Find a challenging question, trust in your findings and don’t pay too much attention to the naysayers. That is the advice that Nobel laureates Sir Timothy Hunt, Dr Sydney Brenner and Professor Harald zur Hausen would give to other scientists, particularly those at the start of their own careers.
APBN editors Carmen Loh and Catherine Ong interviewed the eminent scientists during the Global Young Scientists Summit (GYSS 2017) held earlier this year in Singapore. Organised by the National Research Foundation Singapore at the Singapore University of Technology and Design from 15-20 January 2017, the event spanned plenary lectures, panel discussions and interactive sessions with distinguished speakers.
I. Interview with Sir Timothy Hunt
For Sir Timothy Hunt, the road to the Nobel Prize began with the case of the mysterious disappearing protein. As a scientist studying the development of fertilised sea urchin eggs in 1982, he noticed that one of their proteins vanished each time the eggs’ cells divided, only to return, build up and then disappear again during the next division.
“I immediately knew that I had stumbled upon something very important, because proteins don’t just disappear like that,” he told APBN.
The protein, which Sir Tim Hunt named cyclin after its peculiar behaviour, turned out to control cells’ growth, duplication and division – a process that is crucial to life – and not just in sea urchin eggs too. Sir Tim Hunt later discovered cyclins in other species, and they have also been found in human beings.
In 2001, Sir Tim Hunt and two other scientists were awarded the Nobel Prize in Physiology or Medicine for their discoveries of key molecules, including cyclins, that regulate cells’ life cycle. Their Nobel citation noted that “these fundamental discoveries have a great impact on all aspects of cell growth”, and opened new possibilities for cancer treatment, since the disease is caused by unchecked cell division.
During Sir Tim Hunt’s GYSS 2017 talk, which was titled “Switches and Latches: The Control of Cell Division”, he elaborated on his discovery of cyclins as well as the mechanics of cell division. He also gave some advice to young scientists in his interview with APBN.
APBN: You’ve advised young scientists to set well-defined questions for themselves, and to keep experiments simple. Why?
Sir Hunt: You get little credit for solving trivial problems, but wrestling with big problems is impractical and unlikely to yield much result. Questions such as ‘how does the brain work’ or ‘how do you recognise a face’ are perfectly good questions, but they are not scientific questions, because the answers are multifactorial. A good problem is something that’s well-defined, lies in your area of expertise and is challenging but not too challenging. I’m a big believer in simple experiments because if you do complicated ones they usually don’t work.
You’ve also said that a little disrespectfulness can be helpful for scientists. Why?
It’s important for the young to realise that they need to be a bit naughtier and more sceptical. As a scientist you have to work hard and think hard, keep your feet on the ground, eyes on the horizon and nose on the grindstone, but being a little bit disrespectful is helpful too. When I discovered the sea urchin egg protein disappearing, nobody had ever suggested it or even thought about it before, because people would have said that it was quite impossible for proteins to go away.
What are some of your current projects?
I’m retired, but I have an office in the Okinawa Institute of Science and Technology (OIST) Graduate University in Okinawa, Japan, and I follow the work of various scientists. I offer encouragement and try to help them where I can. I’m also going to co-teach a course at OIST and am involved in writing problems for textbooks. I’m also trying to convert a book on molecular biology, which I co-wrote with Dr John Wilson (a professor at the Baylor College of Medicine in the United States), into a computer-based platform with multiple choice questions. I’ve got plenty to do!
II. Featuring Dr Sydney Brenner
When Dr Sydney Brenner won the Nobel Prize in Physiology or Medicine in 2002, he delivered a lecture titled “Nature’s Gift to Science”. The object of that accolade: a worm called Caenorhabditis elegans (C. elegans) that grows to just 1 millimetre long and has a life cycle of about three days.
In the 1960s, Dr Brenner was looking for a suitable species to investigate cell differentiation and organ development. The C. elegans’ small size and short life cycle enables thousands of them to be grown in a single petri dish and genetic changes to be observed quickly.
In a 1974 scientific paper outlining his choice of the worm for research, he added that it has a small number of cells, about half of which are neurons, making it a simpler organism for studies. It is also transparent, lending itself to observations of its cells under a microscope.
Before long, Dr Brenner had established the worm as a model organism for research in developmental biology and neurology. Scientists have used it to study ageing, cell death, human diseases such as Alzheimer’s disease and other fields.
When Dr Brenner was awarded the Nobel Prize for his work on the C. elegans, along with two other scientists who had built on that research, the citation noted that it had “provided a unique opportunity to link genetic analysis to cell division, differentiation and organ development – and to follow these processes under the microscope”.
Dr Brenner’s distinguished career has spanned other species. His research on the puffer fish – called fugu in Japanese – showed that its genome shared many similarities with the human genome, making it a useful model for studies of the latter.
With other scientists, he also discovered messenger RNA, which conveys genetic information from DNA for the production of proteins and enzymes.
In his GYSS 2017 lecture, titled “Reconstruction of the Past”, Dr Brenner gave an overview of the history of life since it began on Earth some two billion years ago, and how human beings are one of its products through evolution.
“Animals learn, and have memories and complicated social traits, as do insects such as bees, wasps and plants. But the human being is something different. Human beings have ideas, and they can see a future,” he said.
He urged GYSS 2017 participants to study the human brain and its potential, saying that this could become the most important biological study of the future. In his interview with APBN, he added that scientific research is challenging but worthwhile: “If you choose this life, it’s a hard life, but there’s nothing like it.”
He noted that scientists should develop their own ideas and try to prove them. Speaking to the GYSS 2017 participants, he said: “You are the future, so take responsibility for it.”
III. Interview with Professor Harald zur Hausen
Scientists need to have a thick skin and trust in their findings. Professor Harald zur Hausen, who gave this advice in his interview with APBN, knows its wisdom better than most.
In the late 1960s, most scientists believed that cervical cancer was caused by the herpes simplex type 2 virus. After examining many cervical cancer cells and failing to find any trace of the virus, however, Professor zur Hausen came to believe that another virus, the human papilloma virus (HPV), was responsible instead.
It took about 10 years, however, before he identified HPV-16 and HPV-18, two types of the HPV virus which are responsible for about 70 per cent of all cervical cancer cases. Since then, scientists have discovered that HPV also causes anal, penile and other cancers. Pharmaceutical companies have developed vaccines against HPV.
Professor zur Hausen’s vindication reached an apex in 2008, when he was awarded the Nobel Prize in Physiology or Medicine for his discoveries. His Nobel citation noted that he had gone against “current dogma”, and that the vaccines developed from his research could “reduce the need for surgery and the global burden of cervical cancer”.
“It was a long journey with many frustrating experiences along the way,” Professor zur Hausen told APBN. “People would tell us that we were on the wrong track, and that our work was nonsense. That’s why I always tell young scientists that you need a thick skin in science, and, in some instances, it’s good not to listen too carefully to your peers.”
In recent years, his other research has also garnered headlines. He is looking into the connection between red meat consumption and cancer.
“Epidemiological investigations have pointed for a long period of time to a potential link between red meat consumption and colon cancer as well as some other cancers. We believe that consuming red meat, specifically beef, is the risk factor for the development of colon cancer,” he said.
His work with other scientists has so far identified and isolated 22 types of virus-like infectious agents from cow serum and milk. “Of those that we have tested, all of them turned out to be infectious or lead to genetic activity in human cells,” he said. This means that they could increase people’s risk of developing diseases such as cancer and multiple sclerosis.
He noted that it might be too difficult to ask people to give up red meat and dairy products such as milk. “Our dream is to develop vaccines that can be given to new-born cattle, and by vaccinating cattle protect humans from the meat factors. It should also be possible to vaccinate human beings, but it would be easier to quickly develop a vaccine for cattle than for people,” he said.
In the meantime, he urged mothers to breastfeed their babies for at least six months if possible, as their milk contains sugars that can provide protection against some infections. He said: “Cattle have other types of sugar in their milk which have protective effects for their young calves. It’s something that has developed over the course of evolution, that we have some sugars that are protective during this particularly vulnerable period of life.”