12 February 2002

STRANGE CLONEFELLOWS/HUSHING UP ADULT STEM CELLS/2 NEW CLONING STUDIES

"the political struggle against human cloning and eugenics in coming years [may] be a battle not of left versus right but of right versus wrong, in which those who seem at first sight strange bedfellows strive together to thwart scientific hubris and foster a deeper respect for the intrinsic worth of human life." (item 3)

"The cloning process probably always fails to achieve the accuracy of natural reproduction, says Solter. 'Whether the clone dies next day or next year depends on how badly it misses' " (item 2)

"An article published in Science earlier last year showed that mice cloned from embryonic stem cells by nuclear transfer suffered many genetic defects due to the genetic instability of the embryonic stem cells. The Washington Post reported that a key phrase referring to the genetic instability of the embryonic stem cells that might "limit their use in clinical application", was removed days before the paper appeared in print." (item 1)

1. ISIS Report: Hushing Up Adult Stem Cells
2. 2 new cloning studies have scientists scratching their heads.
3. Strange Clonefellows; The left-right anti-cloning coalition

***

1. ISIS Report: Hushing Up Adult Stem Cells

The science and technology of adult stem cells are running streets ahead of embryonic stem cells. But are the scientific establishment and the mainstream press hushing that up? Dr. Mae-Wan Ho and Prof. Joe Cummins review recent advances that make embryonic stem cells research unethical and unnecessary. Adult stem cells isolated from different tissues are developmentally as flexible as embryonic stem cells. Adult stem cells have been used successfully to repair damaged heart, and to treat a variety of disorders from auto-immune disease to cancer. Furthermore, they can be multiplied for many generations in the laboratory, and established cell lines obtained.

If you wish to see the complete report with references, please consider becoming a member or friend of ISIS. Full details here.

The British science journal, Nature, did a series of 'insight' articles on stem cells last November. Senior editor Natalie DeWitt refers to the excitement fuelled by "the controversial evidence that adult stem cells have a much higher degree of developmental potential than was previously imagined".

Almost none of the articles address adult stem cells directly, and where they do, the reader is given the impression that adult stem cells are simply not as good as embryonic stem cells. In the final article on 'ethical and social considerations', author Anne McLaren deplores attempts to "hype adult stem cells at the expense of ES cells". And while admitting that ES cells from somatic cell nuclear transfer, SCNT (involved in 'therapeutic human cloning') "may never prove economic for routine clinical treatment", "they could nonetheless make an immensely valuable contribution to medical research".

McLaren mentioned "a point of view" that SCNT presents no ethical problems, "because the entity to which it gives rise is not an embryo as defined as the product of fusion between sperm and egg, but an artefact, possessing no moral significance". The process did result in Dolly the sheep, but, "Is Dolly perhaps not a sheep, but merely an ovine cyborg?" She asked. So, by a clever escape clause, the bio-ethicist made the moral problem disappear in front of our very eyes.

By the same token, we should not object to reproductive human cloning, for such cloned humans are merely 'cyborgs'. Nor should we object to making cyborgs that serve real humans in any way we please. (Although it would be problematic to define who the real humans are.) Clearly that could not have been her intention. Her intention was to support embryonic stem cell research.

"Let a thousand stem cell lines bloom" she urged, "but let them bloom in full view of all, so that they can be subject to scientific and ethical review, freely available for research and one day, perhaps, for treating diseases." She has thus pre-empted public opposition to isolating embryonic stem cells from human embryos created by SCNT, and to research done on those cells.

Ironically, the company acknowledged for financial support of the series had a full page advertisement at the beginning of the series, where it describes itself as a company that "develops off-the-shelf cellular products based on the human mesenchymal stem cell (hMSC)". MSC is the best-characterised stem cell to-date, adult or embryonic. Contrary to the claims of the Nature 'insight', the scientific establishment has been hyping embryonic stem cells at the expense of adult stem cells, and has already been caught doing so.

An article published in Science earlier last year showed that mice cloned from embryonic stem cells by nuclear transfer suffered many genetic defects due to the genetic instability of the embryonic stem cells. The Washington Post reported that a key phrase referring to the genetic instability of the embryonic stem cells that might "limit their use in clinical application", was removed days before the paper appeared in print.

The Statistical Assessment Service (STATS), a non-partisan group dedicated to truth telling in political debates that involve science, found that the mainstream media had given great prominence to the potential of embryonic stem cells while under-reporting or completely ignoring research breakthroughs involving adult stem cells or alternate sources.

The US National Bioethics Advisory Commission (NBAC) recommended to Clinton to support embryonic stem cell research, but stipulated that this is "justifiable only if no less morally problematic alternatives are available for advancing the research."

It is now clear that such morally less problematic alternatives do exist, in readily available sources of adult stem cells, especially from patients requiring the treatment. We were among those who pointed this out a year ago ("The Unnecessary evil of 'therapeutic' human cloning" ISIS News 7/8, February 2001 www.i-sis.org.uk), and numerous subsequent advances have proved our case.

The main protagonists of embryonic stem cell research are the scientists working with those cells. A typical case made on why embryonic stem cell research should be supported goes like this.

Embryonic stem cells are 'pluripotent', ie, they can make every cell type of the body, while adult stem cells are 'multipotent' and can make many, but not all cell types. Consequently, adult stem cells may be immensely useful for treatment of some human disease, but unable to make certain cell types required for treatment of other, unspecified, diseases. Adult stem cells, unlike those derived from the embryo, cannot be expanded in culture without losing developmental potential. Finally, many of the claims of adult stem have not appeared as peer-reviewed publications.

In fact, all those arguments have long been overtaken by events. There are many excellent peer-reviewed publications showing that adult stem cells may be just as developmentally flexible as embryonic stem cells, that these stem cells show much greater promise in repairing damaged tissues and treatment of other diseases, and that they can give rise to established cell lines, if needed. Furthermore, unlike stem cells isolated from the embryo, they do not carry the same risks of cancer or uncontrollable growth after transplant, and they can be isolated from patients requiring treatment, thus avoiding all problems of immune rejection and the need for immune suppressive drugs that carry their own risks.

The developmental potential of adult stem cells has been documented in numerous publications. For example, bone marrow cells enriched for hematopoietic (blood) stem cells (HSC) can differentiate into mature liver cells in the liver of rodents and humans. Mouse bone marrow cells can generate skeletal muscle cells in the body, and skeletal muscle cells can give bone marrow cells. Bone marrow could be reconstituted from cultured brain, and glial and neurons cells were obtained from bone marrow.

More recently, a 'pluripotent neural stem cell' was isolated from adult mouse brain, where it constitutes 1 in 300 cells of the brain. It not only gave rise to all types of cells in the brain, but when cultured with a muscle cell line, developed into muscle cells. These neural stem cells can be grown indefinitely in culture.

Researchers have also provided definitive proof that one single adult stem cell from bone marrow can reconstitute the bone marrow of a mouse destroyed by irradiation, as well as develop into practically all the tissues of the body. Established cell lines have been obtained from one type of bone marrow stem cells.

Another source of readily available adult stem cells turns out to be skin. Skin stem cells can make neurons, glia, smooth muscle and fat cells. Again, cell lines have been established that kept their pluripotency for at least one year.

Embryonic stem cells are promoted on ground that they are developmentally more flexible than adult stem cells. But too much flexibility may not be desirable. Transplant of embryonic cells into the brains of Parkinson's patients turned into an irredeemable nightmare because the cells grew uncontrollably. Embryonic stem cells also show genetic instability and carry considerable risks of cancer (see ISIS News 11/12 www.i-sis.org.uk). When injected under the skin of certain mice, they grow into teratomas, tumours consisting of a jumble of tissue types, from gut to skin to teeth; and the same happens when injected into the brain.

A new paper in PNAS reports how mouse embryonic stem cells injected into the brain of adult rats developed into neurons. The rats had previously had their dopamine-producing neurons damaged and showed a characteristic tendency to move in circles toward the damaged side of the brain, mimicking Parkinson's disease.

Actually, six of the 25 rats injected showed no evidence that the mouse embryonic stem cells had survived. Five died with teratomas in the brain. The 14 remaining had mouse stem-cell derived neurons in their brain, but showed only a modest 40% behavioural improvement over untreated controls.

Injected adult stem cells are different, they grow into other tissues only when appropriate growth factors are applied, or when given other external cues. Indeed, adult stem cells already have a record of relatively safe, effective therapy, especially when cells from the patients themselves are used.

We reported on the use of the patient's own bone marrow cells to mend damaged heart in ISIS News 11/12 (www.i-sis.org.uk). The patient's bone
marrow stem cells have also been successfully used to treat juvenile chronic arthritis, severe systemic lupus erythematosus, an auto-immune disorder with multiple organ dysfunction, and Crohn's disease affecting the bowels.

Bone marrow transplant from the daughter provided 'killer cells' that were tolerated by her mother, thereby ridding the mother of an otherwise untreatable cancer.

It is clear that human embryonic stem cell research is both unethical and unnecessary, and should not be supported, least of all with public finance. An indication of the promise of adult stem cells relative to embryonic stem cells is that private finance for the former is outstripping the latter two to one.

Our tax money should not be spent to indulge the whims of scientists who cannot see beyond their own self-centred narrow interest, and who are totally insensitive to the moral concerns of the rest of humanity.
...
This article can be found on the I-SIS website at http://www.i-sis.org.uk/

***

2. Double take on cloning
Two new cloning studies have scientists scratching their heads

11 February 2002
JOHN WHITFIELD
http://www.nature.com/nsu/020204/020204-15.html

The world's labs are home to a steadily growing number of cloned animals. "From a practical viewpoint, cloning is more or less solved," says Davor Solter of the Max Planck institute for Immunobiology, Freiburg, Germany. "But the really important questions are so hard we don't know how to approach them."

One of the biggest of those questions is what happens when researchers try to reprogram adult cells to develop into new embryos. Two studies now provide vital clues. But an answer is still a long way off.

Japanese researchers have found that cloned mice sicken and die earlier than their normal counterparts1. A US team has gone a long way towards proving that adult cells that are fully committed to doing a particular job can become new embryos2.

Atsuo Ogura, of the National Institute of Infectious Diseases in Tokyo, and his colleagues compared 12 cloned mice with 7 normal mice and 6 that were created by injecting sperm DNA into an egg, to replicate the manipulation used in cloning.

Of the 12 cloned mice, 10 died of pneumonia and liver disease before they were 800 days old (the normal mouse lifespan). One normal mouse and two that were produced by sperm injection died during this time.

Most clones die either before birth or soon after. Ogura's results suggest that the odds are still stacked against animals' throughout their lifespan. "It is very probable that, at least for some clones, unpredictable defects will appear in the long run," says Ogura.

The cloning process probably always fails to achieve the accuracy of natural reproduction, says Solter. "Whether the clones dies next day or next year depends on how badly it misses," he suggests.

But Tony Perry, of biotechnology company Advanced Cell Technology, based in Worcester, Massachusetts, believes that the study "gives us great cause for hope". He feels that the results hint that clones' problems might be caused by the techniques used to create them, rather than by fundamental biological inadequacies.

Technical refinements, says Perry, might give rise to healthier clones. "What's needed is standardization," to move the technology from being an art to a science, he says.

Secret of cells' success

Biologists have long tried to work out what makes some cells yield successful clones.

One possibility is that the animals that make the grade were cloned from one of the rare stem cells found in adult bodies. These have more potential to develop into different tissue types than the majority of cells, which are fully committed to a particular job.

To rule out this possibility, one needs to create clones from a cell that carries a badge of rank. Cells in the immune system called lymphocytes have genetic rearrangements that distinguish them from the body's other cells - making them ideal for this purpose.

Konrad Hochedlinger and Rudolf Jaenisch, of the Whitehead Institute in Cambridge, Massachusetts, took DNA from a lymphocyte and put it into an egg. They did not let this egg develop into a mouse, but instead extracted embryonic stem cells from the early-stage embryo, and then created clones from these. Embryonic stem cells have a higher cloning success rate than cells from adult bodies.

One thousand attempts yielded two stem-cell cultures, which gave rise to 21 live-born mice from 260 attempts.

"We've proved that you can reprogramme mature cells, but that it's very, very inefficient," says Jaenisch. Jaenisch and Hochedlinger's two stem cell lines from 1,000 attempts compares unfavourably with Dolly the sheep, for example, who was the single success from 277 attempts. Jaenisch argues that this strengthens the idea that previous clones were indeed made from cells that weren't fully set on a particular course.

Solter is not so sure. "I don't think this proves you can clone from a differentiated cell, and, on the other hand, I don't think it proves that all successful clones were from adult stem cells," he contends.

"It's a step forward, but it's really a warm-up act for the main event, which would be cloning directly from a lymphocyte," says Perry.

References
Ogonuki, N. et al. Early death of mice cloned from somatic cells. Nature Genetics advance online publication, (2002).
http://www.nature.com/doifinder/10.1038/ng841
Hochedlinger, K. & Jaenisch, R. Monoclonal mice generated by nuclear transfer from mature N and T donor cells. Nature advance online publication, (2002).
http://www.nature.com/doifinder/10.1038/nature718

© Nature News Service / Macmillan Magazines Ltd 2002

***

3. Strange Clonefellows; The left-right anti-cloning coalition

BY WESLEY J. SMITH
The Weekly Standard February 11, 2002, Vol. 7, No. 21

A GREAT DEFICIENCY in the media's reporting of debates about public policy is their tendency to reduce messy democratic discourse to a sterile, never-ending face-off between "The Left" and "The Right." One year, The Right launches an offensive and advances a half-mile. The next year, The Left counterattacks and regains the lost ground. This caricature has certainly dominated the reporting of the debate over human cloning, which is usually portrayed as a contest between religious opponents of abortion and medical researchers striving to benefit human-kind. The stereotype was epitomized in a January 17, 2002, Washington Post story by science reporter Rick Weiss. Implying that opponents of human cloning are the moral equivalent of the Taliban, Weiss wrote: In November, researchers announced that they had made the first human embryo clones, giving immediacy to warnings by religious conservatives and others that science is no longer serving the nation's moral will. At the same time, the United States was fighting a war to free a faraway nation from the grip of religious conservatives who were denounced for imposing their moral code on others.

The Post ombudsman gently rebuked Weiss for his "real or perceived bias," but the fact that he made the comparison, and that no editor removed it, is revealing. In reality, the opponents of human cloning are not so easily categorized. For one thing, they include many secular activists associated with the pro- choice left. Last year, in a lopsided bipartisan vote, the House of Representatives passed the Weldon bill (H. 2505), which would outlaw both research and reproductive human cloning. Among those supporting the ban were 21 House members whose voting records on abortion were at least 75 percent pro-choice as scored by the National Abortion Rights Action League (NARAL). Now, 68 leftist activists have signed a "Statement in Support of Legislation to Prohibit Cloning." Among them are such notables as activist Jeremy Rifkin, New York University professor Todd Gitlin, novelist Norman Mailer, Commonweal editor Margaret O'Brien, Abortion Access Project director Susan Yanow, New Age spiritual leader Matthew Fox, and Judy Norsigian, author of the feminist manifesto Our Bodies, Ourselves.

Among arguments against the cloning of human life, these leftists stress the "commercial eugenics" that the new technologies threaten to unleash. They write: We are also concerned about the increasing bio-industrialization of life by the scientific community and life science companies and shocked and dismayed that clonal human embryos have been patented and declared to be human "inventions." We oppose efforts to reduce human life and its various parts and processes to the status of mere research tools, manufactured products, commodities, and utilities. These are points that conservative opponents of cloning have been making for a long time, with limited effect thanks to the media's obsession with the politics of abortion. That may change, now that some leaders of the American left are becoming fully engaged in the drive to ban human cloning. If it does, the chances of outlawing human cloning will improve dramatically.

Still, the question lingers: Can these strange bedfellows of right and left work closely together for as long as it takes to prevail against a Brave New World? Or, to put it another way, can deep differences over fundamental issues such as abortion be set aside long enough to prevent the threatened flood of human cloning? Jeremy Rifkin, who led what may have been the first anti-cloning demonstration more than twenty years ago at the First National Conference on Biotechnology, hopes so. While acknowledging that he is "very uncomfortable" working alongside people and groups with whose stances on other issues he profoundly disagrees, Rifkin believes that the struggle to defeat human cloning cuts a broad diagonal across the standard left/right divide. "Cloning pits believers in the 'intrinsic' value of human life against those who measure human life based on its 'utility,'" with conservatives, moderates, and liberals found in both camps, Rifkin says. Moreover, he believes that the cloning debate "will be as pivotal to the morality of the next hundred years as the struggle over slavery was to the Nineteenth Century."

Opponents of human cloning are not far from victory. With the House having passed a strong cloning ban, and President Bush endorsing efforts to outlaw human cloning, the advocates of cloning will make their last stand in the Senate. There, the Brownback bill (S. 1899) to outlaw human cloning, almost identical to the Weldon bill, is being countered by two pseudo-bans. Both the Harkin/Specter bill (S. 1893) and the Feinstein bill (S. 1758) claim to outlaw human "reproductive cloning," but both would explicitly permit cloning for research. In actuality, such proposals would open the floodgates to the cloning of human life, so long as the human embryos created thereby were never implanted in a uterus. Indeed, Feinstein's bill, which senators Clinton, Kennedy, and Boxer are supporting, is radically pro-human cloning. Not only would it permit Big Biotech researchers to clone human life without restriction, it would also preempt states from outlawing human cloning in their jurisdictions.

Where is all of this leading? If Brownback is passed, the human cloning agenda will be stopped in its tracks in the United States. That would permit researchers here to focus on uncontroversial and promising research into the development of medical therapies using adult and alternative sources of stem cells. If Brownback fails, or if either Feinstein or Harkin passes, hundreds and even thousands of human clones will soon be manufactured -- inevitably leading to reproductive cloning, since there would be no realistic way to prevent some scientist somewhere from implanting a cloned embryo into a woman desiring to give birth to the first human clone. A ban on "reproductive cloning" thus would actually open the door to the very act it purported to prohibit. But that would not be the end of it. The human cloning agenda is not limited to medical research or the development of new reproductive technologies. The ultimate goal for many proponents of human cloning is to use clones to model and perfect genetic engineering techniques that would permit scientists to seize control of human evolution. Clone embryos are deemed superior for this purpose to embryos created through fertilization because the former can be made in large supply, giving scientists many genetically identical embryos on which to experiment. This would make it easier for researchers to learn how to manipulate embryos so as to carry the genetic traits they want to foster. Once this was accomplished, many cell lines could easily be extracted for further research by repeatedly remaking the same clone embryo. Eventually, this technology would be applied to embryos ­ both natural and cloned -- destined for implantation, gestation, and birth. In the end, such practices would permit the new eugenics celebrated by Princeton biologist Lee M. Silver in Remaking Eden: Cloning and Beyond in a Brave New World. Embryos could be screened for genotype, leading to genetically modified human beings.

Nothing in the Feinstein or Harkin bill would prohibit such research. This is precisely why Rifkin and many others on the left fervently seek to outlaw all human cloning.

"Cloning would permit us to apply engineering standards to procreation. Our children would be selected based on quality controls, production outcomes, efficiency, and utility" -- in other words, the values of the assembly line. "Once we start engineering human life, we will lose our empathy," Rifkin warns. "Should that happen, we will have lost the human equation."

This is a compelling argument that people of all political stripes and religious sensibilities may be able to rally around regardless of their differences. If they do, the political struggle against human cloning and eugenics in coming years will be a battle not of left versus right but of right versus wrong, in which those who seem at first sight strange bedfellows strive together to thwart scientific hubris and foster a deeper respect for the intrinsic worth of human life.
 

Wesley J. Smith, a frequent contributor to THE WEEKLY STANDARD, is the author of Culture of Death: The Assault on Medical Ethics in America.