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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Thursday, 26 July 2012

Why does the Duke error matter?

Right. As you know, I like to keep things as objective as possible. So I give fair warning that following one more excursion into the land of facts and evidence, I will give my subjective opinion.

First, more evidence. Let's return to that 2001 paper. As I've shown, it repeatedly describes the dosage regime used in the trial as 5mg/kg. Now, as you know, an earlier trial in Rotterdam had already been published in The Lancet in 2000. Here's how the Duke paper refers to the Rotterdam trial:

Similar cardiac improvements in four infants treated with rhGAA from rabbit milk for 9 months have recently been reported15; however, the doses of rhGAA from rabbit milk necessary for the therapeutic effects were 4 times higher than the present study of rhGAA from CHO cells.

To be clear, the two trials each used enzyme produced by a different method. Rotterdam used enzyme produced in the milk of transgenic animals, whereas Duke used enzyme produced by CHO cells in culture.  The Duke paper is explicitly stating above that their method was better because the dosage used was lower.

In other words they were making an argument based on dosage data that they presumably knew to be false.

And now the subjective part:

This wasn't a case of careless error-checking. It's hard to avoid the conclusion that this was a deliberate omission of data, designed to support the argument that a specific product required a lower dose - an argument now shown to be false.

As a scientist, I find this absolutely shocking. It is a violation of the standards of openness and transparency on which good science relies.

The question is why this occurred. It's probably worth bearing in mind that, once ERT had been shown to work, there was obviously money to be made. And where that money went would depend on the method chosen to produce the enzyme. As you know, the CHO cell method described in the 2001 paper was the production method chosen.

There's also the fact that credit for ERT for Pompe disease is a big thing - perhaps having published last, the temptation to try to gain priority over the previous publication was too much to resist.

Or perhaps, in some way and for some as yet unknown reason, the authors managed to convince themselves that it was OK to withhold the data in the service of some greater good. A human failing - politicians do it all the time - but not one allowable in science.

I have some thoughts on what should happen next but time for a breather.

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