History of Biotechnology

"As Gods

By Matthew Cobb

Basic, 442 pages, $35

The intricate Byzantine mosaics that decorate the eastern apse of the hilltop Cathedral of San Giusto in Trieste, Italy, depict two lithe archangels, Gabriel and Michael. The long, curved, feathery wings that emanate from their backs before meandering elegantly to the ground immediately mark these creatures as existing beyond nature as we currently know it. Imagining such fabulous cross-species chimeras as these, and other mythological creatures such as centaurs, was a prescient ancient anticipation of the potential genetic future of humankind.

In his wonderful book "As Gods," a thoughtful, lively and evocative exposition of the history of genetic engineering, English zoologist Matthew Cobb teaches us how, just a few centuries after the completion of the San Giusto mosaics, scientists began learning how to create chimeras in the real world. Developing the ability to cut and paste the hereditary material that determines the form of living things has permanently changed humankind's relationship with the natural world.

Mr. Cobb references a canon of works including Francis Bacon's visionary "New Atlantis" (1626), in which the author optimistically speculated that plants and animals might be artificially manipulated to produce "New Kindes" of "Perfect Creatures"; Mary Shelley's "Frankenstein" (1818), which invoked the dangers of tinkering with nature; and Aldous Huxley's dystopian "Brave New World" (1932). The author's point is that such fictional forays into biological possibility were both the imaginary precursors and the intellectual substrate for the eventual realization of genetic manipulation. They showed what might be done, while suggesting that such interventions had the potential to subvert the ground rules of human nature and society, in both favorable and unfavorable ways.

The ability to directly manipulate genetic material, and to connect the genes of one species with those of another into hybrid genetic structures, had its origins in the work of one man: the Brooklynite and Stanford biochemist Paul Berg. 

As Mr. Cobb chronicles, in 1967 a fellow Stanford biochemist, Arthur Kornberg, had shown that it was possible to synthesize viral DNA in a test tube and to join the bits together using an enzyme. The newly synthesized DNA even functioned efficiently within cells. 

Kornberg generously shared his enzyme reagents with Berg, who by 1972 had successfully combined pieces of genetic material from different species into a single piece of "recombinant" DNA.

Mr. Cobb describes how Herb Boyer transformed this method into a more user-friendly version at the University of California San Francisco; he calls this the moment that "the age of genetic engineering" began. 

Soon after, Mr. Boyer and Stanford geneticist Stanley Cohen sat down in a kosher deli near Waikiki Beach in Honolulu. As they "scribbled on paper napkins" in November 1972, the researchers realized the genes of any species could be inserted into bacterial DNA. The bacteria could then be tricked into synthesizing the protein encoded by the foreign gene.

This process, now known as gene "cloning," was a significant feat. It democratized recombinant biology, established the foundations for the modern biotechnology industry and made the manipulation of life into a global enterprise. 

Toward the end of 1975, Mr. Boyer was approached by an unemployed MIT graduate named Bob Swanson, who entertained a vague possibility that recombinant gene technology might be exploited to generate what Berg had described as "new forms of medicine" produced by "tailor-made organisms."

The work of Mr. Boyer and Swanson resulted in the formation of Genentech, the first-ever biotechnology company. 

The founders went on to synthesize recombinant human insulin molecules in bacteria. Humulin, as this became known, was approved by the FDA for the treatment of diabetes. 

Based on this definitive demonstration of recombinant biology's commercial potential, Genentech's stock soared on the day of its original IPO in 1980, which this newspaper described as "one of the most spectacular debuts in memory."

Accompanying the tremendous successes of the new genetic gold rush was the self-evident fact that the ability to restructure genetic material raised substantive philosophical and ethical issues. Indeed, following Kornberg's early experiments, his collaborator referenced a forthcoming "second Genesis."

Further advances in genetic engineering, including the advent of Crispr-based gene editing, and more recently, the demonstration that the genomes of simple organisms such as bacteria and yeast can be redesigned and synthesized from scratch, have made such issues even more compelling. The irresponsible use of Crispr by the Chinese scientist He Jiankui -- he employed the technique to edit the hereditary material of three human embryos -- has demonstrated the ease with which such methods can be abused.

In his December 1980 Nobel Prize acceptance speech, Paul Berg anticipated such issues when he noted that there was an "apprehension about probing the nature of life itself" and questioned whether "certain inquiries at the edge of our knowledge and our ignorance should cease for fear of what we could discover or create." Indeed, the author informs us early on in "As Gods" that his impetus for writing the book originated from his own concern about the systematic normalization of genetic engineering and the disconnect between its increasing sophistication and the absence of a serious effort to comprehend and articulate its potential consequences. The ability to manipulate DNA ushered in an unprecedented and potentially calamitous new scientific reality. Visceral realizations of new versions of living things, which had hitherto been impossible, were now plausible.

Berg concluded his Nobel speech by stating that he preferred to be "more optimistic" about the future of genetic engineering. He cited the biologist Peter Medawar, who had said that "to deride the hope of progress is the ultimate fatuity, the last word in the poverty of spirit and meanness of mind." So while we should not, and cannot, turn our back on the hope of progress -- which might reasonably include the elimination of all human diseases -- there is a need for more intense and serious dialogue. Matthew Cobb is very clear that this conversation should include more than just scientific specialists. In short, we may need to imagine not just new forms of life but a new sort of forum, in which to debate humankind's future and define the basis of a manifesto for life.

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Mr. Woolfson is the author of "Life Without Genes" and "An Intelligent Person's Guide to Genetics."" [1]

1. REVIEW --- Books: Present at the Creation
Woolfson, Adrian. 
Wall Street Journal, Eastern edition; New York, N.Y. [New York, N.Y]. 12 Nov 2022: C.9.