Marty Chalfie is a world-renowned scientist whose lab uses the nematode Caenorhabditis elegans to investigate aspects of nerve cell development and function. In 2008 he was jointly awarded the Nobel Prize in Chemistry for his work on establishing green fluorescent protein (GFP) as a biological marker. He is currently at the Crick on sabbatical from his position as a professor in the Department of Biological Sciences at Columbia University, New York and gave a Crick lecture on 30 May on ‘The continuing need for useless knowledge’ explaining the importance of giving scientists freedom to explore the world regardless of the perceived usefulness, or not, of their research.

So what has brought you to the Crick? 

I'm here on sabbatical - every six years or so I get some time off from my university post. I wanted to get away and do some reading, which I've not done very much of, and some writing, which I've done a little bit more of. I'm interacting with the people in my lab more than when I'm physically there. That's one of the great things about the sabbatical, you get a chance to refresh your thinking and get excited again. I also wanted to be able to interact with new people and talk to them about their science. 

When I was a postdoc at the MRC Laboratory of Molecular Biology in Cambridge, we would have people that spent a semester on sabbatical with us - they weren’t doing any experiments, but they were thinking about their projects, I thought at the time that it was a wonderful thing. It’s good to get other influences and find out what people are excited about. One of the group leaders here, Nathan Goehring, also works on C. elegans so I’ve been sitting in on his lab meetings and I attended the London worm meeting here at the Crick, which has been great.

You’ve spoken previously about your thoughts on academic publishing and how journal impact factors have become a misleading metric. How do you think academic publishing is changing?

I think one of the really wonderful, and important, things that has happened in biology over the last seven years or so has been the general acceptance of preprint archives. The papers published here are not peer reviewed, so, as a reader, you have to do the peer review, you have to do the thinking.

Several years ago, Francis Collins, the then head of NIH, told me an idea that I have used ever since: to have a lab journal club using only unpublished papers that had been deposited in preprint servers. We discuss everything about the paper; did we understand why the experiments were done? Did we understand the figures? Were there typos? Are there additional experiments that we could suggest? We use it as a stepping stone to think more deeply about the science.

It’s a wonderful training exercise for students. They are in charge of the discussion, taking notes and collecting all the comments, and they send them back to the corresponding author. This is a win-win situation; we get to evaluate the paper and consider its relevance to our work and they get important feedback. We invite people to do that to our papers too.

I think publication remains important – if you don’t publish, your work can’t have any impact. And there is a little bit of the tyranny of the journals with people feeling that they must publish in journals with a certain numerical value. But in reality, impact factors don’t say anything about the quality of the paper, how well the work has been done or the importance of the work. With that comes the peer review process, which is useful, it’s important to get feedback, but it doesn’t tell you that something is right or wrong, it just tells you that this work has been evaluated.

The work that your Nobel prize was awarded for was published in 1994. When you were first thinking about using GFP as a marker, did you have an idea of the scope of research it could be used for?

From the first minute I heard about GFP, I spent the rest of the seminar ignoring the talk and just thinking about what we could possibly do with it. If it worked – and that was an ‘if’ – we could use it to ask, where, when and how much of a gene is active in a living organism and all you have to do is shine a blue light on it! Cells, tissues, animals, plants didn’t need to be fixed, you could have a dynamic view of what’s happening. 

Did I have an idea of the scope discoveries that people were going to make using this technology? No, I don't think anyone is capable of thinking about all the implications of their finding. But I knew it was going to be exciting! There were things that people did subsequently that were really interesting, such as Geoffrey Waldo’s work on protein folding – I thought that was a brilliant idea. His work used the technology in a way that I couldn’t have imagined.

The Nobel is a strange prize. You don't have to be the smartest person, or the most prolific. You don't have to be published in a particular journal, or have the most funding - you are evaluated on the usefulness of the work as a way of changing how people do, or think, about science. And so what made GFP important was not any of the stuff that we had done, but the fact that so many people found it to be a useful tool. It's a little bit strange that you get honoured for something that other people did - but I didn't turn it down!

In your Crick lecture you argue that ‘useless knowledge’ is needed as much today as in the past to improve human well-being and health. What do you mean by this?

I think it's very understandable that people are often interested in biomedical research as a way to immediately address some problem, whether it's pancreatic cancer or Alzheimer's disease or autism. But to enable the cure or treatment, we really have to ask people to view it in context of the whole process and the many discoveries in basic science that happen along the way, and are necessary.

Take the COVID mRNA vaccines for example. From the outside, the rapid deployment was an astonishing achievement – and it really was! But this technology was many, many years in the making. Decades were spent developing a deep understanding of this technology.

With almost every significant advance in science, the ideas are built on basic research. It’s important that we let people know that the greatest achievements in biomedicine are going to be made by constantly doing two things; building up the base of scientific understanding and applying it to disease research.

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