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Patenting human stem cells: medical lifeline or ethical high water?
On its tireless quest for healthier and longer lives, humanity faces untapped healing potential, but also latent pitfalls – both ethical and legal
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For some, the use of a shipping metaphor to illustrate the relationship between an evolving field of biomedical investigation and its legal and ethical implications borders on insensitive. For others, it is just a catchy way to attract attention to a subject that is, by its very nature, a sensitive one. These different responses underscore the challenges facing not only the scientific world but also policy-makers and the legal fraternity, as technology progresses into the post-genomic era of regenerative medicine.
"The debate is a manifestation of the adjustment of society to technological developments. It prepares the intellectual and emotional ground for people to cope with the effects of much more sophisticated biological technologies," note at the European Patent Office Leo Giannotti and Berthold Rutz
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. "We are moving from an understanding of basic principles, to a much more fine-grained level of manipulation over processes". The quest for longer, healthier lives underpins all of these developments.
Getting the terms right
Terms such as ‘tissue engineering', ‘cell therapy', ‘embryonic stem cells' often fill headlines because they conjure up images of human embryo factories, clones of famous dictators and other such extremes which, while selling newspapers, do little to help readers understand complex, thought-provoking subjects.
But provoking thought need not be the same as frustrating mistrust or ire, suggest experts at the EPO. Indeed, it would make no harm if the science of cell therapy and stem cell research - and its potential medical benefits - were better explained in the first place in the mainstream media.
The science has come a long way since James Till and Ernest McCulloch first proved the existence of blood forming stem cells more than 40 years ago while working at the Ontario Cancer Institute in Toronto. Yet, surprisingly little progress has been made in improving public understanding and preparedness for the biomedical revolution that their discovery would herald.
A distinction is made between adult and foetal stem cells, which are typically only capable of differentiation into a limited number of cell types, and embryonic stem cells which have no apparent limit to their shape-shifting ability - making them scientifically very attractive, but no less controversial.
The problem with many reports and bioethics opinions, EPO Examiner Aliki Nichogiannopoulou explains, is that they fail to properly distinguish stem cells obtained from the adult human body from those harvested from human embryos.
Ethical challenges
Not enough attention is paid to these distinctions, says Nichogiannopoulou. "In the press, embryonic stem cells are too often bundled together with other body elements (like adult and foetal blood forming, neural or skin stem cells), when they should be treated separately. Embryonic stem cells are a product of technical intervention by scientists. They don't exist in nature."
Concern about human embryonic stem cells largely results from the fact that they are obtained from early-stage embryos. "Applying current technologies to harvest these cells, the embryo has to be destroyed: this raises fairly clear ethical questions for most people," Nichogiannopoulou emphasises.
The future and much-vaunted promise of regenerative medicine, some fear, lies in the hands of a master cell which is - for many scientists in parts of the world - untouchable.
Legal boundaries
How this is treated on the legal front, varies markedly within the European Union and worldwide (2) . An increasing share of biological research is either illegal or unpopular in some countries, either because of concerns about genetic engineering, or because of religiously motivated opposition. The attitudes of Christians, Jews, Muslims, Buddhists, Hindus and Shinto's to stem cell therapy diverge. Nations with broader boundaries pick up the slack.
Nichogiannopoulou points out that there is no simple ethical, or even technical, solution to the moral dilemma that Europe faces in deciding what is acceptable or even desirable in human embryonic stem cell research, or any research involving human embryos, for that matter.
Scientists in the USA have recently proposed technical alternatives to the conventional and ethically problematic ‘harvesting' of embryonic stem cells in a way they believe circumvents the ethical problems.
In one report, a group headed by R. Lanza suggests removing a single cell from an eight-cell-stage embryo to derive stem cells, while leaving the remaining seven-cell embryo undamaged to develop to term (3) . "There are major reservations with this proposal," Nichogiannopoulou remarks. "This technology implies cloning the embryo by splitting and sacrificing one clone for research, while allowing its identical twin to develop". In a separate report, R. Jaenisch and his colleagues put forward a technology where embryos are first rendered unable to survive before being destroyed in order to derive embryonic stem cells (4) . R. Lanza commented on this technology by saying that it is a deliberate creation of crippled embryos to circumvent the ethical problems of using healthy ones.
For the time being, all human embryo research is performed on surplus embryos donated by couples undergoing in vitro fertilization (IVF). Embryo research opponents fear that, once we step on the slippery slope of acceptance of research on surplus IVF embryos, the next step will be the creation of embryos for research purposes, - i.e. for destruction only - which they deem not acceptable. A different voice from European bioethicists and stem cell researchers, suggests that the judgement on ethical acceptability of a certain technology should be based on the question of the acceptance of the consequences of this technology among the general population. In other words, the ethical question of what one should or should not do would come down to the question: what kind of world do I want my children and their children to live in?
"It remains to be seen which approach will prevail, and - to use the terminology of the decision of the EPO Board of Appeal T356/93, defining the term "morality" in Article 53(a) EPC - establish accepted standards of conduct for the European culture," Nichogiannopoulou concludes.
- Regenerative medicine: repairing or reconstructing tissue or parts of the human body (such as liver, heart, bladder) lost or damaged due to trauma, disease and genetic factors - key to this is the development of synthetic scaffolds and their interaction with cells.
- Cell therapy: a form of regenerative medicine similar to transplantation but using the cells of the organ, instead of the whole organ; it includes techniques such as blood transfusions.
- Stem cell therapy: a form of regenerative medicine using stem cells. These cells can develop into almost any form of body tissue, and have the potential to replace any other cell in the body. They can be either applied directly in the body, or used to grow replacement tissue in a laboratory. For years, leukaemia has been treated using blood-forming stem cells from the bone marrow or, more recently, the umbilical cord. Today, stem cells can be obtained from: 1. embryos - presently surplus embryos donated by couples undergoing in vitro fertilization (IVF) (supernumerary embryos which would otherwise be discarded); 2. foetuses - aborted and donated upon informed consent; and 3. adults - upon informed consent by the donor (e.g. bone marrow, umbilical cord, skin stem cells).
From the perspective of patenting
In her almost eight years at the EPO, patent examiner has seen the number of biotechnology applications jump from around 3,000 in 1996 to some 8,000 in 2005. "Patent applications are being filed not only by the large pharmaceutical firms and, now, biotechnology companies, but increasingly from universities and spin-off research institutions," she says. "There is a vast range of different applications to sift through, from ethically uncontroversial life science developments, such as new uses of DNA microarrays or new medical cell therapies, to ethically problematic applications considering human embryo-derived cells and their uses".
Trained in molecular immunology at the Max-Planck-Institute in Freiburg and completing her PhD thesis on stem cell biology at Harvard Medical School, she spent the early part of her career in the field of adult, foetal and embryonic stem cell research at Harvard. She took up her position as an examiner at the EPO in Munich in September 1998 and, since 2004, is dedicating part of her time to EPO's Patent Law department, in DG5.
Not unlike any promising new technology, stem cell research has resulted in a bevy of patent applications. "Any application involving human embryos would face patenting problems," stresses Nichogiannopoulou, "regardless of whether they involve stem cells".
While it is generally possible to obtain patent protection for stem cell related inventions, some jurisdictions place restrictions on the patentability of embryonic stem cells as such, or methods using such cells
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, while others do not. For instance, in the USA human embryonic stem cells and their uses are patentable.
Foetal and adult stem cells, such as haematopoietic stem cells (from which all red and white blood cells develop), have been patented in Europe for some time now. They fall under the EPC's Rule 23e, explicitly allowing the patenting of isolated elements of the human body as long as they do not constitute a mere discovery. On the other hand, under EPC Rule 23d(a) and (c), processes for cloning human beings and uses of human embryos for industrial or commercial purposes are not patentable.
However, embryonic stem cells as such are not mentioned in the EPC or the relevant EU Directive
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. Recognising that patentability of human embryonic stem cells is a highly critical matter which is passionately debated, and considering such patentability as being an outstandingly important point of law, a technical Board of Appeal has in decision T 1374/04 dated 21 April 2006, referred the question to the Enlarged Board of Appeal, whose decision is now pending as G02/06.
Stem cell research has resulted in a bevy of patent
applications. (click to enlarge)
April 2006, Brussels
- Journalist: Christian Nielsen, European Service Network
- Expert opinion: Aliki Nichogiannopoulou and Berthold Rutz at the EPO
- Chart: Silvio Endrizzi, EPO
- Photo portrait: Richard Roscoe
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Research and coordination: Leo Giannotti, EPO
References
(1) L. Giannotti and B. Rutz (2006): 'Forever young: regenerative medicine, tissue engineering, stem cells' - EPO SR-Brief #04/2006
(2) ‘Regulations in EU Member States and Non-EU countries regarding human embryonic stem cell research' (EU Survey, Status July 2004)
(3) Y. Chung et al. in Nature published online 16 October 2005; 10.1038/nature04277
(4) A. Meissner and R. Jaenisch in Nature published online 16 October 2005; 10.1038/nature04257
(5) B. Rutz and S. Yeats: 'Patenting of stem cell related inventions in Europe' Biotechnology Journal, 2006, 1; 10.1002/biot.200600021
(6) EU Directive (98/44/EC): ‘Legal protection of biotechnological inventions' http://europa.eu.int/scadplus/leg/en/lvb/l26026.htm