Exploring the ethical issues surrounding a new technique that aims to address mitochondrial DNA mutations
Within the last month, an announcement has been made in the journal Nature regarding a new procedure which could eventually help women with dysfunctional mitochondria [1].The team of scientists based at the University of Newcastle, UK have been able to grow human embryos after merging DNA from two fertilised eggs.
In brief, the procedure involves removing two ‘pronuclei’ from the egg and sperm (which contains the parents’ DNA) after fertilisation has taken. These pronuclei are then transferred and injected into a second embryo which possesses healthy mitochondria but which has had its own nuclear material removed.
Why is this technique so revolutionary?
One of the key components of a cell, mitochondria are the ‘powerhouse’ or ‘cell battery’ of the cell helping to constitute the cell’s energy source thereby controlling cell cycle and cell growth. However where mitochondria are found to be faulty and not working correctly fatal heart, liver, neurological and muscle conditions can ensue.
With at least 1 in 10,000 adults in the UK affected by genetic disorders which arise from dysfunctional mitochondria [2], establishing a technique which holds the potential of being a successful form of treatment is surely something to be celebrated. However, before this technique becomes a widely accessible form of clinical treatment there are a number of ethical questions which need addressing which arise from the midst of such cutting edge research.
Germline intervention
First, given the fact that mitochondria are inherited, carrying out any form of alteration in this regard constitutes a form of germline, or heritable, genetic engineering. There are basically two forms of genetic engineering; somatic and germline modifications. Somatic modifications involve genetic changes to cells other than egg or sperm cells. Thus the traits are not passed onto future generations. Germline intervention, on the other hand, involves genetic changes made in eggs, sperm or early embryos; modified genes would appear not only in the person who developed from that gamete or embryo, but also have as yet unknown effects on subsequent generations. Consequently it is germline intervention that sparks the most controversy.
At first simply discussing the changing of the power source of a cell (or what could be termed the metabolism of the cell) does not seem as controversial as deciding to change the genetic make up of your child so he or she is able to live longer, be healthier or more intelligent. But it is the combination of the inheritable nature of the change with that of the unknown risks and consequences of this pioneering technique that raise ethical concerns in the minds of many. Issues arise concerning the commodification of the body and the rise of the designer baby as well as concerns over the yet unknown health implications and uncertainties.
It is because of these very reasons that the international community has voiced its concern over germline intervention. For instance, the Council of Europe’s Convention on Human Rights and Biomedicine specifically addresses germline manipulation [3]. Article 13 offers that interventions aiming to modify the human genome “may only be undertaken for preventative, diagnostic or therapeutic purposes and only if its aim is not to introduce any modification in the genome of any descendants” [4]. This position is further upheld by the decision taken at the fifty-first World Health Assembly of The World Health Organization (WHO) which reaffirmed that “germ-cell therapy, where there is an intention or possibility of altering the genes passed on to the next generation, should not be permitted in the foreseeable future” [5].
Moreover, the comparison can be made between the use of intracytoplasmic sperm injection (ICSI) with this new mitochondria DNA (mtDNA) therapy. ICSI has been for some time regarded as a treatment to overcome male infertility. The procedure involves injecting sperm directly into an egg. However a recent report by the American Society of Reproductive Medicine now indicates that certain conditions may carry an increased risk for transmission of genetic abnormalities to offspring via ICSI [6].
Returning to the question of mtDNA therapy, on the one hand it is obvious that the fact that the changes are inheritable is one of the reasons why the technique has been developed in the first place so that dysfunctional mitochondria diseases can be eradicated. On the other, as seen in the example of ICSI what may appear to be achieved in the first instance may bring about other implications in the future given the inheritability of the change.
Issues of safety
Second, even based on the work carried out by the team from Newcastle, an unhealthy amount of mtDNA is transferred over with the pronuclei from the donor egg. Despite refining the transfer process to such an extent that the team reached breakthrough levels of less than 2 per cent donor mitochondria, nevertheless the manipulated embryos still contained traces of donor ‘disease’ mitochondria [7]. Should even the smallest of traces be present, it would still be enough that the resultant embryo would be adversely affect in terms of biological functioning and could still result in mitochondria disease.
Moreover, furthering testing would need to take place before the therapy can become a clinical treatment and crucially that would require the technique having to be tested in healthy embryos. The Newcastle team’s work centres around abnormally fertilized embryos generated during in vitro fertilization (IVF) treatments that would have otherwise been discarded. Czech Republic developmental biologist Josef Fulka further comments that the manipulation itself may even increase the risk of epigenetic abnormalities in future offspring. Such risks could only be mitigated if the technique is continually tested on healthy human embryos throughout their life; experiments which are near impossible to perform [8].
Just changing the battery?
Third, there is perhaps a more fundamental question at stake which turns the understanding of human life on its head. This new technique draws upon the involvement of three people participating in the creation of an embryo as opposed to two; the common state of affairs in natural reproduction. The mother and father would supply 99.8 per cent of its DNA, with a small amount from another woman, the mitochondria donor [9].
In response to this question of a ‘three parent embryo’, Professor Doug Turnbull, co-author of the study, draws upon the comparison of a laptop battery to argue otherwise. If mitochondria are compared to that of a power source for a laptop, the battery of the laptop may be changed any number of times without any degree of harm or change occurring to the information stored on the laptop. Consequently, there is no real reason to consider the mitochondria donor as a parent of the embryo [10] .
Nevertheless, taking pronuclear DNA in isolation does not result in the creation of an embryo. An embryo only develops when the DNA material is placed into an egg which has been emptied of its DNA. In many respects the level of importance and value of the pronuclei increases depending on its contextualisation; becoming important when placed in an emptied egg or embryo and left to develop. To use Turnball’s laptop analogy, the information contained on the hard drive of the laptop may not be affected by changing the battery, but if you do not have a battery in the first place the information cannot be accessed or used at all rendering it of little value or use.
Three-parents?
Fourth, and in many respects a related issue to the previous point, is the danger that such a technique is considered solely from a reductionist perspective, prevalent in contemporary science not least biology and specifically genetics. In brief, a reductionalist perspective seeks to take the complexity of any given system and understand it from the bottom up. The outcome is that a reductionalist methodology results in a reductionalist ontology; the system is explained wholly by the properties of its components parts. Therefore, in a case where an embryo is created using three ‘parents’ it is not too far removed to consider that all three are valid creators of life and as such develop the corresponding parenthood bonds and mutual belonging that is to be expected between creator and creature.
What is wrong with this idea? As Dr. Calum Mackellar has discussed [11], should a scientist in the future create a new life form using various parts from a number of deceased individuals who would be considered the parent of that life? Is it solely the scientist or is it a case that each of the deceased individuals plays a part in the parenthood of the new life form? The technique pioneered by the team at Newcastle moves beyond the understanding of parenthood involved in natural reproduction and begins to add complexity to the issue, not least in terms of the future child getting to grips with who exactly his or her parents are; a question which is of clear importance to offspring. This is demonstrated through recent research into the experiences of individuals conceived by donor insemination who search for their donor and/or ‘donor siblings’.
Recent research reports that in recent years a significant increase has been seen among those children conceived by donor insemination in finding and contacting their donor and donor sibling relatives [12]. According to the study, the primary motivation for most donor children to find their donor parents and donor siblings is out of curiosity. Nevertheless the desire to know more about their personal and genetic identity also motivated many to search out their donors, citing that without such information it was as though something was missing from their sense of identity.
Citing findings carried out by Scheib and Ruby in 2008 they found that parents hoped that establishing contact with their child’s half siblings would "give their child a sense of kinship" [13]. It is noted that on the basis of genetic relatedness new family formations are being created. If this is the case in the example of sperm donation, how much more could this same question come to the fore should the therapy developed by the Newcastle team become a form of clinical treatment. The value and importance of identity, parental bonds and parenthood are not unnecessary ‘baggage’ that is limited to natural reproduction. Clearly, these are questions which transcend reproductive boundaries and need to be carefully weighed and discussed if creating human life by more novel techniques are to be considered and experimented with further.
Conclusion
Whatever the good intentions initially, carrying out germline modifications causes various concerns to be raised. Succinctly, these concerns centre around questions of justice and the (ab)use of technology by one generation affecting another.
Clearly the challenge to this generation is to develop and foster a culture that continues to promote the advancement of science and technology (including eradicating fatal diseases) but in partnership with a philosophy which seeks to see human beings flourish freely both now and in future generations, thus avoiding any pursuit of “the power to make its descendants what it pleases” [14]. Conversely, if we dismiss such a challenge as merely ethical scare mongering which slows down scientific advancement, the reality may well be as C.S. Lewis feared that “all men who live after it are the patients of that power” [15].
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[1] L. Craven, H.A. Tuppen, G. D. Greggains, S.J. Harbottle, J.L. Murphy, L.M. Cree, A.P. Murdoch, P.F. Chinnery, R.W. Taylor, R.N. Lightowlers, M. Herbert, D.M. Turnbull, "Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease", Nature advance online publication, 14 April 2010, http://www.nature.com/nature/journal/vaop/ncurrent/full/nature08958.html [accessed 23rd April 2010]
[2] Ibid.
[3] Council of Europe Treaty Office. 2010. “Convention for the protection of Human Rights and dignity of the human being with regard to the application of biology and medicine: Convention on Human Rights and Biomedicine CETS No.: 164" Council of Europe, <http://conventions.coe.int/treaty/en/Treaties/Html/164.htm > [accessed 27th April 2010]
[4] Council of Europe Treaty Office. 2010. “Convention for the protection of Human Rights and dignity of the human being with regard to the application of biology and medicine: Convention on Human Rights and Biomedicine CETS No.: 164 - Status page" Council of Europe, <http://conventions.coe.int/Treaty/Commun/ChercheSig.asp?NT=164&CM=&DF=&CL=ENG > [accessed 27th April 2010]
[5] World Health Organization, Fifty –First World Health Assembly, April 8, 1998, Implementation of resolutions and decisions, A51/6 Add.1, para. 16, http://apps.who.int/gb/archive/pdf_files/WHA51/ea6a1.pdf [accessed 26th April 2010].
[6] American Society of Reproductive Medicine Practice Committee, "Fearful of designer babies and long-term health uncertainties", American Society for Reproductive Medicine Vol. 90, Suppl 3, November 2008, http://www.asrm.org/uploadedFiles/ASRM_Content/News_and_Publications/Practice_Guidelines/Committee_Opinions/Genetic_considerations%281%29.pdf [accessed 23rd March 2010]
[7] Jef Akst, "Nuclei swap to stop disease?" 14th April 2010, The Scientist.com, http://www.the-scientist.com/blog/display/57287/ [accessed 23rd April 2010]
[8] Ibid.
[9] Mark Henderson, "Babies with three parents may be key to preventing genetic disorders", The Times Online 15th April 2010, http://www.timesonline.co.uk/tol/news/science/genetics/article7097547.ece [accessed 23rd April 2010]
[10] Brandon Keim, "3-Parent Embryos Could Prevent Disease, But Raise Ethical Issues", Wired Science Blog, 14th April 2010, http://www.wired.com/wiredscience/2010/04/mitochondria-engineering/#ixzz0mDgkoSTv [accessed 23rd April 2010]
[11] C. Mackellar, "Who are the real creators of a living being?" BioNews Comment, 19th April 2010, http://bionews.org.uk/page_58833.asp [accessed 23rd April 2010]
[12] V. Jadvaa, T. Freemana, W. Kramerb, S. Golomboka, “Experiences of offspring searching for and contacting their donor siblings and donor”, Reproductive Biomedicine Online, Volume 20, Issue 4 (April 2010), pp. 523-532, http://www.rbmojournal.com/article/S1472-6483%2810%2900002-7/fulltext#section26 [accessed 28th April 2010]
[13] Ibid.
[14] C.S. Lewis, “The Abolition of Man, Chapter 3” in C.S. Lewis: Selected Books, (London: HarperCollins Publishers, 2002) p.420.
[15] Ibid.
