Dr J C Pompe

Dr J C Pompe
Discoverer of Pompe disease

About this blog

What you can read here is the story of the development of enzyme replacement therapy (ERT), the first effective treatment for Pompe disease. It is an incredible story, rich with events, characters and science. Above all, it is the story of an international community of scientists, doctors, patients and companies, working together towards a common goal.

It is not a story that features in Geeta Anand's book, The Cure , or the film based on it, Extraordinary Measures despite the fact that they are ostensibly about the development of ERT for Pompe ( you can link straight to the relevant articles covering the events described in the book and film here, here and here).

This blog represents my small attempt to set the record straight and to give the story back to its rightful owners - the international Pompe community. It is written here in roughly chronological order i.e. you'll need to start at the bottom of the April 2009 archive page and work your way up.

It is also a personal account and, although I've tried to make it as objective as possible, there is an inevitable degree of subjectivity. For that reason I have included contributions from other members of the worldwide Pompe community and would be delighted to receive more. Feedback is also welcome.

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Saturday, 4 April 2009

Joannes Cassianus Pompe 1901 -1945

I can think of no better place to start the story of Pompe disease than with Joannes Cassianus Pompe, the scientist who first described the disease which now bears his name. It is important to note that the disease had undoubtedly been around for a very, very long time, prior to its discovery. In fact, I would say (warning: people often look askance when I say this and your attention is drawn to the disclaimer at the right) that it was around in the time of the dinosaurs. "Evidence?", you cry? Well, if it is found in both mammals and in birds (and it is) it's a fair bet that it was found in the common ancestor of mammals and birds - which pre-dates the dinosaurs. All of which makes its eventual discovery all the more impressive as a piece of scientific observation and detective work.















In putting together this article, I have drawn heavily from information and images supplied by Dr R C C Pottkamp of the Netherlands Institute for War Documentation, whose help I very gratefully acknowledge.

The image above is a contemporary drawing of the great man. I scanned it, with permission, from the 1979 PhD thesis of Christa Loonen (The Variability of Pompe's Disease: A clinical, biochemical and genetic study of glycogen storage disease type 2, or acid maltase deficiency - also drawn on here) one of the dedicated band of Dutch scientists and doctors who did so much to take forward Pompe's work. But more of them later.

Joannes Cassianus Pompe was born in Utrecht on 9 September 1901. He studied medicine at the University of Utrecht and during this time came across the symptoms of what is now known as infantile Pompe disease, which he described in his 1932 publication Over idiopathische hypertrophie van het hart. On December 27, 1930, Dr Pompe had carried out a postmortem on a 7-month old girl who had died of pneumonia. He found the enlarged heart now known to be charactertic of the infantile form of the disease and had some microscope slides prepared. These showed that the muscle tissue was distorted into an oval mesh.

He realised after detailed examination, that this appearance was due to the accumulation of something forcing the muscle tissue to distort in that way. This isn't as obvious as it appears now - when you look at fishing net, would you conclude that it has been forced into that shape by the air filling the holes? He then tried to discover what the accumulated substance was and had the idea that it might be glycogen. Subsequent testing showed that to be the case.

Pompe was perhaps guided in that direction by his colleagues Professor Snapper and Dr van Creveld. They had published a paper in 1928 desribing what is now known as Von Gierke disease, or glycogen storage disease type 1. In fact, the girl on whom Pompe carried out his post-mortem had been the patient of Professor Snapper. You can imagine that these colleagues might have encouraged Dr Pompe in establishing the idea that here was a second type of glycogen storage disease, also an inborn error of metabolism. It is interesting to speculate (and that's all it is, pure speculation on my part) that having missed out on 'naming' glycogen storage disease type 1, Snapper and van Creveld were keen to promote 'Pompe disease' as the name for the new type (there was some competition, as a German pathologist, W Putschar, made the same discovery, just a few months later!).

Dr Pompe graduated in 1936 in the subject 'cardiomegalia glycogenica', indicating that this had been a continuing subject of study for him. After a spell at the St. Canisius Hospital in Nijmegen, he was appointed as Pathologist at Hospital of Our Lady (OLCG) in Amsterdam, where he worked from June 1939 until his death.

The workplace was appropriate as he was known as a very devout Catholic, as well as an admirer of Sophocles and the Dutch poet Vondel. The overall picture is of a 'renaissance man' - a man of both science and the arts, as well as a dedicated family man. He was also, as we shall see, a hero, for Pompe, no doubt led by his strong Christian beliefs, became active in the wartime in the wartime Dutch resistance.


To the right is a photograph of Dr Pompe in the uniform of a Captain of the Dutch army (Medical reserve), thought to have been taken in 1939-40. Following the Nazi invasion of the Netherlands on 10 May 1940, he was mobilised and was involved in the fighting that lasted until 15 May.

Following the fall of the Netherlands, Dr Pompe became involved with the Dutch resistance. At first he was involved in finding hiding places for Jews. Through this he made contact with the operator of an illegal transmitter.

Pompe's laboratory was somewhat isolated from the rest of the hospital. So much so that at least two men who were hidden in the OLVG worked in the laboratory during the daytime! He therefore suggested that it would make a good hiding place for the transmitter and in sometime in November-December 1944 it was installed in the animal house (where the experimental animals were kept) beneath his laboratory. The transmitter was used to send messages to the UK on behalf of the resistance.

The transmitter was eventually detected by the Germans and on Sunday 25 February 1945, at 10 am, 40-50 members of the German Military Police entered the hospital and made straight for the animal house. The wireless operator, Pierre Antoine Coronel, was broadcasting at the time and tried to resist. He was subject to summary execution in the courtyard of the hospital. After the war, a street was named after him in Amsterdam - Coronel Street. Several hospital staff were arrested.

During the raid, Dr Pompe had been at Sunday mass and on returning to hospital was warned by patients of what had occurred. He went home to tell his wife that he needed to go into hiding. While leaving the house he was arrested in front of his wife and children, who were threatened with rifles.

While some of the imprisoned staff were eventually released, Dr Pompe, Louis Berben (the man in charge of the animals) and a male nurse, Piet van Doorn, were kept in jail.

On April 14, 1945, the resistance blew up a railway bridge near St Pancras, destroying an army train in the process. As a reprisal, 20 Dutch prisoners, including Dr Pompe and Louis Berben were shot. They were taken in a sealed truck to a meadow near St Pancras and, at around 9pm on 15 April, shot in two groups. The bodies were buried in a mass grave in the sand dunes near Overveen. On the same day, Piet van Doorn was also shot, in retaliation for another attack on a railway.

A monument was erected to the victims after the war (colour photographs below, courtesy of Maryze Schoneveld van der Linde's brother).
















In addition, a tile panel was erected above the main entrance of the OLVG, in remembrance of Dr Pompe and the other employees who were shot. This is currently held in storage, following redevelopment of the hospital.


Apologies if the reader feels I have gone on at too much length here. However, I have to confess that I am in awe of such bravery in the face of seemingly insurmountable evil and so wanted to give a fuller picture of the man who is at the start of our story - his intellect and his courage. Truly, there is much to admire about Joannes Cassianus Pompe.

One last comment. I have been gathering this information for some time and have found myself almost reluctant to write it up. The reason is that the German patient group are amongst the leading lights of the international Pompe community and I would be unhappy if this article were thought to be, in some way, anti-German. It is certainly not intended to be so. It is worth bearing in mind that the first country to fall victim to the Nazis was Germany itself (over 3 million German citizens were imprisoned by the Nazis and around 77,000 executed), that they were aided and abetted by home-grown Nazi movements and sympathisers in other countries and that perhaps the bravest of all the anti-Nazi movements was the German resistance. Lastly, I don't think we need to think too hard to realise the fate of any family touched by genetic disease under a Nazi regime.

10 comments:

  1. Thank you for starting this blog Kevin. I think it is a brilliant initiative. I will try to post comments regularly, related to the issues treated in each post. In relation to this one I can only say that Pompe was a great man, and, no doubt, an example to all of us. Also I would like to point out that Pompe disease is present not only in mammals and birds but apparently also in fish (reference:Tørud B et al. Myocardial glycogen storage disease in farmed rainbow trout, Oncorhynchus mykiss (Walbaum). J Fish Dis 2006; 29: 535-40.) In the refered article it is stated that "lesions in cardiac myocytes had a striking resemblance to glycogenosis type II (Pompe disease), a rare autosomal recessive lysosomal storage disease in humans". Therefore, Pompe disease, or some form of it, was already present in the common ancestors of mammals, birds and fish, at least 400 or 500 hundred millions years before life passed from the oceans into the land.

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  2. In my previous comment a made a mistake, what I wanted to say was: Therefore, Pompe disease, or some form of it, was likely present in the common ancestors of mammals, birds and fish, at least 400 or 500 hundred millions years ago, that is before life passed from the oceans into the land.

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  3. Thanks Javier! I look forward to your contributions. thanks for the fish story - excellent!

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  4. A translation of the notice published in the newspaper by his family, following the end of WW2. Translation by Bet Cook.

    We recently received confirmation that our loved Husband and Father

    Dr. JOANNES CASSIANUS POMPE
    Physician

    Pathologist-Anatomist at the O.L.Vrouwe Gasthuis



    was captured by German Occupying Forces during faithful service
    to his country, and executed by firing-squad on 15th April 1945, at 8.30pm, in St,Pancras, near Alkmaar.
    He lived for his family and suffering humanity, he died a hero’s
    death for his country.
    God, Whom he served with devotion, have mercy on his soul.


    A.POMPE – STORDIAU
    KEES,TREESJE.


    Amsterdam, 29th June 1945
    Honthorststraat 52

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  5. Translation by Bet Cook of Obituary notice of J C Pompe.

    Pray for

    Dr. JOANNES CASSIANUS POMPE, Physician

    Pathologist-Anatomist at the O.L.Vrouwe Gasthuis
    in Amsterdam.

    In life, the faithful husband of
    Augusta Maria Constantia Stordiau

    Born 9th September 1901 in Utrecht, executed by a German
    firing-squad on 15th April 1945, at St.Pancras, near Alkmaar,
    and buried in the RC Cemetery at Utrecht.
    ________________


    He lived and worked for his wife and both children.
    He was absorbed, with serious self-critique, in his chosen profession and, through his work, he was familiar with death.
    He died for his country in surrender to God’s Holy Will.
    He did not think of himself, but thought of others, of suffering humankind, and of the Dutch people in oppression and need.
    He loved truth, in his profession and in his association with others.
    He loved beauty, especially in the tragic forms of Sophocles and Vondel.
    He was truly a man, brave and faithful, generous and devout, loved by his family, esteemed by friends and colleagues, a model and support for those who turned to him.
    God, and also the Holy Scriptures, continually occupied his thoughts.
    In the prime of his life, God called him Home.
    Lord, have mercy in Your judgement, give comfort and strength to his wife and children, be a Loving Father to him and his family.
    Our Lady, we ask you to intercede for him and his family.


    Our Father, hear our prayers.

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  6. Translation (again by Bet Cook - thanks Bet!) of Dr Pompe's resignation letter. All dcotors had to belong to the Nazi medical association. Pompe was resigning because he refused to do this. Note that he asks the hospital if they wish him to continue his work. As it is dated 1943, and he was still working there at the time of his arrest in 1945, we can assume that the hospital, at some level, chose to ignore the Nazi law too.

    RC NURSING
    ONZE LIEVE VROUWE GASTHUIS
    LABORATORY FOR PATHOLOGY AND ANATOMY
    _______________
    TELEPHONE 52300
    POSTGIRO 32044
    _______________ AMSTERDAM, 24TH March 1943.




    To the Board of Directors of the
    Onze Lieve Vrouwe Gasthuis
    AMSTERDAM.

    Honourable Gentlemen,

    With this I inform you that, as of today, I have given up my entitlement
    to practice in my profession of physician, as set out in article 5 –
    sub 2 of the Physicians Regulations.

    Under present circumstances, and with the limitations imposed on me
    under these new conditions, I ask you to advise me, if you wish that I
    should continue with my duties.



    Your faithful servant,

    J.C.Pompe

    ( J.C.Pompe)

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  7. I really appreciate your post and you explain each and every point very well.Thanks for sharing this information.And I’ll love to read your next post too.

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  8. Hi, very interesting this. Came here via the Well-blog of the NYTimes. One little thing: the abbreviation for the Onze Lieve Vrouwe Gasthuis is OLVG, but the first time you mentioned it you spelled it OLCG.
    I'll keep on reading!

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  9. I'm a physician. I have known about Pompe disease by its more medical name, Type Two Glycogen Storage Disease. Recently someone asked me if I know about Pompe disease, and to be sure I looked it up, realized sure I know it, and found my way to this blog. I am so grateful to learn so much more about Dr. Pompe, via this blog. Powerful, principled, and kind human being .

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