The Last Word On Nothing

I don’t have a problem with screenwriters fudging scientific truths as long as they: are internally consistent with their made-up science; and manipulate the facts in the name of telling a good story.

Rise of the Planet of the Apes, which came out on Friday, follows the first rule and tries to follow the second (more on that later), so I’m not upset that it gets a few things wrong about gene therapy. Still, I feel it’s my duty to tell you what was not quite right, and describe a few real advances in the field.

Gene therapy is conceptually simple: researchers use stripped-down viruses as vehicles to carry a healthy gene into cells to fix or replace a broken one. Since its clinical debut in 1990, the approach has cured a handful individuals of rare immune disorders and congenital forms of blindness.

In Apes, James Franco plays an earnest scientist who injects a gene therapy into his father’s bloodstream to try to cure his Alzheimer’s. A review from the Atlantic nicely summarizes the set-up: (Spoiler alert!)

A pharmaceutical chemist named Will Rodman (James Franco) has been testing a new anti-Alzheimer’s gene therapy on chimpanzees, who undergo astonishing cognitive enhancements as a result. Alas, just as he is selling his corporate board of directors on the need to conduct human trials, his star subject, a chimp named “Bright Eyes,” rampages violently into the boardroom and is shot dead by security. The board, needless to say, is not amused, and Will’s project is canceled. He soon discovers, though, that Bright Eyes has left behind a newborn son, whom he takes home and names Caesar. The young chimp has inherited his mother’s augmented intelligence…

…and, after being cruelly treated by humans, leads an uprising of super-intelligent apes.

My first qualm is over that inheritance idea. It’s possible, I think, theoretically, for a mother to pass on a gene therapy to her baby. That’s because some gene therapies use retroviruses, which worm their way into the genome to deliver the new genes. Once integrated into the genome, they could be passed down to offspring just like any other gene. In the movie, however, Bright Eyes gets pregnant before she goes to Will’s testing facility. So that means that Caesar’s genome was already set before his mother was exposed to the new therapy. The only other way a mother can transmit things to her fetus is through the placenta, which most viruses can’t cross. What’s more, retroviruses used for gene therapy degrade soon after they’ve released their DNA packages.

That’s just a technicality, though. What about the more provocative claim that gene therapy could lead to “cognitive enhancements”? It’s not totally crazy.

One of the biggest obstacles for gene therapy is that the patient’s immune system usually mounts an attack on the virus delivering the new gene. (The film nodded to this: Years after Will’s therapy had cured his father of Alzheimer’s, the father’s immune system produces antibodies that reject the therapy.) One way to avoid this response is to insert the virus into an area of the body that is somewhat roped off from the immune soldiers in the bloodstream. One of these spots happens to be the brain, which is protected from the blood by a dense sheet of cells called the blood-brain barrier.

The brain is a good target for gene therapy.* But what about those cognitive enhancements? Genes encode proteins, so gene therapy is basically a type of protein replacement. If there are particular proteins that help the brain learn, then gene therapy could provide them. In the film, Will explains that his gene therapy works by boosting neurogenesis, the birth of new neurons, a process that is thought to be important for memory. So the question is, are there genes that encode proteins that are known to trigger neurogenesis?

Sure. There is no single gene that is mutated in Alzheimer’s, a degenerative disease in which brain cells die and form characteristic plaques and tangles. But there are genes that encode proteins that help neurons grow and thrive. In 2005, researchers used gene therapy to deliver a growth factor gene directly into the brains of six people with Alzheimer’s disease. Over the next couple of years, their cognitive decline slowed significantly.

To sum up, Apes exaggerated what gene therapy can do, and fudged a few technical details. Its worst crime, however, was in its muddled story.

When I entered the movie theater, I thought I knew the point the writers would be making: that animal testing, particularly when mixed with corporate greed, leads to calamity. If that was their intent, they failed. The driving force behind the testing was Will, a sympathetic protagonist, who did it for a noble cause: treating his father’s devastating disease. During the experiments, the apes were treated extremely well; it was only outside the walls of the pharmaceutical company that they were abused. An evil corporate executive character makes an appearance, but his actions don’t have anything to do with the eventual rise of the angry apes.

The only message I can draw from the film is the opposite of what was probably intended. Animal testing is a Good Thing: science gave the apes the edge they needed to escape from their evil captors and frolic in the forest in peace.

—

*Gene therapy may work for other brain diseases, too. In March, researchers reported results from a randomized clinical trial of 45 patients with Parkinson’s disease. For half of these volunteers, a gene called GAD was injected directly into a region that’s overactive in the disease. GAD makes a protein that helps dial down brain signaling. The participants who received the new gene saw significant improvements on tests of gait, posture, and hand movements compared with those who received a sham surgery.