The Takeaway: Molecular biologist Ken Storey looks to the natural world to study suspended animation — particularly, turning metabolism on and off — and its implications on human health.

“Labs are like a rock and roll group where everybody’s playing your song,” Ken Storey says. “I write and develop the songs. It’s a constant training up new players, teaching them instruments, giving them huge credit, and they go on to fame and fortune. And then you take on new players.”

To continue the metaphor, Storey’s lab, at Carleton University in Ottawa, Ontario, has written the melodies for a lot of scientific hits. You may not have heard them yet, though — mostly because their lyrics are all about red devil squid, giant tuna, thirteen lined ground squirrels, wood frogs, and lemurs. Or, more specifically, about the way those animals practice the metabolic miracle of surviving extreme environmental stresses like deep cold, oxygen deprivation, and desiccation.

“They turn off their nuclei and all of their genes,” he says. “You can’t do that without dying. Then they turn off all the processes in all of their cells. You can’t do that either. If you drew a graph of it, it would look like they were alive, and that they died, and then they came back to life. Anything that has a time constant of ‘dead’ in the middle of their graph but that is not actually dead, that’s what we study.”

You may soon start hearing the covers of Storey’s songs. His melodies have major implications on futuristic human-centric molecular physiology tech that might not be far off at all: elongating the time transplant organs can last outside the body; hibernation-like stasis for Mars-bound astronauts. We asked Storey about the molecular processes of suspended animation and its implications for human health.

Before You Start: Terms to Know

Suspended animation: The ability to temporarily suspend or minimize vital bodily functions, including metabolism and heart rate, while remaining alive.

Molecular physiology: The study of biochemical interactions at the subcellular level.

Elastic limit: The furthest point to which something — including biochemistry — can be stretched.

Krogh’s Principle: A theory, created by August Krogh, that "for such a large number of problems there will be some animal of choice, or a few such animals, on which it can be most conveniently studied."

Normothermic organ transplant: An organ transplant technique in which organs, particularly the heart, are kept warm and in a similar physiological state as when they are inside the body.

How would you describe the work your lab does to a non-scientist?

What we study is how animals live in suspended animation. I’m talking about animals that can turn off their entire metabolism and appear to be dead. It’s studying how you turn on and off the fires of life: metabolic processes.

For example: bears that hibernate turn off their metabolisms and live in suspended animation through winter. Or frogs that freeze and are still alive even though they are filled with ice, all of their processes are in suspended animation. Everything you do, they still do — after they come back to life. We study things which will be necessary for astronauts in order to turn them off for long periods of travel and then turn them back on. We study things necessary for human organs to shut them off after the donor gives them off and keeps them off until turned on for the recipient. Anything that has a time constant of dead in the middle but not that dead is what we study.

How is the work you do novel? Where does it fit into the context of molecular physiology?

We come upon a lemur. It’s a primate. It can sort of hibernate — something different, called torpor. Nothing is known about the molecular processes that make torpor possible. We come in with money and shiny machines and discover everything there is to know about lemur torpor. Then we translate the physiology — the way it sleeps, the slowing of its metabolic rate, the cooling of its body temperature, its lack of response to stimuli — to the next layer deeper. What’s happening on the molecular level? The 25,000 proteins that lemur is making, the 20,000 genes it’s turning off, all those molecules it’s synthesizing, we can tell how that is being regulated.

We are the first ones to understand this sort of thing because we can get the animals. But others will follow. I like to think that we break trail. It’s not trail blazing, creating this thorough, deep trail. I’m much lighter weight than that. I’m the first one taking snowshoes out into the deep snow, so that others can see it’s a trail at all.

For example, take marsupials. Some can hibernate. The question was, how can they do it? We were the first to look at a marsupial and do everything at a molecular level. Using a suite of techniques, we analyzed thousands of different targets and put those targets together in three dimensions. We do transcriptomics of them. Now everybody’s doing it.

That’s how it should be. I didn’t work on any of these things five years ago. The stuff I was working on five years ago, I started it, and then other people supplanted me. Other people work on frozen frogs now. They didn’t at the beginning. I’m a transitional figure: I go in and do my thing — I look at a biological problem and try to show people that it can be solved at a molecular level — and then I move on to another biological problem.

I’m interested at the molecular level. It’s called molecular physiology. You have a ground squirrel whose temp is zero. Let me see how they manage to rearrange all their tissues and cells. I study the first 14 pages of a biochemical textbook and then explain how it can be done in an extreme manner.

Physical things have something called elastic limits. Take a piece of wood and bend it until it breaks. That’s it’s elastic limit. I look at the bendability of metabolism. Of how cells work. Of how your brain turns on and off. Of how you can think thoughts. How you can pump ions in your kidney. I look at that biochemical limit where you can stretch mechanisms: the elastic limits of molecular biology, how you turn on and off genes, or biochemistry, how you turn on and off pathways.

How do you think about fundamental biology versus clinical translation, and how has your lab contributed to both?

As far as fundamental biology, I take things that zoologists and biologists — whole animal researchers — do, and reduce them. I’m a reductionist. Down to cells and parts of cells. Those molecular mechanisms that underlie the whole of biology.

What I do on the other side of the coin, is I show clinical researchers — practical researchers — that these animals are good models, and that the tools they use are applicable to clinical problems.

In doing one thing, and taking an entire complex biological system and reducing it to its various mechanisms, I then expose those mechanisms to people working on rats in a lab, and show them that the rat isn’t the best model. Just by existing and doing what I do, it exposes new methods and new methodologies to people doing really good medical science.

It’s an old principle called the Krogh’s principle: that nature has given us the perfect animal to study a problem, and you just need to find that animal. So we look at microRNAs, the little tiny molecules, in brand new animals that work in brand new ways. And then we have to turn off limbs

Given your work, what do you think is possible from the standpoint of biological intervention?

So frogs freeze. Biologists discovered that by freezing them in trunks of car. We were the ones that worked out the basic metabolic, biochemical, and structural mechanisms. Over time we found newer and newer methodologies — RNA and the role of sugar. And now there is company called Sylvatica — which is richer than you can imagine, and named after our frog we were studying — that studies the freezing of organs. They work with universities and researchers all across North America freezing and thawing human cells and skin in clinical setting.

I didn’t create that company. The reason is something my dad said. He said, “If you’re so smart why aren’t you rich?” So I will readily admit that we throw up good ideas and other smarter people who need the money snatch them up.

So frozen frogs has moved into companies and universities. So has the freezing of organs from rats and mice, as well as the freezing of peripherals: pancreatic cells, skin, corneas, and other things. There is an active community out there. Low temperature biochemistry of various kind of cells, which has clinical aspects.

The other kind of thing we do with that is metabolic rate depression. How do you turn off cells and organs without freezing them? Part of that is cold hibernation, but part of that is warm hibernation, which is the static turning off of an organ even though that organ’s temperature is high. That has already moved into the clinics — and there’s a series of papers now on what’s called normothermic organ transplant.

Organ transplant now is an amalgam of what nature does. Transplant existed long before I came into the field. You cool down an organ, you don’t profuse it, you put it on ice, and then your run it between cities. You have six hours for a heart, 18 hours for a kidney. There was an upper lethal limit where we couldn’t fix molecular problems caused by a cold human organ. Because cooling down hurt it, not perfusing it hurt it, and then not having any oxygen hurt it — then put oxygen back hurt it too.

Now they do what a marsupial or bear does. They hibernate, turn off all their metabolism, but stay warm. It’s way simpler. You don’t do cold stuff. You don’t have to protect your cells and membranes.

So why did they start cooling shit down in the first place? It’s logical. But by showing that it happens this warm way in nature, by showing that room temperature can be done in humans — boom, we’re good.

In terms of your lab’s focus, what’s the most important unanswered question?

Turning off an entire human. Now we’re trying to make that work on primate arms — but it’s not the same as the core of a human. Not the same as turning off human metabolism and living in some form of suspended animation. You’ve seen it in the movies, hanging from the ceiling in coma. It is hella difficult.

It’s one of the things that’s going to become limiting in all these “go to the stars” plans. Let’s let Elon musk build a ship. It’s not that they’re focusing on the wrong things. Its significantly difficult to get huge hunk of metal off planet. But in all of their tales, they have these pods that humans are going to live in in suspended animation so we can make it to Alpha Centauri.

The correct answer is, no, that is not going to happen. There is currently no mechanism that allow that to happen. We wanna go from here to there, but there is no mechanism to do it. There is no known path. So you try to break trail and see if there are other paths.

Recent Studies from the Storey Lab

The implications of applying natural molecular mechanisms to organ transplant techniques.

A look at the biochemical adaptations that allow freeze tolerance in nature.

Exploring the pathway that regulates the longevity of various organisms in relation to dietary conditions.

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