MAD SCIENCE
New Federal Guidelines Will Allow
Creation of Human-Animals Chimeras

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Credit: Urbanlegends
The strange, half-human creatures in the image above are neither real nor a hoax; they are elements of a sculpture by Australian artist Patricia Piccinini entitled "The Young Family," which, in turn, is part of a larger installation called "We Are Family," described by Jane Silversmith of the Australian Council for the Arts as an exploration of "the changing relationship between what is considered natural and what is considered artificial."
THIS IS A PHOTOGRAPH OF AN ART SCULPTURE - IT IS NOT REAL

Stem Cell Research Guide Permits Creation of Human-Animal Chimeras
From Environment News Service <www.ens-newswire.com>

WASHINGTON, DC, 
April 27, 2005 (ENS)

A new set of guidelines for human embryonic stem cell research issued Monday by the National Academies of Sciences would permit the creation of human-animal hybrids, but would not allow them to breed. The guidelines permit the introduction of human embryonic stem cells into nonhuman mammals, "under circumstances where no other experiment can provide the information needed."

Private research on human embryonic stem cells should be guided by responsible practices, and oversight committees should be established to ensure these practices are followed, say the National Academies' National Research Council and Institute of Medicine in the new set of guidelines.

The National Academies, a self-selected group of scientists that advises the federal government, has published the non-binding set of guidelines in the hope that they will be adopted by all research organizations. The guidelines recommend ethical practices for handling human embryonic stem cell lines.

Stem cells usually are taken after three to five days from a blastocyst - a mass of about 150 cells that occurs at an early stage of human development before implantation in the uterus.

Under the guidelines, research organizations would establish Embryonic Stem Cell Research Oversight (ESCRO) committees, but not as replacements for other research compliance bodies such as institutional review boards already required by federal regulations.

In addition to experts in biology and stem cell research, ESCRO committees should include legal and ethical experts as well as representatives of the public, the guidelines recommend.

"Heightened oversight is essential to assure the public that stem cell research is being carried out in an ethical manner," said committee co-chair Dr. Jonathan Moreno, professor of biomedical ethics and director of the Center for Biomedical Ethics at the University of Virginia-Charlottesville. In addition to his position at the Center for Biomedical Ethics, Dr.

Jonathan Moreno is president of the American Society for Bioethics and Humanities, and is a member of the Council on Accreditation of the Association of Human Research Protection Programs. He is also a member of the Board on Health Sciences Policy of the Institute of Medicine. (Photo courtesy U. Virginia) "The oversight we call for will, in many instances, set a higher standard than required by existing laws or regulations," said Moreno. "And while we were hesitant to recommend another bureaucratic oversight entity, the burden in this case is justified, given the novel and controversial nature of embryonic stem cell research."

Because there is widespread agreement in the international scientific community about the potential value of human embryonic stem cell research, the volume of this research has expanded since 1998, despite restrictions in the United States, said the committee.

"A standard set of requirements for deriving, storing, distributing, and using embryonic stem cell lines - one to which the entire U.S. scientific community adheres - is the best way for this research to move forward," said the guidelines committee co-chair Dr. Richard Hynes, a professor of Cancer Research and a Howard Hughes Medical Institute investigator at the Massachusetts Institute of Technology.

Dr. Richard Hynes is a cancer research specialist, a fellow of the Royal Society of London, the American Academy of Arts and Sciences, the American Association for the Advancement of Science, and a member of the National Academy of Sciences and the Institute of Medicine. (Photo courtesy MIT) Federal funding for stem cell research is restricted to research involving existing stem cell lines, but privately funded research continues. Despite the public perception that this research is unregulated, in fact it is governed by federal regulations that protect human donors, set animal care standards, and mandate safety reviews of lab work that involves genetic alteration of stem cell lines.

Still, the guidelines say, ESCRO committees should review proposals for research that takes stem cells from excess blastocysts at in vitro fertilization clinics or from blastocysts created expressly for stem cell research.

They also should review any proposed use of blastocysts created by nuclear transfer, often referred to as therapeutic cloning.

Nuclear transfer, the technique currently used in the cloning of adult animals, is the transfer of a nucleus from one cell to another, creating a new cell with a different nucleus. All cloning experiments of adult mammals have used a variation of nuclear transfer.

"Nuclear transfer must not be used for reproductive cloning," the guidelines committee warned, reiterating a recommendation from a previous National Academies report.

The guidelines open a path for experiments that create animals that contain some introduced human embyronic stem cells.

These hybrid part human, part animal creatures, called chimeras, would be "valuable in understanding the etiology and progression of human disease and in testing new drugs, and will be necessary in preclinical testing of human embryonic stem cells and their derivatives," the guidelines committee said. Chimeras might also be used to grow organs, such as livers, to transplant into humans.

Today, faulty human heart valves are sometimes replaced with valves taken from cows and pigs, making the recipient a human-animal chimera, and the procedure is considered acceptable.

But new ethical issues are raised by the mixing of human embryonic stem cells with embryonic animals to create new species.

Human embryonic stem cells should be introduced into nonhuman mammals "only under circumstances where no other experiment can provide the information needed," the guidelines say.

The danger is experiments in which there is a possibility that human cells could contribute in a "major organized way" to the brain of an animal. These experiments "require strong scientific justification," the committee warned. Microscopic view of a human blastocyst. Once implanted in the uterus, it is ready to become a human being. (Photo courtesy RHS) The guidelines say no animal embryonic stem cells should be transplanted into a human blastocyst, and approval by an ESCRO committee should be secured before any human embryonic stem cells are put into an animal.

"No human embryonic stem cells should be put into nonhuman primate blastocysts," the guidelines say, and "no animal into which human embryonic stem cells have been introduced should be allowed to breed," the committee warned.

In its new guidelines, the National Academies committee also addressed ethical issues concerning stem cell donors.

Donor consent must be obtained before a blastocyst is used to generate stem cells, and donors should be informed that they have the right to withdraw their consent at any point before a stem cell line is derived, the guidelines say.

Practices for obtaining consent should be scrutinized for potential conflict of interests. For example, researchers proposing to derive stem cells should not influence decisions about creating embryos for fertility treatment.

Consent forms should inform the donor that embryos will be destroyed in the process of deriving stem cells and that the resulting cell lines may be kept for many years. The forms also should state that cells might be manipulated genetically or transplanted into animals for preclinical testing.

The guidelines also emphasize that no payments should be made to donors. Blastocysts left over at in vitro fertilization clinics may not be donated for research without consent, and researchers should not ask fertility doctors to create more embryos than necessary for reproductive treatments. According to the guidelines, donors should be told that information about them, including their names, may be retained and could become known by those who derive or work with resulting stem cell lines, but that donors' identities will be encoded and not readily ascertainable. They should be asked whether they want to receive information obtained through studies of the cell lines.

Donors also need to be told that although research involving their stem cells may have commercial potential, donors will not share in any financial benefit, the guidelines say.

Proposals to generate additional human embryonic stem cell lines by any means should be reviewed and approved by an ESCRO committee, the guidelines say.

Human embryos used for research should not be grown in culture for longer than 14 days, or until the point when the body axis and central nervous system - called the primitive streak - begin to form, according to the guidelines.

In addition to the oversight of an ESCRO committee, an institutional review board (IRB) should review the donation of somatic cells to be used in creating a blastocyst via nuclear transfer, the guidelines say.

Research on existing anonymous or coded embryonic stem cell lines does not require IRB review unless the cells are going to be transplanted into patients or the donor's identity is likely to become known by researchers. Researchers working on previously derived stem cell lines should provide documentation on the origin of the cell lines, including evidence that the procurement process was reviewed by an institutional review board, to newly formed ESCRO committees, the guidelines committee said.

The ESCRO committee should maintain a registry of stem cell lines banked at an institution, the guidelines recommend. The registry should include a proof of informed consent, a medical history of the donors, and a characterization of any genetic markers on the cell lines. Repositories of stem cell lines also need a secure coding system to protect the identity of donors.

The committee urged the formation of a national independent body to periodically review whether the guidelines need to be updated in light of unforeseen advances in stem cell science and evolving public attitudes.

The National Academies developed the guidelines on behalf of the scientific community and without government involvement. Although compliance is voluntary, the committee called on private funders, professional societies, journals, research institutions, and others involved in embryonic stem cell studies, to require adherence to the guidelines.

The full report is online at: http://books.nap.edu/catalog/11278.html.
Click "Read it online Free."

For details on members of the guidelines committee, visit: http://www4.nas.edu/webcr.nsf/CommitteeDisplay/BLSX-K-04-03-B?OpenDocument For the basics of stem cell research, visit the National Institutes of
Health at: http://stemcells.nih.gov/info/scireport/appendixA.asp

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SOURCE: Organic Consumers Association


The National Institutes of Health Resource or Stem Cell Research
Pig-human Chimeras Contain Cell Surprise
13 January 2004



Pigs grown from fetuses into which human stem cells were injected have surprised scientists by having cells in which the DNA from the two species is mixed at the most intimate level.

It is the first time such fused cells have been seen in living creatures. The discovery could have serious implications for xenotransplantation – the use of animal tissue and organs in humans – and even the origin of diseases such as HIV.

The adult pigs that had received human stem cells as fetuses were found to have pig cells, human cells and the hybrid cells in their blood and organs.

“What we found was completely unexpected. We found that the human and pig cells had totally fused in the animals’ bodies,” said Jeffrey Platt, director of the Mayo Clinic Transplantation Biology Program.


Nuclear mix

The hybrid cells had both human and pig surface markers. But, most surprisingly, the hybrid cell nuclei were found to have chromosomal DNA that contained both human and pig genes. The researchers found that about 60 per cent of the animals’ non-pig cells were hybrids, with the remainder being fully human.


Importantly, the team also found that porcine endogenous retrovirus (PERV), which is present in almost all pigs, was also present in the hybrid cells. Previous laboratory work has shown that while PERVs in pig cells cannot infect human cells, those in hybrid cells can. The discovery therefore suggests a serious potential problem for xenotransplantation.

The work also suggests a possible route of infection for other viruses that have crossed from animals to humans.

“Perhaps HIV managed to jump from primates to humans through infected blood from a bite, which allowed the stem cells from the two species to fuse,” Platt told New Scientist. “When the genes recombined, perhaps the virus was reawakened.”

Body plan

Chimeric animals containing human cells have been created before. New Scientist reported in December on the growing of human liver cells in sheep. The work, by Esmail Zanjani and colleagues at the University of Nevada, Reno, aims to provide human tissue for transplantation into people.


“The new work is certainly very interesting,” Zanjani told New Scientist. “But the question is how widespread and how many of these hybrid cells were found? If they are very rare – and we haven’t found any in our experiments – then I don’t think it is that important.”

Zanjani says it is “possible” that HIV had spread to humans through a type of human-primate cell fusion, but adds that much more research needs to be done.

In Platt’s experiments, the human stem cells were injected into the pig fetuses about a third of the way through gestation. In Zanjani’s work, the cells were injected about halfway through.

The injections must be given after the body plan of the fetus has developed, but before the immune system is active. The former ensures the animals look like normal pigs and sheep. The latter prevents the human stem cells being rejected.

SOURCE: New Scientist - Journal reference: Federation of American Societies for Experimental Biology Journal (DOI: 1096/fj.03-00962fje)
Vacanti Mouse



The Vacanti mouse

The Vacanti mouse was a laboratory mouse that had what looked like a human ear grown on its back. The "ear" was actually an ear-shaped cartilage structure grown by seeding cow cartilage cells into a biodegradable ear-shaped mold and then implanted under the skin of the mouse, then the cartilage naturally grew by itself.


The earmouse, as it became known, was created by Charles Vacanti and colleagues in the Department of Anesthesiology (University of Massachusetts Medical School) and their results were published in 1997. The mouse itself is called a nude mouse, a commonly used strain of immunocompromised mouse, preventing a transplant rejection.


The photo of the mouse was passed around the internet, mainly via email, sometimes with little to no text accompanying it leading many people to speculate whether the photo was real. In the late 1990s, the picture prompted a wave of protests against genetic engineering—although in this specific experiment no genetic manipulation was performed. Even the strain of mouse used is not genetically modified; it is the result of a spontaneous natural genetic mutation.


Bioengineering Body Parts - EuroStemCell



Researchers have used the method to grow organs within the mouse
but also form external body parts such as ears and noses - Source


Reference: Cao, Y.; Vacanti, J. P.; Paige, K. T.; Upton, J.; Vacanti, C. A. (1997). "Transplantation of chondrocytes utilizing a polymer-cell construct to produce tissue-engineered cartilage in the shape of a human ear". Plastic and reconstructive surgery

Source: Wikipedia


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