John Brumell: the light and the space to figure things out


This is the first thing I see when I reach the Cell Biology Lab at the Hospital for Sick Children. After fumbling my way through security and fobs and confusing elevators, I meet the director of the lab in this beautiful lounge. This is actually what we spend the first 15 minutes talking about: the architecture, the way this vista and lounge area connects three floors of research in a communal space of air and light. Dr. John Brumell speaks about watching the Nobel awards, FIFA World Cup and the action of city in this space. How all of this space and light induces collaboration, new ideas, and quick problem solving.

Dr. Brumell is Co-director at the Inflammatory Bowel Disease Centre at the Hospital for Sick Children, Head and Senior Scientist at the Research Institute for Cell Biology, a Professor in the Department of Molecular Genetics at the University of Toronto, and the Pitblado Chair in Cell Biology at the Hospital for Sick Children

He is also the father of one of my son's best buddies and one of the funniest people I have ever met. Over the years, we have commiserated about grant writing, we've toasted each other's grant successes and bemoaned the roadblocks at many a social gathering. John is also the instigator of this series of interviews about the art-science intersection. Ironically he has been the most elusive to pin down for an interview date. It was John who related to me his view that artists and scientists do the same thing: walk into the dark, try to illuminate it, then walk further into a new darkness. We try to explain or describe reality due to a commitment to our own curiosities and to the darkness itself.

photo courtesy of Sick Kids Hospital


John shows me the lab offices, and continues to explain how architecture and design inform the way the lab works. The interns and assistants have desks along the outside by the windows and the leaders and directors are in offices in the centre.

"It brings us out of our offices." he says.

In fact most of the good conversations happen in the wide space between the window-side desks and doors to the leaders' offices.

"This is where the problem-solving happens."

I think it is remarkable that there is such a deep awareness of how space creates the intellectual and emotional relationships that build a workplace. Another assumption I had -- that dancers hold the lion's share of spatial awareness and sensitivity -- has been debunked. I am glad and inspired by it.

The lab itself is nothing like I expected: sterile, orderly,  cold. It is none of those things. It too is airy and light. Filled with equipment and supplies, clean but lived-in. John casually picks up and shows me a petri dish filled with "maybe 2 million salmonella bacteria".

Lucy: My first big question is how did you wind up here? What was the spark that took you to this place ?

John: Oh....well like any career there have been lots of mentors and influences along the way, but a lot of what drives you into a career like this is basic personality. When I was a kid I had a mom who was a nurse and father who was in the business world who then became an entrepreneur. So that was the perfect training for being in the health world.You have to appreciate medicine and science, and it's kind of like you're running a franchise at the same time.

As a kid I was into natural things...I remember my neighbour's older brother caught a fish and opened it up, pulled out all the organs, the swim bladder, the intestines. and I was fascinated....that's how they controlled their buoyancy? that's how that works? Long before the grade 9 experiment when you had to dissect a frog, remember?

Lucy: oh yes, I remember.

John: This was with a real live fresh fish. The stories my mom would tell me. As a nurse there are somethings she'd see that were miraculous and somethings that were horrific. This would just be common discussion at the dinner table. I would hear about what happens to a guy that falls off a motorcycle at high speed.

Lucy: Was your mom an emergency room nurse?

John: She kind of did everything over the years.

She could tell you the problems of a diabetic. She taught me how to put needles in a person. For my PhD I took blood and she was the one who taught me how to do it properly. Delivering babies to 11 years olds -- it blows your mind -- but for her it was the natural world of the hospital.

My dad was in sales and started several different companies...That creative entrepreneurial "see-an-opportunity-and-go-for-it" had a big imprint on me. Sometimes in science we have to see beyond the known.

I have this discussion with my students where I say this is a cool possibility, we should look into this. And they go and look at the literature and come back and say "there's absolutely nothing written on this why would you think it's a good idea?" and I have to say "That's the point." We don't want to discover the known, but the unknown.

Those were my early influences and my personality predisposing me to a career in science. The traits of a good scientist will make you good in business, good as an artist, many things.

It just worked out that I had a really great chemistry teacher in grade 11 and that solidified my interest in science before i had lots of interests...I actually thought about becoming an electrician...This chemistry teacher got me excited. And I liked math so I thought I'd be an chemical engineer.

I did chemistry at at the University of Western Ontario, and realized I didn't want to do engineering. I discovered Bio chemistry. Again I had a great professor. I realized this was the chemistry of life and that's what I cared about. I didn't care about electrons and orbitals and chemical bonds. I wanted to see the bigger picture.

That's the nuts and bolts of cellular stuff. Over the years many of the best discoveries have come from biochemists because they went into fields without preconceived notions of those fields. I went into microbiology without ever having read a microbiology textbook. A colleague of mine, who almost won the Nobel prize -- said his advantage when he went into immunology was that he never read an immunology text book. He moved into that field without being tainted by old-school views.

Lucy: I've heard that in several different contexts:  if you go into a field with whatever expertise you have, but without the dogma or rules that have already been laid out, you're able to manouevre and innovate because you haven't heard the "no". So you go that way and then someone says "but you can't go that way" and you say "But I'm already here."

John: I think one of the beauties of science is that you can have people come in from the outside and blow things up. You can. Because we don't have dictators or tyrants at the top of the food chain crushing the new ideas at the bottom. We don't. We might try but we just can't. Because the data stands, the ideas will rise.

There's a lot of discussion right now about a turmoil in the bioscience world. It revolves around biological reproducibility. About studies that are published but their data can't be reproduced by other scientists. There's almost a suggestion of fraud in some cases. It shows an ignorance of what we're dealing with. It's bioscience. We're trying to reverse engineer something that has evolved over 2 billion years and every step of that evolution has been by accident. And we're putting this up against computers, which have evolved over 80 years in very specific deliberate design.

Lucy: But there are people who deliberately mislead for profit or reputation?

John: The amount of real fraud out there is small, I think. When you see different results to the same problems, I think "they are all right!" When I started my lab, not even my career, but my lab, 17 years ago there was the idea of autophagy and a couple people knew about it, while everyone else ignored it. Looking at protein degradation experiments, they made strong statements about what was happening but they were missing out on this beast that controls everything -- autophagy. They know that now but back then.....I have a quote here from a peer review of a paper a colleague and I submitted:

"All these discrepancies should be resolved or explained in the manuscript"

Everything had to be explained. We were shocked. This idea that you could explain everything in one paper.

We're still missing a lot and we know that. We have to battle the idea that everything is known.

Lucy: That's interesting because I think of that as being the conservative minded approach to science, especially the religious conservative view of science. That it needs to explain everything. But that's not actually what science does.

To hear that this is more broadly within your field ---

John: It's our enemy.

Lucy: I guess in every field there is conservatism. The old guard that is threatened by the new?

John: It kind of kills the romance too. You're trying to train your students to see there is so much opportunity, so much to discover. And they get that comment that you have to nitpick every detail of your data.

Lucy: But that process of nitpicking your data would never end.

John: Exactly. This is a relatively new thing. Ten or fifteen years ago, you could say "interestingly we observed this and it doesn't fit our model, but we'll report it."

Lucy: But now they could come down on you if you didn't explain that detail?

John: Now you sweep it under the rug and you don't talk about it.

Lucy: That's sad. Because that one little thing could be what sparks a whole new solution to a problem.

John: I know. In older papers there are nuggets that you could run with for a new study.

Lucy: A springboard.

John: There is a famous one. We showed that listeria is a bacteria that grows inside the cytosol of cells. The gel-like expansive part of the cell. In this paper we found it could grow inside the vacuous compartments. The whole field to this point had said "no, this doesn't happen" but we saw these results and I called my colleague at Harvard. He said "I've seen it once before."

He pulled out a paper from ten years before, on immunology and infection and buried in this paper was this image of the bacteria in the vacuous parts. We knew what we had found was real. So I called the senior author of this paper -- famous guy, probably going to win the Nobel prize soon --  I asked him if had any more samples.

He didn't but he said he'd reinfect the mice and send fresh samples. We got the images and it supported our findings too. From that we could see that the bacteria actually spend most of their time in the vacuous parts. They go into the gel-like part to spread.

Lucy: What you discovered was kind of like the bacterial home base.

John: Yes. It was kind of a flashy paper we published because it turned the idea of listeria on its head. And because we looked at an unexplained detail in a decade-old paper.

Lucy: I love that your work includes a colleague saying "I will reinfect some mice for you."

So is Listeria your disease? every medical research scientist seems to have their own.

John: Ha. So true. I have a colleague in Virginia who says she's gonorrhea. She has a sign in her office that says "I don't have gonorrhea, but I'm working on it"

Mine are salmonella and listeria. As a cell biologist it is fascinating how they grow in our cells, including our immune system cells. Those cells hunt disease and infection, and these two diseases use them like a playground.

We're studying the mechanisms of how these bacteria can overcome defences and gain nutrients, replicate. How they spread from cell to cell. That's really important in animals cells -- how they can do this and evade the immune system the whole time. How do our cells fight back? Even in the face of toxins we usually win. We can suppress pretty much everything.

That's the main playground we work with. We look at these things in a dynamic context. With our new microscopes we are able to see the dynamic events and really see the interactions.

***

John shows me the microscope labs. A darkened, deep closet-shaped room. A young man is at work there conjuring up colourized images from his microscope straight to the screen of his computer. 

Networks and nebula of green and red appear on a black depth of background.

"Have you ever noticed how these cells resemble images from the Hubble Telescope -- images of star formations and deaths?" I asked.

"No. Really?"

"Absolutely."

Things are constantly revealing themselves as echoes, repetitions, fine-threaded and interconnected webs.

******

John: Our colleagues who are looking at inflammatory diseases are finding that the machinery that we are studying is effected. The ability to handle microbes is altered in people with chronic inflammatory disease.

Lucy: Interesting.....

John: It makes sense because we are in a dirty world. Ad we need a lot of defences to fight them. So if you are missing some or them it can cause disorder that stays with you. In working a pediatric hospital we are dealing with kids in the early stages of the disorders and we are usually able to find some genetic component and study it.

We can look at listeria and take out a gene really commonly affected in kids with Crohn's disease and ask how it affects the interaction. Usually its very dramatic -- it spreads faster or kills the cells better.

Lucy: My very basic understanding of an immune system tells me that if the immune system is compromised it will be further compromised.

John pulls out a box of plush toys "Giant microbes Blood Cells 1,000,000 times the actual size! Contains White Blood Cell, Red Blood Cell, Plasma, Platelets and Antibody". He just happens to have it in his office.

photo courtesy of giantmicrobes.com



Lucy: I could've used this when my mom was sick because it was hard for me to understand all the jargon about her white blood cell count and why and how that effected or revealed what was going on with her cancer.

John: The state of the art is that now we understand how many microbes are in our intestines and our blood and everywhere. Microbes are escaping every time our body works hard at something.

Lucy: It's amazing that any of us are alive when we think of the millions of things constantly going wrong, or battling all the time. We're so resilient and so fragile. How do we hold it together for 70-100 years

John: And that's very recent. You know not that long ago it was like 25. You were ready to pass on your genes at 11. It's very hard in the modern world to take in that information but my mom was a nurse and it was common. The younger they were the quicker they got up and left the hospital after giving birth to a baby. When the standard was a week in the hospital after a birth, the very young were up and out right away. That's how nature works.

Lucy: You just had a baby in the field, right?

John: And then the baby got up and walked. Like deer.

Lucy: Ha. But seriously, it's quite shocking how quickly things are changing for a complex species that should take a really long time - for the adaptations of evolution to show up.

John: Look at how big these kids are!

Lucy: Yeah I know -- you and I each have one of those. Jake and Pablo are both tall for their age, but they are not alone. The growth tables may have to change, at least in this part of the world?

John:  I have friend working in cell size research and how it relates to organism size and he's finding that there are these amazing evolutionary trade offs in this constant race. Cells speed up how fast they grow, how big they get, how quickly they divide and the trade off is fitness or lifespan. Dinosaurs are a good example. How big they got so quickly. Lifespan is related. There are zombies in nature, but no vampires. You can't just go on forever......well you could argue that stem cells kind of can but.....

Lucy: That was another interview I did! With Cindi Morshead.

John: Zombies are real.

Lucy: I was reading something about this in a book by Alanna Mitchell, I think. tell me more.

John: Zombies are aging-related and infection-related. As you age some of your cells become zombies, kind of damaged, kind of disheveled looking, metabolizing but not fully. They refuse to die. unless you shoot them right in the head.

Lucy: Of course. Do they slowly travel up towards your head muttering "brains...brains"?

John: Of course. But it's a really interesting thing because they're finding if you can clear out some of these cells, you look better. They have seen it in mice, these sort of disheveled old mice wind up looking like handsome George Clooney mice.

Lucy: Don't let the cosmetics industry hear about this.

John: There will be creams that remove senescent cells from your face.

Lucy: Can't wait for the commercials with the little zombies getting shot.


We could keep talking for hours but John must get back to his research and I must get to rehearsal. So we'll end our conversation with zombie jokes and retrace our steps through the beautiful lounge and back to the elevators.

On my way out of the building and back to the subway,  I feel light and optimistic walking through the 'hospital district'. I have often wondered about how saddening it may be to study disease, especially in a clinical or research hospital setting. 'Enlightenment' means knowledge or deeper awareness, but the word could also mean the lightening of a load.  Walking through these tall, many-windowed buildings where the researchers have the opportunity to look at the sky frequently, I consider the interconnectivity of architecture, nature, and curiosity  -- all evident in Dr. John Brumell's lab -- create a lighter world.

Until the zombie apocalpyse of course.



****


Art + Science interviews are made possible with the generous support of the Chalmers Family Fund Fellowship program, administered by the Ontario Arts Council.


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