The starting materials are in our warehouse, where samples are taken…
“We began to practice the medical profession in the far-off times when Professor Alfred Fournier’s wise, extensive teachings were universally abided by as a fundamental doctrine of the syphilis specialists’ knowledge, in which everyone considered mercury the main, almost exclusive remedy for syphilis – it was called a specific drug – with no remote signs then of a therapeutic “plus ultra”…
Questions of simple details were discussed, such as the advantages and disadvantages of injections of mercury di-iodide, grey oil and calemolanos, and those classical, very common, strictly periodic and intermittent mercury frictions, recommended by Fournier, followed by prolonged swallowing of strong doses of potassium iodide and that, in Spain, used to end up with a ritual visit to the famous Archena (Murcia) baths. They had been the basis of the cures for many decades and they began to be taken out of practice.
And hardly any clinic – Gaucher – dared to advise the use of arsenic for treating syphilis”.
…That are meticulously examined in the analysis laboratory…
“Fate, that counts so much in the life of mankind, had in store for our lives – directed towards studying the dermo-syphilis speciality from the lecture halls – the opportunity to practice in a rather exotic environment with a special, large clientele, in which the afflictions of syphilis were extraordinarily abundant. There were many cases of those malignant, corrosive, mutilating lesions that we had only seen on some occasion in the University Clinic and many times in book illustrations and on the plastic exhibits in the anatomical museums.
The peculiarity was that these were patients who, until then, had never been exposed to the impurities caused by contact with or the insertion of mercury, in whom the syphilis was completely free to develop without being held back by therapeutic brakes that would restrict its devastation”.
…and purified if necessary
“A very short time before, the mysterious, invisible syphilis germ first seen by Bordet had finally been discovered by Schaudin and Hoffman, wise Germans who, in pursuit of the Louis citorrites, stumbled on the pale spiral, later the spirochete and finally Schaudin Treponema.
And a few months later, another German biologist, Wassermann, while testing in syphilis the complementary deviation phenomenon discovered by Bordet, found the reaction that was named after him, which was an invaluable diagnostic resource for many years. Later, once its technique had been perfected and expanded by the flocculation reactions, it would become an essential therapeutic guide, as it is today”.
Manufacture of arsenic acids starts…
“In those times, we began to know something about a new drug – atoxyl – which, used to combat trypanosomiasis following Uhlenhut’s indications, was extremely successfully tested in the treatment of syphilis. This success was almost immediately tarnished due to the frequent repetition of accidents – optic neuritis – that were as serious as they were irreparable.
It was the second half of the year 1910 and autumn was approaching when another wise German, Ehrlich, as a result of many years of patient work, informed the world of a new product – Salvarsan – , which is also labelled with a number – 606. The until then routine therapeutics of syphilis would have to be revolutionized”.
…By isolating the components sought.
“A very simple incident had the momentous consequence of fulfilling our efforts and interests, for we were appointed to form part of an official Commission that, in Spain, had been entrusted with studying and clinically testing Salvarsan, better know and made popular by its numerical name: 606.
The Commission acted seriously and conscientiously on abundant, well-selected clinical material, generously provided with phials of Salvarsan and also using what was then extremely modern means of research, which consisted of testing the Treponemas under the ultramicroscope and the practice of the Wassermann reaction”.
Some products are converted into others…
“Once its work was finished, the Commission recorded the results obtained in a Report in which it proclaimed the evident, extraordinary effectiveness of Salvarsan when administered intravenously. It rejected intramuscular injections since they were too painful (Alt), and it showed reasonable reserves regarding the persistence of the cures obtained.
And, indeed, the universally observed facts did not take long to justify our precautions”.
…By introducing new radicals into the molecules.
“Ehrlich, based on apparently exact, irreproachable laboratory research, had actually stated that syphilis was completely cured with a single injection of Salvarsan. When a dosage of one centigram per kilo of weight was administered, it would cause the destruction of all the existing Treponemas in the infected body.
But in the human clinic, reality did not confirm such promising conclusions. Although the almost instant, marvellous effectiveness of an injection of Salvarsan in the most serious syphilitic lesions was true, it was soon seen that, in many cases, once it reached a certain level, it stopped and would not progress further on the improvement obtained. In order to continue with it, more injections were required”.
The products are dried in large vacuum ovens.
“It was also proven that, in the majority of the patients, once clinical recovery was achieved, the Wassermann reaction was still positive.
Ehrlich’s sterilisans magna therapy had failed…”o…”
The arsenic acids obtained are used to start the manufacture of arsenobenzenes.
“From here on, many syphilis specialists (in Spain, Azua), in their struggle to cure syphilis, opted to either repeat the Salvarsan injections or to alternate them with series of mercury injections. Therefore, to some extent they returned to the chronic intermittent treatment of syphilis advocated by Fournier.
Once the Commission had ended, when we returned to attend to our special clientele with abundant amounts of the new drug, you can imagine how many fast and brilliant results we were able to achieve”.
All the operations must be performed in a vacuum or inert atmosphere.
“Meanwhile, Ehrlich continued with his brilliant research that led him to modify Salvarsan first with sodium Salvarsan and then with Neosalvarsan, with the code number 914, which, if it did not have advantages over Salvarsan, at least simplified the technique considerably, reducing it to such a simple thing as giving a small intravenous injection.
Fortunately, Salvarsan was only remembered for that prior, extremely delicate neutralization of the solution’s acidity using caustic soda, for that risky, enormous 200 cc injection, for that complicated Schreiber syringe with its double stopcock and even for Azua’s ingenious injecting device.
But with the new medication, Neosalvarsan, fast and universally adopted, not everything was a reason for rejoicing…”
An intricate network of pipes: water, stema, coolant, different classes of vacuum, and pressurized gases,…
“Apart from the awkward incident of the extravasated injection that caused painful swellings and abscesses that were slow to heal, and the dramatic nitritoid crises, other very varied and serious accidents were awaiting the doctor.
These were the incredible erythrodermias, the alarming purpura cases and the fatal haemorrhagic encephalitis cases. Post-neosalvarsan ictericias were also frequent and cranial neuritis was not rare”.
…Guarantee the services centralized in the machine room.
“With these elements, the black legend of Salvarsan and Neosalvarsan was created to which the French doctors contributed considerably, who had felt, and still feel, an instinctive, unyielding hostility towards the Tudors.
But time was not going by in vain, and the clinical and research work was not giving fruitless results.
The neosalvarsan treatment criteria, generally along with mercurial treatments, was improving and being methodized, and through successive modifications (Stern, Noguchy, Calmette, etc.), the Wassermann reaction technique was perfected as well as the Treponema research technique. We immediately applied the progress to the clinical work we were entrusted with”.
Powerful deep vacuum pumps are needed for several operations…
“In 1914, with the outbreak of the European war and the establishment of the hermetic Germany blockage by the allies, the Neosalvarsan stock in Spain soon ran out. That was when a few informed doctors hyperbolically valued the neosalvarsan injections, while the rest had to turn to the slow mercury remedies again. For those who were used to the amazing action of Neosalvarsan, it meant something like changing from a fast car to a slow ox cart.
Since years before, the chemists and practitioners in the neighbouring country, who are even more French than therapeutic, had been trying to spread the use of certain arsenic preparations (among them hectine), with the hope of them being more successful than Ehrlich’s drug”.
…Such as drying the product in special ovens.
“As a result of the war, with patents and manufacturing privileges abolished, the French chemical industry, driven by the double incentive of necessity and competition, launched numerous substitutes for Salvarsan and Neosalvarsan. They were simple chemical type variants of arsenic benzene. They were distributed under the names of Sulfarsenol, Rodarsan, Treparsenan and their corresponding Neosulfarsenol, Neorodarsan, Neotreparsenan, etc., while the English were creating Arsphenamine and Neoarsphenamine.
During the war, too often in France and sometimes in Germany, due to rushed, defective production, the sorrowful black series of arsenic preparations made their appearance. They were so-called due to the many serious accidents they caused. For this reason, and for others that cannot be so easily confessed, the black legend was intensified, fuelled by the abundant publications about tragic and even mortal neosalvarsan accidents.
It was also during the European war when our attendance for many months at a dermo-venereological Clinic known worldwide allowed us to learn something about methods and techniques that, until then, were unknown or hardly known in Spain”.
A laboratory checks the whole manufacturing process step by step.
“Shortly after the end of the war, in the countries that had been at war – and in the neutral countries too, for we were all affected – the spread of syphilis made it seem a serious pandemic.
The threatening progress of the illness was first controlled and then reduced to proportions we shall call normal thanks to the methodical general use of the neosalvarsan treatments. A medication has never been able to prove to be so completely and permanently effective through universal experience, extensive to millions of observations, as on that occasion. And the obvious effectiveness of the prophylaxis due to the treatment has never been able to be better evidenced”.
The alcohols and other volatile products are removed.
“The black legend, the slandering label of the neosalvarsan drug, was destroyed, for next to so many million recoveries, what could some serious or fatal accidents mean?…”
This is followed by chemical analysis…
“Throughout the course of the first years of peace, marked improvements were achieved in the diagnosis and treatment of syphilis. The distribution of the paraboloidal or black background condensers helped to find Treponema, the colouring procedures of which had already been perfected by the silver impregnation method (Fontana), while continuous perfectioning of the Wassermann type colorimetric reactions, and especially Porges’ discovery of the agglutinating faculty of the syphilitic serums on the lipic suspensions, cleared the way to the most sensitive and specific agglutination reactions (Meinicke, Kahn, Garriga, Müller, etc.). On the other hand, when Ehrlich’s theory on intraorganic parasitotrope therapy was in full regression, the research done by Wagner von Jauregg, Kirle, etc., using the exaltation of natural defenses through paludization and the protein therapy, allowed positive results to be achieved in those syndromes – tabes, general paralysis – which had, until then, been inaccessible for the most daring and violent therapeutic assaults. Finally, Levaditi, continuing Balzer’s studies, managed to find certain bismuth preparations with immediate effectiveness in the treatment of syphilis”.
…And biological testing in animals.
“But to be fair, we have to admit that on the amazing popularity that the bismuth drug reached, two circumstances had a powerful influence: the worldwide prestige of its birthplace – the Pasteur Institute in Paris – and – why not say it? – the persistent horror of many doctors at the fearful neosalvarsan accidents, which were still appearing in certain medical publications with shocking perseverance”.
When all the results are favourable, the Neo-Faes is dosed and packaged in ampoules…
“It was then when circumstances, that do not have to be given in detail, fulfilled our hopes by placing us in charge of a Clinic in which, due to the type and number of its patients and to its very wide range of diagnostic and therapeutic research resources, we were able to dedicate ourselves for many years to studying the different types of neosalvarsan treatment. We used from Sicard’s minimum daily dosages to Thompsom’s daring dosages and Leredde’s unusual ones, as well as practicing Hoffmann’s maximal “frühbehandlund” (early treatment); where we compared the results of purely arsenic treatments with mixed treatments – arsenic with mercury and arsenic with bismuth; where we tried to rehabilitate the scorned mercury by using high dosages of it intravenously; where we tested numerous series of bismuth preparations (Trepol, Neotrepol, Casbis, Wismulen, Muthanol, Quimby, Rubyl, etc.); where we tried our luck with unfortunate tabes and general paralysis patients with Gennerich’s endolumbar treatment, in spite of turning to salvarsanized serums and to arsenic and bismuth solutions, without obtaining, in any of the cases, the excellent results that were so commended by some famous neurologist (lafora); where we checked in a series of patients the usefulness of paludization and vaccine pyrotherapy in the treatment of syphilis, even having the nerve to try such a strong thing as paludizing syphilis and young individuals (Sáinz de Aja); where we ourselves witnessed the sunrise, the zenith and the fleeting sunset of the metalic salvarsans (Silbersalvarsán and NeoSilbersalvarsán); where we saw the categorical failure of the arsenic compounds (Stovarsol, Spirocid and Treparsol) administered orally, which someone proclaimed to be unbeatable (Clement Simon); etc., etc.”.
…That are sealed in an absolute vacuum, automatically checked using a special electrical procedure.
“And all this while carrying out a multitude of analytical or diagnostic complementary investigations like Noguchy’s intradermoreaction to lutein; the search for Treponema in the exudation of lesions, in the ganglion juice and in the phial drops produced by vejigatorio cantaridado; the preparation and trial of Frei’s antigen in the diagnosis of the then very recent Nicolas-Favre disease; the comparative tests of the serial serological reactions depending on different methods…”
Neo-Faes (Neoarsenobenzol) is ready for distribution.
“Until then, when treating syphilis we always used imported products, and almost exclusively Neosalvarsan.
But for some years a group of brave technicians and financers, following scientific and economic incentives, had tackled the company to manufacture in Spain a preparation that substituted and, if possible, was better than Neosalvarsan.
And that is how NEO-FAES was born.
And that is how, when in charge of our Clinic equipped with a very wide range of research resources and brimming with patients among whom those recently affected by syphilis constituted a legion, we were able, after many thousands of intravenous injections of the national product NEO-FAES, to compare its results with those obtained previously in identical conditions with the genuine Neosalvarsan. The observations were noted in detail in many hundreds of clinical files”.
* Texts: Dr. Sebastian Lazo García (year 1940).
* Photographs: Faes Group photographic archive.