The Top Eight Nanometers: A Review of Human Nature on PBS

By Robert Cook-Deegan

If you are interested in (or teach) the implications of contemporary genetics, you will want to watch the Nova documentary Human Nature, which will premiere on PBS on Wednesday, September 9, 2020.

Like the other documentaries, this one raises the prospect of “designer babies” and alludes to the history of eugenics and Nazi racial hygiene, but it is distinctive in its focus on genome editing and the recent history of the development of the technology called CRISPR, the most precise and elegant tool for editing DNA to date.

Human Nature joins a line of documentaries about “the new biotechnology” that stretch back to Horizon’s Brave New Babies (1982), Nova’s Cracking the Code of Life (2001), WNET/Thirteen’s five-part DNA (2003), Nova’s Cracking Your Genetic Code (2012), and PBS’s The Gene: An Intimate History (2020).

Human Nature, which is 92 minutes long, starts with an excerpt from a prescient October 1966 talk by the late Robert Sinsheimer at Caltech. Speaking years before the molecular genetic miracles of the 1970s—recombinant DNA and DNA sequencing—Sinsheimer foresaw the potential for deliberate biological engineering they would bring. He invoked “the end of the beginning,” and now 54 years later we’re still there. Sinsheimer delivered his talk just 13 years after James Watson and Francis Crick described the structure of DNA, which other scientists then built on to reveal the triplet code that translates nucleic acid sequence to the amino acid composition of proteins—the molecules that do most of the work in living cells. Sinsheimer invoked a metaphor of the billion-year history of the Grand Canyon, with modern science appearing only in the top few micrometers of topsoil on the canyon’s edge. The CRISPR revolution really began in 2012, just eight years ago, so it constitutes just the top eight nanometers of this modern science timeline.

Sinsheimer invoked a metaphor of the billion-year history of the Grand Canyon, with modern science appearing only in the top few micrometers of topsoil on the canyon’s edge. The CRISPR revolution really began in 2012, just eight years ago, so it constitutes just the top eight nanometers of this modern science timeline.

Human Nature then skips forward to the present day, and CRISPR, a major advance since Sinsheimer’s time, becomes the star of the show. CRISPR is a series of repeating DNA sequences that were discovered as part of the adaptive immune system of bacteria that have been engineered to do semicontrolled DNA editing. CRISPR’s sidekick in this story is Cas9 and other associated proteins that cut and repair DNA. The human potential for genome editing is illustrated by David Sanchez, a multiracial child who is deeply thoughtful and uncannily insightful about his life with sickle cell disease, whose appearances become a leitmotif throughout the film.

Human Nature goes further into the discovery and development of CRISPR than other documentaries. Teachers of history of biology, or social implications of technology, will find this story beautifully illustrates the serendipitous origins of a powerful technology. Francisco Mojica at the University of Alicante in Spain started studying microbes in high-salt environments with no particular vision of editing genomes to cure disease. Yet he and his colleagues laid the foundation for a technological revolution that will affect medicine, agriculture, and the environment.

Building on Mojica’s discoveries, the triad of Jennifer Doudna, Emmanuel Charpentier, and Feng Zhang entered the scene and made CRISPR-Cas9 a genetic engineering dynamo. These three get their time on camera, especially Jennifer Doudna, whose rhetorical skills span a vast dynamic range from molecular detail to the social themes explored in her recent book, A Crack in Creation.

Francisco Mojica at the University of Alicante in Spain started studying microbes in high-salt environments with no particular vision of editing genomes to cure disease. Yet he and his colleagues laid the foundation for a technological revolution that will affect medicine, agriculture, and the environment.

Two scholars of law and bioethics, Alta Charo and Hank Greely, explore the ethical and legal implications of the technology. Charo cochaired the National Academies study on human genome editing, and Greely’s book The End of Sex made him an obvious pick, combining deep scholarship with a delightful sense of humor.

Human Nature takes a short turn into eugenics and racial hygiene. For more depth on the subject, consider Part 5 of WNET/Thirteen’s documentary DNA, “Pandora’s Box.” One of its highlights is the stupendously awkward body language of the molecular biologist Benno Muller-Hill as he takes James Watson through the killing chambers of the Holocaust. Muller-Hill’s 1984 chronicle of Nazi racial hygiene, Murderous Science, caused eruptions in Germany when it came out, and Watson inexplicably chooses a moment in the death chamber to expound on the latent virtues of eugenics. That indelicate choice makes riveting teaching material, much more than the minutes devoted to eugenics and racial hygiene in Human Nature.

Human Nature is several steps up, however, from another recent documentary on contemporary molecular genetics, Ken Burns’s The Gene: An Intimate History, which was hobbled by sloppy history and incoherent documentary narrative, despite some bright spots including the geneticist Wendy Chung and patients struggling with genetic disease.

Human Nature also is distinctive in not spending much time on the highly public but premature (and criminal) experiments of the Chinese researcher He Jiankui, wisely relegating that sorry PR misadventure to a text postscript.

One feature conspicuously and unfortunately missing from this CRISPR narrative is the powerful role that money and business decisions will likely play in influencing when and how genome editing will be used. Human Nature fails to reckon with the fact that CRISPR’s future will be determined as much or more by what makes dollars than what makes sense.

The confluence of business and science is more thoroughly explored in Betsey Arledge’s Cracking the Code of Life (2004). That Nova documentary chronicled the competition between the publicly funded Genome Project and the privately funded effort to build a human reference genome by the private firm Celera. In contrast, the corporate influence on CRISPR is entirely missing from Human Nature, with nary a mention of the almighty dollar.

One feature conspicuously and unfortunately missing from this CRISPR narrative is the powerful role that money and business decisions will likely play in influencing when and how genome editing will be used.

This omission is problematic because it distorts how people will understand the true potential of CRISPR technology. The applications being most aggressively explored, and addressed most thoroughly in Human Nature, are for human health (gene therapy), where prospects of profit are great. Yet the possibilities for nonhuman genetic alterations could significantly transform the world. For example, CRISPR has vast potential for environmental remediation by engineering plants to sequester carbon dioxide, keeping it out of the atmosphere where it can drive climate change. And if the technology were used to limit the transmission of mosquito- and tick-borne diseases, it could have significant public health benefits. These and a host of other applications have great social promise (and peril) but limited prospects for profit—themes that Human Nature simply does not explore.

Human Nature, even when interviewing researchers at firms exploring pig genetic engineering and human gene therapy, silently passes over the significance of business interests. It skips over a high-stakes patent battle that CRISPR-involved universities are fighting. And it ignores the fateful decision of those universities to outsource much of the control over the technology to different clusters of start-up firms, described by Jorge Contreras and Jacob Sherkow in Science (February 17, 2017). By giving the exclusive rights to crucial CRISPR patents to biotech start-ups that cannot possibly pursue the full range of gene editing applications, the universities likely constrained how the technology will evolve. Yet the crass business aspects of the story are not even mentioned. Someone else will have to cover that crucial part of the story.

Human Nature is an excellent way to spend 92 minutes, introducing CRISPR and some of its implications, and it can be confidently used in teaching. If you care about genetics—and the peculiar and limiting ways in which biotechnology is framed—you will want to watch it.