Dissertation Ideas

From BrothersBrothers


To Obtain

  1. The Gold Standard
  2. Article: Evidence-based medicine, clinical uncertainty, and learning to doctor. Timmermans
  3. The Body Multiple
  4. The Ontogeny of Information: Developmental Systems and Evolution - This is a reference from Dupre's book, talking about the role of DNA as "the master molecule", viewed as the "unmoved mover."

To Read


Conversation with Ellen:

  1. Take as the overall theme: Care of patients in particular provider-patient relationship (i.e. what we do and how we decide what to do). What does decision-making look like in this setting, with integration of personal knowledge and experience with patients and generalized data? How do introduction of technologies, including WGS and the informatics tools that are used to deliver those results, influence the way we navigate those influences?
  2. This theme is then the basis for addressing the more specific problem of dealing with genetic risk estimates, especially with respect to (1) determining when to tell them to patients and (2) determining which interventions to perform in response to them
  3. Since there is no synthesized model for medical decision-making, and EBM is clearly problematic here (due to no evidence, and due to conceptual problems with applying it in such a setting), a helpful technique will be to analogize from other practices in medicine, perhaps framing these as heuristics for dealing with uncertainty.


  1. I could do a chapter (or maybe a separate article) on genetic risk, taking my own risk for MI, and explore using different tools (the Mayo risk estimate tool, genetic test, family history alone, cholesterol markers alone, etc) to demonstrate that risk estimates vary, and that the formalization of risk in a specific number over-represents the certainty of such an event happening.
  2. Kuhn's definition of Disciplinary Matrix provides a way to frame what medicine is as a conceptual community as opposed to a practice (exemplars, values, etc), also Polanyi's "tacit knowledge"
  3. Clearly, practical reasoning (Aquinas and MacIntyre) is very important here, as well.


  1. Misunderstandings about risk derive from more fundamentals blindspots about role of mathematical models and values in science
  2. Scientific theories, framed as mathematical models, are what Berkeley call "mathematical hypotheses." The world does not exist as numbers of mathematical equations; mathematical models are derived from observation and gain support as they successfully represent, and sometimes predict, the way a particular natural event occurs.
  3. As Kuhn observes, paradigm shifts in science occur when paradigms, often based on specific mathematical models, are viewed as failing to respond to problems. This has traditionally assumed to mean that the model fails to predict or represent certain features of the field of study (such as the Ptolemaic models' increasing complexity as it required modifications to fit observed patterns in the solar system).
  4. There are a number of reasons that such a model may fail, however. A model might fail because it predicts a outcomes based on a certain set of variables. When a new variable comes to be recognized as having an effect on such systems, mathematical models that don't account for that variable could be viewed as failing. Possible examples include something like cervical cancer, when HPV came to be appreciated as the significant cause or stomach cancer + H. Pylori. Obesity would be a great example of the way that various models repeatedly fail as factors thought to be important fail to carry explanatory power: first endocrine, then psychological, then much later genetics.
  5. Ice cube melting is an example of a process that can be modeled quite successfully. This is because the important variables are assumedly all now known, and ice cubes can be represented quite effectively in models, since their characteristics are quite homogenous. (this is from Gorowitz and MacIntyre)
  6. However, more complex phenomenon like hurricanes cannot be modeled with complete accuracy. This is not, however, because the important variables are not known. On the contrary, the appreciation of physics related to air flow over warm water is quite well understood. In this way, the general features of hurricanes can be modeled effectively. But the reason that specific hurricanes cannot be modeled successfully is that inputs into such models in the real world are large in number, complex, and difficult to collect through available technologies. So the paths of hurricanes are represented as probability paths.
  7. Human risk for disease is similar. Many of the causes of many disease are well appreciated. The cause of CF has been known since ____. However, the course of health and wellness are extraordinarily complex such that in many cases the variables that are important in the development of a range of disease are not all known, even though some important inputs may be known. In addition, the histories of humans are even more complex than that of earthquakes, and infinitely more so than ice cubes (again, these examples are those of Gorowitz and MacIntyre). The ability to predict the onset of disease in an individual, then, varies on the basis of the comprehensive of available models in terms of the number of variables it can take account of, and also the inputs that are present in the history and ongoing life story of patients.
  8. Risk estimates for individuals emerge within this context of incomplete knowledge of biological systems and incomplete knowledge of particulars. This fact is demonstrated by the availability of co-existing models to predict disease. For example, MI risk estimate tools. The online Mayo Tool says one thing, 23inMe says another, etc. Each of these models is incomplete in the number of variables it is able to account for, and even the inputs it takes into account are snapshots, they can't account for the history of individuals, such as changes in cholesterol over time.
  9. A significant problem with risk estimates, then, is that they represent predictions for the future in mathematical terms in a way that explicitly communicates a probability (Your risk for having an MI is 20%), but lacks the ability to also communicate the success of the model, or, in other words, the probability of the probability. Disease risk predictions, like weather predictions, become confused with other scientific mathematical models. Even these models are "mathematical hypotheses," albeit ones that have succeeded in representing the pertinent systems accurately through a long history of experiments. But because that historical success comes to support a conflation between the natural reality and the mathematical modeling of that reality, a type of misunderstanding about the nature of scientific models becomes imported into disease risk models.


  1. Dupre's book provides an account of the different frames for thinking about genetics/genomics. There seems to be a potential harm in implementing genomic understandings into a world that still treats of DNA in the frame of classical genetics.


  1. Is evidence-based medicine a form of theoria or a form of phronesis? It appears to be an attempt for theoria to bridge the gap from the theoretical to the practical, using a skeletal account of phronesis that involves only deciding which evidence is most pertinent to a particular patient.
  2. While the problems with this account vis a vis phronesis are obvious, it's problems vis a vis theoria are even more important. EBM requires professional judgement on the part of the provider - Which evidence applies here? What are the implications of studies that don't quite fit? This is closely linked with another concern - that EBM does not generate desirable outcomes in all cases. Evidence generated in the ways currently used are based on relatively heterogeneous groups. The failure of EBM is based on two elements: the concern that available evidence isn't applicable, and the concern that available evidence is for heterogenous groups, and thus imperfectly predicts outcomes.
  3. Personalized Medicine has emerged from a deep anxiety about this shortcoming of EBM. Personalized Medicine is based on the commitment that (1) the application of evidence should be relatively straightforward (minimize professional judgement and, thus, contingency) and (2) the evidence applied should be for homogenous groups into which the patient fits perfectly. This is why the term "stratified" is sometimes used.
  4. The problem with Personalized Medicine, though, is that attempts to "fix" EBM but brings no new conceptual innovation to the situation. Personalized Medicine is, in fact, EBM repackaged. It could even be said that Personalized Medicine is a more fundamentalist version of EBM.
  5. One question, then, is whether PM effectively addresses the practical (i.e. translational) goals of medicine based on theoria, or are practical reasoning approaches more appropriate. Put more directly, can PM do something EBM can't, or does PM, like EBM, require practical reasoning to succeed?