Posts Tagged ‘hypothesis-driven’

No hypothetical vaccines please!

14 January, 2011

A new editorial in Elsevier’s Vaccine, by Gregory Poland and JR Hollingworth, gives one much food for thought…especially if one and one’s associates are engaged in vaccinology, however quixotic that quest may be.

Especially quixotic when certain editors take 11 months not to publish one’s HIV vaccine paper, but that’s a story for another day…!

The article is entitled “From Science II to Vaccinology II: A new epistemology“, and is a thoughtful and quite intellectually challenging piece of work.

I have previously indicated that I am not a fan of hypothesis-driven science, however well entrenched it is in the psyches of most who practice it – in fact, I have gone as far as claiming elsewhere (thanks, Alan C!):

“Profound Insight No. 1: hypotheses are the refuge of the linear-thinking.

…I am quite serious in disliking hypothesis-driven science: I think it is a irredeemably reductionist approach, which does not easily allow for Big Picture overviews, and which closes out many promising avenues of investigation or even of thought. And I teach people how to formulate them so they can get grants and publications in later life, but I still think HDS is a tyranny that should be actively subverted wherever possible.”

And here we have two eminent scientists agreeing with me!  Not that they know that they are (or care, I am sure), and nor is it important – for what they have done is write a tight and carefully reasoned justification for moving away from the classical approach in vaccinology, as the complexities of the immune system and responses to pathogens and vaccines render the reductionist approach inadequate to address the problems at hand, and especially those presented by rapidly-mutating viruses.

This really is quite a profound suggestion for change, as the world of vaccinology is notoriously conservative, and it is really difficult to get people even to discuss only mildly paradigm-nudging concepts – oh, like cellular responses possibly being as important for protection against papillomaviruses as sterilising antibody responses? – let alone publish them.

Their final paragraph is especially apposite:

As we move into the world of Vaccinology II, or the “second golden age of vaccinology”, success will come only with the willingness to minimize the current Newtonian framework of thinking, and to adapt a new framework (Science II) that requires novel advanced bioinformatic and chaos theory-like analytic approaches, as well as multi-level systems biology approaches to studying currently unpredictable and uncertain self-organizing complex systems such as host immune response generation. Such work is difficult, expensive, challenging, and absolutely necessary if major advances are to occur in vaccine biology generally, and vaccine immunogenetics specifically.

This is fundamental stuff: I sincerely hope people in the field of HIV vaccines in particular give it some heed, as there the funding paradigm has actually shifted back towards requiring that everything be “hypothesis-driven”  – and I think this is a retrograde step, when the funding agencies (NIH, Gates Foundation) need to take more, rather than fewer risks, if we are to make any meaningful progress in our lifetimes.

While I am also not a fan of “systems biology” – because I think it is a catch-all term for what amounts to multidisciplinary research, and many of its proponents are brash snake-oil salesmen – modern vaccinology  really is a fertile field to plough using the new approaches.  Poland and Hollingworth put it well:

Similarly, as applied to understanding host variations as causative of inter-individual heterogeneity in immune responses  to such viruses, a Newtonian–Descartian view is entirely inadequate….

Rather than general principles, Vaccinology II and the new biology  is increasingly informed by principles such as pattern recognition, systems with non-linear qualities, and complex networks—often  focused at the individual, rather than population, level.

Amen to that.  Now, to get some money to do that…!!  B-)


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