Most people have seen an image produced by cryo-electron microscopy, or cryo-EM, in their biology or chemistry class and didn’t even realize it. While the method only produces pictures of molecules, the process of developing this high-resolution, accurate depiction of a biomolecule took over 30 years to perfect.
The arrival of cryo-EM is so important that Jacques Dubochet, Richard Henderson and Joachim Frank received the Nobel Prize in Chemistry for their work in October 2017. The Royal Swedish Academy of Science, the organization that presents Nobel Prizes, described the tool as something that “has moved biochemistry into a new era.”
Cryo-electron microscopy involves shooting a beam of electrons through a frozen biomolecular sample. The material that coats a sample, typically liquid ethane, enables researchers to capture an image that determines the structure of the molecule.
The approach is much more advanced and precise than previous methods of X-ray crystallography and nuclear magnetic resonance, or NMR.
“(Cryo-EM is) much, much more adaptable to lots of different types of biological questions than NMR or X-ray crystallography,” said Cryo-EM Specialist Sara Butcher to the American Chemical Society.
While X-ray crystallography and NMR produce accurate results, cryo-EM has the ability to view larger, more complex structures, some of which can be magnified up to 100 times more.
People from all areas of the sciences recognize its impact, including students at Guilford.
Junior Ella Coscia says she prefers seeing cryo-EM diagrams in her textbooks as opposed to more dated models.
“For me, I can visualize (molecules) better … If I can see how (they) interact, I remember it,” said Coscia.
Outside of education, cryo-EM has been vital toward saving countless lives. The tool has defined structures for a number of human protein molecules, receptors and more that are needed to battle illnesses like cancer, the Zika virus and HIV.
Because of these large-scale impacts, President of the American Chemical Society Allison Campbell believes the researchers truly deserved winning the Nobel Prize in Chemistry.
“This enables us as scientists to look at molecules and the arrangement of atoms in molecules in the resulting structure,” said Campbell to CEN Online. “It doesn’t really matter that it’s a biomolecule … it’s all about chemistry.”
The story of cryo-electron microscopy began before its images became mainstream within the scientific field. One of the recipients of the Nobel Prize, Richard Henderson, launched the journey in 1975 when he used electron microscopy, sans immersion in liquid ethane, to develop a rough 3-D model of a molecule. In the 1980s, Frank created a process that converted 2-D electron microscopy into 3-D structures.
While Frank was perfecting his image-processing technology, Dubochet devised multiple methods for rapidly freezing biomolecular samples. Because of Dubochet’s efforts, Henderson was able to obtain the first cryo-EM structure of a biomolecule named bacteriorhodopsin in 1990.
Although bacteriorhodopsin was relatively easy to capture because of its simple structure, it was the catalyst for improvements that made cryo-EM a commonly used method for many scientists.
As the 2000s produced even more accurate electron detectors, cryo-EM technology has become more accurate and less expensive, enough to where it is now commercially available for any scientist to utilize.
The journey took over 30 years, and cryo-electron microscopy is now arguably more than deserving of its 2017 Nobel Prize.