Instructions For Building An Animal.

"From One Cell

By Ben Stanger

Norton, 368 pages, $30

In the 1960s, the polymathic Cambridge scientist Sydney Brenner contributed to the deciphering of the genetic code -- the mechanism specifying how the DNA sequences of genes are translated into the amino-acid sequences of proteins. In the 1970s, Brenner set out to define another code: the generative biological rules that determine how the genes within a single cell delineate the three-dimensional organization of multicellular organisms. "How genes might specify the complex structures found in higher organisms," he wrote in a paper on the genetics of the tiny transparent worm C. elegans, "is a major unsolved problem of biology."

Once cracked, this generative code of living things could convey humankind with an unimaginable ability to modify the structures of living things. It also has the potential to help us address such enigmas as why we get ill and the mechanism behind aging. Brenner's brilliance was to realize that a problem of this importance and complexity would only be tractable if studied in simple model organisms. The otherwise inconsequential C. elegans was perfectly suited to this task. It comprised only 959 cells and had a conveniently short three-day reproductive cycle.

Decades later, despite considerable progress in the field of evolutionary development, or evo-devo, the generative rules of biology have not yet been adequately defined. In his insightful and erudite "From One Cell," the University of Pennsylvania doctor and researcher Ben Stanger details the "foundational discoveries" that have contributed to our current understanding. All were made in model systems of differing complexities, ranging from viruses and bacteria to sea anemones, flies, frogs and mice.

The relevance of such organisms to the biology of human beings was summarized by the French scientist Jacques Monod, who stated that "What is true for E. coli is true for the elephant." This maxim referenced the universality of biological structures and the biochemical unity of all life on Earth, resulting from its shared evolutionary origin. A similar sentiment was expressed by the 19th-century French embryologist Etienne Geoffroy Saint-Hilaire, who stated that there is, "philosophically speaking, only a single animal." Nature, in her parsimony, appears to have used a similar method for building all animals, and indeed all living things.

The key conundrum in the development of a human being from a zygote -- the single-celled product of the fusion of an egg and sperm -- is how a uniform set of genetic instructions is differentially programmed to produce multiple cell types that self-organize into a distinct three-dimensional form. We now know that the secret to building organisms resides in gene regulation. Different cell types activate and repress genes in distinct ways, just as in an orchestra a cellist and an oboist might look at the same score but follow only their designated parts. The unique regulatory fingerprint superimposed onto a cell's genome is known as its epigenome, which is established through chemical modifications to regulatory regions of genes and the histone proteins they associate with.

Dr. Stanger artfully guides us through key experiments that contributed to the foundations of our knowledge about embryonic development, and he provides sketches along the way of some of the researchers involved. The author also highlights the role played by serendipity and Nature's coquettish revelation of unexpected phenomena. When the bow-tie-wearing "child of privilege" Ernest McCulloch found himself thrown together with James Till who was "raised on a farm in rural Saskatchewan," it was Till's pragmatism coupled with McCulloch's impetuosity that led to the discovery of the first multipotent stem cell, capable of generating a full set of human blood cells.

Another illuminating passage is the author's account of John Gurdon, the quintessential English gentleman, Nobel laureate and discoverer of nuclear cloning. Mr. Gurdon's achievements stemmed from his frustrated attempts at studying entomology, and he only developed the manual dexterity necessary to manipulate cell nuclei through his hobby, the construction of miniature scale models of trains, boats and planes. That Mr. Gurdon came last in a biology class of 250 students in high school illustrates a recurrent theme in science. Many high achievers have atypical intellectual abilities not captured by conventional "intelligence" metrics.

The book contains several intriguing revelations. One is that "tumors do not invent new biology, but instead use existing biology in new ways." They inappropriately activate genes invoked in embryogenesis. Development and cancer are intertwined, the author explains, with each cancer being in effect "its own species." Another surprise is the ease with which substantive biological modifications can be achieved. The Japanese Nobel laureate Shinya Yamanaka showed, in a trick worthy of the escapologist Harry Houdini, that differentiated cells could be coaxed to "travel back in time" and revert to an undifferentiated pluripotent state capable of generating all cell types.

Dr. Stanger briefly touches on the therapeutic potential of Dr. Yamanaka's induced pluripotent stem cells and the recent misuse of genome editing. But he does not address the most powerful genome-modification method of all. The emerging new science of synthetic genomics coupled with artificial intelligence should enable genomes to be authored and synthesized from scratch. This will play a pivotal role in defining the generative laws of biology. Once such rules have been defined, they will have the potential to significantly influence the future of our species.

The author largely avoids any discussion of the potential risks and utilities of such discoveries, stating that he does not wish to conjure up "some fantastical image of a utopian or dystopian future." But we do need to discuss the future, one way or another. To state that "the benefits must be weighed against the risks" is inadequate in an environment where, as the author puts it, "gaps continue to widen between scientists and the public" as well as between "scientists and other scientists."

Avoiding any substantive discussion of potential consequences is unfortunately common in contemporary popular accounts of molecular genetics. It would be more responsible for authors and experts to forthrightly address them.

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Mr. Woolfson is the author of "An Intelligent Person's Guide to Genetics."" [1]

 

 Judging by the fact that we humans still do not know how to quickly guess the spatial structures of proteins, knowing only their sequences in the genome, although artificial intelligence is perfectly capable of this, only artificial intelligence will be able to create and synthesize genomes from scratch, artificial intelligence again will not explain to us, how does it do it. After all, determining the structure of proteins is the basis of all this work, because the structure of proteins is the basis of most structures and functions in living things.Artificial intelligence just sees patterns that we do not see.

 

1. REVIEW --- Books: Instructions For Building An Animal. Woolfson, Adrian. 
Wall Street Journal, Eastern edition; New York, N.Y.. 12 Aug 2023: C.9.