Brüstle in the Dock: ISCC v Comptroller General of Patents, Opinion of AG Cruz Villalón

As BioNews 763 reported recently, Advocate General Cruz Villalón has advised the Court of Justice of the European Union (CJEU) that human parthenotes are not 'human embryos'. The fact that he had to do so raises serious concerns about the ability of Europe's leading court to interpret bioethical legislation and challenges the authority of one of its most notorious cases.

International Stem Cell Corporation (ISCC) devised methods for provoking human eggs to divide into clusters of pluripotent stem cells, known as parthenotes, and methods for turning such cells into corneal cells. ISCC applied for UK patents to the methods and resulting materials, but was refused by the Comptroller General of Patents on the basis of the CJEU's notorious 2011 decision in Brüstle v Greenpeace. This held that, because '… any non-fertilised human ovum whose division and further development have been stimulated by parthenogenesis' is 'capable of commencing the process of development of a human being' it is a 'human embryo' for purposes of the Biotechnology Directive (Directive 98/44). As such, it is unpatentable for industrial or commercial purposes by Article 6.

The CJEU's logic rests on two legal and scientific pillars: first, that a parthenote is capable of commencing human development; second, that a capacity for such development is the determining feature of a 'human embryo' under Directive 98/44. Although Advocate General Cruz Villalón's Opinion in International Stem Cell Corporation v Comptroller General of Patents is confined to toppling the first pillar, it effectively undermines the second.

The reference

The question referred to the CJEU by the English High Court included a scientific statement, which I have underlined, that flatly contradicts pillar one:

Are unfertilised human ova whose division and further development have been stimulated by parthenogenesis, and which, in contrast to fertilised ova, contain only pluripotent cells and are incapable of developing into human beings included in the term "human embryos" in Article 6(2)(c) of Directive 98/44/EC1 on the Legal Protection of Biotechnological Inventions?

Advocate General Cruz Villalón answers that, no, human parthenotes should not be included in the term and should not, therefore, be precluded from patent protection in the EU on that basis. He adds some interesting downstream detail of no relevance to the case (that the Directive permits individual Member States to exercise their moral whim to prohibit patenting and that parthenotes could yet become 'human embryos' if genetic manipulation rendered them capable of human development), but these are distractions. The stark fact is that the CJEU's legal advisor is saying it based its ruling on bunk and advising it to reconsider. So how did the CJEU make such a mistake? Is it an isolated incident? Could it happen again?

Where did it all go so wrong?

On the face of it, the answer is provided by the CJEU's statement in Brüstle that, although CNR organisms (think Dolly) and parthenotes 'have not, strictly speaking, been the object of fertilisation, due to the effect of the technique used to obtain them they are, as apparent from the written observations presented to the Court, capable of commencing the process of development of a human being, just as an embryo created by fertilisation of an ovum can do so'. On the basis of the same 'written observations', the Court also held that parthenotes are a source of totipotent cells (cells that are capable of developing, in principle, into a baby).

The Advocate General with responsibility for examining the Brüstle evidence, Yves Bot, had assured the Court that a parthenote was 'capable of commencing the process of development of a human being' on the basis of technical information provided to him. Yet, as Advocate General Villalón's ISCC Opinion tartly remarks, 'Had the [Brüstle] Court been aware of the fundamental difference between parthenotes and non-fertilised ova subjected to somatic-cell nuclear transfer and nevertheless wanted to establish a functional equivalence between the two, it would certainly have discussed this difference'.

Over and over again, the Opinion points to the CJEU's poor scientific grasp in Brüstle, citing observations by the French, Swedish and UK governments, the European Commission and ISCC. The Commission diplomatically suggested that the written submissions had 'proved erroneous in the light of scientific developments', as if such developments had taken place after the Brüstle case. They hadn't: Azim Surani's famous imprinting experiments dated from the mid-1980s. At the end of the day, the CJEU had been misled.

It was hardly the only scientific gaffe in Brüstle. Although M. Bot's Opinion correctly emphasised that a 'human embryo' required a body (an incident of Article 5 of Directive 98/44) and the point of bodily formation is understood in microbiological detail (it's not conception) he glossed this, without any scientific or legal foundation whatever, as 'the capacity to develop into a complete human being'. So, in wrapping up ISCC, the CJEU will doubtless agree with Advocate General Villalón that the fundamental test of a 'human embryo' is its 'inherent capacity of developing into a human being', but squirm in the knowledge that even this is founded on bunk.