||Chimeras, Cloning and Freak Human-Animal Hybrids
November 23, 2004
With the United States officially abandoning its attempt to get a UN treaty banning cloning, and revelations about cloning worldwide, it is becoming obvious that the doors are about to become wide open for public cloning efforts.
Not that cloning hasn't been going on all along. In November of 2001, CNN reported that a human embryo was created through cloning. Even earlier, in 1999, the BBC reported on a human hybrid clone. And these are just the efforts the public is being told about. The technology has been around for decades and human clones have already been created.
Beyond that, there's the ultimately disturbing "scientific" trend of creating human-animal hybrids, or chimeras for "therapeutic" and other "important" reasons.
That's mice with human brain cells and pigs with human blood -- and there are no federal guidelines in place to stop scientists from creating these freaks for whatever reasons they might claim.
But don't take our word for it, take the Washington Post's in the article below. Here's an excerpt:
"During one recent meeting, scientists disagreed on such basic issues as whether it would be unethical for a human embryo to begin its development in an animal's womb, and whether a mouse would be better or worse off with a brain made of human neurons.."
There are programs going on across the country to create chimeras, many in tax-funded Universities, including the University of Pennsylvania's School of Medicine, which creates chimeric mice by introducing Embryonic Stem cells into early mice embryos.
That's just one project of many. A simple google search on chimeric mice produces a plethora of unsettling results. And that's just mice...
Of Mice, Men and In-Between
Scientists Debate Blending Of Human, Animal Forms
Washington Post | November 20, 2004
By Rick Weiss
In Minnesota, pigs are being born with human blood in their veins.
In Nevada, there are sheep whose livers and hearts are largely human.
In California, mice peer from their cages with human brain cells firing inside their skulls.
These are not outcasts from "The Island of Dr. Moreau," the 1896 novel by H.G. Wells in which a rogue doctor develops creatures that are part animal and part human. They are real creations of real scientists, stretching the boundaries of stem cell research.
Biologists call these hybrid animals chimeras, after the mythical Greek creature with a lion's head, a goat's body and a serpent's tail. They are the products of experiments in which human stem cells were added to developing animal fetuses.
Chimeras are allowing scientists to watch, for the first time, how nascent human cells and organs mature and interact -- not in the cold isolation of laboratory dishes but inside the bodies of living creatures. Some are already revealing deep secrets of human biology and pointing the way toward new medical treatments.
But with no federal guidelines in place, an awkward question hovers above the work: How human must a chimera be before more stringent research rules should kick in?
The National Academy of Sciences, which advises the federal government, has been studying the issue and hopes to make recommendations by February. Yet the range of opinions it has received so far suggests that reaching consensus may be difficult.
During one recent meeting, scientists disagreed on such basic issues as whether it would be unethical for a human embryo to begin its development in an animal's womb, and whether a mouse would be better or worse off with a brain made of human neurons.
"This is an area where we really need to come to a reasonable consensus," said James Battey, chairman of the National Institutes of Health's Stem Cell Task Force. "We need to establish some kind of guidelines as to what the scientific community ought to do and ought not to do."
Beyond Twins and Moms
Chimeras (ki-MER-ahs) -- meaning mixtures of two or more individuals in a single body -- are not inherently unnatural. Most twins carry at least a few cells from the sibling with whom they shared a womb, and most mothers carry in their blood at least a few cells from each child they have born.
Recipients of organ transplants are also chimeras, as are the many people whose defective heart valves have been replaced with those from pigs or cows. And scientists for years have added human genes to bacteria and even to farm animals -- feats of genetic engineering that allow those critters to make human proteins such as insulin for use as medicines.
"Chimeras are not as strange and alien as at first blush they seem," said Henry Greely, a law professor and ethicist at Stanford University who has reviewed proposals to create human-mouse chimeras there.
But chimerism becomes a more sensitive topic when it involves growing entire human organs inside animals. And it becomes especially sensitive when it deals in brain cells, the building blocks of the organ credited with making humans human.
In experiments like those, Greely told the academy last month, "there is a nontrivial risk of conferring some significant aspects of humanity" on the animal.
Greely and his colleagues did not conclude that such experiments should never be done. Indeed, he and many other philosophers have been wrestling with the question of why so many people believe it is wrong to breach the species barrier.
Does the repugnance reflect an understanding of an important natural law? Or is it just another cultural bias, like the once widespread rejection of interracial marriage?
Many turn to the Bible's repeated invocation that animals should multiply "after their kind" as evidence that such experiments are wrong. Others, however, have concluded that the core problem is not necessarily the creation of chimeras but rather the way they are likely to be treated.
Imagine, said Robert Streiffer, a professor of philosophy and bioethics at the University of Wisconsin, a human-chimpanzee chimera endowed with speech and an enhanced potential to learn -- what some have called a "humanzee."
"There's a knee-jerk reaction that enhancing the moral status of an animal is bad," Streiffer said. "But if you did it, and you gave it the protections it deserves, how could the animal complain?"
Unfortunately, said Harvard political philosopher Michael J. Sandel, speaking last fall at a meeting of the President's Council on Bioethics, such protections are unlikely.
"Chances are we would make them perform menial jobs or dangerous jobs," Sandel said. "That would be an objection."
A Research Breakthrough
The potential power of chimeras as research tools became clear about a decade ago in a series of dramatic experiments by Evan Balaban, now at McGill University in Montreal. Balaban took small sections of brain from developing quails and transplanted them into the developing brains of chickens.
The resulting chickens exhibited vocal trills and head bobs unique to quails, proving that the transplanted parts of the brain contained the neural circuitry for quail calls. It also offered astonishing proof that complex behaviors could be transferred across species.
No one has proposed similar experiments between, say, humans and apes. But the discovery of human embryonic stem cells in 1998 allowed researchers to envision related experiments that might reveal a lot about how embryos grow.
The cells, found in 5-day-old human embryos, multiply prolifically and -- unlike adult cells -- have the potential to turn into any of the body's 200 or so cell types.
Scientists hope to cultivate them in laboratory dishes and grow replacement tissues for patients. But with those applications years away, the cells are gaining in popularity for basic research.
The most radical experiment, still not conducted, would be to inject human stem cells into an animal embryo and then transfer that chimeric embryo into an animal's womb. Scientists suspect the proliferating human cells would spread throughout the animal embryo as it matured into a fetus and integrate themselves into every organ.
Such "humanized" animals could have countless uses. They would almost certainly provide better ways to test a new drug's efficacy and toxicity, for example, than the ordinary mice typically used today.
But few scientists are eager to do that experiment. The risk, they say, is that some human cells will find their way to the developing testes or ovaries, where they might grow into human sperm and eggs. If two such chimeras -- say, mice -- were to mate, a human embryo might form, trapped in a mouse.
Not everyone agrees that this would be a terrible result.
"What would be so dreadful?" asked Ann McLaren, a renowned developmental biologist at the University of Cambridge in England. After all, she said, no human embryo could develop successfully in a mouse womb. It would simply die, she told the academy. No harm done.
But others disagree -- if only out of fear of a public backlash.
"Certainly you'd get a negative response from people to have a human embryo trying to grow in the wrong place," said Cynthia B. Cohen, a senior research fellow at Georgetown University's Kennedy Institute of Ethics and a member of Canada's Stem Cell Oversight Committee, which supported a ban on such experiments there.
But what about experiments in which scientists add human stem cells not to an animal embryo but to an animal fetus, which has already made its eggs and sperm? Then the only question is how human a creature one dares to make.
In one ongoing set of experiments, Jeffrey L. Platt at the Mayo Clinic in Rochester, Minn., has created human-pig chimeras by adding human-blood-forming stem cells to pig fetuses. The resulting pigs have both pig and human blood in their vessels. And it's not just pig blood cells being swept along with human blood cells; some of the cells themselves have merged, creating hybrids.
It is important to have learned that human and pig cells can fuse, Platt said, because he and others have been considering transplanting modified pig organs into people and have been wondering if that might pose a risk of pig viruses getting into patient's cells. Now scientists know the risk is real, he said, because the viruses may gain access when the two cells fuse.
In other experiments led by Esmail Zanjani, chairman of animal biotechnology at the University of Nevada at Reno, scientists have been adding human stem cells to sheep fetuses. The team now has sheep whose livers are up to 80 percent human -- and make all the compounds human livers make.
Zanjani's goal is to make the humanized livers available to people who need transplants. The sheep portions will be rejected by the immune system, he predicted, while the human part will take root.
"I don't see why anyone would raise objections to our work," Zanjani said in an interview.
Perhaps the most ambitious efforts to make use of chimeras come from Irving Weissman, director of Stanford University's Institute of Cancer/Stem Cell Biology and Medicine. Weissman helped make the first mouse with a nearly complete human immune system -- an animal that has proved invaluable for tests of new drugs against the AIDS virus, which does not infect conventional mice.
More recently his team injected human neural stem cells into mouse fetuses, creating mice whose brains are about 1 percent human. By dissecting the mice at various stages, the researchers were able to see how the added brain cells moved about as they multiplied and made connections with mouse cells.
Already, he said, they have learned things they "never would have learned had there been a bioethical ban."
Now he wants to add human brain stem cells that have the defects that cause Parkinson's disease, Lou Gehrig's disease and other brain ailments -- and study how those cells make connections.
Scientists suspect that these diseases, though they manifest themselves in adulthood, begin when something goes wrong early in development. If those errors can be found, researchers would have a much better chance of designing useful drugs, Weissman said. And those drugs could be tested in the chimeras in ways not possible in patients.
Now Weissman says he is thinking about making chimeric mice whose brains are 100 percent human. He proposes keeping tabs on the mice as they develop. If the brains look as if they are taking on a distinctly human architecture -- a development that could hint at a glimmer of humanness -- they could be killed, he said. If they look as if they are organizing themselves in a mouse brain architecture, they could be used for research.
So far this is just a "thought experiment," Weissman said, but he asked the university's ethics group for an opinion anyway.
"Everyone said the mice would be useful," he said. "But no one was sure if it should be done."
U.S. Drops Effort for Treaty Banning Cloning New York Times | November 20, 2004
By WARREN HOGE
UNITED NATIONS, Nov. 19 - Faced with polarizing division in the 191-member General Assembly, the United States on Friday abandoned its aggressively pursued attempt to obtain a United Nations treaty banning all human cloning, including that done in the name of medical research.
The outcome - an agreement to come up with a nonbinding declaration against cloning to reproduce humans - fell far short of the American goal and represented a setback for President Bush. He called for a worldwide ban on all cloning when he addressed the United Nations General Assembly in August, and he made limiting stem cell and other related research an issue in his presidential campaign.
All 191 United Nations members have agreed on the need for a treaty to prohibit reproductive cloning. But a vote has been stalled for three years by sharp differences over whether to broaden the ban, as the United States wishes, to prohibit cloning to create stem cells for research, part of a field known as therapeutic cloning.
The push for a total ban has set the Bush administration against close allies like Britain and much of the world's scientific establishment, who contend that it would block research on cancer, Alzheimer's disease, Parkinson's disease, diabetes, spinal cord injuries, multiple sclerosis and other conditions. The White House argues that enough stem cells from human embryos exist for research and that cloning an embryo for any reason is unethical.
Negotiations have been going on for more than a year in the General Assembly's legal committee, which draws up treaties. A vote was scheduled for Friday on two competing versions, but with scant hope of the kind of consensus emerging considered necessary for an effective treaty.
The United States backed a resolution proposed by Costa Rica to outlaw all forms of human cloning, while opponents of such an absolute prohibition supported a Belgian measure banning reproductive cloning outright and offering nations three options for therapeutic cloning: outlawing it, putting a moratorium on the practice, or regulating it through national legislation to prevent misuse.
Instead of proceeding to a showdown vote on Friday night, the committee agreed instead to take up a nonbinding declaration proposed by Italy with ambiguous language that avoided raising objections and to schedule meetings in February to shape the final wording. The Italians' proposal prohibits "any attempts to create human life through cloning processes and any research intended to achieve that aim."
Regardless of what language emerges, the result will be a declaration, not a treaty, which would have been the outcome had either the Costa Rican or Belgian versions been adopted. Because of that, nations will be under considerably less pressure to change their existing views on cloning.
"A declaration is important for what it's not," said Bernard Siegel, the executive director of the Genetics Policy Institute, who had lobbied against the American-led campaign. "It is not a treaty, it is nonbinding, and it will have no chilling effect on therapeutic cloning, and stem cell research will advance. We consider this a triumph."
Human embryo created through cloning
CNN | November 26, 2001
WASHINGTON (CNN) -- Scientists at a technology company said Sunday they have created human embryos through cloning, drawing criticism from President Bush and lawmakers and raising new ethical questions.
Advanced Cell Technology Inc. of Worcester, Massachusetts, said the experiment was aimed not at creating a human being but at mining the embryo for stem cells used to treat disease.
Stem cells are a kind of master cell that can grow into any kind of cell in the body. The company's study was also published in an online scientific journal.
"I'm just trying to help people who are sick, and really that's our focus," said Dr. Michael West, the company's president and CEO. He called the development "the first, halting steps" toward a new area of medicine.
Speaking on CNN's "Late Edition with Wolf Blitzer," West disputed the suggestion the work amounted to the creation of a human being.
"We're talking about making human cellular life, not a human life," West said.
"A human life, we know scientifically, begins upwards, even into two weeks, of human development, where this little ball of cells decides, 'I'm going to become one person or I am going to be two persons.' It hasn't decided yet."
West said the breakthrough in what he called "therapeutic cloning" could lead to advances in fighting a variety of ailments, including Parkinson's disease and diabetes.
He said his company was not interested in cloning human beings and did not create the embryos for reproductive purposes.
The news drew immediate criticism from some lawmakers.
"I think that people are concerned about the ethical problems here," Sen. Richard Shelby, R-Alabama, said on NBC's "Meet the Press." He said he expected lawmakers would soon take up the issue.
"I believe it will be a big debate, but at end of day I don't believe we'll let cloning of human embryos," Shelby said.
"I find it very, very troubling, and I think most of Congress would," Sen. Patrick Leahy, Democrat of Vermont, said on NBC.
A White House spokeswoman reaffirmed President Bush's opposition to human cloning.
"The president has made it clear that he is 100 percent opposed to any type of cloning of human embryos," said spokeswoman Jennifer Millerwise. "The president supported the House legislation to ban human cloning which passed overwhelmingly."
Last summer, the House of Representatives voted to ban human cloning and set penalties of up to 10 years in prison and a $1 million fine for those convicted of attempting to clone humans.
The measure was never taken up by the Senate, so it never became law.
Sen. Richard Durbin, D-Illinois, said he hoped the Senate could find a compromise that would allow some cloning research to continue, without opening the door to the creation of human beings through clones.
"We in the Senate have to draw that line so it's a reasonable line, so we can continue medical science and breakthroughs, without crossing that line into something none of us want to see," he said on CNN's "Late Edition."
In the study, published in the online Journal of Regenerative Medicine, scientists removed the DNA from human egg cells and replaced it with DNA from a human body cell. The egg cells began to develop "to an embryonic state," according to a press release from the company.
Of the eight eggs, two divided to form early embryos of four cells and one progressed to a six-cell stage before it stopped dividing.
"These are exciting preliminary developments," said Robert P. Lanza, vice president of medical and scientific development at ACT and one of the authors of the paper.
"This work sets the stage for human therapeutic cloning as a potentially limitless source of immune-compatible cells for tissue engineering and transplantation medicine.
"Our intention is not to create cloned human beings," Lanza said, "but rather to make lifesaving therapies for a wide range of human disease conditions including diabetes, strokes, cancer, AIDS and neurodegenerative disorders such as Parkinson's and Alzheimer's disease."
Though he described the advance as a "very primitive development," the director of the Center for Bioethics at the University of Pennsylvania deemed it a "significant" one.
"When you get to the point where you've made a human embryo, even for research purposes ... it's a line that's crossed," Arthur Caplan told CNN.
The medical ethicist said an argument could be made for using the technology to create cells that could be used to treat diseases.
"If you could make cell lines from these creations and turn them into something that the body wouldn't reject ... that would be a wonderful breakthrough in terms of being able to offer cures to people."
Earlier this year, Italian fertility doctor Severino Antinori and U.S. researcher Panos Zavos announced plans to clone humans. They said hundreds of couples had volunteered for controversial procedure.
The announcement was criticized by officials in several countries, and Italian authorities threatened to ban Antinori from practicing medicine if he goes ahead with the experiment.
Another organization, Clonaid, moved its research into human cloning outside of the United States after being investigated by the federal government.
Clonaid was founded by members of a religion called the Raelian movement, which believes extraterrestrial scientists created life on Earth and that cloning is a way of achieving eternal life.
The Food and Drug Administration investigated the company after its research director, Brigitte Boisselier, told a congressional hearing the company wanted to clone a human in the United States.
Details of human hybrid clone revealed
BBC | June 18, 1999
The embryo clone: A collection of stem cells produced using nuclear transfer
Details of the first hybrid human embryo clone have been released.
The watershed achievement in biotechnology actually happened last November, but more information was revealed on Thursday. It was achieved using a cell from a man's leg and a cow's egg.
The scientists who created the clone see it as a significant step forward in the search for a way of producing human stem cells.
These are "master" cells that can develop into any type of cell - skin, bone, blood, etc. They are believed to have the potential to provide perfect-match tissue for transplantation and the treatment of diseases such as Parkinson's.
But this development will also see a significant heightening of the debate over the ethics of human cloning and, indeed, what it means to be a human.
Advanced Cell Technology (ACT), a leading, private biotechnology company, made the first human embryo clone and let it develop for twelve days before destroying it. In a normal pregnancy, an embryo implants into the womb wall after 14 days.
Dr Robert Lanza, ACT's director of tissue engineering, told the Daily Mail newspaper that the embryo could not be seen as a person before 14 days. The company said it had released news of the discovery to try to allay fears over the artificial conception of life.
It is believed that many more hybrid embryos have been created in the same way and destroyed since November.
No child clones
ACT said it had no intention of attempting to use the human cloning procedure to start a pregnancy - its aim was "therapeutic cloning" not "reproductive cloning", it said.
Lord Robert Winston, a British fertility expert, said the research was "totally ethical".
But opponents said the development of the technology made the eventual birth of a human clone inevitable. This, they said, would have profound implications for the nature of family relationships, the law and health.
The technology used to create the clone was very similar to that used to make Dolly the sheep clone. Over 200 embryos were used before Dolly finally appeared, showing that cloning is not a well-understood or easy-to-perform technique.
It is believed ACT used a cow's egg. This had its DNA removed and replaced with human DNA. The new cell was then chemically persuaded to behave like a new embryo and start dividing. This is how ACT hope to cultivate stem cells.
But Dr Maisam Mitalipova, a pioneer of this human-cow type of cloning, told the Daily Mail: "We didn't get good quality embryos and so they may not get good quality stem cells."
Another US company, Geron, is also reported to be attempting to make human embryo clones for therapeutic purposes.
It recently bought all the shares in Roslin Bio-Med, a company set up to commercialise the cloning expertise of the Roslin Institute, Scotland, where Dolly the sheep was created.
Geron has not publicly stated whether its attempts have been successful and it may be that ACT achieved the feat first.