinois. Sauvage works at the University of Strasbourg in France, and Feringa is at the University of Groningen in the Netherlands.

The prize continues a tradition of the Royal Swedish Academy honoring research done decades ago -  in this case, in the 1980s and '90s.

The field of molecular machines got its real start in 1991, when Stoddart created what is now known as a rotaxane, in which a linear molecule serves as an "axle" poking through a ring-shaped molecule. With two bulky molecules at either end of the axle, Stoddart found, the ring could hop back and forth, creating "the first molecular shuttle," as Nature called it last year in a story about molecular machines.

A key question at the time was whether the tiny machines would have to be built up atom by atom, or whether traditional techniques of organic chemistry would work, said Donna Nelson, president of the nonprofit American Chemical Society and chemistry professor at the University of Oklahoma. It turned out to be the latter, which made the synthesis somewhat more straightforward but by no means easy. "There really are challenges in synthesizing these things," she told STAT. "But they achieved it, and the results have been really fantastic."

With later modifications, Stoddart's designs raised hopes that such nano-Legos might one day be combined with molecular sensors that respond to particular compounds in the body to open a nanoscale container to deliver a dose of medication at a precisely targeted place inside a patient. But that idea is still in development.

The first synthetic molecular motors that Feringa and his team built, beginning in 1999, contained twin paddle-like molecules connected by a chemical bond that broke when exposed to light, making the paddles spin in one direction. Feringa later used similar molecular motors to build a four-wheel-drive "nanocar."

Researchers have exploited the light-activated mechanism that Feringa devised to develop some 100 drug-like compounds that switch on or off in response to light, Nature reported last year. A European team, for instance, invented a form of the anti-cancer drug combretastatin A-4 that promises to be less toxic to healthy cells: The scientists constructed the drug in two pieces that come together and become active only in the presence of light, much as Feringa did with his light-sensitive nano-paddles.

Drugs powered by molecular motors, the scientists wrote, "are promising as a new class of precision chemotherapeutics whose toxicity may be spatiotemporally constrained." Mouse studies are underway to test this idea.

Lab-made molecules whose parts come together when exposed to light might also be used to treat macular degeneration or retinitis pigmentosa, scientists reported last year: Such a "photoswitchable molecule" restored some visual function to blind mice, US scientists reported in 2014.

By figuring out how to manipulate some of the smallest forms of matter, Stoddart and Sauvage also created molecular versions of cultural symbols such as the trefoil knot, Solomon's knot, and the Borromean rings - though that was what the Nobel committee called "a diversion" from their truly prize-winning work.

Asked what his work might one day be used for, Feringa told reporters, "There are endless opportunities. … Think of a tiny micro-robot that a doctor in the future will inject into your blood and that goes to search for a cancer cell or goes to deliver a drug."

This story has been updated with more information about the winners and their work.