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6 posts from August 2010

August 31, 2010

Which dishes are you willing to eat from?

by David Kent

This month, the food supply chain in the UK dropped the ball, and unbeknownst to the final consumer, meat from the offspring of a cloned animal ended up on dinner plates. This caused a stir in a country that has traditionally been quite wary of genetically modified foods and prompted much discussion from the public and the scientific community as well as prompting 35 David Cameron-masked protesters to show up outside Parliament. As I mentioned in my last entry, the British system is extremely effective in getting good information out to its citizens and this news story was quickly met with informed discussion, including a great radio interview with Sir Ian Wilmut (whose group cloned Dolly the sheep) and Robin Lovell-Badge (a well-respected cell biologist). In the BBC clip, the motivations for cloning cattle are clearly laid out, some basic information is provided, and some excellent questions are posed including whether or not the introduction of meat and milk from clones or their offspring should be de-regulated in the United Kingdom. Members of the European Parliament have recently called for an immediate moratorium on such food sources and are striving for a complete ban.

Cloning animals for improved meat and milk production is something that the United States has been doing regularly since the 2008 US Food and Drug Administration report determined that “meat and milk from clones of cattle, swine, and goats, and the offspring of all clones, are as safe to eat as food from conventionally bred animals”. The amount of cloned meat and milk in the food chain is difficult to estimate, but is quite prevalent due to higher milk/meat yields from these animals. The bulls that caused the above-mentioned panic in the UK were purchased privately from an American farm derived from a cloned animal. The BBC’s Science and Environment web site has put up a simple video clip that describes the cloning process in the United States.

It appears that the scientific community does not have major health or safety concerns when it comes to the consumption of food from cloned animals or their offspring (though, the logic appears to be simply that nobody has had problems yet or, if it was really bad, the cloned animal itself would have died). The real dilemma comes when one parses out the ethical issues of the cloning process and asks “should we be doing this in the first place?”   Even though it has improved substantially over the last decade, the cloning process still results in some abnormal offspring that either die or cause the surrogate mother substantial stress.  Additionally, with the metric of “yield” (read “money”) as the primary driver, there is a risk that a move away from overall genetic variation might lose some other genetic benefits that currently exist in the breeding population. 

In the end it seems, as usual, that the best solution is “somewhere in between” the EU and America, moving forward cautiously with rigorous testing to ensure that the products being brought to market are of the highest quality and the practices that get them there are respectful of the animals that feed us. 

August 26, 2010

New law may be the only way out for researchers affected by US stem cell injunction

by Ubaka Ogbogu

On August 23, 2010, United States federal district judge Royce C. Lamberth issued a preliminary injunction that overturned President Obama's recent reform of US federal policy on human embryonic stem cell (hESC) research. The injunction -- which will remain in effect until a permanent order is issued upon final determination of the merits of the case -- temporarily shuts down federal funding for all research involving the destruction of human embryos (or more to the point, all research based on materials derived from destroyed embryos, or traceable to a process involving the destruction of embryos). This means that unless and until the injunction is overturned, federal funds can no longer be used to support stem cell derivation from human embryos, or the research use of stem cells derived from human embryos, and that labs currently undertaking hESC research with federal monies would either have to stop their experiments, seek and obtain private funding to continue their research, or move to jurisdictions that support hESC research. The ruling is thus potentially more restrictive than President George W. Bush's policy, which allowed funding for research using hESC lines already in existence by August 9, 2001.

Below, I provide a primer on US federal policy on hESC research for those readers who are not familiar with the subject, followed by a breakdown of the Lamberth decision.

U.S. Federal Policy on HESC Research

  • In the US, there are no federal laws directly regulating hESC research (as exists in Canada, for example). Instead, federal policy is based on the so-called Dickey-Wicker Amendment, a rider to federal spending legislation which prohibits the use of federal funds for creation of human embryos for research purposes or for research in which human embryos are "destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero." In effect, states can set their own policies, and researchers could seek and obtain private funds to conduct research affected by the policy.
  • Since 1999, successive US governments have interpreted the Dickey-Wicker Amendment as stating that federal funds cannot be used to support research on embryos, including derivation of hESC lines for research purposes, since this process involves the destruction of embryos. Beyond this clear rule, the application of the Amendment to research on hESC lines has been based on a clever but (in my opinion and Justice Lamberth's) erroneous interpretation, which holds that since hESC lines are not embryos, the Amendment does not apply, and as such, federal funds could be allocated for research on the lines.
  • In line with this interpretation, President Bush announced a funding policy that allowed the use of federal funds only for research on hESC lines created on or prior to the date his policy took effect. On March 9, 2009, President Obama issued an executive order that removed Bush's restrictions and paved the way for a new policy that broadened the provision of federal funding to include research on hESC lines derived from supernumerary IVF embryos created for reproductive purposes.
  • While a significant improvement on the Bush era policy, Obama's policy was modest at best. It failed to bring US policy in step with research policy in other jurisdictions such as the United Kingdom, Singapore, and the State of California, where various derivation methods are allowed, including the creation of embryos specifically for stem cell derivation purposes. More significantly, the policy was never put forward for or backed by legislative sanction, making it vulnerable to judicial challenge on the basis that it violates the higher-ranked Dickey-Wicker Amendment.

The Lamberth Decision

  • The case involves a motion for preliminary injunction brought by a group of plaintiffs led by two adult stem cell researchers who claimed that allowing federal funding for hESC research violates the Dickey-Wicker Amendment and places them at an irreversible disadvantage of facing increased competition for NIHís limited resources. As is typical of the symbolism often surrounding the debate over embryo research, "Embryos" are one of the named plaintiffs in the case.
  • On the violation issue, the judge agreed with the plaintiffs that the language of the Amendment clearly prohibits the use of federal funds for all research in which a human embryo is destroyed. The judge rejected the governmentís argument that the Amendment supported the interpretation that research hESC is not research on embryos but a separate and distinct "piece of research".
  • Having concluded that the government's interpretation is contrary to law, the judge agreed with the plaintiffs that it was necessary to grant them a preliminary injunction because (a) their case likely to succeed on the merits following a full hearing and final determination; (b) they would suffer irreparable harm from increased competition for limited NIH funding, especially since no compensation could redress that harm if NIH were to disburse limited research funds to hESC research on the basis of a policy that violates the law; (c) the hardship they would suffer if the injunction were denied (increased competition and potential threats to their means of livelihood) was greater than that facing hESC researchers (as the injunction would simply preserve the existing state of affairs) or individuals who could benefit from therapies resulting from the research (which were still speculative); and (d) it is in the public interest to grant the injunction that would implement the law as contained in the Dickey-Wicker Amendment.

From both a technical legal perspective and with respect to the existing US federal policy on hESC research, the judge's decision makes sense. Basing policy on clever but misguided legal interpretations is disingenuous at best. Also, if President Obama and the Democrat-controlled Congress are really serious about supporting, in the Presidentís words, "responsible, scientifically worthy human stem cell research, including human embryonic stem research, to the extent permitted by law," the courageous and proper thing to do would be to remove the Dickey-Wicker restrictions by enacting both the alternative interpretation and other scientifically informed and ethically responsible embryo research methods into law. While I am not completely persuaded that the plaintiffs' "increased competition" claim is real or imminent -- NIH typically put out distinct calls for both areas of research and there's nothing to suggest that the calls disproportionately prioritize or favour hESC research proposal -- the fact remains that US law currently prohibits federal funding for embryo research.   

August 25, 2010

Biosynthetic corneas restore vision

 Griffith_smRight now, you're seeing this blog post thanks to your cornea. In concert with your eye's lens, the cornea refracts light and allows you to distinguish the letters on this page from the background. But your cornea is vulnerable to disease -- clouding of the cornea is the most common cause of blindness. And although treating these diseases, such as keratonocus (also called central corneal scarring) is possible through surgery, it has typically required donated human corneas for transplantation. Findings published today in the journal Science Translational Medicine, however, may offer a biosynthetic solution to the tissue donation bottleneck.

Led by Dr. May Griffith (pictured) of the Ottawa Hospital Research Institute, the University of Ottawa and Linköping University and supported in part by the Stem Cell Network, the study publishes the results of a early phase clinical trial wherein biosynthetic cornea were implanted in 10 Swedish patients with advanced keratonocus. Vision improved in six of the 10 patients, and the results were comparable to conventional transplantation with donated human corneas.

The implanted biosynthetic corneas acted like a scaffold, wherein the implantation triggered the patients' own remaining corneal tissue to grow into the implant, leading to a "regenerated" cornea that appeared normal and healthy. Further, the researchers found that the biosynthetic cornea reacted like normal ones, reacting to touch and producing tears to keep the eye oxygenated.

The findings offer hope to those waiting for corneal transplants, and perhaps even for the visually impaired with other afflictions, according to Dr. Per Fagerholm, an eye surgeon at Linköping University in Sweden, one of the institutions collaborating on the study.

“We are very encouraged by these results and by the great potential of biosynthetic corneas,” said Dr. Fagerholm. “Further biomaterial enhancements and modifications to the surgical technique are ongoing, and new studies are being planned that will extend the use of the biosynthetic cornea to a wider range of sight-threatening conditions requiring transplantation.”

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Read the news release.

Read the Stem Cell Network's summary on eye disease.

August 16, 2010

Vascularization: A tissue engineering roadblock

by Allison Van Winkle

There are currently over 100,000 people in the United States on the waiting list for an organ transplant. Between January and March of 2010, fewer than 7,000 patients received transplants. Imagine, as an alternative to donated live tissue, a tissue-engineered alternative, such as a bioartificial liver or pancreas. Tissue engineered products could substantially decrease the waiting time required for transplantation, while restoring degenerated function as effectively as a live tissue transplant.

There are many research hurdles that must be overcome prior to the development of a tissue-engineered organ replacement. Cell populations must be identified, expanded into large numbers, differentiated and/or purified to a desired type of cell. The cells must orientate into a three-dimensional environment of sufficient size, possibly using a scaffold. However, as the size of the scaffold increases it becomes more difficult to deliver nutrients and oxygen to the cells, along with the simultaneous removal of waste.   

In vivo, this is accomplished through a complex network of vascularisation. In the body, cells are usually within 100 µm of a blood vessel. Currently, in tissue-engineered products, cells can be up to centimetres away from a nutrient source. The need for vascularisation to be developed in vitro is currently considered one of the main roadblocks to the clinical use of tissue-engineered devices.

There are several vascularisation approaches currently being researched. These include:

  1. Growth factors. The use of growth factors may be used to stimulate the growth of blood vessels from patient to the tissue-engineered product. However, this method has been found to have a low efficiency in clinical trials.
  2. Multiple transplantation. The tissue-engineered product is implanted into a highly vascularised area, such as muscle tissue, to encourage the growth of blood vessels. The tissue-engineered device is then transplanted to the area of interest. While feasible, this process is unlikely to translate to clinical application, due to the complex process requiring multiple steps and/or surgeries.
  3. Supply of blood vessel forming cells. The use of endothelial lineage cells in the tissue-engineered device could promote the growth of blood vessels. However, this results in a tissue-engineered product containing multiple cell types, increasing the complexity of cell culturing and product development, as product purity and consistency becomes increasingly difficult to maintain.
The supply of blood vessel forming cells seems a promising research area; however a source of many endothelial cells is required. Immediate isolation of endothelial cells from the skin is inefficient with respect to obtaining enough cells for clinical use. However, the use of mesenchymal stem cells or endothelial precursor cells as a source of blood vessel forming cells may help overcome this tissue engineering roadblock. These cells could possibly be obtained non-invasively from a patient and expanded in vitro to large, clinically relevant numbers.

August 11, 2010

U.K. Government to Dissolve Stem Cell Research Regulators and Transfer Functions to New Agency

by Ubaka Ogbogu

The U.K. Government has announced plans to dissolve the Human Fertilisation and Embryology Authority (HFEA) and the Human Tissue Authority (HTA) – two independent regulators primarily responsible for stem cell research oversight in the U.K. – and to transfer their functions to a new yet-to-be-named research regulator. The HFEA was created under the 1990 Human Fertilisation and Embryology Act to independently regulatte and monitor the use of gametes and embryos in fertility treatment and in research. Its role therefore includes oversight of stem cell research activities involving the use of gametes and embryos. The HTA provides guidance on the implementation of U.K. and European Union (EU) legislation designed to ensure the safe and ethical use of human tissues (other than gametes and embryos), and is primarily responsible for licensing and inspecting institutions that store and use human tissue for research, treatment, teaching and other purposes. The changes are expected to take effect on or before June 2015, and are part of an extensive review of “arm’s length bodies” (ALBs) – independent national organizations undertaking executive functions under the auspices of the Department of Health (DH) – that began in 2004. The HFEA and HTA are both ALBs. For details of the review of ALBs, see here and here.

According to the DH report announcing the changes, the rationales for the reforms are to establish a resilient and coherent regulatory system by “placing responsibility for…different aspects of medical research regulation within one arm’s-length body” and to “streamline the process of gaining permission to undertake medical research, making it more attractive to universities and health institutions.” Both rationales suggest that the era of heightened or special regulatory focus on gamete, embryo and tissue research may be coming to an end. However, it is important to note that the U.K. oversight system for stem cell research has been an exemplary model of science governance; one that has adapted well to the social and scientific twists and turns in the regulatory lifecycle of stem cell research. In 2008, the U.K. Parliament revised and updated the legislation governing the regulation and licensing of the use of embryos in research, thus bringing it into conformity with improved research knowledge. A variety of legislation, directives and codes of practice have been established for effective regulation of tissues, cells, gametes and embryos, and to ensure harmonization with EU-wide regulatory initiatives. The HFEA is by far the greatest success story of the U.K. regulatory system – the institution has been very responsive to regulatory tasks and demands, and has responsibly managed the various contesting interests jostling for recognition in the world of stem cell research regulation. By contrast, Canada’s gamete and embryo research legislation has not been updated since its enactment in 2004 (a stipulated Parliamentary review expired in 2009), there have been few significant updates to our stem cell research oversight policies, and the national agency charged with licensing and monitoring research has been largely stagnant and ineffective.

August 04, 2010

Science, science, everywhere… British people really care

By David Kent

While many would argue that inspiring discovery and critical examination are losing the battle to fact regurgitation and grades in school systems everywhere, it seems that the British populous still appears to think that science is much more interesting than do most North Americans. I’ve written about how the UK has an excellent set of resources for equipping the public, and politicians in particular, with high quality scientific information. Combined, these resources give multiple media from which differently inclined learners can pick up scientific information.  A few great examples are listed below:

Café Scientifique was started in the UK and has been since picked up by numerous countries. It is a remarkably simple concept involving scientists coming out of the lab and into a pub to chat informally with the public about scientific issues. Cambridge’s version has put them online in collaboration with The Naked Scientists, who, incidentally, are another great example of science outreach for the public with their popular radio show.  

The British Royal Society, now 350 years old, is an impressive consolidation of informationresearch support, and policy advice and should be held as a model for Canada’s Royal Society to engage the public and Government.  

The UK also boasts a series of science festivals, huge organizations of specialized scientists (>80,000 members), dedicated charities and foundations, excellent topical science workshops for school children, and science events in libraries and museums.

While Canada does have many great programs like Let’s Talk Science, ActuaCurioCity, innovative web movements as we saw with the Webby winning Canadian Stem Cell Foundation and excellent radio and television programs, they are vastly outnumbered by such programs in the UK – especially from the public broadcasting organisation, the BBC

In saying all of this, I must be fair to disclose that the majority of my time in the UK has been in Cambridge, London, and Edinburgh so the regional picture may differ substantially, but the one thing that certainly stands clear is the level of science awareness in the national Parliament. The UK even had a Science Party run candidates in the last election. Even though it is still not ideally equipped with science advice and information, politicians here in the UK are light years ahead due to an extremely active and well received community of scientists. 

The litany of science-based organizations could easily consume an entire article, but readers of this blog will likely appreciate a run down of the information that is transmitted regarding stem cells. 

When it comes to advice given to Government, the first port of call is the arms-length Council for Science and Technology, whose previous incarnation published first a high quality briefing on stem cells for Parliamentarians in 2002 and another important report on regulations of stem cell therapies in 2004. Furthermore, there have been debates in, and reports from the House of Lords discussing many of the ethical and social concerns with a pretty reasonable grasp of the main scientific issues at play (i.e.: the distinction between embryonic and adult stem cell research and therapeutic vs. reproductive cloning). 

Perhaps most innovative is an program established by the Department for Business, Innovation & Skills called ScienceWise Dialogue, which held a two-year public dialogue project discussing issues in stem cell research and produced a remarkably detailed report that gives an overview of Britons’ opinions on stem cell research.   

While this information is surely available from the scientific community in many countries, the British public and their politicians seem to be more willing to lend an ear. Perhaps this is due to the hyperactivity of the public engagement in the sciences or the long and storied history of British-led scientific discoveries, or perhaps it simply has to do with building an infrastructure of organizations and scientific adviser positions to get scientists and policy makers in the same room at the same time.