The Centaur has left the barn

NYTimes/Op-EdSection

What Rough Beasts?

By Maureen Dowd
May 7, 2005

I love chimeras.

I've seen just about every werewolf, Dracula and mermaid movie ever made, I have a Medusa magnet on my refrigerator, and the Sphinx of Greek mythology is a role model for her lethal brand of mystery.

So when chimeras reared up in science news, I grabbed my disintegrating copy of Edith Hamilton's "Mythology" to refresh my memory on the Chimera, the she-monster with a lion's head, a goat's body and a serpent's tail: "A fearful creature, great and swift of foot and strong/Whose breath was flame unquenchable."Bellerophon, "a bold and beautiful young man" on flying Pegasus, shot arrows down at the flaming monster and killed her. Chimeras with "generally sinister powers," as Nicholas Wade whote in The Times [copied below], seemed to be a lesson in "the pre-Darwinian notion that species are fixed and penalties are severe" for crossing boundaries.

Chimeras got attention again in the mid-80's, Sharon Begley of The Wall Street Journal noted, when embryonic goat cells were merged with embryonic sheep cells to produce a "geep," when a human-mouse chimera was born and when "scientists took brain-to-be tissue from quail embryos and transplanted it into chicken embryos. Once hatched, the chicks made sounds like baby quails."

The U.S. Patent Office balked at an attempt last year to patent a "humanzee," a human-chimp chimera. But as the Stanford University bioethicist Henry Greely told Ms. Begley: "The centaur has left the barn."

Knowing that mixing up species in a Circean blender conjures up nightmarish images, the National Academy of Sciences addressed the matter last month - stepping into the stem-cell vacuum left by the government and issuing research guidelines.

While research on chimeras may be valuable, the guidelines, in a fit of "Island of Dr. Moreau" queasiness, suggested bans on inserting human embryonic stem cells into an early human embryo, apes or monkeys.

The idea is to avoid animals with human sex cells or brain cells, Mr. Wade wrote. "There is a remote possibility that an animal with eggs made of human cells could mate with an animal bearing human sperm. To avoid human conception in such circumstances, the academy says chimeric animals should not be allowed to mate," he explained. Human cells in an animal brain could also be a problem. As Janet Rowley, a University of Chicago biologist, told a White House ethics panel: "All of us are aware of the concern that we're going to have a human brain in a mouse with a person saying, 'Let me out.' "

Mary Shelley was right. Playing Creator is tricky - even if you chase down your accidents with torches.

President Bush's experiments in Afghanistan and Iraq created his own chimeras, by injecting feudal and tribal societies with the cells of democracy, and blending warring factions and sects. Some of the forces unleashed are promising; others are frightening.

In a chilling classified report to Congress last week, Gen. Richard Myers, chairman of the Joint Chiefs, conceded that Iraq and Afghanistan operations had restricted the Pentagon's ability to handle other conflicts.

That's an ominous admission in light of North Korea's rush toward nukes, which was spurred on by the Iraq invasion and North Korea's conviction that, in bargaining with Mr. Bush, real weapons trump imaginary - or chimerical - ones.

The U.S. invasion also spawned a torture scandal, and its own chimeric (alas, not chimerical) blend of former enemies - the Baathists and foreign jihadists - with access to Iraqi weapons caches.

The Republican Party is now a chimera, too, a mutant of old guard Republicans, who want government kept out of our lives, and evangelical Christians, who want government to legislate religion into our lives.

But exploiting God for political ends has set off powerful, scary forces in America: a retreat on teaching evolution, most recently in Kansas; fights over sex education, even in the blue states and blue suburbs of Maryland; a demonizing of gays; and a fear of stem cell research, which could lead to more of a "culture of life" than keeping one vegetative woman hooked up to a feeding tube.

Even as scientists issue rules on chimeras in labs, a spine-tingling he-monster with the power to drag us back into the pre-Darwinian dark ages is slouching around Washington. It's a fire-breathing creature with the head of W., the body of Bill Frist and the serpent tail of Tom DeLay.

NYTimes Op-Ed

Chimeras on the Horizon, but Don't Expect Centaurs

by Nicholas Wade
May 3, 2005

Common ground for ethical research on human embryonic stem cells may have been laid by the National Academy of Sciences in the well-received guidelines it proposed last week. But if research on human embryonic stem cells ever gets going, people will be hearing a lot more about chimeras, creatures composed of more than one kind of cell. The world of chimeras holds weirdnesses that may require some getting used to.
The original chimera, a tripartite medley of lion, goat and snake, was a mere monster, but mythology is populated with half-human chimeras - centaurs, sphinxes, werewolves, minotaurs and mermaids, and the gorgon Medusa. These creatures hold generally sinister powers, as if to advertise the pre-Darwinian notion that species are fixed and penalties are severe for transgressing the boundaries between them.

Biologists have been generating chimeras for years, though until now of a generally bland variety. If you mix the embryonic cells of a black mouse and a white mouse, you get a patchwork mouse, in which the cells from the two donors contribute to the coat and to tissues throughout the body. Cells can also be added at a later stage to specific organs; people who carry pig heart valves are, at least technically, chimeric.

The promise of embryonic stem cells is that since all the tissues of the body are derived from them, they are a kind of universal clay. If biologists succeed in learning how to shape the clay into specific organs, like pancreas glands, heart muscle or kidneys, physicians may be able to provide replacement parts on demand.

Developing these new organs, and testing them to the standards required by the Food and Drug Administration, will require growing human organs in animals.

Such creations - of pigs with human hearts, monkeys with human larynxes - are likely to be unsettling to many.

"I think people would be horrified," said Dr. William Hansen, an expert in mythology at Indiana University.

Chimeras grip the imagination because people are both fascinated and repulsed by the defiance of natural order. "They promote a sense of wonder and awe and for many of us that is an enjoyable feeling; they are a safe form of danger as in watching a scary movie," Dr. Hansen said.

From the biologists' point of view, animals made to grow human tissues do not really raise novel issues because they can be categorized as animals with added human parts. Biologists are more concerned about animals in which human cells have become seeded throughout the system.

"The mixing of species is something people do worry about and their fears need to be addressed," said Dr. Richard O. Hynes of the Massachusetts Institute of Technology, the co-chairman of the National Academy of Sciences committee that issued the research guidelines.

Foreseeing the need for chimeras if stem cell research gets near to therapy, Dr. Hynes's committee delved into the ethics of chimera manufacture, defining the two cases in which human-animal chimeras could raise awkward issues. One involves incorporating human cells into the germ line; the other is involves using a human brain, creating a human or half human mind imprisoned in an animal body.

In the case of human cells' invading the germ line, the chimeric animals might then carry human eggs and sperm, and in mating could therefore generate a fertilized human egg. Hardly anyone would desire to be conceived by a pair of mice. To forestall such discomforting possibilities, the committee ruled that chimeric animals should not be allowed to mate.

Still, there may in the future be good reason to generate mice that produce human oocytes, as the unfertilized egg is called. Tissues made from embryonic stem cells are likely to be perceived as foreign by the patient's immune system. One way around this problem is to create the embryonic stem cells from a patient's own tissues, by transferring a nucleus from the patient's skin cell into a human oocyte whose own nucleus has been removed.

These nuclear transfers, which are also the way that cloned animals are made, are at present highly inefficient and require some 200 oocytes for each successful cloning. Acquiring oocytes from volunteers is not a trivial procedure, and the academy's recommendation that women who volunteer should not be paid is unlikely to increase supply. Chimeric mice that make human oocytes could be the answer.

There are also sound scientific reasons for creating mice with human brain cells, an experiment that has long been contemplated by Dr. Irving Weissman of Stanford. Many serious human diseases arise through the loss of certain types of brain cell. To test if these can be replaced with human neural stem cells, Dr. Weissman injected human brain cells into a mouse embryo and showed that they followed the rules for mouse neural stem cells, migrating to the olfactory bulb to create a regular stream of new odor-detecting neurons.

The mice may have been perplexed by their deficient sense of smell but probably not greatly so because human cells constituted less than 1 percent of their brain. Dr. Weissman decided it would be useful to have a mouse with a much larger percentage of human brain cells, but he sought ethical guidance before trying the experiment.

He plans to let such mice develop as fetuses and to curtail the experiment before birth, to see if their human brains cells have arranged themselves in the architecture of a mouse brain or human brain.

Given the nine months it takes for a human brain to be constructed, it seems unlikely that the developmental program of the human neurons would have time to unfold very far in the 20-day gestation of a mouse.

Contrary to the plot of every good horror movie, the biologists' chimera cookbook contains only recipes of medical interest. But if there were no limits, could they in fact turn chimeras of myth into reality? That depends on the creature.

If embryonic cells from human and horse were mixed together,the cells of each species would try to contribute to each part of the body, as in the patchwork mouse, but in this case with goals so incompatible it is hard to see any viable creature being formed. Centaurs, in any case, have six limbs, and that would be fine for an insect but violates the standard mammalian body plan.

A much greater chance of creating a viable chimeric creature would come from injecting human embryonic stem cells into a monkey or ape. For this reason the academy committee has firmly ruled out such experiments as unethical. But to continue a little on the path of fantasy, humans are still very similar to chimpanzees, their closest surviving cousins, and an embryo constructed of cells from each may be viable enough to be born.

This chimerical creature would probably not be as enjoyable as the chimeras of mythology but more of a problem human - a Caliban-like personage with bad manners and difficult habits.

"If something were half human and half animal, what would our moral responsibilities be?" says Richard Doerflinger of the United States Conference of Catholic Bishops. "It might be immoral to kill such a creature. It's wrong to create creatures whose moral stature we are perplexed about."

Evidently the first rule of chimeric chemistry is not to make creatures whose behavior straddles the perceived division between the human and animal worlds.