Sunday 15 January 2012

Science nay-sayers, why the rush?

I get annoyed at the repeated premature announcements that scientific breakthrough X or Y has not yielded the benefits it promised. This week's Nature Biotechnology, for example, features an editorial entitled "What happened to personalised medicine?" with the tag line:
"Personalized medicine falls a long way short of the predictive and preventative healthcare paradigm it once promised."
Notice the past tense? "It once promised." Personalised medicine as a concept has failed, apparently.

The article then says:
"In some respects, 2011 was a banner year for personalized medicine. Academic medical centers began to demonstrate the feasibility of routine clinical genotyping as a means of guiding treatment selection in oncology. The US Food and Drug Administration released its companion diagnostics draft guidance. Sanofi, Pfizer and AstraZeneca signed deals with Medco and WellPoint for access to their large databases of patient data. Cancer Research UK's Stratified Medicine Programme was launched to demonstrate how genetic tests can be used to match National Health Service cancer patients to treatments. And two new targeted oncology therapies, Roche/Genentech's Zelboraf and Pfizer's Xalkori, were approved in conjunction with companion diagnostics for BRAFV600E and structural variants of anaplastic lymphoma kinase (ALK), respectively.

All are no doubt important steps, but illustrative of a rather pedestrian form of progress in personalized care rather than a march to the future."
So, it's not that it's failing to deliver anything. It's just happening too slow. The same thing happened with the Human Genome Project (HGP). This was "completed" less than a decade ago but people have already proclaimed that it has failed to deliver because we haven't been overwhelmed with a deluge of new HGP-derived drugs. The average drug development time is 10-15 years, I think, and that's when you already understand a fair amount about the target. So, even if the genome project truly was "complete" then it is still unrealistic and unfair to have expected it to already have yielded dozens of new therapeutics, even if you ignore the fact that novel targets arising from the genome project are, by definition, going to start off with practically nothing known except the sequence.

Annotation is still ongoing but the current state is over three billion nucleotides, approx 21,000 high confidence protein-coding genes plus over 47,000 gene predictions. This is a lot of data to deal with and it is naive beyond belief to think that the "answers" are just going to magically fall out in a few years. Going back to personalised medicine, the current Ensembl release has over 45 million variants and even this is not enough data. To really make sense of the role of genetic variants, we need a lot more genomes from both patient and control populations, and these patient populations need to be sensibly stratified by, e.g. treatment response. Such data is beginning to come but it is still early days, plus we still don't really know how to analyse all this data.

Biology is flaming complicated and the more we learn, the more messy and complicated it gets. Expecting us to unlock the secrets of first "The Human Genome" and then human variability in a few years goes beyond naive or arrogant, it's ridiculous.

I'm a big believer in The Human Genome Project and it really has changed the world already, even if its "promise" in terms of new drugs etc. will take many more years to be realised. (And this realisation will probably come mostly from Academia rather tha pharma.) I'm also a big believer in the concept of personalised medicine - the tailoring of treatment to the individual based on their particular genetic background. The fact is, however, that whilst this is totally the right road to be heading down, it's going to be a very long and windy road, no doubt with a few wrong-turns and dead-ends along the way.

To be fair, the rest of the editorial does then raise some pertinent points about things that need to happen to facilitate our journey down the road towards personalised medicine. These include better incorporation of the human "microbiome" - in sheer numerical terms, we have far more bacterial cells, genes and proteins in our bodies that human ones - and increased incentives for pharma companies to develop diagnostics as well as treatments. I just wish that the whole thing hadn't been given such a negative spin from the outset. It seems that with live in a world where everything needs to be over-hyped initially and then over-criticised when it doesn't live up to the over-hyping. I say, stop that: it's silly.

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