Few nations have gone as far as the UK to elevate stem-cell research into an anchor of its national life-science effort. In September 2007, the UK’s Human Fertilization and Embryology Authority ended eight months of debate by agreeing to allow research into chimera animal-human embryos, but on a case-by-case basis and under regulations limiting authorized projects to those deemed “necessary and desirable.”
Four months later, HFEA approved one-year research licenses for teams of scientists at Kings College London and Newcastle University to carry out research using the embryos, subject to a series of detailed conditions. That decision appeared to bear fruit earlier this month when the Newcastle University team, led by Lyle Armstrong, announced it had created the UK’s first chimera embryos by injecting DNA from human skin cells into eggs taken from cow ovaries.
The embryos survived three days, and “the next step is to get the embryos to survive to around six days when we can hopefully derive stem cells from them,” Newcastle Professor John Burn told the BBC on April 1.
On May 2, the bill is to be formally presented to the House of Commons, Britain’s lower house of Parliament, for its first reading, when legislation is not usually debated. The Human Fertilization and Embryology Bill, which has been approved by the upper house, the House of Lords, would explicitly allow research using hybrid embryos like those created by the Newcastle team.
BioRegion News discussed the legislation and the broader political and legal climates for stem-cell research in the UK with Gareth Morgan, an associate specializing in life sciences and healthcare in the intellectual property practice group of the law firm Taylor Wessing, which has offices in Europe, Dubai, and China.
The House of Lords earlier this year approved a bill that would allow stem-cell research using hybrid embryos. What is the status of that legislation?
That bill is now in the House of Commons. The first vote on it is going to be the acid test for the bill. That is effectively when the Commons will have a look at it cause by clause. And in that reading, if any amendment is going to be made to the bill, and any clauses taken out – for example, if they want to amend the clause that permits the creation of animal-human hybrids, that is when the amendment will be made.
How supportive of the bill is Prime Minister Gordon Brown?
What Gordon Brown has done is, as per usual, he tried to toe a middle line, if you like, between the two factions that he has in his party. There’s one faction that’s pro-science and wants the bill to go through in its current form. But the UK cabinet actually contains quite a few staunch Catholics who are opposed to certain elements of the bill.
Do they hold any more or less sway under Brown than they did under his predecessor Tony Blair?
I think the bill is probably having an easier passage because Brown is there. Most people still expect the bill to get through unscathed, even though Gordon Brown has allowed a free vote for [members of Parliament].
The way the votes usually work in the Commons is that usually the political parties will whip the MPs – it’s not as painful as it sounds. It simply means the MPs have to vote in party political blocs. If the leadership of the Labor or Tory parties supports a certain bill, then the whole of the party will vote one way, and there’s no room for private conscience. But what Gordon Brown has done for this bill is, on the first reading when the MPs debate it clause by clause, he has allowed a free vote for Labor MPs, so any Labor MP who is minded to vote against any particular provision of the bill may do it.
What effect does the January decision have, both short-term till now, and longer-term over the next couple of years, in terms of building a life-science cluster in the UK anchored on stem cell research?
I think certainly the fact that the HFEA has debated this internally and has received legal advice on the status of this research under the current legislation, and decided that it was work that did need to be licensed, and they reviewed the two projects carefully and found they did qualify for licenses under the current legislation, I think that is a huge positive for UK stem cell research.
Firstly, it does allow these two projects, which had been in limbo, to proceed. The first applications to the HFEA for these two particular projects were made almost 12 months before the licenses were granted, so the projects had been on hold for quite a long time. And the fact that the two groups are up and running and are publishing results and are issuing press releases, again is a positive. I’m sure there will be a certain view among MPs that, ‘Well, if the work is already being done, aren’t we sort of shutting the stable door after the horse has bolted by trying to outlaw it in the current legislation?’ I think quite a few MPs will take the view that they might vote for the bill on those grounds.
So it’s certainly a positive for stem-cell science in the UK. This has sort of clouded a bit of a wider issue as to whether the whole hybrid human-animal embryo research field is actually going to be an advance in stem cell biology. There’s no doubt that it will increase the number of embryonic stem cells available, simply because it will allow greater access to – because animal eggs are a lot easier to get hold of. And you’re not wasting human eggs that would otherwise be used in [in vitro fertilization], for example. There’s no doubt it will increase the number of embryonic stem cells that are available for research. However, nobody really knows whether animal-human hybrids are actually going to give results that can be mapped onto humans. In general, the amount of animal DNA in those cells is small. But hybrid cells are notoriously unstable, and so there is a possibility may not provide the sort of advances that are being hoped for. And it may be that the reprogramming work that’s going on in a lot of labs in Japan and the US may actually hold a lot more promise.
What institutions are anchoring the UK’s stem-cell research effort?
The HFEA covers any work that involves the creation or manipulation of human embryos. However, in relation to stem cell work, per se, provided you actually don’t have stem cells that are derived from embryos, the sort of regulation that is in place is pretty minimal, and most of it is voluntary in the UK.
The UK Stem Cell Bank, although it does provide access now to a wide variety of human stem cell lines, it does actually require you to sign up to certain codes of practice if you want to access those cells. However, if you are using a cell that doesn’t come from the UK stem cell bank, then prima facie you don’t really have to comply with any code of conduct for your research in the UK. So the granting bodies, if you like, are equivalent to the [US] NIH, which would be the [British Medical Research Council] and the [Biotechnology and Biological Sciences Research Council], the government funding bodies – they would be the people who would be reviewing the projects that are sent in for funding, and would be granting the money for the research. That’s the sort of level that the research would actually be regulated at. So there’s no legal regulation of it per se.
Is HFEA looking to approve additional research groups to carry out stem cell work, in addition to the two it approved last January?
The two licenses were only issued in relation to human-animal hybrid work. There are multiple labs across the UK working on stem cells and embryonic stem cells. It’s just that that work is pretty non-controversial in the UK, and so it doesn’t hit the headlines. I’m not altogether sure how many of the labs are going to want to attempt to create animal-human hybrids, because it is a tricky process. I don’t think that has been made that clear, really, in the coverage to date. This is actually a new suggested process, and it’s quite tricky to create human embryos by nuclear transfer in any event. So when you layer over that the complexity that you’re going into an animal egg, rather than a human egg, it becomes doubly complex.
How long of a cluster-development effort will this be? Generational, or can this be done in 10 years or less?
The Kings group and the department that is working with embryonic stem cells, it’s here to stay. It’s very well established. I can’t see legislation changes affecting that, unless they outlaw the work altogether.
Which regions of the UK are most likely to attract stem-cell research activity?
Stephen Minger’s lab and Chris Shaw’s lab [both at the Stem Cell Biology Laboratory at the Wolfson Center for Age Related Diseases at King's College London] is obviously one of the main areas. Also, Newcastle, where the other license has been granted, has set itself up to be an area of stem cell excellence. And at Cambridge [University], you have people like Martin Bobrow, a professor of medical genetics, and he’s also very active in this field. Those would probably be the three main areas. You have a legacy of stem cell work in Scotland, probably following the research center that created Dolly the sheep, the Roslyn Institute [in Edinburgh]. That is another area where stem cell science is based in the UK.
How much commercial spinout activity has there been from stem-cell research in the UK to date?
That’s a tricky question. There’s a bit of a paradox between the US and the UK in this respect. In the US, it’s very difficult to get access to certain stem cell lines and to get your funding for research on certain stem cell lines. However, you can pretty much patent anything. In Europe, it’s the other way around – certainly in the UK, where you’re free to do a lot of the work, and you’re free to get funded for the work. But at the moment, the UK Patent Office is completely undecided as to the level of patent protection it will now give to inventions in this area. The key to successfully commercializing science in any area is the ability to obtain a monopoly right on it and to exploit that. Until the European Patent Office has sorted itself out on the whole stem cell issue, it’s going to be tricky to see where this work is going commercially.
Also, you have to look at the nature of the work as well. It’s likely that a lot of this work may not lead to traditional drug therapies. It may actually lead to individual patient treatments. The sort of work may be that individual patients end up being treated with their own cells. Perhaps cells that are then modified to use in patented chemicals or patented processes. It’s fascinating to see how this might develop because it is possible that the treatments may not actually be patent-protected.
Does the structure of the National Health Service help or hinder the development of a stem-cell cluster in the UK?
This is anecdotal evidence: I went to [a Medicines and Healthcare products Regulatory Agency] conference relating to advanced therapy medical products. There’s a new regulation coming in Europe at the end of this year that will bring in any cell-based products – not just stem cells, but any autologous cell-based products as well. The sort of treatments where you take a biopsy of cells from a patient, say knee cartilage, and you effectively use that as a transplant, an implant, to repair a patient’s knee. That sort of treatment wasn’t really well regulated prior to this new regulation coming in.
It was an interesting conference, mainly because we had two commercial companies talk about the relative merits of doing research and clinical trials on these sorts of products in the UK as opposed to other countries around the world and in Europe. The bottom line was a little depressing, actually: It was that the NHS doesn’t really support clinical trials as well as it should, and patient availability isn’t as good as it should be in the UK, as compared to, for example, some countries in Eastern Europe, and certainly as regards to countries like India and China.
What is the latest with the European Union stem-cell patenting court case?
There are two patent applications [of the Wisconsin Alumni Research Board] that have been referred to the Enlarged Board of Appeal in the European Patent Office. The Wisconsin board prevailed in the US, but in Europe, they are still in limbo. The US PTO has an equivalent procedure, but it’s almost like a re-examination procedure, whereby an appeal board will actually look again at the application, to check whether the granting body or examining body made the right decision the first time around. It has gone through two rounds of appeals so far, and this is the highest level of appeal. The question has been with the enlarged board for almost two years as of this summer. We are hoping for a decision relatively soon.
What effect has the European litigation had on stem-cell research and commercial activity?
I think it is commercial activity that has been held back, not research. Research is done in little patchwork fashion around Europe, mainly because there are a fair few countries, especially in southern Europe, which are, again, staunchly Catholic, and object to this type of work being done per se. In a place like Italy, it’s very difficult to do stem cell work and especially embryonic stem cell work – whereas in the UK and the Netherlands, for example, it’s a lot easier.
How much of the commercial activity has shifted to Asia or the US as a result of the European litigation?
Because of the ease of actually doing the research, we are hanging on to most of it. Ultimately, most academic labs, although it’s nice to be able to see your name on patents, and to think the tech transfer office is being kept very busy and licensing your inventions, in practical terms, most academics don’t give two hots about the availability of patents. They will continue working. Stephen Minger is a classic example of a scientist who is attracted to the UK and is staying here.
Any move to develop stem-cell laws applying solely to the UK, or will it defer to the EU?
As soon as there is a ruling at the European Patent Office, everyone expects the UK Patent Office to fall into line with that. The UK Patent Office at the moment does have a policy of permitting some stem cell related inventions, and not others. The distinction is they will allow claims that claim pluripotent stem cells, but not totipotent stem cells. [Pluripotent stem cells could develop into multiple lines, though not every cell in the human body; totipotent stem cells have the ability to divide and produce all the differentiated cells in an organism — Ed.]
The difference that they maintain is that the totipotent stem cell has the potential to develop into the human body, which is banned under the European patent convention. It is an awful way of trying to draw a line, because obviously you can then envisage stem cells that could develop into every cell line in the body, bar one. Simply because of that property, they are patentable in the UK. It seems a little crazy, and I’m not so sure how workable that distinction has actually been in practice.