Episode 9: Beyond the Hypothesis (Transcript)

Peter  0:00 

What are your thoughts? What are you feeling right now?

Dr. Clevers  0:02 

I’m on a tropical island. Sweet, sweet fruits. Very relaxed. Enjoying the sun doing nothing.

Peter  0:12 

So what it was, was a gummy worm. The reason why I picked the gummy worm and I like your interpretation of it. The reason why I picked the gummy worm is because it kind of looks like an intestine with its ridges and I thought that was really interesting that they put the effort into making these ridges into gummy worms. Why not just make a smooth surface …

Dr. Clevers  0:30 

Can I have another one?

Peter  0:44 

Hi, and welcome back to The Gastronauts Podcast. My name is Peter and I’ll be your host. Here at Gastronauts we are committed to exploring communication throughout the body, with a particular focus on the crosstalk between gut and brain. We invite experts in this field to share both their research and their incredible journeys. So come join me as we explore the steps that go into shaping a scientist on the Gastronauts podcast.

Today, we have Dr. Hans Clevers, the director of research at the Princess Máxima Center for pediatric oncology and a professor of molecular genetics at Utrecht University. For those of you who study the gut or use organoids in your research, he needs no introduction. Dr. Clevers was the first to discover stem cells in the intestine and that the disruption of a downstream effector of the Wnt pathway, TCF4 abolishes stem cell crypts. He also showed that activating Wnt mutations underlie the development of colon cancer. He developed the first organoids through culturing living stem cells in the intestinal tract and has been awarded the Louis-Jeantet Prize for Medicine, the Breakthrough Prize in Life Sciences, the Heineken Prize from the Royal Netherlands Academy of the Arts and Sciences to name a few and has authored over 600 publications with over 100,000 citations. We really appreciate you taking the time to be on our podcast, Dr. Clevers.

I want to start by discussing your scientific journey. In hindsight, it is always easier to explain a career decision as planned; however, you have been very open about your initial thoughts on pursuing a career in both medicine and science. Can you take us through a few different big-decision moments in your career and what went through your head and what helped you make those decisions?

Dr. Clevers  2:48 

Yeah, so I’m actually 62 so I’m not the youngest anymore. When I was a young kid, I already knew that I was going to be a scientist. I was interested in biology. I read all the discovery stories of Africa and the bulls. And so when I was 18, in Holland, you go to university at 18. I picked up biology and was actually quite disappointed because it was still […] 19th century science, very descriptive, lots of Latin names, taxonomy, very little [instruments or] tools that you could do much with. Because this was [1975], this was just before molecular biology, DNA technology was just being developed and spread around the world. So I then also went to medical school. I completed two studies in the course of my master’s in biology. I spent some time at NIH; I spent a year in Nairobi, and that’s when I started learning about monoclonal antibodies that had just been developed, and about the first gene cloning experiments and I realized biology is probably going through a revolution now, but I also liked socially the medical environment, […] the clinical environment much more than the lab environment In labs, you’re locked up with a few people that you have selected. It’s much more social- you see the entire population of your city combined, all the young, poor, rich- you have nurses, you have the doctors, you have the students, you have the patients. In a lab, it’s 10 – 15 people, always the same. But so I then got a training position, pediatrics in Utrecht. They asked me, well, because of your double background, why don’t you start some research and you can do a PhD, which we don’t leave University with a PhD, we leave with a masters. So I started some research. And in that year, I realized although socially, it’s not always the simplest environment, really I’m a scientist. I’m not a doctor. And I then gave up that training position, wrote four papers on a project that I designed myself entirely, and didn’t end up in the biggest journals. Also, I was an immunologist. Essentially, I wrote two pairs of papers: on T cells and I repeated the exact same thing on B cells. And that already I think people started looking at me, “how can you be interested in T cells and be interested in B cells- you have to choose.” And that [is] something I I’ve learned that you don’t have to confine yourself to, to a discipline. But then I also realized I had to learn molecular biology from scratch. And I got a postdoc position in Boston in a lab of a Dutch PI, Terhorst. And I learned to clone TCL genes, and I was still a molecular biologist. And that is when I although was a tough time: 4 years. In the end, it worked out well and that’s when I realized this was the right decision for me. I’m a scientist. I find hospitals fantastic places, […] also the patients are better off if I’m in the lab and not with the patients.

Peter  5:47 

Yeah, so you mentioned- I know this is a while back at this point, but you mentioned that other people in the clinic and mentioned maybe you should go into research. Was there any hesitation or reservation thinking that, “oh, if I leave medicine now, I won’t ever come back to it at that time.” I think now you certainly have established yourself as a scientist, but at the time, did you have any concerns?

Dr. Clevers  6:06 

It was a real decision point for many reasons, but one thing is that the medical profession is a hard profession; it’s not easy. You have to be able to work hard. You have to be social. You have to be smart. But what I could see is that most doctors that would bring this with them, have a nice life, they have a good career. They work hard, but everybody understands what they do. There’s not this hierarchy, you have a few top doctors and then all sorts of other levels of doctors. There’s not this constant competition that you have in science. On the other hand, I knew that I am a scientist that says. Im not really sure I’m going to be a successful scientist, but that’s where my passion is. So I actually sat with my father for quite some time and asked him for advice. He said, it’s your decision. That’s if you if that’s where your heart is, go there. But it’s extremely risky because a career in science is very unpredictable […] As a doctor, you know, by the end of your day, you know, whether you have the skills to be a good doctor. As a scientist, even after a PhD or a postdoc, you don’t know whether you have the skills and the luck and persistence to be a PI and everything with it for many, many years because it’s just very hard work.

Peter  7:17

So when do you know that you have the stuff to be a scientist?

Dr. Clevers  7:20

Well when we first started discovering things [that were really just] small but were important. I was probably eight years into being a PI when I realized that we’re now doing things that […] people find interesting. And it was luck. So we’ve apparently made a few choices of where to go with the with the science, but it might also have not happened. And there’s also if you’re too long without a significant new insight, that is the end of your career, even if you’re as good as somebody else who did get an insight and got this boost to the career.

Peter  7:57 

But you mentioned earlier that people were telling you can either be a T cell scientist or a B cell scientist and you saw this not true- you can always pivot your research in the direction that you want it to go. Could you elaborate or unpack a little bit more about that?

Dr. Clevers  8:08 

Yeah, I can maybe describe the trajectory of my lab, which is very abstract. It’s because almost everything we did failed, and I forgot about it, but my [early] people actually know all this, because they went through that. So we started as a lab that wanted to find transcription factors in T cells. And knowing that these genes, although the genome was known in the late 80s, at all was still a decade away. But we knew that transcription factors are very important for cell decisions. And so we cloned a few amongst them, [and one] was a gene called TCF1. And then it took about five to six years until we realized that this was a crucial transcription factor, but not so much for T cells, but for early development in any kind of animal. It’s part of the Wnt pathway. So then I basically changed my lab from a molecular immunology lab. We had fruit flies, we had frogs, all these in collaborations. We have zebrafish, we did lots of mouse genetics. And then we finally hit on this link with the gut. And then I again converted my lab from a developmental model organism lab to a gut lab and we had to get to know somebody who knew histology and paraffin sectioning.

Peter  9:19 

Do you have any hesitation with making that switch?

Dr. Clevers  9:21 

No, it’s part of the personality of me, but also you sense that the lab around you starts to, I don’t know how that works, but has the same personality as yourself. I don’t know whether the lab programs me or I program the lab, so as long as the technologies around it doesn’t really matter if you need DNA sequencing. It doesn’t matter if it’s a zebrafish, or yeast or human cancer, sequencing is sequencing. So we’ve always been going in areas where we at least knew that we have mastered the technology and then the biological questions in the end [everything that] we’ve discovered is always simple. So there’s a few things if I can, if I look back, because I’ve been doing this now for 30 years, that have been very well for us. One is no fear [and] an enormous amount of trust. And that’s what I learned from my PhD advisor. So you can trust other scientists, you can share unpublished information you can, and you always get more bang [for your buck], because if people trust you, they are easy collaborators, they will help you when you need them. And it’s more fun. So there’s a lot of paranoia in science, which I think is sort of self-fulfilling. Because if you’re paranoid about your neighbor, bad things will happen. And if you’re open to your neighbor, that’s one thing. So trust, and courage so you can make a difference in somebody else’s discipline. If you bring in the right technologies and a good way of thinking, you can actually make a discovery. You have to have good collaborators to protect you from stupid mistakes, but also introduce you into that community. We’ve done that a lot. So we’ve written on fruit fly genetics on zebrafish genetics on the highest level journals, but always with a collaborator in that field that had helped us. And then one thing that I’ve often said is, I strongly discouraged my lab to formulate hypotheses. Now this is not how science is supposed to work. So my strong sense is if you enter a field where little there’s known and where you don’t really know the questions, you can ask. So don’t ask strong questions that are looking for strong answers where you already know the answer, because that’s your hypothesis. Just be open-minded, go into experiments, build a robust experimental system, and just watch. Watch and watch and watch. And then the human brain always immediately comes up with solutions, which other hypotheses, but you can sit down with a number of smart people and come up with 1000 solutions to your problems that could all be true. And evolution has picked one randomly. So why would your brain- I think it’s very arrogant to sit down and formulate a hypothesis in a field where you know nothing. And the human brain also works in that way that once you have your hypothesis, you will publish the hypothesis. You’ll find the evidence that it’s true. And that’s I think, where many non-fraudulent but papers are produced that turned out to be wrong, because in that process, you lose your open-mindedness. That’s not how our brains are comfortable to work with. So that’s something that I see a lot in my lab and somebody says, experiment fails, I say, “why? Did you drop it on the ground?” No, no, no, because you know, this is the result I got, and I should have gotten this. This is because you have your hypothesis. Get rid of your hypothesis and look at the results with an open mind […] So I think for discovery science, this is really the way to go. You cannot write grants, you cannot write papers [in which] you refuse to work with hypotheses, but it’s for me at least has been the most productive way of doing this. I guess a more applied science like in clinical science where you have to have a strong question and you have to have a hypothesis and there’s only a few answers: a drug will or will not work. So there it works. But for this open end where, you have no clue what you’re looking at and what the processes are, the hypotheses will blind you rather than help you.

Peter  13:21 

Yeah, one thing that you just said that really resonated with me was the fact that our context really biases our hypotheses. Where we are situated in a particular lab, or where we are in the world biases or informs our decision on how we approach science. And this is why it’s important to have collaborations with people who have different viewpoints than your own. In an era where communication internationally is just a few clicks on your computer away, what do you see the value in, in these large […] scientific organizations or societies that bring people together for an international conference? And if you were in charge of one of these conferences, how would you run it so that you would have effective communication?

Dr. Clevers  13:58 

That is a very good question. So for me, personally, these meetings [where] I’m a speaker, I have good access to the other speakers. So that’s where I get my information from. That’s where I build my, my networks, my collaborators. And that’s where I hear about the newest technologies about who to trust, who not to trust, what works, what doesn’t work. I rarely read papers. So I don’t read- I read Nature and Science but not the second or only the first part about the political things. So because we review a lot of papers so there’s a source of information so […] I would advise anybody you know, [when] you get asked to review, review. Because it gives you connections with journals; you learn a lot you learned before it’s appears half a year later in print. And so that’s for me, and I guess for many people, the face to face is still very important and Skype works well once you know people and you collaborate, so it’s a very good way of collaborating long distance. I guess for young people, it’s these larger meetings really, for me when I was young, you get a very good sense of who’s who in the field, you know what’s happening? What’s the general thinking, you know, what is the argumentation in this field? Or do people like or don’t like? Where are the open questions? On whose toes will I step if I say this? […] so I’m not really sure what I would do if we would organize meetings- I spend lots of time in meetings. I would organize them very differently. I would have more young people into podium. Shorter talks to basically get them exposed to, to communicate to audiences. Yeah, I think they get-togethers like large poster sessions with free beer work fantastically well. But the face to face at least for me, I’m not from the millennial generation, is very important. And many of the papers that that that we’ve written often result from talking to someone, get a good idea together, work it out together and you create a lot of friendships along the way as well.

Peter  16:15 

You talked about […] not stepping on other people’s toes, but the value of a lot of these conferences is to know who’s in the field. I saw recently that you tweeted some classic images from Lieberkühn’s thesis regarding the structure of the gut, and then some of Joseph Paneth’s pictures of the Paneth cells. I was wondering what drew you to these pictures in particular and what about these scientists encourage you to tweet about them?

Dr. Clevers  16:36 

Yeah. Well, so of course, these two have written extensively about guts and Lieberkuhn, who lived in the 1700s was German but worked in Holland did a PhD, which my students were very happy to read that it was only 32 pages. But then I could point out this actually written in Latin, so… well as a as a medical student, I had a very good memory, which isn’t so good anymore. But there’s many structures and diseases and phenomena that have a person’s name attached to it […] and nobody ever knows, you know, [for example], who was Merkel? And so I’ve made it a bit of a hobby to try to figure out, you know, who was this person? Why, and often they’re not the first discoverers, but for some reason they were the most visible person. Actually between Europe and the US, there are differences; like Kahler for us is multiple myeloma. Now I don’t think the US uses Kahler’s disease for this, but it was discovered by a German called Kahler. So I’d like to dig up these […]  just a hobby, and to find something that’s 300 years old, and it would be sitting in a museum and nobody knew what it was. So I found this thesis and then I realized this is really good.

Peter  17:50 

Do you encourage your graduate students to go through and the history of science as well?

Dr. Clevers  17:54 

Not really. So what I do a lot with my graduate students is discuss the process of science, and all the different decisions you take and what information is true, everything published, and doubt what was published. And so that I do a lot. I try to create a culture of interrogation and also try to explain that when you argue with somebody or you criticize or you have remarks about the work of somebody, you’re not criticizing the person, you’re criticizing something that the person says because it feels very personal. When you the paper gets reviewed, you see the review report, it hurts when it’s negative. But the process intended not to hurt you, but actually  say something about the same bit of work that you have. So that’s something is that I do a lot with my students.

Peter  18:45 

If you could travel back in time and have a conversation with any scientist, who would it be in what would you talk about?

Dr. Clevers  18:51 

Yeah, there’s a guy, Leblond, who is my personal hero, who is I think, originally French [and] migrated, because his wife is Jewish, migrated to Montreal in Canada, French Canada, and was still an active scientist at a very high age when he was 94-95, actively engaged, and many of his original discoveries [were] when he worked in the Curie University in Paris where radioactivity was discovered. So he learned how to use radio labels and he started applying them in biological systems. He saw the first label DNA, the first to label protein, the first to label sugars. Essentially, I think, he discovered stem cell hierarchies by showing how labels travel through the skin. For instance, he was the first to show that all cells make protein- quite a quite a spectacular finding because people believed that the liver makes all protein and the rest just take it up from serum. He was the first to show the ER Golgi secretory pathway. So he could have earned three, four Nobel prizes. Those papers are published in journals and were repeated later and several people got Nobel Prizes [for this work]. He’s always a bit a bit neglected. I don’t know why. But also everything we published about the gut stem cells. After the fact I found out that he had published sort of theoretical papers that predicted everything. So this is like a string of maybe 10 Nature, Cell, Science papers, we can now safely say after they have published that they were not original, because actually Leblond, CP Leblond had already published the hypotheses.

Peter  20:27

What would you like to ask him?

Dr. Clevers  20:28

What would have liked to ask him? I think, how his findings relate to disease, the various diseases of the gut. He doesn’t say much about [his views] in his papers. But it’s clear that he was a pathologist. He must have been looking at all of these structures from a pathological point of view.

Peter  20:47 

I think that’s fascinating. And personally, I like to get to know the scientists behind the science and I know a lot of times for people who are key figures in the field, they publish books, and we really like to know what their frame of mind is or what their reference and viewpoints are, but oftentimes when we’re judging the science currently in when we’re reviewing […] some article during a journal club, we […] dissociate the scientists from the science and I was wondering, at what point do you think we should look at the context that the scientist is working in when we’re evaluating their work?

Dr. Clevers  21:20 

I think always. So my thought when I started science was this is this is an extremely rational activity that you know, you sit, you’re smart, you design, you test, that’s how you define hypothesis, you design experiments that would contradict what you’re thinking and you would re-formulate your hypotheses. Over the years, I’ve learned that in experimental biological sciences that’s not how it works. I think 80-90% of what happens leading up to a discovery is random events between people. It’s characters of individuals, and eventually when that turns into a potential discovery, then we go into this mode that people think scientists always do. You become very rational you do your experiments you do your controls and this and that and then you write your paper as if you would always be looking for that particular phenomenon which you basically stumbled across it and you interpreted it well. So I think that first 80% that’s the biggest difference between people who constantly make discoveries and people who are extremely smart and know everything but don’t make discoveries that […] actually in this process of searching, stepping into dark [and] changing opinions, talking to people, hooking up with people, that that is where the discoveries really arise and then once use you see the light then you switch to this mode and that is the second part is you can learn. For a doctor there’s much more of the second part; so if you’re a clinician a lot of what you do once you know, it is this disease then you do this and these are the tests I do this how I follow up. For us is much less so, in basic exploratory science. So the context of a person that contacts you know why this person all of a sudden switch from this model system or that model system? What happened in his life that he meets somebody? Did he do that? That is that is crucial if you want to really, it would be good if you could make the discovery process more efficient, because we waste most experiments, as everybody knows, end up on the floor. And if you could make that process more efficient, that would be fantastic. So I’ve been talking a lot to colleagues knows more senior scientists who have made discoveries and they also don’t know exactly how this works. And it would be great […] but a lot of it is in the social interactions in the unexpected ideas that pop up because somebody says something, you make a link with something you’re thinking and all of a sudden there is an answer.

Peter  23:49 

I think that’s a nice way to paint it because a lot of people who aren’t in the scientific field think it’s a very isolated process. You’re working on a project you’re kind of hitting your head against the wall, kind of racking your brains but you need to reach out to other people and communicate with them to see if they have some other framework for you to think about.

Dr. Clevers. 24:04

Exactly.

Peter  24:06 

I also noticed on the other aspect of your Twitter, you posted a couple of animations or videos. Could you tell me a little bit about what got you into using videos or animations to explain science?

Dr. Clevers  24:18 

Yeah, so I’ve always I used to draw a lot as a kid. I collect art paintings. And so I’ve always been drawn by the visual. So stepping back I learned how to write papers over the years and what I used to do for a long time, so I spend endless amounts of time on the title and the summary. And if the title and the summary don’t draw attention, build up some tension and resolve. The storyline of a scientific paper is extremely important. And if you cannot write up your story in 125 words, which some of these journals [require], then there’s something wrong with the stories. There’s two stories or there’s only three quarters of a story or the order is wrong. If you cannot produce a 100 character title that has the message and draws attention has all the keywords, there’s something wrong with what you’re trying to communicate. So that I knew that for a long time. Then I got into contact with this guy who was, I think a physics PhD student, and he never graduated. He had this extreme talent- I think he uses the Pixar software. And the way we started working together is whenever I thought, we have a really nice discovery, I will do my title, my summary and we then try to write a script, they have a one minute audio, video animation video. And he would look at it, we talk he said, Well, this doesn’t work, and then he would turn it into so he gave a lot of images. Now what does this look like ? And he asked how many cells are there? How fast the move? So really, a lot of this is really correct modeling in these as many 40 or 50 animations now. Then he makes a cartoon of how we think the animation should go. And then we’ll go back and forth. And then I’ll say, well, that’s not what I said. Then read your text. This is what you say. I said, well, I meant something else. Yeah, so text is very ambiguous. And it’s clear that to listen to people talk or to read, particularly to two people talk, you get tired and lecture can last 45 minutes, but then it’s done. So and part of it, I think, because it takes a lot of brainpower to interpret what the person is trying to communicate. So once we figured out, okay, this is what I mean and okay, now I understand it, then he would make this movie and then it will be back and forth. And then when the movie is there, all of a sudden, everybody who watches the movie is effortless. They just look at when I give talks- I have many but often what I used to do is I would first show the experiments and summarize in the video, but I didn’t realize what works much better is if I first showed a video, people know the story and you see it and it’s the moment that it moves, people sit up, and they watch and it’s effortless to enjoy. And it’s artistically well done. And then I just showed the slides that show the evidence for what I just said. So you can say show, much more in 45 minutes you could ever do if you’re just talking and showing static slides. I also see when it’s playing- I speak a lot for lay audience like politicians or an artist [or] journalists, and the moment it moves, everybody pays attention. So the more I have movement on the screen, the easier people find it to just stay with me and I can communicate much, much more information through these visuals and they could ever do. Probably the people who are in in animations probably know this, I just discovered this. And the way they are made […] originally, they were made for scientific audiences. But it turns out that it works [for] any lay person with some education, know what the stomach looks like. You zoom in, they know what they’re looking at. They know more or less what a cell looks like […] so they understand immediately. The enjoy the aesthetics, they would not enjoy the aesthetics of a table. So in papers, I have very few tables or blocks […] You want different kinds of variables in the paper, and definitely colorful ones. You don’t want just numbers or lines.

Peter  28:20 

Do you feel like working on these animations has influenced how you write your papers? And is there kind of now a different type of structure or some principles that you follow when you’re writing?

Dr. Clevers  28:29 

Yeah, so this is writing this script, but it’s a bit like writing a summary but at the same time, you have to it’s not only the summary where you have you know, 10 sentences or so of a paper but you also have all the support that you would have that you use the entire paper for. So animation essentially captures everything that’s in the paper in one minute. And so I must say that I now find myself thinking, is this story ready to be submitted? Is a complete? Is it exciting? Will people like this? What is the real message here? When I think through the eyes of the animator, I get a much better sense of you know, what we need [is] a single message, we don’t need three message. We don’t need […] to prove five times what we know is true. We just show it once. And then we have all the backup evidence if needed. So to make a sort of an abstracted, clean, aesthetically pleasant representation of the work that I think in these animations works best.

Peter  29:27 

Really neat. How do you feel like how you frame a picture has influenced how you think about questions in science, when you’re doing this animation, you need to have this kind of viewpoint or this needs to be zoomed in here. Does that affect how you think about when you’re conversing with other people about their science? Like, oh, should we focus more on this part of the scientific process?

Dr. Clevers  29:47 

Yeah, sort of? Well, there are what you’re asking. There are several questions that have arisen in the process of making these animations because, like where cells come from where do they go and why? Why does this go there. So when you visualize the process you’re looking at you actually, you note the holes in your knowledge? Well, we’re not looking at this at all, but it’s a big issue because we don’t know where the cell will go next, or why it dies here and not there. So I guess it’s formalizes, in a way, a process of asking questions or seeing where the openings still are, or where the research can go, because literally you can see in these animations, we know this, we know this, but we don’t know this. So we just keep it out of the current animation [and it’s where] we should really be moving the [of] in the lab.

Peter  30:41 

I want to ask one quick question about your lab work. I know you have pioneered the field of organoids. And people are using organoids. And they’re using kind of spheroids, tumoroids. They’re developing a lot of different in vitro systems to model […] high throughput personalized screening of therapeutics. Where do you see the field going? And what do you think the current limitations of organoids are.

Dr. Clevers  31:03 

There are two types of organoids. The type that we developed is based on the stem cells or stem cell activities that are present in adults, in born bodies. And so every organ will have its own stem cell function. And then there’s the embryonic stem cell-based organoids that [built] brain that we cannot do or built our kidney or heart. So we basically use stem cells that maintain or repair tissues, [which is a] very different, very different approach. So for our approach, and I won’t speak for the other field, but for our approach, it is, like the best lab models, extremely reductionist, so it is an abstraction of reality. The original mini guts grown from one stem cell was aesthetically very nice because you start from one cell, it builds a gut. It’s very surprising that’s possible at all, and we still don’t understand much of that process. But is a complete gut, it has no immune cells, it has no muscle. It has no nerves, no blood vessels. So I think the big challenge is now is to, and this looks extremely promising, add additional layers. My approach would always be start as reductionist, as simple as you can. Add one variable, figure out how it works, add another variable and slowly build up the system. There’s a strong tendency with many scientists to say well there’s not a real life this is not how it works; it’s much more complex. And then they add everything together, and reviewers will tell us, you have to add this and that, but then I no longer know what I’m looking at. It’s too noisy. But that’s the style of research. So I thought I see now people are adding the microbiome by injecting and scientists many guts people adding organs, nerve cells, muscle cells, co-culturing […] You can you can have a piece of gut and a piece of brain and see how they communicate so that I think the developments that are currently happening in any place is just adding more complexity and getting closer to what a real organ looks like. Having said that, I must say there have been a large number of discoveries made by many labs in these extremely simplified systems that could then be checked in mice or in humans and patients, and confirmed to be true. So I think the power of modern science has been reductionism to a large extent and these organoids are an ideal model for that approach.

Peter  33:25 

Well, thank you so much for your time, Dr. Clevers.

Dr. Clevers  33:27 

Okay, thank you.

Peter  33:39 

Dr. Clevers shared a few of the things that went through his mind over his extensive research career. And one of the things that really stood out to me was the importance in trying to interpret your results without any preconceived notions. Natural processes are incredible, and it is important for scientists to really appreciate all the facets of the process. When you think you have a handle of these biological phenomena try and portray it as a movie. Use your imagination to piece together your observations and direct your future scientific questions by filling in the missing parts. I want to thank you all so much for listening, and we’ll see you on the next episode. For more of our content, you can follow us on Twitter @gutbrains or visit our website at thinkgastronauts.com. The Gastronauts Podcast would be impossible without the incredible team that we have here. Meredith Schmehl is our producer and theme music composer. And special thanks to the founders of Gastronauts, Dr. Diego Bohórquez, and the Bohórquez laboratory.