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Human tissue revival

Royal Free Hospital professor of surgery Brian Davidson

Brian Davidson and his team (left: Emma Lawrence, right: Amir Gander).
DAVIDSON: 'Most people would now rather do their research work on rat, mouse or rabbit'

The Alder Hey scandal and regulatory red tape have deterred doctors from studying body parts for too long. Keith Cooper meets a surgeon with a mission to restore confidence in human tissue research

Human tissue. Removing it, storing and studying it. All have been essential to medical research for as long as it’s been around.

It’s the stuff of infamy too, of course, for gothic fiction and, mercifully rarer, real-life medical malpractice.

The pathologist Dick van Velzen was struck off the medical register in 2004, after the GMC heard he had removed and stored parts of children’s bodies without their parents’ consent.

Professor van Velzen, who worked at Alder Hey Children’s Hospital in Liverpool, ‘undermined the trust placed in medical practitioners to such an extent it has damaged the medical profession as a whole’, in the words of the GMC’s fitness-to-practise panel.

Since then, rules and regulations around the study of human parts have been tightened and they are tightening still.

The Human Tissue Authority, a watchdog established in the wake of Alder Hey, is due to bring into force the first major revision of its rulebook in April, further pushing up standards and pressing the need for dignity and consent when handling body parts.

Other steps in human tissue research are also being quietly made by a medical professor and surgeon from a modest office on the seventh floor of the Royal Free Hospital in Hampstead.

From here, professor of surgery Brian Davidson and his team are building a new centre and system, which he hopes will bring much-needed order to the way human tissue is collected and used for research.

For as the regulations, introduced since Alder Hey tightened controls around access to human tissue, they have also deterred many researchers from using it. Some opt instead for animal tissue, inferior as it is for many medical studies.

 

Sitting on resources

Researchers who do secure official permission to collect and test human tissue – be they individual researchers or big pharma firms – do not routinely share samples with others. And even if they did, there would be no guarantee of the quality and consistency of those shared. There’s no agreement on how collections are consented for, or how data on them is formatted and attached. Not yet, at least.

These are the issues that the UK Clinical Research Collaboration Tissue Directory and Coordination Centre, which Professor Davidson leads, seeks to address.

‘The strengthening of the process for consenting, ethics approval and licensing since Alder Hey has been a bit of a double-edged sword,’ he says.

‘This complexity has put people off from pursuing research projects that otherwise would have been useful to society. Most people would now rather do their research work on rat, mouse or rabbit rather than human tissue,’ he adds.

‘But any cancer development work on an animal is not going to be representative of what happens with patients.

‘The thing that is holding us up as a UK scientific group – academically and commercially – is a lack of a reproducible and viable system to provide the tissue. It is this kind of system, one that can reliably offer high-quality samples to answer highly specific research questions, that this centre is seeking to help establish in the UK.’

The public-facing part of the centre that Professor Davidson leads is an online directory of biobanks. The directory already allows researchers to log on and search for tissue samples according to type of disease and age and gender of the donor.

Such a centre is something many involved in research, funders included, are keen to see.

 

Common standards

Biobanks come in all shapes and sizes: from warehouses – staffed by robots, run by big institutions – to small collections held by multiple, lone researchers. The one at the Royal Free is another joint venture with UCL, has held a licence with the Human Tissue Authority since 2008 and counts one million samples in its collection.

But no one knows how many there are, where they are, or how well their samples are stored. As in any area of study, the quality of material matters, as does the data attached. Part of the job of the centre is to find and encourage biobanks to join the directory and agree a common set of standards for those that do.

In effect, the centre acts as a bridge between researchers and the biobanks that collect and store tissues. The centre’s staff work directly with a biobank on the first floor of the Royal Free, which is independent of the centre and has links with other biobanks through the UK Confederation of Cancer Biobanks. Its staff collect and supply samples for researchers linked to UCL.

The online directory, as more and more biobanks sign up, will increasingly allow researchers to discover if samples they need are already available throughout the UK.

Natalie Banner, a policy adviser at the Wellcome Trust, which helps fund Professor Davidson’s centre, says biobanks are an ‘enormously valuable resource’ for research but that coordinating their operations is a welcome but ‘monumental task’.

‘The value of biobanks can be significantly enhanced if enabled to coordinate and work together,’ she adds.

Better coordination would allow samples collected by one biobank for a single, highly specialised study to be used by other researchers for different lines of inquiry.

Pooling the resources of multiple banks makes possible the kind of sample sizes that researchers need in some fields, such as genomics, where many thousands are required. More uniform standards and approaches to consent and labelling across biobanks could also be improved through better coordination, Dr Banner adds.

 

Ethical framework

In taking on this ‘monumental task’, Professor Davidson hopes to reinvigorate the medical research community’s enthusiasm for the study of human tissue, mired as it has become in the new rules and the challenging ethical questions that truly innovative research often raise.

He wants to improve access to tissue, help standardise how tissues are collected, stored and disposed of. All this, within an ethical framework that is far removed from the Alder Hey scandal of the 90s.

His drive draws on decades of personal experience as a researcher and liver transplant surgeon.

After an early career in his native Scotland in the 80s, he worked as a surgical registrar around Leicester, before moving to London for a lectureship and research post.

His early research work, at UCL and the Institute of Cancer Research, looked at bowel cancer and its spread to the liver. After completing his surgical training, he joined the liver transplant team at the Royal Free, one of just a handful at that time in the mid-90s, when the procedure was in its infancy.

‘It was a clinical area with lots of opportunities and unanswered questions to address with research and clinical trials and that really interested me,’ Professor Davidson says of those early days. ‘This was a new area of surgery; when I was a registrar nobody did liver surgery and now it’s routine practice.’

With this once-pioneering surgery now commonplace, Professor Davidson’s research focuses on finding innovative ways to preserve – and even treat – livers and their cells, donated for transplantation and research.

 

Clinical use

Much of his work is at an ‘experimental stage’, he admits. The examples he gives certainly seem futuristic, such as hooking up organs to machines or keeping cancers alive to test treatments.

‘We are evaluating machines that could improve organs, which are not functioning, through a process called conditioning,’ he says.

‘They wash out the liver or keep it at body temperature, supplying it with oxygen and blood. This is not just about reducing the damage done to the organ before it dies but trying to improve its function to make it viable for clinical use.’

Then there’s experiments on livers considered unsuitable for transplantation – known as ‘human organ discards’– which have been donated for research as well as clinical use.

‘These human livers have the potential for bio-engineering to produce new livers,’ he says.

Healthy sections of rejected livers can also be used to test the toxicity of new drugs; diseased parts or whole organs can be kept alive to check the effectiveness of new treatments.

‘The opportunity for having a whole organ system to test is unbelievably unique,’ Professor Davidson says. ‘An organ might have been removed for transplantation ... but you then have an organ that you can keep viable and alive to study that cancer biology. Although that might sound a bit far-fetched, we’ve done work on that for a significant period of time.’

 

Frontier mentality

Pushing forward the frontiers of medical research, as such experimental studies do, would not have been possible without biobanks, Professor Davidson says.  But they do raise new ethical questions which must be addressed, he admits. ‘The ethical issues of getting a licence to do research on human tissues is a problem that hits a lot of researchers,’ he says.

He hopes, however, that the expertise, the national biobanks directory, and the system that he and his team are developing at the Royal Free will help ease any unnecessary brakes on research that these ethical questions raise.

Under the system he has set up, any patients in hospitals affiliated to UCL are asked whether they will donate part of their tissues for research. ‘We want to make it routine,’ he says. ‘Most patients don’t think about it twice. The problem is that patients are not asked.’

But another key role of the centre is to ensure that tissue is not taken and stored for no good reason, as in Alder Hey. ‘Biobanking should never be true biobanking,’ Professor Davidson adds. ‘It should be a biorepository which is interim so you don’t have any long-term collections that don’t have a planned utilisation.

‘We don’t bank,’ he says. ‘We store samples when we need them for research. So it’s not: collect every tissue in the UK but collect samples for which there is a clear need.’ Such an approach should be encouraged for all biobanks, Professor Davidson says.

‘There should be absolute transparency for every tissue collection in the UK,’ he says. ‘We could then monitor whether biobanks are collecting and monitoring tissues correctly. You could find out whether tissues are being used appropriately.

‘If a biobank has collected 10,000 tissues but never for any publishable research, that is not satisfactory; that has to be changed. All those patients will have donated their tissues and they are just sitting there. There’s a responsibility to society which can be properly addressed here.’

As an ethical approach, it’s a far cry from the infamous hoarding uncovered at Alder Hey in the 90s, and it sums up his vision for the centre: to spread and embed good practice across the UK.

It’s a move that is welcomed by the former Department of Health official who helped draft the Human Tissue Act 2004, the then Government’s response to Alder Hey. 

Hugh Whittall, now director of the Nuffield Council on Bioethics, told BMA News that the DH had found in its investigations after Alder Hey that a lot of tissue banking wasn’t well managed.

‘A move towards more technical and professional biobanking is a good move in terms of making that tissue available for a research environment. Having a more formalised, more managed set of standards is really important.’

Read Natalie Banner’s blog on human tissue ‘Coordination and cooperation in bio banking’

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