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Brainless Embryos Suggest Bioelectricity Guides Growth (quantamagazine.org)
108 points by Erlangolem on Mar 15, 2018 | hide | past | web | favorite | 35 comments

Everything in biological systems depends on everything else; all variables are global, all methods are public, and all definitions are recursive. It's all spaghetti code- there is nothing like the separation of functionality that we impose on our designed artefacts for the sake of our limited minds. A signal needed to be sent from one place to another, and the brain has the machinery for endocrine functions already, so why not have it handle it? So while this is a quite valid and interesting result, it's not nearly as exciting as the popular press is going to make it out to be.

I appreciate the code architecture observations, but this result is exciting as hell. I am fascinated by ontogeny. Who knows? A century from now, lots of currently unimaginable things could be traced back to this.

It's like slapping new functionality onto the existing codebase where it fits. Selection then is your test suite. You slap on until your tests are all green.

> “Where does shape come from? What makes an elephant different from a snake?” he asked. DNA can make proteins inside cells, he said, but “there is nothing in the genome that directly specifies anatomy.” To develop properly, he maintains, tissues need spatial cues that must come from other sources in the embryo. At least some of that guidance, he and his team believe, is electrical.

I don't get it. Where does that electrical guidance came from? The brain. Where did the brain came from? The DNA.

If DNA is the ony information that makes it from a parent to offspring (and we can grow organisms in a petri dish from fertilized eggs) is the DNA, then whatever electrical guidance or other abstraction must have been encoded in the DNA first. (Plus some constants encoded in the enviroment.)

> If DNA is the ony information that makes it from a parent to offspring

I don't think this assumption is warranted. Human embryos develop in utero, not in eggs like amphibians. They are connected to the mother through an umbilical and immersed in amniotic fluid. Both the umbilical and the amniotic fluid are full of chemical signals in many forms, not just hormones. Human embryos (and all mammals, really) develop in symbiosis with their mother.

What you are saying is another one of these CS-centric views of the world that only focus on where the information for development comes from; that the development of the brain is somehow encoded in DNA, and that the entire development of a human is therefore also encoded in the DNA.

I've come to doubt this view, not only because of mammal development, but the fact that immune systems and digestion (the microbiome of the GI) develops in response to the available biodiversity of food and encountered pathogens.

So the view that we just put the little DNA program in a dish and feed it raw materials and energy and out pops a fully-formed human is just false.

Humans develop in cooperation with, and in response to, the environment.

It's a bit like staring at the code of a machine learning model and expecting to figure out how it works. The system (a human) contains a lot of code (DNA) but also responds to data (training set)--much more so than we ever realized.

> It's a bit like staring at the code of a machine learning model and expecting to figure out how it works. The system (a human) contains a lot of code (DNA) but also responds to data (training set)--much more so than we ever realized.

Or like a Smalltalk programming environment, which consists of an image with live, editable objects, not just a static text program.

One should not overemphasize the environment either, especially for the early development that's discussed in the article (embriogenesis). Cognition, immutinity and the microbiome become relevant much later.

That's correct.

A neighbor comment mentions the shape of the uterus, but AFAIK this only matters in later stages of development (extrauterine pregnancies happen, and are quite deadly unless aborted since most tissues are not meant to be invaded by the placenta).

Some of the non-electric signals are given by gradients of expression of the Homeobox genes.

There is also a process of mutual differentiation where neighbouring tissues cause each other to differentiate. For example, holoprosencephaly happens when the brain fails to (fully) develop into two hemispheres.

The most severe cases results in the formation of a single eye that in turn induces gross face deformity (Cyclopia, with a nose stub above the single eye).

The mildest cases result mostly in normal people with a lack of smell and a single top central incisor.




I've been told that the geometry of the womb influences this in humans, I don't know how true that is.

Everything old is new again. Early 20th-century biologists were exploring the role of fields in the development of embryos. This line of inquiry was snuffed out when DNA came along. See https://en.wikipedia.org/wiki/Morphogenetic_field#Historical...

From the article:

> The rationale [...] was that “since DNA is what is inherited, information stored in the genes must specify all that is needed to develop.”

> The extreme form of this view is “to explain everything by saying ‘it is in the genes,’ or DNA, and this trend has been reinforced by the increasingly powerful and affordable DNA sequencing technologies,” Huang said. “But we need to zoom out: Before molecular biology imposed our myopic tunnel vision, biologists were much more open to organism-level principles.”

> The tide now seems to be turning, according to Herrera-Rincon and others. “It’s too simplistic to consider the genome as the only source of biological information,” she said.

(emphasis added)

If genes are all-powerful, there is no hope for those who begin to deteriorate. But if our bio-electric fields are more important than our genes, there is much greater possibility for improving our health than the geneticists have led us to believe.

I think any sane biologist will agree that there are layers upon layers of complexity on top of genotype. But the first layer is still DNA. There is a difference between gene-centric and gene-only. The former gives biologist an anchor point to begin their research, the latter is ridiculous.

> But the first layer is still DNA.

This would be one hypothesis. The article is about how the competing field of inquiry ("bioelectricity") has been mistakenly ignored for the past 60+ years.

What if the field is more important than the genes?

Your idea of "morphogenetic fields" is fundamentally incorrect; re-read the wikipedia article you linked to, the word "electricity" doesn't appear in it at all. It's talking about "fields" of chemical gradients which control the development of tissues; that kind of idea has been established developmental biology for over a century.

Meanwhile, in terms of the parent article, yes- it turns out that "bioelectricity" is an important part of the embryonic development. But this is not at all serving the same role as DNA; DNA stores durable information, whereas these fields are being used for, essentially, intercellular communication. I would think that the fact that the researchers successfully replace a frog's entire brain, for developmental purposes, with a simple tweak to an ion channel, pretty clearly demonstrates that the amount of vital information being carried this way is minimal.

Nice. I assumed NGF interactions with other developmental signalers like SHH, BMP, etc was the mechanism of action in this anyways.

It's been a while since I was in a devo lab, but I've watched a few presentations regarding wound healing and denervation such as seen in paraplegics with sacral ulcers. The hypothesis was that the nerves were gone and therefore NGF and other trophic factors were gone leading to impaired healing. I'm assuming healing and development are nearly synonymous in some tissues. Like you said, it's not the electrical signals that necessarily matter that much, it's the chemicals produced by the nerves.

The point I was trying to make is that there is no "more" or "less" important. There are just multiple layers of complexity that are all required to form the end result. DNA being the first layer just means the information that sets up the environment for bioelectric/epigenetic/whatever mechanisms still originates from DNA. Is it possible that there is some kind of mysterious force/particle that creates DNA? Anything is possible I guess. But that just seems like anomaly hunting at this point.

The discussion of what layer we should concentrate our research on has been going on for a long time actually. I remember reading some passionate arguments a decade or so ago about how we should concentrate on cells as the basic unit of biology.

I agree. Epigenetic studies hold the key to making reasonable interventions into genetic conditions.

While genetic screening is desirable, it is going to take a long while before we can have it on a species level. But if we can develop chemo-electric interventions that can alter the progression of genetic conditions, that would be a fresh change in the field, impacting many lives.

As we hit the physical limitations of interventions based on central dogma(which is still years away), we will have to look elsewhere, with an emphasis on the temporal progression of gene expression with respect to different variables. This is going to be difficult, but I can hopeful that some controlled processes might turn out in the future - given our data processing abilities.

This sounds equivalent to saying, "Ha, it wasn't DNA that governs proteins in cells, it was RNA all along". Chemical gradients, ion gradients, morphogens, etc, may all play super important indepensible roles in embryo development, but those things in turn are still driven by genes.

> there is nothing in the genome that directly specifies anatomy

What about HOX genes?


Don’t homeotic genes* explain anatomical development pretty well?

* https://en.m.wikipedia.org/wiki/Homeotic_gene

Yeah, but, that's the instruction manual. This seems more like identifying part of the toolkit.

For anyone interested in this subject, I highly suggest Life Unfolding: How the human body creates itself[1], by Jamie Davies. No one really knows the full story, but what we do know or suspect is pretty amazing.

[1] https://www.amazon.com/Life-Unfolding-human-creates-itself-e...

There are some interesting studies by Michael Levine at Tufts that looks at bioelectric field's effect on flatworm regeneration. And there are some cool experiments done in salamanders that looks at nerve dependent regeneration (aneurogenic limb).

Is it possible that some forms of cancer may be a result of something going wrong with bioelectric signaling, causing abnormal tissue growth?

I think cancers are always associated with a genetic mutation within the cancerous cells. But that break down occurs due to damage or a failure in repair mechanisms. The plausible causes for either are legion. There's a lot of woo out there though with the words bio and electrical combined, heck Brent Farve is even hyping it in late night infomercials.

Thoughtful suggestion, brainless embryos.

i wonder if this is true for neurons in the brain as well.

Highly likely. Some years ago I listened to a lecture by a woman who was researching electrical waves in the retina (which is in practice a specialized extension of the brain). https://en.wikipedia.org/wiki/Retinal_waves

I've seen studies showing dendrites following electric fields. (20 years ago, no links sadly).

Interesting, but can you mine BitCoins with it?

Totally off topic, but maybe the machines in the Matrix needed human brains to solve a proof-of-work puzzle that was more efficiently computed with a human neurocortex. Morpheus just used a battery because it would have taken too long to explain blockchains and ICO's to Neo.

I'm not generally one for the concept of "head-canon," but I think this is now my head-canon for The Matrix.

You see, the Matrix itself is the proof-of-work puzzle, formatted for compatibility with the neocortex. The simulation of a circa-1999 metropolis is not just something to keep the humans' brains occupied while they power the machines; its very substance is a cryptographic hashing process in the form of a simulated world, which also explains why everyone has to be in the same Matrix rather than instanced versions. Agent Smith's real job was just to prevent 51% attacks!

This might work but then what is Neo's power?


That's actually sort of what the original story was. I mean, no blockchains, but the battery thing was introduced because the studio didn't like the idea of humans as CPUs.

Please don't do this here.

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