March 06, 2005
Stanford Prof Plans Mouse With Human Brain Cells

Adult stem cell researcher Irving Weissman, M.D. of the Stanford School of Medicine wants to develop mice that have a lot of human neurons in their brains.

So Stanford asked where it should draw the line. It is the first university in the nation to tackle the philosophical question: When does a chimera stop being an animal and start becoming a person, suggesting that research should end? The report foreshadows the release of guidelines on stem-cell research, including chimeras, by the National Academy of Sciences this spring.

``We concluded that if we see any signs of human brain structures . . . or if the mouse shows human-like behaviors, like improved memory or problem-solving, it's time to stop,'' said law and genetics Professor Henry T. Greely, director of the Center for Law and the Biosciences and leader of the committee.

``We think if he takes appropriate caution -- including stopping at each step along the way, to see what's happening -- the research is ethical,'' he said.

What I find especially interesting about this report is the reticence to see animals made smarter. What is their motivation for this restriction? Is it that they do not want lab animals made intelligent because then experimentation on them would become too much like experimentation on sentient humans?

Or do they object more generally to modification of other species to make them become as smart as humans? If the latter, what are their reasons for opposing this move? Certainly one can think of reasons to oppose such a development. The human race could find its existence threatened if we genetically engineered some predator species to be as smart as we are. Imagine smart lions and tigers with no empathy for the human species hunting us down to eat. For that matter, imagine genetically engineered human psychopaths with no empathy for the human species. They already occur naturally in smaller numbers. Will some people ever choose to use biotechnology to produce offspring with little or no empathy?

Or is the objection to making smart mice with human neurons just the creepiness factor? Are the committee members either creeped out by that notion or afraid the public will be? In the longer run discoveries of which genetic variations raise intelligence will point to ways to increase the intelligence of mice without the need to use human neurons. Higher intelligence will be achievable in mice by use of genetic engineering to change the sequences of existing mouse genes.

Weissman's motivation here is that he wants better animal models of human diseases. He is not initially aiming to create mice that have 100% human nerve cell brains. He just needs enough human neuronal cells in the brains of a mouse model to recreate manifestations of human neurological disorders such as Lou Gehrig's disease (a.k.a. Amyotrophic Lateral Sclerosis or ALS), schizophrenia, stroke, and other neurological disorders. The ability to replicate human diseases outside of humans is an enormously valuable approach to investigating the mechanism that cause diseases and to test potential therapeutic approaches for treating and curing diseases.

For some interesting insights and an overview of the state of stem cell research see Weissman's July 14, 2004 testimony on adult stem cell research to the US Senatoe Committee on Commerce, Science, & Transportation.

On the subject of cross-species hybrids the US Patent Office has just rejected an attempt to patent the idea of creating a human-animal chimera hybrid.

The U.S. Patent and Trademark Office rejected the claim, saying the hybrid -- designed for use in medical research but not yet created -- would be too closely related to a human to be patentable.

Paradoxically, the rejection was a victory of sorts for the inventor, Stuart Newman of New York Medical College in Valhalla, N.Y. An opponent of patents on living things, he had no intention of making the creatures. His goal was to set a legal precedent that would keep others from profiting from any similar "inventions."

Newman does not want to see people create chimeras. So he is trying to reduce the business incentive for doing so. However, I do not believe the question of whether to create chimeras is going to be decided based on expected return on investment. Some potential projects hold sufficient allure that even absent a large chance of profit there are wealthy people who will attempt them once attempts to do so become cheap enough. For examples of this phenomenon look at the groups (some of them driven by spiritual beliefs) that are trying to clone humans. Or how about people who build airplanes and other devices for the challenge and for the fame that sometimes results.

I think the development of smarter animals and the development of chimeras are both inevitable. These developments can be delayed by regulations and restrictions on government funding. But the expense and difficulty of attempting these efforts will eventually drop to the point that the barriers in the way of attempts to do these things will fall so low that they will happen. The streets find their own uses for technology.

Update: Michael J. Fox is helping to get the broad public ready for future talking mice.

Supporters of stem cell research at Stanford University include the actor Michael J Fox, who suffers from Parkinson's disease. Fox provided the voice for Stuart Little, Hollywood's version of the "human mouse'', who talks, has human parents and lives in a New York apartment.

I picture a Back To The Future sequel where talking mice go along for a ride in a Delorean.

Update II: Also see my previous post Human-Mouse Hybrid Creation Debated.

Share |      Randall Parker, 2005 March 06 03:34 PM  Biotech Hybrids

Steel Turman said at March 6, 2005 8:50 PM:

The short story Flowers for Algernon comes to mind. So does the Cliff Robertson movie Charlie.

Randall Parker said at March 6, 2005 9:11 PM:


I think of the David Brin books Startide Rising and The Uplift Wars.

Jody said at March 6, 2005 9:33 PM:

Brin also immediately came to my mind...

nectarflowed said at March 7, 2005 2:59 AM:

Neuroscience is no longer an obscure area; hopefully, people will eventually stop relying on "gut feelings" and other supernatural beliefs for policy decisions.

Robert Bradbury said at March 7, 2005 9:48 AM:

I think the debate is silly. What better way to
allow humans to live in the arctic or the desert
travel on long planetary voyages (by making them
more energy efficient, giving them natural
radiation resistance, etc.). The ways to
do these things are to give them new genetic
components that enable these capabilities.
Of course it would be unwise to test these
components if one hadn't tested them in mice
or other species first. Interestingly, a
greater radiation resistance would probably
significantly decrease cancer rates.

We are already at the point where we give lots
of mice with small fractions of the human genome
to make them better experimental animals upon
which to test drugs and other therapies. We also
routinely kill them (or our cats do...). What
is wrong with providing different fractions or
larger fractions of the human genome?

It makes no sense to me.

Eric said at March 7, 2005 10:10 AM:

Greely is a lawyer, in addition to being a ethicist. His notion of ethical research strikes me as practical (as compared to theoretical). What he seems to be saying is: let us know up front that you're not trying to make smart mice, stop at every step to insure that you haven't done so, and if you do create smart mice, stop advancing the research. Basically, he doesn't want to wake up one day and have the front cover of every newspaper saying that Stanford is playing God. I think his ethical position is that we have to ease people into new things: don't shock them.

I wouldn't exactly call that 'ethics' but it is probably good public policy.

Robert Silvetz said at March 7, 2005 11:15 AM:

So much fuss... can we get a smart AND conscious mouse first?

And this stopping all the time for endless reviews... they will never get done....

Randall Parker said at March 7, 2005 11:19 AM:

Robert Silvetz,

I'm sure that the Chinese will not stop for endless reviews.

Kurt said at March 7, 2005 11:23 AM:

I think that Greely seems to have a more rational point of view than most "bio-ethicists" do. It is a real concern, because if we really do make intelligent mice and there is the potential for sentience, would that not mean that we are now dealing with sentient beings with the same rights of self-determination as human individuals? If sentience can be produced in animals, then to use them as "lab rats" is ethically the same as human experimentation. The are Nuremburg protocols that deal with this.

I read somewhere that felines (cats) have brain structures that are more similar to primates and humans than any other class of mammal, including rodents such as mice. Sentient felines perhaps?

This does remind me of a story about intelligent mice that I read as a child (in the mid 70's) called "The Mice of NIMH" or something like that. I always wondered if this was possible. More recently is David Brin's "Uplift" series of novels that deal with this possibility.

To be honest, I am not any more keen on sentient animals (and the exploitation there of) than I am of using "true AI" to create our "replacement". I definitely think the research should go forward, but there should be some review along the way.

In the long run (30 years or so), controls are unlikely to work. If it costs several 100K to do make these mice today, it will no doubt be possible to make them for several 10K 10 years later and perhaps several thousand dollars 20 years later.

The first mammalian clonings cost several million dollars to do. Today, it can be done for 50K (at least thats what Genetic Savings and clone charges for a cat cloning) and it will become much cheaper in the future.

Think of it as biotechnological version of Moore's Law.

Ken said at March 7, 2005 12:38 PM:

The problem with "full speed ahead", is that you could end up creating an actual person that's hopelessly crippled.

A person, at least on this planet, is really nothing more than a functioning human brain. Put a scaled-down but human brain in a mouse, and you could end up with a really stupid person with no hands and a really short lifespan. (And if you did, how would you know? Until you can figure out just what it is in the brain that gives rise to personhood, you don't know.) That would be extremely cruel.

Eric said at March 7, 2005 12:38 PM:

And this stopping all the time for endless reviews... they will never get done....

I'm not sure they mean stop for review, so much as test the behavior of each chimera. Nobody wants to review someone else's intermediate steps in detail; it would be a waste of their time.

If this is all they had to agree to in order to do their experiments, then it's probably a good deal. It's better than fighting against legislation.

Maurice Bernstein, M.D. said at March 7, 2005 1:08 PM:

I am pessimistic about regulation, control or restriction of research. The world is large and whatever will happen will happen. And once two chimera mice mate, if they still can reproduce, well.. there will be more chimera mice on the planet. ..Maurice.

toby said at March 7, 2005 1:50 PM:

I think they're just worried that then we really *will* need to build a better mousetrap.

Maurice Bernstein, M.D, said at March 7, 2005 7:30 PM:

I wanted to explain why I am pessimistic about restricting the chimera research. I look now how nations are unwilling though I think they would be able to stop genocide in this world, which has the potential for significant changes in the nature of the populations and the environment and can have a relatively immediate effect on millions of human beings. Based on this observation, I don't think that nations will or can do anything to prevent or regulate the development of simply "intelligent mice". ..Maurice.

Divus Masterei said at March 8, 2005 4:38 PM:

##"Some potential projects hold sufficient allure that even absent a large chance of profit there are wealthy people who will attempt them once attempts to do so become cheap enough."

hmmm... That is true.

##"The are Nuremburg protocols that deal with this."

Whaaa? The means justify the ends, human experimentation if it has an adequate chance of saving countless lives is worth it.

##"The problem with "full speed ahead", is that you could end up creating an actual person that's hopelessly crippled."

Tis the same problem with modern day natural reproduction, is it not? The chances of some sort of catastrophe are not zero, yet people do it and they don't care, and the benefit is often less than could be obtained out of some adequate experiments(not saying these are so...). People go and say: "OH, my kid's born f@cked up, he'll die in a few days"... tsk, tsk, tsk, there were risks in conceiving naturally.

Throughout the ages there have been countless who've suffered and died as a result of the act of reproduction, results that've gone bad. These have been necessary human sacrifices for the continuation of the species, but the time is coming when sacrifices, even those so-called "natural" ones will be no longer necessary.

Flo Schrader said at October 19, 2005 9:03 AM:

I think that if scientist are to create an animal that has the ability to talk it should be the dog. As we all know they are mans best friend, so why not create them to talk to us.

Cori said at November 8, 2005 8:47 PM:

i am all for the testing.

say we do testing for 'y' years and 'x' chimera lives are lost, whether they are human mice or mice pigs or whatever, it is irrelevant.
well, after 'y' years we DO find a cure or sufficient prevention methoed for some horrible deadly disease. then an infinite number of lives will be saved by this cure or prevention method. 'z' number of people will be cured of the disease and live and 'a' number of people in future generations will never become infected. correct me if im wrong but im pretty sure that

limit as 'a' approaches infinity of x / (z + a) is zero

lim x
a -> infinity ------- = 0
(z + a)

so after any progress is made, the losses caused by the research become infintessimal.

Cori said at November 8, 2005 8:50 PM:

... i figured it would mess up the problem in its proper notaion... pay no attention to lines 9 - 11 on my previous post.

Legion said at February 15, 2007 6:43 PM:

why exactly would you want to kill the mouse if it showed any hint of human behaviour?
It seems to me that that is when the progress is being made. That is if your trying to make a actual chimera and not just a furry factory that would produce things that we need. Just imagine a mouse or any other animal that had the mental capacity of a real human being. I would love to do that. Except i really dont support stem cell.

Xion Shimazu said at January 28, 2008 11:38 AM:

I agree with legion on this one... on some things... Why give life to just take it away? especially if there's no oppurtunity for the species to show it's full potential? it's like the rabbit-human chimeras made overseas, they were terminated after only a few months in order to harvest their stem cells. It's a waste of resources AND time. Killing because they acheived the potential expected of them... no wonder animal rights protests breathe down the scientific community's back so hard.

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