Your cells die every day. Don’t worry, your body is protecting itself. In a process known as apoptosis or programmed cell death, cells that are no longer needed commit suicide. Some cells are only required for a short time, they maybe infected by a virus or develop harmful cancerous mutations. Cell death is also an essential part of development from an embryo. For example mouse paws begin as spade-like structures and only form the individual digits as the cells in between die . During apoptosis the cells fragment into smaller apoptotic bodies, and their cell surface is flipped open to display lipid molecules called phosphatidylserines, which act as an “eat me” signal to recruit cells called macrophages to engulf them, before their contents spill out and damage the surrounding tissue. This is a process known as efferocytosis.
However cell death is not always so orderly. Some cells suffer premature death known as necrosis, where they burst open for various reasons such as infection, physical trauma or extreme temperatures. However as the cell’s contents are released into the open, an inflammatory response is triggered, so the macrophages sent to engulf these cells release substances that can damage the surrounding tissue, resulting in a build-up of dead cells.
It is this damaging chain of events that often occurs in atherosclerosis; the build-up of fatty plaques which can block arteries or trigger blood clots leading to heart attacks, strokes or tissue death, known as ischaemia. As fatty lipid molecules (primarily LDL or ‘bad’ cholesterol) build up in arteries, they act like damage signals. Macrophages recognise these damage signals as if it is phosphatidylserine, and engulf the lipids to become what is known as a foam cell; a cell full of lipid. A healthy macrophage can repackage the LDL into larger HDL cholesterol, which is released back into the bloodstream to be excreted by the liver. The foam cell can also leave the atherosclerotic plaque to be disposed of via lymphatic vessels, thus shrinking the plaque.
However, foam cells can be overwhelmed by engulfing excess cholesterol, increasing harmful inflammatory signals, stress and apoptosis. But all is not lost here. If other macrophages clear the dying foam cells, less harm will be done. The problem is the increased inflammation renders efferocytosis defective, resulting in a process called secondary necrosis. Here apoptotic bodies swell and burst open, as they haven’t been cleared in time. As a result, a large amount of cell debris builds up inside the atherosclerotic plaque, creating what is referred to as a necrotic core. The core is pro-thrombotic when it is exposed to clotting factors in the bloodstream.
Re-organising the world's largest public health service could not only damage healthcare provision but also medical innovation
In March 2012, the Conservative and Liberal Democrat coalition government (also cynically known as the Con-Demned coalition) passed the Health and Social Care Act through parliament. The Act permits radical re-organisation of England’s world-renowned National Health Service (NHS). The scale of re-organisation, perhaps a misnomer for extensive privatisation, has raised serious concerns about the level of healthcare that will remain freely available to taxpayers. One concern that has not been discussed in great detail is how NHS privatisation will affect the future of medicine i.e. training future doctors and advancing medical innovation.
The Labour party founded the NHS in 1948, pledging to deliver high quality healthcare to all citizens regardless of wealth, and funded entirely by taxpayers . The NHS has since expanded into the largest publicly funded health service in the world featuring world-renowned hospitals, and allowing patients to benefit from various health services they could not otherwise afford, ranging from dentists to open-heart surgery. As a result, the NHS is most beloved in the UK with consistently high levels of satisfaction expressed by patients. The majority of today’s population was born with the aid of NHS services, and many rely on state-funded healthcare during their lifetime. The UK’s life expectancy has also continued to rise since the NHS was founded. The UK was recently rated as having the best health service amongst 12 developed countries, including the US, Australia and Germany . A vibrant health organisation placing skilled health professionals and scientists under one roof has fostered numerous medical discoveries, revolutionising healthcare not only within the NHS, but throughout the world. Examples include: the link between smoking and lung cancer, the UK’s first ever heart transplant, and the world’s first ‘test tube’ baby born as a result of in vitro fertilisation (IVF) .
So how will the re-organisation permitted by the Health and Social Act affect the ability of the NHS to deliver medical innovation? Squeezing of the NHS budget and increasing staff workloads in recent years already prompted a large migration of doctors to countries like Australia, in the hunt for reasonable salaries and a more manageable work-life balance. The loss of such valuable talent has harmed medical training and clinical research in the NHS. The transfer of services and facilities from the state to the private sector inevitably means profit is valued more than patient welfare. As a result we have already witnessed a multitude of hospital closures and staff redundancies, and this will aggravate existing problems. Unite the Union argues that the private sector may ‘cherry-pick’ more profitable services and surgical procedures causing a loss of low-demand but still vital services for some patients, and further opportunities to train junior doctors and medical students .
Most hospitals collaborate with academic research laboratories providing patient samples for research experiments. Hospital mergers and closures will drastically cut the number of collaborations and the pool of samples available for such research, thus limiting the rate at which progress can be made towards the next medical therapy. The private sector may even decide to charge for medical training and access to patient samples and clinical research facilities, elevating costs for medical students and researchers (generally funded by the taxpayer or charities) respectively.
On the contrary, the government states that the private sector will play a greater role in medical research through an increase in academic-industry collaborations . Such a move would be advantageous in obtaining funding for medical research, as private companies tend to offer more funding than research councils and charities. But naturally private investors will expect something in return. We are well aware that pharmaceutical companies have failed to invest in research on diseases plaguing developing counties, due to the lack of financial return . Pharmaceutical companies often spend millions of pounds investing in the development of one drug, aiming to earn the money back from sales of the drug, which developing states cannot afford to pay for. Hence a similar trend could occur in the UK, where pharmaceutical and medical device companies may refuse to invest in research to develop treatments for rare diseases due to low prospects in profiting, or they may develop treatments but charge colossal amounts unaffordable for patients. With strengthening of academic-industry collaborations also comes the probability that more state and charity funding of academic research will result in discoveries that subsequently rely on industry to produce the treatment, and ultimately reap the profits.
Of course these possibilities are hypothetical, but we have already seen evidence both within the NHS and in other scenarios that these negative consequences are unfolding and could severely jeopardise standards of healthcare delivery and the future of medical innovation, not only in the UK but worldwide. Are these consequences we want to live with? And in case you are wondering what is motivating this large-scale privatisation of the NHS, take a look at this: http://socialinvestigations.blogspot.co.uk/2012/02/nhs-privatisation-compilation-of.html
Please join the People's March for the NHS, further details here: http://999callfornhs.org.uk
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 Book by Ben Goldacre (2012) Bad Pharma: How Medicine is Broken, and How We Can Fix It, Fourth Estate, UK.
An annual sum of approximately £2.8 billion is spent on academic medical research in the UK – £1.2 billion of which is sourced from medical charities . Despite only being a fraction of the amount spent on medical research in the US, the UK is second only to the US in terms of research output, with more articles and citations per researcher than any other country . But how much research with a medical aim is actually converted into a benefit for patients? Is it all money well spent? These are the questions being asked as we endure an economic downturn, while patients seek the next miracle cure.
When it comes to investigating a medical problem, the mind-set of a scientist can be somewhat different to what a layperson might expect. They are often driven by their fascination in the mechanisms of disease. But often their sources of funding are either the government or charities relying on the generosity of members of the public. These sources award funding to researchers with the hope that they will make the next discovery or innovation to improve prevention, diagnosis or treatment of disease and ultimately save lives. One could, however, argue that extensive work is necessary to fully understand the problem before any steps towards translational research can be made. So are scientists doing enough to translate their findings to the clinic? And hence do they justify the funding they receive?
Perhaps herein lies a problem with the way scientific research is recognised. Scientists build their reputation on a myriad of publications, ideally in high impact factor journals, and the ability to attract large grants. Hence we often see publication of a research paper as the end point of a research project. The peer-review process is important to judge the quality of the study and whether its results and conclusions are reliable. Thus it is necessary to ensure the safety and efficacy of any potential therapeutics in question. Unfortunately, at times the peer-review system can be flawed, as journal editors prioritise studies with positive results, particularly on so-called “trendy topics,” such as the use of stem cells in regenerative medicine. This can lead to controversies such as the recent Nature publication claiming that exposing adult cells to an acidic environment converts them to 'totipotent' stem cells . Its credibility is now under investigation and a subsequent questionnaire given to stem cell researchers by New Scientist led to a small proportion of scientists admitting they had felt pressure from their peers to submit incomplete data for publication and even falsify data, which in some cases has been published despite the peer review process, although it must be emphasised that the proportion of scientists making these claims is extremely small . Negative data is often ignored even though it could be highly informative on the efficacy of a particular treatment or understanding the pathogenesis of disease. Hence researchers choose not to submit a paper showing negative data as they are resigned to believe it will never be accepted for publication. While initiatives such as the Journal for Negative Results in Biomedicine  aim to counteract this problem, they have yet to gain widespread recognition.
This sets a dangerous precedent for many reasons. Several groups may come up with the same idea that a particular protein may be detrimental in cancer for example. However if a group has already carried out a study, which showed no effect, the rest of the scientific community will never know. Thus other groups will waste time and resources on a study, which has already been performed, possibly many times over. What is of great concern is that therapies that have no beneficial effect in treating disease may still be produced and given to patients because studies showing a beneficial effect have been published while studies showing no benefit have not. Ben Goldacre brilliantly explains the publication bias of clinical trials in his recent TedMed talk . Publication bias has been extensively studied with regard to clinical trials but less attention has been paid to basic scientific studies, which experience the same kind of discrimination and whose results are the first step in producing potential therapies.
But with success in publishing comes a greater chance of success with grant applications, as having a good track record proves your ability to produce high quality science. Recently there has been a developing trend towards awarding larger grants to more prominent scientists over a longer period of time in an effort to inspire greater discoveries. But could such an initiative change scientists’ motivation towards obtaining larger amounts of funding rather than producing sound science that is ultimately beneficial to the public? A recent study in Canada suggests researchers receiving additional funding were not more productive . It appears that awarding smaller grants to more researchers boosts productivity.
The inability to translate biomedical research findings could be attributed to the increasing divide between researchers and clinicians, which is a relatively recent phenomenon. While clinicians performed early research, the emergence of molecular biology 40 years ago led to specialised research by biomedical scientists, who have greatly increased the understanding of disease in recent decades, but it appears few have meaningful collaborations with clinicians or industry. This is possibly due to reluctance among basic scientists to delve into the clinical situation while clinicians, whose time is occupied with patients, have difficulty not only performing research but also just keeping in touch with the latest literature, which is increasingly complex.
Fortunately this problem is being realised by more individuals in the scientific community. Funding organisations are making a concerted effort to encourage multi-disciplinary research enforcing collaborations between biomedical scientists, engineers and clinicians. The National Institutes of Health (NIH) in the US have created a translational research initiative, pumping funding into the creation of numerous Clinical and Translational Science Centres (CTSCs) across the country. These research centres are at the early stages of their development in many cases but have still yielded some positive signs thus far. Much of the research conducted in CTSCs is driven towards drug development and there have been many drug targets identified which have led to drug development and even the initiation of clinical trials for example against cancer, neurological diseases, and cardiac disorders (through the advancement of regenerative medicine). However it is not clear what proportion of research within CTSCs has been successful in achieving a translational output.
Similar efforts have been seen in the UK with the creation of specialist research centres such as the British Heart Foundation Centres of Research Excellence and MRC (Medical Research Council) UK Centre in Allergic Mechanisms of Asthma. These facilities provide scientists with state-of-the-art facilities, renewed sources of funding and a stronger platform to foster multi-disciplinary collaborations. There has been a strong initiative to bring academics closer to the clinical setting with the creation of the National Institute of Health Research (NIHR), acting as a bridge between basic research and the delivery of improvements to the clinic. The NIHR has several aims: funding research for the benefit of patients, such as public health research or the development of innovative medical technologies; increasing the reliability and open access to medical research literature to better inform patients, clinicians, and policy-makers in their decision making with regards to medical practice; and improving the healthcare infrastructure. Various teams have also been set up to facilitate partnerships with industry to develop pharmaceuticals, medical technologies, and improvements in the healthcare environment.
It is evident that the increasing need to translate basic scientific research to the clinical setting is being recognised by funding agencies and national healthcare institutions. The increase in funding and provision of modern research facilities is encouraging for the future of medicine. Scientific developments over the next decade will be the true testament of the success of current translational research programmes.
This post is an updated version (as of March 2014) of what was originally published on the Oxbridge Biotech Roundtable Review in July 2013.
 Association of Medical Research Charities (AMRC) http://www.amrc.org.uk/home/
 International Comparative Performance of the UK Research Base – 2011. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/32489/11-p123-international-comparative-performance-uk-research-base-2011.pdf
 Stem cell scientists reveal 'unethical' work pressures http://www.newscientist.com/article/dn25281-stem-cell-scientists-reveal-unethical-work-pressures.html#.Uzcltdxg42w
 Journal of Negative Results in Biomedicine http://www.jnrbm.com
 What doctors don’t know about the drugs they prescribe by Ben Goldacre, TedMed 2012. http://www.ted.com/talks/ben_goldacre_what_doctors_don_t_know_about_the_drugs_they_prescribe.html
 Big Science vs. Little Science: How Scientific Impact Scales with Funding, (2013), Jean-Michel Fortin, David J. Currie, PLOS One 8(6): e65263.
Dr. Anusha Seneviratne
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