The Lübeck vaccine disaster

Der Totentanz von Lübeck, 1930

The world's first vaccine was invented by Englishman Edward Jenner in 1796. He made people immune to the dreaded disease, smallpox, by inoculating his patients with pus from the blisters of milkmaids infected with cowpox.

This must have struck his compatriots as odd, as the satirical print on the left shows. But in reality it was quite logical.

For centuries, large parts of the world had used variolations, which involved taking pus from people with smallpox and scratching it into the skin of healthy people. The infected person got smallpox, and blisters developed around the wound, but when the infection entered through the skin instead of through the respiratory tract, the disease was milder, and the patient recovered (usually) and became immune.

Edward Jenner vaccinates his patients. The blood spurts, while cows grow out of the limbs and heads of his poor patients.

In a variolation, the patient was exposed to infection from the deadly smallpox, Latin: variola, and this was not without danger. Around one percent died from the treatment, and there was also a risk that the handling of smallpox infection would start an epidemic.

It was known that there were two types of smallpox: the black smallpox, variola major, which was the most virulent with a mortality rate of 30%, and the white smallpox, variola minor with a mortality rate of 1%. In principle, the trick was to use the mildest variant for the variolations.

Jenner had discovered an even more harmless form of smallpox. He had observed that milkmaids never got smallpox, and he claimed that they had been infected by the cows, but that cowpox, variolae vaccinae, was harmless to humans. He found a milkmaid with fresh sores, and he scratched some of the pus from these sores into the skin of an 8-year-old boy.

The boy developed a fever and malaise, but recovered after 10 days. A month later, Jenner infected the boy again, this time by standard variolation — that is, with the deadly virus. This time, the boy did not get sick, and Jenner concluded that variolae vaccinae had made the boy immune to smallpox.

Tuberculosis

From an anti-vaccination magazine

After this, it took over a hundred years before a similar method was used against another of humanity's scourges, tuberculosis. TB is one of the worst killers; also known as "the white plague". It can affect all organs and bones, and in Norway, the disease was responsible for half of all deaths of people between 15 and 40 years of age until the 1930s.(1)

There were many challenges: The first was that bovine tuberculosis was dangerous to humans. In fact, one of the first steps in the fight against tuberculosis was to start pasteurizing milk, so that it would no longer infect humans.

But the interaction was more complex, because human tuberculosis was harmless to cows. This meant that bovine tuberculosis could actually be eradicated by "vaccinating" the cows with human tuberculosis. One reason why this is not a good idea is that humans could then risk getting tuberculosis by drinking unpasteurized milk.(2)

Conversely, it could be useful to have passive tuberculosis in the body as long as there was tuberculosis in society. On the Danish island Bornholm, bovine tuberculosis was successfully eradicated in the 1930s, but this meant that Bornholm residents more often than before got tuberculosis when they traveled to tuberculous Copenhagen, because bovine tuberculosis had acted as a natural vaccine.(3)

It was also not sufficient to inject antibodies, as had been successful in the fight against diphtheria and tetanus, for example. The disease lived inside the cells, so live bacteria had to be used to penetrate the cells.

Albert Calmette

Albert Calmette

In 1908, Albert Calmette announced that he and his assistant, Camille Guérin, had succeeded in growing bovine tuberculosis bacteria on a mixture of ox bile, glycerin, and potato pieces. When they re-seeded ("passed") the strain every 14 days, it gradually lost its ability to infect. They named this strain BCG after themselves: Bacillus Calmette-Guérin.

In 1911 after 120 "passings" they tried an experiment with eight heifers. Seven of the heifers were inoculated with BCG in increasing doses, while the eighth was left unvaccinated as a control. None of the seven developed tuberculosis, which told Calmette that BCG was harmless. They then inoculated all eight calves with live bovine tuberculosis. The seven calves that had received BCG showed no symptoms, but the eighth died of TB after 34 days. This told Calmette that BCG had an immunizing effect.

Calmette's research was interrupted by World War I. The Germans invaded Lille and emptied his laboratories of instruments and usable metals. His wife, together with other prominent women in Lille, was arrested and sent to a prison camp near Hanover.

Calmette himself was arrested because the Germans believed his carrier pigeons were being used to send messages to the French army. The Germans did not believe his explanation that the birds were being used for experiments with TB, and Calmette was sentenced to death. At the last minute, he persuaded a German pathologist, Dr. med. Pfeiffer, to perform an autopsy on the pigeons. Fortunately, Pfeiffer chose to perform an autopsy on the most emaciated pigeon. The pigeon showed all the classic signs of TB, and Calmette was released.

After the war, in the 1920s, Calmette was up to 230 "passages", and BCG had been tested on various experimental animals including monkeys. They also began to vaccinate some infants.

Calmette's vaccine met with resistance. His strategy was to point out the harmlessness of BCG and at the same time postulate some very great risks in not having children vaccinated. When doctors criticized his laboratory experiments, he responded with statistics, and when statisticians criticized his figures, he responded by referring to the increasing number of children who had been vaccinated without harm.

At the bottom of this page I am trying to organize links to the British Medical Journal where Calmette was particularly criticized by Major Greenwood.(4) One of Calmette's blunders was to cite a study of 78 newborn children of tubercular parents. Among children whose parents were in the last stage of the disease, 30.8% of the newborns died; if the parents were in an advanced stage, 25% died.

Such tremendous mortality rates sounded like a strong argument for giving newborns Calmette's new vaccine, without quibbling about safety and efficacy. But Greenwood located the study in question (table on the right); and where did the figure 78 come from?

Calmette had simply added the numbers in the left column together: 23+13+36+6=78. In doing so, he had counted all the living children twice and all the dead thrice. The study included only 36 children, which increased the statistical uncertainty. It was true enough that 30.8% of the children with a dying parent had also died themselves, but the sample was very small: 4 out of 13 children, and similarly, the 25% of those with parents in advanced conditions constituted only 2 children out of 8.

Greenwood ended his series with a merciless conclusion:

If Dr. Calmette had stated that, on experimental grounds, he was satisfied that his method of vaccination was a valuable prophylactic, […] I should have felt that my knowledge of the literature and technique of modern immunology was so amateurish that it would have been an impertinence to bandy words with an investigator who has devoted his life to such studies.

But Dr. Calmette has not adopted this course; he has deliberately appealed to the statistical method, and, in my submission, his use of that method has been so gravely defective that no confidence can be placed either in his statistical inferences or in the reliability of the data which he has assembled. The collection of data is at least as delicate a business as their analysis, and a writer who shows so little respect for logic in analysis is not likely to have been more circumspect in assembling data for analysis. I see no hope of obtaining statistical data from France.
(British Medical Journal, 12^th May 1928, p. 794, right column. My emphasis; see external link)

Ironically, the percentage, 30.8%, was very close to the 30.7% of children in Lübeck who ended up dying during the vaccination in Lübeck.

Urging of the parents

Fight against Tuberculosis

In the late summer of 1929, a package sent from the Pasteur Institute to Professor Georg Deycke arrived at the hospital in Lübeck.

The BCG culture was propagated, and in February 1930, prospective parents in the city could read the urgent call to the right in the newspapers and in yellow flyers. The wording was largely the same as that used by Calmette in Béziers, "Lutte contre la Tuberculose", and the tactic was the same as that used in similar campaigns since then — most recently in connection with covid19.

First of all, the risk of the disease was overstated:

25 percent of children whose parents have tuberculosis or who grow up in a family with someone with tuberculosis die of tuberculosis.

Along with them, sooner or later, many children of healthy parents who grow up in a healthy environment but are occasionally exposed to infection from strangers die from it.(5)

It was these figures that statisticians like Greenwood had criticized, as we have just seen. Greenwood estimated the figures to be closer to a quarter of this. But Calmette doubled down: It wasn't just parents with tuberculosis who should be afraid. Everyone should be afraid, and the responsibility was the parents':

Therefore, do everything you can to protect your children from this disease.

[…]

Do everything for the health and life of your children;

At the same time, the risks of the vaccine were downplayed:

This protective remedy is completely harmless: It does not cause any health problems.

It is given to infants as a simple drink. […]

A significant difference between the German and French exhortations was the absence of the word "vaccine". Calmette had earlier had the flyer translated into German, where the word "Impfung" was used several times.(6) The problem may have been that "Impfung" — like the English "inoculate" and "ingrafting" — are words taken from horticulture, rather than medicine.

Obituary for Günther Pangel

On the German flyers, BCG was instead referred to as a protective remedy: "das Calmettesche Mittel" (twice), "Schutzmittel", and "Mittel".

There was also no indication that this was a new and relatively untested technology. Parents could easily have thought it was some kind of dietary supplement, »given to infants as a simple drink«.

And that's exactly what some of the parents complained about when the disaster became clear: They had no idea they had let their children participate in an experiment (pictured left).

On Sunday morning, July 6th, our dear little Günther died at the age of 16 weeks after a serious illness lasting 8 weeks from the terrible consequences of the Calmette vaccination.

It is with great pain that we mourn the death of our promising child, on whom doctors carried out a dangerous experiment without our knowledge.
(My emphasis)

The disaster in Lübeck

Newspaper from Berlin: Lübecker Totentanz

Lübeck: wet nurse and child

Already before the vaccination started officially, BCG had been given to three children who were at special risk.

The very first of these children, Griese, was vaccinated on 9/12/1929 and developed swollen cervical lymph glands on 15/1/1930. Professor Deycke decided that it had to be due to congenital TB. Even though it is very rare for a tuberculous mother to infect her unborn child, no doctors at the hospital objected. As Erich Frey, who later were to represent the Lübeck parents in court, said: »Endless disaster could have been avoided if only one person had doubted this diagnosis«.

The program therefore started as planned on 24^th February 1930. The vaccine was given orally with milk in three doses during the child's first 10 days of life.

The first child died on March 31^st, but not from TB, and no autopsy was performed.

The next child died on April 17^th. The cause of death was TB, but permission was not granted for an autopsy.

Another child died on April 20^th of TB, but the autopsy showed that the disease was in the lungs, and it was concluded that the child had been infected by his tuberculous mother through the respiratory tract rather than by BCG, which was supposed to affect the stomach and intestines.

On April 24^th and 25^th, two more children died, and now the doctors realized the disaster. The distribution of the vaccine stopped, and Professor Deycke destroyed the rest of the vaccine. Unfortunately, they neglected to inform private doctors and midwives, who therefore continued with the vaccinations. Right up until 30/4, children received the 2nd and 3rd doses.

On May 14^th the Berlin newspaper Vossische Zeitung seems to be the first to have alerted the public. Three days later, on May 17^th, the number of dead children had reached 12 and Vossische Zeitung used the headline "Der Lübecker Totentanz" as an allusion to the famous painting in St. Mary's Church (pictured left). One might think that this was morbid and inappropriate humor, but the fact is that dances of death have always been deadly serious (see Julius Moses).

17/7 1930: Two more children.

On July 17^th, the number of dead had reached 59 out of the 251 vaccinated children, but the Lübecker Volksbote thought they could see a light in the darkness: Two more children had died, but there had been no new cases of the disease in the last 8 days (pictured right). However, the optimism was unfounded: There were two deaths on the 18th, one on the 23rd, one on the 30th and another eight in August.

A total of 251 children had received the vaccine. In this group, 77 died in their first three years of life. Of these, 72 died with or from tuberculosis. In 68 of the cases, the diagnosis was confirmed by autopsy. Five children died of other causes, with the 4 cases confirmed by autopsy.

Among the 164 unvaccinated children, 19 died in their first three years of life, none of them from tuberculosis.

An X-ray examination of the 174 children surviving the vaccine showed that 127 had had TB. Six of them suffered from permanent damage.

The trial

The baby in the cradle

A lengthy investigation began. Had the BCG reverted to a virulent bovine tuberculosis, or had it been infected by a live TB? Was it even certain that the children had died from a bovine TB?

The questions were not made any easier by the fact that Deycke had destroyed the remaining stock of BCG. Therefore the summoned experts had to make do with a few organs and stool samples from the dead children. The bacillus could not be seen under a microscope, so the researchers were forced to inoculate the individual samples into guinea pigs and rabbits, wait for weeks and months, before finally dissecting the animals to see whether they were infected with bovine or human tuberculosis.

This was time-consuming and it took more than a year before the trial began, on October 12^th, 1931. The defendants were Dr. Altstaedt from the Lübeck health board, Professor Georg Deycke from the city hospital, Professor Max Klotz from the children's clinic and nurse Anna D. B. Schütze.

Naturopaths were quick to satirize.

The case attracted so many spectators that it had to be held in a sports hall. The parents of the many dead and sick children showed up; the emerging Nazi movement was interested in whether the arch-enemy, France, had poisoned good Germanic children; the communists accused the system of practicing "class medicine" because there were fewer deaths among the rich children in the private hospitals. The Social Democrat Julius Moses had criticized medical experiments for many years, and without being against vaccines as such, he preferred to see workers' housing and wages improved;

The naturopaths could of course rejoice at this great failure of established medicine (pictured left), but they shouldn't smile too loudly. Three of the children, including Günther Pangels, whose obituary we have just read, had died with TB. They had been given injections by a certain Dr. Genter — presumably an unknown quack with a homemade concoction — who, due to poor hygiene, had caused coli infection from open abscesses. The court concluded that in these cases Dr. Genter's injection had exacerbated the tuberculosis. The trial against Dr. Genter was scheduled for the following year.(7)

After 76 court days, the verdict was handed down on February 6^th 1932. Deycke was sentenced to two years in prison for negligent homicide and negligent bodily harm, while Altstaedt was sentenced to 15 months in prison for the same. Back home in France, Calmette had followed the case in the newspapers. Here, in the last year of his life (he died in 1933), he had been called a "murderer" on the street, and he had feared a long series of lawsuits. Now he could breathe a sigh of relief

What went wrong? And what can we learn?

anti-Calmette.

The BCG vaccine was shipped from the Pasteur Institute on July 27^th. According to Calmette, the same strain was sent to Mexico and Riga without problems, and later a sub-culture of this was used to vaccinate 3,016 people, also without problems.

Inside the package was a note with an important instruction: The incubator containing the BCG must not receive other microbes, especially no other tuberculosis bacilli. The latter was emphasized in italics: "surtout aucun autre bacille tuberculeux".(8)

That's how it was at first, because all the lab's other TB cultures had been lost due to thermostat failure in the summer. But on September 9^th the hospital received from Kiel a strain of live tuberculosis, which for inexplicable reasons was called "Werner". It was obvious that "Werner" had infected the BCG.

Let's look at the mistakes that were made.

1. As mentioned, the risks of not getting vaccinated were exaggerated. The truth was that none of the 19 unvaccinated children who died had died of TB, so there was no immediate threat.

2. In contrast, they emphasized how safe the vaccine was. Here, Calmette probably only meant that BCG could not cause TB, but as the parents in Lübeck were to discover, lots of other things could go wrong.

3. The parents were not told that it was an experiment, and the word "Impfung" was omitted. We have already looked at Günther Pangel's obituary, where his parents felt deceived, and his father repeated this as a witness in court:

   Pandemics are here to stay.

   Immediately after the birth of my child, I had a brief conversation with the midwife, […]
   She only spoke of a protective feeding.
   If she had explained the nature of the Calmette remedy to me,
   if she had told me that it was an "Impfung",
   I would never have consented to the use of the Calmette-remedy.(9)

4. The Lübeck laboratory had cultivated the BCG together with live tuberculosis bacteria despite the fact that the delivery note explicitly warned against this (see earlier footnote(8)). It was only late in the trial that Deycke had to admit that BCG and "Werner" had not only been stored in the same room, but even in the same incubator.

5. The package insert also stated that the product's harmlessness should be ensured through animal testing. For each "re-seeding", BCG was to be tested on two guinea pigs, which should be observed for at least 4-5 months.(10) This was omitted. Instead, a follow-up examination of the children was planned after six months.

   It must be reiterated that none of the 19 unvaccinated children who died had TB. Thus there was no reason to rush through the vaccination program without the necessary checks.

6. Overall, Deycke's behavior was strange: Why did he keep the two strains in the same cabinet? What did he even need the virulent strain for? Why didn't he follow the instructions regarding growth media? Why did he insist on growing BCG himself when neither his laboratory nor his staff were suitable? He could just have imported BCG ready made from France

   A rumor went that Deycke had been convinced that BCG was not effective enough and had therefore "boosted" it with the virulent virus. Calmette denied this rumor so often that it managed to spread.

   In any case, there is some indication that Deycke's ambition had run away with him. He himself had been researching tuberculosis for many years, and had written Praktisches Lehrbuch der Tuberkulose, 1920 (2. edition 1922). Maybe he wanted to put his own stamp on the German vaccine?

7. The midwives often held the children's noses when they administered the vaccine dosed in the lukewarm milk. Therefore, the vaccine could easily enter the trachea and cause TB in the lungs and middle ear.

   The first child to be autopsied had TB in the lungs, and this meant that BCG was not immediately suspected. Six of the surviving children had permanent damages consisting of varying degrees of deafness due to TB in the middle ear.

8. Instead of waiting for the children to die and get autopsied, the authorities should have looked out for other danger signals. Instead they had disregarded the midwives' reports regarding the children's "not entirely satisfactory weight gain" and their "blemished skin". There was also a certain enmity between Professor Deycke and Professor Klotz, the director of the children's hospital, who did not provide Deycke with any further information regarding sick "BCG children" in his clinic.

9. When the doctors realized the catastrophe, Deycke destroyed the rest of the vaccine stockpile and the subculture. This made it significantly more difficult for the authorities to figure out what had gone wrong afterwards.

10. The hospital stopped using BCG, but in order not to "worry" the parents (or to arouse suspicion), the 2^nd and 3^rd doses were given in the form of a harmless but ineffective alternative (MTbR, invented by Hans Much).

11. Private doctors and midwives were not informed, so they continued to administer the 2^nd and 3^rd doses.

    The stained glass windows in St. Mary's Church.

12. Instead of raising the alarm, a very ambiguous message was written to the parents.

    We would like to draw your attention to the fact that, for reasons that are still unclear, health problems have been observed in some children following the protective feeding.
    If your child is not already under medical care, we advise you to consult your doctor immediately in the event of a health problem, showing this letter.(11)

Perhaps the worst thing about the disaster was that it resulted in Germany stopping the use of BCG and other vaccines.

It was only after World War II that the Danish Red Cross and the Danish State Serum Institute with support from WHO and UNICEF started a campaign to vaccinate the population of the war-torn Europe to prevent epidemics.

This time, the patients were first tested with tuberculin, and only those who were tuberculin negative (i.e. those who did not already have the bacteria in their bodies) were vaccinated with BCG. By 1948, more than 1½ million children and adolescents had been tested in Poland, Hungary, Czechoslovakia, Germany, Italy and Greece, of whom 430,000 were subsequently vaccinated (which means that almost 3 out of 4 had TB in their bodies).

The campaign continued until 1952, when 24 million children in 10 European countries had been vaccinated.(12)

External Links

• Die Säuglingstuberkulose in Lübeck, 1935. The first chapter (pp. 1-24) is by Albert Moegling with statistics about the epidemic.
• En målrettet indsats i bekæmpelsen af en folkesygdom (pp. 96-126). The Danish State Serum Institute (Danish text)
• B. C. G.-vaksinen mot tuberkulose, printed in Naturen. No. 3, March 1937, 61^th year, p. 72. (Norwegian text)
• Menschenversuche in der Weimarer Republik, 2004, pp. 201-224
• Fortschritt und Fortschrittsglaube by Christian Bonah, pp. 20-29. Here page 24.

The British Medical Journal:

• Prophylactic vaccination of the newly born against tuberculosis. 14^th May 1927, page 896. Major Greenwood
• Prophylactic vaccination of the newly born against tuberculosis. 28^th May 1927, page 987. Short answer from Calmette.
• Prophylactic vaccination of the newly born against tuberculosis. 11^th June 1927
• A criticism of "B.C.G." 3^rd March 1928 (anonymous)
• Professor Calmette's Statistical Study Of B.C.G. Vaccination, 12^th May 1928, Major Greenwood, pp. 793-795
• The Lübeck catastrophe - a general review, 6^th June 1931, pp. 986-88. A summary before the trial started (anonymous).
  Note: The author writes that BCG and the virulent strain were kept in separate rooms. That was what Deycke claimed at that time.

Further information

• The child in Lübeck (1463)
• The child in Lübeck (1701)
• The child in Lübeck (the stained glass windows)
• Nurse with child in Dodendantz
• Nurse with child in Copenhagen's dance of death
• The children in Erfurt
• The child in La Danse Macabre
• The child in Der Doten dantz mit figuren
• The child in Heidelsberg's block book
• The child in Basel
• The child in Füssen
• The child in Bleibach
• The child in Holbein's dance of death-alphabet
• The child in Holbein's great dance of death
• The child in Mors de la Pomme
• The child in Les Accidens de l'Homme

Footnotes: (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12)

Dansk The dance of death Miscellanea Vaccine