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Looking Deeper into Life: How a Nobel Prize Winner Advanced Microscopy

By Madison Dougherty, Biochemistry and Molecular Biology ‘18

 

Author’s Note:

“I was encouraged to attend and review Nobel Prize winner Eric Betzig’s lectures on campus, and I am extremely glad that I did. As a Biochemistry and Molecular Biology major, I did not think that I would find microscopy very interesting, but after listening to Betzig talk about his developments in the field, I felt a new sense of appreciation for microscopy, and even for telescopes and space. If you are interested in astronomy, physics, chemistry, biology, or all of the above, I highly encourage you to watch and absorb the wealth of information that he has to share with the scientific community. Full video presentations of Betzig’s lectures can be found on the CBS Storer Lectureship website: http://biology.ucdavis.edu/seminars-and-events/storer-endowment/past-lectures/2016-2017.html

 

 

This February, UC Davis welcomed Dr. Eric Betzig to speak for the Storer Lectureship in Life Sciences, where he presented his scientific developments in the field of microscopy over the course of two separate lectures. In 2014, Betzig was jointly awarded the Nobel Prize in Chemistry for the development of super-resolved fluorescence microscopy, along with Stefan W. Hell and William E. Moerner. Throughout his academic and industrial career, Betzig moved around the country multiple times and contributed to numerous projects, and in 2005 took a position with the Howard Hughes Medical Institute’s (HHMI) Janelia Research Campus. This summer, he and his wife will leave Janelia to perform research at UC Berkeley.

In his first lecture, which was aimed at the general public, Betzig focused on the historical similarities between microscopy and astronomy, and how these similarities shaped his interests in science. As a child, Betzig had dreams of becoming an astronaut, and his bedroom walls were plastered with images taken by the Hale telescope. To this day, he incorporates his love for space into his work in biology, striving to see deeper and deeper into the unknown and surpass preconceived limitations. Betzig explained telescopes and microscopes to the audience by describing the way that these instruments give us “a larger pupil than our own,” which in turn allows us to see objects with greater clarity. However, as technological advancements allowed them to see more, scientists encountered atmospheric effects called aberrations that diminished the resolution of the images they obtained. This eventually led to the development of Adaptive Optics (AO) in the 1990s, where lasers were applied to samples instead of lights, and computers then corrected for aberrations and focused the images to give the best resolution possible. AO was first used in telescopes, but it is now used in microscopy as well. At this point in the lecture, Betzig joked that “microscopists are the retarded step-children” of astronomers, doing everything fifty years later and stealing their ideas.

Later, Betzig detailed a trip that he and his friend Harald Hess took to Florida State University, where they were introduced to photoactive fluorescent molecules. The application of these molecules would contribute to Betzig’s development of his Nobel Prize winning super-resolved fluorescence microscopy eight years later. Back in 2006, however, Betzig and Hess realized that the use of this technology in microscopy could go further. Thus, they were inspired to create a method of their own called photoactivated localization microscopy (PALM). Both unemployed at the time, they put in $25,000 each and set up the equipment in Hess’s living room because Hess “wasn’t married and there was no one to complain,” Betzig joked. PALM applies extremely low intensity violet light to samples, and turns on the signals for only a subset of molecules at one time. Repeating these signals and changing the targeted subsets allows them to determine the exact center of every molecule, and look at “thick samples with great densities and superb resolution,” according to Betzig.

Betzig’s second lecture, geared toward the scientific community, primarily focused on specific technologies that he has worked on, and how these technologies influenced his development of lattice light sheet microscopy. The lattice light sheet uses seven parallel Bessel beams that pass through a sample, giving a real time image of what cells and molecules look like in their natural live states. Combined with AO, this technology equips microscopists with the tools to analyze living cells and the single molecules that comprise them for long periods of time without destroying their structures. This provides scientists with continuous images of entire cellular processes. Betzig spoke adamantly about the complexity of biological specimen, explaining that the only way to truly discover how these organisms behave in nature is to observe them while they are still alive.

A humble man, Betzig spent hardly any time discussing the work that led to his receipt of the Nobel Prize in Chemistry. He did, however, detail what he sees for the future of microscopy. He explained that the only way people are truly going to understand life is by studying it with high resolution among all four dimensions across space and time. “Biology is anything but static,” he said, adding that “the thing that defines life is that it’s animate.” Betzig’s lab at Janelia is currently studying the functions of the brain, using microscopy to analyze and map out neurons. The lab members also publish resources online that explicitly detail how the lattice light sheet microscope is built so that other groups can utilize it, and Betzig expressed that all scientists are free to use the Janelia microscopes. Betzig believes that these technologies needs to be made available to everyone in order for it to have a meaningful impact on scientific studies. As Betzig moves to UC Berkeley, he will continue his research in microscopy in hopes of developing even better imaging technology.

After his talks, Betzig took questions from the audience and was able to express how impressed he is with the advancements that commercial technology and science has given the world. He also gave some advice to undergraduate students, saying that whether you pursue science or something else, it is vital to “do the thing that you feel passionate about,” and that “if you’re going to be a scientist and have your own lab, do it because you love it and cannot imagine doing anything else.”

Dr. Eric Betzig’s contributions to microscopy are valuable to biologists everywhere. It is minds like his that help further scientific advancements and give more people the opportunity to understand the wonders of the biological world.

 

Sources:

 

Adaptive optics. (2017, February 24). Retrieved February 25, 2017, from https://en.wikipedia.org/wiki/Adaptive_optics

 

Betzig, E. (n.d.). Eric Betzig- Biography. Retrieved February 25, 2017, from https://www.janelia.org/people/eric-betzig

 

Israel, B. (2016, September 27). Nobel Prize winner to join UC Berkeley faculty. Retrieved February 25, 2017, from http://news.berkeley.edu/2016/09/27/nobel-prize-winner-to-join-uc-berkeley-faculty/

 

Nobel Committee for Chemistry. (2014, October 8). Press Release. Retrieved March 12, 2017, from https://www.nobelprize.org/nobel_prizes/chemistry/laureates/2014/press.html

 

Photoactivated localization microscopy. (2017, February 23). Retrieved February 25, 2017, from https://en.wikipedia.org/wiki/Photoactivated_localization_microscopy

 

Edited by Lauren Uchiyama, Rachel Hull, & Nicole Strossman