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[NOTE: The following article on "therapeutic" and "reproductive" cloning is at best rambling. Thus I have emphasized in "underline" those phrases that need quick attention. My own comments are bracketed and in "block". The main thrust of this article is that using SCNT with adult donor cells is genetically too risky for reproductive purposes(!). Therefore, it would be better to use SCNT with embryonic donor cells. To justify this research it is necessary for the authors to: as usual, frame the issue only in terms of "therapeutic" and "reproductive", rather than admit that there are many cloning techniques available to be used in addition to SCNT; deny the objective reality of the cloned (or uncloned) human embryo as a fully existing human being whose embryonic "stem cells" are to be mined; subtly switch back and forth between "therapeutic" and "reproductive" cloning, and between human embryos and animal embryos to blur important distinctions; redefine "therapeutic cloning" so as not to involve any human embryo whatsoever; resort to the ole "pre-embryo" trick to assuage consciences; and redefine as "normal" what is in fact empirically "abnormal". A whole lot of redefining going on here -- just to confuse you! (emphases added) -- DNI]
Cloning Secrets Prove Elusive; Despite Successes, Creation Seems Hit And Miss
BY LISA M. KRIEGER
Knight Ridder Newspapers
Posted on Fri, Sep. 12, 2003
http://www.macon.com/mld/macon/news/nation/6754639.htm
SAN JOSE, Calif. - (KRT) - The birth of a lab-built lamb in 1996 seemed to defy nature. Her premature death this year shows that nature, in fact, still holds some secrets.
In the years since the creation of the world's first cloned animal, Dolly, scientists have discovered that life is far more complicated than a Xerox machine.
It will never be certain if Dolly's demise, at age 6, was linked to her birth. But hundreds of subsequent clones - some dead, others damaged - are revealing several missteps taken on the road to create life in the lab.
So complex is the process that the prospect of human reproductive cloning, claimed by a group called the Raelians last year, seems not only foolhardy but highly dangerous and unethical. So-called "therapeutic cloning," which builds only tissue and not an entire organism, seems much safer.
[[Note the total refusal to acknowledge right from the start the objective scientific fact that these cloned "therapeutic" tissues that are "built" must be derived from a cloned human embryo, a living human being, a living human organism who is destroyed in the process of retrieving his/her cloned stem cells. This article is all part of the effort initiated recently by Dr. Irving Weisman (Stanford University), who wants to redefine "therapeutic cloning" as "not cloning" -- not the cloning of a human being, that is! The immediate product of "therapeutic cloning" is not an embryo, he claims, but just a bunch of stem cells! (This, BTW, is the same definition given by then-Director of NIH Harold Varmus in his recent testimony before a Congressional committee on stem cell research!). Seems silly, really. Missed an entire step there -- i.e., it is the new living human embryo that is the immediate product of "therapeutic whatever" from whence come the stem cells! Bioethicist Art Caplan prefers to redefine this human embryo as "an embryo-like thing"! All pseudo-scientific substitutes for the mythological "pre-embryo" with its "reduced moral status". But all these verbal maneuvers and manipulations won't work as long as there are scientific libraries still open around the world. -- DNI]]
"Reproductive cloning is an inefficient and error-prone process that results in the failure of most clones during development," say Konrad Hochedlinger of the Massachusetts Institute of Technology and Rudolf Jaenisch of the Whitehead Institute for Biomedical Research of Cambridge, Mass., in a recent issue of The New England Journal of Medicine.
[[Reproductive cloning is no different than therapeutic cloning insofar as they both involve the immediate reproduction of a new living human being. Only what these human beings will be used for is different. Therefore, the very same problematic cloning processes used to reproduce these human embryos will result in the same genetic errors in all of the human embryos reproduced for either purpose.
One issue that these "scientists" consistently fail to address, at least publicly, is this: If human embryos cloned only for the purpose of producing "therapeutic" cells, tissues and organs are so profusely genetically flawed, then just how "therapeutic" could these cloned cells possibly be when injected, or when cloned tissues or organs are transplanted, into already sick patients? And what possible good would it do to spend trillions of dollars to set up cloned tissue and organ cultures and laboratories when the application of such genetically flawed cloned materials would most probably harm rather than heal these patients? What knowledge or information about normal human cells, tissues or organs could such abnormal genetically flawed cloned materials provide "for the advancement of scientific knowledge", and at what cost? -- DNI]]
Many cloned embryos are miscarried; others have abnormalities. Although accurate statistics are hard to come by, Jaenisch and Hochedlinger estimate that 1 to 10 percent of cloned embryos from adult donor cells develop completely, depending on the species. Another estimate, by Michael West and Robert Lanza of Advanced Cell Technology, puts the number at closer to 50 percent or less.
[[Note the subtle shift back and forth between "therapeutic" cloning and "reproductive" cloning in this article. And I thought these scientists were all in agreement that considerations of and attempts at reproductive cloning was off the table! Translated into human terms, this means for the public that if human reproductive cloning is to succeed, it will require research that will reproduce abnormal human embryos, most of whom will die in utero. Repeat: in utero. Ultimately human subjects, i.e., women, will have to be used in such purely experimental research projects in order to empirically verify the "therapeutic" information needed to reproduce "normal" cloned human babies. But such reproductive cloning will not be called "experimental research" (which it is). After all, what woman would knowingly and willingly subject herself and her "wanted" baby to such genetic trials and errors? Rather, it will be called an "innovative therapy" (just as current clinical IVF procedures are mislabeled "innovative therapies"). But it is really reproductive cloning experimental research -- and most such so-called "therapies" will probably be carried out in IVF clinics. -- DNI]]
To get Dolly the sheep, it took 277 tries; Carbon Copy, the cloned kitten, came after 86 failures. Only 33 monkey embryos have been created after 738 attempts - and none have produced a live birth.
It is through these failures, say scientists, that improvements can be made in the future safety and efficiency of reproductive cloning.
[[Precisely, and this is the cost. Note that in research ethics the means used must be as ethical as the end or goal. Here, the means used involve not only the deliberate killing of innocent living human embryos during the process of "therapeutic" cloning in order to gain new information about genetic defects in these embryos, but also the use of women's bodies in order to gain new information about how such cloned embryos will succeed (or not) in utero - reproductive cloning research. It is perfectly clear that scientists are intent on human reproductive cloning -- as long as it can be made "safe" -- however they may choose to define that term. But ethically, in both therapeutic and in reproductive cloning, the means used are grossly unethical, and thus both such research protocols are grossly unethical per se. -- DNI]]
"Further studies will try to identify ways to reduce and perhaps eliminate the losses during pregnancy and infancy," wrote Michael West of the cloning company Advanced Cell Technology of Worcester, Mass., in the journal Nature-Biotechnology. "More work needs to be done to study these animals as they age and reproduce, and to determine why the incidence of abnormalities is high under some circumstances and absent in others."
[[It is often not clearly understood that in order for a scientist to make a new scientific claim and justify it as objective fact, scientists are professionally required to follow the scientific method -- or at least they used to be. This method would require that scientists empirically verify their genetic interventions by means of "testing" the short and long term results of such genetic interventions in utero and even long after birth -- thus empirically verifying the cause and effect link between their experimental interventions and any genetic effects in the developing human embryo/fetus in utero and beyond. This would often necessitate elective abortions in order for the scientists to physically examine their research "results". Moreover, such empirical findings must also be replicated by many other investigators and laboratories before becoming accepted as objective fact. Now, just how many abnormal cloned human beings, just how many elective abortions, and just how many unsuspecting women's bodies, is this effort going to require in order to pass scientific rigor even on the theoretical level alone? -- DNI]]
The concept behind cloning seems deceptively simple. By replacing the genetic material of an egg with that of a donated adult cell, it should be possible to create an exact copy of another living creature.
Achieving this goal is another matter.
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In the most definitive analysis to date, published July 17, Hochedlinger and Jaenisch assert four major conclusions about cloning research:
___Most clones die early while developing in the uterus. Only a few survive to birth or beyond.
___Clones that live often have common abnormalities, regardless of the type of donor cells or the species of animal used.
___These abnormalities seem linked to aberrant gene expression, most likely caused by faulty "reprogramming" of the genes that drive normal embryo development.
___The dismal inefficiency of cloning is linked to the state of the donor cell.
[[Now comes the build-up to the argument that it would be better to use donor cells derived from the earliest embryos rather than use donor cells derived from adults. -- DNI]]
Donor cells that are more "differentiated" - that is, they have matured further along life's developmental pathway - offer less success.
"You see different health outcomes among different species," said Ben Carlson, spokesman for Genetic Savings and Clone in Sausalito, Calif., which cloned the first cat. "And within a single species, you see a range of outcomes depending on who is doing the research and what techniques they're using."
Many cloning problems arise because of the key difference between normal fertilization and cloning, scientists have learned.
A normal fertilized egg contains genetic material from sperm and egg. The genes in the sperm and egg, when united, turn on or off in a precise pattern that is in perfect readiness for the complex development of an embryo.
It is the process of fertilization that provides the zygote, or "pre-embryo," with the ability to direct normal development. This programming ability ensures the proper activation of genes during embryonic development.
[[Note, still, the use of the junk science term "pre-embryo"! These scientists know perfectly well that scientifically there is no such thing as a "pre-embryo", but they also know that the use of this fake term is a terrific way to manipulate public opinion. If the immediate product of either fertilization or cloning is just a "pre-embryo", then it is perfectly acceptable to destroy it in order to do these experiments, since it only has a "reduced moral status". But if the immediate product of fertilization or cloning is a real live human embryo, a living human being, well then that gets a little touchy.
It is truly amazing -- and a disgusting testimony to the lack of veracity and honest intentions of these new-age scientists -- that they are still trying to fool the public with such junk science. The question we should all ask ourselves is, if they are so willing to continuously lie about this simple scientific fact, what other scientific facts are they willing to lie about in order to manipulate not only the public, but also their funders and supporters? Why should we trust anything they tell us?
To see just how out of control science has become, let me share with you an e-mail forwarded to me by one of my students who knows full well how fake the term "pre-embryo" is and why it is used. She recently noticed the use of the term on a web site for a well-established IVF clinic in the South East, and inquired of them why they were still using this scientifically fake term long-rejected by the International Nomina Embryologica Committee. Here is the reply she received from one of their IVF "scientists":
"Dear XXX: sorry for the confusion. Our website is constantly being updated of late, and as it is such a broad and long established website, there is much apparent inconsistency over terminology. However, to answer your question directly: the term "pre-embryo" has been proposed as the appropriate term to refer to an undifferentiated entity that has not even established whether it will be one or two individuals (twinning?), and in a sense (up till day 3 of develpment) has not even kicked in its own embryonic genetic gameplan. [[Note: all of which is also junk science - DNI] Hence, the term "pre-embryo", being an entity preceding an "actual" embryo. All glorious semantics really - and frankly it is what it is, and this oddity is still used especially by many in the IVF world who have "graduated" from The Jones Institute in Norfolk, VA. Therefore shd you wish to attempt a "fix" on this term, refer to Howard &Georgeanna Jones. As to "human embryologists" this simply defines them as embryologists working with human embryos as opposed to any other species. Nothing more. You cd semantically take exception to this terminology also, as most "human embryologists" are nothing more than clinical early stage embryo jockeys, with little true appreciation of classical embryology as a discipline within biology - this wd probably include me, who, past day 7 of development has only an amateurish grasp of subsequent embryological development. [[Note: and these are the "expert" human embryologists on whom we as a society are to rely so heavily? No wonder they don't really know what they are doing. Real human embryologists should worry about these fradulent "scientists" passing themselves off as such! - DNI]] The question to ask yourself really is: was this really worth worrying abt?
sincerely,
XXX"
An astounding admission. Scary. I think this revealing statement speaks volumes for itself, and needs no further comment. -- DNI]]
The central problem with cloning is this: Since clones do not undergo fertilization, this programming does not occur. So the genes of the donated cells are not in a state of perfect readiness.
This leads to errors in a process called "imprinting," during which genes in the embryo are switched on or off. Cloned animals seem to lack the ability to generate the right pattern of imprinting. Since imprinted genes are important for fetal growth and placental function, aberrant expression of these genes might account for the fetal and placental abnormalities in clones, according to Jaenisch.
When the donated adult cell is merged with the egg, the egg tries its best to reprogram - but it doesn't do very well. All the right genes are correctly reprogrammed in only a tiny minority of clones.
The nucleus of the donated adult cell tends to be already very specialized, or differentiated, for a particular function. To make matters worse, its instructions are typically locked away and cannot be changed. So this donated cell's DNA is not reprogrammed correctly to switch on genes that drive normal embryo development.
"The clone remembers where they came from - who the donor was," said Jaenisch, attending a cloning conference at Stanford University School of Medicine last spring.
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The type of donor cell has been linked to specific defects. For example, clones derived from so-called cumulus cells become obese. Those derived from Sertoli cells die prematurely.
Animals cloned from immature cells are born far hardier and far more likely to survive normally, he said.
[[Which is to say, the more immature the cells are that are used in cloning, the more likely the embryo is to survive "normally". Therefore, he implies, we should use cells "derived" from early human embryos (reproduced either sexually or asexually) for cloning experiments to reproduce new cloned human embryos who can be either used for "therapeutic" purposes, or implanted for "reproductive" purposes. "Surplus" human embryos (frozen or otherwise) reproduced sexually in IVF laboratories and clinics are plentiful and could provide a constant and continuous source of "immature cells" for researchers and clinicians to use in these human cloning experiments. And once cloned human embryos are asexually reproduced, they too will provide a constant and continuous source of "immature cells" for all interested parties. After all, for these "salesmen", the immediate product of any human reproductive process is just a "pre-embryo, just a bunch of stem cells, or an "embryo-like thing"! No human embryos, therefore no human beings involved. Therefore no ethical issues involved. These human beings have been redefined away. -- DNI]]
"For a donor nucleus to support development, it must properly activate genes important for early embryonic development - and suppress the genes" that are active "in the original donor cell," Jaenisch wrote.
"The challenge is how to reset the 'adult' pattern of genetic expression to an 'embryonic' one," Jaenisch said.
[[Oppps! Doesn't Jaenisch mean "to a pre-embryonic one"?! So you see, they know perfectly well what their proposed research entails -- the direct intentional destruction of living human embryos in order to artificially clone new living human embryos -- patronizingly called "therapeutic cloning" --, and the direct intentional reproduction of abnormal living human embryos to be tested in human women in order to verify their experiments -- patronizingly called "reproductive cloning". -- DNI]]
Occasionally, the fusion of cloning is perfect - and the resulting fused cell carries the correctly programmed genetic instructions so it can divide as if it were a fertilized egg, producing a healthy offspring.
But the recent death of Dolly the sheep is a sobering reminder of how complex and poorly understood the process remains. It will never be known whether her demise was related to her creation. Many middle-aged sheep confined to barns develop health problems. But ailments - a progressive lung infection, arthritis and premature aging - suggest trouble.
Such so-called "normal" clones may have abnormal regulation of many genes, researchers caution. Jaenisch has examined 10,000 mouse genes in the livers and placentas of cloned mice and found that hundreds of the genes exhibited abnormal patterns of activity.
This may explain the high rate of miscarriages, as well as respiratory distress and defects of the kidneys, liver, heart and brain. Cloned creatures sometimes experience rapid aging.
[[How can these "scientists" define such embryos as "normal"? More manipulation of words in order to manipulate the public? Sounds, like Humpty Dumpty's musings in Through the Looking Glass, "When I use a word, it means just what I choose it to mean -- neither more nor less. ... The question is, which is to be master -- that's all." - DNI]]
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To succeed in reproductive cloning, scientists say, they need to understand how those instructions get reset. The unlocking and resetting of instructions - without making changes to the genetic code - is called epigenetic reprogramming.
If scientists are able to master reprogramming, is it possible that the cell could be assured of developing into a healthy new organism - instead of continuing to do its old specified cellular functions, Jaenisch and Hochedlinger write.
There may be other approaches to skirting roadblocks to cloning. It is known, for instance, that animals cloned from embryonic stem cells, instead of adult cells, survive much better.
[[Ah, here is the pitch. If we want fewer abnormal (or normal?) embryos, then we must use diploid cells taken from early human embryos, instead of taking them from adults. Of course, he neglects to mention, again, that the "embryonic stem cells" must come from embryos -- living human beings who could either be destroyed, or be rendered abnormal (or normal") themselves, in the process of obtaining their stem cells. The logic of their "ethics" works only if they deny the reality of the living human beings who will be thus effected, only if they are considered "pre-embryos" or just a bunch of stem cells -- or just "women". And so they do, with no regard whatsoever for intellectual honestly or scientific integrity. What else will they say without intellectual honesty or scientific integrity in order to manipulate the public?
But let's face it. Scientists have known for a long time that the use of the somatic cell nuclear transplant (SCNT) cloning technique is far too risky -- even if using embryonic cells as donors. They also know that they don't need to use SCNT if they want to clone human beings. They could more easily use several other cloning techniques, e.g., twinning (because these early embryonic cells are all totipotent), pronuclei transfer, etc. -- and such cloning techniques have already been refined for decades now in IVF and in transgenic animal research. Not new. Genetically safer. All they need is access to IVF-reproduced human embryos. No problem. All they have to do is redefine "twinning" as not a form of cloning -- it is just an "innovative technique". However, human molecular genetic texts internationally all agree that twinning is the premiere form of cloning. But that won't stop Humpty Dumpty. He'll just redefine "twinning" as something else -- something appealing that by-passes the "public yuk factor", and people will never know the difference. -- DNI]]
In a case where abnormal placentas were a problem, normal babies were born if special steps were taken to save them prior to birth.
Even in conventional human reproduction, there is a 4 percent rate of birth defects, notes Carlson of Genetic Savings and Clone. With in vitro fertilization and other techniques, the rate is higher.
"The question becomes, how far do we have to go in improving the outcomes of cloned cats and dogs so that when we offer pet cloning services to the public, they'll feel comfortable with their odds of getting healthy results?
[[Excuse me, I thought we were just talking about human reproductive cloning! Do these "scientists" really mean us to believe that the real purpose of this article and of reproductive cloning is for producing cloned cats and dogs? Where are the animal rights groups? Are you confused? Good. You're supposed to be. That's the purpose of the article. -- DNI]]
"What is a level at which someone will say: 'That is an acceptable risk?'"
[[To whom?? -- DNI]]
© 2003, San Jose Mercury News (San Jose, Calif.).
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