New Tech, New Rules: Organoids and Ethics at the CJEU

Introduction

Last week, while attending a conference, organized by the Petrie-Flom Center in conjunction with a number of other Harvard institutions, on the ethics of early embryo research and the future of the 14-day rule, I was struck by the presentations on recent developments in stem cell technology. The speakers outlined fascinating developments in human brain organoids. And, since my own cranial organoid is becoming increasingly single track, I started wondering about the potential patentability of such inventions.

An intestinal organoid grown from Lgr5+ stem cells

An intestinal organoid grown from Lgr5+ stem cells

By way of very brief explanation, a human brain organoid is a structure of cells created in vitro through the stimulation of human stem cells. A recent paper has concluded that, given the right conditions for their development, these cell cultures can grow to resemble a 20 week-old human brain in vivo in a number of important respects.

At the conference, Dr John Aach, of the Department of Genetics at Harvard Medical School highlighted the potential of these technologies to form the basis of innovative research and treatments. However, he also highlighted new ethical questions posed by them. In particular, (and I fear I may be grossly oversimplifying his much more subtle presentation) he noted that a sufficiently developed human brain organoid might have the capacity to feel pain. Such technologies might fall to be regulated alongside human embryos created for research. In most jurisdictions, developing an embryo beyond 14 days of gestation is prohibited, whether by law or soft regulation. The rule originally struck a balance between the interests of research and the demands of ethics: day 14 usually marks the appearance of the primitive streak in an embryo and presents a convenient point to place an ethical limitation on research.  Dr Aach noted, however, that a brain organoid does not fall under the traditional definition of embryo. As such, its development is not necessarily subject to the 14-day rule. And yet, the creation of a clump of cells that feels pain is clearly a cause for ethical concern. He argued that the time has come to re-examine the rule in light of technological advancements like organoids. Its replacement, he argued, should not be based on canonical limits but on the underlying moral concerns.

The European patent system has been wrestling with these concerns for some time, particularly with regard to inventions involving human embryos. I’d like to briefly examine the Brustle and International Stem Cell decisions to see how new technologies like human brain organoids might fare under a European patent examination.

Brustle v Greenpeace

The 2011 decision of the Courts of Justice of the European Union (“CJEU”) in Brustle arose out of a German patent application. The claim focused on the production of neural cells that had potential applications in treatments for Alzheimer’s and Parkinson’s. Ordinarily, the production of these cells involved the destruction of human embryos. However, the inventor proposed a new method of differentiating the neural precursor cells from pluripotent stem cells, making it unnecessary to destroy mature human embryos.

The problem arose out of Article 6 of the 1998 Biotech Directive. Article 6 forbids patents on the use of human embryos for industrial or commercial purposes and it was argued that the pluripotent stem cells also fell afoul of the prohibition. The CJEU was called on to interpret the phrase “human embryo”. It found that the Directive focused, not on the protection of human life, but of the human body. As such, it was unnecessary to engage in any moral or philosophical examination of where the protection should begin. Article 6 simply prohibited patents on anything “capable of commencing the process of development of a human being” (paragraph 36). The CJEU remanded the case back to the German courts to determine whether the invention in question was covered by the prohibition.

However, the case was strongly criticized for its specific inclusion of parthenotes in its definition of embryos. Parthenotes are created by chemically stimulating the cellular division of an unfertilized ovum. They are a source of pluripotent stem cells but, because they lack paternal DNA, they cannot pass the first few days of development and cannot develop into human beings.

International Stem Cell Corporation v Comptroller General of Patents, Designs and Trademarks

This particular canonical definition remained in force until the 2014 International Stem Cell decision. The claim in question related to exactly those parthenotes that were expressly excluded in Brustle. A more reflective CJEU reconsidered the blunt prohibition on patenting anything “capable of commencing the process of development”. Instead, they noted that the underlying concern of the entire 1998 Directive is the protection of human dignity. As such the prohibition does not apply immediately to anything that could commence the process of development but instead applies to anything functionally equivalent to an embryo: anything with the “inherent capacity of developing into a human being”. They determined that parthenotes do not possess that capacity and so are patent eligible.

Organoids and Moral Concerns

Objections to patents on human brain organoids could be brought under either the prohibition of patents on embryos or the prohibition of patents on elements of the human body. However, they seem to escape these two potential obstacles.

First, despite their embryonic origins, they do not possess the inherent capacity to develop a human being and, as such, do not fall afoul of the prohibition on patents of uses of embryos. Second, in principle, an isolated element of the human body that has some industrial (and especially medicinal) application is patentable under the Biotech Directive. The human brain organoids and other, similar, inventions then, seem ripe for patenting under the jurisdiction of the CJEU. However, an application that goes through the European Patent Office would have to face the specter of Article 53(a) and its catch-all prohibition against patents on immoral inventions. What we need now is a thoughtful consideration of the underlying moral principles, not a reversion to canon. The CJEU has determined that the objection to a patent on embryos is not based simply on the fact that a human body is involved: the objection goes deeper than that. It goes to human dignity and some intrinsic capacity of an entity to become a person. However, if, like me, you get a twist in your gut at the thought of a patent issued on a collection of human cells that can feel pain, that definition may not be enough.

Be Sociable, Share!