Jacques Dubochet, Nobel laureate and former EMBL group leader, reflects on a key aha moment
By Jacques Dubochet
A question I had as a child, which kept turning over and over in my mind, was thinking about planet Earth and asking: where exactly am I on it? As the night drew in, I saw shadows cast on the ground – shadows cast by me – and I knew that tomorrow it was going to be light again. To find out what was going on, I took a trip to my local library. You could call what drove me curiosity. But I wouldn’t call it that. Trying to understand what was around me, this was just a way of life.
Much later, as a scientist, I wanted to understand how water was made. Although it is a remarkable substance, it causes a lot of trouble for people trying to zoom in on life at high resolution using an electron microscope. If a person tries to use an electron microscope to study structures in a sample – such as the membrane of a virus or a cell from a mouse’s ovary – the microscope’s powerful vacuum will cause liquid water in the sample to evaporate. The structures left behind are warped or may even be destroyed. Although freezing a sample would prevent the water from evaporating, frustratingly, the ice crystals that form during the freezing process wreak similar havoc. So, along with my team, I set out to vitrify water – a way of freezing liquid water so quickly that ice crystals don’t form. This way, it would be possible to see tiny structures intact.
It was serendipity, luck, and some major failures that led me to the key aha moment
It was serendipity, luck, and – from time to time – some major failures that led me to the key aha moment that is part of the reason I was awarded the Nobel Prize.
This moment happened at EMBL in Heidelberg in 1980 when Alasdair McDowall, a technician in my lab, was attempting to vitrify small droplets of water on films to be used in an electron microscope. One day, after changing our cooling device by replacing liquid nitrogen with liquid ethane, he called me to the microscope because he saw something that he didn’t understand. It was a frozen droplet of some amorphous material – since it didn’t have any ice crystals, we figured it couldn’t be water. We warmed it slowly to try to see how it evaporated, in order to try to find out what the droplet was made of. At 135 Kelvin – or around minus 138 degrees Celsius – the droplet transformed in a moment into polycrystals that we immediately recognised as ice crystals. So the frozen droplet we had seen before had been exactly what we had been told was impossible to create: vitrified water. I remember just at this moment I told Alasdair, ‘here we have something essential.’
Then it took the work of many people over the next 35 years to advance cryo-electron microscopy techniques to the point that some individual atoms can be seen. Using cryo-electron microscopy, people have seen the structure of the Hepatitis B virus, the Zika virus, and rhinovirus C, which is associated with acute asthma in children.
Science is unity and physics, biology, chemistry are all different intertwined ways of understanding the same reality
I am a biophysicist and never thought of myself as a chemist. Nevertheless, in the end, I shared the Nobel Prize in chemistry. This may be understood in two ways. One is that I have reached my highest level of incompetence! A better way, perhaps, is that science is unity and physics, biology, chemistry are all different intertwined ways of understanding the same reality – a reality that is much bigger than we can wrap our little heads around.
Jacques Dubochet, who was EMBL Heidelberg Group Leader from 1978 to 1986, will speak at Revolutions in Structural Biology, a conference celebrating the 100th anniversary of Sir John Kendrew, at EMBL Heidelberg in Germany on 17 November 2017.