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January 28, 2005

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It's like these scientists never watch movies. First robot soldiers for Iraq. Didn't they watch Terminator? Now human-brained rats. Ben, anyone? :)

I think the safety issue of the experiment,as you mentioned, the problem of diseases jumping species is a serious one, (exhibit A: Mad Cow Disease).

The whole article you quote is silly, but just to pick a nit, re this bit:

then doing in vitro fertilization to produce a child whose parents are a pair of mice.

I think they're talking about implanting the fertilized egg into a human host, so the mice would be the genetic parents without doing the hard labor.

Regarding cellular chimeras, I wish I had something serious to say, but all I could think of was this old dirty joke.

Prof H.:

I think you're dancing around the idea of consciousness. What makes us human is our human notion of self-consciousness. Are other animals self-aware? hard to tell. can they describe to us what their notion of self awareness is? no. at least, not yet.

If human consciousness is inextricably linked to the physical architecture of the human brain, then at some point we need to be concerned that implanting enough human brain cells into an orangutan, for example, will lead to something that is actually part human . . . i.e., have quasi human consciousness.

that, i think, is the repellant part.

Francis

Uh oh--you just *know* where this will lead. . .

They're Pinky and The Brain
Yes Pinky and The Brain
One is a genius, the other's insane
They're laboratory mice, their genes have been spliced
They're dinky, they're Pinky and The Brain Brain Brain Brain Brain


Before each night is done, their plan will be unfurled
By the dawning of the sun they'll take over the world
They're Pinky and The Brain
Yes Pinky and The Brain
The Twilight Campaign is easy to explain
They'll prove they're mousy worth, and overthrow the earth
They're dinky, they're Pinky and The Brain Brain Brain
Brain Brain Brain Brain Brain Narf!


bioethics.net cited Mrs. Frisby and the Rats of NIMH, which is what I've always thought of in this context.

Francis: I think what I meant to be arguing is: human consciousness, insofar as we understand it at all, seems to depend on the architecture of the brain. If I'm right to say that introducing human neural cells will not produce human brain architecture in most cases, then I think it won't produce a sort of hybrid consciousness. Except possibly in the very specific case I mentioned at the end.

kenB: you're right, but now what I don't get is: in what sense could mice be "the genetic parents" of a human child? I go back to the article and see this: "genetically engineering mice to produce human sperm and eggs". Well, last time I checked, human sperm and eggs get their DNA from the organism whose sperm and eggs they are; they don't just up and create a whole new genome from scratch. Or rather: they can mix and match bits from each strand of DNA in the original organism, but they can't create a human genome when the existing organism is a mouse. So what this 'genetic engineering mice to produce human sperm and eggs' could possibly be, I don't know.

What is possible is to implant human eggs/sperm, or else human germ cells (the precursor to eggs and sperm) into a mouse, so that the mouse will grow human eggs or sperm. But then the mice would not be the genetic parents; the donors of the transplanted eggs/sperm/germ cells would be. And as I noted in the post, a mouse couldn't possibly be the gestational parent of a human child. So in what sense is the mouse the child's parents at all? All it seems to have done is incubated the eggs or sperm.

And why anyone would ever do such an experiment is a complete mystery. We can do IVF by much less roundabout routes.

"I think you're dancing around the idea of consciousness. What makes us human is our human notion of self-consciousness. Are other animals self-aware? hard to tell. can they describe to us what their notion of self awareness is? no. at least, not yet."

What is the observable evidence you can draw on to determine whether an entity is self-conscious (besides wearing baggy clothing. Ha! I think we mean 'self-aware'). Personally, I think our notion of human consciousness is 2 parts anthropocentric hubris, 1 part abstract thinking ability. I'm quite sure that orangutans, for example, are conscious and self-aware in every way you can articulate to some degree or another and are demonstrably more self-aware than, for example, an infant or the severely handicapped.

My grasp of brain physiology is weak at best, but doesn't the power of the human brain depend on the cortical folding that puts neurons located at some distance on the cortical plane in much closer contact? If the folds are the architecture, then the implanted human neurons are just disconnected little spark plugs.

Beyond that, there's the likelihood that consciousness is not some sort of internal brain phenomenon but rather a sensation arising from the brain's harnessing of the senses, one of which (if I only knew how to classify it) must be speech. (Let's end, in other words, the idea of the senses as passive inputs. Knocking somebody upside the head is a sensory output.)

Sorry to wander afield, but the post is provocative.

sidereal: I didn't address that part of francis' comment, and I agree with you completely. Chimps and bonobos seem clearly to be self-conscious -- at least they do things like pass the mirror tests. Note for those who don't know what these are: put some odorless undetectable dye on an animal's forehead, where it can't see it. (You can do this while the animal is anaesthetized, so that it doesn't know you've done it.) Put the animal in front of a mirror. Does the animal, seeing that the mirror-animal has a big red spot on its forehead, touch its own forehead to investigate? Or does it assume that the mirror-animal is just another animal with a funny spot? If the former, so the argument goes, it can form the thought: that's me! I have a spot on my forehead! -- or something equivalent to that. If the animal fails, it doesn't seem to me to follow that it has no such thought. It might, for instance, just not be very interested in spots.

Anyways, I don't know offhand what research has been done on orangutan self-consciousness, but I find it hard to imagine that they don't have it. The question would be, is it somehow 'humanized'? What would this even mean?

What I think might be unique to humans is the ability to consider, explicitly, their reasons for action. (I mean: thinking something like: yes, I want do do X, but is that a good reason for doing X? I'm also assuming that we can act on the result, even if we don't always, so that it's not a purely idle question.) This is quite important, and puts all sorts of power over your own conduct within your grasp, power you wouldn't otherwise have. E.g., the ability to construct an ideal to try to live by, or a general principle to act on. I think these are extraordinarily powerful cognitive tools. (Powerful in a sort of mathematical sense ('a powerful result'), not a large guy with muscles sense.)

Great, just great! They are going to grow human brains in mice and outsource all the white collar jobs to the labs :(

Further on in the article hilzoy links to, the researcher working on 'human brains in mice' says he's already created mice whose brains were 'about 1%' human. But the article doesn't say in what way those brains were human: whether they simply contained 1% human brain cells, or whether the brain structure was 1% human (in terms of cortical folds, say). And it doesn't say anything about how that 1%, however it was measured, affected the mouse's thought patterns or behavior.

The same researcher does say he wants to try creating a 100% human brain in a mouse precisely to see if the mouse exhibits 'human cognitive behavior.' If he can pull it off, and the mouse does exhibit human cognitive behavior, then we've got a huge moral dilemma on our hands:

If something can think like a human, does that make it human? How do you define what 'thinking like a human' is? By cognitive potential? By genome? By the so-far unquantifiable criterion of 'self-awareness'? By capacity for moral thought?

Part of me is appalled by the idea of creating human-like consciousness in creatures that have no rights. Creating a human brain in a mouse for the explicit purpose of seeing if that mouse can achieve human cognition... and then experimenting on it and dissecting it... strikes me as profoundly criminal.

But another part of me is fascinated. Human biological processes are only possible because we ('we' meaning just about all of the macrofauna) are walking colonies, really, of various lifeforms. The micro-flora and -fauna in our digestive tract; the mitochondria in our cells: they're not 'us,' they're autonomous things that live in us. I vaguely remember reading somewhere that even our brain function depends on a colony of autonomous critters that lives in our synapses or axons or something - but I don't remember specifics; maybe someone else here does.

And viruses, my god, viruses! They're Nature's way of getting the genetic material from one species into another. Viruses might be one mechanism for how we acquired the colonies that make us possible. Are viruses essential to evolution? Is there a limit to evolutionary viral transference, past which an organism can't function? What might 'humankind' look like in, say, 5 million years, or 10 million, if we continue to evolve?

So that part of me - the one that wonders how much evolutionary change, and how much radical change, is possible - is fascinated by these experiments.

Relax. This is just more of mice running experiments on us.

I, for one, welcome our new mouse/human masters.

Slarti, that slays me. Absolutely slays me.

Seriously: how long have you been waiting to use that line?

Given the abundance of opportunities for humor presented by the monumental blockbuster that is HGTTG, I may still have a few left to use at the Restaurant.

Glad I was able to tickle you, Anarch. That'll be $12.50, plus whatever sales tax applies where you live.

Speaking of. . .

Is there anyone not infinitely stoked/worried about this?

I've done repeated simulations, and determined that that movie could not have been made in the time allotted.

Still, I'm at 11.

I'm not getting my hopes up. I'm rather afraid it'll turn out to be almost, but not quite, entirely unlike the original. (Radio series, that is).

I'm cautiously optimistic, but I'm still curious, as I posted in my own blog, as to why Zaphod appears to have the wrong number of nearly everything in this photo. Still, Stephen Fry as the voice of the Guide, and Alan Rickman as Marvin are wonderful choices.

hilzoy: "no one is now proposing injecting animal neurons or neural stem cells into human brains, and if they did, I can't see how it would pass normal ethics review"

At risk of shocking everyone, I don't see this as necessarily unethical. For example, suppose that one wanted to try to cure Huntington's chorea, Parkinson's disease, or any other disease where a small part of the brain goes wrong but the cortex (generally considered the concious, thinking part of the brain) was intact. One method that has been proposed and, to a certain extent, experimentally used is to transplant neural tissue or stem cells into the affected area of the brain to try to regrow that area.

Now, suppose that it might be easier or safer to use mouse neural stem cells to regrow the substantia nigra or whatever part you want to fix. (For various technical reasons, I suspect that human stem cells would be the better choice, but for the purposes of arguing the ethical point, please assume for the moment that mouse cells work better for some reason.) Would it be wrong to inject stem cells into someone's brain, regrow the affected area, and allow them to live a relatively normal life, just because the stem cells used were non-human?

BTW: Porcine valves are treated with some fairly nasty chemicals (formaldehyde, I think, although I'm not sure) to make them non-immunogenic and non-infectious. So the risk of acquiring random pig viruses is probably lower than it would at first appear.

Dianne: I wasn't clear; when I said that injecting nonhuman neural stem cells into human beings probably wouldn't make it past normal ethics review, I was thinking about the combination of (a) safety issues and (b) lack of obvious clinical rationale, leaving aside any special moral issues that injecting these cells into humans might raise.

Is it only the valves that are so treated? Can they do that with e.g. livers?

Given the abundance of opportunities for humor presented by the monumental blockbuster that is HGTTG, I may still have a few left to use at the Restaurant.

Yes, but how many others are there (beyond the obvious fjord jokes) that make essential use of your handle?

"Is it only the valves that are so treated? Can they do that with e.g. livers?"

Unfortunately, no. The problem is that while the valve can be made of dead and fixed tissue (it only has to act as a mechanical barrier which allows flow only at the right time in the right direction) but a transplanted organ has to be alive and capable of doing all the complex things cells do. So the valves can be fixed in formalin and still work, but transplanted organs have to be fresh and healthy (which, unfortunately, also means immunogenic and potentially infectious.) The point of a pig valve as opposed to a mechanical one is that the body's coagulation system sees the pig valve's surface as something that is supposed to be in the circulatory system and therefore doesn't make clots around it like it would a mechanical (ie metal or plastic) valve. Does that make sense or have I thoroughly confused the issue now?

No, that makes perfect sense. If your answer had been 'yes, they can do that with any tissue'. then I would have been thoroughly confused, since I have always been given to understand that there are serious problems with non-human viruses and xenotransplantation. As it is, I'm not. Thanks.

I was going to say the same thing about the child with mice parents. Fertilisation would occurr in the mouse and before the embryo gets anywhere near the stage of being embedded in the mouse uterine wall, it would be transferred to a human host.

This is done a lot when creating transgenic animals, especially in the livestock industry. I've not actually heard that it has been tried, or is going to be tried in humans

"Seriously: how long have you been waiting to use that line?"

Since he chose his name, ten million years ago, I figure.

"I've done repeated simulations, and determined that that movie could not have been made in the time allotted."

What movie?

"I was going to say the same thing about the child with mice parents."

The same thing as what?

Oh, oops, 3 year old thread. Never mind.

By transplanting human neurons into a mouse with almost with no mouse neurons would create a human consciencness in the mouse.
As far as conducting experiments on a mouse with a LIVING brain (with human consciencness!) within an ANIMAL lab is simply unethical.

hi
hi

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