We thank Drs. Marret, Gentili, Bonnet, and Dagnino for their interest in our article and the comments and annotations in their letters. We should perhaps clarify that our study was not intended to cover all the information on coca leaf and its ramifications, which are, nonetheless, fascinating, but to highlight the early history, which has always been a bit obscure. This is the reason that the first part of the article focuses on the sixteenth century and the rest on issues regarding local anesthesia.

We essentially agree with the comments contained of Drs. Marret, Gentili, and Bonnet about Thomas Moréno y Maïz, M.D., Ph.D. (more appropriately spelled, in Spanish, Tomás Moreno y Maíz; Paris, France). 1He was, indeed, a pioneer, the first to conduct rigorous experimentation in animals to evaluate the effects of cocaine; we believe that this is reflected in the article we published in Anesthesiology. 2 

With respect to the remarks in the above text on Basil (or Vassily) von Anrep, M.D., (Department of Pharmacology and Pharmacotherapy, University of Würzburg, Würzburg, Bavaria, Germany; 1852–1927), 3we merely note that although he repeatedly cites the Moreno y Maíz article in his classic study published in 1880 (page 39, page 40, and page 43), 4the novelty of his contribution was that he experimented in human beings (ibid. , page 47), highlighting the anesthetic effect at the end of his 17 conclusions (page 73).

With further regard to von Anrep and in reply to Dr. Dagnino, we wish to thank the authors for this information, 3of which we were unaware, and regret only that we have been subsequently unable to access the original publication. In any event, we point out that only 21/2 months elapsed between September 15, 1884, 5when ophthalmologist Carl Koller (1857–1944) announced his discovery at the Heidelberg Congress (September 15–16, 1884; Heidelberg, Baden-Württemberg, Germany), and December 6 of that year, when Richard John Hall (18??–1897) and Dr. William Stewart Halsted (1852–1922) reported blocking a nerve trunk 6; moreover, because it was not until they read Dr. Henry D. Noyes’ article 7released on October 11 that they knew of Koller’s work, the actual interim was no more than 11/2 months. Consequently, von Anrep’s contribution in this regard is particularly relevant.

We agree, with respect to Koller, that his discovery may have been serendipitous, but as we noted in our article, he did go to the trouble of running experimental tests to verify his finding before reporting it to the Heidelberg Congress. 2 

Universidad Complutense de Madrid, Madrid, Spain.calata@odon.ucm.es

Moréno y Maïz T: Recherches chimiques et physiologiques sur l’érythroxylum coca du Perou et la cocaïne. Paris, Louis Leclerc Libraire-Editeur, 1868
Calatayud J, González A: History of the development and evolution of local anesthesia since the coca leaf. Anesthesiology 2003; 98:1503–8
Yentis SM, and Vlassakov KV: Vassily von Anrep, forgotten pioneer of regional anesthesia. Anesthesiology 1999; 90:890–5
von Anrep B: Ueber die physiologische Wirkung des Cocaïn. E Pfluger Arch Ges Physiol 1880; 21:38–77
Liljestrand G: Carl Koller and the development of local anesthesia. Acta Physiol Scand Suppl 1967; 299:3–30
Hall RJ: Hydrochlorate of cocaine. N Y Med J 1884; 40:643–4
Noyes HD: The ophthalmological congress in Heidelberg. Med Rec 1884; 26:417–8