Craziness in Science

Albert Einstein showing his tongue behind a jumble of scientific formulas

In movies, science makes new realities possible; we can time travel, dinosaurs come back to life, and humans develop arachnid-like abilities after being bitten by a radioactive spider. Most times, science is associated with failing experiments and disastrous outcomes – and some pretty crazy scientist characters. Being a scientist yourself, you are probably familiar with failing experiments and more or less disastrous outcomes, but probably you see significant differences between you and your movie counterparts. Or… are you simply biased? In the end, crazy people rarely consider themselves crazy and on campus you are surrounded by like-minded folks. Are we a bunch of crazy people? In an attempt to find out, I met two RMU scientists who recently won a crazy idea call. Find out whether this makes them crazy and whether craziness in science can be a good thing!

Hi Renée and Tom! Could you please introduce yourself?

Renée: I am Renée Maas, 2nd year PhD student in the Experimental and Genetic Cardiology group. I have been working here for more than 5 years. Back then I started as technician intern and I only left for my master’s internship in Stanford. All these years, I have been working on the genetic heart mutation in the phospholamban (PLN) gene using iPSC-derived cardiomyocytes.

Tom: My name is Tom Bracco Gartner, I am medical doctor in cardiac surgery department and this is my last year as PhD candidate in the Experimental Cardiology group. I am improving in vitro models for cardiac diseases, mainly fibrosis, with special focus on biomechanics. I have 3 months left, before I start my residency in cardiac surgery.

Renée Maas (left) and Tom Bracco Gartner (right)

This summer, you won the Crazy Idea Call from the PLN Genetic Heart Disease Foundation. What is your idea about?

Tom: We combined our research interests to model PLN cardiomyopathy. I am good at working with cardiac fibroblasts and modeling systems, which we developed together with TU Eindhoven. Renée, on the other hand, knows far more than me about cardiomyocytes and PLN.

Renée: Tom is technically very strong, whereas I am more into biology. Together, we want to combine his heart-on-a-chip and fibrotic readouts with the phenotypic events observed in PLN cells. Although there is a whole consortium for PLN modeling, the fibrotic aspect has never been included in any experimental approach. We know that many human PLN patients develop fibrosis, but mice with PLN mutations do not, which makes them inappropriate test models. We want to make a human in vitro model to study the mechanism of fibrosis in PLN and to screen for drugs. Actually, this doesn’t sound crazy at all, does it?

Tom: I was about to say that!

Renée: The PLN Genetic Heart Disease Foundation also changed the name from ‘Crazy Idea Call’ to ‘Out of the Box Grant’. Our idea is more about combining different interests and techniques to answer a question that nobody has tackled so far.

Tom: Yes, this is the only crazy thing here; the fact that nobody has been looking into fibrosis in PLN cardiomyopathy until now. Most modeling systems look at cardiomyocytes, which are arguably the most interesting cell types in cardiomyopathy. However, they do not cover the entire spectrum of the disease.

Did you come up with your project specifically for the call or did you already have the idea?

Renée: We have been talking about this idea before, but we started to think about the details when the PLN Genetic Heart Disease Foundation opened the call. Actually, I have already won it once before! The foundation is very active in supplying small grants for young researchers, who might have the most crazy ideas but lack immediate support from the PI to execute them. The Out of the Box Grant allows you to apply for it yourself, which is also a good exercise in grant writing. We gave it a shot, while our PI thought we were crazy. But that’s exactly what the call was all about.

Crazy ideas or out of the box thinking is sometimes considered risky and hence prone to failure. What is your opinion on that?

Renée: With our proposal, we kind of played it safe by grounding our plans on logical combinations of aspects. In the end, there is always some background to a proposal. As scientists we are trained to think like that, to build our hypotheses on facts. Even Tom’s crazy astronaut ideas are built on facts!

Tom: laughs That’s true! My supervisor and me were thinking about how the heart of astronauts is loaded differently in space than in normal gravity since they have higher risks of heart disease after return. This kind of brainstorming is more crazy, but also more inspirational.

The cardiac surgery department has a pretty crazy but inspirational idea, too: they want to investigate whether we can cure hearts outside the body. The idea started with taking out heart transplants for longer survival. Then, they wondered whether we could optimise imperfect ones before transplantation, and crazy thinking made the idea even bigger. Why not cure patient hearts outside the body with targeted immune or gene therapies?

A rocket flying through the sky
Moonshots bring science forward.

Tom: This reminds me of the moonshots of RegMed XB. They are extremely ambitious and perhaps more crazy than our ideas, but even if they don’t reach their goals… they will find out interesting stuff about the heart that we would otherwise not be able to find out. It’s going to be worth it anyways! The moonshots are also connecting clinical and basic scientists to cure the heart from in- and outside. We should think big, and more diverse teams will achieve more, I think.

Would it be helpful to have a crazy character by nature? Would you describe yourself as crazy or willing to take risks, private and/or professionally?

Renée: Oh, we can be quite crazy. Tom, do you remember…

Tom: …wait, this is off record, right?

[…]

Renée: Well, with regard to professional life, I like to think about how we can optimise lab work efficiency and scalability, from high throughput screenings to automated cell culture. I would like to obtain bigger grants in future to invest into more advanced lab equipment. We would need that for our in vitro model: the more complex you go, the more crazy your demands for your equipment become. How do you analyze 100 gels per day, or culture 30 stem cell lines simultaneously…?

Tom: That’s not really crazy though.

Renée:  Let’s call it ambitious. I know that many people would be interested in tackling these issues, but I like to speak up about it.

Tom: Does that make you crazy?

Renée:  Probably to the contrary, lab work optimisation would prevent many people from going crazy. And about you, Tom, you might not necessarily be crazy, but you took the most crazy steps on your career path. I remember how I trained you how to isolate RNA a few years ago and now you are making a heart-on-a-chip!

Tom: Yeah, starting a PhD was definitely a crazy idea for me. I have never been in a lab before, but somehow it seems to work out. But I don’t think that you need to be crazy to become a scientist.

Renée: You only need a lot of creativity. Nowadays, if you want to publish a paper, you need to combine different models, ideas and readouts. And creative ideas often arise from out of the box thinking…

So, you would recommend your peers to think outside of the box?

Renée: Of course! I think labs could do it more often. For example, they could organise brain storm sessions on a regular basis. We did it a few times and it was really nice!

Tom: I agree, there are quite a lot of crazy ideas in the minds of young researchers. We should discuss them, and break them down into steps that are actually doable. In the end, most ideas are not that crazy after all.

A person sitting inside a box, thinking
Think outside of the box!

It starts as crazy idea, but in the end it is a crazy good idea?

Renée: Exactly! As I said, you need to combine expertise for papers to make it a complete story. It would be nice for PIs to get more input from different perspectives. For PhD candidates, this is maybe more difficult to initiate as we need to focus on our own work. But you’re not crazy if you think outside the box and collaborate with someone from a complete different field, go for it!

Do you think that RMCU is a good place to combine expertise?

Renée: That’s for sure! We collaborate with the lots of people from different groups with different expertises!

Tom: We are closely working together within RMCU, but also within cardiology. It is really cool to see everybody with different backgrounds working on different things. RMCU offers a wonderful environment.

Renée: You can just walk up to someone during lunch, and people are very willing to help.

Is there anything else you want to share with your peers?

Renée: Yes! The PLN Genetic Heart Disease Foundation offers the Out of the Box grant every six months. So, if you have a crazy or creative idea, hand it in! The grant focuses in turn on more fundamental questions and on steps that bring us closer to a cure for PLN cardiomyopathy. Whether you are in the field, or from another field that can provide new assays, you are welcome to pitch!

Thank you for your time, Tom and Renée! Good luck with your crazy (good) research!

 

This blog is written by Katja Jansen (RMU communications officer (2019-2020) and PhD candidate in Drug Innovation (2016-2020)).