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    Human-Animal Chimeras: From Mythology To Biotechnology
    By Lee Silver | February 15th 2007 01:41 PM | 18 comments | Print | E-mail | Track Comments
    Blurring boundaries

    High up on the bluffs overlooking the Pacific Ocean in southern California, strange animals scurry about in their cages. They eat, drink, copulate and occasionally try to run away from human hands that enter their confined quarters. If you didn't know better, you would think they were ordinary mice. But these particular animals contain a hidden component not present in their naturally conceived cousins. Inside their brains are living human neurons that help them to see, hear and think.


    Fred Gage, a biologist at the Salk Institute, has created these part-human animals to understand how human neurons degrade or die in people suffering from neurodegenerative diseases such as Parkinson's and Alzheimer's. Studying and perturbing brain cells in their natural environment—which is to say, inside a functioning brain—provide the best hope for developing therapies to prevent or overcome disease symptoms. But experimentation on human brains is obviously unacceptable, and so scientists are hoping that animals with a small percentage of human brain cells will provide a substitute for human subjects.


    Many people, however, are deeply disturbed by this research. U.S. President George W. Bush believes that scientists like Gage have stepped across a moral line that must be defended, even at the cost of biomedical progress. In his 2006 State of the Union address, he implored Congress to "pass legislation to prohibit the most egregious abuses of medical research [including] creating human-animal hybrids," because "human life is a gift from our Creator" that should never be "devalued."


    Animal chimeras: from absurdity to reality


    To understand the fear and anger evoked by chimeras, it is useful to go back in scientific history to March 1984, when an animal unlike any other ever born, or seen, adorned the cover of Nature, the international journal of science. The journal's audience of scientists was treated to an unforgettable photograph of an animal with a head that was mostly goat, an upper torso that was wooly sheep, with other body parts that alternated between the two species types. "It behaved like a goat," according to its creator, Danish embryologist Steen Willadsen , "but did not quite smell like one, preferring the company of sheep." This first geep (as the animal became christened) was physically healthy, long-lived, and even fertile. Additional geeps were created by Willadsen over the next several years.

    The geep is an alluring example of a laboratory-created chimera, named by scientists in honor of the creature from Greek mythology with the head of a lion, the torso of a goat, and a tail sprouting the head of a venomous snake. Like other mythological species composites, the chimera was imagined as a monster because it violated a perceived "natural order" in which each species is divinely created as a separate and unique category. Indeed, a chimera's potential violation of nature was so profound that rational thinkers have always assumed it couldn't possibly exist, and the word chimera has become a metaphor for a wishful idea without any basis in reality.


    Willadsen, unlike most scientists, was unwilling to accept the natural limitations imposed by traditional beliefs. "The role of the [biological] scientist," he said, "is to break the laws of nature, rather than to establish, let alone accept them." With this spark of irreverence, Willadsen created not only geeps but other species composites including a cow-sheep creature that he cooked and ate after completing his analysis. (The same refusal to accept conventional wisdom provided him with the confidence to bypass fertilization in the invention of the cloning technology used to create Dolly and thousands of other subsequently cloned animals.) Building upon Willadsen's pioneering work, other scientists combined even more distant species, creating chicken-turtle and chicken-mouse fetuses, for example (which were dissected before hatching). In all of these instances, chimeras were used as models to study basic biological processes.


    Animal rights activists who reject all types of animal experimentation will obviously object to chimera creation as well. But, in fact, chimeric animals are no more likely to suffer than any other animal bred by people for food or research. Each of Willadsen's chimeras was created in a petri dish by mixing together cells from two embryos. The cells stuck together, but didn't fuse, which is why the composite embryos produced animals with species-distinct component parts.


    (A chimera is different than a hybrid, which is formed by cross-species fertilization. A hybrid animal like the mule has cells that are all genetically equivalent and halfway between a donkey and a horse. George W. Bush was obviously not aware of this distinction when he gave his State of the Union address.)


    Because of the fundamental similarity in the body plans of all vertebrate species, live-born chimeras are typically healthy -- albeit bizarre-looking -- animals. And so dual-animal-species chimera production should pose no ethical problems beyond those encountered in traditional animal research.


    Stem cells and animal-human chimeras


    Until the year 2000, chimera production and analysis was just an esoteric tool for basic research on animal development, with little direct clinical relevance. But explosive advances in stem cell biology have provided scientists with the ability to create animal chimeras containing human component parts, and these partial-human chimeras could potentially revolutionize biomedical analysis and therapy.


    The significance of stem cells lies in the fact that they are, in essence, embryonic or otherwise immature precursors to the cells that function within our mature tissues and organs. The mother of all stem cells is the embryonic stem (ES) cell, which exists naturally in 10-day old embryos. ES cells have the capacity to form everything in the human body. During normal development, ES cells divide repeatedly, giving rise to an array of stem cell types that each have a more restricted capacity to form only one or a few tissues or organs.


    Human stem cells at many different stages, from embryonic to adult, can now be cultivated in laboratory petri dishes. And chimeras can now be produced by inserting these stem cells into animal fetuses or embryos. Biomedical scientists are hopeful that a more sophisticated understanding and ability to control both animal development and human stem cells will someday allow the production of animals with human organs formed in place of animal organs.


    Remarkably, progress along these lines has already been made. Alan Flake at Children's Hospital in Philadelphia and Esmail Zanjani at the University of Nevada, incorporated human stem cells into early sheep fetuses while they were growing in their mothers' wombs. After birth, a wide variety of lamb tissues including blood, cartilage, muscle and heart displayed human contributions of up to 40%, although external body features were always entirely animal-like.


    In another type of chimera experiment, Yair Reisner at the Weizmann Institute in Israel implanted nondescript human kidney stem cells into mice, and coaxed the cells to multiply and develop into miniature, but fully functional, human kidneys that actually secrete urine. Results obtained from these lines of research and others suggest that the personalized therapeutic potential of stem cells might be most fully exploited in conjunction with the developmental potential provided through chimeras to create fully functional, replacement kidneys, livers, and hearts.


    Where is the line?


    Although pigs with human hearts will, upon first description, cause people to shudder, education and self-interest is likely to drive the acceptance of chimeras developed strictly for organ transplantation. As long as they look like animals and behave like animals, most people will view them as animals because internal organs by themselves do not tug upon our emotions.  (But ask yourself whether an animal such as the following is acceptable to provide an arm to someone who lost their own in accident.)

    The debate line shifts, however, when scientists begin to chimerize the essential features of mentality that distinguish us as human beings. Educated people understand that human mentality emerges from human brains, which is why chimeric mice with human brain cells are liable to perturb many more people.


    Last December, Gage injected human embryonic stem cells into the brain regions of developing mouse fetuses still inside their mother's uterus. The human cells became "active human neurons that successfully integrate into the adult mouse forebrain," where higher brain function is localized, Gage explained. Although Gage's mice have brains that are less than 1 percent human, Stanford professor Irving Weissman believes that mice with brains made entirely of human cells would make a better "model" for human neurological diseases, and he's proposed creating them. Would a mouse with a 100 percent human brain cross a moral red line?


    No biologist thinks a mouse-size brain filled with human cells could produce anything remotely resembling human consciousness.  But the presence of a biologically human brain inside an organism able to propel and feed itself is typically accepted as clear biological evidence that the organism is a human being. This logic would force an ethical person to grant the chimeric mouse I've just described a right to life, which is patently absurd. Yet if we follow our intuition and decide that this mouse is not a human being, we are forced to conclude that the presence of a fully-human brain inside an alert, responsive organism is not a sufficient criterion for inclusion within the family of human beings, which not only violates common sense but challenges the very foundation of universal human rights.


    The moral conundrums provoked by animal-human chimeras multiply tremendously when the companion species is not a mouse but a non-human primate with a far larger brain capacity. So far, scientists have only integrated small numbers of human neurons into monkey brains. Although members of the scientific community have no intention of creating chimeras with even minimal human-specific mental attributes, the fact is that modern biotechnology has moved such ambiguous beings from the realm of mythology to the realm of possibility. And this fact elicits the greatest challenge to western thought, which is that the existence of a strict line separating human beings from non-human beings may simply by a figment of our imagination.


    Comments

    Hank
    Yesterday you went to bat for GM foods and today you are discussing chimeras????

    I have the feeling your column will give us a reason to get out of bed every day.

    This is great stuff.

    Kimberly Crandell
    I have to admit, as I read this I kept flipping back and forth as to whether I thought this field of experimentation was "good science" or "morally wrong". Some applications of the development of these chimeras seemed promising, while others seemed alarming. No wonder this is fueling some debate... I can't even decide myself how I feel about it.

    But would a pig whose heart was injected with human stem cells potentially make a heart that would be less likely to be rejected after transplant? Would Baby Fae, who received a baboon heart for transplant in 1984, have fared better if the baboon's heart had been injected with human stem cells during development? And regardless... would the developmental differences discovered in such hearts help us better understand ways to treat heart disease in humans? I think science is meant to continually expand into new areas... but I am also at a loss as to how to universally define where "the line" lies, and what crosses it or not.

    Lee Silver
    Dear Science Mom:  I don't think there is any simple answer to where we should draw the line.  At some point, society will have to make that decision by balancing the potential for medical advances with a societal sense of what deserves to be treated with dignity and not allowed to be experimented with.

    As far as the actual science goes, the idea is *not* to inject heart stem cells into pig hearts, but rather to put the human stem cells into an embryo at a much earlier stage before heart development has taken place. With the tricks of genetics and experimental embryology, scientists would try to get the fetus to develop a heart that is 100% human (and 100% derived from the patient's own cells) within a pig body. Transplantation would involve replacing the patient's old heart with HER OWN new heart. This is still just a dream, but the science is moving very quickly.



    Do pigs live long enough for the replacement heart to be of use in many cases?

    Most people who could benefit from a replacement heart are not "spring chickens."

    Do pigs live long enough for the replacement heart to be of use in many cases?

    Most people who could benefit from a replacement heart are not "spring chickens."

    ha well this is awesome but weird imagine some time in the future (hopefully not that far) were they would have a gorilla and make its brain 100% human brain it would be like a person feeling everything but with a gorilla body :|
    god id be scared :(

    Hank
    It won't be that exciting. More like raising replacement hearts for people (inside the body of an animal ) that are created from the person's own cells and thus a perfect match - though I agree the football players you could make by using gorilla bodies would take the game to a brand new level.

    Forget about the football players with gorilla bodies. They could not run fast enough for the National Football League (NFL). Even the largest human linemen are amazingly quick, as a result of the natural selection produced by multi-million dollar contracts being awarded to a very small number of people.

    Human-gorilla hormones, however might replace steroids as the leading performance-enhancing substance, if the NFL ever got serious about enforcing the existing steroid ban. Or if anyone found a test for human-growth hormone, now untraceable. Gorilla-growth hormone anyone?

    Then there is the fact that all of this might not turn out for the best. there could be draw backs and the people who's body reject the change, if this is ever considered it will have to be tested over and over, and even if it passes safety measurements, things have to be done carefully, because, once agian, there is the fact of a person rejecting this and the result of the regected mix could be something we have never seen before.

    Not long ago, I've found out that scientist in China developed a 15% human 85% sheep chimera for organ donor use. Chances are, whosoever kills that chimera will harvest the meat, and that meat will most likely find it's way to your local grocery store meat department some day. I don't think very highly of eating the flesh of a creature who is 15% (or any percent) one of us. That's cannibalism.
    I've read a question on another blog site,"Does it have a soul?'.
    As a born again christian, I've thought about that. If such a creature does have a soul, rest assured that soul is marred by man's sin if it has the seed of man in it. A bed sheet that is only 15% unclean is not a clean bed sheet.
    A nonchristian soul of man is an unclean soul. Therefore, if the creature does have a soul, that soul is not sinless.
    But any reasonable person knows that any creature who has only 15% human intelligence will never have his or her soul held accountable, if they do have a soul. Othewise the soul of that creature would be bound for Hell.
    I suppose the issue of one's soul would be different for a chimera who was 70%, 80% or 95% human, who had intelligence like the rest of us, was able to have fluent conversations with us and understood the issues of right from wrong. If given the opportinity, I'll sit down with a creature who is mostly mankind, with an open Bible, and talk to him (or her) for a while.
    If I witness to a creature who has no eternal soul, I guess no harm has been done...But if I fail to witness to a creature who does have an eternal soul marred with man's sin, that creature's soul remains bound for Hell.
    Besides that...I would dearly love to see one of those chimeras, after trusting the Lord for his or her spiritual needs, begin speaking to those atheistic scientists, who developed them, about their spiritual needs too. It would surely freak those scientists out...They need to be.
    As I mentioned two paragraphs back, not wanting to fail to witness to a creature who has an eternal soul marred with man's sin, that includes us who are not chimeras also.
    It is already a known fact that every one of us has an eternal soul marred with man's sin. And unless you died as a child who was below the age of accountability, or was severely mentally underdeveloped and cannot understand such issues, You will never see the Kingdom of God if you leave this life some day never turning your life over to God's only begotten Son, our Lord Jesus Christ.
    One night, in the loft bedroom of my home in rual Akkansas, I called upon the Lord for forgiveness of my sins... Humbled as a child... Willing to repent from sin and serve God... Believing Jesus was born of a virgin... Believing Jesus lived in a body of flesh among mankind, And believing Jesus died on the cross for our sins and rose from the dead on the third day thereafter and is alive today.
    Here is a sobering thought. 153,000 of us die around the world every day. Almost two deaths every second around the clock. It never stops.
    If you leave this world without Christ in your life, there will be the day you will stand before God in judgement and hear Him say," Depart from me you worker of iniquity. I never knew you".
    And on that day, it will have been too late a long time ago to do anything for you as you stand in judgement, naked, in the shame if sin,and no robe or raiment to cover your shame and no way to hide it.
    Just hypothetically speaking, suppose a human chimera does have a soul. And this particular chimera trusted the Lord one day and is in Heaven on that Judgement Day (I somehow picture a chimera like Patricia Piccinini's artwork of the human dog chimera with pups)....And there is this particular Hell bound soul who never trusted the Lord. And while that lost soul is being Judged, he lookes a far off and takes notice of the soul of that chimera stareing and gawking at him. And only because that chimera accepted Christ as saviour, she stands saved among the rest of us christians. And only because that Hell bound soul left this life rejecting Christ, he's on his way to the Lake of Fire... Inspite of him being 100% human...Who was suppose to be smarter than that chimera. How much envy would that fuel? That chimera is a creature that Hell bound soul once deemed dumb. Those issues will be the last thing concerning that Hell bound soul when he hears God command one of his angels,"Bind him hand and foot, and cast him into the Lake of Fire which burns with fire and brimstone for ever".
    Some people believe the Lake of Fire is the molten core of the Earth. I cannot even picture in my mind how fearful it must be for those Hell bound souls to watch those angels approach them with those chains to bind them.
    I can imagine that chimera staring and gawking at that Hell bound soul getting bound up tightly in chains by that angel. And that chimera pointing and saying,"Oooooh, look". I can also imagine other christians (100% human) stareing at that Hell bound soul getting bound up, with the same fascination as a child who watches a spider wrap up a fly. I suppose that Hell bound soul would hysterically scream at that chimera,'WHAT ARE YOU LOOKING AT, FREAK ?!" and to everyone else,"GET YOUR EYES OFF ME!" I'm almost sure they'll all just laugh at him. Who Hell bound souls were means nothing in that new world. And christians are brethren to christians. As that Hell bound soul is being taken away, in a severity of shame far beyond our comprehention, to the Lake of Fire, I can imagine that chimera saying,"There was a day he called me stupid for being part animal. He wasn't even smart enough to accept Christ as saviour, and I did...Who's stupid now?" Good works without Christ will not save you either. One day it will all burn like hay and stubble. And so will you if you never become a christian.
    If you consider me a "Jesus nut" and call me stupid by now, that's OK by me. If you never accept Christ as your saviour, I'll watch an angel bind you up someday. And I will say," There was a day he (or she) called me stipid for witnessing for Christ. He (or she) wasn't even smart enough to accept Christ as saviour, and I did...Who's stupid now?"
    107 people die around the world each minute. Multiply the number of minutes it took you to read my comment by 107. That's how many souls left this life while you were reading what I wrote. Matthew 7: 13 & 14 warns that few will make it to Heaven and many will be bound for Hell. Many souls died without Christ since you began reading my blog comment...I plead you not to become one of them.

    The interesting thing is, that allot of our " systems" like religion, philosopy, moral etc are already in trouble answering those questions like:

    what makes us different from any other species?
    how does " haven " or " hell" ( if they excist at all) deal with that?

    May be the devil or God have both trouble to decide, if that chimera soul should be playing harp, or be in the cooking pot of the devil....well like earlier said...Chimeras might end up in the cooking pot anyways.
    A 50% 50% human pig or pig human can still be eaten ...can it ?

    there is of course the possibility of coexistence of 2 opposite sides at one time.
    ( good examples to be found in Physics )

    Fortunately the house keepers of God call "Priests" have an answer to those question, like they always do. I am glad.

    May be they( Chimeras) will then belong to the axis of the evil, which makes the whole complexity of our world fortunatelly so easy to understand for the public. Of course God is always on the correct side, since he has nothing to do with his male function creation called "devil"..

    Chimeras shake the foundation of all we know.....but we are only at the beginning of that development.

    Will we have major “cleaning activism”, propelled by some fanatics, who think about the human race as a "clean" race, determined to rule the rest of the evolution and the universe( in fact only a fraction of that human race is ruling the world right now)

    Will those Chimeras be the new slaves of our future world, because they are not 100% human?

    A few years ago people had to die because they were not 100% Aryans. May be those future Chimeras face the same fate driven by some well educated intelligent, people, who have answers to this complex matter....by just killing them.

    Where is the fine line between our and other species?...if there is any at all...remember how you looked like in your own early embryonal stages.
    Did you always look like a human? really?

    thoughts?

    We belived along time, that the Newton Physics was correct ...until Einstein discovered something else.( does everybody now about him already)

    what do we belive now...related to our own species?

    http://en.wikipedia.org/wiki/Uncertainty_principle

    Of course there is the opinion, Chimeras are a funny thing and useful for the daily life. I am sure the interested reader comes up with all kind of creations and ideas what kind of “mix” would fit in his/her live.( There will be designer competions about it...I am sure!)

    Anyway...that planet keeps turning

    May be we are all just live in different forms....like water has different forms.

    So if Chimears are live after all, why do we not look at them like it?

    Wow!
    Does this mean that some brainchild scientist could hybridize (chimerize) a cat (felis cattus) with a human? I believe that this has already happened at UC Berkley to generate non alergenic kitties, but I mean real half and half human and cats? Think of the potential for really cute, cuddly nekojin complete with georgous looks and cat ears and tails! Lets do this! To Hades with the nay sayers! I will be first in line to take one home with me, to give a nice bowl of milk and (echm) take to bed...

    ADT

    After searching a lot of mythology books online, I can only suggest going to Askdiana.net and improve your knowledge.

    I happen to be a human chimera who is a true hermaphrodite. A twin set that never became twins (male 46XY + female 46 XX). I had no choice in the course of biological oddity but I certainly do not see myself as a freak. I am rare but I am alive. I believe this is true because God's fingerprints are upon my very rare but unique genetic signature. I have to believe that I am meant to be part of the natural diversity that can happen in this world. As I best understand this there are only 18 others in the whole world like me. While there are 40 cases of chimerism, only 19 of us were boy/girl twin sets. The rest were boy/boy or girl/girl twin sets. It would seem that we are a part of natural secetion, genetic mutation, and maybe even a hint of evolution to come. Maybe the world would benefit from studying what is different and not well understood-- rather than taking a closed-minded stance that different somehow equals bad! Genetic variance is how we are a species survives--so why would anyone find a person who is differently-born a threat?

    they can make a human-cat-smurf hybrid to create the real Na'Vi race! OMG

    Ok so you guys do sheep, chickens, mouse, turtle. Why not put human DNA into a snake? or another creature that we don't usually study that much if you could try something new then all these animals like reptiles and lizards that would be awesome.

    I think that the reason for the "no snake thing" is that snakes can be dangerous and very vital. I, personally, wouldn't want to be combined with a snake. Anyways, snakes would be hard to handle and experiment with, they squirm way to much.

    If we are creating Chimeras, does that mean we'd be considered CANNIBALS because we are eating animals with human DNA inside of them? I mean...... is the saying "You are what you eat"..... if so then that's creepy. I love this article but it is very unnerving :-/ In my opinion, i say KEEP MOVING FORWARD and try it...... but there must be certain boundaries.