The recent approval by the FDA of Novartis’ new Kymriah gene therapy for leukaemia is undoubtedly a cause for celebration. What’s not to celebrate about a drug that causes remission in 83% of the children who are its targeted patients? And doesn’t this represent the leap towards advanced therapies that our industry prides itself upon? But as I repeatedly stress in this column, our industry is a complex adaptive system. This means that, like the apocryphal butterfly flapping its wings, one event can trigger others in very unexpected ways. I’m trying to be positive, but the evolutionary scientist in me is worried that Kymriah is a portent of something much less desirable. As usual, allow me to digress into the science before I return to my article point.
Every significant evolutionary change that led to the world we know today began with a relatively small event that, at the time, probably seemed either benign, trivial or both. We think, for example, that all modern humans outside Africa can trace themselves to a single small tribe that managed to migrate across from the Horn of Africa to Arabia during a brief period of lower sea levels. The genetic map of Europe and then of the world was changed by small mutations that allowed tribes in the central Asian steppes to tolerate lactose, breed more and spread across the continent.
More recently, the emergence of new infectious diseases can often be traced to localised and apparently unimportant mutations that allow species-jumping. The point is that, were we to have noticed these changes at the time, we may not have given those events much significance because they affected only a small population in a small way. To the extent that we thought about them at all, we might have assumed that some of them at least had wholly positive outcomes. But evolution doesn’t have an outcome in mind and it certainly doesn’t have a positive intent, although the survival of the mutated genes makes it seem that way to our post-hoc logic.
Many mutations have unintended consequences, a phenomenon known to geneticists as pleiotropy. It is our sensitivity to this phenomenon that makes us concerned about genetic engineering, for example and is thought to explain diseases such as sickle cell anaemia and cystic fibrosis.
How is this relevant to Kymriah and the other advances in gene and cell therapy that it is part of? Surely, there can be no harm in curing this fatal childhood disease? And in any case, this development concerns only a tiny fraction of the small number of people who are diagnosed with this disease each year.
Well, all those things are true. For the small number of people concerned, this is without doubt an unalloyed blessing. And even though the treatment is expensive at $475,000, the impact on healthcare costs overall is probably trivial.
But think for a moment in the long term and of the wider picture, as is necessary when considering the evolution of the life science industry. Kymriah is only one example. It is part of a trend towards commercialisation of this new technology. And while at the moment such therapies are targeted at small populations, they will in time be targeted at much more common conditions and much larger populations. We might reasonably expect the cost to decrease over time but the reality is that these complex, personalised technologies will always be very expensive in both absolute and relative terms. Even in rich countries with generous payers, such treatments will not be affordable to the masses. If so, that’s undesirable but is it a major problem?
Most economists and politicians agree that the social inequality that we now see increasing around the world is a bad thing. Even those who have no problem with its morality are concerned that it will lead to political instability. But it is one thing to covet thy neighbours’ ox or their second home and another thing entirely to covet the health of their children. It takes little imagination to conceive of a world in which the children of a small upper class can survive diseases that kill the offspring of the masses painfully and prematurely. It is even less of an imaginative leap to see how that leads to social unrest of the most violent kind. And if that happens, historians will trace its origins to those technological developments that today look nothing but positive.
Of course, this is not a problem created by the industry alone and nor is it one that the industry can solve alone. However, the industry is a component of this pessimistic prediction and surely has an important role in anticipating and avoiding that dystopian vision.
