I'm sending a section where I focussed on Beta cell replacement/transplantation and Xenotransplantation which involves animals. I had already explained both procedures so this was my analysis section but I did also look at other treatments🙂Enjoy! Hopefully there have been updates since but please let me know if I can send you anything else I found
Treatments still requiring considerable development
β-cell replacement/transplantation
One of the treatment options currently being explored is the replacement of the β-cells in the pancreas which have been destroyed by T1D.
To create genetically engineered β-cells scientists must modify an existing cell in such a way that it gains the ability to sense glucose levels and produce and then secrete insulin accordingly when required. One type of cell which is a likely candidate for modification is a hepatocyte as many of its cellular process are common to those found in β-cells (N.Petrovsky, 2002). Hepatocytes make up 80% of the mass of the liver, and unlike β-cells they are readily available. Hepatocytes also contain lots of rough and smooth endoplasmic reticulum for the synthesis of proteins and lipids and have many stacks of Golgi membranes (Bowen, 2017) which are involved in the storing, processing and packing of proteins and lipids. Since insulin is a hormone made from protein, it may be possible that, with some modification, hepatocytes could be converted into insulin producing cells for someone with T1D. The only problem would be creating a suitable glucose sensing mechanism within these cells so that they would be able to regulate the amount of insulin released. (N.Petrovsky, 2002)
A different approach has been explored by a collaboration between German and Spanish University departments who in 2015 evaluated the potential of blood monocyte adult stem cells to treat Diabetes Mellitus and end stage liver diseases by modifying the monocytes into cells similar to pancreatic islet and hepatocyte like cells respectively (M. Ruhnke, 2005). Monocyte cells are a specific type of white blood cell which are produced in the bone marrow; these cells then pass through the blood stream making up approximately 1 to 10% of the white blood cells in the circulatory system (MD, Copyrighted 2017). Once in the blood stream, monocytes migrate to the liver, spleen, lungs and bone marrow tissue where they mature into macrophages (MD, Copyrighted 2017), white blood cells which destroy harmful bacteria (José Ignacio Saldana, Accessed 2017). The human monocyte cells in this study were stimulated with several hormones and growth mediums until they began to show traits of islets and hepatocytes (mentioned in the study above) and then were left to replicate. The new hepatocyte cells were xenotransplanted into diabetic mice with end stage liver disease and were successful in replicating the role of any original hepatocyte cell. (M. Ruhnke, 2005) The new islet cells were also highly successful when xenotransplanted into diabetic mice being treated with immunosuppressant drugs; the modified cells reliably secreted insulin according to blood glucose levels and normalized these levels in the blood. (M. Ruhnke, 2005)
If industry were able to highly specialise these techniques at mass production, whole tissues and organs could be regenerated for patients, thus cutting down the numbers of patients waiting on transplant lists (M. Ruhnke, 2005). The only drawbacks with this technique is that organs will of course take time to grow and mature until they become suitable for transplantation; growing organs in itself could present a lot more difficulties and require new techniques as scientists are still on trials with mice. When growing organs, scientists would also have to work by standards set by the Human Tissue Act 2004 which will be covered in the next section, however the stem cell research would not apply to the Human Fertilisation & Embryology Act 1990 (as amended) for reasons which will also be covered in the following section.
Xenotransplantation
Studies in Japan have shown promising progress with xenotransplantation and in 2013 Japanese scientists stated that a human organ grown in an animal could “bring relief to millions with diabetes within twelve months” and become a realistic option in “as little as five years” (Weller, 2013). Unfortunately it does not seem this was a wholly accurate statement as we are now in 2017 and T1D is still very much a current and rising world-wide problem. The hybrid embryonic blend of human stem cells and host animal DNA is known as a chimeric embryo (Weller, 2013). The technique for taking human stem cells and implanting them in the embryo of a pig and then transferring this embryo to the womb of a pig has already been tested on rats and mice and is very well established (Weller, 2013). However one of the problems the Japanese scientists encountered is that Japanese law only allows embryonic cell tests in laboratory conditions for a maximum of 14 days and the implantation of any material into the womb of an animal is still prohibited (Weller, 2013).
Difficulties in using animals for scientific purposes arise from moral and ethical arguments. In the UK, The Animals (Scientific Procedures) Act 1986 protects “all living vertebrae other than man and any living cephalopod” and exists to regulate procedures carried out on animals for “scientific research and testing” as well as the “breeding and supply of certain species of animals for use in regulated procedures” and “the breeding of animals for the use of their organs or tissues in procedures” (Office, 2016). However we must also consider the implications of incorporating human DNA into that of animals’. One of the things regulated by The Human Fertilisation and Embryology Act 1990 (as amended) is the “creation and use of human admixed embryos (human/animal hybrid embryos)” (Office, 2016). The October 2009 amendments allowed the creation of “human/animal hybrid embryos for the use in research, where the human DNA would be dominant”, but also prohibited “the placing of such embryos in either a human or an animal”, (Office, 2016) similarly to Japanese law. Finally, the use of xenografts is also implicated in the Human Tissue Act 2004 as the regulating law for “the storage and use of body parts, organs and tissue for scheduled purposes” and “material other than gametes which consists of or includes human cells”. (Office, 2016)
In terms of The Animals (Scientific Procedures) Act 1986, it is possible to gain a licence for breeding animals for the use of their organs under regulations from the UK government published in February 2016 (“Guidance on the use of Human Material in Animals”), section b)i) “avoidance, prevention, diagnosis or treatment of a disease” (Office, 2016). Although it is currently unclear as to where the stem cells would be sourced from, there are several options to explore such as the monocytes and hepatocytes in the studies previously mentioned, but also embryonic stem cells. The Human Fertilisation & Embryology Act 1990 (as amended) states that “embryos or human admixed embryos cannot be kept or used after the appearance of the primitive streak or for longer than 14 days” , the “primitive streak” being a vital part in the development of an embryo where the cells begin to differentiate (Tremblay, 2010). Interestingly there is no licensing structure for the human stem cells and the rules of the Human Fertilisation & Embryology Act 1990 (as amended) do not apply once stem cells are extracted from an embryo (Office, 2016). Similarly to The Animals (Scientific Procedures) Act 1986, Human Tissue Act 2004 does deem the use of xenotransplantation “technically feasible” under Category 1: “to test the development and function of the cells and their possible problems before studies are carried out in humans” (Office, 2016). Despite there being several opportunities in the system allowing xenotransplantation, there are several bodies against the use of animals in science altogether.
Animal charity Peta UK actively promote that animals “are not ours to wear, experiment on, use for entertainment or abuse in any other way” (UK, Copyrighted 2017) and class any form of medical experimentation as cruelty. In 2004 a survey funded by the medical charity Wellcome Trust showed that when presented with nine options to overcome the shortage of kidney donors in the UK, the most disapproved of by the public was that of “genetically modifying animals so that their organs could be implanted into humans without being rejected by their immune systems” (Sample, 2004) i.e. xenotransplantation. This criticism by the general public is mostly attributed to the concern of cross species transmission of disease from transplanted organs and the idea that breeding animals on “organ farms” is considered unethical (Sample, 2004), however it could also be attributed by misinformation and misrepresentations of popular science. This survey could reflect the negative stigmatism around animals in science created by such misinformation and misrepresentations. In short, whilst it is possible to agree with animal rights and defend them, it is also possible to appreciate that there is a distinct difference between inflicting chemical burns upon an animal to test cosmetics compared to breeding animals for organs but treating them well whilst they are living. It would be interesting to see how the public opinion may change in the future if there was more transparency encouraged between manufacturing laboratories and customers but this is currently beyond the scope of this dissertation.
Regardless of opinions in 2004, the 2015 annual report from the Animals In Science Regulation Unit recognised that “the need for clearer guidance on the use of animals containing human material was becoming a pressing matter” (Knapton, 2016). In January 2016 The Home Office ruled that human-animal chimeras will be allowed if the “benefits outweigh the risks”, and published the first guidance on the use of animal human chimeras (Knapton, 2016) which has been referenced in this dissertation (Office, 2016). The risks mentioned in this article include animals taking on human traits behavioral traits or intelligence or inflicting pain on animals (Knapton, 2016) but could also be extended to compatibility between animal and human organs and cross species disease transmission which will be covered within the next section.
The 2016 guidance was published in hope that the new regulations would help supply the desperate demand for hearts, livers and kidneys in the UK. The techniques used to grow human organs in animals is not unfamiliar; “dozens” of pigs and sheep in the USA have already been implanted with mixed DNA embryos, 20 of which were implanted in labs at the Salk Institute and the University of Minnesota over 2015 (Knapton, 2016). Scientists have also been able to manipulate mice, breeding them to have a human immune system (Knapton, 2016). In terms of transplanting organs, pigs would be the most favorable choice as their organs are already very similar to ours and pig heart valves are already used in human heart surgery in the UK (Pick, 2007). The main concern over the use of pigs was the possible spreading of retroviruses, incurable viruses which use the hosts DNA to replicate themselves (Clugston, 2014). A well-known example of a retrovirus in the human population is the HIV virus; this virus permanently damages the immune system of the host leaving them prone to infections and serious conditions such as cancer but can be treated with a daily dose of prescription drugs (Trust, Copyrighted 2017)
However, an article published online in August 2017 by the Independent newspaper declared that scientists had managed to overcome one of the main problems preventing xenotransplantation by “removing threatening viruses from the animals’ DNA” (Griffin, 2017). These scientists used gene editing techniques to remove a section of the pig’s DNA, meaning that these pigs would then be unable to spread retroviruses on to human patients (Griffin, 2017). By removing one the main obstacles which was once thought of as impossible in the science world, it has been proved that technology is quickly evolving. It is possible that the public’s attitude will also change and become more accepting as new treatments become available; for example when organ transplants were first introduced in the 1960’s and 1970’s the public generally opposed the idea until their effectiveness was statistically proven over time (Griffin, 2017).
The prospect of xenotransplantation has been described as holding “great promise” as a solution to the shortage of organ donors and a major turning point for research into retroviruses such as the HIV virus previously mentioned (Griffin, 2017). Unfortunately, despite the removal of a major barrier preventing xenotransplantation, this procedure is not yet possible due to the ethical concerns previously mentioned and possible compatibility issues between human and pig organs (Griffin, 2017).
As a leading diabetes charity in Britain, Diabetes UK asserts that “many people with diabetes would not be leading the lives they are today if the major advances in understanding and treating diabetes had not been made through research, some of which has involved the use of animals” (UK, 2016); without fully condoning animal research, Diabetes UK claims to “support the principle of using animals in science when it is necessary” (UK, 2016). Any research funded by Diabetes UK must follow the “Three R’s”, fundamental values all of which are enforced by the Home Office. The first of the three “R”’s is “Replace”; non animal alternatives must be used as much as possible (UK, 2016). The second “R” stands for “Reduce”; the numbers of animals used in experiments must be kept to a minimum (UK, 2016). The final “R” is “Refine”; the care and attention of all animals must be maximized (UK, 2016). Any experiment using animals must conform to strict criteria, however a member of the public is still able to adopt a research a project or contact the charity if they wish to fund research projects not involving animals (UK, 2016).
In the interview I conducted with Mr. Anthony J Clarkson as previously mentioned (The Assistant Director of Organ Donation and Nursing for NHS Blood and Transplant) Mr. Clarkson stated that, although we are “quite far away” from xenotransplantation, it should be given “serious consideration” as is it likely that the demand for organs will increase in the future and that clinicians are “not going to be able to get [the organs] all from humans” (Clarkson, 2017). My second question for Mr. Clarkson was “Is there was any prospect of the NHS backing xenotransplantation should it become an effective treatment?” to which Mr. Clarkson replied “if the costs and the benefits stacked up” then it is likely that the NHS “probably would” support xenotransplantation (Clarkson, 2017). Mr. Clarkson also pointed out the expenses of kidney dialysis, and stated that if “patients were able to have their transplant, continue to work, continue to contribute to society, pay taxes and so on” he could “not see any reason” for the NHS to not financially cover xenotransplantation should it become a successful treatment (Clarkson, 2017).
I can post the relevant paragraphs here or I can send you more of my project directly?