Sequencing in polio, baseball pitching and cancer: sometimes the order of events matters

This piece originally appeared in the Timmerman Report.

What do the polio virus, baseball pitch choice and cancer have in common?

The answer, of course, is sequencing. But not in the “figure out the DNA” way (although that’s involved). Instead in the “what comes first” way. Confused? Read on!

A big perk of Seattle is proximity to great institutions of biomedical research like the University of Washington and the Fred Hutchinson Cancer Research Center. Ever since my graduate student days in genetics at UC-Berkeley I’ve enjoyed going to seminars–especially seminars that are outside my field of study. Very little beats a good seminar for giving you a quick, condensed view of the state of a field of research. A bad seminar…well…we all could use more sleep, right?

In early October, Raul Andino of UCSF came to the Hutch to talk about his work on viral evolution. His team has been examining a clever real-world system to track the evolution of viruses. The near-eradication of polio (one of the great public heath victories of the past century) has led to the curious problem that as of the middle of this year most new cases of polio arose as a result of vaccination efforts. The live, attenuated vaccine that’s used in the developing world can, in very rare cases, mutate in just the wrong ways in its host, leading to the creation of a virulent strain that can infect others. In the US we use an inactivated polio vaccine which requires several injections; in much of the developing world the oral polio virus is preferred due to its ease of administration, lower cost, and immunization profile. The Andino lab realized that by studying these isolated outbreaks, which all originated with the same, genetically identical progenitor, they could test a hypothesis about the adaptive landscape of virulence evolution. Continue reading


The innovators dilemma in biopharma part 3. What would disruption look like?

All opinions are my own and do not necessarily reflect those of Novo Nordisk.

h/t to @Frank_S_David, @scientre, and the LinkedIn Group Big Ideas in Pharma Innovation and R&D Productivity for links and ideas

Part 1 is here.

Part 2 is here.

In the previous parts to this series I’ve covered both why the biopharma industry is ripe for disruption, and what the markets might be that could support a nascent, potentially disruptive technology until it matures enough to allow it to supplant the current dominant industry players.  In this final part I’d like to ask what disruption would look like and provide some examples of directions and companies that exemplify what are, to my mind, these sorts of disruptive technologies and approaches. With, I might add, the complete and utter knowledge that I’m wrong about who and what specifically will be disruptive! But in any case, before we can identify disruption, it’s worthwhile to ask what are the key elements of biopharma drug development that serve as real bottlenecks to affecting  human health, since these are the elements most likely to provide an avenue for disruption. Continue reading

The Innovator’s Dilemma in biopharma part 2. Where are the markets for disruptive tech?

All opinions are my own and do not necessarily reflect those of Novo Nordisk.

h/t to @Frank_S_David, @scientre, and the LinkedIn Group Big Ideas in Pharma Innovation and R&D Productivity for links and ideas

Biopharma may be ripe for disruptive innovation to come in and overturn their markets but that doesn’t mean it will happen. There are constraints beyond those of pure business, including the simple fact that treating diseases is really difficult and we don’t know as much as we would like about how biology really works. I see today’s biopharma market as a victim of its own success. The 80s and 90s saw the creation of truly life-changing, effective drugs like statins, and that has set the bar high enough that I think we’ve passed the inflection point at which approaches like high-throughput screening are becoming less likely to yield a substantial improvement in effectiveness. I’ve used the analogy before of drug development occurring on an adaptive landscape (Figure 2), with every improvement moving up a hill towards the theoretical perfect medicine at the apex. The higher up the hill one gets, the harder it is to move uphill and most efforts move sideways or down, simply because there’s more territory in those directions. This is a constraint that a disruptive innovation would have to overcome in some way.

Figure 2

Figure 2: The adaptive landscape for drug development.  Yes I drew this myself.  I would plug the drawing program, except I think they’d probably prefer not to be associated with this image. Continue reading