Del 10: The Cajal Club har också firat metodens 50-årsjubileum


…tillsammans med FENS (Federation of European Neurosciences) Detta skedde i Barcelona den 15 juli 2012 och tillkännagavs på internet så här:

FENS Special Event Sponsored by the Cajal Club:

The Falck-Hillarp histofluorescence method: 50 year anniversary
In 2012, it is 50 years since the publication of the Falck-Hillarp histofluorescence method (Falck, Hillarp, Thieme and Torp, J. Histochem. Cytochem, 10: 348-354, 1962). This method was the first approach that allowed visualization of transmitter-specific systems at the microscopic level, and had a ground-breaking impact on the development of our understanding of the anatomy, pharmacology and function of the monoamine systems in the CNS and PNS. In the early 1960s, dopamine, noradrenaline, adrenaline and serotonin were known to be present in the brain, but it was the application of the new formaldehyde histofluorescence method that made it possible to link these putative transmitters to specific neuronal systems and map their distribution and anatomical projections in great detail. In the 1980s the Falck-Hillarp method was superseded by more flexible and accessible microscopic techniques, in particular the powerful immunohistochemical method and the in situ hybridization technique. Leading scientists who played a central role in the study of catecholamine and serotonin systems during this dynamic period will give a brief personal account of selected key events, followed by an open Q&A session with participation of members in the audience.

Den eller de som skrev denna presentation har inte tagit hänsyn till den absolut första publikationen om fluorescensmetoden, nämligen Falck, B. and A. Torp, New evidence for the localization of noradrenaline in adrenergic nerve terminals. Med. exp. 1962, 6: 169-172 (Med Exp 1962) . Detta antyder starkt att Arvid Carlssons myt om metodens uppkomst (Arvid Carlsson 1965) fortfarande hålles vid liv.

Jag skrev till kontaktpersonen för arrangemanget, Dr. Charles E. Ribak, Department of Anatomy & Neurobiology, School of Medicine, UC Irvine, Irvine, CA 92697-1275, presenterade mig som Falck i namnkombinationen Falck-Hillarp och berättade om metodens tillkomst. Dr. Ribak föreföll förundrad över det faktum att en av oss fortfarande var i livet. Men han visade sig vara en ytterst hederlig person, som hade förståelse för mina synpunkter. Han beredde möjlighet för mig att vara med i Barcelona genom att ordna resebidrag och, trots stora svårigheter att ändra i mötesprogrammet, ge mig 8 minuter för att presentera ett inlägg i diskussionen. Efter grundligt övervägande avstod jag från detta generösa erbjudande, helt enkelt av den anledningen att den eller de som författat mötespresentationen eller lämnat referensuppgiften till densamma antagligen skulle finnas med i auditoriet där också Annica Dahlström fanns. (Hon var nämligen ledamot i panelen som bestod av: Kjell Fuxe (Stockholm, Sweden), Annica Dahlstrom (Goteborg, Sweden), Yves Agid (Paris, France), Floyd Bloom (La Jolla, USA), Larry Swanson (Los Angeles, USA), Anders Björklund (Lund, Sweden)) Av dessa var Anders Björklund och Larry Swanson medlemmar i programkommittén.

Detta skulle innebära obehaget att, genom att framlägga den sanna historien, berätta för de involverade en självklar sanning som de är väl medvetna om. Nästan uppträda som åklagare hur goda bevis jag än har mot de ”åtalade” och behöva påtala frånvaron av etik och moral. Som att fråga Annica Dahlström hur det kan komma sig att hon fortfarande 2001 kunde publicera denna verklighetsfrämmande myt om metoden som tillverkades på en enda eftermiddag (se denna hemsidas del 7 ”Myten publicerad”). Hon vet att hon publicerade en lögn därför att hon är en professionell forskare som väl känner till basala publikationer och kan utvärdera dem.

Jag skrev därför till Charles Ribak 2012-06-30:

Dear Charles,

As scientists we have the obligation adequately to refer to publications which affect our own activity. The author(s) of FENS´s notice regarding The Falck-Hillarp histofluorescence method: 50 years in perspective has not fulfilled this obligation. Needless to say it is important to know exactly which publications shall be celebrated at this FENS Special Event sponsored by the Cajal Club. I wrote to you on April 19 as follows:

I would like to inform you that an error has slipped into the notice of the Cajal Club´s FENS Special Event: The Falck-Hillarp histofluorescence method: 50 years in perspective. In this notice it says: “In 2012 it is 50 years since the publication of the Falck-Hillarp histofluorescence method (Falck, Hillarp, Thieme and Torp, J. Histochem. Cytochem,  10: 348-354, 1962).  This method, following in the footsteps of classical neuroanatomy, was the first approach that allowed visualization of transmitter-specific systems at the microscopic level.” This reference is not correct. That paper reports results regarding the chemical background of the method, a study that was initiated by the fact that a usable histochemical method for visualization of the monoamines in question had come into being. The first paper on the histofluorescence method which thus preceded the above-mentioned paper is:  Falck, B. and A. Torp, New evidence for the localization of noradrenaline in adrenergic nerve terminals. Med. exp. 1962, 6: 169-172.

There are many proofs of this that can be referred to. I gave you one in the same letter:

”In December 2008 I was invited to THE FIRST INTERNATIONAL HILLARP AMINE CONFERENCE at the Karolinska Institute in Stockholm. Remarkably, mine and Torps paper was not mentioned in the invitation notice. I wrote to the arrangers and called attention to this. The lectures were published in a special issue of Progress in Neurobiology and in the Introduction they (Ann-Charlotte Granholm, Lana Skirboll, Marianne Schultzberg;  Chemical signaling in the nervous system in health and disease: Nils-Åke Hillarp’s legacy. Progress in Neurobiology 2010, 90, 71-74) described the development of the fluorescence method with the following words (page 73):
”An intense research had begun already in 1959 to develop histochemistry of the monoamines, largely headed by Bengt Falck in collaboration with Nils-Ake Hillarp and Arvid Carlsson (see Carlsson et al., 1961, 1962; Falck and Torp, 1962; Falck, 1962). The development of the method in the first set of experiments included freeze-drying of the tissues, exposure to iodine, embedding, and sectioning. These experiments were the forerunners of using dry formaldehyde gas as the reaction agent and were mostly carried out in Falck’s laboratory in Lund, since Arvid Carlsson’s laboratory in Göteborg, where Hillarp was working at the time, did not have the histological equipment for the studies. Hillarp always recognized his collaborators, especially Bengt Falck, for development of this vast and expanding field. In his own words from an expert opinion in 1963 (originally written in Swedish): ”Falck and Torp were the first to be able to demonstrate accumulation of adrenergic transmitters in sympathetic nerve terminals. This has enabled us, for the first time, to directly demonstrate and study the extent and structure of the entire adrenergic innervation apparatus throughout the various tissues and organs of the body. Without any doubt, Falck has hereby delivered the most important contribution to neurohistology since the era of Golgi and Cajal. Additionally, it has now become possible to localize the monoamines in the brain on a cellular level which is of fundamental importance for the understanding of the functions of these amines within the CNS.”

But you answered: ”Thank  you for your email about the error in the 50 year celebration. At this time, I have to let it ride as it is because it is too late to change any of the announcements. I hope  you understand.” To be honest I did not understand at first. When is it ever too late to correct an untrue historical statement particularly in connection with the Cajal Club? Soon afterwards I realized that other forces lie behind the presentation and the arrangements of the panel discussion at this FENS Special Event, which determined that Falck et al., 1962 and not Falck and Torp, 1962 (see: > Appendix > Facsimile of the article by B. Falck and A. Torp: New evidence for the localization of noradrenalin in adrenergic nerve terminals Med.exp. 1962, 6: 169–172) was the first publication of the histofluorescence method. You, Charles, clearly saw the true story of how the method came about. I have wondered much what is the motivation to renounce the existence of the article by Falck and Torp (1962) and why it has become such a delicate subject to refer to.

The first person to deliberately turn a blind eye to its existence was Arvid Carlsson, Emeritus Professor of Pharmacology and Nobel Laureate in Medicine and Physiology in 2000. In a public report to the Karolinska Institute 1965 he stated that this method of fluorescence microscopy resulted from less than one day’s work during the second half-year 1961! He did this against his better knowledge. Only 3 years earlier he was asked by the Medical Faculty, University of Lund, Sweden) to evaluate my research merits in connection with my application for a position as research assistant and in that context he also read the above-mentioned publication by Falck and Torp (1962). I quote the following from his expert statement (originally written in Swedish):

 ”Falck, together with his coworker A. Torp, have invested extensive efforts to elucidate the histochemistry of chatecholamines. Their first important result was the demonstration of a new type of chromaffin cell, capable of storing dopamine. But what is far more important is that — largely because of Falck´s technical ability and scientific imagination — it has been possible to elaborate extremely sensitive fluorescense-microscopic techniques aiming at histochemical demonstration of catecholamines and 5-hydroxytryptamine. One of these methods has enabled Falck and Torp — as the very first — to demonstrate that the transmitter of adrenergic nerves, noradrenalin, is accumulated in the nerve terminal — a result that, according to professor U. von Euler, is one of the most important advances within this field during the past twenty years. Not least important is that it is now possible, without difficulty, to demonstrate and study the adrenergic innervation mechanisms in all tissues of the body. This must be characterized as no less than revolutionary.”

He cannot possibly mean that this statement implies  ”less than one day´s work in 1961”!

Arvid Carlsson and Annica Dahlstrom have in various contexts, individually or together, promoted this ”less-than-one-day-myth”. Besides being a downright lie it is an insult to the competent and hardworking coworkers that I worked with in my laboratory in the beginning of 1960 when the developmental work with the fluorescence method started (cf. ).

This myth, or in more clear words, downright lie, has unfortunately been accepted by quite a few scientists. Altogether, the distortion of the history behind the Falck-Hillarp method has become such a sensitive affair so many will not have it mentioned in context with scientific symposia and consequently conceal the Falck and Torp, 1962 publication.

I appreciate it very much that you, in spite of the difficulties involved with the task, offered me the possibility to speak for 8 minutes about the historic paper that I co-authored 50 years ago. That tells a lot about your high level of honesty and objective attitude! The difficulty in this task is that that the person(s) who is/are responsible for the notice of the meeting and who excluded the first publication of the jubilee object is/are present as is also Annica Dahlstrom. I am not afraid of telling these people the truth, but it feels unpleasant to tell them a truism that they are well aware of, like pointing them out and reproaching them for their lack of ethics and morality. Like asking Annica Dahlstrom why she still can publish this mendacious story in 2001 – see Part 7 ”The myth was published”. She knows that she published a lie because she is a professional scientist who can find basic publications and evaluate them but the question remains why did she not have the courage to avow her rape of the truth.

The correspondence is just as damning as the spoken word. So, I think I choose to abstain from going to Barcelona, but I would appreciate enormously if you would forward this correspondence to the participants. Please share with me any thoughts they might express regarding the history behind the development of the Falck-Hillarp method. I would like to thank you ever so much for the generosity you have showed me since I first wrote to you in February that I had accidentally discovered via the Internet this FENS Special Event sponsored by the Cajal Club. Not only was I kindly invited to attend the meeting but you also fixed an anonymous donor who agreed to support my travel expenses. I will never forget your kindness. All the best,

Bengt F

Allt sammantaget kan konstateras att det finns krafter som har intresse av att hålla liv i nobelpristagaren Arvid Carlssons motbjudande myt som säger att Falck-Hillarp fluorescensmetod kom till efter en enda eftermiddags arbete 1961. Motbjudande är ett milt ord, 1962 kunde han i en officiell handling berätta den sanna historien (Arvid Carlsson, Sakkunnigutlåtande), bara tre (3!) år senare så presenterade han sin myt i en annan officiell handling (Arvid Carlsson 1965)!


Historien fortsätter… Del 11: Till slut