Mission Critical: How Translation-Focused Disease Foundations May Save Medical Research

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  • Patients waiting for medical research to produce important new cures are finding bad news almost everywhere they turn.

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  • Pharmaceutical companies are suffering from a much-discussed innovation crisis:

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  • At the heart of this innovation crisis is the misalignment of two very different cultures.

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Successfully translating scientific discoveries requires a sense of urgency, which some disease foundations seem to have, and many big pharmas appear to need.

Patients waiting expectantly for medical research to produce important new cures are finding bad news almost everywhere they turn.

Pharmaceutical companies are suffering from a much-discussed innovation crisis, as old drugs lose patent protection without new drugs to replace them; meanwhile, the small biotechs that could potentially bail big pharma out struggle to raise capital .

University scientists, for their part, are beset by an unseemly credibility crisis, as the intrinsic fragility of medical research is now vividly apparent from the soaring number of high-profile retractions, and the well-documented difficulty of reproducing many published findings outside the originator's lab.

At the heart of this crisis is the misalignment of two very different cultures.

Academic scientists tend to focus on publishing papers, and usually assume that the results will eventually be useful. They place a high value on novelty, and relatively less value on whether the data are robust, easily reproducible by others, or truly relevant to human disease. Captivating data from putative laboratory models of disease generate publications, even if the model is not very predictive of human disease - and unfortunately, most models aren't.

Conversely, big companies traditionally focus on generating efficiencies through scale, and on developing reproducible processes. This works very well for manufacturing, reasonably well for large late-stage clinical trials, and essentially not at all for early-stage (discovery) research.

The result has been two systems that operate nearly independently, yet fundamentally, should be seamlessly connected; industry is absolutely dependent on the creativity-driven research of university scientists, and these scientists in turn absolutely require industry to develop their preliminary ideas into reliable products (and could probably also benefit from the opportunity to pressure-test their results in a rigorous and systematic fashion).

The answer, I suspect, may come not from either industry or academia, but rather from an emerging third party: translation-focused disease foundations.

Consider the example of the Myelin Repair Foundation (MRF, with which I have no relationship). Trying to develop solutions to restore the myelin lost in multiple sclerosis, the MRF is interested in the entire drug development "value chain," from academic research to ultimate application, but has placed distinctive emphasis on the translational step, the part where promising academic advances are rendered sufficiently robust for industrial use. They strive to reduce the activation energy required for a company to study a drug, and have even developed their own lab to facilitate this - put together and staffed by biopharma vets.

In some ways, the MRF functions like a contract research organization for multiple sclerosis, capable of validating and robustifying preclinical assays, and developing and analyzing potential biomarkers for use in clinical studies. This approach represents a stark contrast from the more traditional disease-foundation route of simply plowing money into basic academic research and clinical trials, or the recent foundation trend of funding new companies (or specific projects within companies ). Here, the explicit goal is to enable translation by building out the capabilities required to achieve it.

MRF's research facility differs from an academic center in that no academic center would - or (arguably) should -- put in the effort to industrialize the assays to the level required by industry - it's not that interesting, and probably not publishable.

It's also somewhat different from a big pharma translational effort in that, as a non-profit, it's a lot easier to get academic assistance (as well as access to university-derived IP), and even more importantly, there's a clear and enduring sense of mission. While pharmas tend to switch therapeutic focus with each change in management (and each new influx of management consultants), disease-focused non-profits are steadfast about their mission - a dedication that will persist years down the line.

We don't know yet if this relatively recent effort will ultimately yield useful new drugs; however, I'm optimistic about the approach, which seems easily applicable to a range of other diseases - certainly, I'd imagine many disease foundations might do well to borrow a page from the MRF playbook.

I also suspect there are implications for universities and companies here. In focusing on the translational challenges, the MRF has helped many academic investigators appreciate both the challenges and the complexities of translating lab work into drugs - a process into which most had very little visibility. While the pharmascolds consistently fret that exposing academics to industry will be both stultifying and corrupting, in fact, such a dialog could help university researchers recognize the vast distance between a published paper and an approved drug.

The lessons for pharma are arguably even more profound - after all, this would seem to represent just the sort of stuff industry can do, and in some cases, has been doing. Yet I suspect MRF will be more successful at enabling translation than most pharmas, for many reasons but none more important than their primal sense of urgency.

MRF, like other disease research foundations, are impassioned and mission-oriented - their mindset isn't the rational, corporate, "should we do this? Let's make a decision analysis chart!" but rather, tends to be much more the sort of thing you hear from entrepreneurs - "we will do this - and will kick through walls if necessary to succeed."

Big pharma has not been able to generate the sort of urgency and passion so characteristic of start-ups, and so obviously evident in the MRF. Sadly, there's a full literature by this point devoted to the often dismal culture of big pharmas; I've discussed it here and here, Bruce Booth has a characteristically smart new piece here; former pharma CEO Jean-Pierre Garnier has a classic discussion here.

Big pharma and academic researchers have made tentative efforts to engage the other, but these overtures have not been remarkably successful (a point sure to surface at this weekend's Sage Congress focused on accelerating knowledge turns through data sharing and open communication). Academics tend not to recognize just how far away their laboratory experiments are from application, and often undervalue the work, insight, and exceptional expertise required to ultimately deliver an approved product. Meanwhile, industry typically operates in a structured, deliberate, constrained fashion that doesn't resonate easily with most academics.

To be sure, many pharma companies, under an "open innovation" mandate, have pursued associations with academics to stimulate the translation of promising discoveries; Pfizer's relationship with UCSF, involving co-localized investigators and an effort to identify targets addressable with biological therapeutics, offers a representative example.

Academic centers, for their part, have highlighted the need to be more translational, in some cases even setting up compound screening facilities to identify promising leads. Yet I know few colleagues in either academia or industry who are remotely optimistic about these solutions.

I'm not sure big pharma should give up basic research entirely, but I think they'd do well to pursue it in a few key areas that represent long-term commitments, and can be pursued with passion and focus under the leadership of the very unusual person who combines the creativity of an academic researcher, the commitment of a patient advocate, and has enough industry experience to understand what the program must achieve to succeed. Then, fund this small team and try to stay out of their way.

This approach, combined with a scientifically-savvy, adequately empowered business development function (Booth's comments here resonate), and intensified engagement with and support of translation-focused disease foundations (a model that I fervently hope will be fruitful and multiply), could result in a promising future for big pharma, a sustainable future for the biomedical innovation ecosystem, and most importantly, a healthier future for patients.

David Shaywitz is an adjunct scholar at the American Enterprise Institute.

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