Skip to main content

I used to calculate the structure of viruses by hand

He described the virus that causes the common cold and found a cure for it. Biophysicist Michael G. Rossmann gave a lecture at Masaryk University.

At 86, biophysicist Michael G. Rossmann continues to work at Purdue University and studies viruses that are capable of attacking bacteria.

Virtually everyone knows what it is like to come down with a cold, accompanied by a runny nose and sore throat. There are dozens of viruses that cause the common cold, but the most prevalent one is rhinovirus, whose structure down to the atomic scale was mapped in 1985 by biophysicist Michael G. Rossmann.

This scientist, who at the beginning of his career had to painstakingly calculate the structure of organic molecules manually, talked about the history of structural virology in a March lecture, part of the Mendel Lectures series at Masaryk University in Brno. He explains his interest in what viruses look like in the following way: “To understand how things work, we need to understand what they consist of. You can figure out how a car engine works by dismantling it and putting it back together.”

However, his path to virology was anything but straight. Rossmann hails from Germany, but he left the country when he was nine years old. His mother was Jewish and although he was brought up as a Quaker – a Christian religious movement – it was not easy for him to grow up in Germany at that time. As he recalls, “I was sent to a boarding school in the Netherlands. In the summer of 1939, we left for the UK and I couldn’t return to school after the summer holidays, because the war had broken out.”

And so he started to learn English and go to school in the UK. As he had been interested in science since the age of twelve, he went on to study mathematics and physics at the University of London. After finishing his studies in 1953, he moved to Glasgow and taught physics at the local technical college. “However, I wasn’t very happy about what I was doing – or rather not doing. I wanted to continue my studies and, most importantly, do research,” says Rossmann.

This led him to contact Kathleen Lonsdale, an eminent Irish scientist and the first woman elected a Fellow of the Royal Society. Lonsdale was a crystallographer: she studied the structure of crystalline substances using X-rays. She accepted Rossmann as her student, but as he was not awarded a scholarship, he could not afford to follow her to London.

“While I was waiting for the decision about the scholarship, I read literature related to crystallography and I realized that there was another eminent crystallographer – Professor Robertson – right there in Glasgow. So, I became his student and was able to continue teaching at the same time,” says Rossmann about the beginning of his research career. The first structures that he studied were aromatic hydrocarbons, with a specific focus on segments of their chemical bonds.

Searching for the cause of colds
Later on, Rossmann transferred to the University of Cambridge, where he joined the team led by Max Perutz, a future Nobel laureate. He was interested in the structure of proteins, specifically myoglobin and haemoglobin; the latter is present in red blood cells and its function is to transport oxygen to tissues. “It was this research that made me think about whether we could also discern the structure of viruses,” says Rossmann.

“What viruses look like” was not a new question: James Watson and Francis Crick, who discovered the structure of DNA, thought that these non-cellular organisms consisted of identical subunits and that they were in some ways symmetrical. “This was basically confirmed in the case of haemoglobin, as we found that it consisted of four polypeptide chains and had a symmetrical structure,” explains Rossmann, who fondly remembers the time he spent at the University of Cambridge. In his words, it had a very creative and stimulating atmosphere.

However, his work at the prestigious university ended after several years and as he could not find a suitable position in the UK, he moved to Indiana and started an X-ray crystallography lab at Purdue University. “I wanted to work with viruses as soon as I started working there. However, collecting and processing so much data was a major hurdle at the time,” says Rossmann, adding that the computers of that era simply lacked the processing power for such a task.

For this reason, he decided to work on different molecules that are similar to viruses: dehydrogenases. This research brought a great deal of new knowledge. He was the first to describe a structure that helps proteins bind nucleotides and which now bears his name.

Moreover, his study of dehydrogenases helped him obtain sufficient resources for his virus research. “We started with plant viruses. They were easier to come by, because Purdue is full of greenhouses where we could grow plants and get enough material for our study,” explains Rossmann.

However, Rossmann and his team soon moved on to the study of human viruses. They chose the smallest ones – picornaviruses. As Rossmann says, “After six years of work, we managed to describe the structure of a virus that causes the common cold.” He points out that this allowed scientists to discover how the viruses attack cells and how they can be fought. He also participated in research that aimed to develop a cure for colds. While the researchers managed to discover a substance that could eliminate the virus, the drug was not approved for sale due to its side effects.

Are viruses the new antibiotics?
There are thousands of known viruses with different structures. Michael G. Rossmann describes the development of viruses as follows: “New viruses are created within the host cell. They are immature and are not even infectious, as that would destroy their host. They only leave their host cell after a certain period of time, when they are developed enough to be able to attack other cells and reproduce.”

Some viruses are enclosed within a membrane. These include the influenza virus, the dengue virus, and the Zika virus. Due to this envelope, it is difficult to study their structure using crystallography. Researchers therefore use electron microscopy. “Studying viruses is much simpler today than when I started. We have cutting-edge microscopes and computer technology at our disposal. When I came to Purdue, I was the only structural biologist at the whole university – now we have our own building,” Rossmann says with a smile.

The storied scientific career of this now 86-year-old researcher continues to develop. He still works at Purdue University (Indiana, US), where he studies viruses that are capable of attacking bacteria. These could potentially take the place of antibiotics, as bacteria are increasingly resistant to standard treatments, but they might also be used in targeted therapy to attack cancer cells.