REVIEW: Extraordinary Measures

A Father’s Love and a Scientist’s Dedication in a Race against Time

Extraordinary Measures film poster ©2010 CBS Films, all rights reserved

Imagine this scenario: you are a young married professional, a rising star in a well-respected pharmaceutical company. You have three children, two of which suffer from a rare, inherited genetic disease for which there is no cure. They will die in about a year or two. What do you do? Inspired by the book The Cure: How a Father Raised $100 Million – and Bucked the Medical Establishment – In a Quest to Save His Children by Pulitzer Prize-winning journalist Geeta Anand, Extraordinary Measures is a drama about the real-life story of John Crowley (Brendan Fraser) and Dr. Robert Stonehill (Harrison Ford) as they work feverishly to find a cure for the disease afflicting Crowley’s children. The dramatic caveat is that said cure is based solely on a scientific theory. CBS Films’ motion picture debut touches on a myriad of salient modern-day issues, including personal morality, risk taking, scientific funding, pharmaceutical business practices, the dedication to science, professional relationships, and a man’s love for his family. For the full ScriptPhD.com review, please click “continue reading”.


REVIEW: Extraordinary Measures
ScriptPhD Grade: B+

Extraordinary Measures opens with an ambitious John Crowley (Brendan Fraser) rising up the corporate ladder in the global biopharmaceutical company Bristol-Myers Squibb. Despite two of his three children having a rare genetic disorder called Pompe Disease (pronounced Pom-pay). The family lives a relatively normal life, where birthday parties are celebrated and the children remain upbeat despite their condition. By day Mr. Crowley is a businessman, husband and father, by night he is lunging himself into the daunting world of reading scientific journals in the field of biochemistry, attempting to find and contact any scientist he feels may be on track to developing a cure for his two children. Throughout all of his heroic efforts, he is faithfully supported by his wife Aileen Crowley (Keri Russell).

A graphic comparing the glycobiology of normal lysosome organelles and those afflicted by Pompe's Disease. Treatment with enzyme replacement therapy restores normal function in disease sufferers.

During one Mr. Crowley’s many nights of pouring through scientific papers, he comes across the research of Robert Stonehill, MD, PhD. Dr. Stonehill is a role based on the real-life glycobiologist Dr. William Canfield. What is glycobiology and how does that involve Pompe disease? A glycobiologist is a scientist who studies sugars, and the enzymes which add sugar molecules to proteins. It is these enzymatic chemical modifications where Dr. Canfield is a leading expert and researcher. Pompe Disease is a rare (estimated at 1 in every 40,000 births), inherited and often fatal disorder that disables the heart and muscles (excellent overview). It is caused by mutations in a gene that makes an enzyme called alpha-glucosidase (GAA). Normally, the body uses GAA to break down glycogen, a stored form of sugar used for energy, in muscle cells. But in Pompe Disease, mutations in the GAA gene reduce or completely eliminate this essential enzyme. Excessive amounts of glycogen accumulate everywhere in the body, but the cells of the heart and skeletal muscles are the most seriously affected. Researchers have identified up to 70 different mutations in the GAA gene that cause the symptoms of Pompe disease, which can vary widely in terms of age of onset and severity. The severity of the disease and the age of onset are related to the degree of enzyme deficiency. If a person has only one mutated form of this gene and one normal copy, they are only a “carrier”—that is, they can pass it down to their children, but they themselves do not develop the disease. A person needs to have both copies of the mutated gene in order to have the disease. The Crowley children inherited the mutations for this disease from each parent.

The movie portrays Dr. Stonehill as a brilliant, albeit eccentric, scientist as dedicated to the pursuit of science as he is a cure, and Mr. Crowley as a devoted, loving father who will not quit in his search for a cure. Convinced Dr. Stonehill is on the right track to producing a therapy for Pompe disease, Mr. Crowley is able to meet Dr. Stonehill, currently working as a scientist at a university. Dr. Stonehill, while brilliant and confident in his scientific research and theories, admits that ultimately his work is only theoretical, and not yet empirically proven. Mr. Crowley asks Dr. Stonehill what would it take to get his research from the bench to the bedside of his children and others like them. In short, and bitterly reflective of modern pharmaceutical realities, Dr. Stonehill replies “money.” Dr. Stonehill informs Mr. Crowley that not all sound theories in science are funded, the competition for grant money is fierce. In addition, while Dr. Stonehill loves his research he is frustrated by the university owning the patent rights to his ideas. At this point, Mr. Crowley informs Dr. Stonehill there is a Pompe Disease Foundation which will fund his research. They agree to meet again later in time.

In a scene from Extraordinary Measures, Dr. Stonehill (Ford) and John Crowley (Fraser) discuss the science of their cure for Pompe Disease.

During this time, Mr. Crowley, who is still working for Bristol Myers Squibb, begins to realize his continued employment with the pharmaceutical behemoth might forever endanger finding a cure for his children. Concurrently, he and his wife struggle with the quandary of letting nature take its course versus the moral/ethical implications of trying to fix their children’s condition. Should Mr. Crowley quit his good-paying position, and leave to pursue a cure? Mr. Crowley and Dr. Stonehill decide to start a business together, seek out venture capitalists and ultimately receive the funds necessary to start a small biotechnology company. The issues (and there are many!) of starting and running a biotech company, something neither of them has ever done, are adroitly explored throughout the movie. When investors realize the company is burning through millions of dollars, they give Crowley and Stonehill an ultimatum: merge with someone who can make this drug or we are turning out the lights for good.

The company they form, Priozyme (the actual erstwhile Novazyme), is eventually bought by the fictitious pharma giant called Zymagen. In real life, Zymagen was actually the biotech company Genzyme. Zymagen already has three Pompe research teams, which Dr. Stonehill arrogantly believes this is because they don’t really know what they are doing. Dr. Stonehill is made the chief scientist for what is now Zymagen’s 4th Pompe research team. Mr. Crowley is made the Senior Vice President for the Pompe project, much to the dismay of Zymagen scientists, due to his lack of scientific training. Extraordinary Measures does a good job of portraying the acquisition as a clash between personalities (which is rampant in science) and the often-embraced adage in the scientific community that non-scientists cannot contribute to or advance scientific research to a measurable degree. In addition to Dr. Stonehill’s personality not being received well by Zymagen, Mr. Crowley has his own problems with their corporate leadership. At Zymagen each Pompe disease research team works on its own. The teams do not collaborate with each other at all, with no sharing of information. The corporate leadership believes this brings out the best; Mr. Crowley believes this significantly slows down scientific progress.

Ultimately, although Dr. Stonehill’s candidate enzyme is selected for clinical trials, a bevy of ethical concerns and scientific roadblocks stand in the way of getting the discovery past the laboratory and on the way to FDA approval. Mr. Crowley, who selflessly gave up virtually everything towards the discovery of a Pompe cure, must make the ultimate sacrifice in order to ensure that it is able to help his children. Incidentally, on April 28, 2006 the Food and Drug Administration granted marketing approval for Myozyme® (alglucosidase alfa) in the U.S., indicated for use in patients with Pompe disease (GAA deficiency). While Extraordinary Measures doesn’t get into the gritty details of the true politics behind a lot of pharmaceutical company drug target choices, funding and scientific arm-wrestling, it does an excellent job of giving the lay public a general overview, which has been (with the exception of the brilliant The Constant Gardner) largely cinematically absent. For anyone curious about the drug discovery process, and the anguish both on the part of families and scientists desperately hoping for a cure, this movie is a must-see.

Brendan Fraser on playing the real John Crowley: click here.

The real-life Crowley Family.

Extraordinary Measures goes into wide release on January 22, 2009 in theatres nationwide

Trailer:

NeuroScribe obtained a BS in Biology, and a PhD in Cell Biology with a strong emphasis in Neuroscience. When he’s not busy freelancing for ScriptPhD.com he is out in the field perfecting his photography, reading science policy, and throwing some Frisbee.

~*NeuroScribe*~
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7 thoughts on “REVIEW: Extraordinary Measures”

  1. My mother has been in the pharmaceutical industry for as long as I’ve been alive. A long, looooooooong time ago, she actually worked with rats. I still remember them. Now, she’s in procurement and contracts (which actually is beneficial to me as an artist). The articles within this review hit home for me.

  2. I loved the movie “Extraordinary Measures” as I had never even heard of this disease. I think people need to be made aware of Pompe Disease through movies like this one. Ignorance is not bliss and I am glad I saw this movie!

    1. What a lovely comment. I completely agree! It’s part of the responsibility of science in entertainment to not just give us enjoyable films, but educational experiences and, in the case of “Extraordinary Measure”, an opportunity to save lives. Cheers!

  3. Not just a great film and a heart-touching movie ever shown. It is also about a determination that somehow, knowledge and theories must put into a factual entity that may possibly help humans. I salute for that!

  4. I just finished watching this movie, and have been moved & re-invigorated. I myself have held many positions on the clinical side, taking care of patients. Ten years ago I moved into clinical research. I have worked in a myriad of indications both pharma & device, that being said I have been feeling overwhelmed and burnt out due to the pace to deliver the 4 programs I’m currently working on, which are in the final months prior to NDA submission to the FDA. The movie did a wonderful job highlighting just the basics hurdles that programs face internally a biotechs and subsequently the sponsor companies of the trials. I am proud of my profession this afternoon & will share/recommend this film to others who struggle to understand the process, and those of us insiders who resent the almost inhuman timelines & great personal sacrifice, to be able to deliver sound, safe, efficacious vital medicines to the world.

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