Big Science Hits the Big Screen

The pain and suffering afflicting innocent children from a rare genetic disease, and its conquest through biotechnology, would hardly seem to be a winning formula for a blockbuster at your local Cineplex. So it is surprising to see that this formula has been adopted twice in films with big-name casts and large budgets. The films' implications are important for the public's vision of modern medical science, especially at a time where science literacy among the public is said to be at an all-time low.

The films have many similarities. Lorenzo's Oil (Universal Pictures; Directed by George Miller) and Extraordinary Measures (CBS Films; Directed by Tom Vaughn) both depict families who attempt to discover and implement cures for their children's genetic diseases when they find no remedy in current medical science. Both are "based on actual events" and both are beautifully filmed and edited. Both present a great amount of scientific detail and make a powerful case for the lavish support that medical research enjoys. Both have feel-good endings that, amazingly enough, turn out to be largely accurate.

On the down side, both have a lot of contrived conflict situations, invented characters, juxtaposed events, and hyperbole. But perhaps the most interesting aspect of the films for those in the field of biotechnology is the acknowledgement of the tremendous progress biomedical science has made during the past two decades.

Lorenzo's Oil, released in 1992, portrays the life of Augusto and Michaela Odone as they struggle to find a treatment for adrenoleukodystrophy (ALD), an X-linked recessive disease in which the myelin sheath covering the nerve axons deteriorates. Because of a mutation in the peroxisomal membrane transport protein, there is a failure of beta oxidation of long-chain fatty acids (VLCFAs) that accumulate in the circulatory tract, causing the loss of myelin and leading to fatal disease. The Odones discovered that a mixture of erucic and oleic acids (combined with dietary restrictions) could lower the serum levels of the VLCFAs. While the clinical benefits of the treatment were in doubt initially, long-term studies have confirmed that the oil can indeed prevent, but not reverse, some damage caused by the mutation.

In the coda of the film, a group of young boys are shown with a voice-over claiming that they benefited from the oil. At that time, there was no solid evidence to support this claim. Miller, the director, was criticized for playing "fast and loose" with the facts. But later, long-term studies seemed to back the claims of the therapy's benefit.

There is another fascinating epilogue to the story. Hugo Moser, the father of ALD research, wrote a critical review of the movie in which he took Miller to task for introducing a non-existent controversy between researchers and the ALD parental support group. However, in later writings, he emphasized the positive effects of the oil treatment, based on long-term studies.

Almost two decades later, in 2010, Extraordinary Measures hit the theaters. It received mixed reviews and did not do well at the box office. This film portrays the Crowleys, a real-life couple who, once again, buck the medical establishment in an effort to save their children from the ravages of a rare genetic disorder, in this case, Pompe's disease. Harrison Ford plays an eccentric and irascible molecular biologist, Robert Stonehill of the University of Nebraska, who was patterned after the real-life investigator, William Canfield of the University of Oklahoma Health Sciences Center.

Much of the film was shot in Portland and Seattle, even though Canfield's company, Novazyme, was based at an incubator at Presbyterian Health Foundation Research Park, in Oklahoma City. Crowley joined Novazyme in March of 2000 as CEO and pursued the research that eventually played a role in the successful therapy of the disease. In 2003, the affected Crowley children received the enzyme replacement therapy for Pompe disease developed by Genzyme. The children are still on respirators today. Crowley and Canfield sold the company to Genzyme in Boston in 2001.

Crowley is now the CEO of a highly successful biotechnology company that specializes in drugs that cause errant enzymes to fold properly.

Lorenzo's Oil was made at a time when the human genome, routine gene cloning, knockout animal models of genetic disorders, and microarray screening did not exist. The Odones' discovery was not based on current technology and their experimentation on human subjects would be inexcusable today. Their work, however, was credible as a literal "mom and pop" therapy.

Today's high-tech universe in which one can manipulate molecules based on three-dimensional computer models, gene identification and cloning is rapid and routine. In addition, human-subjects committees and ethical guidelines for clinical trials are all pervasive have greatly improved?.

Future breakthroughs in the treatment of genetic disorders will come from big laboratories and legions of scientists in white lab coats. Although an angry loner battling the system provides a much more romantic plotline than an executive who works within the framework of the establishment to achieve his goals, there are legions of genetic disease waiting to be cured and their obliteration will be not documented on the big screen. But this industry's work and achievements will continue to save lives.

K. John Morrow, Jr., PhD, president of Newport Biotech Consultants in Newport, KY, kjohnmorrowjr@insightbb.com.