Biological Miracle – Wood Frog

> Nobody yet understands what starts the wood frog’s heart after being frozen and inert for the entire northern winter.

To me, that's the most fascinating part of the (already quite fascinating) story. Frog is frozen solid, there is no (to our knowledge) heartbeat or brain activity. It thaws and something happens that gets it going again.

I have trouble imagining what that mechanism could even look like. Tiny portion of brain responsible for keeping track of frozen-ness? Some chemical signaling from within the body cavity?

a chemical reaction that is sensitive to temperature.

my poor knowledge of biology says it's a deeply unsatisfying "heart beats when enough of the body has thawed for it to beat."

If the heart depends on the brain at all in frogs.

Maybe something like a bit flip but for neurons happens in the frog's brain from the sun's radiation or something.

Or the elasticity of the heart and muscles.

The frog is not frozen solid.

Interestingly, you can freeze a rat solid in liquid nitrogen--completely solid right through--and then thaw them out in a microwave and they actually survive. Well, many of them survive. For a while. Okay, it's not good for the rats but it's still crazy that it works.

It doesn't, even in humans. There is an independent circuit of special muscle cells right on it that keeps it beating.

So starting and stopping the heart in a controlled manner is pretty interesting, because it has to be well-timed, and there are few obvious and reliable inputs to control it, especially when thawing.

If it gets frozen in a heavily contracted form, unthawing it will trigger at least one half-beat: could that be enough to restart it?

Hard to imagine that this is significant, given that the (un)thawing is likely quite slow.

Did not think that my early morning would be spend trying to imagine how thawing a frog works. :)

What puzzles me is... it is not just the heart but the entire circulatory system.

Maybe it is that thawing happens in reverse with the extremities, then the rest of the system thawing, with the heart being last. Would be a biological advantage in this case for the heart to be centrally located.

Where can I read more about this? If this was a fact I think people would be way more excited about cryonics. Casually browsing wikipedia suggests that we are not there yet with the ability to thawn large animals or even organs.

Why doesn't my heart keep beating if my brain dies then? Or would it?

I can't source this because I read it years ago, but I believe that there is some science that says that a major factor (not the only major factor, but a major factor) is body mass and volume. Essentially, the speed at which the core organs go from operating temperature to frozen is crucial, and it's also important for them to be deprived of oxygen when that happens. Humans are just... too big.

Good point for sure.

I understand that it would keep beating until you are provided oxygen. That’s my understanding understanding of brain death at least.

> Maybe it is that thawing happens in reverse with the extremities, then the rest of the system thawing, with the heart being last

FTA: In spring, the wood frog thaws from the inside outward. First the heart starts beating. Then the brain activates. Finally, the legs move.

From https://en.wikipedia.org/wiki/James_Lovelock

"In the mid-1950s, Lovelock experimented with the cryopreservation of rodents, determining that hamsters could be frozen and revived successfully.[14] Hamsters were frozen with 60% of the water in the brain crystallised into ice with no adverse effects recorded. Other organs were shown to be susceptible to damage.[15]"

And there's a Tom Scott's interview with James Lovelock:

https://www.youtube.com/watch?v=2tdiKTSdE9Y

I skimmed https://en.wikipedia.org/wiki/Sinoatrial_node#Function. Here's my guess at what is going on:

In humans (and I guess many animals), the thing that controls the heart beat is a structure in the heart called the Sinoatrial node. Each cell in the SA node has an ability to generate its own rhythmic electrical impulse. I imagine that when one of these cells thaws out in a Wood frog, it immediately starts producing its rhythmic pulse. It has to get in sync with the rest of the cells in the Sinoatrial node before the heart will beat correctly, so the cells have a mechanism to communicate their rhythm with their neighbours. I guess each cycle, each cell adjusts its phase a little towards the average phase of its neighbours and thus a consensus will be reached.

Maybe the system relies on average heat randomness to bootstrap again ..

Fireflies eventually manage to more or less sync up and they’re completely separate organisms - tiny cells with physical connections inside the body should be able to make it work.

Wouldn’t it be crazy if only worked on hamsters

Yeah, I was wondering about that too, but on the other hand, there are possibilities:

You don't need a brain to execute "programmed behavior" in a body, the cells have enough "compute" in the regulatory networks of their DNA, RNA and proteins to do that on their own (and in fact do it all the time as part if their normal functioning. That's what "metabolism" means.)

Another question would be where the cells take the energy to execute that program if blood circulation has halted and there is no oxygen. But then on the other hand, at that point they are filled to the brim with glucose. So I wonder if this isn't just to prevent freezing but also as an energy reserve for the "restart".

(Sorry for the bad programming analogies in this post, please don't take them too literally)

The article says that, but it can’t be the normal meaning of thaw. Thermodynamically, onbiously the innermost portion of the volume is going to warm last. But in terms of the frog’s system restart order, that order makes sense.

I was checking youtube to see if I could see that happen but failed - they were all about thawing rats to feed to snakes. There was however a goldfish dropped in liquid nitrogen briefly and recovering https://www.youtube.com/watch?v=wwolYFGM9pU

Most likely it isnt that the heart stops or starts in response to freezing. The heartbeat signal probably runs 24/7 unless inhibited by freezing. So as soon as it thaws, the signaling bit resumes its pulsing and the rest of the heart begins to beats as it also thaws. The order in which organs thaw would be regulated by sugar levels. Remember too that at this scale frogs can absorb much of their needed O2 through their skin. A steady heartbeat isn't as essential as it is with us.

Probably because the brain controls breathing and so the oxygen runs out quickly

"Even in humans"- thats a pretty steep assumption.

I am fully aware that if the human heart is severed from the brainstem it will develop A rhythm.

But what about other mammals? Dunno. Not going to assume.

Theres also the tidbit that frogs are not mammals.

The inside of the frog isn't actually frozen, because it's glucose-flushed.

So the sequence is more:

   1. Outside of frog thaws
   2. ??
   3. Heart starts beating

There are ways to adjust cooling rates... for example route the blood externally and chill it like they do in some kinds of surgery.

This frog is alive. It could detect that long-term thaw is imminent (say from sensors on its skin) and start some processes that produce heat around its heart.

The point is that whatever control a frog heart may have, it's not cerebral. It must be a very low-level circuit, which can be modulated from outside, but which remains autonomous.

I was going to say that's silly, but I guess we need to be able to hold our breath sometimes.

I'm thinking that there has to be something that is still keeping the rhythm going, maybe an extremely faint signal, all throughout that dormant period

These experiments are exactly why people were excited about cryonics, until they realized that it doesn't work on anything much larger than a rat.

You have to thaw them right down to the core very quickly; you need to get the heart pumping or the thawed extremities will die with no bloodflow. There's no way to heat a human's core that fast without causing unsurvivable burns to their outside. (Even the rats wound up with nasty, sometimes fatal burns.)