Stem cells

Stem cells

Stem cells

Stem STEM CELL SCIENCE IN THE UK Key facts about research, regulation and funders cells

Stem cells

Stem cell research is one of the most exciting areas of 21st-century science. It offers a potentially revolutionary way to repair diseased and damaged body tissues, replacing them with healthy new cells. A huge amount of research is needed, however, to understand exactly how stem cells work and how their potential can be harnessed for treatments. Stem cells offer hope for common conditions such as Parkinson’s disease, diabetes, cancer and Alzheimer’s disease, which affect vast numbers of people in the UK and around the world, and for which there are treatments but currently no cures.

They are found in a number of places in the human body and occur at the very earliest stages of development through to adulthood. Scientists believe that the most effective way of discovering potential treatments is to undertake research on all types of human stem cells obtained from the various stages of development at which they are found, including very early embryos. All over the world, stem cell research has become the subject of scientific excitement, public curiosity, moral reflection and regulatory challenge. The UK is well positioned, because of its rigorous regulatory regime and its commitment to this research, to identify and realise the therapeutic potential of stem cells.

It also has world-class researchers in developmental and reproductive biology and the UK Stem Cell Bank. These strengths present valuable opportunities to influence the international agenda, drive the application of basic research to clinical benefits and attract skilled scientists and international investment in stem cell research. The UK’s lead on stem cell research began in the 1970s when scientists at Cambridge University, led by Sir Martin Evans, isolated the mouse embryonic stem cell. Sir Martin, who was supported by the Medical Research Council (MRC) between the 1970s and 1990s, went on to be awarded the Nobel Prize in Physiology or Medicine for 2007.

Also in Cambridge in the 1970s, Professor Robert Edwards and Dr Patrick Steptoe fertilised first animal and then human eggs outside the body, a discovery that led to the birth of the first ‘test-tube baby’ through in vitro fertilisation or IVF. It became apparent that moral reflection about the science was urgently required. A committee, chaired by Baroness Warnock, was convened to examine the ethical issues, including whether medical research on human embryos could ever be justified. Their conclusions were embodied in a landmark piece of legislation, the Human Fertilisation and Embryology Act 1990, which allowed scientists to use human embryos for a restricted range of research.

Since 2001, this range has explicitly included research into the therapeutic potential of stem cells. Scientists are only allowed to obtain stem cells from very early human embryos that have not developed beyond 14 days and they must demonstrate that the research cannot be done by any other means. A licence to conduct research using embryos must be secured from the Human Fertilisation and Embryology Authority (HFEA). An update of the Act is expected by Autumn 2008.

continued overleaf... Stem THE UK – THE PLACE TO BE FOR STEM CELL RESEARCH cells

Stem cells

UK Stem Cell Initiative The UK Government set up the UK Stem Cell Initiative in March 2005, with the aim of working with the public and private sector to draw up a ten-year vision for UK stem cell research. Led by Sir John Pattison, the initiative involves representatives from the Medical Research Council, the Biotechnology and Biological Sciences Research Council, the Department of Health, the UK Stem Cell Foundation, the Academy of Medical Sciences, medical research charities and industry.

In late 2005 it reported that the UK is a world leader in stem cell research and development – but that more investment is needed if this position is to be maintained. UK Stem Cell Funders Forum The UK Stem Cell Funders Forum was set up in 2006 to take forward the recommendations of the UK Stem Cell Initiative. Its members include research councils, major charities working in stem cell research, UK health departments and the Scottish Executive. The forum allows members to discuss and exchange information on their current stem cell work and funding priorities, to work together to identify barriers to stem cell research and ways to overcome these, and to recognise new areas that could benefit from joint funding.

A further part of the forum’s remit is to coordinate public communication activities for stem cell research. This has been taken on by the Stem Cell Communication Coalition, a group made up of representatives from the forum’s member organisations and from the Royal Society, the UK Stem Cell Bank, the Human Fertilisation and Embryology Authority and the Human Tissue Authority (HTA). Established in 2002, the coalition has coordinated a number of activities including a public survey of attitudes on the use of embryos in medical research.

UK National Stem Cell Network The UK Government launched the UK National Stem Cell Network (UKNSCN) in April 2007.

It is a national body to improve the coordination of stem cell research and the dissemination of research results, in addition to providing a focal point for communication with overseas researchers, the media and the general public. The network’s mission is to promote research activities and events at national level which help to speed the translation of basic stem cell research into therapeutic applications in the control of degenerative diseases such as Alzheimer’s and Parkinson’s, and other conditions such as diabetes.

The UKNSCN is funded through contributions from four UK research councils – the Biotechnology and Biological Sciences Research Council, the Medical Research Council, the Engineering and Physical Sciences Research Council and the Economic and Social Research Council. Injecting altered cells into early mouse embryos. © Vasanta Subramanian, Wellcome Trust

Stem cells

First IVF baby born after Cambridge scientists fertilise human eggs outside the body. Isolation of mouse embryonic stem cells by Cambridge scientists. Formation of the Warnock Committee to examine the moral questions surrounding assisted reproduction and embryo research.

Warnock Report endorses human embryo research into reproductive-related areas but advises tight regulation. Human Fertilisation and Embryology Act passed by both Houses of Parliament. Human Fertilisation and Embryology Authority (HFEA) designated statutory body to enforce provisions of legislation and established in 1991.

Dolly the sheep is cloned by cell nuclear replacement (CNR) techniques at Roslin Institute in Edinburgh. HFEA and Human Genetics Advisory Commission working party recommends that CNR be investigated for therapeutic purposes but not for reproductive cloning. Report by Donaldson Commission, chaired by the Chief Medical Officer, Sir Liam Donaldson, recommends that research using human embryos (created by IVF or CNR) to increase understanding of human disease and disorders and their cell-based treatments should be permitted subject to controls in the 1990 HFE Act. Also that the research councils should be encouraged to establish a programme of stem cell research and consider the feasibility of establishing collections of stem cells for research use.

Human Fertilisation and Embryology (Research Purposes) Regulations designed to implement the recommendations of the Donaldson Commission passed by Parliament; three new purposes added to the 1990 Act. House of Lords appoints a select committee to examine the issues arising from the new regulations, including those of human cloning and stem cell research. Parliament introduces additional legislation prohibiting reproductive cloning.

A House of Lords select committee concludes that stem cells have great therapeutic potential and that research should be conducted on both adult and embryonic stem cells. Also that a stem cell bank should be established and overseen by a steering committee. The UK Stem Cell Bank, funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council established at the National Institute for Biological Standards and Control. The bank to be a repository for stem cells derived from adult, foetal and embryonic tissues and to be open to academics and industrialists from the UK and abroad.

Steering committee established to oversee the bank and the use of stem cell lines and to develop codes of practice. Researchers at King’s College London generate the UK’s first embryonic stem cell line. The International Stem Cell Forum (ISCF) – made up of 21 funders of stem cell research from around the world including the MRC – is established to encourage international collaboration and funding support for stem cell research.

1978 1981 1982 1984 1990 1996 1998 2000 2001 2002 2002 2003 2003 continued overleaf... Stem MILESTONES IN UK STEM CELL RELATED RESEARCH AND REGULATION cells

Stem cells

First stem cell lines deposited in UK Stem Cell Bank by scientists from King’s College London and the Centre for Life in Newcastle. The ISCF starts a review of global ethics and regulation relating to stem cell research. The UK Government sets up the UK Stem Cell Initiative, with the aim of working with the public and private sectors to draw up a ten-year vision for UK stem cell research. The Hinxton Group, a consortium of 60 researchers, ethicists, scientific journal editors and lawyers from 14 countries, reaches a consensus on a set of international guidelines for stem cell research, which they hope will simplify existing rules and aid collaboration.

On behalf of the ISCF, the Australian National Health and Medical Research Council produces a report on intellectual property rights related to stem cell research across the world. It will be key in encouraging further research and development worldwide. American scientists find out how to make stem cells from embryos without destroying the embryo in the process – an advance that could overturn ethical objections. The Biotechnology and Biological Sciences Research Council leads the research councils and relevant government departments in establishing a UK National Stem Cell Network to encourage links between researchers and to encourage development of an integrated national stem cell research community.

The EU Tissues and Cells Directives became UK law via the Human Tissue (Quality and Safety for Human Application) Regulations 2007. Under the Regulations the Human Tissue Authority regulates the procurement, processing, testing, storage, distribution and import/export of tissues and cells for human application. The International Stem Cell Forum publishes the results of a study characterising 59 stem cell lines. The research will help to ensure that future advances in stem cell research involve internationally coordinated quality standards.

Teams of researchers at Cambridge and Oxford universities independently discover a new type of stem cell in mice and rats that is very similar to human embryonic stem cells.

Two independent teams of researchers – at Wisconsin and Kyoto universities – produce human induced pluripotent stem cells. These are thought to be very similar, if not identical, to embryonic stem cells but are made by reprogramming an adult (nonpluripotent) cell. The Hinxton Group meets for a second time and produces a consensus statement on pluripotent stem cell-derived gametes, which discusses social and ethical issues and makes recommendations about policy and practice.

Human Fertilisation and Embryology bill updated to allow use of hybrid embryos in research. 2004 2004 2005 2006 2006 2006 2006 2007 2007 2007 2007 2008 2008

Stem cells

Stem cells, whether they are derived from an early embryo, a foetus or an adult, have two key properties. Firstly, they have the ability to reproduce almost indefinitely and, secondly, they can be directed to generate the specialised cells that make up the tissues and organs of the body. They have exciting potential for the generation of therapies for repair and replacement of damaged and diseased tissues and organs, as models for the testing of new drugs and helping us to understand at a cellular level what goes wrong in many conditions.

Embryonic stem cells A fertilised egg (produced when an egg is penetrated by a sperm cell) is in essence a one-cell embryo. Up until about the eight-cell stage, this very early embryo has the capacity to develop into every cell needed for full human development as well as tissues such as the placenta and umbilical cord. After about five days of development, the embryo consists of a ball of 50 to 100 cells called a blastocyst, which is about the size of a full stop on this page. It is from an inner cell mass within this ball that the embryonic stem cell or ES cell is derived. The cells that comprise it have no fixed destiny – at this stage, there is no trace of any structure such as a nervous system which could, for example, produce sensations of pain.

Although ES cells can be manipulated to generate all the cell types in our bodies, they cannot develop into a complete embryo on their own.

The main source of embryonic stem cells is from surplus embryos donated by couples undergoing in vitro fertilisation (IVF). These would otherwise be destroyed. Developed in the 1970s, IVF is used to treat couples who are having difficulty becoming pregnant. Usually, the woman takes fertility drugs to help her produce more eggs, and these eggs are harvested and fertilised with the man’s sperm in the laboratory. The woman is then given hormone drugs before the fertilised eggs are implanted into her womb. Adult stem cells Adult stem cells are found, for example, in human bone marrow, blood, the eye, the brain and skeletal muscle.

Their purpose is to replace and replenish cells with specialised functions, such as blood cells. Bone marrow transplants are an existing model of adult stem cell therapy. continued overleaf...

FERTILISATION STIMULATED TO DEVELOP FIVE DAYS’ GROWTH DIFFERENTIATION INTO ADULT STEM CELLS SPECIALISATION INTO FINAL CELL TYPES sperm egg fertilised egg totipotent cells blastocyst embryonic stem cells adult stem cells neurons bone tissue blood cells STEM CELLS Stem THE SCIENCE OF STEM CELLS cells

Stem cells

For nearly 40 years, patients with blood disorders such as leukaemia have been treated by introducing haematopoietic stem cells via bone marrow transplants. This has been possible because haematopoietic stem cells are readily accessible, unlike many other adult stem cell types found in our bodies, and they are able to replenish blood cells continuously at high rates.

Adult stem cells do not appear to have the same capabilities as ES cells. However, under laboratory conditions, some scientists claim to have been able to manipulate them to form other cell types. So it may be possible, eventually, to direct these cells to function in other areas of the body and to repopulate body tissues that have been damaged or diseased. In 2006, researchers found a way to reprogramme mouse skin cells and turn them back into cells very similar to embryonic stem cells. A major breakthrough was achieved in 2007 when researchers also achieved this in human cells, opening up a possible new source of pluripotent stem cells, but without the need to use actual embryos.

This technology is at a very early stage and the techniques used to provide the necessary reprogramming require genetic modification and cannot currently be used to develop therapies. Nevertheless, scientists anticipate making rapid progress towards better understanding and refining approaches to generate these cells. The short-term goal is to use them to help model human diseases in the laboratory. The challenge for stem cell research As the one-cell embryo develops, cell differentiation occurs. Differentiation is the increasing specialisation of cells: more specialised cells develop from less specialised cell types.

Since most of our body cells have the same genes, differentiation must involve switching on (expressing) or switching off (repressing) different subsets of genes in individual cells. ES cells grown in the laboratory preserve the power to become any cell in the human body. Their destiny is to differentiate. They are infinitely malleable and one of the challenges for scientists is to direct this process. A crucial task for tapping into the therapeutic potential for stem cells is to teach them how to become, for example, muscle cells for damaged hearts or neurons for damaged brains. Another is to ensure they do not continue to grow in an undifferentiated way and in effect turn into a cancer.

Much basic scientific research needs to be undertaken in order to understand these processes. The adult stem cells in our bodies replenish cells and tissue in their particular location and, in general, appear to be less malleable than ES cells. However, recent experiments have shown they do have the potential to do a lot more than previously suspected. Stem cells from bone marrow have been induced to differentiate into brain and kidney cells. How this happens is not precisely understood. Research is continuing to explore the mechanism of such transformation and to ascertain whether it is possible to direct adult stem cell differentiation to produce cells for therapies.

Cell nuclear replacement Scientists are also exploring a technique called cell nuclear replacement which might potentially provide cells for therapies. In 1996, scientists at the Roslin Institute in Edinburgh produced Dolly the sheep from a mammary cell of a six-year- old sheep. The nucleus of this cell was inserted into a sheep egg cell after the egg’s own nucleus had been removed. This process is known as cell nuclear replacement. Factors in the egg (the cytoplasm) reprogrammed the nucleus of the mammary cell and, in a sense, made it ‘forget’ its original destiny. Instead, the nucleus behaved as if it were inside a one- cell embryo.

The egg was then implanted into a sheep’s womb. This is reproductive cloning. It is illegal in the UK to carry out reproductive cloning in humans.

It may be possible, however, to use cell nuclear replacement techniques for human therapeutic cloning. Although the initial steps in both reproductive and therapeutic cloning are the same, subsequent steps and the underlying purpose could not be more different. In therapeutic cloning, also known as somatic cell nuclear transfer (SCNT), the nucleus of an adult cell, for example a skin cell, from a patient with a condition such as Parkinson’s, would be inserted into a human egg whose own nucleus had been removed. When the cloned embryo reached the blastocyst stage, ES cells would be derived from the inner cell mass.

These cells would be grown in the laboratory and induced to differentiate into the precise cells needed, for example dopamine-producing neurons, which are lacking in the brains of people with Parkinson’s disease. Although much research still needs to be undertaken, this form of stem cell therapy could provide new cells, likely to be genetically identical to the patient, with a greatly reduced risk of rejection, a common problem in any form of transplant operation. However, even if this technology is successful, such personalised medicines would be very costly.

If the patient suffers from a genetic disease, their cells would also contain the genetic defect, and the resulting ES cells would not be used for cell-based therapy. However, the ES cells could be used to study the disease in the laboratory to perhaps find other types of therapy. Some ES cells are derived from embryos that have failed the process of preimplantation genetic diagnosis (PGD) – which involves genetically testing an embryo in a laboratory. Some of these will carry the genetic defect, such as cystic fibrosis, allowing the disease to be studied in the laboratory.

Scientists are exploring the possibility of creating embryos, by using human sperm to fertilise an animal egg (hybrid), or transferring the nuclei of human cells into animal eggs that have had almost all their genetic material removed.

These so-called ‘human admixed embryos’ are a type of SCNT. They could provide a plentiful supply of stem cells and get around the shortages of leftover IVF embryos from which stem cells can be harvested or of human eggs that could be used in the same way. In late 2007, the Human Fertilisation and Embryology Authority granted licences to two teams of researchers to create human admixed embryos.

Stem cells

The Human Fertilisation and Embryology Act of 1990 was enacted to regulate the practice of in vitro fertilisation (IVF) and the creation, use, storage and disposal of embryos produced in this way. It established a regulatory authority, the Human Fertilisation and Embryology Authority (HFEA), which is empowered to approve all embryo research conducted in the UK. Such research is illegal unless it is carried out under a licence granted by the HFEA. In order to receive a licence the applicant must demonstrate that embryo research is necessary and that the proposed research is being done for one of the five purposes specified in the Act: (a)  promoting advances in the treatment of infertility; (b)  increasing knowledge about the causes of congenital disease; (c)  increasing knowledge about the causes of miscarriages; (d)  developing more effective techniques for contraception; (e)  developing methods for detecting the presence of gene or chromosome abnormalities in embryos before implantation; or for such other purposes as may be specified in regulations [paragraph 3(2)].

Such other purposes are limited by the language of the Act to projects which “increase knowledge about the creation and development of embryos, or about disease, or enable such knowledge to be applied” [schedule 2 paragraph 3(3)]. Since the Act was passed, there have been many advances in developmental biology but two stand out: the derivation of human embryonic stem (ES) cells and the cloning of Dolly the sheep in 1996 by cell nuclear replacement (CNR). In response to the cloning of Dolly the sheep, a working party drawn from the HFEA and the Human Genetics Advisory Commission was formed to undertake a public consultation on human cloning.

In their report, ‘Cloning: Issues in science and medicine’ (December 1998), the group recommended that the Secretary of State for Health consider adding two additional purposes for which embryo research could be licensed: the development of therapy for mitochondrial disease and the development of therapeutic treatments for diseased and damaged tissues and organs. Human reproductive cloning was deemed unacceptable. Egg cell manipulation. Images courtesy of MRC Clinical Science Centre continued overleaf...

Stem STEM CELL RESEARCH: REGULATORY ISSUES cells

Stem cells

An expert committee chaired by Sir Liam Donaldson was then appointed and the group was asked to answer two basic questions: should this new type of research be permitted and, if so, were new regulations required? In its 2000 report, the committee recommended that research on embryos (both surplus embryos left over after IVF and embryos created by CNR) be permitted in order to increase understanding of human disease and disorders, and their cell- based therapies. The Human Fertilisation and Embryology (Research Purposes) Regulations were brought forward by the government; they were passed by the House of Commons in December 2000 and by the House of Lords in January 2001.

The regulations added three new purposes to the five in the Act: (a)  increasing knowledge about the development of embryos; (b)  increasing knowledge about serious disease; (c)  enabling such knowledge to be applied in developing treatments for serious disease.

The House of Lords Select Committee on Stem Cell Research was appointed on 7 March 2001 “to consider and report on the issues connected with human cloning and stem cell research” arising from the new regulations. On 27 February 2002, the Committee reported. Among its conclusions was an endorsement of the Department of Health’s (DH) proposals to establish the UK Stem Cell Bank, responsible for the custody of stem cell lines, ensuring their purity and provenance, and monitoring their use. The Committee also recommended that as a condition of granting a research licence, the HFEA should require that a sample of any ES cell line generated in the UK in the course of that research be deposited in the bank.

The creation of embryos (from which stem cells may be derived) and the subsequent storage of these embryos is regulated by the HFEA. This includes embryos created from in vitro fertilisation and cell nuclear replacement. Research projects which involve derivation of stem cells by the creation of embryos must be licensed and approved by the HFEA. Researchers must prove, to an HFEA licence committee’s satisfaction, that the research application fits in with the purposes of the Human Fertilisation and Embryology (HFE) Act 1990 and the HFE Research Regulations 2001 and that it is necessary to use embryos for the research.

In addition to the two licences subsequently granted for human admixed embryos, the HFEA has so far granted two licences to study the derivation of human embryonic stem cell lines using nuclear transfer (therapeutic cloning). The first was in 2004 to researchers at the International Centre for Life at the University of Newcastle, who are investigating new treatments for conditions including diabetes, Parkinson’s and Alzheimer’s disease. The second, in the following year, was to the Roslin Institute in Edinburgh for the study of motor neuron disease. The regulation of stem cells in the UK is affected by two pieces of legislation: the Human Tissue Act 2004 and the Human Tissue (Quality and Safety for Human Application) Regulations 2007, which fully implement the EU Tissues and Cells Directives (EUTCD).

The Human Tissue Act 2004 regulates the removal, storage and use of human bodies, organs, tissue and cells for a number of purposes, including research. The EUTCD – which was brought fully into force in 2007 – creates a common framework that ensures high standards in the procurement, testing, processing, storage, distribution and import/export of tissues and cells across the EU. The primary aim of the Directive is to ensure the quality, safety and traceability of tissue and cells used for human application. It also aims to support the exchange of tissues and cells between member states.

Light micrograph of a human embryo at the two-cell stage of development. Richard G. Rawlins/Custom Medical Stock Photo/ Science Photo Library

Stem cells

Globally, stem cell research is becoming increasingly competitive. Many countries, such as the ones listed below, are progressing considerably in the stem cell research field, due to increasing funding and permissive regulations. In Asia, Japan has invested heavily in stem cell research and Japanese researchers have been responsible for some important recent discoveries. The Chinese government supports all forms of stem cell research and Chinese researchers are carrying out work of international standing and publishing in European and US journals.

Stem cell research is a major priority in Singapore, which has attracted overseas talent with state-of-the-art facilities and generous research funding.

The US remains the world leader in stem cell research. Despite restrictions on federal funding for embryonic stem cell research, the US National Institutes of Health (NIH) spends very considerable amounts on other types of stem cell research. Individual US states, such as California, are investing substantially in all forms of stem cell research, including embryonic stem cell research. Canada spends a large amount on stem cell research and the government established the Canadian Stem Cell Network to coordinate research activity and fund major collaborations with a concentration along product development lines.

Sweden is a world leader in stem cell research, with a regulatory and ethical environment similar to the UK. Due to its permissive laws on stem cell research, Sweden now leads Scandinavia, and possibly even Europe, in this area. Germany has very tight restrictions that have deterred its scientists from working on embryonic stem cells, but it is a world leader in adult stem cell research. Regulation Regulation of stem cell research varies enormously between different countries. Some countries have no legislation at all, and others ban all such research. Some countries have adopted laws that allow embryonic stem cell research, including ‘therapeutic’ cloning and the creation of embryos specially for research purposes.

A large number of countries have adopted compromise policies, permitting some types of embryonic stem cell research and restricting others.

The US has no national laws or regulations to control embryonic stem cell research. However, individual states have introduced their own laws. Some states, such as Florida and Pennsylvania have prohibited embryonic stem cell research. Other states, such as California and Massachussetts, have permissive laws. continued overleaf... Stem INTERNATIONAL ARENA cells

Countries with permissive regulation include the UK as well as Australia, Belgium, China, India, Israel, Japan, Singapore, South Korea and Sweden. Although the UK’s regulations for embryonic stem cell science are permissive, the system for enforcing them is very strict, more so than in many other countries.

Other countries are less permissive. Such countries allow embryonic stem cell research using embryos left over after IVF treatment but may not allow cloning or the creation of embryos specially for research purposes. These countries include Canada, Denmark, France, the Netherlands, New Zealand, Portugal, Spain and Switzerland. There are also a number of countries with tight restrictions or bans on embryonic stem cell research. Within Europe, countries with such laws include Italy, Lithuania, Poland and Slovakia. Different European countries have very different laws on stem cell research. The European Commission will not fund activities that destroy the human embryo, but may fund other research on embryonic stem cells, provided that this research is permissible under the laws of the country where the research is taking place.

There have been a number of attempts to create international rules for stem cell research. For example, the International Societies for Stem Cell Research (ISSCR) has drawn up ethical guidelines for the embryonic stem cell research. These guidelines are voluntary, but scientists are coming under pressure from international journals and funding bodies to prove that their research is being conducted in an ethical manner. In 2005, the United Nations General Assembly adopted a declaration calling on countries to ban all forms of human cloning, including cloning for research purposes. However, the declaration is non-binding and has no legal status.

The International Stem Cell Forum The Medical Research Council (MRC) launched the International Stem Cell Forum (ISCF) in 2003 along with eight other international funding agencies with similar scientific principles and resources. These agencies all shared the MRC’s concerns about the need to create standardised global criteria for creating, storing and maintaining stem cell lines. Today, the ISCF has a total of 21 member organisations in 19 countries. The forum is working on the International Stem Cell Initiative (ISCI). Led by Professor Peter Andrews of the University of Sheffield Centre for Stem Cell Biology, the ISCI has been developing an internationally-agreed set of rules for growing and analysing human embryonic stem cells.

The ISCF published a paper in Nature Biotechnology in June 2007 analysing in detail 59 human embryonic stem cell lines. This international collaborative project is now progressing with US$2million of funding. On behalf of the forum, the Australian National Health and the Medical Research Council have developed a document about intellectual property in stem cell science. It covers the criteria for patenting stem cells throughout the world, identifying techniques that may be subject to patenting, highlights patents already in existence and explains how countries are attempting to ensure ongoing access to stem cell resources.

Led by Canada, the ISCF is also working on a global review of ethics and regulation of stem cell research, which is being carried out by its Ethics Working Party. The group includes ethicists, research scientists, clinicians and lawyers from the forum’s members. Together they are reviewing the different ethical issues and regulations in countries that fund stem cell science, with a particular emphasis on research involving embryonic stem cells. The group aims to draft best practice guidelines for stem cell research and to develop a global register of clinical trials involving stem cells.

Although the commercial, non- therapeutic use of stem cells is already an established part of the process of drug discovery, the commercial and medical benefits from stem cell therapies are still some way off, with the exception of bone marrow stem cell transplants for blood disease such as leukaemia which have been used for many years.

The delay in further treatments is partly due to the stringent tests for safety, quality and efficacy required for these therapies prior to their approval for market by the regulatory agency - the European Agency for the Evaluation of Medicinal Products (EMEA). These pre-clinical and clinical studies will typically take a number of years to complete. It is likely that therapies using adult stem cells will emerge first, with embryonic stem cell therapies following later.

Despite this, several UK public and private stem cell research companies have been established, such as ReNeuron, Stem Cell Sciences, Axordia and NovaThera. UK stem cell companies are working on therapies for conditions such as stroke, Parkinson’s disease, diabetes, cardiac disease and retinal damage of the eye. Some are also marketing their stem cells as drug discovery tools for screening applications in drug development, for example to test metabolism, and in safety tests. Support for commercialisation The UK Stem Cell Bank, which provides a repository for stem cell lines derived from adult, foetal and embryonic tissues, will be a vital resource to company researchers.

The bank is collaborating with commercial partners to achieve cell lines of sufficient stability for use by companies. continued overleaf...

Stem UK COMMERCIALISATION OF STEM CELL RESEARCH cells Blastocyst. © Wellcome Trust

The bank will ensure that cell lines which could ultimately provide the basis for clinical treatment are prepared under Good Manufacturing Practice (GMP), subjected to appropriate safety testing and subsequently handled and stored under quality-controlled conditions. However, some cell lines will require additional tests, which companies themselves may have to carry out. In 2004, the UK Stem Cell Bank set up the first clinical grade GMP facility for human stem cell banking in the European Union.

This was followed in January 2006 by the opening of the UK’s first GMP laboratory for the derivation of clinical grade human embryonic stem cell lines, at the Medical Research Council’s Centre for Stem Cell Biology at Sheffield University.

Companies may also benefit from the UK Stem Cell Foundation, which was established in 2005 to support the transfer of stem cell techniques from the laboratory to the clinic. The foundation aims to raise funds from private donations to directly fund projects where research has indicated potential for direct clinical benefit to patients in the short term. As of early 2008, the MRC had approved five joint awards with the foundation, addressing bone and cartilage repair, liver regeneration and brain repair. The UK Government funds stem cell research in companies directly via its Technology Strategy Board.

This money is available for collaborative R&D projects in specific areas, including bioscience and healthcare, and is allocated to consortia on a competitive basis. The MRC has developed strategies with the Technology Strategy Board for academic and industry cooperation, and there has already been a joint call in regenerative medicine. IVF embryo.

© Anne Falkner

The Alzheimer’s Society is the UK’s leading care and research charity for people with dementia, their families and carers. With more than 250 branches and support groups, it provides information and support for people with any form of dementia and their carers through its publications, helpline, website and local network. It advises professionals, runs quality care services and campaigns for improved health and social care and greater public understanding of dementia. The society funds an innovative programme of biomedical and social research on the causes of, cures for and care for people with the disease.

What is Alzheimer’s disease? Alzheimer’s disease is the most common form of dementia. More than 700,000 people in the UK have dementia, of whom 15,000 are under the age of 65. Dementia affects one in 14 people over the age of 65 and one in six over the age of 80. More than 60 per cent of the people with dementia have Alzheimer’s disease – a progressive, degenerative disease of the brain, which destroys cells and disrupts transmitters that carry messages in the brain. Stem cell research and Alzheimer’s disease In Alzheimer’s disease, nerve cells die in a random way, interrupting the complex interconnections of nerve cells in the cortex, which is the outer layer of the brain.

It is this network of cells that facilitates our memories, personalities and behaviour patterns. Because of the loss of many different nerve cell types in the brain, and the impact that the disease has on communication between cells, developing therapies for Alzheimer’s disease is more complicated and challenging than for some other neurological conditions. Until recently, it was believed that we are born with a certain number of nerve cells and that once these cells die, they cannot be replaced. However, this concept changed after the discovery of a population of brain cells, called neural stem cells (NSCs), which can develop into new nerve cells.

Experiments on animals have shown that implanted NSCs can move towards areas of damage and take on a nerve cell-like structure. This has raised hopes that NSCs may be a useful new therapy for illnesses where nerve cells are lost. However, in Alzheimer’s disease, the loss of nerve cells is very widespread and there are doubts that the there are sufficient NSCs in the adult brain to be able to compensate for this loss, even if we knew how to stimulate them. Research on NSCs has revealed that there may be an alternative strategy for replacing lost nerve cells. Other parts of the body also produce stem cells.

These stem cells seem to have remarkable plasticity – that is, with the appropriate chemical trigger, they can turn into many different cell types, including nerve cells. Indeed, researchers have obtained bone marrow stem cells (MSCs) from rats, grown them in cell culture and have turned them into cells that exhibit the characteristics of nerve cells. This is encouraging because bone marrow is a far more accessible source of stem cells than the brain. continued overleaf...

MSCs are also easy to maintain in the laboratory, can be grown easily and can be frozen and stored for long periods of time. The Alzheimer’s Society has funded stem cell research since 2002 when it awarded a three-year fellowship. The project involved animal models of nerve cell loss and the replacement of nerve cells with MSCs. Since then, we have awarded two further fellowships and one PhD studentship, and funded a project in understanding how stem cells may be useful in the treatment of dementia. The direct benefits of this work in terms of a possible therapy may not be realised for some years.

However, if successful, these projects will indicate whether we may be able to replace dead nerve cells in a widespread and specific manner – something that has long been thought impossible.

Future prospects The society sponsors research through its Quality Research in Dementia (QRD) programme. The focus of QRD is to fund research that has direct benefits on the quality of life for people with dementia and their carers – either through improving care, or by taking us closer to understanding the causes and finding a cure for dementia. A network of 170 lay people with personal experience of dementia is actively involved in setting the research agenda for society, assessing outcomes and guiding the programme. Every application that we seek to support has been prioritised by this consumer network as well as rigorously peer- reviewed by leading international academic researchers.

Stem cell research has consistently been identified as a priority by the QRD consumer network. The Alzheimer’s Society hopes to receive more applications for funding research of this kind. We are delighted to work in collaboration with the MRC and other charities to support this important area of research. ALZHEIMER’S SOCIETY | ASSOCIATION OF MEDICAL RESEARCH CHARITIES | BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL | BRITISH HEART FOUNDATION | CANCER RESEARCH UK | DIABETES UK | HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY | HUMAN TISSUE AUTHORITY | MEDICAL RESEARCH COUNCIL | PARKINSON’S DISEASE SOCIETY | THE ROYAL SOCIETY | SCOTTISH STEM CELL NETWORK | UK STEM CELL BANK | WELLCOME TRUST Contact Alzheimer’s Society Central Office Devon House 58 St Katharine’s Way London E1W 1JX Tel: 020 7423 3500 Fax: 020 7423 3501 www.alzheimers.org.uk

The Association of Medical Research Charities (AMRC) is a membership organisation of the leading UK charities that fund medical and health research. The AMRC aims to provide effective support and leadership for its members and the wider charity sector involved in medical and health research through the provision of information and guidance and a strong and credible representative voice. It does not conduct or provide funding for medical research, but in this pack you will find examples of stem cell research work supported by several of our member charities.

The AMRC produces policy and position statements including on human embryo and stem cell research, and issues regular announcements on these topics, which are available on our website (www.amrc.org.uk).

We also provide web-based information about stem cell research in our ‘issues in debate’ section covering: current debate, regulation, legal framework, advisory system and other guidelines, ethical principles, charity perspective (with links to members particularly active in this area), public opinion, patient and carer perspective and further information. Reflecting public opinion – a 2007 British Market Research Bureau survey showed that 73 per cent of the UK public support embryonic stem cell research under existing or tighter Government regulation – our statement emphasises support for such work within a rigorous regulatory environment, and outlines the potential benefits of this research to the understanding, although not necessarily imminent treatment of a range of conditions.

These include heart disease, diabetes, cancer, Parkinson’s disease, stroke, arthritis and mental illness. The AMRC has been very active in the debate about modernising the Human Fertilisation and Embryology Bill, in particular the use of human-animal hybrid embryos as a source of stem cells for research. We provided evidence and supported amendments to the Bill in its draft stages and as it progressed through Parliament. In April 2007, the AMRC coordinated a joint letter to the Prime Minister signed by 223 medical research charities and patient organisations, demonstrating a strong stance that the law regulating stem cell research should allow the creation of hybrid embryos.

Two such projects were licensed under current law, in January 2008 (www.hfea.gov.uk/en/377.html). Capitalising on our award-winning partnership with Y Touring Theatre Company (www.ytouring.org.uk) on ‘Every Breath,’ a play about the use of animals in medical research, the AMRC is supporting public dialogue on the stem cells debate through a further, similar, partnership. With financial support from the Medical Research Council, Department of Health and AMRC member Action Medical Research, ‘Nobody Lives Forever’ is a play by highly acclaimed writer Judith Johnson which explores the debate around stem cell research.

Y Touring’s productions present a range of arguments, and incorporate a live discussion between audience and cast, who stay in role to field questions. Dr Sophie Petit-Zeman, the AMRC’s Head of External Relations, is scientific consultant to Y Touring for the project, which tours schools and adult audiences through 2008 and will be the basis for a ‘Mega-Debate’ project with the Royal Albert Hall, involving 2,000 young people, in spring 2009. Dr Petit-Zeman is also a coordinating member of the project’s advisory group.

contact details overleaf...

ALZHEIMER’S SOCIETY | ASSOCIATION OF MEDICAL RESEARCH CHARITIES | BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL | BRITISH HEART FOUNDATION | CANCER RESEARCH UK | DIABETES UK | HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY | HUMAN TISSUE AUTHORITY | MEDICAL RESEARCH COUNCIL | PARKINSON’S DISEASE SOCIETY | THE ROYAL SOCIETY | SCOTTISH STEM CELL NETWORK | UK STEM CELL BANK | WELLCOME TRUST Contact Association of Medical Research Charities 61 Gray’s Inn Road London WC1X 8TL Tel: 020 7269 8820 Fax: 020 7269 8821 www.amrc.org.uk

The Biotechnology and Biological Sciences Research Council (BBSRC) is the UK’s principal funder of basic and strategic research across the biosciences, much of which leads to advances and applications in the medical, healthcare, agricultural, veterinary and food sectors. It is funded mainly by the Government’s Science Budget through the Department of Innovation, Universities and Skills (DIUS). The BBSRC works closely with the other research councils through Research Councils UK (RCUK), and is leading the research councils and relevant government departments in establishing a UK National Stem Cell Network to encourage links between researchers and to encourage development of an integrated national stem cell research community, in response to a report from the UK Stem Cell Initiative in 2005.

The BBSRC is also leading the research councils in providing focused communications training for UK stem cell scientists.

The BBSRC operates a variety of procedures to address ethical and societal issues surrounding the biosciences, including those associated with stem cell research. It supports research on both adult and embryonic stem cells. Our position on stem cell science is published on the BBSRC website: http://www.bbsrc.ac.uk/ organisation/policies/position/public_ interest/stem_cells.pdf. BBSRC-funded research has led to several commercial developments in stem cell science, including several spin- out companies. These include Axordia - novel methods for directed differentiation of stem cells, and RegenTec - self- assembling injectable scaffold for tissue repair.

Funding for stem cell research The BBSRC supports pioneering research in the UK on the basic biological properties and behaviour of stem cells from both model organisms and humans. It has played a key role in building up the UK’s research capacity in stem cell science, through targeted funding initiatives and specialist training for researchers. Through its response mode funding scheme, the BBSRC supports stem cell research through grants. It also funds the training of stem cell scientists through its Doctoral Training Grants (DTG) to universities. In both of these schemes the areas of study are chosen by the applicants.

BBSRC spends at least £9million a year supporting stem cell research and training. It co-funds the UK Stem Cell Bank with the Medical Research Council (MRC). Research The focus of much BBSRC-funded research is on providing more knowledge about how stem cells regulate their ability, as unspecialised cells, to either replicate themselves or turn into particular cell types. This information is essential if it is to be possible to use stem cells safely and effectively in therapies and other biomedical applications. This often involves science that is supported in a complementary way by the BBSRC and the MRC.

In 2007, the BBSRC and the MRC started the UK’s biggest ever public consultation on stem cell research, funded by the UK Government’s Sciencewise scheme. The programme aims to gain an insight into public expectations, aspirations, and concerns about this fast moving and challenging area of science, and includes a national programme of workshops and discussion meetings. Contact Chris St Pourcain, Stem Cell Biology, BBSRC Senior Programme Manager, email: christopher.stpourcain @bbsrc.ac.uk. A poster display on stem cell science, ‘Hope not Hype’, produced by the BBSRC and the MRC is accessible at: http://www.

bbsrc.ac.uk/society/meetings/exhibition_ stem_cells/index.html.

contact details overleaf...

ALZHEIMER’S SOCIETY | ASSOCIATION OF MEDICAL RESEARCH CHARITIES | BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL | BRITISH HEART FOUNDATION | CANCER RESEARCH UK | DIABETES UK | HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY | HUMAN TISSUE AUTHORITY | MEDICAL RESEARCH COUNCIL | PARKINSON’S DISEASE SOCIETY | THE ROYAL SOCIETY | SCOTTISH STEM CELL NETWORK | UK STEM CELL BANK | WELLCOME TRUST Contact Biotechnology and Biological Sciences Research Council Polaris House North Star Avenue Swindon SN2 1UH Tel: 01793 413200 Fax: 01793 413201 www.bbsrc.ac.uk

The British Heart Foundation (BHF) is the nation’s heart charity, dedicated to saving lives through pioneering research, patient care, campaigning for change and by providing vital information. We rely on public donations of time and money to continue our work. The BHF is the largest independent funder of cardiovascular science in the UK. We make an annual investment in research of around £50 million, and have a research portfolio of around 1,200 studies at any one time. In our view, if appropriate safeguards are in place, bolstered with the stringent ethical guidelines that exist in the UK, stem cell research is appropriate as there are many achievable benefits for heart patients.

What is heart and circulatory disease? Cardiovascular disease – the term that encompasses all diseases of the heart and circulation – kills more than 200,000 people each year in the UK. The main forms are coronary heart disease and stroke, which together cause around three quarters of these deaths. Coronary heart disease is the UK’s single biggest killer. It occurs when fatty plaques, known as atherosclerosis, build up in the vital coronary arteries that feed the heart. This can be caused by a combination of environmental, lifestyle and biological factors such as smoking, high blood pressure, or the genes we’ve inherited from our parents.

The plaques can narrow our coronary arteries, causing chest pain (‘angina’) and they can rupture and form a blood clot that completely blocks the artery, causing a heart attack.

Thanks to research – a significant part of it BHF-funded – advances in understanding of the disease have enabled effective treatment and prevention strategies to steadily reduce death rates from heart disease since the 1970s. However, more than 2.6 million people in the UK are now living with heart disease, which can be frightening and debilitating. How might stem cells help people with heart disease? Heart attack can cause loss of heart muscle cells and the development of scar tissue, leading to long-term changes in the heart’s size and shape. This can leave people vulnerable to dangerous irregular heart beats and may lead to heart failure, when the heart doesn’t pump effectively.

Our hearts have a limited ability to repair, so heart damage is usually irreversible. There are currently no treatments to ‘patch up’ damaged tissue with healthy heart muscle.

Stem cell therapy could be part of the solution. We hope that in the future, stem cells could prevent the long-term consequences of heart attack injury by repairing or replacing damaged tissue. We may also be able to use a person’s own stem cells to grow heart valves, blood vessels, or even whole hearts for transplant. These replacements would be an exact match to the patient – avoiding immune rejection. Our understanding of stem cells is still in its infancy so the BHF is funding research across many aspects of stem cell biology to help us understand this exciting potential therapy. This knowledge will equip us to move forward and give the best chance of success for large studies with patients in the future.

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Progress made by BHF research teams Some researchers have suggested that injection of a patient’s own bone marrow stem cells into their heart after heart attack may improve the heart’s function. BHF researchers in Leicester investigated and found that, rather than transforming into healthy heart cells, bone marrow stem cell therapy may work by protecting vulnerable heart tissue after heart attack. A team at the UCL Institute of Child Health revealed that stem cells in the outermost layer of the heart can be guided by a specific protein to move deeper inside and help to repair a failing adult heart.

Research funded by the BHF and the Medical Research Council (MRC) showed that a protein called ‘thymosin ß4’ can stimulate new blood vessel generation from these cells in adult mice. Previously it was thought that cells within the adult heart are dormant and that all cells that contribute to heart repair travel from the bone marrow. A team at King’s College, London, has suggested a possible future role for stem cells in protecting heart bypass grafts against atherosclerosis. The researchers found that after surgery the cells lining the grafted blood vessel are lost - leaving it vulnerable to plaque build-up - before being replaced by stem cells from the bone marrow and blood.

Also, in mice engineered to have high cholesterol levels, there were fewer stem cells and accelerated atherosclerosis. This suggests that increasing our stores of stem cells might help to protect patients from atherosclerosis after heart surgery. The team is currently investigating in detail the signals that determine how stem cells can transform into blood vessel wall cells.

Scientists at the National Heart and Lung Institute in London have developed a biological ‘scaffold’ on which human stem cells can survive, grow and begin to develop into heart valves. Engineered human valves may in future replace metal and tissue replacements that have limitations in treating children and adults with valve defects. ALZHEIMER’S SOCIETY | ASSOCIATION OF MEDICAL RESEARCH CHARITIES | BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL | BRITISH HEART FOUNDATION | CANCER RESEARCH UK | DIABETES UK | HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY | HUMAN TISSUE AUTHORITY | MEDICAL RESEARCH COUNCIL | PARKINSON’S DISEASE SOCIETY | THE ROYAL SOCIETY | SCOTTISH STEM CELL NETWORK | UK STEM CELL BANK | WELLCOME TRUST Contact British Heart Foundation 14 Fitzhardinge Street London W1H 6DH Tel: 020 7935 0185 bhf.org.uk

Cancer Research UK is the world’s largest non-governmental organisation dedicated to cancer research. We are committed to tackling cancer by understanding its causes and investigating how best to diagnose, treat and prevent it. We also fund research aimed at providing the best possible support and information to cancer patients and their families. Cancer Research UK is the largest single funder of cancer research in the UK, funding more than 4,250 scientists, doctors and nurses throughout the country. We are also the European leader in anti-cancer drug development. In the financial year of 2006/07, our total scientific spend was £315 million.

Cancer in the UK Cancer is a major disease in the UK. There are around 285,000 new cases of cancer registered each year and around one in three of us will develop cancer at some time in our lives. The disease is more likely to develop later in life, with around 65 per cent of cases diagnosed in people over the age of 65. Cancer is the cause of around a quarter of all deaths in the UK. In 2005, there were around 153,490 deaths from cancer. Over one-fifth of these were from lung cancer, and a quarter from cancers of the large bowel, breast and prostate. Cancer is highly complex and is still only partly understood.

There are more than 200 different types of cancer that can occur anywhere in the body, all with different causes and symptoms and requiring different types of treatment. It is only through a greater understanding of the biology of the disease and its causes that better treatments, and better diagnosis and prevention strategies, will be developed for the future.

Stem cell research and cancer Cancer occurs when cells start to behave abnormally and the regular mechanisms that control cell growth and division are faulty. Cancer cells share many characteristics with stem cells. Consequently a greater understanding of stem cells may be vital to the eventual control of cancer. Stem cells are ‘starter cells’ that have the potential to develop into many different cell types in the body. When a stem cell divides, the resulting cells can either remain as stem cells or, under the correct conditions, become another type of cell with a more specialised function, such as a muscle cell, a red blood cell or a brain cell.

Scientists believe that stem cells may also play a direct role in the development of cancer, as some tumours are thought to develop when normal stem cells become faulty. As a stem cell’s fate is controlled by a number of molecular factors, increasing our understanding of these could help the development of new anti-cancer drugs. Our research Many patients suffering from serious diseases, including cancer, could potentially benefit from carefully regulated research on embryonic stem cells. Although Cancer Research UK does not currently use human embryos for research purposes, we recognise the potential of using embryonic stem cells for research projects which otherwise could not be accomplished.

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Cancer Research UK–funded scientists carried out pioneering research using adult stem cells. Previously, scientists believed that only embryonic stem cells are capable of giving rise to other cell types in the body. However, our scientists showed that adult stem cells in the bone marrow are capable of developing into kidney, liver and epithelial cells. Such findings raise the possibility that doctors will be able to use blood cells to repair kidney and liver damage caused by cancer and other diseases. Our scientists are also studying molecules that might be important in stem cell behaviour.

For example, a study published in 2003 used mouse embryonic stem cells to discover important information about how cancer spreads. The study found key similarities between how cancer cells spread out from a tumour to move around the body and the movement of stem cells as they form new tissues during an embryo’s development. The study identified a molecule involved in this process that could potentially be used as a drug target to help stop cancer spread. Some of our current research is focused on how stem cells in the skin decide to become specialised skin cells called keratinocytes. When this process goes wrong skin cancer can develop, therefore this work could help scientists find ways to prevent and treat skin cancer.

Future research Ongoing studies that increase our understanding of how stem cells respond to signals from their local environment and decide whether to self- renew, specialise or die could ultimately provide insights into the process by which cells become cancerous. These studies will also help scientists identify specific targets for drug development to remove ‘cancer stem cells’. Future stem cell research could also uncover ways of improving outcomes after treatment for cancer. The ultimate application in cancer may be in the ability to regenerate or replace normal tissue following surgical removal of cancerous tissue or its destruction by chemotherapy or radiotherapy.

ALZHEIMER’S SOCIETY | ASSOCIATION OF MEDICAL RESEARCH CHARITIES | BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL | BRITISH HEART FOUNDATION | CANCER RESEARCH UK | DIABETES UK | HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY | HUMAN TISSUE AUTHORITY | MEDICAL RESEARCH COUNCIL | PARKINSON’S DISEASE SOCIETY | THE ROYAL SOCIETY | SCOTTISH STEM CELL NETWORK | UK STEM CELL BANK | WELLCOME TRUST Contact Cancer Research UK P.O. Box 123 Lincoln’s Inn Fields London WC2A 3PX Tel (Supporter Services): 020 7121 6699 Tel (Switchboard): 020 7242 0200 Fax: 020 7269 3100 www.cancerresearchuk.org/ Registered charity number 1089464.

Diabetes UK is the leading UK charity for people with diabetes. With more than 170,000 members, we are one of the largest patient organisations in Europe. Our mission is to ‘improve the lives of people with diabetes and work towards a world without diabetes’. The human and health burden of diabetes is staggering, as is the economic cost. The only way to tackle this is to improve the treatment of diabetes, prevent it from developing in those at risk and, ultimately, find a cure. For this, research is essential and therefore at the heart of the organisation. Diabetes research has a distinguished history in the UK, and Diabetes UK (formerly the British Diabetic Association) has played a key role since its formation in 1934.

Over this time, with the exception of the pharmaceutical industry, Diabetes UK has been one of the major providers of funds for diabetes research in the UK. Research funded by Diabetes UK has been of the highest scientific quality with national and international impact. What is diabetes?

Diabetes is a serious condition where the amount of glucose in the blood is much higher than it should be because the body cannot use it properly. Broadly speaking, there are two major types. Type 1 diabetes occurs when the body destroys its own insulin producing cells in the pancreas leaving the body completely without insulin. It tends to appear before the age of 40 in children or young people and injection of insulin is needed from diagnosis. Type 2 diabetes develops when the body can still make some insulin, but not enough, or when the insulin that is produced does not work as well because the body is less sensitive to it.

It tends to appear in people over the age of 40 but more and more people are being diagnosed with it at earlier ages with some as young as seven. Type 2 diabetes is progressive – over time people may have to shift from managing the condition by diet and exercise and/or tablets to using a combination of diet, exercise, tablets and insulin injections to achieve control.

Diabetes – the challenge The number of people with diabetes is increasing at an alarming rate and it represents one of the biggest public health problems for the 21st century. •  Diabetes occurs in men, women, the young and old and in all races. No group is spared. •  There is no known cure for diabetes and available treatments are limited in controlling the devastating consequences of the condition. •  People with diabetes (or their carers) are responsible for the day-to-day management of their condition. •  Diabetes affects 5 per cent of the world’s population and its prevalence is doubling every generation.

•  The International Diabetes Federation estimates that in 2005 around 333 million people in the world aged 20-79 had diabetes. •  More than 2 million people in the UK have been diagnosed with diabetes. This number is predicted to reach 3 million by 2010. •  It is estimated that up to another 500,000 people in the UK have diabetes but do not know they have it. •  There are up to 345,000 people in the UK with Type 1 diabetes. This is caused by an absolute lack of the hormone insulin, resulting from loss of the body’s pancreatic islet beta cells. •  Around 2 million people have Type 2 diabetes, representing about 85 per cent of diabetes cases.

Type 2 diabetes is due to varying combinations of insulin deficiency and insulin resistance.

•  The incidence of Type 1 diabetes in children is rising at a rate of 3-4 per cent a year. We do not know why. continued overleaf...

•  The increase in Type 2 diabetes is closely linked to an ageing population and rapidly rising numbers of obese or overweight people. •  Diabetes is the leading cause of kidney failure, blindness in adults, and amputations. It can lead to impotence, can affect mental health and wellbeing, and is a major risk factor for heart disease, stroke and birth defects. •  On average, life expectancy is reduced by 15 years in people with Type 1 diabetes and by up to seven years in people with Type 2 diabetes.

In the next 10 years there will be a 25 per cent increase in the number of diabetes-related deaths. •  Diabetes has a large and growing financial impact on the NHS. The clinical supervision and care of people with diabetes is estimated to consume around 10 per cent of the NHS budget (about £25 million a day) and 10 per cent of hospital in-patient resources. The NHS spend on diabetes will rise to around 10 per cent of the NHS budget by 2011.

•  A National Service Framework outlining the standards of care that should be expected by people with diabetes has been in place since 2003 but its full implementation across the NHS has yet to be achieved. Diabetes UK research Diabetes UK is committed to funding research which has the potential to make a difference to the lives of people with diabetes in the short term (three to five years), medium term (five to seven years) and longer term (10 years and beyond). Research applications are considered for funding on the basis of their scientific merit, the potential difference the research could make to the lives of people with diabetes and value for money.

Stem cell research is a key area of interest worldwide as it offers hope to many that in the not too distant future, we may be able to offer exciting new treatments for a wide range of conditions including diabetes. Consultation exercises led by Diabetes UK have shown that, particularly on ethical issues, people with diabetes and their carers are overwhelmingly in support of stem cell research. In December 2001, Diabetes UK’s Board of Trustees agreed to support stem cell research both publicly and financially. Diabetes UK remains committed to stem cell research and to ensuring it does everything it can to maximise the opportunities for working towards novel therapies and a cure for diabetes.

ALZHEIMER’S SOCIETY | ASSOCIATION OF MEDICAL RESEARCH CHARITIES | BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL | BRITISH HEART FOUNDATION | CANCER RESEARCH UK | DIABETES UK | HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY | HUMAN TISSUE AUTHORITY | MEDICAL RESEARCH COUNCIL | PARKINSON’S DISEASE SOCIETY | THE ROYAL SOCIETY | SCOTTISH STEM CELL NETWORK | UK STEM CELL BANK | WELLCOME TRUST Contact Research team Diabetes UK 10 Parkway London NW1 7AA Tel: 020 7424 1076 Fax: 020 7424 1001 Email: research@diabetes.org.uk www.diabetes.org.uk Registered charity number 215199.

The Human Fertilisation and Embryology Authority (HFEA) regulates centres carrying out licensed fertility treatment and human embryo research throughout the UK. In stem cell research, the HFEA regulates those projects that use human embryos to create stem cell lines, scrutinising the steps from the creation of the embryo until the creation of the stem cell line. As the UK’s regulator, the HFEA’s role is to provide ethical and procedural scrutiny of the creation and handling of human embryos to maintain public confidence in the treatment and research sectors. The framework for this is set out in the Human Fertilisation and Embryology Act 1990 (HFE Act).

This states that no research may be conducted on human embryos unless it is licensed by the HFEA.

The Act was amended in 2001 to allow the use of embryos for stem cell research and consequently the HFEA has the responsibility for regulating all human embryonic stem cell research in the UK. Anyone wishing to use human embryos for stem cell research must apply to the HFEA for a licence before they carry out any work. The researchers must demonstrate to the HFEA’s satisfaction that the work proposed is legal, necessitates the use of human embryos and is a desirable use of human embryos. The current law Under the HFE Act (as amended) any research using human embryos must relate to one or more of the following purposes: •  To promote advances in the treatment of infertility •  To increase knowledge about the causes of congenital diseases •  To increase knowledge about the causes of miscarriage •  To enhance knowledge in the development of more effective contraception •  Detection of genetic or chromosomal abnormalities before implantation •  To increase knowledge about the development of embryos •  To increase knowledge about serious disease •  To enable any such knowledge to be applied in developing treatment for serious disease.

The law also explicitly prohibits some key activities •  The genetic structure of the cell must not be altered while it forms part of an embryo •  Research embryos must be destroyed on or before 14 days of development •  No embryo created or used in research may be implanted in a woman (or any animal). The authority and licence committees Decisions on research applications are made by a licence committee made up of members of the HFEA. Members bring to the HFEA a broad range of expertise, from medicine to law and religion to philosophy. The members determine HFEA policies and review treatment and research licence applications.

They are appointed by UK health ministers in accordance with the guidance from the Commissioner for Public Appointments (the ‘Nolan’ guidelines). To ensure that the HFEA has an objective and independent view, the HFE Act requires that the chair, deputy chair and at least half of the HFEA members are lay members (neither doctors nor scientists involved in human embryo research or providing infertility treatment). Applying for a research licence The HFEA has the power to grant research licences for up to three years for individual research projects. All research licence applications and renewals are evaluated by an HFEA Research Licence Committee.

The majority of researchers contact the HFEA to discuss their proposed research before they submit an application for a licence. continued overleaf...

Existing licence holders liaise directly with HFEA staff on renewals and evaluations. The HFEA is committed to processing 90 per cent of research licence applications within three months of receipt of a properly completed application form. Research ethics approval should have been sought from a properly constituted ethics committee before an application is made. An administration fee of £500 (as at March 2008) is payable for most projects. Projects involving the derivation of human embryonic stem cells or cell nuclear replacement incur an administration fee of £750 which reflects on the increased complexity and rigour required for the licensing of such projects.

Following receipt of the application and the fee, the HFEA will commission peer reviewers for the project to determine whether the application: •  Comes within the statutory requirements of the Human Fertilisation and Embryology Act. •  Requires human embryos to fulfil its aims and objectives. •  Requires the numbers and types of embryos described in the application. •  Meets the requirements of the HFEA Code of Practice. If the peer reviews are satisfactory, the HFEA initiates visits to proposed research sites. These visits are conducted by HFEA regulation staff and independent scientific inspectors.

Fuller teams may take part in the visits if the research application is of a novel or complex nature. The primary focus of these visits is to review proposed project protocols, inspect research laboratories and to meet research teams.

The application, the peer reviews and the site visit report are then examined by a Research Licence Committee. Depending on the nature of the research, the committee may also examine research papers and public comment obtained through consultation. In order for a licence to be offered, the Licence Committee has to agree that the proposals pass three tests – are they legal, are they necessary and are they desirable? If a licence is granted, the project is then inspected on a regular basis and the researchers are required to keep detailed records of how they use the embryos and the progress of their research.

Further details, including guidance on completing a research application and information about current and proposed research, can be found on the HFEA website. ALZHEIMER’S SOCIETY | ASSOCIATION OF MEDICAL RESEARCH CHARITIES | BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL | BRITISH HEART FOUNDATION | CANCER RESEARCH UK | DIABETES UK | HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY | HUMAN TISSUE AUTHORITY | MEDICAL RESEARCH COUNCIL | PARKINSON’S DISEASE SOCIETY | THE ROYAL SOCIETY | SCOTTISH STEM CELL NETWORK | UK STEM CELL BANK | WELLCOME TRUST Contact HFEA 21 Bloomsbury Street London WC1B 3HF Tel: 020 7291 8200 Email: admin@hfea.gov.uk www.hfea.gov.uk

The Human Tissue Authority (HTA) was established in 2005 to regulate the removal, storage, use and disposal of human bodies, organs and tissue for a number of Scheduled Purposes set out in the Human Tissue Act 2004 (HT Act). Informed consent, freely given, is the cornerstone of the legislation. The HTA is also a Competent Authority under the EU Tissues and Cells Directive (EUTCD), now transposed into UK law by the Human Tissue (Quality and Safety for Human Application) Regulations 2007 (the Regulations 2007). As part of our remit under the HT Act, we license the storage of tissues and cells (excluding cell lines) used for research, with certain exemptions.

Under the Regulations 2007 we also license a range of activities involving tissues and cells (including cell lines) used for human application. The removal, storage and use of tissue from living people as part of diagnosis or treatment are not part of our statutory remit.

Our strategic aim We aim to create a regulatory system for the removal, use and disposal of human tissue and organs that is clear and consistent and in which professionals, patients, families and members of the public have confidence. The HTA believes that good regulation facilitates good science which in turn leads to improved healthcare. We work closely with interested parties, including the research and stem cell communities, to develop our licensing standards, codes of practice and other advice and guidance. We adhere closely to the principles of better regulation, and work with other regulatory and funding bodies to reduce the burdens on the sectors we regulate.

By raising standards, regulation increases the confidence not only of professionals, but also the public who donate their tissue for potentially life- saving research. We believe that, if the public know there is regulation in this area, their confidence and willingness to donate will increase.

The Human Tissue Act The Human Tissue Authority (HTA) regulates the removal, storage and use of relevant material for a number of Scheduled Purposes (such as research, anatomical examination, public display, and education and training) set out in the HT Act. Relevant material is defined as material that has come from a human body and consists of, or includes, human cells (other than gametes and embryos). The HTA also licenses a number of activities under the HT Act, such as post mortem examination. The HT Act covers England, Wales and Northern Ireland. There is separate legislation in Scotland (the Human Tissue (Scotland) Act 2006) and the HTA performs certain tasks on behalf of the Scottish Government.

These include approving ethical aspects of the donation of solid organs, bone marrow and peripheral blood stem cells from living people.

Both the HT Act and HT (Scotland) Act came into force on 1 September 2006. Again, consent (referred to as ‘authorisation’ in the Scottish legislation) is the cornerstone of the legislation. Regulation of stem cells stored for research In England, Wales and Northern Ireland, the storage of relevant material for research requires a licence under the HT Act, unless it is used for an ethically- approved research project. Material created outside the human body is exempt from the HT Act’s licensing requirements, so storage of cell lines and stem cell lines for research is not licensable. Storage of the tissues and cells used to create these lines may require a licence.

If cell lines or stem cell lines are to be used for human application in the future, an HTA licence under the Regulations 2007 is needed (as described overleaf).

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The EU Tissue and Cells Directive The EU Tissues and Cells Directive (EUTCD) creates a common framework that ensures high standards of tissues and cells for human application across the EU community. Its primary aim is to ensure the quality, safety and traceability of tissue and cells used for treatment. It also aims to support the exchange of tissues and cells between member states. On 5 July 2007, the EUTCD was transposed into UK law via the Human Tissue (Quality and Safety for Human Application) Regulations 2007 (the Regulations 2007).

The HTA is one of two competent authorities in the UK (including Scotland) for implementing the directive. The other is the Human Fertilisation and Embryology Authority (HFEA), which regulates the creation and use of embryos and gametes. The use of embryos to derive stem cells must be licensed and approved by the HFEA. The Regulations 2007 require the HTA to regulate the procurement, testing, processing, storage, distribution and import and export of tissues and cells for human application.

Regulation of stem cells for human application Since 5 July 2007, human tissue or cells intended for human application must comply with all the requirements of the Regulations 2007 and HTA Directions 001/2006, 002/2007 and 004/2007. This includes stem cell lines isolated from any human source, created with the intention of being used for human application. Where an activity is already regulated by the Medicines and Healthcare products Regulatory Agency (MHRA), only the donation, procurement and testing of cells is regulated by the HTA. The Regulations 2007 make it an offence to carry out the following activities without either an HTA licence or under third party agreement with a licensed establishment on whose behalf the third party is acting on.

The activities are procurement, processing, testing, distribution and import and export in relation to tissues or cells for human application.

Any establishment storing tissues or cells (for more than 48 hours) for human application may lawfully carry out this activity only if licensed by the HTA under the Regulations 2007. Storage, unlike the activities listed above, cannot be carried out under a third party agreement. ALZHEIMER’S SOCIETY | ASSOCIATION OF MEDICAL RESEARCH CHARITIES | BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL | BRITISH HEART FOUNDATION | CANCER RESEARCH UK | DIABETES UK | HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY | HUMAN TISSUE AUTHORITY | MEDICAL RESEARCH COUNCIL | PARKINSON’S DISEASE SOCIETY | THE ROYAL SOCIETY | SCOTTISH STEM CELL NETWORK | UK STEM CELL BANK | WELLCOME TRUST Contact Human Tissue Authority Finlaison House 15–17 Furnival Street London EC4A 1AB Tel: 020 7211 3400 E-mail: enquiries@hta.gov.uk www.hta.gov.uk

The Medical Research Council supports the best scientific research to improve human health. Its work ranges from molecular level science to public health medicine and has led to pioneering discoveries in our understanding of the human body and the diseases which affect us all. For 90 years, MRC researchers have been the driving force behind a stream of remarkable advances that have transformed medicine and are benefiting people all over the world. Sir Martin Evans, known as the ‘father of stem cell research’ and supported by the MRC between the 1970s and 1990s, shared the 2007 Nobel Prize in Physiology or Medicine for his work introducing specific gene modifications into mice using embryonic stem cells.

This work was the basis for future targeted manipulation of genes and experimental mammalian genetics – everyday tools used by scientists to improve the understanding of the influence of genes on disease. Today, research at MRC centres, universities and hospitals throughout the UK extends from the laboratory to the bedside and beyond, and is building on past achievements to tackle the major health challenges of the 21st century. The MRC has a major coordinating role both nationally and internationally. It is the driving force behind the International Stem Cell Forum (ISCF), which it launched in 2003 along with eight other international funding agencies.

The MRC is also part of the UK Stem Cell Initiative and funds the UK Stem Cell Bank. It collaborates with the Biotechnology and Biological Sciences Research Council (BBSRC) and the Parkinson’s Disease Society (PDS) in the funding of fellowships in stem cell research. In 2007, the Biotechnology and Biological Sciences Research Council (BBSRC) and the MRC started the UK’s biggest ever public consultation on stem cell research, funded by the UK Government’s Sciencewise scheme. The programme aims to gain an insight into public expectations, aspirations, and concerns about this fast moving and challenging area of science, and includes a national programme of workshops and discussion meetings.

The MRC is reviewing its stem cell and regenerative medicine research strategy with an aim to develop joint strategies with the Technology Strategy Board (TSB) – the executive non-departmental public body which promotes innovation in the UK – and the National Institute for Health Research (NIHR), for academic and industry cooperation. Under the single integrated health research strategy with NIHR, the MRC will lead the stem cell area. MRC research on stem cells Diseases such as diabetes, Alzheimer’s, Parkinson’s, cancer, diabetes and heart disease are some of the most devastating conditions of our time, and are becoming an ever greater priority with an ageing population.

Stem cell therapy is emerging as a revolutionary new way to treat these. If scientists can work out how to control the growth of stem cells, the primitive cells that generate different kinds of tissue, they might eventually be able to use stem cells to provide a plentiful supply of healthy transplant material to repair any diseased or damaged tissue or organ. The MRC is funding research aimed at making this a reality. Our scientists are investigating all aspects of stem cell biology in both embryonic stem cells (ES cells), which have the ability to develop into virtually any human tissue, and adult stem cells which replace damaged or depleted cells in mature tissues.

Work on the basics of stem cells’ identity, propagation, and how they give rise to specialised cell types, will help scientists learn how to control stem cell self-renewal and differentiation in order to achieve safe, efficient, large-scale production of defined cell types. They must also develop ways of delivering stem cells and monitoring their migration within tissues and find out how to combat immune rejection. continued overleaf...

Around the UK, MRC researchers are carrying out pioneering research into embryonic stem cells, including what determines the type of cell they become and how to direct this process. They are also investigating the role of stem cells in cancer. For example, a study of identical twins, by Professor Tariq Enver at the MRC Molecular Haematology Unit and colleagues elsewhere, has for the first time confirmed the existence of cancer stem cells that cause the most common type of childhood leukaemia. MRC teams are also using stem cells to model human disease. For instance, they have used embryonic stem cells to create the first mouse model of human Down’s syndrome, which is caused by the presence of three copies of chromosome 21 instead of the normal two.

The ability of stem cells to turn into specific types of cells has led scientists to attempt to use them to repair or replace parts of the body. Stem cells may offer hope to patients with brain and central nervous system diseases and injuries. Professor Steve Dunnett and colleagues are working on developing cells for future transplantation into patients with Huntington’s and Parkinson’s diseases. They use embryonic or germ line (egg or sperm) cells or a type of foetal cell to provide reliable and renewable sources of nerve cells, with the aim of restoring brain function. At the University of Nottingham, Professor Philip Bath has discovered that bone marrow cells may be able to repair the damage done to the brain by a stroke.

Stem cells also have the potential to restore sight to people with diseases and injuries affecting their eyes. MRC-funded scientists at the University College London Institute of Ophthalmology are researching stem cell transplants to treat people with hereditary retinal disease and age-related macular degeneration – two major causes of vision problems and blindness in the UK. There is also hope for many people with bone problems, such as arthritis and osteoporosis patients, people with bone injuries and those who need joint replacement operations. MRC-funded scientists at Imperial College London have successfully grown cartilage cells from human embryonic stem cells.

Stem cells could be a valuable aid in drug development. Large numbers of a particular type of cell could be grown for use by researchers when testing new therapies. This would be especially useful for screening potential drugs for toxicity or their impact on a disease and might reduce the need for animal testing. The MRC is part of the Stem Cells for Safer Medicines Initiative, a new public-private partnership involving the Government, research councils and industry, which is encouraging the use of stem cells in early drug discovery. ALZHEIMER’S SOCIETY | ASSOCIATION OF MEDICAL RESEARCH CHARITIES | BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL | BRITISH HEART FOUNDATION | CANCER RESEARCH UK | DIABETES UK | HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY | HUMAN TISSUE AUTHORITY | MEDICAL RESEARCH COUNCIL | PARKINSON’S DISEASE SOCIETY | THE ROYAL SOCIETY | SCOTTISH STEM CELL NETWORK | UK STEM CELL BANK | WELLCOME TRUST Contact MRC 20 Park Crescent London W1B 1AL Tel: 020 7636 5422 Fax: 020 7436 6179 www.mrc.ac.uk

Parkinson’s is the second most common neurodegenerative condition in the UK, and most of us will know someone who has been affected. The Parkinson’s Disease Society (PDS) is the leading charity dedicated to supporting people living with Parkinson’s. We believe all people with Parkinson’s and their families should benefit from quality care and support regardless of where they live in the UK. We are achieving this by building a better understanding of the condition and voicing the issues of people with Parkinson’s on a national and local level. At present, there is no cure for Parkinson’s and the causes are unknown.

The Parkinson’s Disease Society is working hard to bridge this gap by stimulating innovative research into the condition. We have a challenging agenda that supports high-quality research at the forefront of the international field. To date, we have invested £35 million in pioneering science throughout the UK. Our goal is to improve the treatment and care for people with Parkinson’s and to find a cure.

What is Parkinson’s? Parkinson’s is a progressive, neurological condition that affects everyday activities, such as walking, talking and writing. It was named after the London doctor Dr James Parkinson, whose famous study An Essay on the Shaking Palsy established Parkinson’s as a recognised medical condition in 1817. Two centuries on, we now know that Parkinson’s develops when nerve cells are lost from the middle of the brain, in a region called the substantia nigra. These cells make dopamine, a chemical messenger that controls and coordinates movement. When around 80 per cent of the cells die, not enough dopamine is produced, which means the brain cannot work properly.

This is when the symptoms of Parkinson’s appear. Scientists are still trying to understand how and why dopamine-producing nerve cells die earlier than they should. Around 120,000 people in the UK have Parkinson’s and 10,000 new cases are diagnosed every year. The condition affects both young and old, and men are slightly more likely to develop Parkinson’s than women. Typically, the symptoms appear after the age of 55, although one in 20 of those diagnosed will be under 40 years old. Parkinson’s is a complicated disorder that changes over a person’s lifetime. There is a broad range of symptoms, which affects each person differently.

No two people will have the same symptoms or the same rate of progression. People may have a tremor, muscle stiffness or move slowly – these are the key characteristics of the condition. People with Parkinson’s may also experience other symptoms not related to movement, such as problems with their bladder and bowel, speech and swallowing, sleeping and memory, as well as hallucinations and depression. This has a tremendous impact on how a person thinks and feels and affects simple, everyday activities and relationships – all that we take for granted.

How can stem cells help people with Parkinson’s? Scientists are searching for a cure for Parkinson’s – a treatment that allows people to lead a normal life, free of symptoms. The symptoms and effects of Parkinson’s are currently managed with a combination of drugs, physiotherapy, occupational therapy, and speech and language therapy. Some people also have surgery such as deep brain stimulation. Unfortunately, a person’s response to anti-Parkinson’s medication can fluctuate during the course of treatment and eventually wear off. These drugs also have some unpleasant side effects and are therefore not a permanent solution.

Similarly, surgery can be helpful for some people but carries a number of potential risks. For these reasons, a huge effort is currently underway to develop new and better treatment options.

One exciting avenue is using stem cells to repair the brain. This is called cell replacement therapy. Stem cells are the building blocks of the human body – they are ‘blank’ cells that have the potential to turn into every type of cell and, therefore, make every tissue and organ. The idea behind healing the brain is simple - we know that the symptoms of Parkinson’s appear when the supply of dopamine falls in the brain. Therefore, replacing the dead dopamine-producing nerve cells with healthy cells would raise dopamine levels. The cells in the different parts of the brain would then be able to communicate, and this would relieve the symptoms.

Scientists are working hard on two cell replacement strategies: continued overleaf...

•  Using stem cells to grow new nerve cells in the laboratory, and then transplanting them into a patient’s brain. •  Encouraging stem cells already in patients’ brains to move towards the part damaged in Parkinson’s, and then triggering them to make new nerve cells. Over the last 20 years, researchers have been investigating foetal tissue transplants as a possible treatment for Parkinson’s. In research that is strictly regulated by the Human Fertilisation and Embryology Authority (HFEA), tissue that contains stem cells is taken from the mid-brain of human foetuses and implanted into the brains of patients with Parkinson’s.

Up to now, around 400 people worldwide have taken part in these experimental trials. Some people have reported improvements in their Parkinson’s symptoms. Scientists do not understand why foetal tissue transplants appear to work in some people but fail in others. They think that it is better suited for younger people (under 60 years old) with milder Parkinson’s. Also, researchers now believe that the answer may not lie with transplanting foetal tissue but growing new nerve cells from stem cells in the laboratory. For that reason, scientists are now looking at other sources of stem cells from embryo, foetal and adult tissues.

To develop a successful treatment, a lot more research needs to be done to optimise and standardise cell transplantations. For example: • What the best source of stem cells? •  How to grow large, reliable quantities of cells that are appropriate for use. •  How to change a stem cell into the right type of nerve cell. •  How to be certain that stem cells are put into and stay in the right part of the brain.

•  How to stop transplanted stem cells from dying or growing uncontrollably into tumours. •  How to be sure that transplanted cells form the right connections in the brain. Unlike cell transplantations, scientists are still debating the second of these strategies - whether the brain has built-in machinery that can repair the damage in Parkinson’s. We know the adult brain has limited sites that house stem cells and generate new nerve cells, albeit at a very slow pace. The idea is to round up these stem cells into the region of the brain affected by Parkinson’s and trigger them to make dopamine-producing nerve cells at a much faster speed.

Initial animal studies appear to suggest that it is possible to recruit stem cells using a combination of growth factors. However, the next challenge is to turn the stem cells into dopamine-producing nerve cells. To achieve this, scientists are experimenting with different recipes of several growth factors, drugs and proteins that stick to genes. The Parkinson’s Disease Society and stem cell research Stem cell therapy is still in its infancy and we know that there are many hurdles to overcome to ensure that researchers can move as swiftly as possible towards a cure. We have been campaigning strongly ALZHEIMER’S SOCIETY | ASSOCIATION OF MEDICAL RESEARCH CHARITIES | BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL | BRITISH HEART FOUNDATION | CANCER RESEARCH UK | DIABETES UK | HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY | HUMAN TISSUE AUTHORITY | MEDICAL RESEARCH COUNCIL | PARKINSON’S DISEASE SOCIETY | THE ROYAL SOCIETY | SCOTTISH STEM CELL NETWORK | UK STEM CELL BANK | WELLCOME TRUST Contact Parkinson’s Disease Society 215 Vauxhall Bridge Road London SW1V 1EJ Tel: 020 7931 8080 Fax: 020 7233 9908 Email: research@parkinsons.org.uk Freephone Helpline: 0808 800 0303 www.parkinsons.org.uk Charity registered in England and Wales number 258197 and in Scotland number SCO37554.

to make sure that all avenues of stem cell research, including use of embryonic stem cells, cell nuclear transfer and cytoplasmic hybrid cells, remain open within the rigorous ethical and regulatory framework that exists within the UK. Since 2001, the society has invested more than £1.6 million in 13 different stem cell research projects throughout UK. We also work closely with other organisations, such as the Medical Research Council (MRC), to develop joint research programmes. Our scientists are investigating embryonic, foetal and adult stem cells. They are working to understand the basics of stem cell biology, how they turn into nerve cells and can be used as a treatment for people with Parkinson’s.

More details on our stem cell projects can be found at www.parkinsons.org.uk/research.

The Royal Society is an independent academy promoting the natural and applied sciences. Founded in 1660, the society has three roles, as the UK academy of science, as a learned society, and as a funding agency. The Royal Society’s position on stem cell and embryo research The Royal Society regularly evaluates and assesses scientific developments in the area of stem cell and embryo research through its independent stem cell group. Background The Royal Society believes that stem cell derived therapies could help to improve or save the lives of many patients worldwide, including those suffering from serious injury or disease.

Therapies may be developed using adult, foetal or embryonic stem cells. It is important that avenues of stem cell research, and stem cell-related technologies, are not closed until they have been fully investigated and proven not to be viable. The Royal Society strongly supports the translation of basic stem cell research into clinical practice when the evidence supports efficacy and safety of clinical use. It is important to be realistic concerning the length of time it may take to develop stem cell research into effective treatments. Human admixed embryos Throughout the development and passage of the Human Fertilisation and Embryology Bill, the Royal Society has emphasised the need for scientific studies using interspecies embryos (now referred to as Human Admixed Embryos).

The Society has given its backing to the creation of human admixed embryos because it feels that the scientific evidence now justifies the development of such techniques. These techniques will enable scientists to produce stem cells without needing to use human eggs, which are in extremely short supply. In addition, this research will facilitate further understanding of basic stem cell biology, for example, how stem cells become different cells in the body, and to understand the genetic causes of disease. These techniques will also enable researchers to determine the importance of communication between the cell nucleus and other components of the cell, including mitochondria (the essential ‘powerhouses’ of the cell).

Legislation and regulation The UK has an international reputation as a leader in stem cell science. Its position as an innovator and world leader in this area can be attributed, at least in part, to the legislative structure and regulatory process which have overseen embryo and stem cell research in this country. The role of the regulator is also crucial to foster public confidence in stem cell and embryo research – its assessment of individual research projects ensures that research in this area is carried out responsibly. Stem cell research is a rapidly advancing field. The UK’s legislative and regulatory framework for embryo research, implemented by the Human Fertilisation and Embryology Authority (HFEA), must continue to ensure that new stem cell techniques are justified both ethically and by scientific need.

The UK must support the safe, successful and rapid translation of basic stem cell research into clinical practice, when the time is right, to achieve the ultimate goal of using stem cells therapeutically. The Royal Society has closely followed the development and progress of the Human Fertilisation and Embryology Bill. We have spoken out in areas where the Society is best placed to provide balanced and sound scientific advice – for example concerning the creation of human admixed embryos for research. We consider commenting on the detailed regulatory requirements for the development of therapeutic treatments to be outside of our remit.

However, we see a benefit in ‘future-proofing’ legislation to allow for stem cells to be used therapeutically, providing that any new advances are fully supported by scientific evidence to ensure they are a safe and appropriate next step. contact details overleaf...

ALZHEIMER’S SOCIETY | ASSOCIATION OF MEDICAL RESEARCH CHARITIES | BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL | BRITISH HEART FOUNDATION | CANCER RESEARCH UK | DIABETES UK | HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY | HUMAN TISSUE AUTHORITY | MEDICAL RESEARCH COUNCIL | PARKINSON’S DISEASE SOCIETY | THE ROYAL SOCIETY | SCOTTISH STEM CELL NETWORK | UK STEM CELL BANK | WELLCOME TRUST Contact The Royal Society 6-9 Carlton House Terrace London SW1Y 5AG Tel: 020 7451 2500 Fax: 020 7930 2170 www.royalsociety.org Registered charity number 207043.

The Scottish Stem Cell Network (SSCN) was launched in 2003 with funding from Scottish Enterprise Edinburgh and Lothian (SEEL), to bring together scientists, clinicians and industry to improve the rate at which stem cell laboratory research in Scotland could be translated into therapeutic benefits for patients and tools for drug discovery.

The SSCN was established to support the interdisciplinary exchanges needed to translate excellent basic research into clinical and economic benefit, and operates with the following mission statement to: •  Develop and consolidate Scotland’s reputation in stem cell biology. •  Create an environment for exchanges of scientific and clinical ideas. •  Foster collaborative links between research scientists and clinicians in the field.

•  Engage the private sector in the development of stem cell technology. •  Lobby government and regulatory authorities in support of the development of the technology. •  Develop national and international links with other centres of excellence. •  Realise the benefits to patients  from effective treatment of degenerative diseases. The SSCN has worked with the entire Scottish stem cell community, which exists within a powerful life science research and technology base including more than 500 organisations and more than 26,000 employees. Scottish universities have become established centres of excellence in medicine, genetics and reprogramming technology, and the country also hosts a significant commercial presence in research and development, including companies such as Cellartis, CXR Biosciences, Scottish BioMedical, Roslin Cells and Geron.

Many Scottish organisations hold Human Fertilisation and Embryology Authority (HFEA) licences issued by the UK to conduct human embryonic stem cell derivation and are working directly with the regulatory authorities to define clinically acceptable processes and facilities for stem cell production. The SSCN works with all of these groups and organisations to create a forum for discussion and learning, critical for the development of the technology. A series of workshops and training events are held every year, covering topics such as the management of intellectual property in the field to new EU legislation on clinical trials.

We also encourage our membership to meet regularly to discuss specific disease areas, such as diabetes, bone and muscle degeneration and heart disease, in the context of both basic science and clinical and commercial development.

A major role of the SSCN has been to engage with the general public and inform open debate at home and abroad. Working with the Scottish Executive, the SSCN sees its role as providing an informed and educated general public to support the full development of the technology in Scotland. Events such as Edinburgh International Science Festival provide an ideal platform from which to address the public, and SSCN have held debates at that event and will continue to do so in the future. In 2006, the SSCN received a £1.8 million grant from Scottish Enterprise to consolidate and expand its activities over a ten year operational period.

The SSCN has formed a non-profit company, with a board of directors to oversee its governance and an Executive office to deliver its objectives. The Executive office is now located within the Royal College of Surgeons in Edinburgh.

contact details overleaf...

ALZHEIMER’S SOCIETY | ASSOCIATION OF MEDICAL RESEARCH CHARITIES | BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL | BRITISH HEART FOUNDATION | CANCER RESEARCH UK | DIABETES UK | HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY | HUMAN TISSUE AUTHORITY | MEDICAL RESEARCH COUNCIL | PARKINSON’S DISEASE SOCIETY | THE ROYAL SOCIETY | SCOTTISH STEM CELL NETWORK | UK STEM CELL BANK | WELLCOME TRUST Contact Scottish Stem Cell Network 15 Hill Place Edinburgh EH8 9DS Tel: 0131 527 3440 Fax: 0131 527 3441 www.sscn.co.uk

The UK Stem Cell Bank was established to help realise the potential of stem cells in cell therapy and will provide a vital resource to support and advance research.

Although cell banks already exist for many other types of cells such as bone marrow and umbilical cord blood, this initiative, with the full backing of the UK Government, is the world’s first stem cell bank of its type. With an international reputation, it reflects the UK’s leading position in stem cell research. The Medical Research Council (MRC) and the Biotechnology and Biological Sciences Research Council (BBSRC) provide the funding for the bank. Since 2002, the bank has been hosted by the National Institute for Biological Standards and Control (NIBSC), a publicly-funded organisation that works within European and international networks to assure the quality and safety of biological medicines.

The bank provides a repository for human stem cell lines derived from adult, foetal and embryonic tissues and operates under appropriate and accredited quality systems to support the development of research grade and clinical grade stem cell lines. It is open to academic and company researchers in the UK and abroad. Staffed by personnel trained to appropriate technical and quality standards, the bank ensures that cell lines which could ultimately provide the basis for clinical treatment are prepared under Good Manufacturing Practice (GMP), subjected to appropriate safety testing and subsequently handled and stored under quality-controlled conditions.

Not only providing high-quality starting materials for the development of stem cell therapy, the bank provides a centralised resource for researchers and reduces the requirement for surplus embryos for the development of stem cell lines by individual research groups. The first human stem cell lines were approved for banking by the Steering Committee in 2004 and the bank is now preparing stocks of 63 human stem cell lines from the UK, Australia, Sweden, India and the USA.

The bank operates in accordance with strict principles of governance laid down by a high level steering committee, and is administered by a local management committee, which includes clinicians, scientists and lay members. It was accredited as a tissue bank for provision of cells for therapy in 2004 by the Medicines and Healthcare products Regulatory Agency under the Department of Health Code of Practice for Tissue Banks and currently holds a license issued by the Human Tissues Authority. contact details overleaf... UK StemCellBank

ALZHEIMER’S SOCIETY | ASSOCIATION OF MEDICAL RESEARCH CHARITIES | BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL | BRITISH HEART FOUNDATION | CANCER RESEARCH UK | DIABETES UK | HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY | HUMAN TISSUE AUTHORITY | MEDICAL RESEARCH COUNCIL | PARKINSON’S DISEASE SOCIETY | THE ROYAL SOCIETY | SCOTTISH STEM CELL NETWORK | UK STEM CELL BANK | WELLCOME TRUST Contact UK Stem Cell Bank National Institute for Biological Standards and Control Blanche Lane South Mimms Potters Bar Hertfordshire EN6 3QG Tel: 01707 641500 Fax: 01707 641578 Email: enquiries@ukstemcellbank.org.uk www.ukstemcellbank.org.uk

The Wellcome Trust is the largest and most diverse biomedical research charity in the world, spending over £650 million every year both in the UK and internationally to support and promote research with the aim of improving the health of humans and animals. At any one time, the Trust funds more than 3,000 principal investigators and their research teams in more than 40 different countries, including both basic biomedical research to deepen our understanding of health and disease, and clinical research to generate new therapies.

The Trust seeks to ensure the research it funds is used responsibly for the common good.

It therefore supports research into the wider ethical and social implications of scientific research, and funds activities that engage the public in science and its related issues. The Wellcome Trust and stem cell research The Wellcome Trust believes that stem cell research offers great potential for the development of new treatments for a wide range of diseases, and has also contributed to a greater understanding of fundamental developmental biology. However, an enormous amount of research is still required to understand how all types of stem cells function, how they can be reliably induced to differentiate into the various lineages and to find out which types of cells may offer the greatest promise for the development of new therapies.

The Trust is therefore willing to fund ethical and accountable research into all types of stem cells.

The Wellcome Trust has commented on a number of proposals in this area. These include: •  The development of the UK Stem Cell Bank • The UK Stem Cell Initiative •  The Department of Health’s (DH) ‘Review of the Human Fertilisation and Embryology Act’, August 2005 •  The DH’s request for comments on the House of Commons Science & Technology Select Committee’s report on ‘Human Reproductive Technologies and the Law’ •  The Report from the Joint Committee on the Human Tissue and Embryos (Draft) Bill.

Wellcome Trust funding for stem cell research The Wellcome Trust funds both human and animal stem cell research through a variety of grants for large programmes, fellowships, PhD studentships and technology transfer initiatives.

These include: Wellcome Trust Centre for Stem Cell Research. The world-class Wellcome Trust Centre for Stem Cell Research is based at the University of Cambridge, led by Professor Austin Smith and Professor Fiona Watt, with over £12 million funding from the Trust. The centre focuses on the genetic and biochemical mechanisms that control how stem cells develop into particular types of cell. This will provide foundations for engineering of stem cells to model particular diseases, drug discovery and regenerative medicine. Type 1 diabetes Professor Kevin Docherty and colleagues at the University of Aberdeen are attempting to generate human embryonic stem cells that can be used to replace the insulin-secreting cell ‘islets’ in the pancreas of patients suffering from type 1 diabetes.

This grant was jointly funded with the Juvenile Diabetes Research Foundation. Manipulating embryonic stem cells Dr Sally Lowell, University of Edinburgh, is exploring whether it is possible to manipulate communication between embryonic stem cells and determine which type of cell they become. This will provide insights into tissue regeneration as well as how to generate useful cell types in a dish, which could be transplanted to repair damaged tissues. continued overleaf...

Restoring vision Attempts at stem cell transplantation to restore vision in diseased retinas have so far failed, with brain and retina derived stem cells showing little evidence of integrating into their new environment. Dr Rachael Pearson, University College London, is examining what factors prevent transplanted cells from connecting up and how best to maximise transplantation. Tissue engineering of teeth Odontis Ltd, a spin-out company from King’s College London, is developing technology to enable patients to grow natural replacement teeth by implanting human stem cells. Benefits include less surgical trauma on implantation, the psychological advantage of having one’s own teeth, and a natural appearance and texture.

Bioethics The Trust recognises that stem cell research raises a number of complex social and ethical issues and funds a range of activities to explore and debate these questions through its Biomedical Ethics Programme. These include: •  Dr Helen Busby from Nottingham University, who is interviewing parents about their views and experiences of cord blood stem cell banking in the UK. •  Professor Erica Haimes from Newcastle University, who is investigating how the views and values of those IVF couples who agree to donate embryos for research and those who refuse to donate embryos differ on embryo experimentation and stem cell therapies.

Public engagement The Wellcome Trust encourages scientists to engage with the public, funding a number of activities and initiatives. These have included ‘Playing God’, in which Suzanne Lee of All Change Arts brought together scientists, medical ethicists and young people to create artworks and performances combining dance, digital images, sound and text. The project explored topical and controversial themes including stem cell research and gene therapy. Further information Funding opportunities for stem cell research •  Biomedical Science Grants www.wellcome.ac.uk/funding/ biomedicalscience •  Biomedical Ethics Awards www.wellcome.ac.uk/biomedicalethics •  History of Medicine Grants www.wellcome.ac.uk/hom ALZHEIMER’S SOCIETY | ASSOCIATION OF MEDICAL RESEARCH CHARITIES | BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL | BRITISH HEART FOUNDATION | CANCER RESEARCH UK | DIABETES UK | HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY | HUMAN TISSUE AUTHORITY | MEDICAL RESEARCH COUNCIL | PARKINSON’S DISEASE SOCIETY | THE ROYAL SOCIETY | SCOTTISH STEM CELL NETWORK | UK STEM CELL BANK | WELLCOME TRUST Contact Wellcome Trust 215 Euston Road London NW1 2BE Tel: 020 7611 8888 Fax: 020 7611 8545 Email: contact@wellcome.ac.uk www.wellcome.ac.uk The Wellcome Trust is a charity registered in England, no.

210183. Its sole Trustee is The Wellcome Trust Limited, a company registered in England, no. 2711000, whose registered office is 215 Euston Road, London NW1 2BE.

•  Public Engagement www.wellcome.ac.uk/engagingscience Other links •  Wellcome Trust policy on stem cell research http://www.wellcome.ac.uk/About-us/ Policy/Policy-and-position-statements/ WTX028577.htm •  Wellcome Science articles on stem cells and cloning http://www.wellcome.ac.uk/News/ News-archive/Browse-by-subject/ Topic/Stem-cells-and-cloning/

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