Kulturkampf: The German Quest for Penicillin
Gilbert Shama looks at the German research into penicillin during the Second World War.
When in 1928 Alexander Fleming noticed that a mould had contaminated one of his petri dishes, apparently dissolving the bacteria growing on it, he was shrewd enough to isolate it in order to examine it more closely. The mould turned out to belong to a group known as the penicillia and was able to produce a substance that even at very low concentrations had the power to destroy many disease-causing bacteria. Fleming called this antibiotic substance ‘penicillin’.
In the years following its discovery, penicillin was to gain a reputation as a useful laboratory tool, but it was the work of two Oxford scientists that was to reveal the drug’s true potential. In 1938 Howard Florey and Ernst Chain set out to study natural antibacterial substances. Early in their investigations they chanced upon penicillin and in a short space of time made enormous progress with their research. Their first achievement was to purify it. This allowed them to show that penicillin could protect animals infected with large doses of normally fatal bacteria. It was these results that convinced the Oxford scientists that they were dealing with an extraordinary new drug. Following normal scientific practice, and the war notwithstanding, they published their results in the medical journal The Lancet.
Florey’s results attracted world attention – including that of German scientists. The latter were only able to read The Lancet because it was sent to Germany from neutral countries such as Sweden and Switzerland. Scientific publications received through these channels were somewhat prized and went first to those with Nazi Party connections. Among them was Theodore Morell, Hitler’s personal physician, who was later to receive the Iron Cross for his discovery of antibiotics. Copies of Florey’s Lancet papers were also dispatched to Japan by submarine.
On hearing of penicillin’s alleged efficacy, senior officials from the German pharmaceutical industry hatched a plan to obtain Fleming’s mould. A Swiss company agreed to act as proxy and approach Florey for it: once they had received it they would simply send it to Germany. However, Florey was tipped off and acted immediately to frustrate the attempt. He wrote to Fleming asking him not to send out cultures to persons or organisations who might then pass them on to Germany.
The practice of supplying cultures to fellow research workers was, and still is, quite normal. Enquiries within German pharmaceutical circles later revealed that a research scientist, a certain Dr Schmidt, at the I.G. Farben works in Marburg, actually had a culture of Fleming’s mould. He had received it some years previously from Fleming himself. Schmidt had kept it without ever having attempted to grow it. With the revival of interest in penicillin he now tried to grow the mould but failed. In desperation he passed his material on to the German pharmaceutical company Schering but its scientists fared no better.
This did not dash German hopes completely. Might not Fleming have sent cultures to other laboratories now under German occupation? There were obvious candidates, and the Pasteur Institute in Paris was high on the list. A German delegation arrived there seeking Fleming’s mould but was persuaded that no such culture was kept by the Institute. In fact this was not the case. Though it is unlikely that French scientists would have seen Florey’s articles and would therefore have been puzzled by German interest in the mould, the idea that the Germans wanted it for their own uses was reason enough to withhold it. A similarly fruitless search by the Germans was conducted at the Institute of Pharmacy in Copenhagen, which also possessed cultures of the mould but withheld them. Later in the war, when the scientists in occupied countries learned about penicillin through BBC radio broadcasts and leaflets dropped by the RAF, they became engaged in clande-stine work to produce it.
The small town of Baarn, near Utrecht in Holland, was the home of the foremost mould collection in the world. The ‘CBS’, as it was called, listed all its cultures in a catalogue that was widely available in Germany; German scientists had simply to apply by post for any they wanted. Although Fleming had not deposited his mould (Penicillium notatum) at Baarn, the collection held a closely related species. The first requests from Germany for the mould started arriving in September 1942. Word about penicillin spread rapidly throughout the German pharmaceutical community, however, and by the middle of 1943, the CBS was receiving a flood of requests from German comp-anies of every description.
It probably did not take German microbiologists long to discover that none of the Baarn cultures produced penicillin. This must have been a blow. There was now only one strategy left; to attempt to isolate penicillia from samples of soil, compost and rotting vegetation. This is not as desperate an alternative as it might seem. When penicillin research and development was effectively transferred to the USA in 1941, American scientists isolated a species of penicillium from a piece of rotting cantaloupe melon which produced higher yields of penicillin than Fleming’s mould. Before long a number of German scientists were engaged in this painstaking process.
These scientists were to a large extent labouring in the dark as little was known of the chemical identity of penicillin. It could only be detected by its ability to kill bacteria on a petri dish. However, the penicillia collectively produce many antibiotics including some that are actually toxic to humans. Identifying penicillia is relatively easy for a trained microbiologist; certifying that the substance ‘dissolving’ bacteria on petri dishes is true penicillin is quite a different matter. This work became easier later in the war when captured British penicillin became available in Germany. It seems likely that some German scientists were working with toxic antibiotics in the mistaken belief that it was penicillin.
Eventually, however, small quantities of penicillin were produced in Germany. Some pharmaceutical companies even started making plans to increase production. However, they were already years behind Anglo- American efforts and their modest successes had come too late.
Why did the German project fail? Firstly, research was too unco-ordinated. Those involved seemed to have had no difficulties collaborating with one another but what was lacking was a central body to co-ordinate research and eliminate duplication of effort. Prior to the discovery of penicillin the best antibacterial drugs available were the sulphonamides. These were a German discovery and although far less effective than penicillin, had earned the pharmace-utical industry there a great deal of money. While these companies now came to dominate penicillin research, their experience in manu-facturing the sulphonamides proved of little relevance in the quest for penicillin. What was needed was industrial experience of cultivating microbes – such experience existed in Germany, but it lay outside the pharmaceutical sector and was never exploited. In the USA, by contrast, firms with industrial microbiology experience played a key role, while a central body co-ordinated research and production. Ironically some participants, such as Merck, were the American subsidiaries of German companies. Merck was to become one of the biggest producers of penicillin in the USA, while its parent company, E. Merck of Darmstadt, was years behind, still experimenting with penicillin production in small metal flasks. Meanwhile, German frustration at not being able to get hold of Fleming’s mould led to allegations in some quarters that the drug was no more than an Allied propaganda weapon. It is impossible to assess to what extent such claims influenced research, but they would certainly not have helped.
Prior to the Allied invasion of Sicily in July 1943, British units in North Africa were severely depleted because of the number of troops suffering from sexually transmitted diseases (STD). After some debate as to its efficacy, penicillin was finally released to treat these men. The effects were miraculous: a single dose of penicillin was sufficient to eradicate STD in a single day in cases where, previously, huge doses of sulphon-amides administered over several days had virtually no effect. There can be no doubt that if penicillin had been widely available in Germany at this time, it would have transformed the treatment of battle casualties and resulted in fewer amputations and deaths. The German armed forces must have been afflicted with STD at comparable rates to those found in British troops – if penicillin has been used to treat such cases it might possibly have tipped the balance in Germany’s favour in some of the key engagements late in the war. As it was, the number of Germans given penicillin in some form or another probably did not amount to more than a few hundred. Interestingly, this number may have included Adolf Hitler who is reputed to have received some for an injured hand following the July 1944 bomb plot against him.
In researching this article I contacted a number of German companies, most of whom were particularly helpful and forthcoming. I found this rather surprising when lawsuits are still being filed against some German companies for their conduct during the war. This attitude was in sharp contrast to the negative responses of a certain French company who played a role in the clandestine wartime manufacture of penicillin: some of the ghosts of 1940-44 have yet to be laid to rest.