How to Build a Dinosaur (16 page)

The different answers to this question have fallen into two schools of thought that date to the Greeks and still have resonance today. One school favored preformation and the other epigenesis. In preformation the organism already exists in some miniature form in the parent. Everything that is needed for the adult form is already there. In epigenesis, however, the raw material of the new creature is shaped and changed as it develops. So the nature of the individual is largely determined during growth.

To imagine a miniature human being, or chicken, for that matter, already existing in the egg is too simplistic to the modern mind, but the essential philosophical difference still resonates. Is every detail of individual human behavior and personality prescribed in the genetic code? That would be a kind of preformation. You could have a gay gene, or a crime gene. But if genes are more like the notes for a musical composition, but without the tempo or orchestration, or even specifying the instrument that is to play it, then development would be closer to epigenesis. Hormones in the mother’s system could affect the development of the fetal brain or the sexual organs, and maternal nutrition or drugs could enhance or harm the development of the embryo. Given the popularity of the idea that playing Mozart to a pregnant mother will be beneficial to the growing embryo, it is clear that the idea of epigenesis still has currency in the modern world.

Science is just now passing out of a period during which genes received so much attention that it seemed all researchers saw biology from a modern preformationist perspective. Now it seems genes don’t tell anything like the full story. New research is giving us an understanding of subtle chemical events that affect the expression of genes and the development of the embryo, chemical events not determined by the genes themselves. This is a new kind of epigenesis and so far, no link has been established to Mozart.

Deep philosophical questions about the essential nature of the new individual aside, we have gained a vast amount of operational knowledge over the course of the past two centuries, in particular the second half of the twentieth century, about how the growth of the embryo is orchestrated, about what directs the astonishing unfolding of form we see in a growing fly, mouse, or human embryo. And it is this knowledge, coupled with our knowledge of genetics, that enables us to think that we might be able to change the course of an embryo’s development so that it grows more in the fashion of one of its ancestors than in the normal way.

Knowledge of the structure of DNA and the genetic code has helped bring us to this point, but it has also misdirected our thinking in some ways. We know that in the genetic code are sequences that produce proteins and that these proteins are crucial in determining different aspects of a growing organism. We know that given certain genes, eyes will be blue. With others, eyes will be brown. In the fruit fly there are genes for crinkly wings, smooth wings, and no wings. We know of diseases that are caused by a change in a single gene. And we know now of genes that cause or increase the risk of diseases.

Still, much of this is a bit like knowing that if you put two chemicals together there will be an explosion. But what is the mechanism? What determines the force and direction of the explosion? What is the chemistry? Well, that’s when things get beautifully complicated.

Over the last quarter century or so scientists have made astonishing progress in embryology, moving toward the goal of being able to write down what would essentially be the “program” for the development of an organism starting with a fertilized egg. That is to say, every gene action and action on a gene that results in growth and development could be cataloged. One would have “the instructions” for a worm, or a fly.

And, in the last twenty years that knowledge of genes and their actions and how they are controlled has been applied to the understanding of evolution. That has given us the field called evolutionary developmental biology, or evo-devo. This understanding can enable us, with a few nudges, to see if we can rewind the tape of evolution from the chicken toward the nonavian dinosaur.

Historically, there has long been an interest in the potential connection between the growth of the embryo—ontogeny—and the evolutionary history of an organism, its phylogeny. This connection was explored in one of the first books by the late Stephen Jay Gould,
Ontogeny and Phylogeny
, published in 1977, when the great importance of regulatory genes in development was just beginning to be recognized. Gould’s book circles around a statement familiar to scholars who know the history of the development of evolutionary theory, although it may sound something like scientific double-talk to most people: that is, the claim of Ernst Haeckel, an early student of the importance of embryology in determining the form of organisms, that “ontogeny recapitulates phylogeny.” He argued that one can see the evolutionary history of a species repeated in the embryonic development of an individual of the species. More precisely, the embryo passes through the adult stages of its ancestors, showing in compressed time and space the course of evolution that produced it. This was intuitively appealing because anyone can see that a human embryo, for example, goes through stages where it looks like some of our ancient ancestors, like fish and amphibians. There are what appear to be gills and a tail.

The idea is oversimplified, however, and had been long discredited by the time Gould was writing his book. What he did was put the statement in its historical context. He argued more than once that mistakes in science could be as useful and enlightening as correct ideas, sometimes more so. And he treated the notion of recapitulation as a mistake that had more substance and interest than its rejection. However Haeckel went wrong, his idea pointed to an important connection between embryology and evolution that had been pursued by scientists but then had been largely abandoned, to the impoverishment of evolutionary theory.

For one thing, Gould argued, changes in timing of embryonic development could make dramatic changes in evolution, particularly when different aspects of development followed different schedules. For instance, an evolutionary change would occur if the developmental path to sexual maturity were speeded up but all other sorts of growth stayed at the original pace. If frogs became sexually mature as tadpoles and never made it to the frog stage, producing a new species of adult tadpoles, that would be quite a dramatic evolutionary step.

Something like this occurred with humans, Gould wrote. In our development, which extends long past the embryo, juvenile stages last much longer than they did in our primate ancestors. Consequently, when we reach sexual maturity we are, physically, at an ancestral juvenile stage. Our mental plasticity that enables lifelong learning could also be a juvenile characteristic that stays with us into old age.

Gould saw that changes in regulation of gene expression would be central to any understanding of the mechanisms of evolutionary change. Of “the growing discussion on the evolutionary significance of changes in gene regulation,” he said, “I predict that this debate will define the major issue in evolutionary biology for the 1980s.” He continued, “I also believe that an understanding of regulation must lie at the center of any rapprochement between molecular and evolutionary biology; for a synthesis of these two biologies will surely take place, if it occurs at all, on the common field of development.”

The synthesis did occur, in the development of evo-devo. Not all scientific disciplines need nicknames, but this one, also called devo-evo by some, was in desperate need of a way to simplify the full descriptor, “evolutionary developmental biology,” or “developmental evolutionary biology.” Gould did not anticipate rewinding the tape of evolution, however. As mentioned earlier, he wrote that the tape could not be rewound and run again with the same result, although he was not talking about laboratory experiments.

 

Sean Carroll at the University of Wisconsin-Madison has been one of the pioneers of the evo-devo field and a very effective popularizer. He gives Gould a lot of credit for foresight. And he points out that although the structure of DNA, the nature of genes, and the nature of genetic changes in populations had been well studied through the 1970s, the evolution of the form, the shape, of organisms had not been deciphered. Indeed, he has written, this was largely because the knowledge of embryology itself was lacking. “How could we make progress on questions involving the evolution of form without a scientific understanding of how form is generated in the first place? ”

To illustrate how recent the change was, he has written that through the 1970s, “no gene that affected the form and evolution of any animal had been characterized. New insights in evolution would require breakthroughs in embryology.”

Those breakthroughs occurred largely among a group of scientists known to themselves and others in related fields as the fly people. That is to say, they defined themselves, and were defined, as is common in science, by the organism that they studied. In this case it was the experimental organism that was the twenty-first century’s experimental hero in many studies of genetics—
Drosophila melanogaster,
otherwise known as the fruit fly.

Experimental biology, and in particular the investigation of how genes and inheritance and development all work together, is divided into camps of researchers who work on one animal “model” or another.
Drosophila
is one, the worm
C. elegans
another, the chicken yet another. The mouse is an animal model that has been very useful for testing drugs and for creating strains that are lacking one gene or another, so-called knockout mice. In this manner scientists have been able to cause obesity, cancer, and diabetes in mice, and even to cause effects that are similar to schizophrenia and Alzheimer’s disease. All the so-called model organisms are relatively easy to maintain in a laboratory and breed quickly enough for researchers to design experiments that will show the effects of genetic change in weeks or months rather than years or decades.

Organisms become laboratory models because a body of work is built up through laboratory studies and researchers can build on previous work. The result is, with luck, a deep and thorough understanding of one system that can then be applied to others, although up until the end of the twentieth century there was little thought that worms and flies would be as similar to people in their genes and organization as they have turned out to be.

Dr. Thomas H. Morgan, of Columbia University, started
Drosophila
on its career. It was used to study the simple rules of Mendelian inheritance and to help scientists understand the growth of an embryo. And this is where the major discoveries were made in controlling genes that turn other genes on and off and that determine the patterns of growth that govern the development from egg to fly.

This body of knowledge was developed in such detail that it would fill libraries. And it is this work that provided an understanding of development that challenged the standard view of evolution at that time, and which turned out to have a shocking relevance to human biology and even behavior. Genes had become the focus of inheritance and evolution. It was quite clear that DNA contained the information from which a fly or worm or human being was made. The genes were transcribed into RNA, a single strand with a mirror genetic code, that was then run through cellular machinery to produce a protein. As described before in the discussion of Mary Schweitzer’s work in looking for ancient molecules, proteins are the molecules that do all the work in the body. An organism is built of proteins, by proteins, for purposes that, so far, are unknown to anyone.

It was also clear that mutations in DNA provided the means for changes in proteins and changes in the external characteristics of organisms. At this time, long before the age of the genome and the comparison of one genome to another, population geneticists and evolutionary biologists worked on the notion that accumulations of small changes (microevolution) led to large changes in species and genus and the outward form of organisms (macroevolution).

Consequently, it was thought that the genes of worms and people, of flies and mice, would have to be very different from one another. Homologous genes, which is to say genes that serve the same purpose in different organisms, were imagined to be rare. Carroll writes, “The greater the disparity in animal form, the less (if anything) the development of two animals would have in common at the level of their genes.” One of the architects of the Modern Synthesis, Ernst Mayr, had written that “the search for homologous genes is quite futile except in very close relatives.”

This was the mainstream view, and before the research on the development of the fly embryo, it made sense. What the fly research did was first to show how development proceeded, itself a profound and thorny scientific problem, and second, to illuminate the path of macroevolution—how different animal forms had first appeared and how they later evolved into new forms. Such major, visible changes were not brought about by the accumulation of many, many tiny changes. Instead it seemed that evolution was working as a self-assembling kit, with many similar parts. The genes that were most powerful in the direction of evolution were those that determined changes in size, shape, number, and location of the basic parts and when, where, and how the parts were put together.

Although evolution and development cannot be separated, the subjects are so complex that it is necessary to take them one at a time. The magnitude of trying to understand how a single cell grows into a fly, frog, pony, or chicken, let alone a human being, is almost impossible to overstate. Scott Gilbert—in a textbook, of all places—captured the extent of the problem vividly. He was writing about Wilhelm Roux, a founder of the field of experimental embryology, who wrote a manifesto in 1894. Roux’s view, Gilbert writes, was that understanding the causes of development was “the greatest problem the human intellect has attempted to solve.” That was so, according to Roux, “since every new cause ascertained only gives rise to fresh questions concerning the cause of this cause.”