“There’s Always More Than Just One Way”: Episode 3 of The Cancer Researcher Podcast

Dr. Alexandra Boitor, the EACR Scientific Officer, is joined by professors Elaine Mardis (US) and Carlos Caldas (UK) to take an overall look at career progression in academia, exploring not only the well-known PhD post-doc PI route, but also how one can combine clinical practice with research.

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Our guests in this episode:
  • Elaine Mardis, professor of neurological surgery at Ohio State University and co-director of the Institute of Genomic Medicine at Nationwide Children’s Hospital in the United States.
  • Carlos Caldas, professor of cancer medicine at University of Cambridge and senior group leader at the Cancer Research UK Cambridge Institute in the United Kingdom.

Episode transcript

Alexandra: Let’s start from the very beginning. I’m sure that all our listeners are eager to find out the recipe for success, to find out how you ended up as who you are today. My first question would be, what determined you to do a PhD in the first place?

Elaine: Well, coercion really! I’ve never been one of those people who had a plan in mind other than that I knew from a very early age that I wanted to be a scientist. I wasn’t really sure what that even meant when I was four or five years old, but certainly those seeds were planted and ultimately for me it was having the person who was eventually my PhD mentor as a biochemistry professor when I was a senior at university and having the whole world of molecular biology open my eyes by his lectures, which put me in the place of starting to have conversations with him.

I was planning to go and do a master’s degree in genetic counselling and he basically talked me out of it and asked me to do a PhD in his laboratory. So for me that was the decision point.

Alexandra: Did you always want to pursue a career in academia then? Did you know that was what you wanted?

Elaine: From the very beginning, I always knew that I wanted to be involved in science. That was sort of my generic description. I didn’t really know what that meant necessarily at the time, but I think I’ve just sort of had a series of happy accidents throughout my career and that was really one of them. I feel that there are different types of people and that’s fine, but I don’t feel like people necessarily have to come to science with a predisposed notion of being within scientific or academic research. That can develop later in life, and may be a consequence of the things that have gone on before.

And I also don’t feel like it’s necessary to have a plan in mind. Sometimes when you have everything carefully charted out and then something doesn’t work, it’s like a show stopper. So this can actually be a negative thing as well as a positive thing.

Carlos: Well, in my case, I’m a physician scientist, so I first trained and have continued to practice as a doctor, so I went to medical school, et cetera. I’m from a different era, so I did medical school in Portugal and did the American Embassy, and then I went to the United States and ended up in what I would consider a cathedral of molecular medicine, UT Southwestern in Dallas. And I was actually the last resident on the ward three years after he won the Nobel prize of Michael Brown. And, you know, Goldstein and Brown got the Nobel prize together for discovering the cholesterol receptor. Neither of them had a PhD. And by the way, their Nobel’s team was one of my mentors When I then moved to Johns Hopkins to do cancer training in medical oncology, he also didn’t have a PhD.

So I went into science because I realised that disease is ultimately disruption of molecular mechanisms, and so in order to understand disease, you have to understand molecular mechanisms. That’s what took me into the science path and actually the influence of individuals.

I said Southwestern in Dallas was a cathedral of molecular medicine. I really mean it! There were lots of individuals that I could name, but in my case, the big influence was Michael Brown himself who basically influenced me to really seek very basic science questions instead of just going on a path of clinical medicine and clinical research, not that there is anything wrong with clinical research.

Ultimately cancer is a disease of genes and protein. You need to understand that at a molecular level in order to advance, and that’s what I decided to do.

Elaine: I think you and others who trained in medicine really come to the pursuit from a very pure perspective because you experienced patients in your day to day.
And I would actually encourage people who have or are pursuing a PhD to get a flavour of that. It can be incredibly motivating.

Carlos: Absolutely, I completely agree with you in that respect. I don’t know if I form an outlier or not, but I am very much driven by curiosity. And I think that to advance in biomedicine, you really have to continue to support basic science. I think it’s very important that we continue to support basic, fundamental discovery-driven science because otherwise translational research will dry off very quickly.

Elaine: Yeah, I completely agree. I do think that those pursuits can be very inspired by and flavoured by being in touch with the medical questions that are at hand.

Alexandra: Going back to what you said earlier, do you think it would be a good idea to have clinical practice included in your PhDs or postdocs? If the subject you’re studying is related to disease like cancer research or neurodegenerative diseases or whatever is related to diseases, or do you think it would be a good thing for someone to volunteer in a hospital on a day-to-day basis to help around just to get a feeling of it?

Elaine: I think either could be very helpful. I think probably contextually in the course of studies, as Carlos and I were just talking about last week in Portugal, right? We live in such an interdisciplinary world now in terms of cancer research, which is all for the better. But it does emphasise that we can’t all come to the table with a basic question that isn’t informed by other perspectives.

So I do feel like at some level, whatever level that is, it can’t be bad because I always fundamentally worry about what I call research in a vacuum. If you’re pursuing something, whether it’s a computational question or an experimental question, if you don’t take into consideration the reality of that disease, or that question in terms of the patients that are involved and the consequences of their disease, diagnosis, et cetera… I think that’s just absenting yourself from that question in context. So to me that is research that is uninformed. And I feel very strongly that research should be informed by context. And so however you need to get that context, that’s what you really should do.

Carlos: Yeah. And there is no universal recipe of how to do that. It can be done when you are an undergrad or it can be done later. It can be done through interacting with people that act as mentors on this. It can be simply to be involved in open days where you show in research in a hospital environment, there are many ways.

Alexandra: So I’m glad you’ve mentioned mentorship. Is that something that played a crucial role in your career progression, having a mentor?

Carlos: I think you look up to people that are role models. I am not convinced that formalised mentorship programs are particularly successful. It is about creating an environment and sometimes having individual people that really touch you in a particular way and influence your decisions or the way you look at things. So I’ve been very fortunate. At medical school in Lisbon I had those people, then I went to UT Southwestern. With several Nobel Prize winners, several members of the National Academy of Sciences and quite a fantastic environment where you were expected to provide outstanding patient care, but then to also really be encouraged understand the mechanism of disease.

And then at Johns Hopkins, again, I was very fortunate to be around Vogelstein at a particular time. He’s been amazingly productive in his career at the time that I was there. You know, P 53 as a tumour suppressor, gene identifying apc, identifying mismatch repair, molecular diagnostics. All of those things were happening right there and then, so I was right at the thick of action, and that was really amazing.

So yes, mentorship is important. I have my reservations about organised mentorship programs, although I think you have to foster an environment where people that are less young like me, they are always prepared to be available to younger people and to give advice and to provide an example on the way they conduct themselves. They do their science with curiosity, with rigor, et cetera. So I’m all for mentorship, but I think mentorship comes from environment more than having organised mentorships. But maybe I’m wrong.

Elaine: No, I agree. I think mentorship is more of an organic process and it’s an observational process. You know, it doesn’t even have to be active. It can be passive, as you said, observing people who hold very rigorous science, who are open to questions and to offering advice when asked, and they take the time. It can actually be very informal but very effective.

Alexandra: Forgive my question, but if the whole mentorship process is to be passive, wouldn’t that run risk to sort of exaggerate the imposter syndrome? Because then you just see the career of that person. Everything they’ve achieved, but you don’t really have access to their personal life. You don’t know about their failures, because sometimes things don’t go exactly how you’ve planned. If in this process you’re just passive, wouldn’t that maybe have a negative impact on you to some extent?

Elaine: It could, but I feel like if you’re motivated, that’s really all you need. Failures will happen. They happen to all of us, but to me, that’s an internal drive to continue to succeed, to pick yourself up and go forward.

You know, certainly people can be inspirational in that regard, but at the end of the day, it comes down to yourself and your own motivation, in my opinion.

Carlos: Yeah, I think, of course, if you decide to come into academic career in science, if you can’t deal with failure, then it’s not for you. I think we have to cope with rejection.

Elaine: Our theme is always science is hard. And that can be many things, all of what you just stated and more.

Alexandra: And on that note, have you ever had to deal with rejection during your career? And how did you handle that?

Elaine: Usually not well!

Carlos: Well, of course. Rejection of papers or rejection of a career move or a grant. Absolutely. And you’ve got to be prepared to deal with it. And you made a point earlier, and I think you are right, you know, there is a risk. In just looking up to people to think that life is rosy and it’s all about success and it’s all about recognition by your peers.

I remind people to look at the history of science and even great discoveries. So for an example in neuroscience, and I’m going to be controversial here because it’s not cancer science, one of the great advancements in neuroscience was the ability to look at cells individually. And that required chromogenic staining which was originally invented by Golgi, but then the guy that adjusted it to brain cells was Ramon y Cajal.

He was this shy guy that was very determined and he just had to deal with rejection for multiple years until eventually he was accepted into a post. This was more than a hundred years ago. And eventually people came and looked at his work and they realised that he had done something really quite extraordinary. He persevered. He’s went on to get the Nobel Prize and is considered one of the godfathers of neuroscience, but he had to deal with failure for many years before he was recognised by his peers.

It’s just one story. I could tell you others. So, looking at the history of science is very important and people sometimes fail to do.

Elaine: Yeah, I completely agree. It’s inspiring on many levels and certainly that’s not the only example of someone who is way out there ahead of the crowd thinking outside of the box and ended up being right. But yeah, he went through a lot of rejection, et cetera. I think the other thing to say about rejection is that it actually is in many ways a valuable time to consult others and sort of understand, especially a failed grant proposal, let’s just say for the sake of argument, understand what is it that I’m not doing well or what could I do better?

In an ideal world, you get that kind of feedback from the review, but that’s not always the case. And so I think early stage career, if your grants are not getting funded, that’s really a setting where you can benefit from the experiences of others who have been successful. In that regard, I would say that really requires you to be open to criticism and to accept that and to take it on because otherwise it’s not worthwhile to get that feedback.

Alexandra: I totally agree. That’s amazing advice. But at the same time, dealing with rejection, that constant improvement, that constant working on yourself and on your research can at times feel overwhelming for some people. And I was wondering whether you have some advice to researchers who feel that way.

Carlos: I think the most important thing for someone starting their career is to pick the right environment and to pick the right type of place for them and for the way they are as a person and as a scientist. But I would say that the great test is to look at how their junior faculty has succeeded. Look at the last 10 people that were recruited, have they made it to tenure? Have they been supported properly? Because the environment is, I would say, as important as anything else. And the environment is the environment with your colleagues on the faculty. And it’ll be more senior than you if you are a junior PI, but it’ll also be the environment that will attract the best students in postdocs.

So I think don’t pick places just because they offer you a great package. Go and look into detail and spend the time and really do your due diligence just properly and look at what has been the success rate of the last 10 or 20 junior PIs that were recruited into that place.

Elaine: I would agree with all of those things, and add one thing, and that is another critical component of the environment is how much grant application support is provided. That is so critical and a lot of places just do not do it well. So is there someone who’s looking out for requests for applications that may be right up your alley and letting you know? So watching over, there are even services that do this now, but you still need someone to funnel it towards you.

And then secondly, what amount of support is available there for you to put together the budget that you need and fill out all of the other necessary paperwork that’s mundane, but critically important for getting the grant submitted on time, et cetera. So that’s a really important part, but maybe not one that people necessarily investigate when they look at a faculty position.

Alexandra: When do you think would be the best time to start investigating this? When you start your PhD, you’re probably a bit too naive to start thinking about this, and it’s unlikely that you know exactly what you want from your career, but when would you start looking at these sort of things? When you start your post-doc or second post-doc, when you start applying for fellowships, when do you think would be the best time to look?

Elaine: I think when you start looking for faculty positions. It’s a good question to ask as you’re interviewing for faculty positions, when you’re talking to other faculty members in the university where you’ve given your job talk and you’re thinking that all of the boxes look like they’re being ticked.

This is one thing to sort of drill down to on the one-on-ones that you have with existing faculty members and say, tell me honestly what amount of grant support is here. What has your experience?

Carlos: I completely agree. And I think, you know, the career is an apprenticeship in a way. So during your PhD, the focus should be of learning what it is to be a scientist. And a scientific method. Then when you pick a postdoc, you need to start thinking about what you would like to do for the next 15 or 20 years, and you’re getting a first taster of it. And then, you know, that is the stage of, of picking your first faculty position.

If you go straight from a postdoc or you decide to get a second postdoc, which a lot of people are doing nowadays, but, but if you go for a faculty position that in the last year, year and a half of your postdoc, you really start looking into it and preparing for it.

Alexandra: Thank you so much for your answers, which I am sure will be very beneficial to our members. And to finish up, I just have one more question that I would like to ask both of you. Reflecting on everything you have achieved in your career so far, what advice would you give to your younger self? Assuming there’s anything that you think you should advise your younger self, maybe you just think that your younger self just did everything as they should have and that that’s fine as well.

Elaine: I think in retrospect, I’ve been really, really fortunate in that regard. I don’t know that I did anything that I would do over again, I suppose. I think one of the challenges is always because I’ve always been involved in team science, just to be clear that it’s very easy at times to enter into collaborations that you immediately or down the road recognise are not healthy.

In other words, and this is actually particularly challenging in computational biology and bioinformatics, is that sort of your expertise is being used, but you’re maybe not being recognised so much for that expertise and the things that you’re contributing. So that would be my only caution, is just make sure that if you go for collaborative science, that what you’re doing is actually being acknowledged.

Stand your ground. And if not, then bail and go in a different direction. I think also in line of what we just talked about with respect to different institutions and environments, if you are going to be involved in team science, make sure when you go to interview that that’s a place that values team science, because that also means that others have broached that barrier and the pursuit of tenure. And that’s a really important attribute that isn’t everywhere right now, even today.

Carlos: Yeah. Well, I don’t have much to add to that. I’ve also been very fortunate along my career. Fantastic places with great mentors and, and so I’m fortunate in that regard. Would there be any decision that I would’ve taken differently career-wise? I don’t think so. I think that when I finished medical school, I knew exactly what I wanted to do, so I did the American Embassy exam and I went to the United States when I finished my fellowship at Johns Hopkins.

You know, I thought about staying in the United States versus coming back to Europe. We made the decision as a family to come back to Europe, and I don’t regret that. And I think that putting together a fantastic breast cancer program in Cambridge, I value my colleagues and like Elaine says, team science and recognising people. If I have one piece of advice is listen to advice, but then follow your own decisions based on both rational consideration of all the variables, and ultimately go with your gut instinct.

Alexandra: I think this has been brilliant advice and thank you very much both of you.

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