Open letter: stem cell patent case could have far-reaching impact

Pubblicato: 
28 Apr 2011
By: 
Emma Kemp

**New: European Court Decision, 18 October 2011** Stem cell scientists have raised serious concerns about the impact of a possible ban on patents for techniques using human embryonic stem cells.

On 10th March the advocate-general of the European Court of Justice, Yves Bot, gave his opinion on a long-running legal debate about a patent filed several years ago in Germany. If the Court follows Bot’s recommendations, patenting of applications using embryonic stem cells will be prohibited on moral grounds.

This week leaders of major stem cell projects in Europe responded to the advocate-general’s statement with the open letter below, published in the journal Nature on 28th April (Nature 472, 418; 2011). The authors, representing both embryonic and adult stem cell research, point to a potential wide-ranging impact on the entire stem cell field if the European Court chooses to uphold Bot’s opinion in a final and legally binding ruling.

Patenting is a key step in the development of academic research findings into new medical treatments. Without the possibility of patent protection, companies are unlikely to invest in the cell manufacturing technologies needed to develop and provide innovative stem cell treatments. In their letter, the scientists state that the advocate-general’s opinion undermines years of funding from the European Commission and individual EU member states for research aimed at developing human embryonic stem cell based therapies. They suggest that citizens may find that new therapies are developed elsewhere and will not be available in Europe, or will be prohibitively expensive.

This case has implications for public perception and funding of research. If the application of embryonic stem cells to develop medical therapies is branded immoral, continued government support will be challenged. Leading stem cell scientists see that as disastrous: the first clinical trials using human embryonic stem cells are now commencing, and there is currently no suitable alternative to these cells.

The consequences are likely to extend beyond those working directly with human embryonic stem cells. Embryonic stem cell studies inform research with other types of stem cells. Researchers fear that prohibition of embryonic stem cell patents could break up existing pan-European research collaborations and cripple the European stem cell research community.

What do you think? You can add your comments below and you may add your signature to the letter if you wish.

The International Society for Stem Cell Research (ISSCR) have also issued a statement on this case.

Open letter from scientists: 'No' to ban on stem-cell patents

Nature 472, 418; 2011
The advocate-general of the European Court of Justice has recommended the prohibition on ethical grounds of patents involving human embryonic stem cells (Nature 471, 280; 2011). We write to express profound concern over this recommendation, as co-ordinators of multinational European stem-cell projects, working with both adult and embryonic stem cells.

Embryonic stem cells are cell lines, not embryos. They are derived using surplus in vitro fertilized eggs donated after fertility treatment and can be maintained indefinitely. As more than 100 established lines are now supplied through national and international cell banks, concern about commercialization of the human embryo is misplaced.

"European discoveries could be translated into applications elsewhere, at a potential cost to the European citizen"

It is premature to suggest that human embryonic stem cells can be replaced in development of therapies. Although induced pluripotent stem cells offer additional possibilities, particularly for disease modelling, the reprogramming process is still imperfect. Scientists working in stem-cell medicine will not be able to deliver clinical benefits without the involvement of biological industry . But innovative companies must have patent protection as an incentive to become active in Europe. The advocate-general’s opinion therefore represents a blow to years of effort to derive biomedical applications from embryonic stem cells in areas such as drug development and cell-replacement therapy. If implemented, European discoveries could be translated into applications elsewhere, at a potential cost to the European citizen. The advocate-general’s opinion will now be considered by members of the court. We trust that they will deliberate on the full implications before making a legally binding ruling.

Peter Andrews (ESTOOLS), Clare Blackburn (EuroStemCell), Anders Bjorklund (NeuroStemcell), Elena Cattaneo (NeuroStemcell), Giulio Cossu (OptiStem), Juergen Hescheler (ESNATS), Olle Lindvall (NeuroStemcell), Marc Peschanski (Stem-HD), Daniel Pipeleers (BetaCellTherapy), David Sassoon (EndoStem), Austin Smith (EuroSyStem), Anna Veiga (hESCreg), Catherine Verfaille (HemiBio)

More justification needed please

I remain ambivalent about the issue of whether or not any use of ES cells should be seen as permanently tainted by their means of derivation, which seems to be the key factor underlying Yves Bot's recommendation.  Possible concerns over "complicity" could be stretched a bit too far when dealing with a cell line that has been in culture for some time and has been through a long chain of hands; otherwise, any of us who have worked with HeLa cells might equally have a lot to answer for and I'm not sure that such ethical concerns should be overwhelming.

 

By contrast, the deliberate creation of embryos for the express purpose of research that necessitates their destruction, especially where this involves recruitment of women to provide eggs in return for some form of financial inducement, looks like a far greater concern to me.  As it happens, the UK appears unique within Europe in this particular regard so far, with little or no evidence to date that this particular step has honestly contributed towards genuine progress in any form of stem cell research (despite some apparent propaganda to the contrary).

 

However, the supposed necessity of patents in order for research to flourish, as asserted above by several commentators, raises additional questions for me.  To what extent should a commercial company be able to claim ownership via patents when the underlying research has already benefitted from increasingly massive injections of public funds?  Are there issues of social justice here that are being overlooked if the financial interests of a patent-holder are considered by some to be paramount – especially when the research may not have been possible to begin with without the broad support of taxpayers across different countries?  And can we be sure that the existence of some patents would not instead have the effect of restricting the wider application of research in the direction of therapies?

 

More attempts to connect the current debate with the following one would seem prudent:

http://www.nature.com/stemcells/2007/0711/071108/full/stemcells.2007.113...

In this regard, I would like to draw particular attention to Jeanne Loring’s comment that unlike “a scientific publication, which encourages other scientists to reproduce a researcher's work, a patent has the force of law to exclude others from working with the patented invention or material”.  Having only just viewed the comments by others, I would especially appreciate hearing Peter Andrews’ perspective on this point, pursuant to his own comments on 27/04/2011.

Listening to unwelcome opinions

There are two other letters to Nature that readers should be aware of here http://www.nature.com/nature/journal/v474/n7349/full/474036a.html and here http://www.nature.com/nature/journal/v474/n7353/full/474579d.html

There are also a couple of illuminating article about the WARF decision which are highly relevant to the present case here http://ugent.academia.edu/SigridSterckx/Papers/130982/Patentability_of_human_embryonic_stem_cells and here http://ugent.academia.edu/SigridSterckx/Papers/182592/Assessing_the_morality_of_the_commercial_exploitation_of_inventions_concerning_uses_of_human_embryos_and_the_relevance_of_moral_complicity 

Clearly companies and individuals seeking patents on hESC related technologies will wish that the ECJ should rule such activities patentable, but companies would be wise not to rely too heavily on legal opinions that reflect their own desires. There is another side of the case and that side may yet prevail.

Treatments are already expensive...

...and difficult to obtain. I'm currently raising money to save my life with stem cell treatment overseas. The provincial attitude of the US and others, like this judge, will set back research by years - years I don't have time to wait.

When will such bans be expanded to include other viable human tissues, like skin, corneas, organs, etc.? Or will we, as was postulated before, start euthanizing our elderly and terminally ill - after all, they're going to die anyway, right? Why not bypass all this ban/don't ban rhetoric and start the death lists now? Isn't it "god's will" that we suffer and die? Let's be humane and end the suffering now...

loathsome, isn't it?

In my opinion, stem cells are equal to any other tissue or organ collected now, and the results of using stem cells can be life-changing!  I have no qualms using stem cells to regenerate my own organs back to a working status. I am willing to travel anywhere at any price to make it happen. 

I want to live! To live a life worth living!

The possibility of a European ban means that I go where treatment is available - China, Russia, South America. People leave the US in droves for "unapproved" medical care. If the ban goes through, Europe will see the same medical diaspora. If such a ban is implemented on a global basis, then I, like so many others, are doomed.

agreed

I totally agree with you Annie. Couldn't say this better!

The Case for Common Sense

The image of Europe-based judicial decisions has become increasingly damaged, in Scotland in particular, by over-reliance on abstract principle and a reluctance to trim judgments according to common sense and practical considerations. As someone with muscular dystrophy, hoping desperately for something that might restore some of my strength, the Advocate General's opinion fills me with frustration and rage.

I am a sufferer of LG MD and

I am a sufferer of LG MD and have read (and understand in laymans terms) the details of the debate.  Stem cells are taken from a four-day-old embryo which would NOT be used to create a baby, though the issue seems to be that it COULD be used to create a baby.  In that case, there is no point allowing abortion, is there?  A four day old embryo is not a 'life' under the vast majority of definitions.  Why not let these embryos be used for something with a purpose as they would otherwise not be used?  The 'anti' campaigners clearly do not know what it is like to suffer from a condition which may benefit from a stem cell treatment.  The delays (such as George W Bush's veto against stem cell treatments) are reducing the chances of survival and improved quality of life for people who can't afford to wait for advances in medicine which will take a long time under favourable conditions.

European Stem Cell Research : Proposed Ban on patent protection

I have a daughter with a rare form of Muscular Dystrophy. I fear for her future. There is currently no cure or treatment and I believe that any move to make it more difficult for investors in treatment, will discourage research initiatives. This in turn will remove all hope of a cure being discovered.

On a wider scale there are other illnesses, such as Alzheimer's, which are going to completely overwhelm our society in the next few years both in terms of the members of the community who are going to develop the conditions and those who are going to have to care for them. Research into finding a cure is absolutely essential or else I fear that there will have to be a policy of mass euthanasia, which I believe to be far less ethical than the use of embryonic stem cells in research.

Time is precious!

 The morality issues should surely be in favour of finding cures for those afflicted by the various diseases that would benefit from Stem Cell Research.  All ways of funding Stem Cell Research should be welcomed and not deterred by patent issues. I have had Muscular Dystrophy nearly all my life and every day is a continuous struggle.  Children with Duchenne Muscular Dystrophy have a shortened life expectancy.  At the present time no cure is available.  I find it difficult to imagine that anyone would want to prevent a child benefiting from research which could find a treatment for their incurable condition.  I find it unbelievable that we are still coming up against barriers and obstacles to do with Stem Cell Research which at the moment is the way forward and progress in finding an eventual cure.  So much time has already been wasted, precious time that children and adults with Muscular Dystrophy and other life threatening conditions don't have.

Problems with patents

It should be noted that the current European patent prohibition is not a novelty. It is clearly stated in Article 6 of Biotech Patents Directive (98/44) which binds all EU members since 1998. The first paragraph of this directive describes inventions as unpatentable where their commercial exploitation would be contrary to ordre public or morality. It goes on to specify in the next paragraph that the prohibitions include particular processes for cloning human beings or for modifying the germline genetic identity of human beings, as well as the use of human embryos for industrial or commercial purposes. None of these practices are patentable. The challenge under discussion basically involves determining exactly what is meant by human embryos.

Whatever the outcome it is difficult to get one's head around the position scientists take on these matters. Wasn't it in 2007 when major US scientists were protesting vociferously against patents issued to the University of Wisconsin?

Sadly there will be no absolute prohibitions on the commercialisation of the human embryo whatever the outcome at the European Court. The case is simply about interpreting patenting laws not about ethics.

Patient and family hopes for Embryonic stem cell research

Recent advances in knowledge arising from research using embryonic stem cells under tightly regulated conditions have given hope to many patients and families living with currently intractible and life limiting conditions that it will one day be possible to develop interventions that will treat, prevent or cure some of these at least. Although the emergence of licenced therapies may be some way in the future, the imposition of barriers that would unreasonably frustrate the legitimate expectations of patients and families that new scientific understanding will be translated into clinically available therapies would be a cruel blow. The use of embryonic stem cells is already rigorously controlled in Europe. Further restrictions on the translation of ethical, high quality science into available therapies provided to patients who need them should  be robustly contested.

Alastair Kent

Director, Genetic Alliance UK (The national alliance of 150+ patient groups supporting those with genetic disorders)

Honesty better than bias, courage more evaluable than fear.

Science and its exploitation must follow separated ways: the development of science should be as free as possible, its exploitation and marketing - while unavoidable - as carefull as possible.

Researches and applications on stem cells are exciting and absolutely moral in principle, at least in my personal opinion. It seems to be simple to understand that stabilized cell lines sufficiently support the needs of the marketing, and that no embryos are in danger for these advancement in science.

However my knowledge is really too little to express an opinion on the benefit of applications for human healths, As an exemple, I do not know enough about the possible oncogenicity of the implant of stem cells derivatives in adult organisms. While I suppose that these aspects are carefully evaluated before proposing a product for trade, the judgement on the final decision on marketable products, like nerve cells precursors, is far from my area of expertise.

I hope that any decisions should be done by honest and enlightened minds, and that courage will win over bias.

European patent threat to stem cell research

Stem cell research has long been dogged by appalling ignorance but this threat from the European Court of Justice defies belief. It cites ethical grounds for its stance, yet the premise for its standpoint is clearly erroneous. As more than 100 established lines are supplied through national and international cell banks, concern about commercialisation of the human embryo is totally  misplaced. This is fact, not supposition.

The advances made in European stem cell research during a time of stasis in the United States have offered hope for millions of people in this and future generations across the length and breadth of the planet. The potential benefits to people’s health and quality of life will also carry a payback to NHS Trusts in Britain and equivalents in Europe and ensure that age-related disease does not equate to being condemned to a long, slow, graceless death.

Our stem cell scientists and their work deserve a better fate than to be sacrificed on an artificially-constructed altar of unwarranted piety. If this patent ban is enforced our top scientisists in Britain and other European countries may well join a new brain drain to the Johnny-cum-lately stem cell sector in America. European governments will have time to reflect on the difference between ethics and synthetics and the cost not just to their economies but to society and the human condition. This proposal is an affront and a contravention to human rights and civil liberties.

The triumph of ethics over commerce

There are countries within Europe which allow the destruction of human embryos for scientific research and other countries where this activity is contrary to custom, law or constitution. If a state wishes to restrict the destruction of human embryos then it will also generally wish to restrict the funding or patenting of research that directly depends on embryo destruction. While scientists in the UK and in other permissive jurisdictions may wish that other countries protected their financial interests in this technology, it is clearly reasonable for a decision at a European level not to require states to respect the patents of technologies produced by practices in other countries which would be illegal in those states. This is a matter of ethical reasoning and state level decision making against commercial interests and pan-European patentability. I sincerely hope that the court finds against the patentability of these technologies. I would also predict that such a decision would in fact provide a stimulus to other forms of stem cell technology.

Dr Jones' reasoning is

Dr Jones' reasoning is fundamentally flawed. Whilst some countries permit and promote stem cell resaerch and others do not it follows that there is absolutely no moral consensus in Europe over whether human embryonic stem cell research is ethical. In such a climate how can a Pan-European body such as the Court of Justice or the European Patent Office make a reasoned judgement over what is or is not ethically acceptable in Europe? The answer is that it cannot. This must be regulated at the state level, there is no place for the EU to enforce its so-called moral opinions when they are not shared by several governments within that block.

More than one tradition in ethics

Dr. David Albert Jones, director of the Anscombe Bioethics Centre, refers to the statement of the Advocate General as the ’triumph of ethics over commerce’, (1) as if there was only one tradition in ethics – his own or that of the Vatican – and (2) without considering what the consequences of this victory over ’commerce’ would imply for the health and quality of life of the large groups of European patients who suffer from presently incurable diseases, and where recent advances in stem cell research offer promising results. Those who belong to other ethical traditions than his are certainly likely to consider this disregard to be unethical.

Dr David Albert Jones applauds the statement of the Advocate General and predicts that this will provide a stimulus to other forms of stem cell technology, presumably based on iPS cells. But recent publications undermine the belief that iPS cells in all contexts can replace stem cell lines derived from the inner cell mass of a blastocyst.

According to its website, ”The Anscombe Bioethics Centre is a Roman Catholic academic institute that engages with the moral questions arising in clinical practice and biomedical research. It brings to bear on those questions principles of natural law, virtue ethics, and the teaching of the Catholic Church, and seeks to develop the implications of that teaching for emerging fields of practice.”

Why should the most restrictive legislations have the upper hand? In his comments Dr. David Albert Jones refers to ’state level decision making against commercial interests and pan-European patentability’ but forgets that the Biotechnology directive, which opens up patenting of genes and stem cells via article 5.2 was also a a result of state-level decision making on a European level. According to this article an element isolated from the human body or otherwise produced by means of a technical process can be patented, provided that the regular patentability requirements are met, even if the structure of that element is identical to that of a natural product. Here again Dr. David Albert Jones shows his talents for selective reasoning.

Destroying embryos is not patentable

Göran Hermerén asks 'Why should the most restrictive legislations have the upper hand?' but of course in many respects it is permissive jurisdictions that have the upper hand. It is states like the UK that seek to use their lack of ethical restrictions to gain financial advantage. During the recent debates over the Human Fertilisation and Embryology Act 2008 it was repeatedly stated that permissive legislation would allow the UK to retain its position ahead of its international competitors. Those who do maintain higher ethical standards (whether on the treatement of animals, research subjects, workers rights, human embryos or in any other area) are constantly undermined by multinationals cherry-picking more permissive jurisdictions for their activities. As a UK citizen I am sometimes ashamed with how the UK sometimes seeks to use lower standards for competetive commercial advantage. 

It is in any case agreed consensus enshrined in European law that processes involving the destruction of human embryos are not patentable (Directive 98/44/EC (42)). The question in dispute is the technical one of whether using cell lines drived from the destruction of human embryos falls under this description. This is at least arguable though we have yet to see which way the Court will decide. 

It should also be noted that when WARF lost its patent application (for the creation of ESCells) this was welcomed by many stem cell scientists in the UK, who did not wish to be restricted by the patents of others. Even from a pragmatic point of view this is more complex than is being presented.

Higher ethical standards indeed....

Dr Jones states that he is often ashamed, as a UK citizen, to observe the UK using lower standards for competitive commercial advantage.  As a UK citizen myself, and one who has worked in numerous foreign institutes in my time, I can categorically state that he is wrong to label the UK with such a derrogatory comment.  Animals used for research in the UK are protected far better than in any other country in which I've worked, and believe me, I should know!  Writing an application for a project licence has become harder and harder as we, the UK, have tightened our restrictions, and increased inspections over the years.  Indeed one of the many complaints foreign scientists have is that our system is incredibly restrictive and full of paperwork - so much the better I say.  As for workers rights, has the good Dr Jones actually ever worked in another country?  I suspect not.  When I worked in the US, I had no rights whatsoever.  Should my PI have decided to fire me (for which he had to give no good reason!) then I would have had to leave the country within 14 days!!  What kind of rights do you call that?  Finally, with regards to research subjects, by which I assume you mean human subjects, has the opinionated Dr Jones ever taken part in a research project?  Again, I have, and I would have no qualms doing it again.  I was treated superbly, and every step of the process was explained in great detail to me.  I was even notified when, months later, several papers were published from the study.

         All in all, my point is that the UK actually tends to have the strictest and LEAST permissible rules, regulations and standards.  I am actually embarassed that other countries have not followed our lead.  Perhaps the good Dr Jones might wish to consider relocating to a country with different standards?!

Good in parts

My point was not that the UK was in all areas the worst, which is far from the case, but that some countries with lower ethical standards may be attractive to muli-national companies.

On animals I would imagine that the UK has among the highest welfare standards in the world, but my point was that UK citizens should think how they regard other countries who use their lower animal welfare standards for commercial advantage. In relation to workers rights and protection of research subjects the UK is neither the best nor the worst. The UK is no doubt more protective of workers than the USA, but for many years it resisted EU legislation (for example on working hours) that pertained throughout the rest of Europe. In relation to research on human subjects the UK has a rigorous system of research ethics committees in which I have confidence (it is noteworthy that the EU has moved to a system of 'one ethics committee approval for work in one country' to streamline applications, but has not had the confidence to make one ethics committee approval in any EU country acceptable in every other - I think for good reason). I suspect I am not alone in having ethical concerns about the apparent global shift for big pharma to move phase I clinical trials outside the EU. Nevertheless UK legislation is more lax than some other countries (for example Germany) in relation to research on subjects who cannot consent. I may well be 'opinionated' but the comparative legal provisions are a matter of public record and it can be seen that the UK is neither the most restrictive nor the most permissive.  

I am proud of the UK in various ethical and regulatory areas (for example, end of life policy, disability rights, animal welfare) but this still leave me room to be ashamed in other areas (for example in relation to the deliberate creation and destruction of human embryos for commercial gain). I am grateful for a German based NGO (Greenpeace) for taking this case to help clarify in a way I hope will improve the legal situation in the EU.  

My central argument was simply that cooperative agreements on matters such as patent protection do and should include ethical limits, and that they do not and should not give automatic advantage to those with the lowest ethical standards (whether the UK is the beneficiary or some other country).

Stem cell patents: ethical aspects

There's further discussion of the ethical aspects of this case in Göran Hermerén's commentary, Stem cell patents: ethical aspects.

 

 I am all for a ban on

 

I am all for a ban on patents on stem cell research. This is a brave step in the right descion. The idea that this would make industrial investment "unlikely" is a scarecrow. But if so, what is the problem? Let the academic sector devleop the potential treatments. This would, on the contrary, benefit Europeans and perhaps also the developing world in that the treatments could be affordable.

research using stem cells and human embryos

As any concern human being should do, I signed the petition related to the case pending in the Court of Justice of the European Union - the name of the Court of Justice after the Lisbon Treaty.

The opinion of the Advocate General if followed by the Court - which I hope will not happen - is biased and fundamentalist. Religious views should not be imposed by Law.

There is however a huge mistake in the informations provided. Since 2006, research using stem cells and even human embryos is legal and needs only to be approved by an independent authority called CNPMA (National Council for Assisted Reproductive Technology - www.cnpma.org.pt).

I urge you to correct that mistake.

Eurico Reis

Why the Advocate General is legally wrong.

While applauding this letter, it should be remarked that judges don't "do" policy: they simply apply the law.  To be effective, the authors and anyone else with views on this matter should direct the Court's attention to how the Advocate General's Opinion clashes with the clear intent of European law.

Last month, CellFate published a Counter-Opinion to the Advocate General, which explains why his decision is legally wrong.  The Counter Opinion is available here

Wait and See

With all due respect to Mr Hitchcock, the EU has made a clear decision that processes which destroy human embryos are not patentable (Directive 98/44/EC (42)). What is in despute is whether  embryonic stem cells "necessitate the prior destruction of human embryos or their use as base material" (see the attorney generals opinion) such that they fall within the scope of the agreed restriction. As with any legal case it will be possible to put arguments for both sides. This indeed is how lawyers make their living. Nevertheless, whether the attorney-general's opinion is legally correct will be determined by the Court. Let us wait and see.

It is easy to take a

It is easy to take a consistent but radical position and thus ban patenting of human ES cells and products or processes related thereto.

It is hard to be pragmatic and differentiate between the beneficial use and abuse of human embryos.

I hope and expect from the European Court of Justice to do the latter.

Regenerative medicine applications

Embryonic stem cells offer a real possibility for applications in regenerative medicine. An embryonic-stem-cell-based clinical trial for a cure for a major cause of blindness is on the horizon in the UK next year, but realization of treatments like this needs commercial development. Companies will be reluctant to invest if they cannot protect some of their procedures with patents. A blanket ban on patenting any method or product derived from human embryonic stem cells will undermine development of new therapies in Europe, leaving the European population unable to benefit from important advances in the next 20 or 30 years. 

Peter Andrews, Arthur Jackson Professor of Biomedical Science, University of Sheffield

Implications for patenting practice across Europe

The Advocate General, Yves Bot, took a remarkably restrictive stance, arguing that hESC lines are permanently stigmatized by their origin, rendering any patents involving the use of hESCs unacceptable.

Should the court follow Yves Bot’s position in the final judgement this would cause current regulations and patenting practice in several member states to be illegal. In the UK and Sweden for example, more than 100 patents relating to hESCs were issued so far. The European Patent Office, too, would have to overhaul its current patenting practice.

Clara Sattler de Sousa e Brito LL.M (Yale) Patent Attorney, Attorney at Law (New York). Partner at patent law firm Liermann-Castell. Patent attorney representing Oliver Brüstle.

The current practice of the

The current practice of the European patent office is the prohibition of patent involving the destruction of human embryos.

The position of the Advocate General is consistent with the European Directive and with the European patent law.

The legal issues of this case

A comment posted above suggests the advocate-general's opinion statement is consistent with European Patent Office practice. I think there is in fact some confusion here. For a clear overview of the legal issues, including the position of the European Patent Office, you may wish to read the article just published by patent lawyer Clara Sattler de Sousa e Brito: Stem cell patents: legal aspects.

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