Lancereaux revisited once again

Sir,

We were surprised once again to read a published response by Connor and Boulton ¹ to our rebuttal of their late 2022 critique ² to our paper published in early 2022 ³ —especially since the second rebuttal ¹ appeared online even before proofs for our response have been received by us. ⁴ Typically, editors publish one critique of a paper and offer the authors of the original paper an opportunity to respond as the last word. Since our paper has now been critiqued twice by Connor and Boulton (and both responses have been published in JMB); in the spirit of fairness, we should be able to respond one final time.

On the matter of “accepted principles of historical methodology,” ¹ not all medical historians agree on every element of historiography but that is beside the point. Our contention is that historical research on pathophysiological topics should not ignore pathophysiological realities, a point one of us (JRW) periodically tries to reinforce to medical historians. ⁵

HC has volunteered that he was known to the editor. ¹ We do not understand the relevance of this revelation to the peer-review of our original paper nor are we in a position to comment on his speculation as to whether the reviewers chosen by the editor “might not have had any expertise in historical methology.” ¹ What we experienced was a rigorous peer-review process to which we responded satisfactorily to all criticisms, as indicated by the correspondence we received from the editor—that is how the process is supposed to work.

On the matter of gross versus histological findings, our original paper described only gross findings. ³ We did not mention “interstitial fibrosis” in that paper; this was discussed in our rebuttal ⁴ to one of the questions raised in the first Connor and Boulton response. ² As we stated, ⁴ the pathological diagnosis associated with pancreatic duct lithiasis (i.e. chronic interstitial pancreatitis, interlobular type) was named and fully described 20 years after Lancereaux's studies, ⁶ and his histological descriptions were based on crude frozen section preparations that many of Lancereaux's contemporaries would have maintained were essentially all but uninterpretable. ⁷ His histological descriptions were not detailed (nor did they merit referencing in the paper ³ ). In a short paper directed at clinicians and medical historians (not pathologists), “fibrocalculous” seemed to be a concise descriptor. Unfortunately, the use of this descriptive term (i.e. as opposed to a specific diagnostic term) has generated confusion. While, of course, diagnostic names often change over time (n.b., Lancereaux did not even give his pathological findings a name—he only described them), the typical gross pathological findings associated with pancreatic duct obstruction caused by calculi cannot have changed over a 20-year timeframe; the findings would be striking then as they still are now. Finally, marked fibrosis does not need to be seen histologically to be diagnosed—it can be felt by palpation or by cross-cutting through tissues as can pancreatic atrophy.

Speculation that Lancereaux was describing the very recently reported entity Fibrocalculous Pancreatic Diabetes ² remains “farfetched” ⁴ to us. We did not mention that the patient was a Belgian cabinet-maker living in Paris in our original paper as it seemed tangential—until Connor and Boulton theorized the patient could have been a colonial officer in a tropical country. ² And in their second rebuttal, they double down on the idea, insisting that “even if they [i.e. we] had disclosed this information in their original paper it would have made no difference to our suggestion.” ¹ What is important is that even if this patient did have Fibrocalculous Pancreatic Diabetes, it would still only reinforce our reason for writing the paper; Lancereaux's diabète maigre (thin diabetes) is not akin to current-day type I diabetes.

Connor and Boulton suggest that we must be unaware that “terminology and conceptualization of disease can change relatively rapidly over time.” ¹ They then write:

If they had understood the importance of this point they might not have written that ‘the fundamental pathological and biological properties of diabetes mellitus cannot have changed profoundly in the past 140 years.’ How then, for example, do they explain the world-wide increase in incidence and prevalence in Type 1 diabetes in just the last few decades. ¹

Connor and Boulton also criticized our statement that it is “biologically implausible to suggest that highly emaciated type I diabetic patients uniformly lived for two or three years after diagnosis …” by saying “we did not use the word ‘uniformly.’” ¹ True, but we did, and it is disingenuous to try to make this distinction, when the papers being critiqued state that all of Lancereaux's thin patients lived 2–3 years after becoming severely symptomatic.^3,4 In their second rebuttal, they combat our analysis by citing two specific examples of patients living “a surprisingly long time until saved by the arrival of insulin.” ⁴ However, part of what they left out of the quotation at the beginning of this paragraph (by invoking “…”) is our terminal phrase “prior to the discovery of insulin, when even Frederick Allen's and Elliot Joslin's rigorous, meticulous life-prolonging dietary therapies could not accomplish such results in the decade immediately preceding the discovery of insulin.” Both of Connor's and Boulton's examples were patients maintained on state-of-the-art dietary therapy after 1920. Such life-prolonging dietary therapy was unknown and none of Lancereaux's patients 40 years earlier had access to this level of meticulous care, yet all survived 2–3 years. It is biologically implausible that any had what we now call type I diabetes.

Connor and Boulton conclude their second rebuttal by suggesting that they have dispensed with our claimed “seminal observation that Lancereaux's clinical and autopsy studies have been erroneously considered to be documentation that the medical world by 1880 was well-aware of two distinct types of DM, resembling current-day type-I and type-II” by simply writing “whether Lancereaux's diabète maigre corresponds to Type 1 diabetes or his diabète gras to Type 2 is difficult to determine on the available evidence.” ¹ Writing this single questionable sentence does not refute our entire analysis—especially when Lancereaux's cases of thin diabetes show pathological changes which categorically exclude a current-day diagnosis of type I diabetes and his untreated thin patients were all middle-aged or older and uniformly survived 2–3 years. The extensive prior literature cited in our original paper ³ claiming that “the medical world by 1880 was well-aware of two distinct types of DM, resembling current-day type-I and type-II” is wrong—despite two rounds of disagreement by Connor and Boulton.