Sir,Enlightenment era German Philosopher Immanuel Kant said that the chemistry of his times was “a Science” but not “the Science,” because the criterion of genuine science was in its “systematization” of reasoning by the rigors of mathematics.[1]Quoting this declaration of Kant, Scottish biologist D’Arcy Thomson introduces his book on biological evolution, apologetically stating that the matter of his discourse will take much time to scale up to Kant's expectation.[1]Ambar Charkarvarty's viewpoint on neural circuitry of visual artistic production and appreciation was a bold attempt on a difficult subject.[2] True to its limits, the author admits that what he has hypothesized was “entirely conceptual” and needing experimental proof. However, he qualifies this hypothesis as “based” on “established principles of neuroanatomy, cognitive neurosciences, and deduction from case studies.”This writer doubts whether the epistemological nature of biology, primarily being an observational science, with very limited element of “theoretical reasoning,” permits one-to-one reasoning as seen in exact sciences like theoretical physics (Immanuel Kant's “the Science”). To prove or disprove that aspirin-clopidogrel combination is better than aspirin alone in preventing vascular events, we need a direct head-to-head comparative observation of the groups with strictest scrutiny of measures to prevent every possible confounder. Here, theoretical knowledge of the “nature” of aspirin and clopidogrel would not allow us to “predict” the outcome of the trial. Indeed, the history of medicine is full of wonderful theoretical possibilities becoming anything but the contrary on actual clinical scrutiny.This brings us to the validity of “inferences” from isolated case reports on patients whose disease might involve multiple isolated or disseminated lesions that may not be discernible by available imaging technologies (MRI, fMRI, PET). Added to this is the incredible complexity of the biological feedback and parallel processing system. For instance, Essen et al. using pathway tracing techniques report 305 pathways interconnecting 32 visual areas in primate brain, with reciprocal connection and multiple feedback loops.[3] Also, the concept of modularity of brain function, though true in certain number of restricted functions, needn’t be true for many multimodal and/or supramodal functions.[4] As the author admits, many workers question the depiction of brain function in serial step-wise manner.[4]In this context, the phenomena demonstrated by single case studies are at best hypotheses that need “quantitative” validation like everything else in biology and medicine. However, because of the rarity of such phenomena and the non-feasibility of experimentally creating identical brain lesions, such “quantitative validation” becomes almost impossible.When hypothesis is made on hypotheses, we would have to call it “metahypothesis.” One wonders if “metahypothesis” has any validity beyond what “metaphysics” has over physics. Indeed, many areas of cognitive neurology are extremely complex that one has to wonder whether the subject matter defies the methods available or ever feasible for its study. On a lighter note, as Emerson M. Pugh said, if the human brain were so simple that humans could understand it, human would be so simple that he couldn’t! Here, a discussion of the “limits of science and the science of limits” will be very pertinent.[5]