Whole Genome Sequencing: Savile Row or Marks & Spencer?

Ron Zimmern

11 June 2014

The launch of the 100,000 Genomes Project and the establishment of Genomics England have created a great deal of concern among some in the medical community. While the prospect of embedding genomic medicine and Whole Genome Sequencing (WGS) throughout the NHS is appealing, colleagues have consistently pointed out the difficulties of interpreting results from WGS, some suggesting that accurate interpretation of a single genome in a clinical context could require several days of expert analysis. Scaling-up and automation of the process, without human intervention (for wider implementation), they argue, could not be trusted; data generated by third parties who provide VCF files using computer algorithms would not be fit for use in a clinical setting. Human expertise was essential for the proper interpretation of WGS information.

I wish to suggest an analogy that might throw some light on this perception. As with all analogies, the comparison will not be exact, but it does illustrate (at least for me) a reason for some of the tensions.

The Savile Row approach

The present way of dealing with WGS data may be likened to the work of a Savile Row tailor who charges perhaps £3,000 for an individually crafted suit. Each suit is carefully made by experts with many years of training and apprenticeship. Every slight anomaly in the person is reflected in the way the suit is tailored. Suits tailored by individuals without the requisite training, in the eyes of a master tailor, would necessarily be of a lower standard, as would the making of suits that relied too heavily on automation. In this analogy Genomics England, by advocating for automated processes in WGS, could be seen as seeking to allow less expert tailors and technology to make up a bespoke suit for the individual – a lower quality product masquerading as the real thing.

Genomic medicine: the Marks and Spencers approach

However, the analogy as set out above does not in my view represent the intentions of Genomics England. It does not seek to create Savile Row suits at a lower cost and of a lower quality, using inferior tailors. What it seeks to achieve is something entirely different: to create an alternative product, a line of mass produced suits, such as one might purchase from Marks & Spencer: coming off a production line, cut and manufactured to its own set of quality standards, allowing no deviation from pre-determined patterns and specifications. These suits would retail at much lower prices and provide a much faster and more affordable opportunity for those in need of a suit. The slightly reduced quality of the individual suit would be made up for by increasing hugely the numbers of those able to afford a suit; and the quality of each suit, whilst less than that of a bespoke tailored version, will nevertheless be guaranteed to a standard level.

Whilst mass produced products are of course different from individually tailored products, they may still be good products, with variation in design, material and size. Automation also has its own advantages: the production line is consistent; quality control ensure consistency of the final products. And because it is likely to be cheaper, automation is also likely to be a more cost effective means of achieving the same ends. The move to automation allows products and services to reach those in the population who would not otherwise have previously been able to access them.

It is this fundamental change of paradigm that is being proposed by Genomics England. This approach will democratise genomics and make WGS available for all who need it; it will allow physicians across all specialties access to tools that will enable them to participate in the practice of genomic medicine. The general ‘customer’ will not receive all the features associated with individualised bespoke tailoring, but, a reasonable ‘fit’ would be guaranteed, as would the quality of the product.

A paradigm shift at the heart of genomic medicine

In recent decades, we have seen such shifts of paradigm in other medical fields. For example, the differential diagnosis of the acute abdomen based on history and symptoms by experienced clinicians was for many years a most effective tool, but it has now been replaced by imaging and other diagnostic procedures. For most, especially the young doctor, these newer, more automated methods for differential diagnosis have replaced the older approach – resulting in a general improvement in the efficiency and consistency of the diagnostic process and a greater benefit to patients. 

At the heart of this transformation for genomic medicine is the issue of standards. What are the quality imperatives that need to be put in place for the different services and purposes to be served by WGS? Context is all important, and, as with suits, the quality will vary according to the needs of the customer. It will be dangerous to take short cuts in certain contexts, yet in most other situations, something of high quality but less perfect may suffice.

It is open for the selected few to wander down Saville Row if such individualised quality is needed, but for the majority the mass produced product will, indeed must, suffice. The Marks & Spencer suit is undoubtedly fit for purpose. It is hoped that the WGS production line provided by Genomics England will have the same sort of utility for those who require WGS within the NHS. We should not harp back on how we used to do things, but have regard to how to do things in the future. In genomics, our ‘Savile Row tailors’ are undoubted experts; but they must rise to the challenge of helping to shape the automated production of the ‘suits’ and to set out the relevant quality standards. Their advanced classical ‘tailoring’ skills must be retained for the rarer occasions when some will still be needed - but they must also embrace the delivery of ‘Marks & Spencer suits’ that will enable many more patients to benefit from genomics.