Science, 2013. From the Center for Bioetichs, University of Minnesota:
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| A human - nude mouse chimera engineered to grow a human outer ear for potential transplantation |
Chimeras are animals composed of cells that originate from two (or more) different
species.
In the research lab, chimeras are created by introducing cells from one species into the developing embryo or fetus of another.
(The name chimera comes from Greek mythology and describes a creature with the head of a lion, the body of a goat, and the tail of a serpent).
In the research lab, chimeras are created by introducing cells from one species into the developing embryo or fetus of another.
(The name chimera comes from Greek mythology and describes a creature with the head of a lion, the body of a goat, and the tail of a serpent).
The first chimeras helped scientists understand questions about
developmental biology. A sheep-goat chimera, created in 1984, had the head of a
goat and the woolly coat of a sheep. i
Chicken-quail chimeras have also been successfully developed. ii, iii
Sheep-Goat Chimera
Courtesy of Dr. Gary B. Anderson -University of California, Davis
Now, researchers are developing human-animal chimeras to study disease processes,
test new drugs, and develop organs for future transplant patients. The chimeras
are produced by introducing human stem cells into developing animal embryos.
The following are some of the major projects utilizing humananimal chimeras
underway in the U.S and internationally:
Sheep-to-humans organ transplant project:
At the University of Nevada at Reno, researchers have added human stem
cells to sheep fetuses to create chimeras that they hope will someday serve as
a reliable source of organs for liver transplant patients. Some sheep now have livers with up to 80% human cells (Yellow
emphasis’ mine) that produce the compounds normally made by human livers.
(The cells are not all in distinct liver lobes but spread throughout the
tissue. The sheep also have human cells in
their hearts and brains). iv, v
Pigs-to-humans organ transplant project:
Mayo Clinic researchers in Minnesota are studying how specially-bred pigs
could be used as sources of organs for human transplant patients. Part of their
work involves determining the risk of transmitting pig diseases to humans who
would receive the organs.vi They have developed a line of pigs that have pig blood cells, human blood cells, and a new kind of blood cells with characteristics of both humans and pigs.vii An unexpected
development in this project may help researchers formulate an explanation for
the appearance of the AIDS virus in humans.
Mice with human brain cells for the study of neurologic diseases and mice with human immune systems for AIDS drug testing:
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| Chimeric mouse |
human. The researchers want to increase that percentage to 100% human brains in mice bodies in
order to better understand the development of Parkinson’s, Alzheimer’s, and Lou
Gehrig’s diseases. Weissman is director of the Stanford Institute of
Cancer/Stem Cell Biology and Medicine, which developed a line of mice with
immune systems that were almost all human. They were able to use the mice to
test the response of the AIDS virus to new drugs. Viii
(All pics except the Sheep-Goat Chimera are inserted by me, and not in the original article)
In 2003, for the first time, researchers at the Shanghai Second Medical
University developed embryos that contained both human and animal DNA. Working with rabbit embryos,
the researchers’ goal was to develop a new source of embryonic stems cells for medical
research. The resulting embryos contained mostly human DNA (derived from skin cells)
and a small amount of rabbit DNA. The researchers harvested the stem cells
after a few days, which destroyed the embryos. ix, x
Hybrids and chimeras are biologically different. A cell
from a chimera contains the genetic material of either one parent species or
the other. While each cell from a hybrid animal, such as a mule, contains
genetic material from both parent species.
 |
| Vervet Monkey with baby from St Kitts |
Monkey-human chimeras for the study of Parkinson’s disease:
At St. Kitts Biomedical Foundation in the Caribbean, scientists are transplanting immature human brain cells deep into the brains of vervet monkeys. Their goal is to
develop a treatment for Parkinson’s disease. They inject immature human brain
cells into the dopamine-producing area of the monkeys’ brains to see whether
the cells can grow and increase dopamine production. (The monkeys are taken
from the overabundant wild population on the island of St. Kitts.) xi
In April, 2005, the National Academies (which advises the federal
government and the public on scientific and medical issues) released
recommended guidelines for embryonic stem cell research, including research on
chimeras. While the guidelines are not legally binding, they are likely to have
a significant impact on research in the U.S. because funding agencies and
professional societies (through which scientists publish their work) are likely
to abide by the guidelines. Xii The complete Guidelines for Human Embryonic Stem Cell
Research are available online at: http://books.nap.edu/catalog/11278.html?onpi_newsdoc04262005.
You can read an announcement and summary of the Guidelines online at http://www4.nationalacademies.org/news.nsf/isbn/0309096537?OpenDocument.
Regulations and recommendations on chimera research generally lag behind ongoing projects and vary across international boundaries. For example, while it is ongoing in other countries, Canada bans research on human-animal chimeras. xiii,xiv,xv
Ethical Issues
Because human-animal chimeras contain human cells—or even tissues or organs
that are primarily human—ethical concerns surround the question of just what or
who chimeras are. Because they were created under laboratory conditions for research purposes, are chimeras lab animals? Or, will chimeras eventually be developed that are too human to be considered otherwise?
Ethical issues of primary concern for bioethicists, researchers, animal
rights activists and others interested in chimeras can be divided into two
broad categories: a) complete opposition to research of this kind and b)
concerns about particular research methods to be used and outcomes that may
ensue.
OPPOSITION TO CHIMERA RESEARCH
There are those who are convinced that human-animal chimera research should
not be performed at all.
The following are their reasons for opposing all such research:
1. Because it involves research on human embryos.
Even if the embryos are not destroyed, the research combines human and
animal genetic material with unknown and perhaps unknowable results.
Richard Doerflinger, Deputy Director of the Secretariat for Pro-Life
Activities at the U.S. Conference of Catholic Bishops, told the The Boston
Globe regarding human-animal chimeras: “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.” Xvi
William Cheshire, a Mayo Clinic associate professor of neurology in
Jacksonville, Florida, and a member of Christian Medical and Dental
Associations expressed his concerns in National Geographic: “Research projects that create human-animal chimeras risk disturbing fragile ecosystems, endanger health, and affront species integrity. We must be cautious not to violate the integrity of humanity or of animal life over which we have a stewardship responsibility.” Xvii
2. Because it disregards the welfare of animals and animal species involved:
The Humane Society of the United States (online at http://www.hsus.org)
communicates its opposition to all chimera research in the position statement,
“Genetic Engineering of Animals”:
"The creation of chimeras (organisms composed of cells from
individuals of two or more species) involves serious ethical concerns that
should be taken into consideration. Creation of chimeras contributes to the
debasement of animals, as
humankind manipulates nature by combining cells of an array of organisms.
As far as current application of chimera research goes, The HSUS is concerned
about pain and distress
that the animals may undergo and calls on the research community to carefully
address the welfare of these animals and to minimize any pain and distress
resulting from this type of animal use.”
3. More specifically, because it disregards the welfare of higher primates involved.
Higher primates, especially chimpanzees, are closely related to humans and
thus may be seen as ideal research subjects in chimera experiments:
Jeremy Rifkin, noted biotechnology activist, opposes chimera research
because it crosses species boundaries. In his view, animals have the right to exist without being tampered with, especially because he finds that other research methods
could lead to the same medical advances. xviii
(Rifkin is the author of The Biotech Century, a best-seller about
the biotech revolution.).
Together with Dr. Stuart A. Newman, a professor of cell biology and anatomy
at New York Medical College, Rifkin applied for a patent on chimera research
techniques, including ones that would combine human and monkey or ape cells
into a single humanzee embryo. In another, human and mouse cells would
form a humouse embryo. Their goal was to challenge biotechnology efforts
that would
produce these chimeras.
Rifkin and Newman were pleased when the U.S. Patent and Trademark Office
(PTO) turned down their application. “By applying for a patent on the humanzee,
humouse, and other part-human embryos and animals, we hoped to alert the
general public to the need for regulations and restrictions in this area,”
Newman said in an interview with Science and Theology News.
While the PTO has been issuing patents on living organisms since a 1980 Supreme Court Decision, the human chimera application was rejected in 2005 primarily because the PTO has no way to determine how “human” an organism can be before it is not patentable by the 13th Amendment's prohibition of slavery, according to Newman. xix
While the PTO has been issuing patents on living organisms since a 1980 Supreme Court Decision, the human chimera application was rejected in 2005 primarily because the PTO has no way to determine how “human” an organism can be before it is not patentable by the 13th Amendment's prohibition of slavery, according to Newman. xix
It is still legal to produce these chimeras without a patent, but may not
be financially feasible for a biotech company to develop products based on
techniques that are not protected by a patent.
—The Humanzee—
“Chimps share 98% of the human genome, and a fully mature
chimp has the equivalent mental abilities and consciousness of a four-year-old
human. Fusing a human and chimpanzee embryo—which researchers say is
feasible—could produce a creature so human that questions regarding its moral
and legal status would throw 4,000 years of ethics into chaos. Would such a
creature enjoy human rights? Would it have to pass some kind of ‘humanness'
test to win its freedom? Would it be forced into doing menial labour or be used
to perform dangerous activities?”
—Jeremy Rifkin “Are you a man or a mouse?” March 15, 2005
The Guardian. Available online at
Concerns About Chimera Research
While not completely opposed to the research, some experts and interested
members of the public raise concerns about techniques and possible outcomes if
initial problems are ignored. Their major concerns are the following:
1. Could chimeras have human brains?
If a chimera's brain is comprised of mostly human neurons with an
appropriate structure, experts are questioning whether a human brain—and mind—could develop within an animal or humananimal body. The National Academies Guidelines for Human
Embryonic Stem Cell Research cautions that experiments in which there is a
possibility that human cells could contribute in a "major organized
way" to the brain of an animal require strong scientific justification. Xx
Projects such as the following give rise to questions regarding chimeras
with human brains:
- Researchers at Stanford University are injecting human neural stem cells into mouse fetuses to study development of neurologic diseases (see project description in Definition section, above). Initial results were mice with brains that were about 1% human, but researchers could increase that percentage to 100% human brains in the laboratory mice.
They anticipate that the
structures of the brain, and certainly the size, would still be mouse-like even
though the neurons of the brain would be 100% human. Responding to concerns
that the experiment could result in brains that were more human than mouse, Stanford University's ethics committee has approved the research on the condition that if the mice developed indicators of human intelligence, such as improved memory or problem-solving, it would be time to stop the project.
- At St. Kitts Biomedical Foundation in the Caribbean, scientists are transplanting immature human brain cells into the brains of vervet monkeys, generating a human-monkey chimera. xxi
This
kind of research could create
An expert panel was convened by John Hopkins University in 2005 to study
the potential for just such human-primate experiments to significantly change
the cognitive and emotional capacities of primates—in effect, to humanize them.
The Working Group on Interspecific Chimeric Brains consisted of
primatologists and other scientists, ethicists, and lawyers. They concluded
that any shift in brain capacities toward the human end of the spectrum would
be more likely to occur if human brain cells were introduced early in the
development of the brains of great apes. Experiments in which small numbers of
human cells were grafted into healthy adult brains of the most distantly related
monkey species were the least likely to raise concerns. Xxii
—The Working Group on Interspecific Chimeric Brains—
"Many of us expected that, once we'd pooled our expertise,
we'd be able to say why human cells would not produce significant changes in
non-human brains.
But the cell biologists and neurologists couldn't specify
limits on what implanted human cells might do, and the primatologists explained
that gaps in our knowledge of normal non-human primate abilities make it difficult
to detect changes. And there's no philosophical consensus on the moral
significance of changes in abilities if we could detect them."
— Mark Greene, Ph.D., professor at the University of Delaware
and Working Group member. In: Johns Hopkins Medicine - Office of Corporate
Communications. Experts discuss use of human stem cells in ape and monkey
brains. July 14, 2005. Available online at http://www.hopkinsmedicine.org/Press_releases/2005/07_14_05.html
2. What is the potential for humanized chimeras?
If human embryonic stem cells were to be injected into an animal embryo
very early in it development, the human cells might spread through every organ system in the animal embryo.
Conversely, animal embryonic stem cells could do the same thing when
introduced into an early stage human embryo. The results of such techniques
could be a humanized animal (or animalized human), with physical features and behaviors that are distinctly human.
Considering this possible outcome, the National Academies' Guidelines
for Human Embryonic Stem Cell Research say that no animal embryonic stem
cells should be transplanted into a human blastocyst (early embryo). In
addition, approval by an Embryonic Stem Cell Research Oversight committee
should be secured before any human embryonic stem cells are put into an animal.
3. Could chimeras mate and produce human offspring?
If a female chimera with human ova (egg cells) mated with a male chimera with human sperm cells, scientists believe that it would be possible for a human fetus to be the result. Potentially, a chimera could give birth to a human. To address this issue, the National Academies Guidelines for Human Embryonic Stem Cell Research states: “No animal into which human embryonic stem cells have been introduced at any stage of development should be allowed to breed.”
If a female chimera with human ova (egg cells) mated with a male chimera with human sperm cells, scientists believe that it would be possible for a human fetus to be the result. Potentially, a chimera could give birth to a human. To address this issue, the National Academies Guidelines for Human Embryonic Stem Cell Research states: “No animal into which human embryonic stem cells have been introduced at any stage of development should be allowed to breed.”
4. How will human-primate chimeras be treated?
While already being used a t St. Kitts Biomedical Foundation (mentioned
above), primates are likely to be the animal of choice in some human-animal
chimera projects because of their close genetic similarities (especially in
chimpanzees) to humans. While the guidelines state that “no human embryonic
stem cells should be put into nonhuman primate blastocysts [early embryos],” they
do not exclude chimera research at a later stage of development. While some
oppose this research outright, others are assuming that human-primate chimeras
will become more widespread in research and question whether they will be
treated as humans or animals.
A.M. Chakrabarty, of the University of Illinois College of Medicine, asks:
"What is a human?
This is not a question of the moral dilemma to define a human but is a legal requirement as to how much human material a chimpanzee must have before it is declared a part human and therefore falls under the protection of the Thirteenth Amendment…
We must move beyond moral and philosophical discussions of hybrid human-nonhuman animals and be prepared to tackle the difficult legal questions that will attend not-so-distant attempts at creating such hybrids say for organ harvesting, for use as a subhuman species to perform hard manual labors, or simply for curiosity’s sake.” xxiii
SE ALSO >>> Human "enhancement"?
Links
The National Academies issued a press release summarizing the recommendations
for stem cell research —including chimera research—made in their publication,
Guidelines for Human Embryonic Stem Cell Research . The April 2005 press release
is online at http://www4.nationalacademies.org/news.nsf/isbn/0309096537?OpenDocument
The complete Guidelines are available online at:
Findings of the Working Group on Interspecific Chimeric Brains are
announced by Johns Hopkins Medicine in this press release, “Experts discuss use
of human stem cells in ape and monkey brains,” dated July 14, 2005 and
available online at: http://www.hopkinsmedicine.org/Press_releases/2005/07_14_05.html
For full results from the Working Group on Interspecific Chimeric Brains,
see:
Mark Green et al. Moral Issues of Primate Neural Grafting Science 309
(5733): 385-386. Available online with subscription at:
For Canada 's regulations on chimera research, see:
Department of Justice—Canada. Assisted Human Reproduction Act, Prohibited
Activities Section 5(1) (i). August 31, 2004. Available online at:
Suggested Reading
“Chimp Genetic Code Opens Human Frontiers” Boyle, Alan. MSNBC September 1, 2005. http://www.msnbc.msn.com/id/9136200/
“Animal-Human Hybrids Spark Controversy”
Mott, Maryann. National Geographic News January 25, 2005. http://news.nationalgeographic.com/news/2005/01/0125_050125_chimeras.html
“Are You a Man or a Mouse?”
Jeremy Rifkin. The Guardian March 15, 2005
“Of Mice, Men and In-Between: Scientists Debate Blending of Human, Animal
Forms” Weiss, Rick. Washington Post November 20, 2004.
“From Myth to Reality”
Johnson, Carolyn. The Boston Globe April 19, 2005.
“The Other Stem-Cell Debate”
Shreeve, Jamie. The New York Times April 10, 2005.
“Science Journal: Chimeras exist, what if some turn out too human?”
Begley, Sharon. Pittsburgh Post-Gazette May 06, 2005 .
Reprinted from The Wall Street Journal.
“U.S. Denies Patent for a Too-Human Hybrid”
Weiss, Rick. Washington Post February 13, 2005
End Notes
i. Bowen, RA. Mosaicism and Chimerism.
Colorado State University Hypertexts for Biomedical Sciences: General and Medical
Genetics. Available online at http://arbl.cvmbs.colostate.edu/hbooks/genetics/medgen/chromo/mosaics.html
Accessed 9/09/05.
ii. Anonymous. Chimera (animal).
Wikipedia, the Free Encyclopedia. Available online at http://en.wikipedia.org/wiki/Chimera_(animal)
Accessed 9/09/05.
iii. Begley S. Chimeras exist, what if some turn out too human?
Pittsburgh Post-Gazette May 06, 2005. Available online at
Reprinted from The Wall Street Journal.
Accessed 9/09/05.
iv. Weiss R. Of Mice, Men and In-Between: Scientists Debate Blending of Human,
Animal Forms.
Washington Post November 20, 2004. Online at http://www.washingtonpost.com/wp-dyn/articles/A63731-2004Nov19.html
Accessed 9/09/05.
v. Associated Press. Scientists create animals that are part-human: Stem cell
experiments leading to genetic mixing of species.
MSNBC: Health. April 29, 2005. Online at http://msnbc.msn.com/id/7681252/
Accessed 9/09/05.
vi. Nellis B. Mayo Genomics Researchers Observe Genetic Fusion of Human,
Animal Cells—May Help Explain Origin of AIDS.
News From Mayo Clinic. January 08, 2004. Available online at
Accessed 9/09/05.
vii. Weiss R. Of Mice, Men and In-Between: Scientists Debate Blending of Human,
Animal Forms.
Washington Post November 20, 2004. Online at http://www.washingtonpost.com/wp-dyn/articles/A63731-2004Nov19.html
Accessed 9/09/05.
viii. Weiss R. Of Mice, Men and In-Between: Scientists Debate Blending of Human,
Animal Forms.
Washington Post November 20, 2004. Online at http://www.washingtonpost.com/wp-dyn/articles/A63731-2004Nov19.html
Accessed 9/09/05.
ix. Mott M. Animal-Human Hybrids Spark Controversy.
National Geographic New. January 25, 2005.
Accessed 9/09/05.
x. Weiss R. Cloning Yields Human-Rabbit Hybrid Embryo.
Washington Post. August 14,
2003.
Reprinted and available online at
Accessed 9/09/05.
xi. Shreeve J. The Other Stem-Cell Debate.
The New York Times April 10, 2005. Available online at
Accessed 9/09/05.
xii. Krieger L. Experts offer stem-cell guides.
The Mercury News April 27,2005. Available online at
Accessed 9/09/05.
xiii. Lamb GM. Guidelines proposed for stem cell research.
The Christian Science Monitor April 27, 2005. Available online at
Accessed 9/09/05.
xiv. Mott M. Animal-Human Hybrids Spark Controversy.
National Geographic News. January 25, 2005.
Online at
Accessed 9/09/05.
xv. Johnson CY. From myth to reality.
The Boston Globe April 19, 2005. Online at
Accessed 9/09/05.
xvi. Mott M. Animal-Human Hybrids Spark Controversy.
National Geographic New. January 25, 2005.
Accessed 9/09/05.
xvii. Mott M. Animal-Human Hybrids Spark Controversy.
National Geographic New. January 25, 2005.
Accessed 9/09/05.
xviii. Donnelly M. The peril and promise of mix-and-match biotech: Is a
proliferation of human-animal mixtures good for either?
Science and Theology News May 23, 2005. Available online at
Accessed 9/09/05.
xix. The National Academies Office of News and Public Information. Guidelines
Released for Embryonic Stem Cell Research. April 26, 2005. Available online at http://www4.nationalacademies.org/news.nsf/isbn/0309096537?OpenDocument
Accessed 9/09/05.
xx. Shreeve J. The Other Stem-Cell Debate.
The New York Times April 10, 2005. Available online from
the Center for Genetics and Society at
Accessed 9/09/05.
xxi. Johns Hopkins Medicine - Office of Corporate Communications. Experts
discuss use of human stem cells in ape and monkey brains. July 14, 2005.
Available online at
Accessed 9/09/05.
xxii. Chakrabarty AM. Crossing Species Boundaries and Making Human-Nonhuman
Hybrids: Moral and Legal Ramifications
The American Journal of Bioethics Summer 2003 3(3):14-15.
Accessed 9/09/05.
http://www.ahc.umn.edu/bioethics/prod/groups/ahc/@pub/@ahc/documents/asset/ahc_75693.pdf
http://www.ahc.umn.edu/bioethics/prod/groups/ahc/@pub/@ahc/documents/asset/ahc_75693.pdf
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