Foreword

GENOMICS, EARTHQUAKES, AND THE EMPEROR’S CLOTHES

By Richard Milner, M.A.
Associate in Anthropology
American Museum of Natural History

Stuart Pivar’s “heretical” ideas on the origin of organic forms, which are the substance of this book, have led me on an unexpected path. After decades of near-complacency about the evolutionary biology I thought I knew, I have found the solid ground beneath me become suddenly untrustworthy, as Darwin felt when he got too close to earthquakes in South America.

When I wrote the above paragraph in early June 2007, I had no clue that an intellectual earthquake was about to rock biology two weeks later, demolishing cherished theories about DNA and the genome, just as Pivar (and, among others, the Harvard geneticist Richard Lewontin) had correctly predicted would eventually happen. I was becoming increasingly skeptical of the established life sciences; even some of its trivial news releases were making me cringe. Take this newspaper clip from June 1, 2007: a biotech company had just presented James D. Watson, co-discoverer of the structure of DNA, with a transcript of his own genome sequence, which filled two CDs. He accepted them with humble graciousness, as the owner of McDonald’s might react to ceremoniously receiving the umpteenth billion hamburger sold.

Promoted as the first printout of a human genome made for under $1 million, I suppose the non-event was meant to demonstrate to the public how the costs of genomic sequencing have plummeted. Was the common man expected to cheer at the imminent trickle-down of this expensive technology? Cheap genome home test kits are just around the corner. But the problem is, except for a few warning markers of disease vulnerability—many of which you could deduce from family history--would the results tell us anything useful or significant?

Writing in Nature, journalist Erika Chek noted that “such personal genomes (as the one made for Watson) are for now largely symbolic, because it’s difficult to draw concrete information about a person’s health from his or her genome.” The earthquake was beginning to rumble.

Genomes are described as “largely symbolic” in Nature, a bastion of the biotech establishment? Were cracks in the edifice suddenly appearing in public view? Genomics has dominated biology for half a century, and had become a holy grail. Many seemed to regard the genetic code, in President Bill Clinton’s phrase, as “the language in which God has written the story of living things.” It was sold to the public as biology’s long-sought Rosetta Stone to understanding how a living thing is formed. When the preliminary completion of the genome was first announced in 2000, Francis Collins, director of the U.S. Human Genome Research Institute, stood by Clinton’s side and proclaimed, “we have caught the first glimpse of our own instruction book.”

The problem was: no one could read the so-called instructions, nor had they the slightest clue as to how they built a living body. Pivar, whose work on structural self-organization is the heart of this book, had concluded several years ago that the adoration of the genome was a scientific wrong turn that should be consigned to the dustbin of history, along with phlogiston, the Homunculus theory, spontaneous generation, and the four humours of the body.

Biology’s underlying rationale, since at least the late 1950s, has been that genes and DNA are like an architect’s blueprints for a house. First the code has to be spelled out in terms of its chemical components, and their sequence. Then, at some point, we could discover how this blueprint is translated into membranes, flesh, and bone. A series of Hollywood blockbuster movies was based on the premise that living dinosaurs could be reconstructed from the DNA inside a fossilized mosquito.

Alas, biologists have awakened from what Lewontin called “the dream of the human genome.” True, much has been learned about DNA over the last few decades, but the function of over 95% of the genetic material was completely unknown, and called “junk DNA,” a label for ignorance. Many genes seem to do nothing but regulate other genes. Some command certain formal features to be repeated many times, and others are simply on-off switches. (Pivar insists that you cannot understand the form and function of the electrical appliances in your kitchen by studying their on and off switches.) Other genes speed up development or slow it down. Some jump around and change places in the sequence, and others reinterpret old patterns in new ways. One very odd thing is that more complex creatures do not necessarily have more genes than simpler ones; a sea urchin for instance, has almost as many genes (23,000) as a person does.

All that accumulation of facts is worthwhile, but Pivar believes it has distracted biologists from the main prize: the origin of form. By the turn of the 21st century, however, it was becoming clear (though few in the biotech enterprise were prepared to admit it) that the emperor wasn’t wearing any clothes. Biologists were stymied about the great unspoken question; how do these genes and the proteins they produce become a plant or animal? Some maverick biologists in several countries broke with the prevailing paradigm to pursue work akin to Pivar’s: a biomechanical view of life, an alternative explanation of how, in Charles Darwin’s phrase, “the birds and the beasts are formed.”

If the genome is indeed a blueprint, then how come no one has achieved even a glimpse of how flesh and blood organisms are built from the genomic plans? It would be as if, on the analogy of an architect’s blueprints, no one ever saw the foreman reading the plans, materials being ordered and gathered, and the workmen at their tasks. No one has yet seen the genomic hod carriers, or brick layers, or roofers, or builders at work. Back in 1888, the German embryologist Wilhelm His accepted August Weismann’s new ideas about the “germ plasm” with this caveat: “I should be the last to discard the law of organic heredity… but the single word ‘heredity’ cannot dispense science from the duty of making every possible inquiry into the mechanism of organic formation. To think that heredity will build organic beings without mechanical means is a piece of unscientific mysticism.”

On June 14, 2007, the earthquake finally hit. The venerable AFP news agency announced that, after four years of study by 35 scientific groups from around the world (joined together for the ENCODE project) the scientists were forced to conclude that their model of the genome was wrong, and that “a cornerstone concept about the chemical code for life is badly flawed.”

Scrutinizing a small percentage of the genome, the scientists had tried to identify the role of every component in forming an organism. They could not even begin to accomplish their self-appointed task and concluded “that an established theory about the genome should be consigned to history.” Pivar had already reserved a place for it somewhere between Phlogiston and the Humours.

In the old view, in between the genes (which comprise only a twentieth of the genetic code) are vast stretches of so-called “junk” DNA, which were thought to be inert evolutionary leftovers. But ENCODE (Encyclopedia of DNA elements) concluded that the genome is actually “a highly complex, interwoven machine with very few inactive stretches,” and the mislabeld “junk” has a crucial role in manufacturing proteins. As science journalist Richard Inham lyrically reported the story to the AFP news agency, “Previously written off as silent, it emerges as a singer with its own discreet voice, part of a vast, interacting molecular choir.”

Most of the genome now appears to be transcribed into RNA, which relays information from the DNA to the cellular machinery. That is a remarkable finding, since it had been thought that only a fraction of the genome was transcribed. Also, it seems to be composed of elements that have no discernable benefits for survival and reproduction, and shows no signs of having been sculpted and winnowed by natural selection.

Back in 2000, Lewontin published It Ain’t Necessarily So: The Dream of the Human Genome and Other Illusions. Lewontin said, among other things, that the accepted genomic model was “wrong in what it claims to explain. First, DNA is not self-reproducing; second, it makes nothing; and third, organisms are not determined by it.” Lewontin asserted that DNA is “a dead molecule, among the most nonreactive chemically intert molecules in the living world,” is produced by a complex cellular machinery of proteins, and does not itself produce proteins.

It’s hard not to imagine that the scientists at the Human Genome Project had conducted a massive preemptive strike against potential critics. Four years ago, when they realized that their theoretical model would not stand for long, they formed a group within the scientific establishment to knock it down themselves and emerge as self-correcting scientists rather than wasters of billions of dollars. Whenever that happens, scientists can always save face. They were not to be seen as a pack of blinded, self-deluded hyenas so much as humble participants in “the self-correcting nature of science.”

What will rise out this rubble? What new theories of how organic form is produced will compete to be the new reigning paradigm? To understand Pivar’s work on how embryos and forms originate, we need to revisit one of his heroes, the nineteenth-century embryologist Wilhelm His.
After studying embryos of various animals in the quest for the origins of form, His found that in their early stages they behaved like bubbles and elastic tubes and bladders. Adopting an experimental approach, he created models in rubber and other flexible materials, and bent, twisted, and inflated them. Sure enough, some of them mimicked the folding and topologies of early-stage embryos. During his lifetime, His was bullied by Ernst Haeckel, who denigrated his methods as Gummischlauchwissenschaft (rubber bladder science). But now, a century and a half later, Pivar thinks he was on the right track, and has picked up where the Goethian embryologists had left off in their quest for the bio-mechanical principles and organic origami that lie behind the forms of all living things.

Pivar found he was not a lone voice crying out in the wilderness. In fact, he is in some very good company. His model, first of all, is based on the idea of structural self-organization – that the properties of matter contain within itself the abilities to organize into spontaneous patterns, like crystals or snowflakes, without the help of genomes or Darwin.

As a graduate student in anthropology at the University of California (Los Angeles and Berkeley) forty years ago, I was raised in the Neo-Darwinian Synthetic Theory, promulgated in the 1950s by Ernst Mayr, Julian Huxley, Theodosius Dobzhansky, and others. These brilliant men sought to integrate many disparate studies, including animal behavior, paleontology, comparative anatomy, and population genetics all under the same tent of evolution by natural selection. Their model of evolution was based on the notion that 1) organisms in populations continually produce a wide range of variations, including many random gene mutations, 2) these can vary in almost infinite directions, with equal randomness, 3) natural selection creates form by winnowing these genes in a non-random (adaptive) manner, and 4) that this takes place gradually over immense periods of time, in a long succession of slightly intermediate forms.

There are two problems with this formulation: 1) Natural selection was repeated endlessly as a mantra, even in cases where it could not be demonstrated to have occurred. Indeed, experimental demonstrations of natural selection from the 1950s through the end of the twentieth century were few and far between. We were all taught about the peppered moths in England that turned from white to black in the polluted woods, and Bumpus’ sparrows, whose median wing shape and lengths were favored in surviving storms, but (apart from a few bacteria and fruitflies) no one saw a new species evolve before their eyes. 2) The second problem was that their view of timing and variation proved to be erroneous. Organisms do NOT vary randomly and all over the place. Variations tend to be constrained and biased – the same ones coming up again and again, and some possibilities NEVER come up. Even in “monstrosities” (what Cuvier named “teratologies”) like three-eyed sheep and six-legged pigs, the same deformities reappear from time to time, the result of similar biased mistakes in development. Moreover, the fossil record seems to indicate that there are long periods of very little change (stasis), followed or (in Stephen Jay Gould’s phrase) “punctuated” by fairly rapid spurts of evolution. Animals still evolve, and long periods of time are still involved, but the kind of gradualism Darwin usually assumed has not been supported by a century of genetics and paleontology.

Oh, no! Natural selection not the be-all and end-all of evolution? In fact, Darwin knew quite well that natural selection does not create form. It winnows out forms that are less successful, but is not the engine that generates such basic patterns as bilateral or radial symmetry, as in the contentious events of the Cambrian “explosion,” when all the forms of modern animals first appeared. Citing natural selection as the “cause” of evolution does not at all address the question of how forms arise, what proportions are useful, and how they develop both in individuals and in species. Natural selection may choose, shape, and direct, I have come to see, but it cannot create. That was my smaller, personal earthquake.

Some years ago, a couple of evolutionary biologists made a study of how toy makers had arrived at the cute face of the most popular teddy bears. Perceptions of cuteness are tied to the facial proportions of human infants – large eyes, very high forehead, small nose and jaws. Toy makers found that the more they enlarged the eyes and shrunk the snouts of their bears, the more they would sell. Eventually, the faces of teddy bears (and Disney and Japanese animated characters) came to resemble human infants. The buyers were not creating or designing the forms, but they were nevertheless shaping their features by consistently selecting them.

Darwin’s champion and “bulldog” Thomas Henry Huxley, who crusaded tirelessly for the ideas of evolution and descent with modification, never felt completely at ease with natural selection. And sad to say, many biologists continue to uphold it as the main driving force of evolution out of habit, and would rather not raise doubts for fear that religious creationists will claim that scientists know “Darwin is wrong.” In the creationist’s limited two-choice universe, if “Darwinism” is an incomplete theory, the only alternative to account for the origins of form is biblical literalism.

Speaking of juvenile facial features, the importance of infantilization appears to be of greater significance than I ever supposed. It is known as neoteny, a slowing down of the rate of development that makes adult humans retain the proportions of juvenile apes. We no longer sport the heavy brow ridges, large canine teeth, and projecting snouts of gorillas or chimps; instead, there has been a change in the timing of human development. Pivar has shown that Steve Gould, whom I thought was an arch proponent of natural selection, harbored grave doubts about its universal efficacy.
In his brilliant (but slyly subversive) book Ontogeny and Phylogeny, Gould unequivocally stated that “Neoteny has been a (probably the) major determinant of human evolution… Human development has slowed down… adaptive features of ancestral juveniles are easily retained.” What surprised me even more was to discover that the importance of neoteny was also trumpeted and championed at length over the years by a distinguished group of scientists, including Karl von Baer, Gavin de Beer, Walter Garstang, J. B. S. Haldane, Julian Huxley, George Gaylord Simpson, Ashley Montague, and, of course, Gould.

One of the pioneers in structural self-organization is Stuart Kauffman, a theoretical biologist and astrophysicist at the University of Calgary, who has written that “Self-organization is a natural property of complex genetic systems. There is ‘order for free’ out there, a spontaneous crystallization of order out of complex systems, with no need for natural selection or any other external force.” Pivar continues Goethe’s quest to find the Urform, the universal factor that generates all organic form. His answer to the origins of form lies in the contortions and deformations of a doughnut-shaped membrane – the torus – which occurs via the mechanical properties of matter.

In this, Pivar is part of the tradition of rational morphology, which had its roots in the 18th century Enlightenment, and strongly influenced such philosophers and thinkers as Kant, Goethe, St. Hilaire, Cuvier, Owen, Bateson, and D’Arcy Thompson. Pivar’s view of spontaneous transformation and origins of form have absolutely nothing to do with mystical creationism, and everything to do with algorithms, fluid mechanics, and topology. Darwinism triumphed, as Lewontin and others have pointed out, not because it was the complete explanation of evolution and the origin of species, but because it attempted to do so within a mechanistic, naturalistic framework – a continuation of the tradition of LaPlace, Newton, and Descartes. Kaufman opines that “If the new science of complexity succeeds, it will broker a marriage between self-organization and selection. It will be a physics of biology.”

Blind adherence to authority in science, as Albert Einstein said, is bad science. Thomas Henry Huxley told his students that he would rather they question authority and explore new views than to parrot his lectures back to him. Indeed, Huxley said, “When science adopts a creed, it commits suicide.” It’s hard to accept constant change and uncertainty about the truth – but that is the soul and mandate of science, and also its excitement – the never-ending quest. But when you’ve got a lab and research funding at stake, it’s not easy to question the basis of what keeps you in business. Molecular biologist Rob Da Salle, head of the American Museum of Natural History’s genomic and molecular biology project, was heard to say, “Pivar’s theory is probably correct, but no one will believe it, including me.”