Human beings now have the technology to rewrite our genetic codes and the codes of every organism on Earth.
What is more, this technology has been around for billions of years—bacteria naturally evolved it as a mechanism to fight off viral invaders—only to be discovered in the early 2000s by researchers working for a Danish yogurt culture company.
The gene-editing technology is an enzyme called Cas9, or CRISPR associated protein 9, and it has already caused a paradigm shift in how basic and clinical research is being conducted in the biological sciences worldwide. But the possibilities for its use are, to put it plainly, nearly limitless.
Curing genetic diseases, engineering life forms to resist the effects of climate change, boosting human intelligence—science fiction is rapidly becoming science fact.
Cas9, the central enzyme in a family of bacterial DNA sequences called CRISPR (clustered regularly interspaced short palindromic repeats), acts as a cutting tool, a tiny genetic scissors to snip up DNA strands.
To tell the history of CRISPR, to explore the science behind it and the societal and ethical implications of it, is the primary goal of “Human Nature,” a new documentary film produced and directed by Adam Bolt, who also directed the Oscar-winning film “Inside Job.” The documentary’s executive producers include journalist Dan Rather.
“In terms of human welfare, CRISPR rivals antibiotics and vaccines. It has already led to new treatments for HIV and new hopes for cancer. In the next decade, it may help eliminate such scourges as Huntington’s disease and muscular dystrophy. But what looms is even more momentous: Scientists are already conducting experiments to modify the DNA of future generations,” the filmmakers wrote in a press release.
Among the voices in the film are CRISPR scientists Jennifer Doudna of the University of California Berkeley and George Church of Harvard University.
Nearly 400 people packed the Lillie Auditorium at the Marine Biological Laboratory in Woods Hole Wednesday evening, July 31, for the “Bringing Science to the Screen” event presented by the Woods Hole Film Festival Film & Science Initiative.
“A number of years ago we were thinking of ways to coalesce what we do with scientists in Woods Hole and to find films that are relevant to this community and encompass the work done at our local institutions,” said Judy Laster, the festival’s founder and director. “Our goal is to bring filmmakers and scientists together to generate discussions with the films as anchors.”
The concept behind “Human Nature” began at a 2016 meeting of scientists and storytellers in Woods Hole organized by MBL Distinguished Scientist Ronald D. Vale, a professor at University of California San Francisco and a Howard Hughes Medical Institute Investigator.
The Wonder Collaborative—a division of Dr. Vale’s science communications initiative, iBiology—presented the film in association with News and Guts Films and Sandbox Films.
Dr. Vale moderated the post-film discussion Wednesday, which included panelists George Daley, dean of Harvard Medical School; Jean-Francois Formela, a partner at Atlas Venture, a biotech firm based in Cambridge; and Regina Sobel, editor and co-writer of the film.
“At the beginning, four scientists and two filmmakers had a two-day planning meeting at MBL and National Academy of Sciences in Woods Hole that nucleated the whole project,” Dr. Vale said before the screening. “We picked the topic of CRISPR and genome editing. We had no script, no detailed plan. We didn’t even know it would be a full-length documentary at that point. The filmmakers presented their ideas of how the science could be interwoven into a story.”
The genome is the basic code that contains “all the information that makes you you,” Dr. Vale said.
“It has a lot of information that makes you healthy, but it also has code that produces some genetic conditions. For many years we could read the three billion letters, or the nucleotides A, G, T and C, in the human genome. Today we can read all three billion letters for under $1,000, cheaper than an airline ticket in most cases, and while we can interpret a lot of the code, a lot of it remains indecipherable and mysterious,” he said.
The four nucleotides are the purine bases, adenine and guanine, that have a double-ring structure and the pyrimidine bases, thymine and cytosine, that have one ring.
Genome editing is not only reading but also rewriting the code.
“Using CRISPR, we can now find one letter in one very specific position in the human genome, and we can, with laser precision, put right what’s wrong. This is an unprecedented opportunity, in the best of circumstances, to correct a number of diseases such as sickle cell anemia or cystic fibrosis,” Dr. Vale said.
Biology has been moving so quickly, it is hard to see where science will go in 10 years, Dr. Vale said, noting that the film’s title plays with the idea of where the boundary is between humans and nature.
“If we can intervene in the development of the code of life, which we now can with the ability to write it, how do we define that boundary? Scientists are deeply involved in that conversation with ethicists and politicians on the thoughtful use of the new power we have to rewrite genomes,” he said. “Also, this technology is not some completely weird thing that showed up from outer space. Man has in very slow and imperfect ways been altering genomes for nearly 10,000 years, primarily through agriculture.”
Early scientists called farmers were effectively altering the genetic properties of organisms through natural selection and selective breeding.
“Most of today’s mammals and all our food are a product of that. Genome editing is now a laser-sharp, precision-focused, latest innovation of technologies that have been around for thousands of years,” Dr. Vale said. “CRISPR is an amazing mechanism that is similar to adaptive immunity in humans, the ways our cells ‘remember’ they were attacked by a bacteria or virus and can recognize and fight them off the next time they appear.”
Researchers can employ Cas9 enzymes, which move through cells “looking for a match between the previous invader and the new DNA that came in,” to make edits.
“Cas9 is a very precise genetic scissors. It scans all 3,000 bases, finds a match and cuts it. The enzyme is looking for a specific sequence of nucleotides; it doesn’t cut wildly. When the cell repairs that cut, it replaces it with a new sequence of nucleotides that researchers can provide” Dr. Vale said.
During the panel discussion, Mr. Formela said the three CRISPR companies he helped found in the past five years are each spending about $200 million a year to turn their discoveries into commercial products.
“Collectively, they’ve already spent in excess of $1 billion. The engineering challenges of CRISPR are massive, and the amount of resources needed is massive,” he said.
The first sickle cell anemia patient received a CRISPR-based therapy earlier this week as the result of a joint venture between Vertex Pharmaceuticals and CRISPR Therapeutics, Dr. Daley said, noting that Vertex also created the non-CRISPR-based “triple combination therapy” to treat the symptoms of cystic fibrosis.
“The reality is their triple therapy is ideally going to be something that a cystic fibrosis patient would be taking for life. Certainly from the perspective of the public good, the NIH [National Institutes of Health] is going to be interested in funding work that would be a singular, one-time intervention and cure. That’s the promise of CRISPR,” he said
Eventually, CRISPR will allow CF patients to receive a single injection and be essentially cured, Mr. Formela said.
“But it’s going to take quite a bit of development and engineering work that is very costly,” he said.
Right now every molecular biology laboratory and biotechnology company in the country is using CRISPR as a general foundation for research, Dr. Vale said.
“It has become a foundation of thinking about doing research on any disease at this point,” he said.
One important undercurrent in the film is a celebration of curiosity-driven science, Dr. Daley said.
“One of the issues we talked about when we came together with the filmmakers here in Woods Hole was we really wanted as much as possible to use this phenomenal story which we found tremendously exciting, the discovery of CRISPR. I mean, you know, yogurt scientists changing the world. We just hoped that the filmmakers could really do justice to this. And when you see this film, you realize how startlingly successful this film has been at that,” he said.
“What you saw in CRISPR is replicated over and over again with so many technologies and so many breakthroughs in medicine, but if you really trace back the origin all the way back, you really find it at a foundation that someone was interested in something and was asking very basic questions about how nature works. If we’re going to advance medicine in new and better ways for the planet, I think it’s also a message that we have to support basic research because you don’t know where the next great discovery will come from,” Dr. Vale said. “It’s become a question of, like many things on our planet right now, what kind of future do we want to have, not as a country but as mankind. It’s really an international conversation.”
“Human Nature” is being shown at film festivals globally and will also be shown at select cinemas and on television in the near future, Ms. Sobel said.