European Court of Justice Renders Stem Cell Decision

By Kevin E. Noonan --

The European Court of Justice (ECJ) today rendered its decision regarding the patent-eligibility of human embryonic stem cells (hESCs) in Europe, and as widely expected has heeded the recommendation of the court's advocate general that hESCs are not patent-eligible subject matter (see "European Court of Justice Considers Embryonic Stem Cell Ban").

The case began in 2004, when Greenpeace sued in German federal court over a German patent to the University of Bonn involving methods for deriving neural cells from hESCs (DE 197568664 C1).  While German laws regarding stem cell research have been characterized as the "most restrictive in Europe," such research is permitted provided that it is performed with pluripotent (rather than totipotent) cells, using cell lines imported from abroad and only cell lines that were made prior to May 2007.  Nevertheless, Greenpeace argued that claims to methods for using hESCs were "immoral and against public order," provisions of European law generally that define subject matter not eligible for patent (there is no corresponding provision under U.S. law).

The German federal court ruled for Greenpeace in 2006, and the university appealed to the German supreme court.  That court decided that it needed to refer the question to the ECJ, since German law was closely patterned on European Union guidelines for biotechnology patenting.  In the "Questions referred" to the ECJ, the German court asked for clarification on the meaning of the term "human embryos" in Article 6(2)(c) of Directive 98/44/EC of the European Parliament and of the Council of 6 July 1998 on the legal protection of biotechnological inventions (OJ 1998 L 213, p. 13), and the expression "uses of human embryos for industrial or commercial purposes," specifically whether this includes any commercial exploitation within the meaning of Article 6(1) of the Directive, especially use for the purposes of scientific research.  Finally, the court asked whether methods for producing hESCs or using them for technical purposes are unpatentable "even if the use of human embryos does not form part of the technical teaching claimed with the patent, but is a necessary precondition for the application of that teaching, (a) because the patent concerns a product whose production necessitates the prior destruction of human embryos or (b) because the patent concerns a process for which such a product is needed as base material."

On March 17, 2011, the ECJ advocate-general, Judge Yves Bot, rendered an opinion that stem cell patents were "contrary to ethics and public policy" because they required "industrial use" of human embryos.  This recommendation was not binding on the ECJ, but it was expected that the court would agree with the advocate-general, since it is rare that such preliminary opinions are overruled.

In its decision, the ECJ cited the Directive on biotechnology as well as the relevant provisions of the TRIPS agreement and Articles 52(1) and 53 of the Convention on the Grant of European Patents relating to broad scope of patent protection (limited, inter alia, by consideration of ordre public or morality).  The court also considered German law (Paragraph 2 of the Patentgesetz) as amended to comply with the Directive, and specifically the prohibition under German law of patenting "uses of human embryos for industrial or commercial purposes" and provisions of German law restricting the uses to which embryos can be put outside the patent context (such as laws against human "cloning").  Nonetheless, the court stated that:

It must be borne in mind that, according to settled case-law, the need for a uniform application of European Union law and the principle of equality require that the terms of a provision of European Union law which makes no express reference to the law of the Member States for the purpose of determining its meaning and scope must normally be given an independent and uniform interpretation throughout the European Union.

This is because, in part:

The lack of a uniform definition of the concept of human embryo would create a risk of the authors of certain biotechnological inventions being tempted to seek their patentability in the Member States which have the narrowest concept of human embryo and are accordingly the most liberal as regards possible patentability, because those inventions would not be patentable in the other Member States. Such a situation would adversely affect the smooth functioning of the internal market which is the aim of the Directive.

The court then contrasted the provisions of Article 6(1) of the Directive, which granted "the administrative authorities and courts of the Member States a wide discretion in applying the exclusion from patentability of inventions whose commercial exploitation would be contrary to ordre public and morality" with Article 6(2), which "allows the Member States no discretion with regard to the unpatentability of the processes and uses which it sets out, since the very purpose of this provision is to delimit the exclusion laid down in Article 6(1)."  Finding that there is no express definition of the term "human embryo" in the Directive, the court's opinion states that it must consider the definition in "the context in which they occur and the purposes of the rules of which they form part," including that the preamble of the Directive delimits patenting by the principle that protecting biologically derived invention "must be consistent with regard for fundamental rights and, in particular, the dignity of the person."  These and other considerations permit the court to conclude that the term "human embryo" should be "understood in a wide sense."  Thus:

{A]ny human ovum must, as soon as fertilised, be regarded as a "human embryo" within the meaning and for the purposes of the application of Article 6(2)(c) of the Directive, if that fertilisation is such as to commence the process of development of a human being.

(In addition, the court puts into the "human embryo" category "cloned" ova (wherein the nucleus of a somatic cell is introduced into an enucleated ovum) and ova stimulated to divide parthenogenetically.)  The court then considered the question of whether a "totipotent" or "pluripotent" human embryonic stem cell would fall within the definition of a human embryo, deciding that these cells' capacity to develop into many or all human tissues was sufficient for them to qualify as a "human embryo."

As to the second question, the court found that uses of hESCs for scientific research is encompassed by the Directive insofar as the use is subject to patent protection, because "clearly the grant of a patent implies, in principle, its industrial or commercial application."  In making this determination the ECJ distinguished uses for "therapeutic or diagnostic" purposes directed to the embryo, which are entitled to patent protection under other provisions of the Directive.  The court also answered the question of whether a process is patent-ineligible where the "purpose is not the use of human embryos, where it concerns a product whose production necessitates the prior destruction of human embryos or a process for which requires a base material obtained by destruction of human embryos," holding that such processes are patent-ineligible because "the removal of a stem cell from a human embryo at the blastocyst stage entails the destruction of that embryo":

Accordingly, on the same grounds as those set out in paragraphs 32 to 35 above, an invention must be regarded as unpatentable, even if the claims of the patent do not concern the use of human embryos, where the implementation of the invention requires the destruction of human embryos.  In that case too, the view must be taken that there is use of human embryos within the meaning of Article 6(2)(c) of the Directive.  The fact that destruction may occur at a stage long before the implementation of the invention, as in the case of the production of embryonic stem cells from a lineage of stem cells the mere production of which implied the destruction of human embryos is, in that regard, irrelevant.

For clarity, the court expressly set forth its decision as follows:

1.   Article 6(2)(c) of Directive 98/44/EC of the European Parliament and of the Council of 6 July 1998 on the legal protection of biotechnological inventions must be interpreted as meaning that:

–   any human ovum after fertilisation, any non-fertilised human ovum into which the cell nucleus from a mature human cell has been transplanted, and any non-fertilised human ovum whose division and further development have been stimulated by parthenogenesis constitute a 'human embryo';

–   it is for the referring court to ascertain, in the light of scientific developments, whether a stem cell obtained from a human embryo at the blastocyst stage constitutes a 'human embryo' within the meaning of Article 6(2)(c) of Directive 98/44.

2.   The exclusion from patentability concerning the use of human embryos for industrial or commercial purposes set out in Article 6(2)(c) of Directive 98/44 also covers the use of human embryos for purposes of scientific research, only use for therapeutic or diagnostic purposes which are applied to the human embryo and are useful to it being patentable.

3.   Article 6(2)(c) of Directive 98/44 excludes an invention from patentability where the technical teaching which is the subject-matter of the patent application requires the prior destruction of human embryos or their use as base material, whatever the stage at which that takes place and even if the description of the technical teaching claimed does not refer to the use of human embryos.

The court's decision is the latest in a series of initiatives by individuals and groups with philosophical objections to patents involving biological materials, particularly material derived from human beings.  These include the Public Patent (PUBPAT) Foundation's attempts to invalidate the Thomson hESC patents in the U.S. (unsuccessful with regard to U.S. Patent Nos. 5,843,780 and 6,200,806 and currently pending against U.S. Patent No. 7,029,913) as well as PUBPAT and the ACLU's challenge to human gene patenting in the AMP v. USPTO (Myriad) case.  Opponents of such patents voice various arguments and rationales against patenting products of human biology, but ultimately the argument is the one raised in Europe, that there are moral objections to the practice.  Such objections are sincerely held by many and it is neither possible nor productive to make arguments on these grounds:  as it is in many public policy debates, these positions tend to be absolutes for some, not subject to merely reasoned argument.  Perhaps the best rejoinder of the argument is to posit the situation if patent opponents prevail (which also comprises a part of the scientists' argument in their letter).  Lack of patent protection will have two concrete and predictable consequences:  lack of financial investment to translate basic scientific discoveries to useful commercial products, and (where possible) reducing or eliminating public disclosure of inventions (and where not possible, investment in other technologies).  Neither outcome is conducive to reducing human morbidity or mortality or improving the human condition.  It is hard to understand how advocating such an outcome can be considered the more moral position.

Even the possibility that the ECJ would adopt the Advocate General's position prompted several stem cell scientists in Europe to send a letter to the court, published in Nature on April 28th, setting forth the case for stem cell patenting.  In the letter, the scientists expressed their "profound concern" in the capacities as "coordinators of multinational European stem-cell projects."  They contended that stem cells are cell lines, not embryos, and that they were derived from "surplus in vitro fertilized eggs donated after fertility treatments" that could not be maintained "indefinitely."  The existence of "more than 100" established stem cell likes make concerns about embryos "misplaced," they asserted, and warned that it may be "premature to suggest that human embryonic stem cells can be replaced" (by iPS cells, for example) in developing stem cell therapies.  A stem cell ban in Europe would prevent scientists from "deliver[ing] clinical benefits without the involvement of biological industry," and such companies "must have patent protection as an incentive" to do their work in Europe.  The consequence of the ECJ ruling as it has today, these scientists predicted, would result in "European discoveries [being] translated into applications elsewhere, at a potential cost to the European citizen."

The ECJ's decision is binding on the member states of the European Community.  Thus, Europe represents a "living laboratory" for the proposition that patenting can retard innovation and that progress can be promoted in the absence of patent protection.  Europe once before took the "moral" position against patenting a particular technology, namely biotechnology, 30 years ago.  As a result, the rest of the world (predominantly the U.S.) was able to develop this technology without European competition, and companies such as Amgen, Genentech, Biogen, and many others became world leaders in translating the fruits of the biotech revolution into commercial products that improved the lives of millions.  Stem cells now provide another opportunity for countries outside of Europe to take (or maintain) the lead in a new technology, regenerative medicine, that has the promise of being just as revolutionary and to provide just as dramatic an improvement in human welfare.  But this opportunity will only exist if the rest of the world, particularly the U.S., once again ignores the siren song of any policy based on any particular version of morality, and continues to permit "anything under the sun made by man" to be patented.

Comments

[Dan Feigelson]

"It is hard to understand how advocating such an outcome can be considered the more moral position."

Kevin, as an undergraduate chemistry major I found little that I learned in class that I could readily share with non-scientists as being applicable to daily life. Thermodynamic versus kinetic control of chemical reactions was the big exception, because it can be thought of as short-term-gain (or path of least resistance) overcoming long-term-gain - and that's something we see all the time. It explains the behavior of politicians in most situations, and I think it explains those who militate against embryonic stem cell research at the expense of ultimately saving lives.

Not that that observation makes things any less frustrating for those of us who support this kind of research. I wonder if the EU will change its tune when its scientists who want to do embryonic stem cell research start moving to friendlier jurisdictions.

[David Koepsell]

I disagree with the moral reason for ineligibility here, as I think being human tissue is irrelevant. Rather, the ethical issue that's really at stake is the patent-eligibility of products of nature, as I argue here and elsewhere: http://nanowares.wordpress.com/2011/09/30/logic-apparently-off-limits-in-the-law/ Unfortunately, the courts and patent offices are too deeply invested in the illogic of "isolation" as invention to change that now. Moreover, unlike the Bush ban on stem cell research funding by the US govt., at least this leaves the door open for all the research and commercialization, just without the benefit of a monopoly.

[Anon]

Not sure the laboratory idea works, Kevin. All this does is reduce the size of the world market where the patent owner enjoys protection.

Whether the stem cell research takes place in Paris, France or Paris, Virginia, the invention can be patented in the USA but not in Europe.

[Kevin E. Noonan]

Dear Anon:

True, but there should be an exodus of stem cell commercialization to countries that protect the IP if IP matters, and less so (or the reverse) if it does not.

We shall see (although being human behavior there are a wealth of confounding variables that could influence the outcome).

Thanks for the comment.

[Berislav Bulat, MD]

Mr Noonan (and Mr Feigelson as well),

from a pro-life scientist's point of view, "the more moral position" is clear enough when one puts himself in the position of the "human embryo understood in the wide sense".

Sacrificing one in the process of acquiring stem cells must not be done without one's own will for the sacrifice - like e.g. organ donors do, sacrifice themselves eith their own free will for the sake of improving human condition (and this would also be morally questionable if the donor would have to be destroyed in the process!)

Why would this apply to embryos - haven't we all been embryos once? Should we not want every single embryo on this world to become what we are now? Is it actually (or morally, if you will) our decision to make?

I think not; that's why I am so relieved to hear such a verdict from the ECJ, understood in the wide sense as I've widen it here...

[Kevin E. Noonan]

Dear Dr. Bulat:

Unfortunately, these decisions cannot be made in a vacuum. Human ESCs are (predominantly) derived from embtryos that would otherwise be discarded. Thus, using them to make hESCs that might cure disease seems a better outcome than destroying them.

Thanks for the comment.

[Skeptical]

Kevin,

Dr. Bulat's view is not in a vacuum.

The moral dilemma that is avoided is that one does not create the business condition that drives a profit from a bad thing (and thus ensures MORE of the bad thing).

Sure, it is a shame that embryos may be discarded. It is FAR more a shame to make a profit from that discarding and thus WANT to "discard" them, or create a sustained "need" (i.e. business need) to keep (and proliferate) the "discarding" by creating the end-point profit motive.

It is a far better MORAL outcome (granted, the assumption of this particular MORAL is accepted) that the business proposition is detroyed at a nascent stage (yes - the play on words is intended), even if some minor good is lost.

[Kevin E. Noonan]

Sorry, Skeptical, meant to get back to this.

I agree that a system where embyros are processed (as in Brave New World) for stem cells could be a bad one, especially if some form of economic coercion was applied.

But I don't think that "profit" is the answer, since the patient who benefits from proposed stem cell treatments certainly "profits" as much (and in some ways more than) the purveyor of the stem cell cure. And, to sound like Congress, the President or the FTC, we all benefit if stem cell treatments reduce morbidity, mortality and the cost of long-term care for currently intractable diseases.

This is especially true if the hESCs come from embryos "left over" from IVF procedures. it is also true for those families that have another child hoping to get a "close enough" genetic match for a sick child who needs a transplant - while having a child is a very personal decision, having a child merely to reap that child's stem cells isn't (in my view) a better outcome than producing an embryo and harvesting the stem cells.

But this posits that these decisions remain personal (your own eggs and sperm) or eleemosynary, not industrial. I agree that any regulations on the industry should be directed towards preventing that outcome.

Of course, there is a book entitled "Red Markets" that has another, opposite take on charitable organ donation, but that's a discussion for another post.

[Berislav Bulat, MD]

Just to make clear, the opposition's stand in this debate is that embryos should not be produced (IVF or any other way other than the copulatory one, for which the term "conceived" is then more appropriate). Period.

Everything then deriving from the sad fact that embryos are being "produced" and most of them then scheduled to be "discarded" musn't be considered as a point to use for "greater good" - since there's something bad (production instead of conceiving) in the roots of this perceived good, as a result there would (will) be negative consequences for everyone involved (this is not a curse, but a logically derived fact).

Therefore, opposed to your opinion, Kevin and others who are against the Court's ruling, the only good in this whole embryo debate is to finally grant them (the embryos) that they are human and thus cannot be subject to any unwilling procedure that could lead to their destruction or to any commercialization what I dearly hope this ruling is a corner stone for.

This might sound like utopist or reactionary idea to you (like you suggest with the implication of my alleged vacuum approach that I think I've never given reason to imply) while the fruits of embryo enginering are at hand, but I believe that this is the only path to the good of everyone, including the sick child you mention in your answer to Skeptical. This opinion of mine is still a bit difficult to support by scientific evidence other than philosophy, ethics and logic, but time will show because stem cell research is still at its beginning and there are still many questions so we need to take more time and slow down in order not to make mistakes.

[Kevin E. Noonan]

Dear Dr. Bulat:

Rules of categorical exclusion have a long history in our species, especially when purportedly based on morality. I respect your decision/opinion that anything that destroys an embryo is anathema, but I think it misguided in a world where sick men, women and children exist and could be helped by stem cell medicine. Most Western countries permit abortion at a woman's choice without any reason other than the recognition that any other regime would enslave her to her biology against her will. How much less "moral" is it to permit stem cells to be harvested from embryos destined for the scrap heap (unless you believe that such embryos should be maintained for all time in a state of suspended animation; I'm not sure that is not just as horrible a prospect).

And remember, if history has taught us anything it is that "morality" is a shifting sand that differs from culture to culture and century to century. But death and disability are real and present, and I think we have an obligation to the living to do what we can to reduce the incidence of both.

Thanks for the comment.

[Skeptical]

Not to open a can of worms, but Dr. Noonan, a woman's choice of abortion being equated to as you put it: "enslave her to her biology against her will" is offensive. The "will" was to engage in an act of procreation. The woman had all the "will" she will ever have at that point. To dissassociate the "will" at that point to a result of that will is not acceptable. There is no "enslaving" in making people accountable for their choices.

I recognize that this is not a legal position, but I am compelled to state it in rebuttal to your comment, which is just as much NOT a legal position. The argument of "enslavement" is an emotional ploy. Let's keep the big picture facts straight.

There is a bigger issue though to be discussed here: that morality is a shifting sand - the concept itself that morality is relativistic is NOT a conclusion that can be blindly accepted. Yes, views on what moral standards should be applied can shift - but morality itself is decidely NOT something that should be shifted hither and non. Relativistic morality MUST be (and I realize how trite this may come across), MUST be aligned with the Nazi debacle, because it was relativistic morality that serves as the credibility cornerstone of all the Nazi atrocities.

We as a society, as a race, simply CANNOT accept the shifting sands argument.

[Kevin E. Noonan]

Dear Skeptical:

I truly didn't mean to offend or raise the emotional level of the debate. Let me try to say what I mean another way:

The choice of whether it is more moral to provide stem cell therapies or protect embryos is one about which people can differ, just like the choice of maintaining or terminating a pregnancy - it is a personal choice (within limits). And cultures differ on how to make that choice - Nazi Germany is not the paradigm. Indeed, that exception probes the rule in this case.

My point is that there are many grounds for making policy, and my moral compass or yours shouldn't be what we use - the political tyrrany of the majority is bad enough without making it a moral tyrrany as well. If we are to look for objective grounds for making policy, it seems to me that the greatest good - treating sick members of our society who have illnesses that cannot be addressed by other means - using resources that will be destroyed otherwise is a sensible choice.

I agree that coercion or true industrialization of the process is not in society's interest, and hence the "Brave New World" reference. But there are plenty of ways to preclude a slide down the perceived slippery slope other than an outright, categorical ban. Such bans are too inflexible and too prone to prevent objective discussions of the pros and cons of societal policy, particularly in a heterogeneous society where personal morals will differ. I think making choices for all of us based on what some (or even most) of us think is "moral" is the wrong way to approach those questions.

But I also realize that reasonable people can differ. Thanks for the discussion.

[Skeptical]

Dr. Noonan,

Thank you for stepping back from the abortion/enslavement discussion point.

However, the larger discussion of shifting sands still does not sit comfortably with me. You paint having a moral compass as the same as imposing moral tyranny. I would respond that without a compass, (and while not a paradigm), Nazi Germany still slides comfortably into position. "The greater good" and "some people benefit" (in fact some people plus many) where justifications used under Nazi Germany for its relativisitic moral position. The slope is steeper and more slippier than you have indicated.

I disagree that moral positions cannot tolerate "objective" discussions and cringe at the semi-polemic of "heterogeneous society" which to me is simply a cop-out (How heterogeneous is STILL a decision to make - we do not accept pedophile philosophies, even though there is an "objective" group of people that would have our society accept such repugnant views).

We must and do draw the line somewhere, and the ideal of moral relativism means an arbitrary and meaningless place is drawn - IF AT ALL.

I too realize that reasonable people can and do differ. We will not resolve this issue here - but i do want to strongly frame the issue "appropriately" (and yes, my "appropriately" will differ from yours).

Also, on another thread I made the comment about seeing you on the Prior User Rights USPTO teleconference. Will you be writing an article on that soon? I would love to have your impression of the speakers (especially the early ones whom I missed).

[Berislav Bulat, MD]

I co-sign Skeptical's posts so I won't let the worms out of the can too far. I would just like to thank Mr. Noonan for the debate and the article as well.

I've strayed to this blog in search for a pro-life comment on the ECJ decision, but here I found even more - a respectful exchange of opinions, so thank you all for that.