The Great Stagnation and Evidence-Based Medicine

For me, the Great Stagnation (Tyler’s term) or the Innovation Shortfall (my term) is concentrated in the biosciences. Here we’ve thrown  enormous scientific, corporate and public resources into biosciences, and made tremendous scientific advances.  Yet the prize of cutting-edge treatments seems further and further away.  Take this new study, which started with a simple hypothesis about sepsis, and ended up with a much more complicated picture:

Researchers from Rhode Island Hospital have identified a protein that plays a dual role in the liver during sepsis. The protein, known as RIP1, acts both as a “death switch” and as a pro-survival mechanism. …Ayala says, “We initially hypothesized that RIP1 was involved in the alteration of the apoptotic death pathway to result in a kind of ‘programmed necrosis’ in the liver. What we actually found was an alternative role for RIP1 in the pathobiology of sepsis in the liver — one that also promotes cellular survival.”…..McNeal says, “The function of RIP1 is much more nuanced than we originally thought.”

These are questions that could not be even asked before. And at every step, the answer turns out to be more complicated than  we thought.

But then it occurred to me. If new research is continually suggesting that  things are really much more complicated than  we thought, how much of the medicine we are actually practicing now is correct? A new report suggests that we should be worried:

Even when following medical guidelines to the letter, doctors often use treatments that have little or no scientific support, U.S. researchers said Monday.

They found only one in seven treatment recommendations from the Infectious Diseases Society of America (IDSA) — a society representing healthcare providers and researchers across the country — were based on high-quality data from clinical trials.

By contrast, more than half the recommendations relied solely on expert opinion or anecdotal evidence.

“Despite tremendous research efforts, there is still a lot of uncertainty as to what is the best patient care,” said Dr. Ole Vielemeyer, an expert in infectious diseases at Drexel University College of Medicine in Philadelphia and one of the study’s authors.

Oh, okay. Let me bring the Great Stagnation, the biosciences revolution, and evidence-based medicine into a single framework.

The conventional wisdom was that breakthroughs in understanding the human genome  would provide better treatments within the existing structure of medicine–like  putting better windows or a new floor or more comfortable furniture into an existing house.  The implicit belief is that we could build on existing medical knowledge, add in the new knowledge of the genome, and quickly get to new products.

But what if the main lesson of the  past ten years is that the house itself has rotten foundations and needs to be rebuilt completely?  What if  the biosciences sector can’t afford to take anything for granted from existing medicine because too much of it is not evidence-based?

This is both bad news and good news.  Starting from scratch and rebuilding foundations is obviously a daunting and expensive task. and helps explain why the biosciences sector has struggled to produce breakthrough treatments.  On the other hand, when you are rebuilding foundations, a lot of progress can be made without anything visible from the outside.

I just know I’m going to get a lot of pushback on this hypothesis.  Take your best shot…I’m just thinking it through now, and I’m quite open to new thoughts.


  1. I’m a natural skeptic, sometimes I don’t trust my doctor. I’ve got foot problems that my regular doctor waved off, so I had to on my own imitative, consult an ortho and a podiatrist (podiatrist helped a lot with custom orthotics).

    In any case, as opposed to the pie in the sky mantras of “personalized medicine”, I came across this article recently documenting how genome sequencing is actually helping (in addition to things like 23andme).

  2. I just know I’m going to get a lot of pushback on this hypothesis. Take your best shot…I’m just thinking it through now, and I’m quite open to new thoughts.

    I sort of agree with you. I suspect that one side-effect of delving deep into the Genome and human biology is that much of our medicine is going to drastically change (for the better). It has happened before – think of how so many medical treatments from the first half of the twentieth century got ditched as medical science advanced.

    Evidence-based medicine is rough, and not kind to many hopeful treatments.

  3. Having gone through the medical process myself because of an injury, which was never diagnosed after seeing a couple dozen doctors, I can attest to their great ignorance. Contrary to the popular conception of doctors as experts who can customize a treatment for a particular condition, presumably synthesizing the results from scientific trials with their own past experience, I found that they were basically ignorant hacks who simply applied standardized solutions using simple heuristics. In fact, because the legal standard is that they must apply only commonly accepted techniques, that’s all they can do if they want to avoid legal risk. This is why I’m so confident that 99% of doctors can be replaced by medical software. What was especially galling was that most would just ignore or assume away the vast areas of knowledge that they are ignorant of. Only one doctor ever forwarded me to a specialist higher up the chain, though of course he still charged me the full fee for the 10 minutes it took him to reach that conclusion. The very fact that evidence-based medicine is a movement that has to be pushed in the medical profession right now speaks to the great con that much of medicine currently is.

    As for your bioscience thesis, there was never that much money poured into it so it’s not like that much investment was lost. As for those who had high hopes for big results, they were either ignorant of the inherent higher complexity of the biosciences or were hucksters selling that pie-in-the-sky outcome to get funding. I don’t really get your point about tying the biosciences to the practice of medicine either. Just because most doctors are incompetent at their job doesn’t mean there doesn’t exist proper scientifically-based medicine that could be augmented by further biosciences research. I would separate between the science of medicine and the practice, though you may be right that the science also may be sparse: I haven’t reviewed it beyond what I needed to for my own condition, which certainly unearthed gaping holes in the research.

  4. Oh, I meant to link to this great Economist article about an early medical decision software pioneer too. The opening anecdote about how doctors 150 years ago ridiculed hand washing as a necessary procedure is a glaring testament to the great and enduring ignorance and stupidity of the medical profession.

  5. Does anybody here ever read Seth Roberts’ blog?

  6. I agree with Ajay. Over the years I have been stunned by doctors’ level of ignorance. I routinely update THEM on the latest literature in their fields.

  7. The latest literature is often wrong. It helps to have some perspective.


  8. Adrian Meli says:

    Mike, great post and I think thought provoking although there are no good answers. It is a lot like our education system I think. The systems have a lot of problems that we need to constantly try to improve and refine but it is not possible to start from scratch. We can say medicine and doctors don’t do a good job, but science is helping and we have longer lives, etc. Like every profession, we have good doctors and lesser skilled ones but it is a tough job and the reimbursement pressures, etc. put limits on their time. I guess I am more hopeful that in the new information/internet age we will make a lot more progress faster though we haven’t hit the S curve yet. With the help of entrepreneurs, philanthropists, the VC community, medical schools, doctors, etc. I am hopeful our collective learning and information will steepen the curve soon! – Adrian Meli

  9. I love it. A Wiki model might help rebuild the house from the ground up. Basic randomized controlled trials (RCT) have not been done on many herbal supplements and other alternative treatments, which Americans spend about $34 billion on a year ( We need an open-source, horizontally organized consumer opt-in RCT system that lets people self-select into short-term trials. The cost is low in the short term, and the benefit is high in terms of (1) potential price breaks (companies *should* support efforts to prove what they sell works — right? :) and (2) data generation.

    The data would have obvious problems. But with large enough n and blocking (which I understand as a form of pre-matching across treatment and control groups), it wouldn’t be garbage. It’s far better than the system we currently have for collecting this data. The model could easily be extended to other consumer goods, functioning as a decentralized, consumer-controlled informal regulatory force. Corporate capture doesn’t matter because it can’t overcome the power of randomization.

    Since herbal supplements are relatively unregulated and outside the medical system in America anyway, this is a natural place for WikiMeds (or whatever) to start. Take it away, Nature’s Way…

  10. Mark Phariss says:

    There is an underappreciated benefit from the push for electronic medical records with regards to evidence-based medicine: data mining. When the whole of current medical practice can be examined as a set of experiments (in the statistical sense), legacy procedures can be subjected to virtual clinical trials. The key is to effectively feed the results back to active practitioners; the risk is that excessive privacy concerns will prohibit the mining of even anonymized medical records.

  11. My take on the post was that the incredible complexity being revealed by advanced technologies, such as DNA sequencing, are also revealing the fragility of current disease classifications. There are some hints of this in the literature, but not as much as one might think. Convincingly overturning an accepted disease classification would probably require a clinical trial-like effort. And presenting less-than-convincing data is difficult. One reason to try would be to bring a new diagnostic to market that would assay for the new classification. But the commercialization path for molecular diagnostics is not at all clear, which can’t be helping investment in the area.

    Nevertheless, there is tremendous innovation occurring in these technologies and in the software that is or will be used to analyze the data. This sentence is key: “On the other hand, when you are rebuilding foundations, a lot of progress can be made without anything visible from the outside.” So, are we really at a technological plateau, as described by Cowen in The Great Stagnation? Or is this more of an implementation plateau where implementation is stifled by cultural or governmental strictures?

    Given that rapid innovation is occurring, which country is best positioned to take advantage of bioscience advances?

  12. no pushback – this is exactly right.

    the biosciences revolution will kick in within 50 years 20 if we’re lucky and big companies get in on the act.

    people don’t even understand what a gene is. the current popular model is that theres a simple mapping between geno and phenotype. there are going to be literally hundreds of levels of interactions between dna, proteins, and traits. then all the traits are going to interact. (see the growing and recent field of proteomics)


  1. [...] Why the human genome project has made much progress in terms of medical outcomes yet.  (Michael Mandel) [...]

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