Thea Tlsty is Professor of Pathology at the University of California, San Francisco. She is funded by our Grand Challenge initiative to lead the STORMing Cancer team, who aim to understand the links between chronic inflammation and cancer. Here, she shares her views on taking risks in a research career.
A diversified research portfolio
When you’re a financial investor, your portfolio includes both risky and very solid investments. The same should happen with scientific investigators and their research projects. In my laboratory, postdoctoral fellows have two projects. One of these we call the ‘bread-and-butter’ project. This is a type of project for which the technology is in place and that will lead to a publishable finding if you do the research properly and interpret the results.
Bread-and-butter projects help early-career researchers hone valuable skills. They get the chance to write papers, present their research at meetings, collaborate with others and think about what they’d need to do to apply for a grant to carry their work forward.
Then there’s another project that people take up when they’ve settled in, usually a couple of months after they’ve joined the laboratory. We call this the ‘nose’ project, as the young scientists are following their nose. They usually come up with a research question, we talk about it, and they design how to address it. This type of training is very important: it helps them build confidence in their ability to ask novel questions.
Nose projects are typically risky, but they teach early-career researchers how to be a leader in the field: how to forge ahead, break boundaries, go into uncharted territory and develop new technologies or new ways of thinking.
Nose projects are typically risky, but they teach early-career researchers how to be a leader in the field.
When to take risks
When a scientist gets their first independent job in academia, they should put some effort into bread-and-butter projects that will give them the credibility they need to establish a career in science. Funders like to see a few papers published in reputable journals coming out of a young person’s laboratory – with them as senior authors – asking good research questions and reporting on properly done research. This gives funders the confidence that the investigator will be able to carry any type of project forward.
But young investigators should also save some of their time, resources and energy for the risky things, the ‘dreamer’ things, the things that nobody else is thinking of. They’re in a perfect position to have bright, fresh, new ideas. That’s not to say that more senior scientists can’t do this, but it means they need to get out of their comfort zone, and some people find that difficult.
Although it’s smart to always have a bread-and-butter project ongoing, investigators can start taking more risks as they become more established. For instance, my team’s work with human tissue, a valuable and rare material, relies on having the connections that give us access to it. So this type of work is probably more challenging for a person who is new to the field.
It’s very helpful to bounce your ideas off a trusted colleague to get their opinion. I have a colleague who was already established in academia and well-known internationally when she came across a major discovery. We went out to dinner and she told me she had two grants on bread-and-butter projects, but no funding to explore her new discovery yet. She was wondering what to do.
A colleague who was already established in academia […] came across a major discovery […] I advised her to “jump in, both feet”.
The new discovery was so promising that I advised her to “jump in, both feet”. She did, and became the founder of a new, breathtaking field. She is now a major player in a company focused on studying this area, which will have much more impact than the work she was doing previously.
Academia and industry
There used to be a tremendous difference between the worlds of academia and industry, but it is now easier to transition between the two. This has had an influence on how risky projects are managed.
A beautiful example is the development of Gleevec® (imatinib mesylate). Gleevec was first conceptualised in an industry setting, but industry were too conservative to want to progress the idea at that stage. Instead, industry scientists approached their academic colleagues and together they formed a team that took forward the work within an academic setting. The project was a huge success, Gleevec returned to industry and was developed as a drug that is now widely used.
My riskiest project
As a postdoc, I discovered that when you injure cells, especially tumour cells, they are more prone to amplify genes. I was able to increase the frequency of gene amplification by five orders of magnitude, which was extremely useful for the biotech industry.
I was then ready to start my own laboratory and I wanted to understand which kind of cells are able to amplify genes and the mechanisms that control this phenomenon. Many people had been studying point mutations, but we did not know how cells controlled gene amplification, deletion or translocation. I was investigating one of the fundamental properties of cancer cells: genetic instability.
It takes time to open a field; it’s best to keep showing people that you know what you’re doing, so that they can trust you and give you room to operate.
At that point I did not take the safest way and did not diversify my portfolio. It was several years before I broke through with my big question. When I did, it was a huge success, and it helped me get my job here at the University of California, San Francisco. But I didn’t have publications for several years and the people who hired me were wondering if perhaps they had made a mistake. It takes time to open a field; it’s best to keep showing people that you know what you’re doing, so that they can trust you and give you room to operate.
Grand Challenge: risk-taking on a large scale
With the Grand Challenge initiative, Cancer Research UK are trying to facilitate revolutionary – rather than incremental – change. I’m of course biased, because I am a Grand Challenge awardee, but I’m convinced Grand Challenge is going to make a huge difference in cancer research worldwide. I have reviewed for many grant-giving bodies in the USA and Europe and none has set up such a forward-thinking initiative.
I’m convinced Grand Challenge is going to make a huge difference in cancer research worldwide.
Notably, the £20 million Grand Challenge awards are aimed at teams that are diverse. One of the ways in which we can create diversity is by having young scientists and trainees bring along their fresh vision to the project. We are doing that in our team. We make sure that they have something that they can publish, but we let them contribute to making an exciting, fresh, totally new kind of biology come together.
This article is based on an interview, which was edited for clarity and length.
Grand Challenge is the most ambitious cancer research initiative in the world: a series of awards of up to £20 million seeking international, multidisciplinary teams willing to take on the toughest challenges in cancer, and providing the freedom to try novel approaches, at scale. We’re currently asking the research community to think big and help us decide what our next Grand Challenges should be.