October 19, 2014

Science and Technology Committee
House of Commons

Center for Genetics and Society submission to the Science and Technology Committee

for the October 22, 2014 evidence hearing on mitochondrial donation

1.       The Center for Genetics and Society (CGS) is a nonprofit public affairs organization based in the United States that works for responsible development, use and societal governance of human biotechnologies. CGS has been closely following the technological and regulatory developments surrounding so-called “mitochondrial donation” both in the U.K. and in the U.S. We welcome the opportunity to submit these comments to the Science and Technology Committee for consideration at its 22 October 2014 evidence hearing.

2.       CGS was established in 2001 in recognition of the profound challenges arising from technological advances that can be used to modify the human germline. These range from safety risks that would be assumed by women and children; to ethical questions of consent, rights, and dignity; to critical social questions of equality and exploitation.

3.       Numerous scientific, ethical, policy and public interest organizations have concluded that “no changes should be made to the DNA of the human germline.” POSTnote 431 characterizes this conclusion as a “consensus.”

4.       If mitochondrial manipulation techniques are permitted in the U.K., this would be accomplished via a Parliamentary vote in favor of an exception to the current prohibition of human germline modification (a policy that has been codified as law in some 40 other countries as well). Although it is important for regulation to be nimble in response to technological innovation, we believe that in this case the current policy situation – that is, the legality of gene therapy and illegality of human germline modification – strikes the right balance of enabling benefits while minimizing harms.

5.       Despite repeated assertions by the Human Fertilisation and Embryology Authority (HFEA) that “there is no evidence that the techniques are unsafe,” significant and growing evidence suggests that this is incorrect. Especially given recent findings, it appears that the techniques are in fact likely to be unsafe.

6.       Every ethical review of mitochondrial manipulation techniques that has been undertaken by the HFEA and the Nuffield Council on Bioethics (NCB) has asserted that they should be considered advisable only if additional research demonstrating acceptable levels of safety and efficacy were to be completed successfully. In the last year, there has been very limited advancement in this endeavor. Instead, other investigators have reported findings that suggest substantial challenges to any demonstration of safety. In other words, there is much needed research that remains to be done, and new research that has been done has exacerbated rather than assuaged concerns.

7.       The NCB recommended that mitochondrial manipulation techniques initially be offered as part of research trials, and that “parental consent to follow up should be mandatory for participation in the trial and extend to future generations.” The proposal on which Members of Parliament will be asked to vote, by contrast, would allow the HFEA to license fertility centers to offer the techniques, and does not provide for follow up of any children born after their use. This would make it impossible to adequately assess the success or failure of the techniques.

8.       We assume that the Committee will be made aware of the current and emerging evidence about mitochondrial function that demonstrates the lack of evidence that mitochondrial manipulation techniques would be safe. Here are two recent reports, and an earlier letter raising still-relevant safety concerns:

• mtDNA Segregation in Heteroplasmic Tissues Is Common In Vivo and Modulated by Haplotype Differences and Developmental Stage, Cell Reports, Joerg Patrick Burgstaller et al., 26 June 2014

• Mitochondrial Replacement, Evolution, and the Clinic, Science , Klaus Reinhardt et al., 20 September 2013

• Nuclear transfer to prevent mitochondrial DNA diseases, The Lancet , Joanna Poulton et al., 2 September 2006

In addition, we list several resources that review and reflect on scientific evidence underlying the growing concerns about safety of mitochondrial manipulation techniques:

• Possessed! The powerful aliens that lurk within you, New Scientist, Garry Hamilton, 22 September 2014

• Three-parent babies: It's more messy than we thought, New Scientist, editorial, 18 September 2014

• Human Genetics Alert Submission to HFEA update on safety of MST/PNT, David King, January 2013

10.   The recent article in New Scientist reviews the accumulating evidence suggesting that comparing mitochondria replacement to “replacing batteries,” as has often been done in public and policy conversations about the proposed techniques, is not only far too simple but also highly misleading. In fact, mitochondria exert great influence on phenotypic traits. The New Scientist reporter writes,

“Most debate around the issue has worked on the assumption that mitochondria are simply cellular powerhouses. However, given their new-found influence over our bodies the implications of this technology may be far more radical than we have assumed.”

11.   Based on theirreview of these recent findings, the editors at New Scientist wrote that

“the emerging science and the issues it raises have not had a proper airing. They urgently need to be brought to parliament's attention, debated and settled before a decision is made.”

The editors in fact reversed their own former position in favor of the techniques, saying that the proposition has turned out to be “more messy than we thought."

12.   POSTnote 431 notes that “allowing mtDNA replacement may have little effect on the consensus not to alter germ line nDNA.” In support of this, it notes that in 2012, the NCB concluded that there is a “distinct material boundary” between mitochondrial DNA (mtDNA) and nuclear DNA (nDNA), and that this allows a “clear legal distinction” to be made. However, the new evidence about the complexity of mitochondrial function highlights the difficulty of drawing a meaningful line between mtDNA and nDNA when it comes to germline manipulations.

13.   Also in support of the assertion that “allowing mtDNA replacement may have little effect on the consensus not to alter germ line nDNA,” POSTnote 431 notes that

“prevention of serious mitochondrial disease is the only purpose for which the current law might allow an embryo with altered DNA to be implanted into a woman. Allowing an embryo with alteration to its DNA to be implanted for any other purpose would require the primary legislation to be re-written, a major undertaking.”

However, the assumption that mitochondrial replacement would be undertaken only for the prevention of serious mitochondrial disease may be wrong. Shoukhrat Mitalipov, the principal developer of maternal spindle transfer, told Science magazine in February 2014 that he believes mitochondrial manipulation should be adopted as a treatment for general age-related infertility.

"No studies clearly indicate the efficacy of treatment" with the technique, Mitalipov says. But clinical trials "would be the way to test it." He would like to go forward with trials in both disease carriers and infertile women. "Mitochondrial diseases are rare, but age-related infertility is a huge problem."

14.   A Parliamentary vote to permit mitochondrial replacement in the U.K. would likely encourage its approval by the U.S. Food and Drug Administration. Although U.K. law would limit its use to preventing transmission of mitochondrial disease, this would not be the case in the U.S, where drugs, devices and procedures can be used for any purpose once they are approved. In other words, this germline-modifying technique would in fact be very likely to spread to additional uses, especially because, as Dr Mitalipov’s observation that “age-related infertility is a huge problem” suggests, there could be a significant market for procedures that claim to treat it.

15.   We believe that such prospects are necessary and appropriate considerations in the current debate, and that those in the U.K. who are being asked to approve mitochondrial DNA replacement should consider the consequences of such a decision for the international consensus against genetic modifications that would be inherited by future generations.

16.   Given the significant safety concerns about the proposed techniques, along with the weighty social and ethical concerns they raise, we strongly recommend leaving the law as it stands.

Respectfully submitted on behalf of the Center for Genetics and Society,

Marcy Darnovsky, PhD