Marsh’s 1892 figure of a polydactyl horse, the “horned horse from Texas.”
Abnormal horses with extra digits have been admired and studied since Caesar’s time. O. C. Marsh, a founder of vertebrate paleontology in America, took a special interest in these aberrant animals and published a long article on “Recent polydactyle horses” in April 1892. Marsh had two major claims upon fame, one dubious—his acrimonious battles with E. D. Cope in collecting and describing vertebrate fossils from the American West—and one unambiguous—his success in deciphering the evolution of horses, the first adequate demonstration of descent provided by the fossil record of vertebrates, and an important support in Darwin’s early battles.
Marsh was puzzled and fascinated by these aberrant horses with extra toes. In most cases, the additional toe is merely a duplicate copy of the functional third digit. But Marsh found that many two- and three-toed horses had harkened back to their ancestors by developing either or both of the side splints into functional (or nearly functional) hoofed toes. (A later, and particularly thorough, German monograph of 1918 concluded that about two-thirds of horses with extra toes had simply duplicated the functional third digit, while about one-third had resuscitated an ancestral feature by developing the vestigial splints of their second or fourth toe into complete, hoofed digits.)
These apparent reversions to previous evolutionary states are called atavisms, after the Latin atavus: literally, great-great-great-grandfather; more generally, simply ancestor. The biological literature is studded with examples of the genre, but they have generally been treated anecdotally as mere curiosities bearing no important evolutionary message. If anything, they are surrounded with the odor of slight embarrassment, as if the progressive process of evolution did not care to be reminded so palpably of its previous imperfections. The synonyms of European colleagues express this feeling directly—“throwback” in England, pas-en-arrière (“backward step”) in France, and Rückschlag (“setback”) in Germany. When granted any general significance, atavisms have been treated as marks of constraint, as indications that an organism’s past lurks just below its present surface and can hold back its future advance.
I would suggest an opposite view—that atavisms teach an important lesson about potential results of small genetic changes, and that they suggest an unconventional approach to the problem of major transitions in evolution. In the traditional view, major transitions are a summation of the small changes that adapt populations ever more finely to their local environments. Several evolutionists, myself included, have become dissatisfied with this vision of smooth extrapolation. Must one group always evolve from another through an insensibly graded series of intermediate forms? Must evolution proceed gene by gene, each tiny change producing a correspondingly small alteration of external appearance? The fossil record rarely records smooth transitions, and it is often difficult even to imagine a function for all hypothetical intermediates between ancestors and their highly modified descendants.
One promising solution to this dilemma recognizes that certain kinds of small genetic changes may have major, discontinuous effects upon morphology. We can make no one-to-one translation between extent of genetic change and degree of alteration in external form. Genes are not attached to independent bits of the body, each responsible for building one small item. Genetic systems are arranged hierarchically; controllers and master switches often activate large blocks of genes. Small changes in the timing of action for these controllers often translate into major and discontinuous alterations of external form. Most dramatic are the so-called homeotic mutants discussed in the following essay.
The current challenge to traditional gradualistic accounts of evolutionary transitions will take root only if genetic systems contain extensive, hidden capacities for expressing small changes as large effects. Atavisms provide the most striking demonstration of this principle that I know. If genetic systems were beanbags of independent items, each responsible for building a single part of the body, then evolutionary change could only occur piece by piece. But genetic systems are integrated products of an organism’s history, and they retain extensive, latent capacities that can often be released by small changes. Horses have never lost the genetic information for producing side toes even though their ancestors settled on a single toe several million years ago. What else might their genetic system maintain, normally unexpressed, but able to serve, if activated, as a possible focus for major and rapid evolutionary change? Atavisms reflect the enormous, latent capacity of genetic systems, not primarily the constraints and limitations imposed by an organism’s past.
My latent interest in atavism was recently kindled by a report of something that has no right to exist if one of our most venerable similes expresses literal truth—hen’s teeth. On February 29, 1980 (enough of a rarity in itself), E. J. Kollar and C. Fisher reported an ingenious technique for coaxing chickens to reveal some surprising genetic flexibility retained from a distant past.
They took epithelial (outer) tissue from the first and second gill arches of a five-day-old chick embryo and combined it with mesenchyme (inner embryonic tissue) of sixteen- to eighteen-day-old mouse embryos taken from the region where first molar teeth form. A fascinating evolutionary tale lies hidden in this simple statement as well. Jaws evolved from bones supporting the anterior gills of ancestral fishes. All vertebrate embryos still develop the anterior gill arches first (as ancestral embryos did) and then transform them during development into jaws (as ancestors did not in retaining the forward gills throughout life). Thus, if the embryonic tissues of chickens still retain any capacity for forming teeth, the epithelium of the anterior gill arches is the place to look.
Kollar and Fisher took the combined embryonic tissue of mouse and chicken and grew it in what might strike readers as a bizarre and unlikely place—the anterior chambers of the eyes of adult nude mice (but where else in an animal’s body can one find an open space, filled with liquid that is not circulating?). In ordinary teeth, made by a single animal, the outer enamel layer forms from epithelial tissue and the underlying dentin and bone from mesenchyme. But mesenchyme cannot form dentin (although it can produce bone) unless it can interact directly with epithelium destined to form enamel. (In embryological jargon, epithelium is a necessary inducer, although only mesenchyme can form dentin.)
When Kollar and Fisher grafted mouse mesenchyme alone into the eyes of their experimental animals, no dentin developed, but only spongy bone—the normal product of mesenchyme when deprived of contact with enamel epithelium as an inducer. But among fifty-five combined grafts of mouse mesenchyme and chick epithelium, ten produced dentin. Thus, chick epithelium is still capable of inducing mesenchyme (from another species in another vertebrate class yet!) to form dentin. Archaeopteryx, the first bird, still possessed teeth, as did several fossils from the early history of birds. But no fossil bird has produced teeth during the past sixty million years, while the toothlessness of all modern birds ranks with wings and feathers as defining characters of the class. Nonetheless, although the system has not been used on its home ground for perhaps a hundred million generations, chick epithelium can still induce the formation of dentin when combined with appropriate mesenchyme (chick mesenchyme itself has probably lost the ability to form dentin, hence the toothlessness of hens and the necessity for using mice).
Kollar and Fisher then found something even more interesting. In four of their grafts, complete teeth had developed! Chick epithelium had not only induced mouse mesenchyme to form dentin; it had also been able to generate enamel matrix proteins. (Dentin must be induced by epithelium, but this epithelium cannot differentiate into enamel unless it, in turn, can interact with the very dentin it has induced. Since chick mesenchyme cannot form dentin, chick epithelium never gets the chance to show its persistent stuff in nature.)
One final point stunned me even more. Kollar and Fisher write of their best tooth: “The entire tooth structure was well formed, with root development in proper relation to the
crown, but the latter did not have the typical first-molar morphology, since it lacked the cusp pattern usually present in intraocular grafts of first-molar rudiments.” In other words, the tooth looks normal, but it does not have the form of a mouse’s molar. The odd form may, of course, simply result from the peculiar interaction of two systems not meant to be joined in nature. But is it possible that we are seeing, in part, the actual form of a latent bird’s tooth—the potential structure that chick epithelium has encoded for sixty million years but has not expressed in the absence of dentin to induce it?
Kollar and Fisher’s work recalled another experiment from the opposite end of a chick, a famous story usually misreported by evolutionary biologists (once, I am embarrassed to say, by myself), as I discovered in tracking down the original source. In 1959, the French embryologist Armand Hampé reported some experiments on the development of leg bones in chick embryos. In ancestral reptiles, the tibia and fibula (the bones between your kneecap and ankle) are equal in length; the ankle region below includes a series of small bones. In Archaeopteryx, the first bird, tibia and fibula are still equal in length, but the ankle bones below have been reduced to two, one articulating with the tibia, the other with the fibula. In most modern birds, however, the fibula has been reduced to a splint. It never reaches the ankle region, while the two ankle bones are “engulfed” by the rapidly growing tibia and fuse with it. Thus, modern birds develop a single structure (the tibia with ankle bones fused to it and the rudimentary fibula at its side), articulating with bones of the foot below.
Hampé reasoned that the fibula might well maintain its capacity for attaining full, ancestral length, but that competition for material by the rapidly growing tibia might deprive it of any opportunity to express this potential. He therefore performed three types of experiments, all directed toward giving the fibula some relief from its imperialistic and normally victorious neighboring bone. In all cases, the fibula attained its ancestral length, equal to the tibia and reaching the ankle region below. In the first, Hampé simply grafted more embryonic tissue into the region of the growing leg bones. The tibia reached its characteristic length, but the region now had enough material “left over” for the fibula. In the second, he altered the direction of growth for tibia and fibula so that the two bones did not remain in intimate contact. In the third, he inserted a mica plate between the two bones; the developing tibia could no longer “grab” material from its less vigorous neighbor and the fibula achieved its full length.
Thus, Hampé recreated an ancestral relationship between two bones by a series of simple manipulations. And this alteration engendered an even more interesting consequence. In normal chicks, the fibula begins its growth in contact with one of the small ankle bones below. But as the tibia enlarges and predominates, this contact breaks at about the fifth day of development. The fibula then retreats to form its splint, while the expanding tibia engulfs both ankle bones to form a single structure. In one case during Hampé’s manipulations, the two ankle bones remained separate and did not fuse with either tibia or fibula (while both ankle bones fused with the tibia, as usual, in the other leg of the same embryo—an untreated control allowed to develop normally). In this bird, Hampé’s simple manipulation not only produced its intended result (expression of an ancestral relationship in leg bones); it also evoked the ancestral pattern of ankle bones as well.
Hampé was able to produce these impressive atavisms by simple manipulations that amount to minor, quantitative changes in timing of development or placement of embryonic tissue. Adding more tissue doesn’t simply make a bigger part with the same proportions; it leads to differential growth of one bone (the fibula) and a change in arrangement of the entire ankle area (two ankle bones, articulating separately to tibia and fibula in some cases, rather than a single tibia with both ankle bones fused to it).
Developmental patterns of an organism’s past persist in latent form. Chicks no longer develop teeth because their own mesenchyme does not form dentin, even though their epithelium can still produce enamel and induce dentin in other animals. Chicks no longer develop separate ankle bones because their fibula no longer keeps pace with the tibia during growth, but the ankle bones develop and retain their identity when fibulas are coaxed to reach their ancestral length. An organism’s past not only constrains its future; it also provides as legacy an enormous reservoir of potential for rapid morphological change based upon small genetic alterations.
Charles Darwin constructed his theory as a two-stage process: variation to supply raw material and natural selection to impart direction. It is frequently (and incorrectly) stated that he said little about variation, embarrassed as he was by ignorance about the mechanism of heredity. Many people believe that he simply treated variation as a “black box,” something to be assumed, mentioned in passing, and then forgotten. After all, if there is always enough variation for natural selection to use, why worry about its nature and causes?
Yet Darwin was obsessed with variation. His books, considered as an ensemble, devote much more attention to variation than to natural selection, for he knew that no satisfactory theory of major evolutionary change could be constructed until the causes of variation and the empirical rules of its form and amount had been elucidated. His longest book is devoted entirely to problems of variation—the two-volume Variation of Animals and Plants Under Domestication (1868). Darwin felt that atavism held the key to many mysteries of variation, and he devoted an entire chapter to it, closing (as I will) with these words:
The fertilized germ of one of the higher animals…is perhaps the most wonderful object in nature…. On the doctrine of reversion [atavism]…the germ becomes a far more marvellous object, for, besides the visible changes which it undergoes, we must believe that it is crowded with invisible characters…separated by hundreds or even thousands of generations from the present time: and these characters, like those written on paper with invisible ink, lie ready to be evolved whenever the organization is disturbed by certain known or unknown conditions.
15 | Helpful Monsters
MY GRANDFATHER, who taught me to play poker and watched the Friday night fights with me every week, once took me to one of the cruelest, yet most fascinating spectacles of decades now thankfully past—the rows of malformed people forced (by an absence of other opportunities) to display themselves to a gawking public at the Ringling Brothers sideshow.
The genteel and legitimate counterpart to such public cruelty is the vast scientific literature on deformed births—a subject dignified with its own formal name as teratology, literally, the study of monsters. Although scientists are as subject as all people to the mixture of awe, horror, and curiosity that draws people to sideshows, teratology has an important rationale beyond primal fascination.
The laws of normal growth are best formulated and understood when the causes of their exceptions can be established. The experimental method itself, a touchstone of scientific procedure, rests upon the notion that induced and controlled departures from the ordinary can lay bare the laws of order. Congenitally malformed bodies are nature’s experiments, uncontrolled by intentional human art to be sure, but sources of insight nonetheless.
The early teratologists sought to understand malformations by classifying them. In the decades before Darwin, French medical anatomists developed three categories: missing parts (monstres par défaut), extra parts (monstres par excès), and normal parts in the wrong places. The folklore of monsters had long recognized the last category in tales of anthropophagi, maneaters with eyes in their shoulders and a mouth on their breast. Shakespeare alluded both to them and to some related colleagues in Othello when he spoke of “The Anthropophagi and men whose heads/Do grow beneath their shoulders.”
But a classification is no more than a set of convenient pigeonholes until the causes of ordering can be specified. And here nineteenth-century teratology got becalmed in its own ignorance of heredity. The establishment of genetics in our century revived a waning interest in teratology, as e
arly Mendelians discovered the mutational basis of several common deformities.
Geneticists had particular success with one common category in the old classification—normal parts in the wrong places. They studied their favorite animal, the fruit fly, Drosophila melanogaster, and found a variety of bizarre transpositions. In the first of two famous examples, the halteres (organs of balance) are transformed into wings, restoring to the aberrant fly its ancestral complement of four (normal flies, as members of the order Diptera, have two wings). In the second, legs or parts of legs replace a variety of structures in the head—antennae and parts of the mouth in particular. Mutations of this sort are called homeotic.
Not all misplacements of parts represent homeosis, and this restriction is a key to the evolutionary message I shall draw further on. William Bateson, who later invented the term genetics, defined as “homeotic” only those parts that replace an organ having the same developmental or evolutionary origin (the word comes from a Greek root for “similar”). Thus, halteres are the evolutionary descendants of wings, while insect antennae, mouthparts, and legs all differentiate from similar precursors in the embryonic segments, and all presumably evolved from an ancestor with a pair of simple and similar appendages on each adult body segment. We might refer to homeosis if a human developed a second pair of arms where his legs should be, but an extra pair of arms on the chest would not qualify.
Homeotic mutants are found on all four pairs of chromosomes in D. melanogaster. A 1976 review by W. J. Ouweneel includes a list that runs to three full pages. But the two most famous, best studied, and elaborate sets of homeotic mutations both reside on the right arm of the third chromosome.