Human cells from cloned embryos in research and therapy
BMJ 2004; 328 doi: https://doi.org/10.1136/bmj.328.7437.415 (Published 19 February 2004) Cite this as: BMJ 2004;328:415All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
It is clearly very important before any use of cells derived from
cloned embrbyos to ensure that they are appropriate for their purpose,
including an asessment of life span of the cells. However, there are a
number of misunderstandings in the letter. First, Dolly did not die of
premature aging. She was euthanised because she had a virally induced lung
tumour. There is no method of detecting the infection before the tumour
develops nor any treatment for the disease.
Secondly, it seems that in the vast majority of cases telomere length is
fully restored in cloned animals, including in sheep. It is not clear why
this was not the case on Dolly. One possibility is that the type of cell
used as nuclear donor influences telomere length, but this hypothesis
remains to be tested.
Competing interests:
I own shares of the Geron Corporation who have also supported some of our research
Competing interests: No competing interests
Leaving aside the ethical considerations, using cloned embryos with
transferred host nuclear material entails some risk which does not appear
to have been considered.
Human fibroblasts have been shown to have shortened DNA
(specifically, loss of telomere from the chromosome tips), which is
proportional to the age of the host, in both cultured [Harley et al, 1990]
and freshly donated cells [Allsopp et al, 1992]. Shortened telomere
length is associated with reduced viability in culture, and has been shown
in individuals with congenital premature aging [Allsopp et al, 1992]. DNA
analysis of cloned sheep has demonstrated abnormally shortened telomeres
[Shiels et al, 1999].
Taking a donor nucleus from the skin, and implanting it into an egg
cell to produce an embryo is therefore likely to produce a cloned embryo
with a restricted life expectancy, with a time of senescence synchronous
to that of the host. In the case of tissue produced in this way to
'repair' pathology -e.g. pancreatic cells to cure type I diabetes-
senescence of the repair at the same time as the donor-recipient might not
be considered a great problem, unless there is a period of accelerated
telomere loss at the stage of embryo growth, in which case, the original
fault is likely to re-emerge.
In the case of an embryo used to produce a child, this could be
disastrous: if the donor nuclear material is taken from a forty year old
(not an unreasonable scenario in assisted fertilisation), the cloned
individual would be born with a life expectancy reduced by forty years.
It will be recalled that Dolly the Sheep died a premature death from
premature aging, and the reason for this should be fully understood before
a human is unnecessarily exposed to the risk of being cloned into an
artificially shortened life.
Martin Mayfield
General Practitioner
Guiseley, Yorkshire
Allsopp RC, Vaziri H, Patterson C, Goldstein S, Younglai EV, Futcher
AB, Greider CW, Harley CB: Telomere length predicts replicative capacity
of human fibroblasts. Proc.Natl.Acad.Sci.USA 89: 10114-10118; 1992.
Harley CB, Futcher AB, Greider CW: Telomeres shorten during ageing of
human fibroblasts. Nature 345: 458-460; 1990.
Shiels PG. Kind AJ. Campbell KH. Waddington D. Wilmut I. Colman A.
Schnieke AE. Analysis of telomere lengths in cloned sheep. [Letter]
Nature. 399(6734):316-7, 1999 May 27
Competing interests:
None declared
Competing interests: No competing interests
Sirs,
I should like to express my scientific opinion about human cloning
and consequently human cells from cloned embryos in research and therapy.
Cloning indicates the possibility to generate two or more organisms,
showing the same genetic equipment starting from unique donor.
Notoriously, this process is based on the strong statement, claiming that
“nucleus”, and I underscore “nucleus”, of every tissue cell of an
individual contains its complete genetic endowment, and, therefore, the
whole information in order to reproduce an organism. Consequently, it is
sufficient and necessary to substitute the “nucleus” of an ovolum with the
cellular “nucleus” of tissue specimen cell, and subsequently activate it
simulating spermatozoon contact. The individual, who will be born, will
show the same genetic endowment as that from whome cellular “nucleus” has
been drawn. At this point, development process of embryo will initiate,
which will be transplanted in a womb, to perform pregnancy. In my opinion,
at the base of such as argument, with which all scientists apparently
agree, there is a fundamental bias, i.e., whole DNA is in the “nucleus”.
By contrast, it is now-a-days well-known, even to laymen, that exists also
the mitochondrial DNA (in almost all cells, of course, but not in all),
localized in well-defined cytoplasmatic structures, varying from 400 to
1200 per cell, which represent cellular “lungs”, providing endo-cellular
free energy. In addition, mit-DNA codes really 13 “essential” proteins,
unavoidable for individual’s life, indepentenly from n-DNA interaction. I
have previously (more than 25 years ago) demonstrated “clinically” (1-4)
(See web site HONCode 233736, www.semeioticabiofisica.it) that it exists a
functional mitochondrial abnormality, that causes the most common and
serious human disease, including Type 2 diabetes (5) and malignancy: I
termed such as mitochondrial cytopathology Congenital Acidosic Enzyme-
Metabolic Histangiopathy (CAEMH). This mitochondrial functional impairment
is different, as regards it seriousness, from individual to individual,
from tissue to tissue of the same individual, as well as from part to part
(from cell to cell) of the same biological system. In a few words, I think
that the present concept of human cloning is not an indication of a
scientific event, but rather one of desolate and arrogant scientism.
1) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica
condizione necessaria non sufficiente della oncogenesi. XI Congr. Naz.
Soc. It. di Microangiologia e Microcircolaz. Abstracts, pg 38, 28
Settembre-1 Ottobre, Bellagio 1983
2) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica. X
Congr. Naz. Soc. It. di Microangiologia e Microcircolazione. Atti, 61. 6-7
Novembre, Siena 1981
3) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica. Una
Patologia Mitocondriale Ignorata. Gazz Med. It. – Arch. Sci. Med. 144, 423
(Infotrieve) 1985
4) Stagnaro S., Polimialgia Reumatica Acuta Benigna Variante. Clin. Ter.
118, 193 (Pub-Med indexed for Medline)
5) Stagnaro S., Diet and Risk of Type 2 Diabetes. N Engl J Med. 2002 Jan
24;346(4):297-298. letter [PubMed –indexed for MEDLINE].
Competing interests:
None declared
Competing interests: No competing interests
A Matter of Nomenclature
Ian Wilmut's leader "Human cells from cloned embryos in research and
therapy" (BMJ, 21st Feb 2004) brings the current research in this area up
to date, and it is not only appropriate but timely as well. The somatic
cell nucleus transfer technology which led to the birth of Dolly the sheep
was the most remarkable development since the birth of Louise Brown using
an in vitro fertilisation technique.
However, Ian Wilmut makes the huge assumption that the hearts and
minds of the "consumers" have been won, which is very far from the truth.
Not only the ordinary people but even the professionals find research in
this area unsettling. The difference between reproductive and therapeutic
cloning is lost in the debate in the lay press. Cloning as a term has
disconcerting connotations for most non-scientific people. Somatic cell
nuclear transfer is a mouthful but describes the process much more
accurately and takes us away from the dreaded word. It would be in
everybody's interests to be precise in their description of their work and
reiterate the difference between therapeutic and reproductive aspects of
the research.
Another area which causes distress among people is the creation and
use of embryos to develop stem cells. There is instinctive emotional
abhorrence of any research which specially creates embryos and discards
them once they are no longer needed. Two things might make this
acceptable; one would be some use of stem cells which can be shown to have
made a real difference to patients' suffering. Patients would not only
accept but actively support the research if it can be shown to tangibly
make a difference to their lives. Another thing would be some other way of
developing stem cells - eg, from adult cells. Even though stem cells are
best obtained from embryos at this stage, there is no reason why in the
future, with more understanding, adult cells could not be reprogrammed to
develop into our stem cells of choice.
The recent report of the development of stem cells from cloned
embryos may be a small step just now, but with developments in structural
genetics and molecular biology, this small step could be the first towards
a complete revolution in medicine. In the meantime, however, it would be
in everybody's interests if the scientists and clinicians involved in the
research take the lay-people with them, making the science easier and
addressing their fears and concerns. For without the people, we might have
revolutionary new modality but nobody to use it on.
Competing interests:
None declared
Competing interests: No competing interests