This article appears in the February 2002 edition of the Catholic Medical Quarterly
Cloning Damages Mitochondrial Genes
1.The role of the female egg
1.1 Female eggs are essential.
Female eggs (ova) contain the cell substance, with its cytoplasm and mitochondrial organelles. Mitochondrial genes are important because:
- The mitochondrial organelles are the power houses of the cell.
- Without mitochondria we could not breathe oxy gen. Without mitochondria our muscles would not work.
- Offspring with damaged or defective mitochondria fail to thrive.
- Offspring depend on the quality of their mother's mitochondria.
- Defective mitochondrial genes cause diseases.
- Mitochondrial diseases occur in the newborn, in children, in adults and in older people.
1.2 Cloned animals have maternal mitochondria
The female egg cell provides the mitochondrial genes without which a cloned animal cannot survive.
- A cloned animal may look like its father, but its genetic structure is not the same.
- The cloned somatic genes build a body that can walk, talk, think, forage for food, reproduce, age and eventually die in oxygen bearing gravitational field.
- The female cell mitochondrial genes enable the cloned animal to breathe oxygen, turn food into energy and control its muscle strength.
- Cloned animals often have defective mitochondria
- Given the range of problems that cloned animals have, there can be no doubt that cloning (somatic cell nuclear transfer) damages the mitochondrial genes in the female egg.
1.3 Evidence that cloned animals have damaged mitochondria
An article in the New Scientist (19th May 2001) considers the suffering caused to animals by cloning. The article states:
- Whatever tests scientists do they cannot predict which cows will be born healthy.
- Biochemically, some live cows ought to be dead.
- At best only 5 to 10 percent of implanted cloned embryos become live calves.
- Around 75 percent of the cloned calves die in the first two months of pregnancy.
- Miscarriages and terminations happen night to the end.
- Every fourth clone born is either stillborn or suffers from a lethal defect.
2. Mitochondrial diseases
2.1 Humans breathe down the female line.
Mitochondrial organelles in the cytoplasm of the female cell provide four essential biochemical pathways, namely,
- The citric acid cycle
- The respiratory chain
- Oxidative phosphorylation, and
- Fatty acid oxidation.
These pathways are responsible for energy transformation.2 Damage to any of these essential pathways accelerates aging in children and adults.
2.2 Detecting mitochondrial damage
Defective mitochondrial genes cannot be detected in the embryo. Don Wolf from the Oregon Regional Primate Research Centre in the United States is quoted in the New Scientist as saying:
- "The idea of screening cloned embryos for chromosome abnormalities, and using imagining to keep tabs on the fetus, is sheer nonsense. Fetuses that look robust at 60 days may die at 61. And clone that dies after five days of life can have normal chromosomes and genes while still in the womb.
- "How in the world" asks Wolf "will they screen out abnormalities when they don t know what to look for?"
2.3 Ageing and Mitochondrial diseases
Inherited mitochondrial diseases have an age related onset of expression. Inherited genes or mutated genes cause the disease. Some occur in child hood, others in adults. The organs affected depend on which components of the mitochondrial genes are damaged:
- Inherited mitochondrial disease4 can cause blindness.
- Defective muscles, including cardiac muscle, and diabetes can occur.
- Even more worryingly, age related mutations increase.
Many years will have to pass before we can be certain that interfering with the female reproductive cell, e.g. by puncturing it for in vitro fertilisation, causes late onset mitochondrial damage. What is abundantly clear is that cloning damages maternal mitochondria.
2.4 Why do mitochondrial diseases appear late in life?
Factors that may explain the late onset of inherited mitochondrial diseases are:
- Premature age related decline due to oxidative damage.
- Inefficient repair due to defective organelles
- Increased age related mutations in the genes. Whatever the reason, late onset defective mitochondrial genes are sometimes expressed in pensioners.
3.1 Ageing begins at conception
Conception begins a genetic process that continues throughout our lives. Ageing is a universal, intrinsic, progressive and eventually deleterious process. Genes have to change a ball of cells into a human being that can stand up, move and reproduce in a gravitational field. Infectious diseases can be con trolled. Accidents can be prevented.
Misuse of harmful substances, such as smoking, alcohol and drugs can be prevented. Fitness programmes can be followed. Nevertheless, eventually all humans die.
The "modem alchemist's dream" is that the ravages of degenerative diseases can be prevented:
- the blind will see,
- the lame will run,
- the bed bound will take up their beds and walk.
Newspaper editors write about immortality, politicians don't want to upset sick people, sick people want and need to follow the dream. Why then should research involving somatic cell nuclear transfer (human cloning) be proscribed? After all it can bring to mankind untold benefits.
3.2 The case for somatic cell nuclear transfer.
The Minister's case for extending the Human Fertilisation and Embryology Act5 focused on:
- Immense potential for people with chronic diseases.
- Given (1) an extension of the 1990 Act is sensible.
- Adult stem cells are not yet an alternative to embryonic stem cell research.
- A strict regulatory framework.
- Stem cell generation (using somatic cell nuclear transfer) has nothing to do with adult cloning.
Making the case for somatic cell nuclear transfer (therapeutic cloning) the Minister stated:
- That "Cell nuclear replacement is a technique for creating stem cells that are genetically compatible with the donor".
- That the Donaldson report concluded that cell nuclear replacement could hold the key to growing stem cells that the diseased body will not reject.
- That under current law, embryo research for reproductive purposes is legal up to fourteen days.
- That the new regulations change the purposes of permitted research to include research into stem cells and research into the understanding and treatment of serious diseases.
- That under the current law, cell nuclear replacement is legal.
- That she did not believe that there are fundamentally new moral issues at stake that were not raised in the 1990 debate.
- That a measure of respect should be given to the human embryo.
- That the scientific case for stem cell research on embryos was extremely strong.
3.3 The case against somatic cell nuclear transfer
- Cells created by somatic cell nuclear transfer are not
genetically compatible with the cells of the donor.
- Even if they were by chance compatible, the mitochondrial genes of the female cell are likely to be damaged.
- To the best of my knowledge the Donaldson report ignores the problem posed by mitochondrial damage
- The current law permits experimentation up to fourteen days
because the committee decided that at fourteen days the embryo has
- Biologically, the embryo implants in the human uterus five to seven days after conception.
- If the blastocyst does not implant, further development is abnormal.
- There is no scientific rationale for the choice of fourteen days.
- If uterine implantation is to be banned, then research on embryos should cease at seven days.
- The current law does not mention somatic cell nuclear transfer
or human cloning. The law simply covers research into treatments
associated with reproduction.
- The overwhelming scientific evidence is that animal cloning causes mitochondrial damage.
- Mitochondrial damage cannot be recognised in the embryo.
- Scientifically flawed research is immoral, and could in no way be considered legal.
- Therefore, embracing somatic cell nuclear transfer in an the amendment to the Human Fertilisation and Embryology Act5, drastically changes the human value of embryos.
- The scientific case for somatic cell nuclear transfer is very
- On the positive side,
- Dreams of a better world depend on the successful development of immortal lines of healthy stem cells.
- On the negative side
- More than fifty stem cell lines will need to be created for each tissue stem cell to be implanted.
- Even then the problems of tissue rejection will not be overcome.
- No one knows how a stem cell develops, but all doctors recognise that they can cause abnormal as well as normal tissue.
- Most of the stem cells generated by somatic cell nuclear transfer will have mitochondrial damage.
- On the positive side,
In summary, the case against somatic cell nuclear transfer experiments on human embryos rests on the fact that research based on flawed science is ethically and morally wrong.
Rather like voting for "warm summers", how could politicians deny the claims of the visible sick? Biologically, the concept of human cloning is a "newspaper editor's dream" rather than a possible, sensible, human activity. The article in the 19th May 2001 New Scientist "The Awful Truth: Why would anyone in their right mind want to clone a baby when animal cloning can go disastrously wrong?" shows why (scientifically) the concept of cloning human babies is abhorrent.
The authors comment:
- "The more (animal) cloners you talk to, the longer the list of
defects you hear about:
- enlarged tongues,
- squashed faces,
- bad kidneys,
- intestinal blockages,
- immune deficiencies,
- diabetes, and
- shortened tendons that twist the young animal s feet into useless curves.
- "There is no pattern; everyone is perplexed"
- Furthermore, "... Four of 12 surrogate mothers died from pregnancy complications".
The reason why cloned animals are defective and cloned stem cells will be defective is that:
Cloning is an unnatural process.
- The nuclear material is not refreshed.
- Replacing the female cell nuclear material damages the cell.
- Electric currents kick start the process.
- Mitochondria are usually damaged.
One researcher stated:
- "We sacrifice the cow and the clone. . . all the heroics in the world can't rescue those animals."
Before the committee supports the modern day alchemist s dream, the committee has to ensure that the researchers:
- Justify the scientific principles that led to parliament approving somatic cell nuclear transfer.
- 'Cloning Special Report. "The Awful Truth: Why would anyone in their right mind want to clone a baby when animal cloning can go disastrously wrong?" Philip Cohen and David Concar. New Scientist 19th May 2001, pages 14-15.
- Page 136, Encyclopedia of Gerontology. Age, Ageing, and the Aged. Volume 2. Academic Press 1999.
- Op. cit. New Scientist 19th May 2001, pages 14-15
- Leber's Hereditary optic atrophy
- Human Fertilisation and Embryology 19th December 2000. The Parliamentary Under-Secretary of State for Health (Yvette Cooper). Hansard.
Professor Peter Millard FRCP is emeritus Professor of Geriatric Medicine St George s Hospital Medical School.