Since the discovery of the structure of DNA in 1953, advances in human genetics, and the treatment of genetic diseases, have progressed at an astonishing rate. In early 2015, Parliament’s debate on the issue has once again raised questions about the ethics, and legality, of so-called ‘designer babies’.

The Parliamentary debate on Mitochondrial Donation Regulations might, for the first time, anywhere in the world make it legally permissible to treat mitochondrial disease by cell donation. The Regulations have been approved by the House of Commons and return to the House of Lords for their vote.

Jim Kinnier Wilson, partner in Penningtons Manches’ award-winning life sciences team, explains some of the technological and legal issues associated with ‘designer’ and ‘three-parent’ babies.

GENE THERAPY

Advances in the manipulation of genetic material have accelerated since 1970, with the discovery and implementation of various techniques that enable DNA to be transferred between cells.

These advances and the increasing ability to sequence DNA and to replicate it (to form copy or cDNA) led to the ability to remove or repair damaged or mutated (changed from the expected sequence for that gene) DNA to alleviate diseases caused by defective proteins from aberrations in the DNA sequence.

Gene therapy is the treatment of a disease by introducing DNA (or its associated polymer RNA) into the cells of a patient. Effectively the mutated host DNA is either inactivated by cutting the relevant gene, or superseded by the addition of a healthy, functional copy of the affected gene. It may also be carried out by removing cells from the patient, modifying them by the methods above and re-introducing the cells back into the patient.

To date gene therapy has only been used to treat adults and children after birth and the treatment provides a temporary solution, as the cells into which modified DNA is transferred will age and die in the normal way. Patients on this kind of treatment therefore need several repeat therapies over their lifetimes.

THE CURRENT LEGAL POSITION

While somatic gene therapy is permitted in the UK by virtue of the Regulation of Advanced Therapeutics (Regulation EC 1394/2007), germ-line gene therapy - where a modification to a gene in a single celled embryo is made - is specifically prohibited.

S3(2) of the Human Fertilisation and Embryology Act 1990 (as amended by the Human Fertilisation and Embryology Act 2008) (the ‘1990 Act’) provides that:

“No person shall place in a woman –

  1. an embryo other than a permitted embryo… or
  2. any gametes other than permitted eggs or permitted sperm…”

The relevant definitions make it clear that to be a permitted egg, sperm or embryo it must be one “whose nuclear or mitochondrial DNA has not been altered”. It is therefore illegal to place a genetically modified embryo into a woman.

MITOCHONDRIAL DONATION – THE ISSUES

Mitochondria are small organelles that transform the food we eat into an energy form that can be used by the cell. They are present in almost all human cells. Mitochondria contain a very small amount of mitochondrial DNA which represents about 0.1% of an individual’s total DNA, with the rest being nuclear DNA, which is an equal combination of DNA from its biological parents.

An individual’s mitochondrial DNA is only inherited from its mother. Unfortunately mothers can carry abnormal mitochondria and thus there can be a risk that such mothers pass on serious disease to their children, even if they show no symptoms themselves. There is no cure for defective mitochondria or its DNA.

It is possible to transplant the nuclear DNA from the egg of a person who has abnormal mitochondria into a donated egg of a person with normal mitochondria, where the donated egg has also had its nuclear DNA removed. Once fertilised, the result is an embryo which is genetically linked to both its parents’ nuclear DNA but carries the mitochondrial DNA of a healthy third person, albeit in a minute amount. Hence the use of the term, “three parent babies”, or more properly “three-person babies”. One commentator has suggested that it would be more correct to call them 2.001 person babies.

However, as the new embryo with healthy mitochondria goes on to develop into a full individual with healthy mitochondria permanently in every cell, critics argue that this technique is, in fact, prohibited germ-line gene therapy.

THE LEGAL QUESTIONS REGARDING THE PROPOSED REGULATIONS

Would passing the Regulations, which would be the first of their kind anywhere in the world, put the UK in breach of its international obligations under the UNESCO Declaration on the Human Genome and Human Rights, as Article 24 prohibits germ-line genetic manipulation?

In fact, Article 24 obliges the International Bioethics Committee of UNESCO to give advice to UNESCO on the identification of practices “such as germ-line interactions” that could be contrary to human dignity. The Article does not state that germ-line interactions are inevitably contrary to human dignity (and thus prohibited by virtue of Article 11 of the Declaration) but that they could be.

DOES MITOCHONDRIAL DONATION INVOLVE THE CREATION OF GENETICALLY ALTERED EMBRYOS?

The Government’s argument is that it does not. There is no definition of ‘alteration’ in the 1990 Act, but it could be argued that it comprises the cutting or enhancement of individual genes within the nuclear or mitochondrial DNA, but does not include swapping a defective set of mitochondrial DNA wholesale for a healthy set of mitochondrial DNA.

If that is right, then donation of complete, unchanged mitochondrial DNA could result in a permitted embryo required by the 1990 Act.

ARE THE REGULATIONS REQUIRED?

It has been suggested that if the Government is right that donation of whole mitochondria does not alter the embryo, that the Regulations are not necessary.

s3ZA(4) provides that for a permitted embryo, not only must there be no alteration to the nuclear or mitochondrial DNA, but that there must also be no cells added to the embryo other than by division of the embryo’s own cells. Thus, without the Regulations (which are heralded by s3ZA(5) ) mitochondrial donation embryos would be prohibited.

The Regulations currently being debated by Parliament follow around seven years of consideration of the various technologies and three assessments of the Human Fertilisation and Embryology Authority (HFEA) which, in principle, find that the techniques should be safe, if and when carried out in humans. The HFEA, however, has recommended further investigations to be undertaken before it would grant a licence.

WILL DESIGNER BABIES BE ALLOWED IF THE REGULATIONS ARE PASSED?

The Regulations do not themselves make mitochondrial donation a legal practice throughout all IVF treatment centres. Instead they will empower the HFEA to grant a licence to undertake mitochondrial donation processes on a named woman’s eggs on the basis that there is a particular risk that any egg of the named woman may have mitochondrial abnormalities caused by mitochondrial DNA and that there is a significant risk that a person with those abnormalities will have or will develop serious mitochondrial disease. 

It is clear that the Mitochondrial Donation Regulations aim to set out a specific, highly-limited exception to the prohibition on genetically altered embryos and germ-line gene therapy. It is envisaged to be applicable only in limited circumstances with a named woman being the subject of an application for licence. It is also estimated that just over 100 babies (out of the 750,000 or so born in the UK each year) might be at risk of serious mitochondrial disease. Of these, it is expected that most may choose traditional IVF with a donated egg (meaning the child is genetically unrelated to its mother), while initially only around ten women might take the option offered by mitochondrial donation.

It is difficult to see a licence being granted for research aimed at creating a non-permitted embryo by the HFEA, ie one whose nuclear DNA has been or would be altered. It would require primary legislation to change the 1990 Act to permit gene editing for embryos. 

As currently drafted, the 1990 Act and the Mitochondrial Donation Regulations do not provide the basis for wholesale designer babies in the United Kingdom.

A longer version of this article was published by LexisNexis in February 2015 - to view the full document, click here.