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Taking science to extremes :

Animal or human?

Chimeras are mythical Greek creatures with a lion's head, a goat's body and a serpent's tail. In H.G. Wells' 1896 novel, Dr. Moreau created creatures that were part human and part animal. But modern day scientists seem to be aspiring to follow in Wells' fictional scientist's footsteps in attempting to bring to life mythical creatures; but partially human this time.

by Rikaza Hassan

Chimeras as defined by contemporary biologists are the creatures born as the successful products of experiments where human stem cells are injected into animal foetuses. Stem cells discovered in 1998 and harvested from five-day old human embryos not only multiply prolifically but unlike adult cells also have the potential to turn into any of the cell types (about 200) of the human body.

Research Toll

Stem cell research has received a lot of flak over the years and in the meantime garnered much support, notably from famous personalities who stood to benefit, such as the late Christopher Reeves. Scientists initially envisioned experiments that would reveal information about embryonic growth and hoped to grow replacement tissues for patients by their cultivation.

However as the materialisation of such applications are still years away, stem cells are now being used as an important tool for other research.



Scientists have been given the opportunity to observe the maturing of burgeoning human cells and their interactions as they grow into organs not in Petri dishes in the frigid isolation of laboratories but within the living, breathing bodies of real creatures. Such research is not just bringing deep seated secrets of human biology out into our grasp but also pointing the way towards novel and more effective medical treatments. Chimeras are giving us the chance to test new drugs as well as experiment on possible new avenues of cure without the use of humans as test subjects.

The potential of chimeras as research tools was recognised almost a decade ago when Evan Balaban, now at McGill University, Montreal, transplanted into the developing brains of chickens small sections of developing quails' brain. His groundbreaking series of experiments produced chickens that exhibited the head bobs and vocal trills exclusive to quails. It proved that the transplanted sections of the brain contained the neural circuitry requisite for quail calls and that it was possible to transfer complex behaviour across species.

Present day Chimeras

The first successful human-animal chimeras were created in 2003 at China's Shanghai Second Medical University. Chinese scientists were able to effectively fuse human cells with rabbit eggs. The embryos were allowed to grow for several days in Petri dishes before they were destroyed in order to gather their stem cells.

Minnesota Mayo Clinic scientist Jeffrey L. Platt injected human-blood-forming stem cells into pig foetuses in an on-going set of experiments to create human-pig chimeras.

Not only do the hybrid pigs have both human and pig blood flowing through their blood vessels, but some of the human and pig blood cells have merged creating further hybrids of the blood cells themselves. The significance is that scientists now know that human and pig cells can fuse. The risk of pig viruses getting into patients' cells is therefore realised when taking into account transplantation of modified pig organs into human beings as the virus can gain admission during fusion of the cells.

The famous gambling town of Reno, Nevada is now garnering fame for breeding sheep with partially human livers, hearts, brains and other organs.

The sheep are one of the most advanced forms of human-animal hybrids created under by a team led by Dr. Esmail Zanjani, Chairman of Animal Biotechnology at the University of Nevada at Reno (UNR). Human cells are injected into the requisite organ of the growing foetus. The pregnant sheep is then euthanised and the effects of the human cells are examined. As a student of UNR involved in the research commented complacently, "they're mice on a larger scale." The aim of the UNR research team is to utilise the sheep to manufacture human organs and tissues as well as create radical lab animals for more effectual testing of experimental drugs.

The most promising of these test animals are the sheep that are growing partly human livers. A majority of the adult sheep used in the experiment contain about ten per cent of liver cells that are human though a few possess as much as forty per cent. The prospect of transplanting partial livers into people whose own are failing is raised by the research since the human liver is able to regenerate. However Dr. Zanjani must eliminate the risk of animal diseases being transferred to the recipients as well as figure out a competent means of separating the human and sheep cells; the human cells don't stick together but are spread out making it a complicated task.

Says Zanjani, defending his research on allegations of creating sheep with human-likeness, "We haven't seen them act as anything but sheep." The university is also being investigated over accusations made by another UNR scientist that at least some of the sheep were being abused.

The most ingenious endeavour in chimera creation carried out was perhaps using the stalwart laboratory guinea pig, mice. The director of Stanford University's Institute of Cancer/Stem Cell Biology and Medicine, Irving Weissman played a major role in making the first mouse with a nearly complete human immune system.

It has demonstrated unequivocally its usefulness for testing new drugs against the AIDS virus which does not infect conventional mice. People with disabilities were also given new hope when paralysed mice were seen to walk after being injected with human stem cells.

Recently Weissman's team created mice with brains, which were about one per cent human by injecting human neural stem cells into mouse foetuses. Dissecting the mice at various stages, the scientists were able to witness how the inserted brain cells moved about as they multiplied and made connections with mouse cells. He now has plans to add human brain cells that contain the defects that cause degenerative brain ailments such as Parkinson's disease, Lou Gehrig's disease and Alzheimers among others.

It is widely suspected that such diseases begin early in development when certain errors occur, even though they are only apparent in late adulthood. If the errors could be found, researchers will have a much better chance at designing ideal medicines as well as be tested on the hybrids as could not be possible in humans.

The stem cell scientist also has hopes of creating mice whose brains are one hundred per cent human by injecting human neurons into the brains of embryonic mice. The experiment would lead to much better understanding of the mysterious way that the brain works.

The chimeric mice would be killed before birth and then dissected. If it showed human brain architecture, he'd look for traces of human cognitive behaviour.

The proposal has already been approved by the college's informal ethics committee and the chair, law professor Hank Greely said that they were satisfied that the size and shape of the mouse brain would prevent the human cells from creating any human traits.

However they recommend monitoring the mice's behaviour closely and killing any that display even a glimmer of human-like behaviour.

Natural Chimeras

Chimeras are however not as alien or unnatural as they seem at first. Most twins carry at least a few cells from the sibling with whom they shared the womb. Also most mothers carry at least a few cells in their blood from each of the children that they have borne.

Organ transplant recipients can also be classed as chimeras as well as the many patients' whose faulty heart valves have been routinely replaced with those from cows or pigs over the years.

Ethics and Repercussions

The most radical in human-animal hybrid experimentation, though as yet not conducted would be to insert human stem cells into an animal embryo and then place it in an animal womb. The possibility is that the proliferating human cells would spread throughout the animal embryo as it grows into a foetus and integrate themselves into each and every organ. Such humanised animals would definitely provide extremely improved means to test the potency and toxicity of a novel drug in experimental stages among other countless uses.

The risk of such an experiment is some of the human cells that have incorporated into the testes and ovaries might grow into human sperm and eggs. If two such chimeras were to mate, a human embryo may form trapped in an animal's womb.

Or, mice for example, could be genetically engineered to specifically produce human sperm and eggs and then by in vitro fertilisation produce a human child whose parents' would be a pair of mice.

Cynthia B. Cohen, a senior research fellow at the Kennedy Institute of Ethics in Georgetown University as well as a member of Canada's Stem Cell Oversight Committee which last year passed an act prohibiting the transfer of a non-human cell into a human embryo or vice versa, believes that the mixing of animal and human gametes diminishes human dignity. "It would deny that there is something distinctive and valuable about human beings that ought to be honoured and protected," she said but also that ethical and legitimate experiments involving stem cells should not be outlawed.

The National Academy of Sciences issued guidelines last month on human-animal chimeric experiments. It recommended that each research institute form a special committee to oversee the research and endorse any proposed experiment.

It also insisted on additional scrutiny in experiments injecting human stem cells into animal brains as well as an outright ban inserting human embryonic stem cells into primate embryos. Adherence to the guidelines is purely voluntary and most stem cell research being carried so far is in accordance with the academy's recommendation.

Anti-biotechnology activist Jeremy Rifkin and New York Medical College professor Stuart Newman who have been tracking the issue of interspecies mixing over the years were behind a creative assault on the issue when they applied for a patent a few years ago for what they referred to as a humanzee, a hypothetical yet very possible creature that was half human and half chimpanzee. They were delighted when their application was rejected this year sighting the proposed invention too human.

Human-chimpanzee chimeras are however a very real possibility. Such a humanzee, for example endowed with the powers of speech and enhanced learning abilities would raise a lot of questions such as if it is right by the animal to raise its moral status and what rights and protection would it deserve.

Harvard political philosopher Michael J. Sandel speaking at a meeting on Bio Ethics last year said that the chances of such rights and protection being given to the animals are unlikely and that they would probably use to "perform menial jobs or dangerous jobs. That would be an objection."

Already pigs have been bred with human blood in Minnesota, Chinese scientists have successfully fused rabbit eggs with human cells, mice in California have been born with partly human brains and in Nevada researchers are farming sheep with human organs.

It may have started off with injecting human genetic material into one of the lowest of life forms, bacteria but the possibility of fusing our circuitry with our closest relatives, the apes is not only existent but also very plausible. How far are we willing to go before our ethics dictate us to stop, or will we draw a line at all?

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