In what Eric Betzig calls a “trial by fire,” postdoc Bi-Chang Chen spent a month at Woods Hole this summer, familiarizing himself with the Bessel sheet microscope while helping students and faculty analyze their samples.

The Bessel beam plane illumination microscope, or “Bessel sheet,” was a work in progress. Betzig’s team had designed it to answer an obvious need of biologists—the ability to visually track movement of the tiniest structures inside living cells. In March 2011, they had described the new technology online in Nature Methods, including as evidence of its power startlingly vivid portrayals of chromosomes sorting themselves in preparation for cell division and a lively cell surface sending out long, thin projections that quickly retract and reappear elsewhere.

The short movies had generated considerable excitement among biologists: there was no doubt that the new microscope surpassed existing technologies in rapidly creating high-resolution, three-dimensional images without damaging living cells. But for Betzig’s team, this acclaim was not the ultimate goal. “We’re not developing technology for technology’s sake,” he says. “We want to create technologies that will have a broad and deep impact on biomedical research.”

Maximizing the microscope’s impact had been foremost in Betzig’s mind from its earliest development. A physicist and engineer by training, Betzig listens carefully to biologists, and their top priorities have not changed since he began developing imaging technologies more than 30 years ago. Biologists want to see smaller structures. They want to see them with more detail, with more speed, and deeper inside a tissue. And they want to see them in healthy, living cells that are unperturbed by the tool they are using.

		Working Retreat: Microscopists & Biologists Connect at Woods Hole Play Slideshow

Betzig and his team had created the Bessel sheet microscope to answer those demands, and after three years of development, they were convinced the instrument could offer researchers unprecedented views of dynamic subcellular processes. But many of the biologists at Janelia Farm are neuroscientists interested in understanding how neurons work together in complete circuits in the brains of fruit flies or mice, and, Betzig says, Bessel beam technology is not ideal for the size and thickness of the samples they want to image. “Our mandate is to develop new imaging technologies for biology, not necessarily just for systems neuroscience. So if we want to find users for these techniques, we have to look outside.”

Word was beginning to spread about the power of the Bessel sheet, but the cultural divide between microscopists and biologists still frustrated the Betzig team. “It takes a surprisingly long time to get new microscopes to biologists,” Gao says. “So we decided to take our latest microscope to Woods Hole to introduce it to them.”

Rapid-Fire Days

The Marine Biological Laboratory is situated on a narrow, salt-swept piece of land in the far southwest corner of Cape Cod. Tourists unload bikes at the nearby ferry landing; fried clams, homemade ice cream, and other indulgences of a beach vacation are in ready supply. The tiny village of Woods Hole wakes up earlier than the usual beach town, however, and working scientists vastly outnumber vacationers.

Hundreds of scientists flock to Woods Hole in summer to immerse themselves in MBL’s unique culture for a few weeks or months. Distanced from routine distractions, most visitors find the MBL experience gratifyingly intense. Between coursework, research, and discussions and debates, time in the lab routinely stretches until 2:00 a.m., for students and faculty alike. “We’re not there to go to the beach,” Gao stresses. “There’s a vacationy feel here; it’s nice outside,” says Betzig, who set aside two weeks during June and July to work with Bessel sheet users at MBL. “But you’re only here a short time, and everyone works really long days.”

Photo: Jared Leeds

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