Sympathy: For holiday reading?

The recent Ford family holiday (terminated by rotavirus!), gave me a chance to read Gary Acton’s book Sympathy for the Devil (subtitled “The definitive true story of Cancer Biotechnology and it’s battle against disease, death and destruction”). It’s not my normal light read, but an ‘e-flier’ hit my inbox in June and I thought it’d be worth a punt.

In short, it was brilliant – I struggled to put it down (even at over 500 pages long). It’s a candid view into the often chaotic world of drug development (see my earlier Sildenafil post) and now that the price has fallen to less than £8 (Kindle edition) it’s a must read, especially for anyone interested, or working, in drug development and/or cancer therapies.

OK, I better come clean first…

**Spoiler alert**

I have more than a passing interest in the book’s subjects. One of the main themes is the collapse of a medium sized biotech company, called Antisoma, of which Gary Acton was on the senior management team. The company failed mainly due to the poor performance of an experimental drug called ASA404. To me this was known as 5,6 dimethylxanthenone 4 acetic acid (or DMXAA) and I worked on the clinical supplies for the phase I trial in the late ’90s. At the time the drug seemed to be a big success, got to phase III, and then suddenly vanished and the book explains the drama behind DMXAA’s – and Antisoma’s – demise. I should also say that some of my colleagues have met Acton, and occasionally see his name cc’ed on emails, but I don’t know him personally. (There….all ‘competing interests’ out in the open – just like all good medical journals!)

The book’s outline and structure.

**Spoiler Alert**

The book is well structured even although it has several different strands. By hanging the technical issues (cancer biology, drug development challenges, genetic manipulation and regulatory history) on the story of Antisoma’s fight to stay alive it feels much more like a novel than a textbook and it splits the whole story up into manageable chunks. Each chapter is further split into nice subsections.

Chapters 1 and 2 cover the rise and fall of Antisoma as well as the commercial risks of drug development. Chapters 3,  8 and 9 are all worrying narratives of difficulties behind designing modern clinical trials and the apparently arbitrary way regulators can approve, or refuse, new cancer medicines. Chapters 4, 6 and 10 deal other Antisoma drug trials  (AS1411 and AS1413), the problems of international clinical trials (especially in developing countries) and the complexities of managing safety data. Chapter 5 is a history of chemotherapy from the early days of optimistic, maverick individuals to the modern molecularly targeted medicines (including  bang up to date 2013 references). Chapter 7 covers for gene therapy. Chapter 11 charts the final demise of Antisoma.

The book starts and ends with the failure of Antisoma’s commercially important phase III clinical trials and the company’s subsequent disintegration. A story only to common in the modern biotech and pharmaceutical industries and one that resonated with me after a previous sojourn with a small start up biotech: the failed trials, the changing regulatory requirements, the dwindling bank balance. (Although unlike Acton, I was a lab monkey and jumped ship before most of the workforce was made redundant with about 1 hours notice!) Acton seems to cleverly give enough details about the personalities involved and inner corporate workings but still keeping it positive.

What’s covered?

What’s not! Acton covers issues such as patent times and recuperating development costs, the ever-increasing burden of regulatory and quality structures, the risk/benefit of chemotherapy drug and complexities of the stark choices facing both clinicians and patients (is it better to take Drug A with 35% success rates, and a 10% chance of death, or Drug B with 50% response and 20% death?), how large organisations can both enhance and restrict innovative research, the power of the regulators over everything, the challenge and rewards of personalised medicine and the requirement for a ‘balance of probabilities’ approach to regulatory approval.

The historical aspect of the book highlights both the painfully slow, incremental, progress of most cancer drug development – akin to trench warfare – and the occasional ‘rapid advance’ made in some special cases (for example Glivec): but also how these serendipitous discoveries were made 50-100 years after the early pioneers had started their investigations and how few cancers we can actually cure, even today.

Writing style.

This book has the technical detail without the jargon, or the ‘academic grammar’. (Note to self: ‘See, it can be done!’) It’s probably best suited to readers with a reasonable knowledge of science, but if you can make sense of New Scientist Sympathy will be a sinch. It’s weighty enough to be useful, but light enough to be easy.

There were lovely turns of phrase throughout the book. The one that stood out to me (although you’d need to be involved in drug development to know the deep angst that this causes) was describing a trial being put on clinical hold as being “…the regulatory equivalent of the naughty chair”.

At over 500 pages Sympathy is long, but no part of the book was  ‘padded’ (and I’m pretty good at skipping textual ‘introns‘) and I read cover to cover. (OK, I missed out the reference and footnotes!)

Annoying stuff.

There are a few niggles. The popular ‘Malcolm Tucker’ expletive (which I won’t repeat – this being a family blog n’all!) is repeated in quick succession at the start and end of the book, but by the middle of the book the occasional use of the word is ‘asterixed out’. This gives a bit of a modular feel to overall text. Occasionally, for me, a small minority of the jokes went a bit far, especially if a particular topic (like the bus to Lourdes) was repeated in within a few pages. That said, Acton is just being as jocular on paper as I’ve experienced in other professional meetings, so it could be seen as fair game. The font size and side borders change for no apparent reason in several sections throughout the version of the paperback I had.

The chapter on gene therapy (7) is fascinating but didn’t add much to the overall story. The detailed discussion of Genentech’s struggles with the FDA over the approval of Avastin in chapter 8 was meaty stuff and posed tough questions about the current regulatory framework and it’s inconsistencies: but it was long (even being subdivided into sub-books) and might not appeal to other readers.

A penultimate personal opinion.

Funnily enough my colleague, Dr Patricia Docherty, and I started working on a new conference poster this week. It’s a review of quality failings in the modern pharmaceutical industry as compared to the official report which promoted the US Congress to set up the forerunner to the FDA . (An early version of the UK Pharm Sci abstract  is here, but that’s a side issue.) The US regulatory framework started with a novel, Upton Sinclair’s ‘The Jungle’: in fact the FDA cite it on their website as the reason for their ‘genesis’. This didn’t come about because of some fancy academic paper, or patient survival survey, it started with a well written work of fiction. While I don’t think Sympathy will do the same thing, I hope that it’ll ruffle enough feathers to lead to change – but, like Acton, I’m not too optimistic.

In summary.

I thought this was great overview of cancer, cancer therapies and the risks and pitfalls of modern biotechnology. As a small cog in a large drug development machine I never see patients, only capsules or vials, and so the descriptions of the difficult choices faced by patients and clinicians were particularly striking. The historical and technical aspects of the book have been useful at a professional level, but at the same time it’s written in a style that make it a good ‘holiday read’. Furthermore, Acton exposes the problems for patients, business and science with the current methods of funding and regulating the development of new medicines. Worryingly it seems that useful therapies are not reaching patients because of failures in the way we, as a society, manage the process of drug development and the book does nothing to quell the unsettling feeling I have that our ‘modus operandi’ cannot adequately deal with issues like stratified medicines, antibiotic resistance and spiralling development and drug costs.

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2 responses to “Sympathy: For holiday reading?

  1. I think I will give it a go Steve. Paul in the office has read it as well. I’ll get the Kindle edition I think – less weight to carry in an overloaded car

  2. Pingback: Lab-coat warriors | Experiment, Experience, Explore and Engage·

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