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Blending of species raises ethical issues

   By Carolyn Y. Johnson The Boston Globe
   Thursday, April 21, 2005
Lines blurred between man and beast

BOSTON In labs around the world, the line between man and beast is
blurring. Herds of pigs are grown with partly human livers in the hopes of
solving the organ-transplant shortage. Mice with human cells are used as
the new "guinea pigs" for testing drugs or figuring out disease. Human
brain cells are grown inside mouse skulls to help better understand
diseases like Parkinson's and Alzheimer's.
.
Scientists are using such chimeras - animals whose bodies are a mosaic,
with their own cells intermixed with those of another animal - to model
diseases, test drugs on live human cells, and harvest organs for transplant.
.
But the blending of species also has raised a host of ethical and
philosophical questions over the past year.
.
Last month, the George W. Bush's Council on Bioethics struggled to
understand when a human-animal chimera is a useful tool, and when it
becomes "high-tech bestiality." The United States turned down a
seven-year-old patent application for a chimpanzee-human mix, the
"humanzee," in February, with patent officers calling on Congress for
guidance. Canada banned the creation of all chimeras last year. And the
National Academy of Sciences is set to release ethical guidelines this
month for researchers who use stem cells to create chimeras.
.
"The question is, where does it all end?" said Stuart Newman, a
developmental biologist from New York Medical College who proposed the
humanzee because he wanted to draw public attention to a morally
questionable but technically feasible scientific project that might follow
from some of today's experiments. "At some point, everyone will be offended."
.
Animal rights advocates argue that any manipulation of animals for human
benefit, whether for dinner or for research, is immoral.
.
Christian teaching holds that the Bible gives people dominion over animals.
.
"That really means stewardship - you cannot abuse them for your good. But
just as you would eat a pig or eat a cow, I see no problem in putting a pig
valve in a human being or a pig kidney within a human being," said Dr.
David Stevens, executive director of the Christian Medical Association, a
U.S. group that advocates the practice of medicine from a religious
perspective.
.
The problem arises, Stevens said, when scientists fundamentally alter what
it means to be human or animal. "If you give an animal a human brain, if
you give an animal human reproductive organs, if you make a human embryo
that's not fully human, that crosses the ethical, moral, and biblical line."
.
The Roman Catholic Church has grave concerns that chimera research may
create beings without a clear moral status. "I think it would be basically
immoral to create a human whose status we could not determine. We'd have an
unresolvable dilemma about how to treat this animal," said Richard
Doerflinger, deputy director of the secretariat for pro-life activities at
the U.S. Conference of Catholic Bishops.
.
The scientists doing work on chimeras see their work as ethical and
responsible and believe it has tremendous potential benefit.
.
Charlotte Kuperwasser, a biologist at Tufts University, created a mouse
with human breast tissue to solve a longstanding problem in research, that
testing drugs by looking at cells in a dish or making a mouse version of
the disease doesn't necessarily help actual patients.
.
Mouse cancers, she said, "'don't look like human tumors. They don't behave
like the actual breast cancer. We can cure mouse breast cancers, but that
can't always translate to the clinic."
.
By adding human breast cells to immune-deficient mice before puberty,
Kuperwasser has been able to watch normal breast development and generate
human cancers rather than mouse ones in her lab animals. Now, she is
working to implant particular patients' cancer into mice to see if they can
test drugs and cures on it without harming the person.
.
In Nebraska, William Beschorner is working to create a human immune system
and humanized liver in a pig. Eventually the biologist hopes to replicate a
particular patient's immune system and then transplant the pig's organs
back into the person, where they would appear familiar to the immune
system, and therefore wouldn't be rejected.
.
Even scientists pause, though, when experiments creep from basic organs to
the seat of human consciousness - the brain - or when stem cells,
controversial in their own right, are added to the mix.
.
Four years ago, Irving Weissman, a stem-cell biologist at Stanford, created
a mouse with human neurons in its brain, hoping that the living model would
provide insights into diseases like Parkinson's and Alzheimer's.
.
The human neurons made up about 1 percent of the mouse brain and were
alive, but it was unclear whether they were functioning. He suggested
another project: creating a mouse with 100 percent human nerve cells in its
brain.
.
He asked an informal committee to review his proposal, and the group
recently drew up guidelines for doing the experiment responsibly.
.
Hank Greely, head of that committee, described one clear limit. "If you see
anything that is not unequivocally mouse behavior, you stop the
experiment," he said.
.
Scientists agree that human brain cells growing in a mouse are unlikely to
humanize a mouse because of the vast differences in skull size and brain
architecture. But in a closely related animal, the threat of an animal
floating somewhere between human and animal becomes more serious.
.
"What is essentially human is really debased," Alfonso Gomez-Lobo, a member
of the Council on Bioethics, said in March. "I often imagine what it would
be like to wake up one day only to realize that I have the body of a
chimpanzee."
.
A chimera is an animal with its own cells and that of another animal
growing side by side in its body. Scientists used to call such animals
"tetraparental," meaning they had four parents - their own, and the parents
of the other cells living in their bodies.
.
The "geep" is an example of a true chimera. Scientists at the University of
California at Davis fused together sheep and goat embryos. In the
offspring, every organ, including the sex organs, were made up of both goat
and sheep cells, which meant that one geep could produce both goat and
sheep sperm.
.
Many other kinds of chimeras are made by adding human cells to animals that
have been genetically altered to have no immune system. Without the immune
system, which would attack foreign cells, scientists can grow human brain
cells or breast cells in another animal, often a mouse.
.
Chimeras surround us, and not just in the lab. Cardiac surgery patients who
receive pig valves to repair their hearts are chimeras. Transplant
recipients, who have another person's bone marrow, kidney, or heart
thumping in their chest, are a kind of chimera, with the cells of another
being living alongside their own.
.
.
See more of the world that matters - click here for home delivery of the
International Herald Tribune.
.
< < Back to Start of Article Lines blurred between man and beast

BOSTON In labs around the world, the line between man and beast is
blurring. Herds of pigs are grown with partly human livers in the hopes of
solving the organ-transplant shortage. Mice with human cells are used as
the new "guinea pigs" for testing drugs or figuring out disease. Human
brain cells are grown inside mouse skulls to help better understand
diseases like Parkinson's and Alzheimer's.
.
Scientists are using such chimeras - animals whose bodies are a mosaic,
with their own cells intermixed with those of another animal - to model
diseases, test drugs on live human cells, and harvest organs for transplant.
.
But the blending of species also has raised a host of ethical and
philosophical questions over the past year.
.
Last month, the George W. Bush's Council on Bioethics struggled to
understand when a human-animal chimera is a useful tool, and when it
becomes "high-tech bestiality." The United States turned down a
seven-year-old patent application for a chimpanzee-human mix, the
"humanzee," in February, with patent officers calling on Congress for
guidance. Canada banned the creation of all chimeras last year. And the
National Academy of Sciences is set to release ethical guidelines this
month for researchers who use stem cells to create chimeras.
.
"The question is, where does it all end?" said Stuart Newman, a
developmental biologist from New York Medical College who proposed the
humanzee because he wanted to draw public attention to a morally
questionable but technically feasible scientific project that might follow
from some of today's experiments. "At some point, everyone will be offended."
.
Animal rights advocates argue that any manipulation of animals for human
benefit, whether for dinner or for research, is immoral.
.
Christian teaching holds that the Bible gives people dominion over animals.
.
"That really means stewardship - you cannot abuse them for your good. But
just as you would eat a pig or eat a cow, I see no problem in putting a pig
valve in a human being or a pig kidney within a human being," said Dr.
David Stevens, executive director of the Christian Medical Association, a
U.S. group that advocates the practice of medicine from a religious
perspective.
.
The problem arises, Stevens said, when scientists fundamentally alter what
it means to be human or animal. "If you give an animal a human brain, if
you give an animal human reproductive organs, if you make a human embryo
that's not fully human, that crosses the ethical, moral, and biblical line."
.
The Roman Catholic Church has grave concerns that chimera research may
create beings without a clear moral status. "I think it would be basically
immoral to create a human whose status we could not determine. We'd have an
unresolvable dilemma about how to treat this animal," said Richard
Doerflinger, deputy director of the secretariat for pro-life activities at
the U.S. Conference of Catholic Bishops.
.
The scientists doing work on chimeras see their work as ethical and
responsible and believe it has tremendous potential benefit.
.
Charlotte Kuperwasser, a biologist at Tufts University, created a mouse
with human breast tissue to solve a longstanding problem in research, that
testing drugs by looking at cells in a dish or making a mouse version of
the disease doesn't necessarily help actual patients.
.
Mouse cancers, she said, "'don't look like human tumors. They don't behave
like the actual breast cancer. We can cure mouse breast cancers, but that
can't always translate to the clinic."
.
By adding human breast cells to immune-deficient mice before puberty,
Kuperwasser has been able to watch normal breast development and generate
human cancers rather than mouse ones in her lab animals. Now, she is
working to implant particular patients' cancer into mice to see if they can
test drugs and cures on it without harming the person.
.
In Nebraska, William Beschorner is working to create a human immune system
and humanized liver in a pig. Eventually the biologist hopes to replicate a
particular patient's immune system and then transplant the pig's organs
back into the person, where they would appear familiar to the immune
system, and therefore wouldn't be rejected.
.
Even scientists pause, though, when experiments creep from basic organs to
the seat of human consciousness - the brain - or when stem cells,
controversial in their own right, are added to the mix.
.
Four years ago, Irving Weissman, a stem-cell biologist at Stanford, created
a mouse with human neurons in its brain, hoping that the living model would
provide insights into diseases like Parkinson's and Alzheimer's.
.
The human neurons made up about 1 percent of the mouse brain and were
alive, but it was unclear whether they were functioning. He suggested
another project: creating a mouse with 100 percent human nerve cells in its
brain.
.
He asked an informal committee to review his proposal, and the group
recently drew up guidelines for doing the experiment responsibly.
.
Hank Greely, head of that committee, described one clear limit. "If you see
anything that is not unequivocally mouse behavior, you stop the
experiment," he said.
.
Scientists agree that human brain cells growing in a mouse are unlikely to
humanize a mouse because of the vast differences in skull size and brain
architecture. But in a closely related animal, the threat of an animal
floating somewhere between human and animal becomes more serious.
.
"What is essentially human is really debased," Alfonso Gomez-Lobo, a member
of the Council on Bioethics, said in March. "I often imagine what it would
be like to wake up one day only to realize that I have the body of a
chimpanzee."
.
A chimera is an animal with its own cells and that of another animal
growing side by side in its body. Scientists used to call such animals
"tetraparental," meaning they had four parents - their own, and the parents
of the other cells living in their bodies.
.
The "geep" is an example of a true chimera. Scientists at the University of
California at Davis fused together sheep and goat embryos. In the
offspring, every organ, including the sex organs, were made up of both goat
and sheep cells, which meant that one geep could produce both goat and
sheep sperm.
.
Many other kinds of chimeras are made by adding human cells to animals that
have been genetically altered to have no immune system. Without the immune
system, which would attack foreign cells, scientists can grow human brain
cells or breast cells in another animal, often a mouse.
.
Chimeras surround us, and not just in the lab. Cardiac surgery patients who
receive pig valves to repair their hearts are chimeras. Transplant
recipients, who have another person's bone marrow, kidney, or heart
thumping in their chest, are a kind of chimera, with the cells of another
being living alongside their own.
.
.
See more of the world that matters - click here for home delivery of the
International Herald Tribune.
.

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