Rare Disease Report

X-Files Finale Saved by Rare Disease

FEBRUARY 23, 2016
Ricki Lewis, PhD
In the error-ridden finale of the long-awaited X Files reboot, mention of a rare genetic disease in the last minutes added a much-needed glimpse of scientific accuracy. But the buzzword-drenched, preposterous plot managed to flame fears of genetics, CRISPR, and, most alarmingly, vaccines.
Framing the return of FBI agents Fox Mulder and Dana Scully were episodes about evil experiments that altered the DNA of unfortunate humans who had been sucked up into spaceships over the years, Scully among them. Episode one of the reboot featured an insulting zoo-like corridor of young children with the malformations of genetic syndromes, induced by the tinkerings of evil alien geneticists.
Conflating Doctors and Scientists
It’s difficult to know where to begin in debunking the depiction of Dr. Scully. The final episode opens with her explaining her background. Right after medical school she joined the FBI to check Mulder’s work on the unexplainable, somehow and suddenly becoming a scientist along the way. But she uses phrases such as “faith in science” and “scientists’ strongly-held beliefs” that no scientist I know would ever use, except Ben Carson.
When, exactly, did Dr. Agent Scully get her PhD? I suggest we start a gofundme campaign to send her to grad school.
Sure, doctors can be scientists. I’m reading the wonderful “When Breath Becomes Air,” by Paul Kalanithi, MD, who describes the two years of his 7-year neurosurgery residency when he did basic neuroscience research, just before learning he had stage 4 lung cancer.
Scully repeatedly talks about “alien DNA” that has “unexplainable aberrant sequences.” The result: “My personal genetic makeup turned up DNA anomalies that I can only classify as alien.” What, exactly, is alien DNA? 
DNA is a chemical, a polymer that varies in its sequence of four building blocks. Is it alien just because it originated on a spaceship or on another world? Did the writers, one of whom I went to grad school with so I know she knows better, forget the wonderful original X-Files episode with alien DNA that had a fifth and sixth nitrogenous base?

Please Don’t Trash Vaccines
Vaccines are central to the plot, and the depiction is just dead wrong. This scares me, because last week I read a few Facebook posts from young parents who assume that vaccines permanently alter DNA. They do not. They stimulate an immune response in an individual. Scully must have missed immunology class as well as biochemistry.
Anyway, all of a sudden, people are getting the open wounds of what can only be anthrax. Not just any people, but military personnel who received anthrax vaccines. Then older people start getting flu. Names of other infectious diseases are rattled off as people start to bleed from their eyes and topple over. Anthrax is the “canary in the coal mine,” Scully dramatically portends as the music swells.
It must be faulty vaccines! Scully wonders if her smallpox vaccine got into her germline. So let’s repeat a scary word and idea: germline, germline, germline.
In the name of emulating real science, other hypotheses are trotted out: global warming, aluminum, and microwaves. Chipotle? To quote Woody Allen in Sleeper, “no deep fat? No steak or cream pies or... hot fudge?”
A charismatic newscaster serves as a device to follow the “immune system decimated by tampering genomes” that is plaguing the world with a “massive variety of contagions.” People are walking around with “pieces of alien DNA in their genomes” he warns, perhaps like the smidgeon of Neanderthal DNA that all of us except those of African ancestry harbor.
ADA Deficiency Explains It All
Enter newbie Scully, the aggressive FBI agent Einstein. The two ponder, as the episode wraps up, what might have happened. And this is where it starts to make sense.
It seems the toppling bleeding people don’t have bad vaccines that suddenly attack them after all. They all have adenosine deaminase deficiency, the ADA gene having been yanked out of the genomes of the people transported to alien spaceships by – CRISPR!
Scully mentions Cas9 and Einstein explains how this form of genome editing works, helpfully pointing out that the anomaly could be a deletion, not an added sequence like Scully thinks. In fact, it would have to be a double deletion because the disease is recessive.
CRISPR turned to the dark side induces genetic disease, like the kids on display in the first episode. Scarier than vaccines!
ADA deficiency is pretty famous as rare diseases go, having been the target of the very first gene therapy clinical trial, in 1990. I tell the story of the first patient, 4-year-old Ashanthi DeSilva, in my book The Forever Fix: Gene Therapy and the Boy Who Saved It. But Scully and Wannabe Scully seem unaware of the disease’s place in the history of genetics. Missed the human genetics course too.
ADA deficiency is a “severe combined immune deficiency,” so-called because it topples both the B cell (antibody) and T cell (cytokine) arms of the immune response. ADA deficiency is like inherited AIDS, and it is treatable with a stem cell transplant or, soon, gene therapy.
Yes! That’s it! But now what to do?
In just a few minutes, Einstein pumps out some of Scully’s blood, which has somehow been made precious with an add-on called the Spartan virus by the cigarette-smoking man (I don’t have the energy to explain that), and they run it out on a gel, which somehow confirms what Scully already knew: her protective DNA sequence is on “chromosome 17 near the centromere, I saw it when I sequenced my genome.” Well no Scully, you’d need a karyotype (chromosome chart)  for that.
Chromosome! Centromere! Genome! Sounds like science!
The two redheads (and their hair looks great while everyone else is bleeding out) get more DNA from Scully and amplify it. PCR, PCR, PCR. Make technospeak into mantras and viewers will assume it makes sense. Some of the detail here escaped me, it went by so fast, but Scully’s genome has something that disables the CRISPRed removal of the ADA gene. I think.
Anyway, in minutes, the two women have fashioned a vaccine (“could be a miracle!” explains scientist Scully) and then she runs around the panicking crowds in Washington DC proclaiming the great news. Finally, she finds Mulder and they truck out one last cliché – only stem cells from their son can save him! – and then the good doctor, scientist, and FBI agent Scully is, once again, in the crosshairs of a hovering spaceship. The light telescopes down to engulf her, and the series ends.


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