Chemotherapy

"Here are my friends, the dyes, they will never fail me"

Paul Ehrlich (Strehlich, March 14, 1854 – Bad Homburg, August 20, 1915)

How the son of a Silesian innkeeper and liqueur distiller, as a medical student, was seduced by the effects of the new chemical dyes on human tissue, which after many years led him to develop a chemical preparation against syphilis, the first chemotherapeutic agent, and thus aroused the anger of many Germans, because syphilis was a punishment from God, you were not allowed to defy him by neutralizing his punishments.

The sensitive doctor was crushed by public attacks, trials and newspaper articles that led to his untimely death in 1915, at least according to his wife, because he himself had contributed significantly to that death.

Berlin, the capital of Prussia, becomes the capital of the new German Empire after the Franco-Prussian War of 1870/1871. In a fierce battle with Louis Pasteur's Paris, attention for scientific research exploded in those days.

There is much to suggest that the great diseases that have plagued mankind for centuries can finally be overcome – purely scientifically.

Scientists become heroes. Dozens of well-known 'microbe hunters' work day and night, looking for the causative agents of those diseases and then for means to combat them. The heroes of the young nation rival each other and form a block against their French colleagues.

Being Jewish in that patriotic environment is not an advantage: Jews remain at the bottom of waiting lists, they get the lesser jobs, they are passed over or put in the waiting room of a 'private teacher' for a longer period of time.

The Jewish doctors and microbiologists compensate for this through their efforts; because of the stupid jobs they have more time for their own research, they can specialize better. They fight to fit in, to be accepted; they are fiercer patriots than the Germans themselves; they work longer and harder.

Paul Ehrlich, of Jewish descent, is a solitary, monomaniac man, interested only in his research, with little regard for the world around him. "I am an outsider in religion, politics and other issues," he tells his biographer.

He too goes through the whole gamut of humiliations. For years he works unpaid, at the expense of his wealthy wife. Later, with the financial support of his father-in-law, he is able to set up a small private laboratory. He sees in his imagination what connects chemistry, biology and medicine.

And know early on how revolutionary this is. Stubborn, he continues silently. As a doctor he does not feel compelled to spend his life on sickbeds alone, as a researcher he has no ambition to teach.

Until he finally finds support and is put in charge of two large research institutes, which can compete with the Institut Pasteur in Paris and the Rockefeller Institute in New York. And he wins the Nobel Prize in Medicine, almost a second.

Only then will he develop chemotherapy – a term he coined himself – and the first antibiotic in history. 'Patience, Geschick (skill), Geld und Glück must have an investigator', is one of Ehrlich's favorite sayings.

He acquires it all. But at a high price.

Ehrlich was born in 1854 in Strehlen (now the Polish city of Strzelin) near Breslau (today Wroclaw), the largest city in Silesia. His father is an innkeeper who also owns a small liquor distillery.

His scientific interest is aroused by his mother's cousin, a well-known pathologist, who lets him look at body cells and the first chemical dyes through a microscope: the shock of his life. Each dye causes its own coloring in human tissue.

How is this possible?

He studied from 1872 in Breslau and Strasbourg, where, to everyone's surprise, his work table gradually became covered with stains in all colours.

He already knows exactly what he wants: 'Success in science presupposes that you fish in not too many waters', and 'I never asked what was going on at the time. You have to recognize the undercurrent, that's the main thing.'

Ehrlich then studies in Freiburg and again in Breslau. Microscopic staining is very fanatically practiced at the University of Breslau.

The great industrial progress is clearly connected with the enormous development of aniline manufacturing of those days, at BASF, Bayer, AGFA and Hoechst. 'The chief colourist of the laboratory,' said a contemporary, 'was 22-year-old Paul Ehrlich, who worked uninterruptedly – with nervous zeal.

We laughed at him because he always walked around with blue, yellow, red and green fingers between us.'

Or, "Ehrlich, that genius eccentric, walked through the laboratory with hands colored up to the wrists, as if he had been in countless paint pots." Ehrlich becomes fascinated by the relationship between certain dyes and certain cells in the body.

Why do certain dyes only attach to certain cell elements? The dyes become travel guides for him through the mysterious landscape of the cells.

In Breslau in 1876, Ehrlich first meets Robert Koch, a simple country doctor who manages to prove that every infectious disease is caused by a specific parasite.

Ehrlich received his doctorate in 1878, aged 24, with Contributions to the theory and practice of tissue staining. As a young doctor he has built up an enormous knowledge of chemistry.

Medicine and chemistry come to a spectacular alliance in those days and Ehrlich is an exponent of that zeitgeist. That same year, the director of the Berlin Charité hospital put him to work. The Charité enjoys great fame.

Students from all over the world come to bustling Berlin, which then has about a million inhabitants.

But the stock of pharmaceuticals is limited. There is quinine for malaria, mercury for syphilis, opium for pain, and digitalis (the poison of foxglove) for heart disease. Nobody knows exactly how they work.

The infectious diseases, the great epidemics such as the plague, cholera, typhoid fever and typhus flare up again and again. No one knows where they come from or how they disappear again. Wound infections are often fatal.

Chronic ailments such as tuberculosis or syphilis are widespread. In 1879 there had been another major plague epidemic in Astrakhan, Russia. How fast could it reach Berlin with the wrong wind? As late as the 1980s, cholera claimed the lives of 250,000 people in Europe.
Like all assistants, Paul Ehrlich lives in a small room in the Charité itself, a few square meters in size.

He has a small laboratory where he concentrates his staining techniques on the shape and structure of the cells, especially those of the red and white blood cells. By allowing the blood to dry in the thinnest possible layers, he quickly reveals its structure.

Ehrlich to his American friend Christian Herter: 'Luck and coincidence naturally play an important role in all experimental research.

Thus I owed the discovery of the fixation of red bodies to chance; in my small laboratory the preparations had been placed on the lid of the stove, because there was no room for anything else.

When I started coloring it the next day, I got to see the most wonderful images, because the maid, who had not seen the pictures, had lit the stove as usual.' A visitor: 'His table, on which stood a microscope, was completely covered with microscopic blood specimens.

Apart from Ehrlich, no one could find their way into it.'

Robert Koch arrives in Berlin in 1880, two years after Ehrlich. The 'hunting for microbes' will then really start. Koch becomes Ehrlich's great inspiration, a man of whom he has a picture on the wall both at work and at home.

Koch has only one goal in mind: to find the causative agent of tuberculosis. In 1881 he injected the first two guinea pigs with tuberculous material.

It is not until the 271st preparation that he sees 'the small, slender, slightly curved rods'. On March 24, 1882, he announced his discovery in a small circle. Among those present is Paul Ehrlich.

Ehrlich later says: 'That evening has always stayed with me as my greatest scientific experience.' Koch was able to make the tuberculosis bacillus visible with color, albeit very weakly. Ehrlich, the great color expert, quickly comes to his rescue.

In the same year 1882, Ehrlich becomes engaged to Hedwig Pinkus, daughter of a wealthy Silesian textile industrialist who will support him financially throughout his life. Friends wonder when he might have had time to get to know a woman.

He married in 1883. Although he lived close to the Charité, he had himself taken by carriage. He sees traveling the road on foot as a waste of time.

He neglects his health. Over breakfast he reads his mail, makes his first notes for the lab and smokes the first of twenty to twenty-five fat cigars, his daily ration. He is forgetful, the prototype of the absent-minded professor.

This goes so far that he writes himself postcards so as not to forget certain tasks.

In 1883 a major cholera epidemic broke out in Egypt. The last epidemic in Germany, with 160,000 deaths, was only seventeen years ago.

The French chemist Louis Pasteur – a hater of Germany, in permanent competition with the Berlin 'microbe hunters' – hastily sends his best men to Egypt to track down the causative agent of cholera.

Even before the French fail - one of them dies on the spot - the German government also sends its best bacteriologists, but by the time Koch and his assistants arrive in Egypt, the epidemic has died down.

Koch moves on to India where he searches for 'material' in the bodies of thousands of dead people.

And he discovers the demonic bacteria: "She looks like a comma." When Koch returns to Berlin via Egypt in 1884, he is welcomed as a victorious general: Germany has once again defeated France.

Self tuberculosis

That is the nervous atmosphere in which Ehrlich has found himself. While the 'microbe hunters' are achieving success, he continues to work on his color analyzes of blood cells. Ehrlich discovers that with certain dyes the intensity of oxygen uptake of cells or organs can be traced.

He will then receive the title of professor by special appointment for that study.

But in 1885 Frerichs, the professor who brought him to the Charité, dies unexpectedly, his protector, the man who first recognized his talent.

The new director doesn't understand Ehrlich's work; he would rather see the young doctor standing by a sick bed than play with his dyes in a laboratory. Ehrlich's relationship with the Charité's leadership deteriorates to the point of despair.

In an autobiographical sketch he later writes: 'When I couldn't take it anymore, I went to a cupboard in my little laboratory, where the countless jars of dyes were kept, and said to myself: 'Here are my friends, they will never let me down.”'

In 1888, during a chance examination of his own saliva, Ehrlich discovered the tuberculosis bacilli so familiar to him. He attributes the illness to the extremely unsanitary conditions in the hospital.

In September he resigns and he leaves with his wife for a long journey south, to the sun, to save his lungs: via Lake Garda and Naples they travel to Cairo and Luxor; a year later they return via Malta and Sicily.

He no longer wants to go to the Charité and hopes for a chair at the university.

He will not get it for fifteen years – clearly for anti-Semitic reasons, biographers later say.

With the support of his father-in-law, Ehrlich set up a small private lab in the Berlin district of Steglitz in which he conducts fundamental research into immunity against plant poisons. He is also working on the relationship between dyes and nerve cells and their possible therapeutic effect.

Immunology, the study of the body's natural defenses, captivated thousands of scientists, physicians and natural scientists in the Western world around 1890.

Robert Koch, now head of a new Institute for Infectious Diseases, announces at a medical congress in August 1890 that he may have developed a drug against tuberculosis, tuberculin. Patients from all over the world, especially wealthy ones, travel to Berlin.

Many die on the way, some just sit dead on the train. But the big breakthrough is yet to come. Ehrlich is placed in charge of a 150-bed TB hospital in the Moabit district and closes his private lab.

He manages to refine Koch's dosages so that in July 1891 he puts him to work at his famous Institute. Unpaid though.

One of his colleagues at the time later wrote: 'If a comparison is possible at all among great men, then I must say that Paul Ehrlich was the champagne of wines. He brimmed with brilliant ideas and had a clear vision of the future of medicine.'

At the time, a leader in Koch's Institute for Infectious Diseases was Emil Behring, who conceived the idea of preserving a body with chemicals, like you protect a ham against bacteria by smoking it. Together with the Japanese Kitasato, Behring had developed an antitoxin against diphtheria in the late 1890s.

At that time, 45,000 children per year died of diphtheria in Germany alone. Behring has also signed a lucrative contract with the chemical company Hoechst to provide all the information that would enable Hoechst to mass-produce the drug.

But Behring isn't chemistry-savvy enough to produce his antitoxin at precise concentrations. Ehrlich can. He intensifies the serum, sets up a standard and can thus claim part of the patent.

Incidentally, every package mentions the patent 'Behring-Ehrlich', but Behring tricks him and Ehrlich does not receive a penny from the license fees. Behring makes a fortune from the serum through Hoechst. Converted into a contemporary currency, millions of euros.

The two friends will never see each other again. Ehrlich: "I helped him into the saddle and he knocked me down."

At the beginning of 1895, Friedrich Althoff, the almighty director of the Ministry of Education and Medical Affairs, assigns the official quality control of all diphtheria serums produced in Germany to Paul Ehrlich's lab department.

That control remains under his direction until his death. And Althoff wants more. He wants to create an independent position for Ehrlich.

He sees the control station run by Ehrlich as a temporary solution. So on June 1, 1896, a separate institute was founded in Steglitz: the Institute for Serum Research and Serum Control. Director Paul Ehrlich.

The 'institute' consists of two small rooms that previously served as a bakery and barn. Ehrlich: "Small – aber mein." And: 'In case of emergency I can also work in a shed. All I need is a tap, a flame and some tissue paper.'

Ehrlich is fascinated by Behring's diphtheria antibody and tries to explain its action.

He concludes that a special attachment group – such as key and lock – connects with the toxin molecule and the corresponding receptor of the body cell, in order to develop its poisonous effect there.

The body cell responds to such compounds by constantly forming new receptors in the blood.

Receptors are like arms outstretched, ready to receive. 'In the blood,' says Ehrlich, 'substance and antibody combine without reaching or damaging the body cell itself.'

That is the principle of chemotherapy. The antibodies must have a specific relationship to the poison - drugs don't work if they don't get linked.

Writes one expert: 'The effect of Ehrlich's thinking at the time of its formulation was very powerful and can only be compared with the effect of the first successful application of Fleming's penicillin in 1942, which caused an avalanche of antibiotics.' In 1902 Ehrlich writes: 'I have made an effort in recent years to disseminate the chemical theory of the action of poison and antidote, and I must credit the widespread adoption of that chemical view.'

But the panacea remains a theory for now. He feels fierce opposition, especially from France – how could it be otherwise – but also from Vienna and Munich. However, Ehrlich is a tough fighter; he campaigns, he manipulates colleagues and scientific friends.

He publishes one text after another. 'He who is not for me is against me', that is how you could summarize his struggle.

A touch of revenge against Behring is never far off: "Look how far he's come without me." No sooner had Ehrlich settled in Steglitz than the question arises whether he wants to move his serum institute to Frankfurt and at the same time establish an Institute for Experimental Therapy there.

In Frankfurt, Mayor Dr. Franz Adickes, who wants to turn his city into a university town. Bringing in independent institutes is the first step.

Incidentally, Marburg, where Emil Behring has his laboratory, is nearby, as are the buildings of Hoechst, the producer of the diphtheria sera that Ehrlich's institute has to monitor.

In the second half of 1896, Adickes and Althoff come to an agreement: the city and the state together provide the necessary funds. The construction of the new institute in Frankfurt's Sandstrasse and the recruitment of staff will take two years.

Ehrlich is delighted to be able to leave Berlin: he is more than tired of the quarrels and rivalries between the scientists - often with Behring as the evil genius -.

And Koch, his spiritual father and shining example, hardly ever stays in Berlin again, as a 'microbe hunter' he travels the world. Moreover, the medical school has not proposed Ehrlich as a candidate for a chair for fifteen years.

One wave of anti-Semitism follows another. Frankfurt becomes the city of its great successes. He is 45 years old, in the prime of his life; his wife 35, his daughters are 15 and 13.

Out of Berlin

In the autumn of 1899, just before the turn of the century, his Royal Institute for Experimental Research can be ceremoniously opened. The institution is primarily responsible for the quality of all serums under state control.

It must also provide support checks for public hygiene, hospitals and doctors of the city of Frankfurt. And finally, Ehrlich commits to continuing research into immunity issues.

It is especially in this last area that he pulls out all the stops, so that a few years later he is already being praised for: 'The chaotic series of new research areas that he has opened up, and which are producing extraordinary results in all directions.' In 1903 he set up a separate cancer department, the first place in the world where cancer research Grossbetrieb is tackled on a large scale.

possessed

Ehrlich works like a man possessed again. Students come from far and wide.

Sir Henry Dale, one of Ehrlich's British collaborators in 1903/04, writes: 'Anyone who visited Ehrlich in those years, after a short but warm welcome, was immediately swept away in a wild stream of excited expositions of Ehrlich's latest discoveries and theories, lavishly illustrated with dye diagrams on any available surface, so that the visitor, even though his own interest and work lies in related scientific research, very quickly feels that the ground is sinking beneath him and he has nothing left but to resign himself to the flood of let words flow over him.'

Hundreds of colored pencils, mostly in blue and red, but also in other colors, are ready to use, in all the pockets of all his coats and vests, on his desk, in all the drawers, both at home and at the institute.

They must be specially cut to a certain length so that he can hold them in the hollow of his hand. So he can impulsively start drawing on any surface.

That could be on the snow-white tablecloth of the hostess, on the cuffs of his interlocutor's shirt, on the door of every house, inside or outside, on the cabinets in his laboratory, on the floor - the rug pulled back for a moment.

Or on the sole of a fellow traveler in a train compartment on the way from Frankfurt to Berlin, as one of them testified. A professor tells how Ehrlich once drew one postcard after another to 'visualize' his theories in a restaurant.

At the end of his presentation he had used more than fifty pieces, which he paid the waiter neatly.

Magic bullets

In the new century, Ehrlich is often invited to lecture abroad. In 1900, for example, by the Royal Society in London. From then on, British scholars invariably, and often for a long time, worked in Frankfurt. Even Americans, Italians and Japanese find their way.

Ehrlich speaks in Paris, Copenhagen, Brussels and twice more in London, where he meets Alexander Fleming, the man who later discovered penicillin. In 1904 he was invited to Chicago, where he received an honorary doctorate.

He is touring the universities of New York, Detroit and Baltimore. And the rooms are always packed to the doors. In this way he gradually builds up a large foreign network.

Ehrlich is convinced that serum therapy, the antibody therapy, is ideal against infectious diseases. He concludes: 'In a sense, the antibodies are like magic bullets that find their own target without harming the organism.

The immunization route must take precedence over all other therapies.

Unfortunately, there are countless infections in which the organism does not produce enough of these magic bullets for various reasons to destroy the causative agents. For example, larger pathogens, protozoa, primal animals, which are responsible for malaria or sleeping sickness.

In all these cases one should try to kill the parasites in the body with chemical means. In this way, chemotherapy replaces serum therapy. One must learn to aim chemically.'

The immensely wealthy widow of the Frankfurt industrialist Georg Speyer, who died of cancer, donated a fortune to the Ehrlich Institute in 1904, one million gold marks, to erect a new building, a new institute called the Georg-Speyer-Haus, specifically for research into the chemotherapy of infectious diseases.

The building can be inaugurated in September 1906.

Syphilis

Syphilis is a human disease, but in 1903 two employees of the Pasteur Institute succeeded in transferring the disease to monkeys, a condition for actually conducting tests.

In early 1905, one of the Charité researchers in Berlin finally discovered the causative agent of syphilis, a spirochete: 'A very fine, very pale, almost invisible screw.'

And a year later, Ehrlich's good friend von Wassermann develops the first usable syphilis test. This also reawakens Ehrlich's interest in syphilis. Italian former students succeed in infecting rabbits (via the corners of the eyes, later via the scrotum) to initiate the research.

He sets to work on the basis of atoxyl, an arsenic-containing agent. Arsenic preparations are promising: making them less sharp, weakening the poison, is succeeding step by step.

Blocke

By that time, Ehrlich has employed a huge team of researchers and lab technicians in his two institutes, and staff to maintain half a zoo, find and breed animals.

He has developed a unique system to enable all those people to work efficiently – to manage them individually.

Every evening he writes a specific colored card (called a block in his own language, from notepad) for each person, stating which tests the lab technician must perform that day, accompanied by all kinds of codes that only Ehrlich understands. (Ehrlich's illegible writing also turns out to be an object of investigation every day.)

He has all those numbered cards copied daily and delivered the next day in the morning. He himself keeps the overview. During the day he visits everyone to discuss the results.

According to his employees, Ehrlich works extremely unorthodox; his suggestions are at odds with all common procedures. And, "He wasn't used to moving slowly in a single direction."

People who don't participate in this system, or who criticize it, arouse his great anger and never stay in service for long. Not all researchers do this. At one point, two of his most handsome employees run off.

On the other hand, many admire his good humor and boundless optimism. Even persistent setbacks do not discourage him.

He always gives everyone hope.

He writes Caricature of Ehrlich every day: every bottle a new experiment, also sheets with assignments for himself, and constantly conducts experiments in his small laboratory room, a room completely filled with test tubes and where he has stored a stock of special chemicals.

All his life he works only with Bunsen burner, test tubes and blotting paper, as in ancient times. And he is proud of that.

Professor Bechhold, who worked with him for many years, wrote afterwards: 'There were thousands of vials of chemicals in his laboratory, among which only he knew his way.

Sketches in all colors were on tables, chairs and on the floor, and especially the walls and door frames were covered with signs and chemical formulas. What I paint is the archetype of disorder. And yet he knew how to order, to organize like no other.

Cancer research involved transferring the various cancer strains to thousands of mice and rats, vaccinating them over a hundred generations or more, and still maintaining an overview. Ehrlich succeeded in that too.

Just as he never lost track of the enormous facts that flowed to him from his own laboratories and clinics.'

Ehrlich and the Russian Ilya Metchnikov, who worked for Pasteur in Paris, jointly receive the Nobel Prize in Medicine in 1908 for their work on immunity. With this, the Nobel Committee in Stockholm keeps the German-French rivalry nicely in balance.

Ehrlich continues his research on syphilis. The arsenic compound 306 is promising. Preparation 418 even more so. He exercises patience. Very planned, Ehrlich continues, despite all the doubts that arise in his environment.

He remains optimistic, insisting that he deliberately puts on blinders and does not want to fish in too many waters: 'That is the secret of success.'

Cigars

Carl von Noorden, professor and a well-known internist and specialist for metabolic disorders, was Ehrlich's 'family doctor' in those years. Ehrlich now suffers from diabetes and arteriosclerosis.

In his diaries from the years 1909/1910, von Noorden writes that it was impossible to talk to his patient about his health. "In no time he was back to his work, his arsenic compounds." In fact, Ehrlich never rests, he works in bed at night and at the breakfast table in the morning.

He eats irregularly or not at all, and moves only by taxi. Only in the passage between his two institutes, which are right next to each other, does he get fresh air.

He has also been smoking 20 to 25 heavy havannas a day since his early years in Berlin. A box. This is delivered every day by a tobacconist from the inner city.

Continuously, from breakfast to the bedroom, Ehrlich smokes his fat cigars. "When I'm excited they calm me down, and when I'm dull they wake me up," he says in a newspaper interview.

He always has such a box under his left arm, wherever he goes or stands, especially when travelling.

When he arrived in Stockholm for the Nobel Prize ceremony in December 1908, he even had two boxes under his arm. 'Shall I free you from this immediately?', says his host on the platform. 'You can have everything from me, except those two boxes,' he answers, laughing.

Ehrlich lives an unhealthy life and his highly educated 'general practitioner' is powerless, as is Ehrlich's wife.

The zealous Japanese

In March 1909, a new Japanese researcher, 26-year-old Sahachiro Hata, arrives at the institute. He turns out to be the dream employee for Ehrlich. He executes all commands at a fast pace and during long working days. Research is moving forward in leaps and bounds.

On June 2, 1909 the breakthrough comes, preparation 606 is a bull's eye. Hata first tests the preparation on birds, later extensively on mice and rats. On June 6 on rabbits with syphilitic corneal inflammation. For the first time, all unwanted side effects disappear.

Hoechst has the drug patented on June 10, 1909.

To test it out, Ehrlich sends the preparation 606, which is given the name Salvarsan (saving arsenic), to a limited number of friendly doctors. On April 18, 1910, at an internist congress in Wiesbaden, he spoke publicly for the first time about the progress he was making.

From then on Ehrlich receives requests for help from all over the world. Syphilis is bearable in its early stages, but every sick person is terrified that the disease will penetrate the brain or spinal cord. It's not just any disease.

Because it is transmitted through sexual intercourse, there is a great taboo on it. Public disgrace and social ostracism are a permanent threat to the patient. The word syphilis itself is taboo.

From July 9, 1910, the extremely complex preparation can be produced in series at the institute.

The patient and cautious Ehrlich still opts for what today is called monitoring: 'We have a foundation, now we have to build a house.' His way of working leads to loud protests because he chooses the testing doctors himself.

So that syphilis patients can only turn to them and other doctors lose their patients. Nevertheless, Ehrlich is lavishly celebrated at a medical congress in September 1910 in Koningsbergen. He can then provide the balance of 10,000 cases.

His speech is constantly interrupted by massive applause.

In no time, 55 employees and three chemists are at work in Frankfurt alone for the production of Salvarsan. Together they produce 12,000 to 14,000 ampoules per day. By the time Ehrlich fully released the product in December 1910, 30,000 syphilis patients had already been treated.

Ehrlich demands from every doctor a report on the use and effect of each ampoule. He refines the composition and dosage of the injection fluid and the injection technique. And if something goes awry, he gets to the bottom of every problematic case himself.

That also destroys his health.

Light and air destroy the quality of Salvarsan. The airtight packed powder must be dissolved in guaranteed distilled water and administered quickly.

After bad experiences with intramuscular injections, he switches to intravenous injections, although very few doctors had experience with them at the time. Salvarsan works perfectly with 'young' syphilis', but is not useful in an end stage.

Nevertheless, many doctors still try it, you never know. And so accidents happen and deaths occur. Ehrlich fights like a lion for every case, fights for his reputation.

Salvarsankrieg

From 1910 onwards articles against Salvarsan and against Ehrlich personally appeared in a certain press. In Berlin, a well-known police doctor campaigns for years; he even manages to get a parliamentary question on the matter.

Fictional figures of the number of deaths attributable to administration of Salvarsan are circulating all the time. A Swiss doctor briefly calculates what the production of Salvarsan would cost him.

Almost nothing. Was Ehrlich perhaps a vulgar Jewish money grab? The man does not understand the complex production at all, nevertheless he is regarded by Ehrlich's enemies as an expert in the field. Ehrlich is very sensitive on that point, he remains on the defensive until his death.

Did the gentlemen think that Salvarsan was bottled like a brewer bottles his beer? Hadn't Hoechst distributed the first 60,000 samples for free? And don't the shares in the profit that Hoechst distributes flow back in full to his research institute?

'Just as the surgeon cuts with a steel blade, the chemotherapist works with a chemical blade. Everyone knows that something can go wrong during an operation,' he writes. Christian newspapers take a different tack: 'Ehrlich undoes the sin against the flesh.

Impure sexual lust is against the will of God, otherwise it would not be punished so terribly.'

From 1911, the preparation 914, Neosalvarsan, a milder version, comes on the market. Ehrlich's life in those years 1912 and 1913 is completely devoted to Salvarsan. And the praise far outweighs the criticism.

Honors, orders (11), memberships of scientific societies (more than 80) and honorary degrees (5, including from Oxford) pour in from all over the world.

But the chemical autodidact is most honored with his membership of the German Chemical Society. He is also nominated twice for a second Nobel Prize, the one for Chemistry. In 1911 he is invited as a speaker at the national physicists congress (where Einstein is also present).

In 1912 he is keynote speaker at the opening of the Kaiser-Wilhelm-Institut (which also hosts Max Planck and Einstein). The Sandstrasse in Frankfurt is renamed Paul-Ehrlich-Strasse in 1912. And at one of his lectures in Berlin, none other than Kaiser Wilhelm II was among the audience.

Over the years, his institute has become something of a place of pilgrimage. Not only are the test reports pouring in from London, New York or Melbourne, but noble and wealthy syphilis patients only want to be treated by Ehrlich, even though he has no hospital available.

Especially foreign visitors are not aware of this.

Prominent people who have been healed by Salvarsan come to thank him personally. And anyone who has name and fame in the medical world and who visits Germany, comes to take a look at the famous Ehrlich. It is bizarre that Ehrlich's office is completely covered with piles of books, magazines and files.

Only his personal chair is free. All visits are therefore made standing.

In January 1914, Ehrlich pays a private visit to Paris with his wife. Dr. Emery, one of the French Salvarsan pioneers, shows him around a local hospital.

He describes Ehrlich as follows: 'Small in stature, thin, with little hair remaining, a short white beard, parchment-like skin, very pale, with bluish veins in the gray eyes; he looked frail and vulnerable.' Emery has then treated three thousand patients with 25,000 injections without a problem arising.

On March 14, 1914, Ehrlich turns sixty. His learned friends and associates try to chart his achievements in a book of nearly seven hundred pages. He is hailed as 'the virtuoso in the art of the test tube test', as 'the born chemist'.

Everyone present at his birthday party is shocked at how old and dead tired he looks.

He looks more like seventy than sixty. Ehrlich has been robbing his body. He still smokes his daily amount of cigars and continues to avoid fresh air.

Sometimes his wife gives the coachman some extra drink money so that he does not drive directly to the institute, but takes a detour through the urban forest. He hardly ever notices, he is so absorbed in his work.

By the spring of 1914, more than a million people had already been treated with Salvarsan. But in June the smear campaign against Ehrlich's person moves from Berlin to Frankfurt.

In those days the question arises whether prostitutes may be treated with Salvarsan on a large scale, possibly against their own will.

Precisely in his own garden, in Frankfurt am Main, a fake journalist published a story in 1913 in which he reveals that prostitutes are being used as guinea pigs for Salvarsan against their will and that many have already died.

The director of the Frankfurt hospital is suing. The court session, which takes place on June 8, 1914, receives national attention. Fierce opponents of Salvarsan – including the Berlin police doctor – and supporters are given the floor.

Ehrlich himself is also called up. The trial shows that 11,000 men and women, including 1,200 prostitutes, had already been successfully treated with Salvarsan in the municipal hospital at that time. That side effects have only occurred in a few cases.

That one woman was indeed treated against her will. The death of three prostitutes has a different cause. The journalist is sentenced to one year in prison for serious insult.

Ehrlich looks very depressed for days, his friends say. He believes that "natural healers, vaccine opponents, quacks, anti-vivisectionists and anti-Semites" conspire against him. His nature cannot withstand all that enmity.

The ever-present anti-Semitic undertone touches him deeply.

The Great War

A few weeks later, on July 28, 1914, the First World War broke out.

Or as British Foreign Secretary Edward Gray puts it: 'The lamps are going out all over Europe; we shall not see them lit again in our lifetime.' Although he thinks the war is pure madness ('Nothing good can come of it') and his many friends in France, Great Britain and the United States are now inaccessible, Ehrlich signs the illustrious manifesto An die Kulturwelt on 4 October.

A group of 93 German scholars states that the war was forced on Germany, that Belgium agreed with the invasion, that Leuven itself is to blame for the destruction of the city, that the beautiful town hall has remained unharmed and even more German propaganda.

Many well-known names appear under that letter, those of the great physicist Max Planck, for example, or the famous Nobel Prize winner Wilhelm Röntgen.

Not surprisingly, the text was written by a Jewish intellectual: many German Jews would like to be 'good Germans', superpatriots. The letter will be resented by many colleagues in the rest of the world long after the war.

By this time, Ehrlich's health is already extremely poor. His wife would continue to underline that the public strife around Salvarsan had strained his strength. He can no longer walk or stand and hardly eats. He stops the ferocious cigar smoking.

His best researchers have to do military service, the others produce serums for the army on a large scale.

The scientific work in his laboratories comes to a standstill. At Christmas 1914 he suffers his first mild heart attack.

In the spring of 1915 he often sits for hours in a white basket chair on the terrace of his garden in the city and looks at nature: the monomaniac researcher who watches the birds for the first time in his life. On August 17, he suffers a second heart attack in a spa in Bad Homburg.

Three days later he is dead. Ehrlich will then be 61.

Despite the war, the Times of London writes respectfully of the German scholar: 'Ehrlich has opened new gates of a hitherto unknown world; at this moment the whole world is his debtor.' In France, Le Figaro sounds more bitter: 'Ehrlich has dishonored himself by signing the Manifesto of the German Intellectuals.

Has regret for this vile act hastened his end?'

Total inflation robs Mrs. Ehrlich of her wealth in 1923. In August 1938 she has yet to experience how the Nazis change the name of Paul-Ehrlich-Strasse in Frankfurt. After the Kristallnacht at the end of 1938, as a Jew, it is difficult for her to leave the country.

In 1939 she can flee to Geneva, in July 1941 she leaves Europe for the United States. She will be 77 then.
Around that time, two researchers picked up Alexander Fleming's penicillin antibiotic, which was discovered in 1928. In 1942 the first patient is treated. Penicillin is less toxic than Salvarsan and will soon replace it in the fight against syphilis.

Fleming, who considers himself Ehrlich's heir and who was one of the first doctors in Britain to use Salvarsan, was in turn awarded the Nobel Prize in 1945. And yes, a few days earlier Frankfurt got another Paul-Ehrlich-Strasse.

Ehrlich was the child of a time when the emergence of the first chemical factories, the development of cell biology, the staining of cells and the discovery of infectious diseases coincided.

Because as a Jew, and even assimilated Jew, he was not given a chance to make a career in government service, he strove for independence.

He found two great protectors in his path: Frerichs, the director of the Charité, who gave him all the space he needed, and Althoff, the enlightened despot at the head of the Ministry of Education and Health, who installed him in Frankfurt with his own institute.

Chemotherapy was a theoretical concept, existing only in Ehrlich's imagination. That is also why he always and everywhere made his famous drawings, a means of propaganda, as it were. The great scientific opposition forced him to the ultimate piece of evidence: Salvarsan.

By conducting each test himself and following the action of each ampoule, he literally worked himself to death.

So did his great example Robert Koch. Or a scientist like Schaudinn, the discoverer of the syphilis causative agent, who died from a test on himself. Because Ehrlich was no exception.

That radical, the urge to go to extremes, to sacrifice one's life for science, certainly also contained something patriotic, the will to bring victory to the young German nation. And quite a few German Jews were more receptive to that than many other Germans.

Anyway, a totally exhausted Ehrlich could no longer withstand the criticism of the outside world, based on envy, ignorance, religious prejudice and, above all, extreme anti-Semitism.

Ehrlich and Sherlock Holmes: two trackers

'This was a lofty chamber, lined and littered with countless bottles. Broad, low tables were scattered about, which bristled with retorts, test-tubes, and little Bunsen lamps, with their flickering flames. There was only one student in the room, who was bending over a distant table absorbed in his work. (…) “I've found it! I've found it,” he shouted to my companion, running towards us with a test-tube in his hand.'
From A Study in Scarlet by Arthur Conan Doyle, 1887: Sherlock Holmes is introduced to the reader.

It was a lofty room, crammed with countless bottles. Large, low tables were scattered about, littered with retorts, test tubes, and small Bunsen burners with their flickering blue flames. There was only one student in the room; he was bent over a table some distance away and was completely absorbed in his work. (…) "I've got it! I've got it!” he shouted to my companion, and he ran towards us with a test tube in his hand.'
— From A Study in Red, by Arthur Conan Doyle, translation by Jean A. Schalekamp, 1964.

Outwardly, Paul Ehrlich hardly resembled Sherlock Holmes: he was short and Holmes was tall. Ehrlich wore a beard, Holmes was clean-shaven. Holmes smoked pipes and also cigars and cigarettes, Ehrlich only cigars, albeit very much.

Sherlock Holmes, when introduced to the reader in Study in Red from 1887, is certainly a chemist by profession, he even works in a hospital laboratory.

He is just designing "an infallible method of testing bloodstains," the Sherlock-Holmes test. Holmes's hands are always covered in splashes of ink and chemical stains. Holmes's ignorance was as remarkable as his knowledge.

He didn't even know that the earth revolved around the sun. "I let her revolve around the moon," he said. His friend and assistant Dr. Watson complains that he touches on a wide variety of subjects at a rapid pace. Holmes thinks only of "the science of deduction and analysis."

Watson calls him "a hound for fox hunting."

Paul Ehrlich has worked in a laboratory all his life. All who knew him speak of his colored fingers and hands. Ehrlich underlined that he had to be monomaniac, that he had to wear blinders, that a researcher should not fish in many waters.

Like a hound for fox hunting? Visitors noticed that he touched on too many subjects at a rapid pace. And was hopelessly scattered.

Ehrlich was not at all interested in culture. He had only one sin: to read crime novels, especially Sherlock Holmes stories. And everyone knew that.

A sin serious enough to include in an autobiographical note for an American colleague in 1905 with the mention: 'deduction'.

Ehrlich was so fond of Sherlock Holmes that it came to the attention of the author Arthur Conan Doyle – also a doctor – so that he sent him his new books signed – 'With compliments to my great colleague'.

It also included an autographed photograph, which Ehrlich had hung on the wall in his study, next to his other idol, the bacteriologist Robert Koch.

It is also surprising that in 1890, when it seemed for a while that Koch had developed a cure for tuberculosis, Conan Doyle immediately traveled to a large medical conference in Berlin. True, it turned out that the four thousand seats were occupied, so he did not get to see Koch.

From Berlin, he wrote an article for the Daily Telegraph in which he explained that all the rumors about a TB drug were very premature. Which was also right.

The writer Conan Doyle worked as a general practitioner for ten years, from 1881 to 1891, as did Dr. Watson in his stories.

Joseph Bell, one of his professors at the University of Edinburgh, was the model for Sherlock Holmes, who always acted like a detective when making a diagnosis.

In any case, Paul Ehrlich was so absorbed in the Sherlock Holmes stories that he frantically annotated them, and quoted from them as and when he saw fit.

The day when a theft was committed in his institute and all kinds of suspicions were expressed, he proudly silenced everyone, because after reading all those detective stories he, Ehrlich, could call himself an expert.

Just like Conan Doyle, who got involved in countless investigations in real life because of his fictional hero.

Nobel laureate Paul Ehrlich even appropriated Holmes' statements. Ehrlich's biography of Ernst Bäumler contains his statement: "I can never remember whether the earth revolves around the sun or the sun revolves around the earth." Holmes in A study in red doesn't know that either.

And when Watson is astounded and explains the relationship between the sun and the earth, Holmes says, "Now that I know it, I shall try my best to forget it again." (…) 'What the devil do I care?' (…) 'If we revolved around the moon, it wouldn't make a dime difference to me or my work.' Ehrlich in Martha Marquardt's biography, "Don't pile up knowledge you'll never need."

Paul Ehrlich had developed a new science with a lot of research, with a lot of deduction, chemotherapy. Just as Sherlock Holmes, a scientific sleuth, also became the inventor of a new science, criminology.

In the evenings after dinner, Paul Ehrlich often asked his wife to play some popular tunes on the piano.

In his home town of Strehlen, his sisters had that task. 'With that music,' he used to say, 'the best ideas come to my mind.' Paul Ehrlich only liked popular music, which was inconsistent with his standing as a doctor.

One day his wife had dragged him to a classical concert.

As he came out he let slip: 'Those were two unforgettable hours.' Just when his wife thought she had finally converted him to better music, he added, "It's been a long time since I've been able to concentrate so well on my arsenic problem."

Ehrlich often spoke of the images he had in his mind: "I can picture every chemical formula in my mind." Or he started drawing with the words: 'I imagine that as follows.'

His image of the magic bullet is a good example of this. He took it from the romantic opera Der Freischütz by Carl Maria von Weber.

In it, a man sells his soul to the devil in exchange for a number of magic bullets with which he can win a sniper tournament and the hand of his great love.

For Ehrlich, that magic bullet became a chemical compound that itself sought out the parasite, and only that parasite, in the body and killed it flawlessly.

Ehrlich wrote to his friend Professor Christian Herter in New York: "I have a special gift for imagining all the ideas and issues in my head." Because cell biology was still in its infancy, and hardly anything was known about how a cell works, Ehrlich's chemotherapy remained largely a work of his imagination for many years.

Another reason why the criticism against him was sometimes so fierce. Herter in another connection, in 1909: 'The imagination of a Darwin or a Pasteur, for example, is as productive an imagination as that of Dante, or Goethe, or even Shakespeare.'