̽��ֱ�� of Cambridge - Kathy Liddell

Healthcare rationing could see unlawful deaths from COVID-19, researchers claim

fpjl2 — Thu, 21 May 2020 10:49:23 +0000

While the initial coronavirus peak is starting to pass – in Europe, at least – without the ventilator shortages many feared, the spectre of a second wave or future outbreak means questions of medical rationing still hold sway.

New research suggests that current ICU protocols and ethical guidelines lack detail, and leave doctors exposed to legal liability if another contagion surge forces them to make painful snap decisions due to insufficient resources.

While the latest analysis focuses on ventilators, ̽��ֱ�� of Cambridge researchers say that many of their arguments apply to other potential medical shortages e.g. a lack of properly staffed ICU beds, dialysis machines or related supplies or equipment.

If shortages lead to denial of treatment based on disability – including ‘chronic illness’ – or age, or treatment withdrawal during sedation, it could violate patient rights and cause unlawful death, argue the Cambridge lawyers.

They say that legal liability could extend to the UK Government if it is required to defend failures to purchase more medical supplies or publish ICU rationing guidance, despite knowledge of risks to life posed by the pandemic.

̽��ֱ��study, published in the Journal of Medical Ethics, is based on UK law, but researchers say it is relevant to other European nations.

“We’re definitely not out of the woods,” said Dr Kathy Liddell, Director of the Cambridge Centre for Law, Medicine and Life Sciences. “With lockdown easing, we might well see a second Covid-19 spike in intensive care units, and health services should be prepared legally as well as medically.”

“ ̽��ֱ��law requires more of hospitals, doctors and clinical commissioning groups than is currently set out in the guidelines provided by the British Medical Association, the Intensive Care Society and medical ethicists.”

“ ̽��ֱ��legal rights of patients matter, and they are not being given the attention they deserve,” she said.

Around 2.5% of Covid-19 patients require mechanical ventilation to live while they fight the virus, and a patient can need assisted breathing for up to three weeks.

Early concerns that the virus would see patient demand overwhelm ventilator supply prompted researchers to investigate the legal limits of ventilator allocation.

They found “little concrete guidance” centrally in the UK, and argue that a shortage could see “postcode lotteries” of patient rights to life saving treatment – as decisions are taken at a local level by hospitals and doctors.

“ ̽��ֱ��guidelines we reviewed differed in many ways,” said co-author Dr Jeff Skopek, from Cambridge’s Faculty of Law. “But they generally had the same goal: save as many lives as possible. While this is of course a worthy goal, it can lead to the violation of patients’ rights – rights are not suspended merely because we are in a crisis.”

̽��ֱ��researchers argue that a ventilator cannot be denied on the grounds that a patient has a disability. “Denying treatment because of a disability, which includes chronic illness, violates the Equalities Act 2010. Denying treatment based on age may also do so,” said Liddell.

“In fact, the Equalities Act requires efforts be taken not to disadvantage disabled people. This may mean giving people with disabilities longer assessment periods on ventilation, or actually not de-prioritising them,” she said.

̽��ֱ��analysis points out that if an initial trial of treatment is proposed, it must not be too short. No one should be taken off a ventilator for reallocation purposes until the trial has been long enough to generate reliable evidence for predicting the patient’s outcome.

Any decision to withhold or remove ventilation must involve consultation with the patient or their family. Moreover, withdrawing a ventilator without bringing the patient out of sedation risks unlawful killing.

“Even though returning to consciousness would be deeply distressing, all patients must be given a chance to breathe independently if they have a meaningful chance of surviving until another ventilator is available,” said Liddell.

If some of these scenarios occur during another virus spike, the researchers say doctors could be directly liable under criminal law for charges such as gross negligence manslaughter, criminal battery or willful neglect.

Even the UK Government could be held responsible. As Skopek highlights, the decision taken by government in April 2020 not to provide a national policy on handling ICU shortages – despite recommendations from its Moral and Ethical Advisory group – could result in a violation of its obligations under Article 8 of the European Convention on Human Rights.

“Without a national policy, the task of drawing up ICU rationing guidelines was left to individual CCGs and hospitals, and many lacked support to ensure their guidelines were legal and ethically sound,” he said.

Added Skopek: “If we end up with another surge in patients that overwhelms our critical care infrastructure, hospitals and doctors may end up acting unlawfully – and worse, patients may end up dying unlawfully.”

Current medical guidelines risk unlawful deaths of patients – with doctors, hospitals, and even the government potentially liable – if a second peak forces hard choices due to shortages of ventilators and other critical care resources.

Hospitals and doctors may end up acting unlawfully – and worse, patients may end up dying unlawfully

Jeff Skopek

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Synthetic organs, nanobots and DNA ‘scissors’: the future of medicine

lw355 — Thu, 12 Oct 2017 08:00:43 +0000

In a new film to coincide with the recent launch of the Cambridge Academy of Therapeutic Sciences, researchers discuss some of the most exciting developments in medical research and set out their vision for the next 50 years.

Professor Jeremy Baumberg from the NanoPhotonics Centre discusses a future in which diagnoses do not have to rely on asking a patient how they are feeling, but rather are carried out by nanomachines that patrol our bodies, looking for and repairing problems. Professor Michelle Oyen from the Department of Engineering talks about using artificial scaffolds to create ‘off-the-shelf’ replacement organs that could help solve the shortage of donated organs. Dr Sanjay Sinha from the Wellcome Trust-MRC Stem Cell Institute sees us using stem cell ‘patches’ to repair damaged hearts and return their function back to normal.

Dr Alasdair Russell from the Cancer Research UK Cambridge Institute describes how recent breakthroughs in the use of CRISPR-Cas9 – a DNA editing tool – will enable us to snip out and replace defective regions of the genome, curing diseases in individual patients; and lawyer Dr Kathy Liddell, from the Cambridge Centre for Law, Medicine and Life Sciences, highlights how research around law and ethics will help to make gene editing safe.

Professor Gillian Griffiths, Director of the Cambridge Institute for Medical Research, envisages us weaponising ‘killer T cells’ – important immune system warriors – to hunt down and destroy even the most evasive of cancer cells.

All of these developments will help transform the field of medicine, says Professor Chris Lowe, Director of the Cambridge Academy of Therapeutic Sciences, who sees this as an exciting time for medicine. New developments have the potential to transform healthcare “right the way from how you handle the patient to actually delivering the final therapeutic product - and that’s the exciting thing”.

Read more about research on future therapeutics in Research Horizons magazine.

Nanobots that patrol our bodies, killer immune cells hunting and destroying cancer cells, biological scissors that cut out defective genes: these are just some of technologies that Cambridge researchers are developing which are set to revolutionise medicine in the future.

̽��ֱ��Future of Medicine

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Snip, snip, cure: correcting defects in the genetic blueprint

lw355 — Fri, 14 Jul 2017 08:01:02 +0000

Dr James Thaventhiran points to a diagram of a 14-year-old boy’s family tree. Some of the symbols are shaded black.

“These family members have a very severe form of immunodeficiency. ̽��ֱ��children get infections and chest problems, the adults have bowel problems, and the father died from cancer during the study. ̽��ֱ��boy himself had a donor bone marrow transplant when he was a teenager, but he remains very unwell, with limited treatment options.”

To understand the cause of the immunodeficiency, Thaventhiran, a clinical immunologist in Cambridge’s Department of Medicine, has been working with colleagues at the Great Northern Children’s Hospital in Newcastle, where the family is being treated.

Theirs is a rare disease, which means the condition affects fewer than 1 in 2,000 people. Most rare diseases are caused by a defect in the genetic blueprint that carries the instruction manual for life. Sometimes the mistake can be as small as a single letter in the three billion letters that make up the genome, yet it can have devastating consequences.

When Thaventhiran and colleagues at the National Institute for Health Research (NIHR) BioResource in Cambridge carried out whole genome sequencing on the boy’s DNA, they discovered a defect that could explain the immunodeficiency. “We believe that just one wrong letter causes a malfunction in an immune cell called a dendritic cell, which is needed to detect infections and cancerous cells.”

Now, hope for an eventual cure for family members affected by the faulty gene is taking shape in the form of ‘molecular scissors’ called CRISPR-Cas9. Discovered in bacteria, the CRISPR-Cas9 system is part of the armoury that bacteria use to protect themselves from the harmful effects of viruses. Today it is being co-opted by scientists worldwide as a way of removing and replacing gene defects.

One part of the CRISPR-Cas9 system acts like a GPS locator that can be programmed to go to an exact place in the genome. ̽��ֱ��other part – the ‘molecular scissors’ – cuts both strands of the faulty DNA and replaces it with DNA that doesn’t have the defect.

“It’s like rewriting DNA with precision,” explains Dr Alasdair Russell. “Unlike other forms of gene therapy, in which cells are given a new working gene but without being able to direct where it ends up in the genome, this technology changes just the faulty gene. It’s precise and it’s ‘scarless’ in that no evidence of the therapy is left within the repaired genome.”

Russell heads up a specialised team in the Cancer Research UK Cambridge Institute to provide a centralised hub for state-of-the-art genome-editing technologies.

“By concentrating skills in one area, it means scientists in different labs don’t reinvent the wheel each time and can keep pace with the field,” he explains. “At full capacity, we aim to be capable of running up to 30 gene-editing projects in parallel.

“What I find amazing about the technology is that it’s tearing down traditional barriers between different disciplines, allowing us to collaborate with clinicians, synthetic biologists, physicists, engineers, computational analysts and industry, on a global scale. ̽��ֱ��technology gives you the opportunity to innovate, rather than imitate. I tell my wife I sometimes feel like Q in James Bond and she laughs.”

Russell’s team is using the technology both to understand disease and to treat it. Together with Cambridge spin-out DefiniGEN, they are rewriting the DNA of a very special type of cell called an induced pluripotent stem cell (iPSC). These are cells that are taken from the skin of a patient and ‘reprogrammed’ to act like one of the body’s stem cells, which have the capacity to develop into almost any other cell of the body.

In this case, they are turning the boy’s skin cells into iPSCs, using CRISPR-Cas9 to correct the defect, and then allowing these corrected cells to develop into the cell type that is affected by the disease – the dendritic cell. “It’s a patient-specific model of the cure in a Petri dish,” says Russell.

̽��ֱ��boy’s family members are among a handful of patients worldwide who are reported to have the same condition and among around 3,500 in the UK who have similar types of immunodeficiency caused by other gene defects. With such a rare group of diseases, explains Thaventhiran, it’s important to locate other patients to increase the chance of understanding what happens and how to treat it.

He and Professor Ken Smith in the Department of Medicine lead a programme to find, research and provide diagnostic services to these patients. So far, 2,000 patients (around 60% of the total affected in the UK) have been recruited and sequenced by the NIHR Bioresource, making it the largest worldwide cohort of patients with primary immunodeficiency."

“We’ve now made 12 iPSC lines from different patients with immunodeficiency,” adds Thaventhiran, who has started a programme for gene editing all of the lines. “This means that for the first time we’ll be able to investigate whether correcting the mutation corrects the defect – it’ll open up new avenues of research into the mechanisms underlying these diseases.”

But it’s the possibility of using the gene-edited cells to cure patients that excites Thaventhiran and Russell. They explain that one option might be to give a patient repeated treatments of their own gene-edited iPSCs. Another would be to take the patient’s blood stem cells, edit them and then return them to the patient.

̽��ֱ��researchers are quick to point out that although the technologies are converging on this possibility of truly personalised medicine, there are still many issues to consider in the fields of ethics, regulation and law.

Dr Kathy Liddell, who leads the Cambridge Centre for Law, Medicine and Life Sciences, agrees: “It’s easy to see the appeal of using gene editing to help patients with serious illnesses. However, new techniques could be used for many purposes, some of which are contentious. For example, the same technique that edits a disease in a child could be applied to an embryo to stop a disease being inherited, or to ‘design’ babies. This raises concerns about eugenics.

“ ̽��ֱ��challenge is to find systems of governance that facilitate important purposes, while limiting, and preferably preventing, unethical purposes. It’s actually very difficult. Rules not only have to be designed, but implemented and enforced. Meanwhile, powerful social drivers push hard against ethical boundaries, and scientific information and ideas travel easily – often too easily – across national borders to unregulated states.”

A further challenge is the business case for carrying out these types of treatments, which are potentially curative but are costly and benefit few patients. One reason why rare diseases are also known as orphan diseases is because in the past they have rarely been adopted by drug companies.

Liddell adds: “CRISPR-Cas9 patent wars are just warming up, demonstrating some of the economic issues at stake. Two US institutions are vigorously prosecuting their own patents, and trying to overturn the others. There will also be cross-licensing battles to follow.”

“ ̽��ֱ��obvious place to start is by correcting diseases caused by just one gene; however, the technology allows us to scale up to several genes, making it something that could benefit many, many different diseases,” adds Russell. “At the moment, the field as a whole is focused on ensuring the technology is safe before it moves into the clinic. But the advantage of it being cheap, precise and scalable should make CRISPR attractive to industry.”

In ten years or so, speculates Russell, we might see bedside ‘CRISPR on a chip’ devices that screen for mutations and ‘edit on the fly’. “I’m really excited by the frontierness of it all,” says Russell. “We feel that we’re right on the precipice of a new personalised medical future.”

Gene editing using ‘molecular scissors’ that snip out and replace faulty DNA could provide an almost unimaginable future for some patients: a complete cure. Cambridge researchers are working towards making the technology cheap and safe, as well as examining the ethical and legal issues surrounding one of the most exciting medical advances of recent times.

I’m really excited by the frontierness of it all. We feel that we’re right on the precipice of a new personalised medical future.

Alasdair Russell

̽��ֱ��District

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Immorality and invention: the “great stem cell debate”

lw355 — Tue, 28 Oct 2014 09:32:44 +0000

Human stem cell research is a thriving field of science worldwide – holding promise for treating diseases such as diabetes, multiple sclerosis and Parkinson’s disease, as well as for furthering our understanding of how we develop from the very earliest stages of life.

But using human embryonic stem (ES) cells to improve the health of other humans has also been the subject of comment, criticism and even court cases. Time magazine dubbed the “complexity and drama” surrounding these cells as the “Great Debate”.

Most notably, the field witnessed the 2001 restriction on funding for ES cell research in the USA by President Bush and the lifting of the ban in 2009 by President Obama. Then in 2011, the Court of Justice of the European Union (CJEU) banned the patenting of inventions derived from human eggs or their equivalent on the basis that they were human embryos, the commercial exploitation of which “would be contrary to… morality.”

While religious bodies and green lobbyists use patent law to elevate the status of the embryo, scientists argue that doing so threatens research that might benefit the health of millions.

International law permits states to refuse patents where necessary to protect morality in their territory. “Yet, how does a patent examiner or a court assess whether an invention is immoral to the point that, unlike other inventions, it can’t be patented? That is a particularly difficult question,” said Dr Kathy Liddell from the Faculty of Law. “It is a conundrum that runs headlong into the complex intersection of law and morality, intellectual property and philosophy.”

It is precisely this intersection that a new research centre in the Faculty will investigate. ̽��ֱ��new centre – funded by the Hatton Trust and the WYNG Foundation – will focus on medical law, ethics and policy relating to controversial issues such as patenting inventions involving DNA and body parts, the regulation of medical research and technologies, assisted reproduction and surrogacy, and the governance of ‘big data’ in the medical field, as well as the regulatory and legislative issues that stem cell research is likely to meet en route from the lab to the clinic.

“These areas need to be considered not as a post hoc rationalisation of events that have already happened, but alongside and ahead of technological advances,” said Liddell, who is centrally involved in the new centre, as well as being Deputy Director of the Faculty’s Centre for Intellectual Property and Law. “To complement the extraordinary science that is happening, we need to consider the ramifications of biomedical advances in a thorough and timely way.”

Liddell’s own research interests relate to the pathway that leads from the research bench to clinically effective treatments. She sees the law’s role as facilitating and supporting this pathway in morally responsible ways.

ES cells are useful because they are at the earliest point of human development and possess the full ‘regenerative toolkit’. In other words, they can develop into any type of cell in the human body. Although stem cells found in the adult human also retain the self-renewing ability to develop into specific tissues, they cannot develop into all the tissue types needed for regenerative medicine; the genetic information needed for some developmental pathways has already been shut down.

“ ̽��ֱ��CJEU was very reluctant to engage with the ethical and public policy debates surrounding human embryos. So it ended up answering the patent law questions with very little reasoning,” added Liddell.

“For me, this was the biggest problem with the judgment. ̽��ֱ��Court has to have the courage, skills, wisdom and accountability to face up to the degree of judicial activism and policy shaping that is inevitable in these controversial areas. Likewise, citizens, researchers and NGOs have to accept that judges have to make difficult ‘calls’ in the face of moral and scientific uncertainty. They simply can’t please everyone in a morally pluralist society.”

Julian Hitchcock, a specialist in life science intellectual property at London law firm Lawford Davies Denoon, who advises government and the Wellcome Trust on stem cell law, agrees: “ ̽��ֱ��problem I see is that the CJEU’s decision sends the message that scientists engaged in stem cell research are immoral. Moreover, the CJEU’s decision is being used to attempt wider assaults on research, such as in a Citizens’ Initiative called ‘One of Us’ which suggested that the principle of human dignity applies from the point of conception. Had this initiative succeeded, not only would it have undermined research funding, but it would also have impeded the fulfilment of urgent Millennium Development Goals.”

Meanwhile, the great stem cell debate continues, with a recent challenge in the High Court by the International Stem Cell Corporation over a decision by the Patent Office that unfertilised human eggs that have been stimulated to divide (turning them into so-called parthenotes) be included in the term ‘human embryos’. ̽��ֱ��implication is that parthenote inventions would also fall within the CJEU’s zone of unpatentable inventions. ̽��ֱ��High Court referred the issue to the CJEU and, in July this year, the Court was advised to reject part of the decision by the Advocate General.

“It’s a very complex area of the law – both highly technical and highly controversial. By supporting people to develop expertise in the life sciences and the law, we can better respond to these important discussions,” said Liddell.

Hitchcock added: “Formulating laws and policies that are responsive to the needs of research, and which carry the support of the public, requires a deep understanding of the ways that biology and law intersect, as well as imaginative thinking, powerful advocacy and the courage to fight an often embattled corner.”

“ ̽��ֱ��quintessential justification for patent protection has always been that it’s important for protecting investment in research and commercialisation,” said Liddell.

“We have yet to see whether the lack of patent protection for inventions involving human embryos has had a chilling effect on the transition of ideas to clinical realities, or whether it has nudged research in new, but similarly effective, directions that avoid the moral dilemmas and legal uncertainties of using embryos. We may never know – it is very difficult to gather this sort of empirical data. But for society to benefit properly and fully from medical advances, we do know that we need to be ready to enter any and all debates that wrestle with their ethical and moral implications.”

Inset images: Human embryonic stem cells via Wikimedia; Dr Kathy Liddell

Human stem cell research holds promise for combating some of the most recalcitrant of diseases and for regenerating damaged bodies. It is also an ethical, legal and political minefield.

How does a patent examiner or a court assess whether an invention is immoral to the point that, unlike other inventions, it can’t be patented? That is a particularly difficult question

Kathy Liddell

̽��ֱ��District

Mines

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