No hypothetical vaccines please!

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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4 Responses to “No hypothetical vaccines please!”

  1. Tweets that mention No hypothetical vaccines please! « ViroBlogy -- Says:

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  2. DMcILROY Says:

    Come on, you’re kidding me, right?

    Thoughtful and intellectually challenging piece of work? Intellectually challenged more like. The few bits you have quoted seem to me to be a typical example of pseudointellectual jargon-filled claptrap.
    Never trust a text which includes “Newtonian-Descartian view” – that’s what I say. For a start, anyone who thinks Descartes did anything useful in science, and deserves to be mentioned in the same breath as Newton, has taken too many philosophy classes, and not read enough history of science. Descartes’ optics? Not a patch on Newton’s. Descartes’ model of brain-muscle signalling? Interesting analogy-driven hypotheses untested by experiment – turns out, rather unsurprisingly, to be wrong.

    However, if we put this matter aside for a minute, and enquire what we are supposed to replace the most spectacularly successful method (I would say Galilean-Baconian science – nothing to do with bloody Descartes) for obtaining correct information about nature with, all we get is a woolly “multi-level systems biology approach”. Honestly, this is not going to replace traditional scientific inquiry. That is, having an idea about the
    way something works, making a prediction about how the system will behave if this idea is correct, then testing that prediction by experiment.

    With respect to vaccinology, I do wonder whether we should really expect that every infectious disease will turn out to be susceptible to vaccination. In all the examples for which vaccination is effective, at least some of the individuals infected are able to eliminate the pathogen entirely. These individuals cannot subsequently be reinfected by the same virus. So in a sense, vaccination aims to recapitulate one particular aspect of natural infection.

    On the other hand, for some viruses (HIV, CMV) host immune responses are incapable of resolving the infection in 100% of infected individuals. So there is no natural counterpart for vaccination to “aim for”.

  3. DMcILROY Says:

    Well, I thought reading the whole article might calm me down a bit – but I’m afraid it didn’t work entirely.

    To a certain extent, I think it’s the rhetorical form that the authors use that annoys me so much. It’s full of grand claims that we need “a new theoretical scientific framework” that I still feel are completely unjustified.

    On the other hand, if they had just pointed out that; 1) we really don’t have any working model whereby we can use what we know about the immunology at the cellular and molecular level to make viable predictions about what will and will not work in terms of vaccine design.
    and 2) we need to work on getting this kind of model in order to develop better vaccines; then I would pretty much go along with what they say.

  4. Ed Rybicki Says:

    Hi Dorian:

    Yes, well, as one whose philosophical learnings and leanings are mostly informed by a famous Monty Python song – yes, the one that has “Descartes, Descartes was a drunken fart” as a line – I must defer to your doubtless French sojourn-inspired philosophical knowledge.

    And yes, I thought the language was unnecessarily dense as well (there was a philosopher as well as vaccinologist involved…?), but the novelty of someone else actually thinking like me rose-tinted my vision.

    But what you said:

    “1) we really don’t have any working model whereby we can use what we know about the immunology at the cellular and molecular level to make viable predictions about what will and will not work in terms of vaccine design.
    and 2) we need to work on getting this kind of model in order to develop better vaccines”

    – pretty much sums it up.

    And to sum further: things are complex enough that we don’t have time to tease out individual narrow hypotheses and tests. Full steam ahead and let’s just discover the sh1t out of it.


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