The Insider: Kidneys for sale – Dispatches

September 27, 2007

With the demand for donor kidneys continuing to outstrip supply, Professor Nadey Hakin proposes a controversial alternative to the current ineffective strategies. In this short documentary Professor Hakin, world president of The International College of Surgeons, advocates forcefully that the UK should adopt a policy of genuine and significant payment to individuals willing to donate a kidney. This is not a new proposal, but is subject to certain taboo with many concerned about the exploitation of the poor. With this in mind, the programme sets out a strong case for donor payment as a route out of the current crisis. Read the rest of this entry »

“The ultimate upgrade” – Doctor Who & the Cybermen (parts 1 & 2)

September 20, 2007

In a two part episode concerning the Doctor’s encounter with the Cybermen, The Rise of the Cybermen and The Age of Steel rehearse a number of important bioethical issues regarding the feasibility and acceptability of “the ultimate upgrade” (00:24:15) – that is, the downloading and/or replicating of characteristics and functions of the human brain into a machine.

John Lumick (The Rise of the Cybermen. BBC, 2006)

In brief, The Rise of the Cybermen and The Age of Steel concern the efforts of John Lumick – a dying cybernetics genius in a parallel world – to prolong his life by downloading or replicating his conciousness in a mechanical body. This is described in terms of “a brain welded to an exoskeleton” (00:00:20). However, Lumick sees the cybermen project as, not only, his way to circumvent the wheelchair we see him in and his immanent death, but also, as the future of the human species – what he refers to as “our greatest step into cyberspace” (00:24:56). In order to secure this future Lumick unleashes the Cybermen on human society where they go about suggesting that “upgrading is compulsory” (00:41:53) and that humans “are inferior and will be reborn as Cybermen” (00:45:01).

The Cybermen (The Rise of the Cybermen. BBC, 2006)

As the story progresses the slippage and ambiguity in the terms ‘treatment’ and ‘enhancement’ becomes obvious. In The Age of Steel it is noted that “this all started out as a way of prolonging life” (00:07:21), though that the project has now become one which “takes the living and turns them into…machines” (00:04:30). Though this issue of mechanical enhancement of humans, including their effective replacement by super – or post – human cyborgs, is presented negatively in the action and dialogue that ensues, these episodes of Doctor Who do acknowledge the view that this type of extreme augmentation can be seen as the next step up on the evolutionary ladder. Indeed the Cybermen are referred to as a new species and describe themselves “human point two” (The Rise of the Cybermen: 00:41:51).

While both episodes are interesting, though provoking and exciting, it is The Rise of the Cybermen, that provides the best opportunity to explore and elaborate current themes in the bioethics of enhancement, including:

  • the distinction between treatment and enhancement of human beings by mechanical means
  • the boundary and difference between humans and machines
  • the idea and practical use of a hierarchy of ethical values in society
  • and, the interaction between science and regulatory and political structures in technological decision-making

These issues are explored in detail in the BioethicsBytes Extended Commentary that will shortly be available to accompany this post.

The Rise of the Cybermen was first broadcast on BBC1 on May 13th 2006 at 19.00 (TRILT identifier: 0059521F), followed by The Age of Steel on BBC1 on May 20th 2006 at 18.35 (TRILT identifier: 00597007).

The drug trial that went wrong – Dispatches

September 10, 2007

In March 2006, six men were taken seriously ill whilst acting as ‘healthy volunteers’ in a clinical trial at an independent research facility run by American company Parexel on the site of Northwick Park Hospital, London.  This episode of the documentary series Dispatches (Channel 4, 28th September 2006) tries to uncover what might have caused an apparently routine safety trial to go so dramatically wrong.  As well as discussing the case with a number of experts on clinical trials, investigative journalist Brian Deer spends a lot of time talking with Ryan Wilson, the man most badly affected by the trials.  In keeping with this genre of reporting, there is also the compulsory pursuit of a representative from Parexel, in the vain hope he might talk on camera.

Each volunteer was to be paid £2000 for their involvement in the trial and subsequent follow-up. Of eight volunteers in total, two received the placebo.  Having received the trial drug TGN1412, a monoclonal antibody, all of the other six very quickly started to suffer serious side-effects, including pain, nausea and falling blood pressure. The victims were transferred to the NHS intensive care unit on the same site, where their treatment was complicated by the fact that the drug was, of course, unknown to them and hence there was no previous treatment regime with which they could compare. What was clear, however, was that their symptoms fitted with “cytokine release syndrome”, a set of responses already seen previously as a consequence of other antibody-based therapies such as Rituximab.

Although four of the ill men were able to go home 48 hours later, Ryan Wilson was in a coma for 16 days and spent a total of 140 days in the hospital. Loss of blood to his extremities during the ordeal resulted in “dry gangrene” or mumification of his toes and some fingers leaving them like stone.

TGN1412 was developed by a small German biotech company TeGenero (who were forced into bankrupcy after this trial went so wrong).  Brian Deer discusses the situation with a former investor in the company, who (at 24:30) argues that the science of the trial was justified, but the administration of the drug was the serious flaw – it would have been better for each volunteer to have been given the medicine in turn rather than at the same time, thereby allowing for monitoring of potential side-effects before delivering the drug to the next volunteer.

Brian Deer then considers the merit, and adequacy, of animal testing before going on to interview Prof Terry Hamblin, an expert on monoclonal antibodies.  At the behest of the programme, Prof Hamblin re-read the documentation that had been submitted to the Medicines and Healthcare-products Regulatory Authority (MHRA), the body overseeing clinical trials in the UK.  Like the previous interviewee, he highlights problems with the administration of the drug.  In this instance, the issue is not with the staggering of start times, but with the period of time over which the drug was infused into the patients.  In the animal studies, delivery of the drug to the subject had been slow, carried out over a period of an hour. In the human trial, however, this was reduced to 3 to 6 minutes. Prof Hamblin describes this as “reckless” (28:02) although, as pointed out later, there is at least one monoclonal antibody in clinical use which is administered as a single injection (35:59).  There was also, Hamblin notes, no evidence of side-by-side in vitro testing of the drug with monkey cells and human cells to compare the immune response in both cases – a necessary stage to validate the transfer from an animal model into a human context.

Biotech consultant Dr David Glover, adds his reservations about the design and adminstration of the trial.  Questions he would have liked to have seen addressed in advance include issues about the potency of the drug, about dose calculation and the speed of delivery.  He is concerned that the MHRA may lack necessary expertise to assess trials involving newer biomolecules (such as antibodies) rather than traditional chemical compounds.

Brian Deer puts these criticisms to Prof Kent Woods, Chief Executive of the MHRA. Prof Woods counters that by its very nature, any clinical trial is an experiment – the outcome cannot be known for certain. “There will always be an element of risk” he stated. The important questions about inadequate in vitro testing are put again, although Deer undermines his own position by coming across as rather smug and confrontational.

Towards the end of the programme, Ryan Wilson is shown after surgery, when doctors have managed to save rather more of his feet than he had believed possible. He still expects, however, that his damaged fingers will fall off and the extent to which the drug may have affected his immune system remains to be established.

Later on, Deer considers the potential impact of the TGN1412 incident on future investment in drug trials.  His challenge that potential investors may be happy for volunteers to be collateral damage if it brings a swifter answer to safety questions (and hence saves them money) is sharply dismissed by Biotechnology Investment analyst Ibraheem Mahmood. Mahmood does, however, acknowledge that the more stringency that is put into the testing process as a result of disasters such as the one occurring at Northwick Park, the greater is the cost involved in developing any new drug and therefore a point may be reached when research into medicines for some important conditions may not be financially viable.

The final sections of interest involve discussion of the recruitment of volunteers, the adequacy of briefing they received and the actual management of the trial by Parexel.  In accordance with the law, Ryan Wilson and the other volunteers were asked for “informed written consent” to participate.  The documents do make reference to the possibility of cytokine release, but Wilson is adamant that this was not explained and that he was drawn to statements about nut and shellfish allergy from which he knew he didn’t suffer. Specific warnings about cytokine release syndrome were spelt out rather more fully in TeGenero’s briefing to Parexel but, the programme argues, the precautions were not heeded.  In particular, the advice to have steroids on hand during the trial does not appear to have been followed and some five hours elapsed before any were administered.  Prof Hamblin finds this response unacceptably tardy; even without a specific warning (as provided here), this treatment should have been a first response once the patients’ difficulties were evident.

The film closes with the pursuit and non-interview of the Director of Parexel, and with Ryan Wilson offering his reflections on the whole experience.

In terms of clips that might be used in teaching, the section from 03:49 to 06:10 might be shown with students as a vivid description of the symptoms shown by the volunteers, as witnessed by Raste Khan, who received the placebo. 10:30 to 11:59 includes an interview with Ganesh Suntharalingam (Clinical Director of Intensive Care at Northwick Park) and details what happened next, the difficulties caused by the lack of previous knowledge about the drug, and mention of cytokine release syndrome. There is some nice footage (25:00* to 26:30) of experimental monkeys, culminating in the question: “Was TeGenero acting reasonably when it assumed that tests on little guys like these [Macaque monkeys] would predict what would happen when they put their candidate drug into volunteers like Ryan Wilson and the others?” and, more broadly, whether these animal tests were sufficient to justify transferring to human volunteers. The interviews with Prof Hamblin about problems in the design and performance of the trial runs from 26:30* to 29:20, and with Dr David Glover from 29:58* to 31:04. Prof Woods rebuttal of the criticisms runs (with associated commentary) from 32:23* to 36:28. The section on recruitment and risks is 48:25* to 50:00 and is followed immediately by concerns about slow adminstration of steroids, until 51:20

For more background information on the TGN1412 trial, see this BBC News page (and follow links from the right of that page for earlier articles) and the Dispatches website for further details about the episode.  A copy of the programme, TRILT code 005C50CD , can be obtained from the BUFVC. Those interested in a more thorough appraisal of the events might also like to read a presentation given to the Institute of Clinical Research which, at the time of writing, was available via this link.

* Timings after 15 minutes are inclusive of the advert breaks in the original transmission. The programme is 56 minutes in total and “includes some strong language”, but not within the recommended clips.

Introducing our “Extended commentaries”

September 6, 2007

As the number of resources on BioethicsBytes continues to grow, so too does the range and diversity of the materials we are offering.  We have recently launched a new genre, the BioethicsBytes Extended Commentaries.  As the name implies, these articles pick up on one or more theme arising from a book, film or programme but discuss the issue(s) in a broader context. The Extended Commentaries draw on a wider range of academic texts than would be usual for a standard BioethicBytes review. They will normally be linked to a shorter post on the main blog.

At present there are four Extended Commentaries on:

Transgenics and a world of “limitless possibilities” – concerning issues arising from the first documentary in the Animal Farm series (Channel 4, March and April 2007), including medical v non-medical applications of transgenic organisms, connections with the debate about genetically-modified (GM) food, and a consideration of what is ‘natural’

The “pharmaceutical farm” – discusses speciesism, identity and the ethical treatment of experimental animals, as prompted by the second episode of Animal Farm

Making “creatures that work for us” –  looks at the medical benefits from transgenic animals, the modification of animals for our pleasure (specifically the transgenic GloFish) and the development of animals specifically to counter mankind’s impact on the environment, all of which were issues arising in the third programme of the Animal Farm series

The future of our families? – a consideration of some of the ethical concerns about saviour siblings, including illustrations drawn from Jodi Picoult’s novel My Sister’s Keeper

Further Extended Commentaries will follow in due course.