Please circulate widely and repost, but you must give the URL of the original and preserve all the links back to articles on our website
Cloned food animals declared safe by FDA
2008 the United States Food and Drug Administration (FDA) completed a ‘risk
assessment’ on the introduction of cloned animals into the food supply. It
concluded : “No unique risks for human food consumption were identified in
cattle, swine, or goat clones derived via somatic cell nuclear transfer (SCNT).
No anomalies have been observed in animals produced by cloning that are not
also observed in animals produced by other assisted reproductive technologies
(ARTs) and natural mating.” FDA defines an animal clone as a genetic copy of a
donor animal, similar to identical twins but born at a different time. Most
cloning today uses a process called somatic cell nuclear transfer (SCNT). Just
as with in vitro fertilization, scientists take an immature egg from a
female animal (often from ovaries obtained at the slaughterhouse). But instead of
combining it with sperm, they remove the nucleus, which contains the egg’s
genes, leaving behind the other components necessary for an embryo to develop.
Scientists then add the nucleus containing the desirable traits from a cell
obtained from the animal the farmer wishes to copy. After a few other steps,
the donor nucleus and egg fuse, start dividing, and
an embryo forms. The embryo is then implanted in the uterus of a surrogate dam.
as with in vitro fertilization, which carries it to term . (“Dam” is a term
that livestock breeders use to refer to the female parent of an animal).
The truth about SCNT
has made a substantial submission to the FDA criticizing its misleading stance
on cloning, especially for blurring the distinction between ordinary cloning
(by subdividing the cells of the early embryo) with SCNT, and stressing that
cloned meat and milk are unethical and unsafe  (Is FDA Promoting or
Regulating Cloned Meat and Milk? SiS 33). One key
section of the original submission is reproduced below (see Box).
real story about cloning
At issue is SCNT, the procedure pioneered in creating Dolly the
cloned sheep in 1996 
Death Sentence on Cloning, SiS 19). Cloning from the genetic material of an
adult animal means that all the genetic ‘elite’ qualities of the animal are
proven, so the clones in theory will reproduce those ‘elite’ qualities. More to
the point, it allowed the duplication of genetically modified (GM) animals
without the normal reproduction process, as GM animals tend to be either
sterile or to lose their transgenes or transgene expression in subsequent
generations. Dolly was a rehearsal for the cloning of an ‘elite’ herd of
transgenic animals producing valuable pharmaceuticals in their milk. That
turned out to be a pipedream. Cloning does not faithfully reproduce the
qualities of the adult, elite or otherwise.
The success rate of SCNT is
extremely low, and remains so to this day, between 0 and 5 percent across the
species: sheep, cattle mouse, pig, goat, rabbit, cat, notwithstanding. Here is
how one reviewer among many, Jonathan Hill at the College of Veterinary
Medicine, Cornell University, New York described it when he was opposing human
reproductive cloning .
“In each of the species where
somatic cell cloning has been successful, it has also been very inefficient.
Early first trimester pregnancy rates are less than ½ that normally expected.
Immediately following initial positive diagnosis of pregnancy, extraordinarily
high rates of embryonic loss occur, where up to 80% of pregnancies miscarry by
the second semester. In late gestation, placental and fetal abnormalities
occur at a much higher than normal rate, and finally lowered viability at birth
So hundreds of reconstituted eggs
have to be created to get dozens of embryos good enough to be implanted into
surrogate mothers just to end up with a few clones born live.
Those few clones that survive after
birth are by no means healthy: “Postnatal viability is markedly lower for many
cloned animals….Neonatal viability has been shown to be compromised due to
The remaining that seem apparently
healthy are not without problems, for “closer investigations have revealed that
even some of these apparently normal animals are subtly different from one
another and from the naturally produced population… What is of significant
concern is that placental development and the intrauterine environment for many
clones is suboptimal and this alone may impact on their health in later life.”
This was borne out by numerous
laboratories involved in cloning. In one experiment , 988 SCNT embryos were
transferred into cows resulting in 133 calves delivered at term, but only 67
percent survived to weaning at 3 months of age, with an average annual death
rate thereafter of more than 8 percent. The offspring of SCNT clones fare
better, though they have not been subjected to more discerning tests either.
Dolly had to be put down prematurely
at age six on account of severe illnesses, and the company PPL therapeutics
that helped to create Dolly failed to find a backer for its GM alpha-1
anti-trypsin produced in cloned transgenic sheep’s milk, and had to slaughter
its flock of 3 000 transgenic sheep in 2003  (Animal Pharm
Folds, SiS 19). Thus, SCNT has proven neither technically
successful nor economically viable.
Many, including Ian Wilmut, the
creator of Dolly, saw that as the end of SCNT cloning for producing animals,
and have since concentrated efforts into creating embryonic stem cells for
tissue replacement. But that too is misguided and ethically unjustified as many
clinical successes in tissue replacement have been documented using the
patient’s own adult stem cells while embryonic stem cells have yet to prove
themselves in a single clinical application so far  (No Case for
Embryonic Stem Cells Research, SiS 25).
The major problem with SCNT clones and with embryonic stem
cells made by SCNT cloning is the large numbers of genome-wide epigenetic
errors in gene expression associated with the nuclear transfer process,
resulting in the high failure rates of clones, and in the eyes of many
scientists, precludes the safe use of SCNT-derived embryonic stem cells in
tissue replacement .
Microarray analysis of more than 10
000 gene in clones found that about 4 percent of the genes in the placenta are
different from normal, with a smaller number of genes also affected in the
SCNT animals are not true clones
is a further aspect that distinguishes SCNT from other clones, in that the
animals created are not true clones with respect to the mitochondrial (mt)
genome. A US law defines assisted reproduction technologies (ARTs) as those that involve the handling
of both sperm and eggs. The vast majority of these involve in vitro
fertilization (IVF), in which oocytes are removed from
the mother’s body and fertilized with sperm in the laboratory, and returning
the embryo to the woman’s body. Fertilization of the oocyte is achieved either
through incubating sperm and oocytes together (classic
IVF) or through direct injection of a single sperm into the oocyte under the microscopic
in mammals, individual animals contain only maternally inherited mtDNA, as
paternal (sperm)-derived mitochondria are usually eliminated during early
development. Somatic cell nuclear transfer (SCNT) bypasses the normal routes mtDNA
inheritance and introduces not only a different nuclear genome into the
recipient cytoplast, the enucleated oocyte, but also
accompanying mtDNA. This mtDNA ‘heteroplasmy’ due to persistence and
replication of both oocyte mtDNA and somatic cell mtDNA means that offspring
generated by SCNT are not true clones. More importantly, the
consequences of the heteroplasmy, or possible incompatibility between nuclear
and mtDNA genotypes on subsequent development and function of the embryo, foetus
and offspring are unknown. Following sexual reproduction, mitochondrial
function requires the biparental control of maternally inherited mtDNA. SCNT-associated
incompatibility between the recipient cell mt and transplanted nuclear genomes ,may
result in energy imbalance and initiate mtDNA disease, or disruption of normal
developmental event .
heteroplasmy must not be ignored
clones would contain both the nuclear and cytoplasmic genotype of the nucleus donor, which is not the case for clones from SCNT. It has
been possible to strip most of the mitochondria from the donor cell by treating
with ethidium bromide a dye molecule that inserts itself among the stacked
bases of mitochondrial DNA. When the nucleus of the somatic cell lacking
mitochondria is injected into the egg from which the nucleus has been removed
the resulting cloned embryo and maturing animal is homoplasmic (having only egg
mitochondria [12-14]. The resulting animal clones are homoplasmic but they are
certainly not true clones because they have the nucleus of the cloned animal
but the mt genome of the egg. That distinction may seem academic, but the role
of the mitochondria in development and disease is profound. The importance of induced
dysfunctions related to nuclear reprogramming following SCNT cloning is very
consequential (see Box). That impact has been the focus of a great deal of
discussion and has not been denied or completely ignored by FDA. But FDA
continues to claim that the cloned animals are true clones while they are
heteroplasmy in cloned animals
humans as in other mammals, mt genome is strictly maternally inherited.
Mitochondrial heteroplasmy arises through mutations in the egg mitochondria.
Mitochondrial heteroplasmy may also be found in the tissues of individuals, but
that condition is not inherited. In contrast, SCNT gives rise to mitochondrial
heteroplasmy. It has been observed that the efficiency of bovine somatic cell
nuclear transfer (SCNT) depends on donor-host compatibility. The reprogramming
of the donor nucleus is influenced by the donor-host compatibility of the
mitochondria . In nuclear transfer-derived embryos, nuclear-encoded
mitochondrial DNA transcription and replication factors persist, but not in
embryos generated through in vitro fertilization. Consequently,
nucleo-mitochondrial interaction following nuclear transfer is out of sequence
as the onset of mitochondrial replication is a post-implantation event .
using nucleus from fibroblast from the ears of Holstein cattle transferred into
the eggs of Lund yellow cows were all heteroplasmic
for donor-egg mitochondria . Donor mtDNAs in SCNT pigs could be transmitted
to progeny . Moreover, once heteroplasmy was transmitted to progeny of SCNT-derived
pigs, it appeared that the introduced mitochondrial populations become fixed
and maternally-derived heteroplasmy was more readily maintained in subsequent
generations. There are numerous further publications dealing with SCNT-derived
mt heteroplasmy, which establish that the phenomenon is a typical consequence
of SCNT. It is very clear that FDA’s claim that cloned food animals are
identical to the donor animal and that the progeny of such animals bear only
the genes of the SCNT donor is false and misleading.
associated with mitochondrial heteroplasmy
diseases associated with mt heteroplasmy are transmitted through the mother
alone. The defects frequently include brain and nerve
defects or heart defects. One approach to curing such diseases has been
developed using monkey clones to closely mimic human clones. Donor mitotic nuclei
from mt-diseased eggs are transferred to eggs from which the nucleus has been
removed. The healthy nuclei from the diseased eggs divide in the healthy eggs that
provide a full complement of healthy mitochondria in both stem cell lines and
in complete embryos. Infant female monkeys developed from the transplanted were
free of diseased mitochondria, and capable of giving birth to disease free
infants. The method is presented as a way of preventing mitochondrial disease
transmission in affected human families .
in mtDNA may cause maternally-inherited cardiomyopathy and heart failure. In
homoplasmy, all mtDNA copies contain the mutation. In heteroplasmy there is a
mixture of normal and mutant copies of mtDNA. The clinical phenotype of an
affected individual depends on the type of genetic defect and the ratios of
mutant and normal mtDNA in affected tissues. These included a novel
heteroplasmic mutation in tRNA serine in a patient with sudden cardiac death .
A well-characterized pathological mutation at a nucleotide position of human
mitochondrial DNA was introduced into human teratocarcinoma NT2 cells. In
cloned and mixed populations of NT2 cells heteroplasmic for the mutation, there was invariably a tendency toward increasing levels of
mutant mtDNA as the cells multiplied. Rapid human teratocarcinoma NT2 cell multiplication was frequently followed by
complete loss of mtDNA. These findings support the idea that pathological mt
DNA mutations are particularly deleterious in specific cell types, which can
explain some of the tissue-specific aspects of mtDNA diseases. Moreover, these
findings suggest that mitochondrial DNA depletion may be an important and
widespread feature of mtDNA disease .
diseases have been extensively studied and reviewed in recent years . Mitochondrial
disorders may be caused by defects of nuclear DNA or mtDNA. Nuclear gene defects
may be inherited in an autosomal recessive or autosomal dominant manner. MtDNA
defects are transmitted by maternal inheritance. MtDNA deletions generally occur
de novo and thus cause disease in one family member only, with no
significant risk to other family members. MtDNA point mutations and
duplications may be transmitted down the maternal line. The father of an ill
individual is not at risk of having the disease-causing mtDNA mutation, but the
mother of a ill person (usually) has the mitochondrial mutation and may or may
not have symptoms. A male does not transmit the mtDNA mutation to his
offspring. A female harboring a heteroplasmic mtDNA point mutation may transmit
a variable amount of mutant mtDNA to her offspring, resulting in considerable clinical
variability among sibs within the same family. Prenatal genetic testing and
interpretation of test results for mtDNA disorders are difficult because of
mtDNA heteroplasmy. Consuming meat from cloned animals is unlikely to cause
mitochondrial disease but consuming meat from heteroplasmic animals is
entirely new to human experience worldwide and such animals are bound to have many hidden defects.
Cloning and the law
plays a key role in dealing with arbitrary and capricious bureaucratic rulings.
The views expressed in articles from law journals show widely different appraisals of FDA in regulating foods from cloned animals,
Jennifer Butler, a lawyer and professional molecular biologist, has a clear
understanding of the cloning process and heteroplasmy. Her article includes a
valuable history of FDA and an excellent proposal that FDA should be replaced
with an agency better equipped to deal with technologies involved in genetic
modification and animal cloning . A group of lawyers from Proskauer LLP New
York reviewed the risks involved in marketing meat from cloned animals or in consuming
dairy products from cloned animals, and urged the FDA to institute effective
tracking and diagnostics to allow adequate evaluation of the true health
risks. But there was no mention of heteroplasmy, and
FDA’s claim that the animals are true clones implicitly accepted . John Murphy, a lawyer and a professional chemical engineer,
commented that there were no valid safety concerns over consuming food from
cloned animals and moral concerns were tangential and overboard. He further
concluded that labelling of the
products of cloned animals is not valid based on unspecified scientific grounds
. Butler is the clearly the only lawyer who has made a thorough and
comprehensive study of food animal cloning, and hence can speak the most
authoritatively on the issue.
food animals are not true replicas of the animal donating the nucleus in SCNT.
The cloned animals contain heteroplasmic mixtures of mitochondrial genes from both
the somatic cell and from the egg receiving the somatic cell nucleus. In nature,
only the maternal parent provides mitochondrial genes. SCNT is a process
entirely new to nature, and also departs
significantly from in vitro fertilization. Mitochondrial heteroplasmy,
and ensuing mitochondrial depletion, has been implicated in diseases affecting
the brain, the central nervous system and the heart. FDA wrongly claims
that the heteroplasmic offspring of SCNT are true
clones, thereby exposing its pronouncement as public relations propaganda and not
science. There is no evident cure for the mitochondrial heteropasmy in SCNT, and
for that reason all animals created by SCNT and their offspring are illegal for
commercial release, apart from being unethical and unsafe for consumption.
5. Hill JR. Abnormal in
utero development of cloned animals: implications for human cloning.
Commentary. Differentiation 2002, 69, 174-8. Depart of Clinical Sciences College of Veterinary Medicine, Cornell University, New York.
6. Wells DN, Forsyth JT,
McMillan V and Obeck B. The health of somatic cell cloned cattle and their
offspring. Cloning Stem Cells 2004, 6, 101-10.
12. Lee JH, Peters A, Fisher
P, Bowles EJ, St John JC, Campbell KH. Generation of mtDNA homoplasmic cloned
lambs. Cell Reprogram. 2010, 12(3), 347-55.
13. Bowles EJ, Lee JH,
Alberio R, Lloyd RE, Stekel D, Campbell KH, St John JC. Contrasting effects of
in vitro fertilization and nuclear transfer on the expression of mtDNA
replication factors. Genetics 2007, 176(3), 1511-26.
14. Lloyd RE, Lee JH,
Alberio R, Bowles EJ, Ramalho-Santos J, Campbell KH, St John JC. Aberrant
nucleo-cytoplasmic cross-talk results in donor cell mtDNA persistence in cloned
embryos. Genetics 2006, 172(4), 2515-27
15. Yan ZH, Zhou YY, Fu J,
Jiao F, Zhao LW, Guan PF, Huang SZ, Zeng YT, Zeng F. Donor-host mitochondrial
compatibility improves efficiency of bovine somatic cell nuclear transfer. BMC
Dev Biol 2010, 10, 31.
16. Lloyd RE, Lee JH,
Alberio R, Bowles EJ, Ramalho-Santos J, Campbell KH, St John JC. Aberrant
nucleo-cytoplasmic cross-talk results in donor cell mtDNA persistence in cloned
embryos. Genetics 2006, 172(4), 2515-27.
17. Han ZM, Chen DY, Li JS,
Sun QY, Wan QH, Kou ZH, Rao G, Lei L, Liu ZH, Fang SG. Mitochondrial DNA
heteroplasmy in calves cloned by using adult somatic cell. Mol Reprod Dev
2004, 67(2), 207-14.
18. Takeda K, Tasai M,
Iwamoto M, Akita T, Tagami T, Nirasawa K, Hanada H, Onishi A. Transmission of
mitochondrial DNA in pigs and progeny derived from nuclear transfer of Meishan
pig fibroblast cells. Mol Reprod Dev 2006, 73(3), 306-12.
19. Tachibana M, Sparman M,
Sritanaudomchai H, Ma H, Clepper L, Woodward J, Li Y, Ramsey C, Kolotushkina O,
Mitalipov S. Mitochondrial gene replacement in primate offspring and embryonic
stem cells. Nature 2009, 461(7262), 367-72
20. Zaragoza MV, Fass J,
Diegoli M, Lin D, Arbustini E. Mitochondrial DNA variant discovery and
evaluation in human Cardiomyopathies through next-generation sequencing PLoS
One 2010, 5(8), e12295.
21. Turner CJ, Granycome C,
Hurst R, Pohler E, Juhola MK, Juhola MI, Jacobs HT, Sutherland L, Holt
IJ.Systematic segregation to mutant mitochondrial DNA and accompanying loss of
mitochondrial DNA in human NT2 teratocarcinoma. Cybrids Genetics. 2005, 170(4),1879-85.
22. Chinnery PF. Mitochondrial
disorders overview. In: Pagon RA, Bird TC, Dolan CR, Stephens K (eds). GeneReviews
[Internet]. Seattle (WA): University of Washington, Seattle; 1993-2000 Jun 8
[updated 2010 Sep 16].
23. Butler JE. Cloned animal
products in the human food chain: FDA should protect American consumers. Food
Drug Law J 2009, 64(3), 473-501.
24. Solomon LM, Noll RC,
Mordkoff DS, Murphy P, Rolerson M.A brave new beef: The US Food and Drug
Administration's review of the safety of cloned animal products. Gend Med 2009,
25. Murphy JF. Mandatory
labeling of food made from cloned animals: grappling with moral objections to
the production of safe products. Food Drug Law J 2008, 63(1), 131-50.
Justin Comment left 14th October 2010 19:07:18 Dear writers,
I appreciate your concern for my diet, but calm down, it's bad for your health. As your own article points out, there is NO HEALTH CONCERN.
Heteroplamic mitochondria derived from SCNT has been know about yes, but it is also more common in nature than you might think. Even supposed "pure breed" equine have been shown to exhibit this.
Also, the sperm contains its own MT. Far less than a donor cell, but even in nature there is dreaded heteroplasmy a least for a while.
OK technically speaking they may not be an exact replica, but have you seen the cloned equine being produced. They are beautiful! You think people are going to buy a steak from a sick animal? NO only the strong will survive. So instead of playing lawyer over a technicality, why don't you go work on something useful. And finally, there were not and aren't any laws being broken!
Rory Short Comment left 6th November 2010 17:05:09 It seems to me that we have here an excellent example of human greed over riding any and all concerns about possible negative consequences of a technology.
joe cummins Comment left 15th October 2010 12:12:05 Replying to Justin: Thank you for your interesting comment. I should point out that your diet has not been a matter of concern , however, it does seem to be a matter worthy of grave concern. I hope that you survive it. FDA defines an animal clone as a genetic copy of a donor animal, similar to identical twins Identical twins arise as a split of an embryo and those twins have identical maternal mitochondrial genes. In contrast clones contain mitochondria from the egg and from the somatic cell donating the nucleus to the clone. FDA made false claims about somatic cell nuclear cloning and any regulation of food flowing from knowingly false claims is certainly illegal.
Your comments on equine clones are peculiar and it is not clear whether you are eating cloned horses or riding them or both. I find that your comment on frequent heteropasmy in horses is not born out by the scientific literature. For example 'We detected no heteroplasmy or deviations from strict and stable maternal inheritance when examining four maternal lineages, each represented by six to eight horses, separated by up to five generations from a common ancestral mare' S Marklund,et al Extensive mtDNA diversity in horses revealed by PCR–SSCP analysis Animal Genetics Volume 26, Issue 3, pages 193–196, June 1995
michael Comment left 12th October 2010 09:09:48 As a retired farmer, with grandchildren endangered by ubiquitous dietary terrorism, I fully understand the importance of this message.
It may take at least three re-reads, dictionary at hand, to get the hang of the fine detail, but the content deserves it.
ps A post to your webmaster returned with this note:-
A message that you sent could not be delivered to one or more of its
recipients. This is a permanent error. The following address(es) failed:
No Such User Here"