Published 14 March 2024 by Hanna Kurlanda-Witek
Breaking the Diffraction Limit
This year marks the 10th anniversary of the Nobel Prize in Chemistry, “for the development of super-resolved fluorescence microscopy,” which was awarded to Eric Betzig, Stefan Hell, and W.E. Moerner. During an interview in Lindau in occasion of #LINO23, Stefan Hell talked about his past work, how the landscape has changed for young researchers since he started out in science, and why he attends the Lindau Nobel Laureate Meetings almost every year.
Early Days
When Stefan Hell decided to solve the problem of breaking the diffraction limit to enable lens-based high-resolution optical microscopy, he was unaware of how difficult it would be to gain support for his idea. Hell himself described his years as a younger scientist in his Nobel biography and it speaks volumes of Hell’s tenacity and belief in his research despite the closed doors and meager funding. Most of his colleagues believed breaking the diffraction limit would remain “an academic curiosity.”
“I was convinced I was on the right track,” said Hell, when asked how he managed to persevere. “I believed that if you have the right arguments then you might eventually succeed, but I was aware of the risks.”
Working on the single problem of vastly improving the resolution of fluorescence microscopy, Hell was driven by figuring out the basic principles rather than the technology. Solving the question was what ultimately motivated him. Yet from a more practical side, Hell anticipated the positive side of the uncertainty.
“There is a period of high risk, but once you’re established you have a lot of personal freedom. You can make up your mind in the morning on what you’re going to work on. I found that very attractive and I found the road to that goal very attractive.”
A Scientist’s Life
Finding an independent research position was an uphill task thirty years ago, as there was a surplus of physicists. “It has changed for the better,” admits Hell, “But the downside is that not many of those who get independent positions eventually get tenure. It’s part of the way science works, there should be alternative career paths.” It’s not a perfect scenario but making a living as a scientist outside academia was hard in the past and is much easier now for Young Scientists. “Companies are constantly looking for highly qualified scientists.”
Post-Nobel Work
After developing stimulated emission depletion microscopy (STED), for which he was awarded the Nobel Prize, Hell continued the quest for attaining the highest possible resolution by developing MINFLUX and MINSTED – powerful imaging techniques with nanometer resolution, meaning that molecules can now be resolved in an image even if they are as close together as the size of a molecule itself. This was not possible ten years back. The added benefit is that this imaging doesn’t require any special facilities or conditions, but normal lenses and it is used at room temperature. When asked about the accessibility and availability of these microscopes, Hell has no doubt that more and more scientists will use them. “Of course, new techniques are initially more expensive, but the costs will come down with time.” Feedback from users is positive and even Nobel Prize winners are using MINFLUX in their current research.
The Highlight of the Year
Stefan Hell has attended nearly all the Lindau Nobel Laureate Meetings since he was awarded the Nobel Prize. What makes them so special?
“I don’t travel much, but this is one of the few meetings I go to. It’s the highlight of the year, I really enjoy it,” he said.
Hell appreciates the opportunity to speak to Young Scientists and emphasizes that it’s important for them to share their personal and professional difficulties with Nobel Laureates. “They can see us Nobel Laureates as normal people, like anyone else. They see that we live a life. They ask us for advice which we can relate to; we had to face tough decisions as well.”
“And of course, the types of conversations you get here are mind-boggling,” said Hell. “You get extremely good talks from the Young Scientists and of course the Nobel Laureates. Although I’ve been here seven times, I must say that listening to these talks is really refreshing.”