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Max Planck Florida Institute: Finely Focused

In 1873, German physicist and optical pioneer Ernst Abbe discovered the limits of “microscope resolution” — how precisely an optical instrument can focus light, and thus how small an item can be seen clearly. Abbe found that the laws of physics make it impossible to get resolution on objects smaller than half the wavelength of light — about 200 nanometers. That’s really small, a fifth of a thousandth of a millimeter, or about a hundredth the width of a human hair.

Abbe’s discovery of the “diffraction barrier” was a breakthrough, but it was also bad news for researchers. Microbiology had been born thanks to microscopes, and much of scientists’ understanding of biology had come from being able to see microbiology at work.

For scientists, it was akin to learning that they’d be able see details on the facade of a building without being able to observe how the people inside lived. Post-Abbe, researchers knew they’d be able to see larger parts of cells but never examine a cell in molecular detail — unable, for example, to observe molecules forming synapses between nerve cells. Or see how proteins aggregate in disease.

That was the state of affairs until 2000, when another German physicist, Stefan Hell, proved he could do an end-around past the resolution barrier by using lasers and fluorescence. His microscope sees down to 20 nanometers, a 10-fold step beyond the diffraction barrier.

For that solution, he and two other researchers — who came up separately with their own end-around — were awarded the Nobel Prize in chemistry in 2014. “Due to their achievements, the optical microscope can now peer into the nanoworld,” the Royal Swedish Academy of Sciences said in announcing the award. “Today, nanoscopy is used worldwide, and new knowledge of the greatest benefit to mankind is produced on a daily basis.”

Perhaps some of that new knowledge will be discovered soon in Jupiter, Florida, home of the Max Planck Florida Institute for Neuroscience. Hell, 54, arrives there in January for a sabbatical from his job at the Max Planck Institute in Germany. The Florida institute also has become the U.S. base for Abberior Instruments America (a play on Abbe’s name and “superior”), Hell’s small firm that makes and sells his microscopes to research universities and organizations.

Max Planck Florida purchased one earlier this year — an “unprecedented level of imaging,” institute scientific director and CEO David Fitzpatrick says. And Abberior has based a second there so it can show scientists around the nation its potential. “It was a very easy choice to come here because there’s been such a good reputation that has been built up here,” Hell says.

Traditional microscopes allowed resolution no better than half the wavelength of light, meaning a scientist could see a cell, but not the individual molecules inside the cell. Stefan Hell came up with a way to bypass that limitation.

Hell’s approach uses two laser beams. The first scans across what the researcher wishes to view and “excites” the molecules inside the cell that fluoresce. A second laser then “quenches” — turns off — the fluorescing molecules aside from those within a certain desired volume. The researchers know exactly where the beam hits the sample and use that information to process the image.

The image on the left at the bottom shows the resolution that’s possible with a traditional microscope; the image on the right shows the molecular-level detail that can be seen using Hell’s microscope.

Increased stature

The arrival of Hell and his company highlights the role Max Planck Florida plays in global science and Florida. The Florida location is the first and only offshoot of the 83-institute Max Planck Society outside Europe, birthed in 2009 thanks to $94 million in state dollars and another $94 million in local support from Palm Beach County, the town of Jupiter and Boca Raton-based Florida Atlantic University. The local support funded a custom 100,000-sq.-ft. facility on FAU’s Jupiter campus.

The state recruited Max Planck near the end of Florida’s incentive-laden campaign to build a life-science industry here, a binge that began in 2003 with the $510 million that state and local governments put out to create Scripps Florida in Jupiter. That was followed by hundreds of millions more on other life-science ventures, most of which haven’t prospered. One, VGTI in Port St. Lucie, failed, and others have struggled, including Sanford Burnham Prebys in Orlando, which wants to leave.

Max Planck Florida appears to be on firmer financial ground than some of its recruited peers. By 2015, the institute said it had grown to 144 employees, who made an average of $66,806 (its promise to the state for the incentives was to pay at least $64,770 on average). It’s overseen by a powerhouse board of top executives from its German parent, high-profile local entrepreneurs and philanthropists George Elmore and Alex Dreyfoos, former FBI Director Louis J. Freeh and multimillionaires and former CEOs of GlaxoSmithKline, Pace Communications, General Dynamics and Wyeth. The non-profit Max Planck Florida managed a $55,511 gain after expenses on $25.4 million in revenue in 2015, according to its tax filing for that year.

Florida, however, expects more than mere survival from its life-science investment. And so far no spinoff companies — let alone firms employing large numbers — have come out of Max Planck Florida.

Fitzpatrick says that while spinoffs haven’t materialized, the promised science has. Each Max Planck institute has its own specialty. In Jupiter, that specialty is using and developing new imaging technology to study the brain at its most foundational, trying to understand how it works in order to understand why it sometimes doesn’t.

In the last two years, the top-flight scientists that Max Planck has recruited to Florida have had 40 research papers published, including 25 in prestigious publications such as Nature, Science and Cell.

“This is science of the highest quality,” says Fitzpatrick, who arrived in 2011 from Duke University’s med school, where he was the James B. Duke professor of neurobiology and director of the Duke Institute for Brain Sciences. “I remember telling people ‘just give us five years and you’ll see what we will be able to produce.’ And, of course, at the time I didn’t really know what we would be able to produce, but we’ve done exceedingly well.” As an endorsement of its success, the parent society now provides financial support for the Florida institute.

In 2015, the institute’s other scientific director, Ryohei Yasuda, won a five-year, $4.8-million Pioneer award from the National Institutes of Health to fund research on the brain to gain insights into dementia, autism and other disorders. Only 13 Pioneer awards are given nationally to recognize groundbreaking approaches. (Next door at Scripps Florida, scientist Matthew Disney also won a Pioneer award in 2015.)

In his lab earlier this year, Yasuda demonstrated how he works, standing in a darkened room filled by a baby grand piano-sized array of lasers and devices aligned to let him observe how neurons’ dendritic spines function to exchange signals. “To look at a tiny thing, we need a big setup,” he says.

Hell’s Abberior microscope, conversely, is more compact — roughly the footprint of an upright piano. One system, says U.S. CEO Christian Wurm, can be transported in a suitcase. Abberior microscopes generally start at $200,000. A piano-size version with additional features can cost up to $1 million. That’s expensive but “not outrageously more expensive” than existing tech, Hell says. He estimates there are 20,000 to 30,000 last-generation microscopes in use in U.S. university research and pharma companies, about 30% of the world market, that could be retrofitted with Abberior’s compact system.

Fitzpatrick says the presence of Abberior and the only such microscope in the nation enhances the reputation of the county and state for “best-in-class” research tools. After showing off the microscope in April, south Florida scientists held a sort of reception for Abberior. Scripps and FAU researchers already had put the new microscope through its paces — Max Planck, Scripps, which is across the street from Max Planck, and FAU have agreed to share Jupiter facilities and equipment. (Scripps last year bought a world-class microscope of its own with a $500,000 donation from the Iris and Junming Le Foundation.)

The Jupiter “neuroscience community” is coming together, Fitzpatrick observed. “FAU is a fantastic partner. The scientists at Scripps, we have a fantastic relationship. We all recognize our individual successes really build the whole entity.”

FAU President John Kelly, at the reception, says FAU grad students working with Max Planck already have been credited as researchers in an article in Nature, “one of those impossible scientific journals to get into.” Fitzpatrick helped FAU in its recruitment of Vanderbilt University scientist Randy Blakely [“Neuroscience Pillar”] to head its brain institute. Fitzpatrick and Kelly traveled to Germany together last year for an FAU-Max Planck collaboration and to Tallahassee to promote the area’s agenda. The institutions are sharing equipment and knowledge and, says Kelly, “our students get access to a Nobel Prize winner. Here, in Palm Beach. I love it.”

Hell, the Nobel laureate, hopes his sabbatical year in Jupiter allows him to improve microscope capabilities further. “There is still more to be done,” he says. “This is a fantastic place to do that.”

 

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