Three-Parent Embryos? To Help Cure Mitochondrial Diseases? What is Really Going On?

Dianne N. Irving
Copyright February 4, 2012
Reproduced with Permission

I. Introduction

Interest in "mitochondrial disease" is not new; it is just that it is now being debated publicly in the news. In a recent article, "Scientists want kids with three parents to help eradicate genetic disease", [February 4, 2012), The Daily Telegraph (UK)],1 scientists in Australia want to genetically engineer new human embryos who would not carry, or at least would block, the diseased mitochondria derived from their mothers. This can be done by "mitochondrial transfer", i.e., removing the (assumed) "healthy" mitochondria donated from one woman's oocyte, transferring those "healthy" donated mitochondria to the oocyte of another woman whose oocyte contains diseased mitochondria, and then fertilizing that genetically engineered oocyte with a male sperm.

The aim or purpose of this research is supposedly to help "cure" and "eradicate" mitochondrial diseases. Last month scientists at Newcastle University in England were given $6.5 million to research the same technique.2 But is "eradicating mitochondrial disease" by means of mitochondrial transfer really possible? What is really going on?

II. The hype to "cure diseases" and "infertility"

It really must be noted, and as has been so documented for decades now, that much research is promoted ostensibly to "cure and eradicate diseases". Take human embryonic stem cell research as a paradigm. Despite decades of research and billions of dollars in research grants and funding, to date not a single "disease" has been "cured". Meantime all those efforts and all that money could have gone to support legitimate research - and all those human embryos would not have been destroyed in the process. Isn't it time for vulnerable patients with terrible diseases to wonder if they are not really just being used and taken advantage of for some ulterior purposes? And the burning question regarding "infertility" treatments must be asked: How do vulnerable infertile women know for sure what exactly is being implanted into them? Time for some serious questions, and serious answers?

III. Mitochondrial DNA is part of the whole human genome

What would "mitochondrial transfer" such as proposed by this research do to our understanding of the normal human genome? Apparently many scientists would like it if the human genome is defined only in terms of the nuclear DNA. However, scientifically, the human genome is defined as the total amount of DNA in a human cell, and that includes the nuclear DNA, the mitochondrial DNA which is outside the nucleus in the cytoplasm of the cell, and other cell organelles in the cytoplasm that contain DNA such as the ribosomes, etc. Why don't these scientists know this?:

In animal cells, DNA is found in both the nucleus and the mitochondria. (p. 10) ... The mitochondria also have ribosomes and a limited capacity for protein synthesis. (p. 18) ... The human genome is the term used to describe the total genetic information (DNA content) in human cells. It really comprises two genomes: a complex nuclear genome ... and a simple mitochondrial genome (p. 139).3 (emphases added)

A genome consists of the entire set of chromosomes for any particular organism, and therefore comprises a series of DNA molecules, each of which contains a series of many genes. The ultimate definition of a genome is to determine the sequence of the DNA of each chromosome. (p. 4) ... Genes not residing within the nucleus are generally described as extranuclear; they are transcribed and translated in the same organelle compartment (mitochondrion or chloroplast) in which they reside. By contrast, nuclear genes are expressed by means of cytoplasmic protein synthesis. ... One type of uniparental inheritance is seen in higher animals. Maternal inheritance can be predicted by supposing that the mitochondria are contributed entirely by the ovum and not at all by the sperm. So the mitochondrial genes are derived exclusively from the mother; and in males they are discarded each generation. (p. 81).4 (emphases added)

Therefore, adding the mitochondrial DNA from the oocyte of one woman to the oocyte of a second woman would change the genome, the very unique genetic identity, of the child resulting from the fertilization of that genetically engineered oocyte. So how could one of the researcher proponents of this three-parent child procedure claim that it "would not affect the child's genetic make-up"?5 Of course it would.

IV. "Mitochondrial transfer" is a combination of human genetic engineering and human cloning

It should also be noted that "mitochondrial transfer" involves the genetic engineering of the mother's sex cell - the oocyte - by adding to it the "healthy" mitochondria of another woman. That genetically engineered oocyte of the mother is then fertilized by a male sperm. The child that results, therefore, would have the genetic material from three different human adults, rather than from only the mother and the father as in normal sexual reproduction. The "copying" of the healthy mitochondria derived from a third party in the child that results is a form of genetic cloning. Given the high stakes involved, if researchers are going to perform human genetic engineering and human cloning, shouldn't they be held to the highest scientific-academic standards before being allowed to proceed? Imagine the chaos if they don't really know what they are doing. Imagine the chaos if they do know what they are doing.

V. Why "mitochondrial transfer" won't work

Why don't these researchers understand the obvious inherent dangers to any child genetically engineered by "mitochondrial transfer"? As with so much of this and related research, one wonders about the insufficient academic backgrounds of the researchers engaged in specific scientific projects. Do they not know enough facts of human embryology to know that not just all the genes, not just the nuclear genes, but all the parts and organelles of a cell interact and cooperate with each other in quite specific ways in order to achieve proper growth and development of the cells and tissues? One cannot just add and subtract bits and pieces of one cell to another cell and expect that "reconstructed" cell to retain its original functional specificity. Specifically, do they not know what has also long been known - that there is a unique and critical symbiotic "informational" relationship between the nuclear DNA and the mitochondrial DNA in any given human cell which relationship would be ruptured and confused in the resulting child reproduced with such "mitochondrial transfers"? As published years ago by the European Society of Human Reproduction:

Mitochondria are the organelles responsible for producing the majority of a cell's ATP and also play an essential role in gamete maturation and embryo development. ATP production within the mitochondria is dependent on proteins encoded by both the nuclear and the mitochondrial genomes, therefore co-ordination between the two genomes is vital for cell survival. To assist with this co-ordination, cells normally contain only one type of mitochondrial DNA (mtDNA) termed homoplasmy. Occasionally, however, two or more types of mtDNA are present termed heteroplasmy. This can result from a combination of mutant and wild-type mtDNA molecules or from a combination of wild-type mtDNA variants. As heteroplasmy can result in mitochondrial disease, various mechanisms exist in the natural fertilization process to ensure the maternal-only transmission of mtDNA and the maintenance of homoplasmy in future generations. However, there is now an increasing use of invasive oocyte reconstruction protocols, which tend to bypass mechanisms for the maintenance of homoplasmy, potentially resulting in the transmission of either form of mtDNA heteroplasmy. Indeed, heteroplasmy caused by combinations of wild-type variants has been reported following cytoplasmic transfer (CT) in the human and following nuclear transfer (NT) in various animal species. Other techniques, such as germinal vesicle transfer and pronuclei transfer, have been proposed as methods of preventing transmission of mitochondrial diseases to future generations. However, resulting embryos and offspring may contain mtDNA heteroplasmy, which itself could result in mitochondrial disease. It is therefore essential that uniparental transmission of mtDNA is ensured before these techniques are used therapeutically.6 (emphases added)

And what disabilities (or death) would be caused to these new experimental genetically engineered human embryos by the rupture and scrambling of this informational network? Who would "volunteer" for eventual clinical trials, and how valid would their "informed consent" be?

Similarly, other researchers have acknowledged the inherent problems with "mixing mitochonria", not only for the genetically engineered children so reproduced, but even in terms of using nuclear transfer or cytoplasmic transfer to derive human embryonic stem cells from the resulting genetically engineered human embryos:

Offspring produced by nuclear transfer (NT) have identical nuclear DNA (nDNA). However, mitochondrial DNA (mtDNA) inheritance could vary considerably. ... The introduction of foreign mtDNA into reconstructed recipient eggs has also been demonstrated in mice through pronuclear injection and in humans through cytoplasmic transfer. The mitochondrial triplasmy following M. mulatta NT reported here forces concerns regarding the parental origins of mtDNA in clinically reconstructed eggs. In addition, mtDNA heteroplasmy might result in the embryonic stem cell lines generated for experimental and therapeutic purposes ("therapeutic cloning"). ... [T]the potential to clone truly genetically identical offspring is negated through the presence of mitochondria in the cytoplasm of the recipient oocytes. This arises because mitochondria possess their own distinct genome, mitochondrial DNA (mtDNA). This extranuclear 16.6-kb circular genome is inherited strictly in a maternal fashion through the oocyte. However, those offspring generated through embryo reconstruction techniques can transmit two populations of mtDNA. ...Embryonic cell NT offers the opportunity for further aberrant patterns of mtDNA to arise.7 (emphases added)

It is therefore difficult to imagine why the Australian researchers quoted in the Daily Telegraph article could think that they "could eradicate mitochondrial mutations - which can cause multi-organ failure and fatal heart, liver and muscle conditions - by removing defective genes and replacing them with healthy DNA from a donor." In fact, they could literally cause such conditions. Even "stem cells" derived from such genetically engineered human embryos for "research purposes" would not behave in scientifically predictable manner.

VI. So what is going on?

Given that artificial reproduction of specifically genetically designed human beings is a fundamental violation of human dignity, given that in any research both the goal and the means used to reach that goal must be ethcial, given that so many researchers seem to not have mastered the scientific facts involved in the specific research they are engaging in, given that many researchers simply want the money to fund their work regardless of the consequences to individual human beings and to society, given that some researchers might even be adequately academically qualified and sincere in their efforts, this mad mad rush for the genetic engineering of human beings on every level is also fueled by other darker considerations.8 Time to ask the hard questions - and get real answers -- for a change.


1 Professor Illingworth, in "Scientists want kids with three parents to help eradicate genetic disease", (February 4, 2012), The Daily Telegraph (UK), at: [Back]

2 Dr Ananya Mandal, "Three-parent children may be born in near future in an effort to combat mitochondrial diseases" (January 22, 2012),, at: [Back]

3 Tom Strachan and Andrew P. Read, Human Molecular Genetics 2 (2nd ed.) (New York: John Wiley & Sons, Inc., 1999). [Back]

4 Benjamin Lewin, Genes VII (New York: Oxford University Press, 2000). [Back]

5 "Scientists want kids with three parents to help eradicate genetic disease", (February 4, 2012), The Daily Telegraph (UK), at: [Back]

6 E.C. Spikings, J. Alderson and J.C.St. John, "Transmission of mitochondrial DNA following assisted reproduction and nuclear transfer", Human Reproduction Update 2006 12(4):401-415; doi:10.1093/humupd/dml011; Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology, at: [Back]

7 Justin C. St. John* and Gerald Schatten, "Paternal Mitochondrial DNA Transmission During Nonhuman Primate Nuclear Transfer", Genetics, Vol. 167, 897-905, June 2004; doi:10.1534/genetics.103.025049, at: [Back]

8 See, e.g., D. N. Irving, "Any Human Cell - iPS, Direct Programmed, Embryonic, Fetal or Adult - Can Be Genetically Engineered to Asexually Reproduce New Human Embryos for Purposes of Reproduction ('Infertility')" (November 2011), at: [Back]