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Proteus OX19

August 5, 2009

There are sometimes odd links between two otherwise unrelated diseases. Whether due to parallel evolution or horizontal gene transfer, two bacteria use the same technique as part of their attack on a human being, with correspondingly similar results. Probably the most famous result of this is the CCR5-Δ32 mutation, one copy of which makes people resistant to HIV-1 infection; two makes them almost immune. The peculiarity here is that the gene in question is much more common in people of Northern European descent, with somewhere between ten and fifteen percent of the population having at least one copy while it’s vanishingly rare in, say, sub-Saharan Africans or East Asians. Using a hybrid of math and genetics called coalescent theory, it’s possible to calculate that the mutation must have started to spread in the European population at least 275 years ago, with seven centuries being the likeliest figure. AIDS has been around for a lot less than that.

The theory for how the mutation became so widespread involves finding another disease that uses the same point of attack as HIV-1. The most commonly suggested culprits are smallpox and bubonic plague, both of which have been pestering people for long enough to qualify. In the particular case of plague bacteria, they attack the T-cells of a human’s immune system through the CCR5 receptor on the outside of those cells. HIV-1 does the same. Even though the two diseases act quite differently once inside the cell, they’d be similarly stymied by a change in the CCR5 receptor. The CCR5-Δ32 mutation seems to have become common because Northern Europe was repeatedly struck by epidemics of plague (or chronically infected with smallpox, if you prefer that culprit) for centuries. If you didn’t have the mutation, you died; if you did, you lived to have many children who also had the mutation. The fact that CCR5-Δ32 also confers resistance to HIV-1 is nothing more than coincidence.

The same sort of coincidence ended up saving thousands of lives during World War II.

Start with two bacteria: Rickettsia prowazekii and Proteus vulgaris. The former is better known as typhus, and for centuries it was a scourge on humanity, popping up repeatedly in crowded unsanitary situations like prisons and military camps. Proteus vulgaris, on the other hand, is an entirely boring creature. It can cause urinary tract infections, and it’s dangerous to people who are already badly sick with something else, but that’s about it. It comes into prominence only because of its connection of typhus. One particular strain of the bacteria, Proteus OX19, reacts with the human immune system in the same way as typhus does.

This similarity was discovered during World War I by Arthur Felix and Edward Weil, two Austro-Hungarian doctors following the Eastern Front. Typhus killed millions during that war, and so their discovery quickly led to the Weil-Felix test, which is widely used as a blood test for typhus infection. Formalin-killed Proteus OX19 is mixed with a blood sample taken from a patient, and if the sample clumps, the patient has typhus. Of course, if one were infected with Proteus OX19 one would also test positive, but that kind of infection is rare and considered unlikely in someone suspected of having typhus.

It stayed unlikely until the physician Stanisław Matulewicz of Stalowa Wola, Poland came along. The first vaccines against typhus had been developed in the 1930s, so the disease had been eliminated in Germany but was still around in points east. The German Army was worried about outbreaks to the point of mania, so after the Nazi invasion of Poland, Polish labs were required to report positive tests for typhus for fear that it might infect German soldiers. Catholic Poles who had a positive Weil-Felix test were quarantined, but Jews who tested positive were shot. Many of Matulewicz’s patients were Jewish (there were nearly a dozen Jewish villages surrounding Stalowa Wola) and, desperate to avoid having to use the labs, Matulewicz taught himself how to administer the test. While doing so he incidentally realized that, if he injected a patient with the killed Proteus OX19 that was used for the test, he could provoke a false positive for typhus.

Under normal circumstances there’d be no reason to do so. But by 1942 Poles were being shipped en masse to German slave labour camps, and the Wannsee Conference had kicked off the final phase of the Holocaust among the Jews of Poland and the rest of Nazi-occupied Europe. Under these insane conditions, Dr. Matulewicz and his friend Dr. Eugeniusz Łazowski decided to fake a typhus epidemic to try and save the people of Stalowa Wola.

Dr. Łazowski had been a prisoner-of-war after the collapse of Poland in September of 1939, but had managed to escape by climbing the prison wall and pretending to be the owner of an abandoned horse cart outside the camp until he left the sight of the guards. He settled on the outskirts of Stalowa Wola, backing on to the Jewish shtetl of Rozvedov. There he joined the Polish Resistance and, while it seems the Nazis knew of him, he was left alone on the basis of his usefulness as a doctor and member of the Polish Red Cross.

Both doctors were aware of what the Germans were doing to the people of Poland. Catholic Poles who’d been conscripted for slave labour were sent to them for treatment, and Łazowski’s neighbours in Rozvedov were sent to a concentration camp earlier than most. Rather than see this go on, Dr. Matulewicz told Dr. Łazowski about his way to fool the Weil-Felix test and the two hatched a plan. Whenever one of Łazowski or Matulewicz had a non-Jewish patient—as mentioned earlier, being Jewish and infected with typhus was a capital offense in the Generalgouvernement of Poland—with symptoms resembling the onset of typhus (like many diseases typhus’ initial symptoms are fever, cough, and aches and pains), he would inject him with Proteus OX19 then arrange for a blood test with a Polish lab. When the positive result was obtained, the Germans would be duly informed and when enough people in one area turned up positive, it would be quarantined and deportations would stop. By 1943, Matulewicz and Łazowski had managed to get several thousand people under the protection of a sham quarantine.

The way they had to go ahead with their plan does raise some interesting ethical questions, ones a little too fine for the depths of World War II but still worth pondering. They told no-one what they were doing, including the people they injected; the patients were even led to believe that they had had typhus but somehow recovered from a disease that was often fatal. To throw suspicion off themselves, they would inject some patients and then refer them to other doctors who they thought might ask for a blood test. Rumours of what they were doing eventually leaked out, if only because Germans began to notice that not a lot of people were dying around Stalowa Wola for all that there was supposed to be an epidemic going on.

A good answer to any ethical concerns can be found in how the people of Stalowa Wola’s surrounding towns helped Dr. Łazowski set up an reverse Potemkin village when the Nazis did try to investigate in the winter of 1943-44. By then the villagers knew that the doctors were helping them evade German atrocities, and so when the three investigators arrived they were welcomed with a local feast. Reluctant to step away from the party, the senior doctor dispatched the junior Nazi medicos to do his work; they were then suitably rattled with tales of infection and death en route by Dr. Łazowski. He arranged for several of the people sickest with diseases most resembling typhus to be housed in filthy conditions—and of course injected them with Proteus OX19. After the first few Weil-Felix tests came up positive, the inexperienced investigators wrapped up and reported back to their superiors that, yes, there was an outbreak underway.

By the summer of 1944, Operation Bagration had the Red Army stop with Stalowa Wola just inside their front lines. Łazowski and Matulewicz were among the many Poles marked for death by the Germans should they lose control of Poland, but fortunately the Russians swept forward so quickly that both doctors managed to stay in hiding until their city was under Soviet control.

The need to fake medical results had passed, but Poland still had tragic years under a totalitarian government ahead. Fearful of the new invading army, both the doctors and the citizens of Stalowa Wola stayed quiet about their unusual way of resisting the Nazis. Dr. Matulewicz spent some time practising medicine in Zaire in the late 1950s as part of the Eastern Bloc’s campaign to influence that country’s political development, but he spent most of the rest of his life in Poland. Dr. Łazowski immigrated to the US in 1958. After the fall of the Berlin Wall, both opened up and Łazowski published a memoir entitled Prywatna Wojna, Wspomnienia lekarza-zolnierza 1939-1944 (Private War, the Memories of a Soldier Physician 1939-1944) which, unfortunately, has not been translated into English.

4 Comments leave one →
  1. July 17, 2012 3:51 PM

    Thank you very much for the information … this means a Ox 19 positive (only) is related to urinary infections and not typhus, that’s some good to know.

    • Paul Drye permalink*
      July 17, 2012 4:18 PM

      It might not even mean as much as that. As I understand it, many of the people who are infected with it have no symptoms at all. It is not a very powerful microbe, and is easily fought off.


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