Who says the cinema ignores the lives of scientists?  The recent film ‘Extraordinary Measures,’ based on the true events in the book The Cure by Geeta Anand, tells the story of how a desperate parent guides a scientific breakthrough to clinical trials, thereby saving his childrens’ lives and the scientist’s career.

The story stars John Crowley (Brendan Frasier), who raised $100 million to find a cure for two of his three children living with Pompe disease, a devastating genetic illness with a lifespan of about 9 years.  The film opens with his daughter Megan’s 8^th birthday party at a bowling alley, a stark reminder of both her degenerative state and her sparse life remaining. Pompe disease is one of family of glycogen storage diseases, characterized by a missing or defective glycogen metabolizing enzyme and leading to the build-up of glycogen in the tissues, a muscular dystrophy-like appearance, and dangerous enlargening of the organs.

Missing enzymes like these can’t just be infused, because they won’t enter the affected cells.  The enzyme needs a special biochemical tag – and in the case of Pompe disease, requires the glycobiology expertise of University of Nebraska biochemist Dr. Robert Stonehill (Harrison Ford).  Stonehill is presented in the film as late-night lab rat; a beer drinking, classic rock playing, grumpy stereotype of an academic researcher.  He mostly works (further illustrated by the repeated mention of his two ex-wives?), aside from a bit of bass fishing, and when he leaves the lab late at night its to drink beer and eats ribs at the local watering hole. 

Stonehill is embittered against the academy for its misguided financial focus on football, while his research suffers the setbacks of competing for increasingly limited research funds.  While the film’s sketch of an academic researcher may be accurate to some degree, the most telling truth of his character is his ongoing struggle to keep his research afloat.  The disease he studies is rare and difficult to treat, not exactly the prescription for superfluous funding.  His story is certainly not unique in the world of biological research.

Touches of real science are deftly added to scenes of Stonehill’s laboratory and workspace in the biochemistry annex at UN: the jugs of Fisher chemicals, the note-laden freezers, the centrifuges and vials, a Human Kinome poster on the wall, PNAS journals sprinkled about.

At home in Oregon, Crowley, a Harvard Business School graduate, is a drug marketer for Bristol Myers by day, but by night he cares for his children until their bedtime and then scours the scientific literature on Pompe.  He finds headlines like ‘Stonehill pioneers enzyme research’ and ‘Theory of a cure for Pompe’ written by Stonehill himself.   After Megan is hospitalized and doctors were shocked by a recovery so late in her Pompe life, Crowley abruptly makes a trip to Stonehill’s laboratory in Nebraska.

Stonehill is visibly saddened by Crowley’s situation – two children with Pompe reaching the end of their lives and no treatment in sight.  But he is realistic about the odds – telling Crowley to spend time with his children instead of searching for a miracle.  He’d need $500,000 in the next month to even keep his promising research on track.  But Crowley is not deterred, and back in Oregon he sets up a foundation for Pompe and begins fundraising.

Throughout the film we see Crowley’s oldest child, who is not sick, and as a viewer we worry about his lack of parental attention – but we also see he’s just as concerned as the parents, selling a skateboard to donate to the fundraiser.  In my personal experience, this is not a rare scenario (see my post on San Filippo here: http://open.salon.com/blog/aliquot/2009/10/16/baffled_scientist_no_cure_for_diseases_we_do_understand ).  But the $90,000 Crowley raises initially from friends, family, and a built network of other Pompe families, is just not enough – Stonehill convinces him that the only way to see his enzyme research span bench-to-bedside and enter clinical trials, thereby promising treatment for Crowley’s children, is to start their own biotech company – a start-up using venture capital.

This is when a series of medical and scientific ethical dilemmas subtly enter the film’s subtext.  Currently, Crowley’s medical bills total $40,000 per month, which requires he maintain his current job for its high pay and stable health insurance.  But Crowley rolls the dice, and moves forward with Stonehill, using funds Crowley fineagles from a venture capitalist initially turned off by Stonehill’s defensive and arrogant stance. 

In reality, a scientist like Stonehill would not have been so off-put by the tough questions posed by the venture capital firm – every day scientists are faced with harshly critical peers and a thick skin is something scientists gain early in their career – as well as the ability to defend their own research ideas.  Plus, the venture capitalists' points were valid.  The FDA, who monitors and regulates all clinical trials, is not an agency Stonehill has worked with before, and this is clearly a point of concern for investors.  FDA regulations are strict and labyrinthine, and Stonehill’s work had previously been carried out in cell lines and model species, with enzymes derived from cow parts bought from the local stockyard.  For a clinical trial with human subjects, new and appropriate sources of enzyme and all the necessary details would need to be planned out and optimized through pilot data collection. 

But the initial few million in funding is (astonishingly) quickly obtained and Stonehill sets up the new biotech lab, staffed by young scientists, who Stonehill says aren’t afraid of risk – and you can pay them less.  A truer statement about science has never been uttered.  After a brief period of data collection at breakneck pace, Stonehill and Crowley sell their start-up to a larger biotech company specializing in rare enzyme disorders.  This larger company had been trying for years to bring one of their Pompe  enzymes to market, but they lacked Stonehill’s expertise and groundbreaking ideas on enzyme delivery. 

A price isn’t discussed, but we see Stonehill pin a 6-million dollar check to the bulletin board of his new office space. (Anand’s website provides these details we’re not privy to in the movie version of this story: "Novazyme Pharmaceuticals Inc. (the start-up) went from an endowment of $37,000 to $27 million, and was sold to Genzyme Corp. soon thereafter for a newsbreaking $137.5 million").

Why does Stonehill leave the check pinned up?  Another truism about the scientist: he doesn’t want to cash the check until he’s earned it, by bringing a drug to clinical trials.  And besides, he’s “a scientist , (he doesn’t) care about money.”

At the big biotech, profit is the magic word.  Will this new treatment be profitable? What is the acceptable rate for loss of life to move forward with manufacturing?  Well, the children would need the drug infused for life…and they are diagnosed at birth.  Also, a technology like this could likely be used for similar glycogen storage diseases.  Data collection in preparation for a clinical trial moves forward for 4 color-coded enzymes – three originally developed by the large company, and Stonehill’s revolutionary design. 

The film then introduces us to many of the quandries encountered while doing research for profit: Objectivity vs. being counterproductive and emotional, conflict of interest, pleasing and prodding the FDA for clinical trial status, the best type of clinical trial (infants vs. siblings  with similar genetics), theory vs. therapy, ideas vs. interpersonal skills.

The movie (and the real life story) end with small triumphs.  In real life, Stonehill continues his quest for better enzyme delivery, and small and large biotech firms all over the world strive to create drugs that save lives and create profit, while academic scientists toil away at the groundbreaking ideas that may not be lucrative in the present but hold immeasurable value in the future.

For further reading:

http://extraordinarymeasuresthemovie.com/

(CBS pictures, starring Harrison Ford, Brendan Frasier and Keri Russell)

 http://www.thecurebook.com/

 Pompe Disease: http://www.ninds.nih.gov/disorders/pompe/pompe.htm

 Glycogen storage diseases: http://www.agsdus.org/

 Today’s NYTimes piece on the money-science interface:

http://www.nytimes.com/2010/01/26/science/26tier.html