Wednesday, 8 October 2014

Breaking good: 2014 chemistry Nobel Laureates broke barriers in light microscopy

For over a century, scientists believed it was impossible to see viruses and single molecules with a microscope. But three researchers broke through this "physical limit" and are now Nobel Laureates.
Fluorescence microscopy
Photo: Wikipedia This year's Nobel Prize winners in Chemistry made such high resolution images possible
Just forget all the facts - forget everything you ever learned about light microscopy at school or university (if it was decades ago). Because the three new Nobel Laureates in Chemistry - two Americans and one German - have turned it all on its head.
It used to be fact, and even children at school were taught one basic principle of light microscopy: it's impossible to see things that are smaller than 200 nanometers - that is, a 200 millionth of a millimeter.
So you might be able to see the shapes of very large bacteria or human cells under your microscope, but you won't be able to see smaller structures inside of these cells.
You won't be able to see viruses - and certainly no single molecules.
But things have changed radically since school.
And that is due to the work of Eric Betzig of the Howard Hughes Medical Institute in Ashburn, USA, Stefan Hell of the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany, and William Moerner at Stanford University, USA.
They are awarded the 2014 Nobel Prize in Chemistry "for the development of super-resolved fluorescence microscopy," the Nobel Prize committee announced in Stockholm on Wednesday.
William E. Moerner, Stefan W. Hell, Eric Betzig 
Photo: EPA/STANFORD UNIVERSITY The three Nobel Laureates: William E. Moerner, Stefan W. Hell, Eric Betzig
Unexpected news?
"I was totally surprised," said Stefan Hell after the prize was announcement. Only when he recognized the voice of Staffan Normark of the Nobel Prize committee did he believe the news.
Aside from the Max Planck Institute, Hell also works at the German cancer research center (DKFZ) in Heidelberg.
There, the DKFZ press officers had been expecting Hell would receive a Nobel Prize for years. But not in chemistry. "We only had the Nobel Prize in Physics on our radar," a spokeswoman told DW.
Michael Boersch, now professor at the university hospital in Jena, worked with William Moerner at Stanford University. He told DW: "It's not surprising that Moerner was awarded a Nobel Prize. He was the stand-out candidate for a Nobel Prize in Chemistry."
A phenomenon called fluorescence
"A fundamental law that was true for 150 years was annulled," said Hell's colleague at the Max Planck Institute for Biophysical Chemistry, postdoc Volker Westphal.
Hell says he didn't believe in the so-called physical barrier in light microscopy, which had stipulated it was impossible to see things smaller than 200 nanometers.
"I could not see a chemical reason why it couldn't work out," Hell says. "I realized there must be a way by playing with the molecules and turning them on and off."
Hell linked the cells he wanted to look at with fluorescent dyes. These dyes can, in a sense, be turned on and off. They are excited to a higher energy level by light or other radiation. When the substance returns to its original state, it emits light - the substance glows.
Fluorescence microscopy A cell under fluorescence microscopy
Tiny but visible
Hell developed a special microscopy method which makes use of two laser beams.
One stimulates these fluorescent molecules to glow.
A second laser beam, though, cancels out any glow caused by the first beam - except for that in a nanometer-sized volume.
This way, he yielded images with a resolution much better than conventional light microscopes.
William Moerner and Eric Betzig worked separately on a second method called single-molecule microscopy.
It also relies on fluorescence and the concept of turning individual molecules on and off.
They made it possible to see single molecules under a microscope.
"Moerner was the first who could detect single dye molecules which are only about one nanometer big," says Boersch, adding that that was way back in the 1990s.
Fluoreszence mikroscope
Photo: Jan-Peter Kasper dpa/lth Scientists around the world use fluorescence microscopy to study living objects
Observing living things
There is one thing that makes the methods developed by the three Nobel Laureates very useful for all kinds of applications, says Sven Lidin of the Nobel Prize committee.
With a different kind of microscope, the electron microscope, it was already possible to study very small things, such as cell structures, viruses and single molecules. But to apply this method, all material has to be dead.
"Now we can observe E.coli bacteria without killing them, without fixing them. They can be studied in real time," Lidin says.
Scientists can have a close look at all kinds of living organisms under the light microscope.
Otmar Wiestler, a scientific director at the German cancer research center, says the development is invaluable.
"We can study living cancer cells and observe how they react to certain cancer drugs," he says.
Observing how cancer cells change their structure when they come into contact with certain substances also helps to develop new drugs, Wiestler says.
"We can study synapses and the interaction between viruses and cells."
The technology has been used to study HIV, the virus that leads to AIDS.