The immune system as a metaphor for the Turing Pharma mess

H/T to @DerekLowe for the initial metaphor of Turing as a virus, and to the many, many commenters and journalists who’ve covered this topic.

A few weeks ago when Turing Pharmaceuticals’ plan to jack up the price of Daraprim by 5000% hit the news, I found myself glued to Twitter and other journalistic sources as each day brought a new wave of insults, reactions, condemnations, harangues, plans and concessions. I’ve frankly never seen any piece of biopharma industry news evoke this kind of response. When even U.S. Presidential candidates—well, the Democratic ones, anyway—are compelled to offer their takes and plans for reform, it seems that something fundamental may have changed.1

The question is, what should the biopharma industry take away from this? While a few CEOs such as Biogen Idec’s George Scangos and Novartis’ Joseph Jimenez have spoken out against the price hike, and both PhRMA and BIO have taken actions to repudiate Turing Pharma’s actions, there are still demands that biopharma come out with a clearer, more unified position—or risk being labeled as hypocritical. But that doesn’t seem to be happening. Just recently Ian Read, the CEO of Pfizer, told Evercore ISI that he wasn’t worried about Democratic presidential candidate Hillary Clinton’s proposals to control drug prices. Not the most conciliatory or self-aware comment to make, especially for a CEO who went on the record last year saying Biopharma has a reputation problem. So how to influence the industry to take this problem seriously?

Behavioral economics tells us that framing can be a key component influencing decision making. Among other things, a framing approach makes choices and consequences as real as possible to people through the use of analogy and filters. So I thought to myself, we all work in biology. Maybe a biological analogy might help drive home what’s at stake. And given that immuno-oncology is so hot these days it makes plasma look cool, I thought an immune related frame might be helpful. So let me present the recent pricing fiasco through the lens of the immune system.2

An extended analogy between an immune system response and the reaction to Turing Pharma
Immune system element Analog in the recent Turing Pharma debate
Priming antigens Recent discussions about the price of Sovaldi, and several other new drugs in indications like Hepatitis C, cardiovascular disease, and oncology primed the public to discussions of drug prices. Also, the Affordable Care Act’s influence on employer-provided health plans has led to rising out of pocket costs and therefore higher visibility for prices for medications.
Subthreshold immune response The lack of response to earlier instances of companies hiking the prices of generic drugs for companies like Questcor, Valeant and URL Pharma.
Virulent, triggering pathogenic infection Turing Pharmaceuticals raising the price of Daraprim by 5000%.
Immunization adjuvant Turing CEO Martin Shkreli’s amazingly annoying and provocative internet persona and behavior.
Innate immune response Social media and other responses to the price increase. Phrases like “drug price hikes,” “vulnerable populations,” and “maximizing shareholder value” that serve as pattern recognition motifs that trigger a speedy response like a macrophage engulfing a Staphylococcus bacterium.
Adaptive immune response The various regulatory plans being proposed–price caps, single payer negotiations, transparency initiatives, etc.–to stem drug price increases long-term.
Commensal bacteria Biopharma

 

The response to Turing Pharma didn’t come out of nowhere; there had already been several different factors that led the public to be primed for an affront like the Turing Pharma price hike. Over the last few years several high profile, high priced drugs have entered the market and raised real fears about the affordability of new medicines for conditions like Hepatitis C and high cholesterol that affect a substantial proportion of the US population. In addition, the Cadillac tax and other requirements of the Affordable Care Act appear to be leading to higher out-of-pocket expenses for patients (which is a feature, not a bug), further sensitizing them to drug prices. These developments have created social sensitivity to drug price changes, just as exposure to potential antigens primes the immune system for a stronger later response.

So why didn’t earlier, similar actions by other biopharma companies raise the same response? I think there are two main factors: first, randomness. We live in a world where a multitude of stimuli are clamoring for our attention. In that kind of environment there’s only enough oxygen for a few things to rise to wide-spread attention. I suspect the earlier price increases, some of which were in scale similar to what Turing did, just didn’t break the surface tension of the internet. Which brings me to the other factor: Turing’s CEO.

In vaccination, there’s a continual effort to find new adjuvants. These are substances one adds to a vaccine to really jack up the immune response. Martin Shkreli’s behavior served as a kind of adjuvant, exacerbating the effect of the initial insult of Turing’s pricing change. And that led to the initial, wild, Internet-wide response.

The concept of social shaming was recently examined in Jon Ronson’s book “So you’ve been publicly shamed.” Among the many things the Internet has enabled has been the ability to rapidly pivot on perceived malfeasants and nail them to the wall with a response not unlike that big rolling stone ball that almost squashes Indiana Jones at the opening of “Raiders of the Lost Ark.” Once a negative event does enter the attention economy, vituperation is swift and merciless. However, this innate immune response predictably fades over time. The real, lingering effect is the adaptive immune system of society—regulatory policy, which we see being proposed and debated as the US Presidential election cycle proceeds. The adaptive immune system has memory for certain pathogens, and remains ready to strike them down at a moment’s notice, and society also has a memory for certain acts it wants to remain constantly vigilant against, through laws and regulations.

So the lesson I hope biopharma takes from this extended analogy is the following: it’s too late to keep on doing the same things and hope no one notices. The system’s primed now and already starting to develop its long-term defenses. You’ll note I liken biopharma to commensal bacteria. I do think the industry serves a vital, important, useful role in helping society, just as our commensal microorganisms perform a host of beneficial functions for us. But as these kinds of rent-seeking behaviors proliferate—and not just on the side of generic drugs—the system as a whole will begin treating biopharma as more of a pathogen than a friend and the results could be very unpredictable. After all, the immune response doesn’t think about long-term consequences for the whole; it operates quickly and locally, often with unforeseen consequences. When excessively agitated by certain stimuli, the immune system can enter a chronic state of autoimmunity, creating long-lasting pain and fatigue.

The biopharma industry is blessed with the gifts of intelligence and foresight, and can take actions to head off a more stringent adaptive response from society by being more transparent and ramping down its most immunogenic actions—namely, pricing drugs to the limit of what the market will bear rather than based on a reasoned consideration of innovation and value. Because the alternative, as Robert Nelson of Arch Ventures laid out so starkly in Forbes, could be a crushing of all the good things biopharma can do in the rush to punish for the sins of a few.

 

1Maybe. The internet is notorious for its short attention span. Still, Bernie Sanders already had been calling out for reform on drug prices, so it may well be that this is a controversy that won’t get swept away by the next noisy thing. And, it must be said that at least one Republican candidate did respond to Turing’s price hike. Donald Trump, the candidate with the most experience as a provocateur, felt compelled to call Martin Shkreli a “spoiled brat.”

2I’m not an immunologist by training—I’m a geneticist. But I’ve been working with immunologists for the last seven years, which I think qualifies me to make broad, overly generalized and not entirely accurate analogies for the sake of a good story hook.

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One thought on “The immune system as a metaphor for the Turing Pharma mess

  1. Nice job here. I’m going to be touching on a number of the same points in my next piece for Xconomy that runs Wednesday. The immune system metaphor was interesting. While it would be nice to think that these pricing abuses will change, I don’t see that happening. No political will.

    Best wishes, Stewart

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