Wednesday, July 27, 2016

The Demeaning of Life...Part X

When setting off on this project, I knew nothing about the new field of evodevo and all the revolutionary findings that were turning all of biology on its head. It’s all astoundingly complicated but beautifully logical…Jacques Monod’s “necessity” in action. And, as much as the endless theme of multilayered complexity, embryonic development from unfertilized egg to the realization of a fully functional adult organism exemplifies the phenomenon that I’ve termed “Natural Design.” Nature finds a way to make living things work—the simplest and most efficient way…maybe not perfect, but the best way, given all the physical constraints involved. This section is full of strange terms and concepts which are intended only to lend a sense of the steps involved in building a living thing…each one a part of the great web, each a point in time and the continung evolution of life. So don’t get bogged down in the details. Just marvel.

X.  The Homeobox

Through a variety of experiments, developmental biologists are beginning to learn how the one-dimensional information encoded in the nucleotide sequence of a zygote’s DNA is translated into the three-dimensional form of an animal. There are enough unanswered questions, however, to entertain many future generations of scientists.                                                                                                                                              
                                Neil Campbell, Biology (4th ed., 1996)[1]                                                                                   
As the 21st century approached, biologists—despite all their remarkable findings—still knew very little about the specific role of genes in embryonic development. During the 1970s and 80s, teams of researchers working on different problems were beginning to understand that regulatory enzymes and genes were responsible for various aspects of the initial growth phases, including their coordination and timing.

This culminated in 1983 with the concurrent discovery (by three separate labs on two continents) of a cluster, or complex, of regulatory genes responsible for the orchestration of early developmental stages—the ontogeny—of organisms exhibiting segmented body parts.[2]

Inducing mutations in these types of creatures by manipulating DNA has, since Morgan’s time, been an  invaluable research tool—the key to identifying things such as genes’ specific locations on chromosomes and various of their attributes (for instance, their roles in gene networks, or whether they were dominant or recessive). The discoveries of the 1980s revealed that various deformities seen in fruit flies—such as extra sets of wings or legs gruesomely sprouting from heads—were the result of mutations to groups of genes controlling the fly’s overall body plan. After years of study, it was found that there were eight of these (what are now known as) homeotic genes in two clusters on one of Drosophila’s chromosomes. Significantly, the relative position of the genes in these complexes were found to correspond to the relative head-to-tail order of those body parts affected. Consequently, it was anticipated that these clusters held clues to the general logic behind the fly’s body patterning.

When DNA from the two gene clusters was isolated and analyzed, it was found that proteins coded for by each of the eight homeotic genes had short sections amounting to 180 nucleotides sharing virtually identical sequences. Researchers dubbed them homeobox genes.[3] The abbreviated form, Hox, is still used in reference to regulatory genes involved with segmentation and related structures but the term “homeobox” now covers a wide range of genes central to an organism’s development and growth.

Homeobox genes are part of what is commonly referred to as the genetic tool kit, which metaphorically consists of a number of “tools.” Many of these are transcription factors (as mentioned earlier, DNA binding proteins that switch genes on or off), plus signaling proteins, hormones, and various cellular receptors. Others include cell-type proteins (those that determine a cell’s identity) and coloration proteins. Homeobox genes control ontogeny by sending signals between each other in the form of chemical messengers—gene products—whose transcription they induce.

Hox genes, again, are identity genes—those responsible for an embryo’s head-to-tail development. Some delineate the right and left sides of the body; others establish top and bottom while still others map out general body regions. Hox genes are responsible for switching on circuit cascades of master genes such as the homeotic genes that are in charge of building structures associated with an embryo’s different segments. Homeobox genes, of course, play multiple roles and virtually never work in isolation.

Here’s an outline of how this process plays out in the case of that superstar of lab animals, Drosophila melanogaster:

Like all arthropods, fruit flies are modular in construction, their bodies arranged in three sections—head, thorax, and abdomen—which are further subdivided. (For example: the first thoracic segment bears a pair of legs; the second, another set of legs plus a pair of wings; and a third carrying the last two legs and a pair of modified wings—balancing organs called halteres.) Starting with an undifferentiated egg, segments appear and these become ever more anatomically distinct as development proceeds in a series of steps determined by gene activation. Regional identity information is established by the types and, importantly, concentrations of regulatory proteins that control gene expression. This begins before eggs are even fertilized.

Egg-polarity genes active in nursery cells surrounding and nourishing unfertilized eggs in a female fruit fly’s ovary begin the process of defining an embryo’s body axes. When transcribed, these genes’ mRNA enters the egg cell, remaining near the point of origin. After being fertilized and laid, the mRNA is translated and its DNA-binding protein product begins to slowly diffuse though the egg away from its point of origin, forming a concentration gradient. In the instance of the polarity gene responsible for establishing anterior-posterior regions in the fertilized egg, its highest concentration—near the point where it was introduced—delineates the head end while areas of decreasing concentration sequentially activate segmentation genes that map out the  basic segmentation plan along the anterior-posterior axis. The dorsal-ventral axis is formed in similar fashion.

After the major body axes are laid out, three suites of segmentation genes go to work. Gap genes determine, in succession, the basic subdivisions. Next, pair-rule genes establish pairs of body segments. Finally, segment-polarity genes set up the front-to-back axis of both halves of the paired segments. At this point, the boundaries and  orientation of each of the embryo’s segments are permanently established. The segmentation genes’ protein products, for the most part, are transcription factors that advance the step-wise system of body plan formation; in turn, they activate sets of genes that activate other sets, ending with the homeotic genes that determine the specific anatomy of the embryo’s individual segments.

The sum total of an organism’s development is in the delicately balanced timing and sequence of these master genes being switched on and off, and the duration of their activation. Molecular biologist Sean Carroll, one of the early leaders in the field of evodevo, provides glimpses of the remarkably sophisticated logic employed—yet another exemplary instance of Natural Design on display:

A gene not only may have multiple switches for different subpatterns of expression at a given time, but will frequently have different switches that control entirely different states in development. Tool kit genes are rarely, if ever, devoted to a single developmental operation. Rather, these tools are used and reused again and again in development in different contexts to shape the growing embryo. Switches endow individual tool kit genes with great versatility. Virtually every tool kit gene is controlled by multiple switches. Ten switches or more is not uncommon, and we don’t know what the upper limit, if any, may be…. The developmental steps executed by individual switches and proteins are connected to those of other genes and proteins. Larger sets of interconnected switches and proteins form local “circuits” that  are part of still larger “networks” that govern the development of complex structures. Animal architecture is a product of genetic regulatory network architecture.[4]

Researchers involved with the Drosophila studies that resulted in the initial isolation and elucidation of Hox genes were thrilled by their discoveries. Curious to see if other organisms might possess something analogous, they were shocked to find Hox genes in other animals—barnacles, worms, fish, frogs, mice…and humans. They found that these genes were positioned on chromosomes in the same order as in the fly. Researchers were astonished to realize that these remarkable genes performed the same jobs in each case: specifying the developmental fate of each embryonic segment in the same head-to-tail order. And it was ascertained that in each organism, parts of the Hox gene sequences were virtually identical.

In one famous experiment performed in the 1990s by Swiss developmental biologist Walter Gehring and his colleagues in Basel, the Hox gene responsible for overseeing the construction of a fruit fly’s eyes was manipulated so as to be expressed in different parts of the fly’s body. In this way, eyes were induced to grow on different flies’ legs, wings, and antennae. Gehring’s team then repeated the experiment on Drosophila but used a mouse’s eye-forming gene instead; remarkably, these flies were able to grow normal eyes. In a similar experiment, the eye-forming gene in a frog was replaced by the analogous gene in Drosophila and the frog was also able to grow completely normal eyes. This means that a single gene product is able to function as a switch that turns on eye development in a diverse array of animals.

As a result of these amazing experiments, it now appears that all types of eyes arose from a common ancestor and that the genes involved are highly conserved and have been virtually the same for hundreds of millions of years. Until this discovery, it had been assumed that vision had arisen independently, scores of times, in creatures as   varied as echinoderms, mollusks, and vertebrates. Apparently, though, the genetic tool kit was fully emplaced in ancient organisms—distant relatives of all animals alive today—and that the extremely rapid radiation of forms during the Cambrian period was merely awaiting favorable ecological conditions that would “light the fuse.”   

     ©2016  Tim Forsell                                                                                                                                  
     10 Apr 2016

[1] Campbell. p 990. (A  zygote is a just-fertilized egg cell.)
[2] The breakthrough —another classic case of the phenomenon of multiple discovery (see Shubin, pp 182-83)—was made      independently by researchers at the University of Basel, Switzerland; at Stanford in California, and Indiana University.
[3] Confusingly, the root “homeo” refers to the sequences’ similarity—not because they’re part of homeotic genes. And “box” is microbiologist slang for a sequence of identical (or nearly identical) nucleotide bases found within multiple genes.
[4] Carroll (2005) . pp 123, 129.

Sunday, June 19, 2016

The Demeaning of Life...Part IX

More history…this, about how genes gradually came to be understood. It’s an amazing story—scientific discovery at its very best. This section sets the table for the next one, “Part X…The Homeobox,” which is a sort of  “genetic toolkit” that first came to light in the 1980s and revolutionized our understanding of how genes function. After that, I’ll take a look at the current state of evolutionary theory and that will be followed by a review of origin of life theories. Lining up my ducks….

IX.  From Gemmules to Pangenes to Hox Genes 

The nonstop discoveries in developmental genetics are making it eminently clear that we must expand our vision of evolution, and of evolutionary processes, beyond our present scope. We will have to think differently about—and perhaps totally reconceive—our basic notions of evolution.
                                          Jeffrey Schwartz, Sudden Origins (1999)

There’s a common misconception that, after the publication of On the Origin of Species, Darwin’s concept of evolution by natural selection gained enthusiastic acceptance—at least among scientists. His theory survived the skeptical public’s initial response (which ranged from mild ridicule to outrage). As for his peers: initially, Darwin’s ideas won intellectual support but almost as quickly fell into disrepute. He was by no means at the forefront of evolutionary studies in the years following his rise to fame and notoriety; the period from roughly the 1880s to the time of the modern synthesis has been called the eclipse of Darwinism.[1] This was due in part to the work of early geneticists whose findings were at odds with his speculative theories of natural selection and adaptation. Biology was coming into its own and was perceived as being more “scientific.”

During this phase, there was a good deal of controversy surrounding the matter of how species arise. Oddly, few people seem to be aware that, despite the title of his famous book, Darwin never really tackled the issue—he merely explained how natural selection gave rise to favorable adaptations in plants and animals through the influence of chance variation. For those biologists and geneticists trying to answer the question of speciation (how species originate), Darwin’s theory proved to be of little practical use. In fact, it had the effect of confusing subtle but important distinctions between the processes of evolution and adaptation. Most of the major figures involved with the disputes had their own distinctive theory of speciation, a matter being hotly contested. The problem wasn’t solved by applying tenets of the modern synthesis and remains controversial. Similar to the difficulties faced in trying to comprehensively define “life,” there is still no wholesale agreement on what constitutes a species, nor on how species arise. 
Adding to the quandaries faced by biologists, paleontologists hadn’t yet found evidence in fossil sequences clearly showing the gradual but continuous modification called for by natural selection (a matter Darwin recognized and found deeply troubling). In the words of anthropologist Jeffrey Schwartz:
The perceived need for extraordinary lengths of time over which change could accrue was one of the factors that caused Darwin’s ideas to fall rather quickly out of favor with many in the scientific community. In almost every new edition of his most famous book…he called for greater and greater periods of time over which evolutionarily significant change could be manifested. The earth could not be made older to allow for this model of evolution.
In 1863, William Thomson (the future Lord Kelvin) published a calculation estimating that a primordially hot Earth was probably around 100 (but no more than 200) million years old. Thomson, likely the most respected scientific figure of his time, wasn’t anti-evolution so much as a staunch believer in design. A devout Christian, he saw living things as unmistakable evidence of God’s creation and was happy to use his estimate of Earth’s age to refute Darwin, who admitted that 100 million years was not nearly sufficient time to allow the extremely slow process of natural selection to do its work. Thomson kept revising his figures downward—finally, by 1897, to a mere 20 million years. This obstacle distressed Darwin to the end. (He referred to Thomson as his “sorest trouble.”) Then, only 14 years after Darwin’s death, radioactivity was discovered. Lord Kelvin hadn’t known that radioactive elements in the crust and mantle were slowing the planet’s cooling rate considerably. Later it was learned that isotopes[2] of several radioactive elements could be used to date rocks and by 1941, around the time the modern synthesis was coming together, Earth’s age was estimated to be around two billion years.[3] The controversy faded and, in this respect, Darwin was vindicated.

Then there were problems posed by the early geneticists. Darwin, of course, knew nothing about genes and believed that an offspring’s traits were a blending of those of its parents. He formulated a theory of inheritance, calling it pangenesis, whereby all parts of an individual—tissues and organs—had distinct and independent identities. During all stages of development they shed minute particles he called gemmules, which were capable of reproducing themselves. Darwin hypothesized that these were disseminated throughout a body and were to be found in all its parts at all stages of development. Thus, sex cells containing the adults’ sets of gemmules would be blended to produce their offspring’s traits. Gemmules could be active or dormant and these latter could be expressed in future generations. Active gemmules might be repressed, which explained how features of one parent (but not both) could be present in their offspring. And: gemmules’ ability to multiply and express the organ or tissue from which they arose could account for, say, how a lizard can regenerate its lost tail, a new plant can grow from a cutting, or even how wounds heal. Aside from having no factual basis, it was a neat and elegant theory. Few scientists gave it much credence since there was no experimental evidence indicating that gemmules existed. The theory was finally refuted in the late 19th century when August Weismann demonstrated that whatever was responsible for the inheritance of traits was confined to the nuclei of sex cells.

In coming years, scientists continued struggling with the mysteries of inheritance. There were various theories of orthogenesis which, in one way or another, were predicated on the notion that an organism’s evolution is shaped more by innate internal factors than by outside influences (such as natural selection). There was a revival of the 18th century ideas of Jean-Baptiste Lamarck—known as neo-Lamarckism—that were based on the inheritance of acquired characteristics. Finally, there were the saltationists—those who believed that evolution proceeded by means of sudden, radical mutations and not via the plodding gradualism of natural selection.

One of the latter was Hugo de Vries, the Dutch plant breeder who (along with Karl Correns) later brought Mendel’s work to light. In 1889 he published his own theory of intracellular pangenesis. It was based in part on Darwin’s ideas which, by that time, had been rejected. He renamed Darwin’s hypothetical gemmules, calling them pangens. Unlike Darwin, de Vries believed variation was not the slow, continuous process that natural selection demanded but occurred in sudden jumps, or saltations.[4] His work  with a group of plants prone to sudden and conspicuous mutations (a not uncommon phenomenon in the plant world) led him to believe that novel characteristics could not only arise spontaneously but were heritable as well. De Vries’ views on evolution were more palatable to scientists from many disciplines. (His theory, for instance, didn’t call for an unrealistically ancient Earth, which satisfied those in accord with Lord Kelvin’s position.) In 1900, the year Mendel’s work was rediscovered, de Vries published a book introducing his controversial mutation theory.

British biologist William Bateson was a disciple of Mendel and enthusiastic supporter of de Vries’ theory.[5] In the late 1800s Bateson, after forming comparable views on sudden variation, explored a long-recognized pattern: the tendency of many animals to be made of repeated parts and these parts, in turn, to be constructed of repetitive units. (Arthropods have distinct body segments, vertebrates are organized along segmented spines with paired ribs…limbs had repeated elements, with digits in a wide variety of forms.) Bateson formally defined some of these themes, providing what has proved an extremely useful framework for considering the logic of modular design in animals. He was particularly interested in those malformed sports (“sports of nature”) from his earlier researches, specifically those with body parts—be they legs, teeth, tentacles, or antennae—occurring in atypical numbers or missing altogether. He derived many important ideas from these studies and perhaps Bateson’s greatest insight was realizing that these mutations might well divulge the nature of specific developmental patterns.

In the early years of the 20th century there was a good deal of controversy about the role of chromosomes in heredity. As their behavior during cellular division became better understood, it was realized that chromosomes might be responsible for conveying those units of inheritance that would explain Mendel’s inferences. One obstacle to the idea’s acceptance was that, since there were only a small number of chromosomes, perhaps some as yet unknown, invisible particulate matter was actually the “stuff of inheritance.” Nonetheless, the idea showed much promise and quickly gained traction.

Ironically, one of the early detractors of the new chromosome theory (as well as Mendelian inheritance and Darwinism in general) would turn out to be one of its greatest advocates. Around 1900, American zoologist Thomas Hunt Morgan was working in embryology. Continuously exasperated by finding many of the outstanding problems related to ontogeny leading to dead ends, Morgan admitted defeat. He decided to look into the new-found field of genetics (as did a number of other embryologists around that time) hoping it might shed light on those stubborn dilemmas.

Morgan firmly believed that the key to understanding evolution was to be discovered through genetics but entered the arena quite skeptical (unlike Bateson) about the significance of Mendelian inheritance and its relevance to evolutionary trends. He also rejected Darwin’s heavy emphasis on natural selection, believing its only relevance to the origin of adaptation was among individuals of a species, not to the origin of that  species itself. Morgan had little use for Darwin’s ideas on sexual selection,[6] his views on adaptation—in the sense that adaptation resulting from random variation was the main driver of evolutionary changeand the notion of a violent and incessant struggle for existence. Similar to Bateson and de Vries, Morgan rejected much of Darwin’s theory (but still held the man in great esteem for having brought to the forefront the central questions of evolution). Around the turn of the century he had what proved to be an influential meeting with de Vries. Morgan, a skilled experimentalist, was already aligned with those favoring large-scale mutations (the saltationists) and de Vries convinced him that his mutation theory could be tested.

Beginning in 1908, the fruit fly Drosophila melanogaster became the “organism of choice” for genetic research. The tiny flies pass through an entire generation in only two weeks, produce many offspring, and are easy to rear. In addition, they have only four pairs of chromosomes—abnormally large ones—which are easily visible under a microscope, making their physical manipulation less demanding. By 1909, Morgan (who had taken a professorship at Columbia University) began breeding Drosophila in what became famously known as “the Fly Room.”[7]

The only problem was, they all looked identical. It was already known that the tiny flies produced distinctive mutant forms; for no apparent reason, these aberrant strains would occasionally show up. They would differ from the wild type (normal) flies, for instance, in number of abdominal segments, in having differing wing and antenna forms, or eye color. After two years of patiently breeding wild type flies in the hope of finding one of these abnormal individuals, by sheer chance one of the strains being studied by Morgan’s group mutated into a white-eyed form. With the enthusiastic assistance of numerous long-time colleagues, Morgan began to isolate and breed several types of mutant strains. By cross-breeding these mutants with wild types and observing their offspring, he was able to show that genes were carried on the chromosome and were the physical basis of heredity, thus confirming Mendel’s findings.

Having become a converted proponent of the new chromosome theory, Morgan attempted to demonstrate, at first employing only circumstantial evidence, that a chromosome could carry many genes. Fortunately for him and his collaborators, variations among different strains of fruit fly (in the size, shape, and numbers of bristles) allowed them to begin to map which traits arose from which chromosome. Further, using cunning methods linked to a mode of chromosomal interaction called crossing over, they were able to figure out the genes’ positions relative to one another. Morgan recognized that this routine reordering of gene segments on individual chromosomes was a critical source of introducing variation into a population. Building on Mendel’s hereditary theories, he and his dedicated research team’s discoveries formed the basis for the modern science of genetics. Thomas Hunt Morgan remains a shining example of the pure scientist—one willing to repeatedly adjust intellectual positions in the face of new data.

During the first two decades of the 20th century, population genetics—armed with compelling, testable experimental results—overshadowed several fields that had originally been responsible for a broad acceptance of the modern conception of evolution. (These included paleontology, comparative anatomy, and embryology.) Starting around 1930, some notable embryologists began to alter that trend.

Richard Benedict Goldschmidt, a German Jew who emigrated to America in the 1930s to escape Nazism, was one of the finest geneticists of his day. Modern students of evolution remember him—if at all—for the unfortunately named hopeful monsters (Goldschmidt’s much-ridiculed notion that beneficial evolutionary change can arise instantaneously through radical, chance mutations).[8] This was his way of accounting for the sudden and drastic morphological changes so apparent in the fossil record and, in general, the vast differences in form that Goldschmidt believed couldn’t be accounted for by gradual change. He first presented these views when neo-Darwinism was becoming the prevailing school of thought and, partly due to a tendency to be dismissive and harshly critical of his peers’ work, the unorthodox notions were received with an arguably disproportionate amount of ridicule. (The regrettable name choice for his genetic novelties didn’t help support Goldschmidt’s position.) As it transpired, one of  his novel ideas—that controlling genes responsible for early development could produce significant effects in adults—accurately describes what contemporary developmental biology sees as one of the main sources of mutations.

While still in Germany studying gypsy moths in the late 1920s, Goldschmidt varied temperatures surrounding the larvae and found that this altered the timing of their   development—and, subsequently, their final internal structure. (Other researchers, conducting similar heat-shock experiments on a variety of organisms, were obtaining impressive results.) He began to appreciate that timing was of crucial importance in embryonic development. Later, working with Drosophila, Goldschmidt subjected adult populations to deleterious conditions (such as exposing them to ether fumes for fixed periods of time) that resulted in mutant offspring—some of which had extra sets of wings or sprouted legs where their antennae should be. He saw in these mutations further evidence of the consequence of altering hypothetical timing mechanisms during early stages of ontogeny. Additionally, the freakish changes in number or placement of parts suggested there might be—during this critical early phase—types of special cells that could be induced to become different parts. And finally: that this was somehow  related to modular growth patterns (which Bateson had so perceptively recognized as being central to evolutionary change).

After the neo-Darwinian synthesis became the dominant evolutionary paradigm, embryological  research carried on steadily while population geneticists continued to argue over the mechanisms of speciation and paleontologists remained puzzled by the gaps in their fossil records. After the discovery of DNA, problems that had been lingering for decades fell like dominoes. Some believed that the genetics had entered a humdrum, mop-up phase. Gunther Stent, a researcher who had been in the thick of many of the exhilarating breakthroughs, wrote of the looming decline of a discipline that was “only yesterday an avant-garde but today definitely a workaday field.”

The first major shake-up in decades came in the early 1970s when two graduate students in invertebrate paleontology at Columbia, Niles Eldredge and Stephen Jay Gould, proposed their controversial model of punctuated equilibria. Their own studies focused on hard-shelled creatures preserved in large numbers and thus leaving reasonably intact fossil records. The pattern they saw was not the slow-but-steady transition from older species to new (as specified by Darwin’s theory). Instead, they found that species tended to remain virtually unchanged for long periods, only to suddenly disappear and be replaced just as suddenly by entirely new varieties during occasional periods of rapid morphological change. The two co-wrote and published their landmark paper in 1972.[9] There was an immediate and vocal reaction.

Eldredge and Gould never suggested that new species arose instantaneously (as Goldschmidt believed) or even over a few generations but, in geological time, did so far  more abruptly than would occur during the slow transition called for by natural selection. Nonetheless, their hypothesis is still frequently construed this way and remains controversial. (Creationists take advantage of this misunderstanding to further the notion that evolutionists are conflicted and their “theory” in disarray—a tactic that rankles their adversaries no end.) Much of the opposition from scientists falls along party lines, with a predictably dogmatic response from staunch neo-Darwinists who all along have insisted that Eldredge and Gould’s observations reflect nothing more than normal gaps to be expected in the fossil record (an argument first employed, somewhat reluctantly, by Darwin himself). However, hard-shelled marine organisms leave behind a much more accurate record than do land animals. Paleontologists, for their part, had long been well aware of the pattern and Gould famously wrote in 1980, “The extreme rarity of transitional forms in the fossil record persists as the trade secret of paleontology.”[10]

The piecing together of the complex narrative of heredity and development has  been one of science’s grand triumphs. The characters involved were brilliant and often colorful, their methods models of empirical logic. Still, loose ends remained. Then: a huge step forward for both embryology and evolutionary theory occurred in the early 1980s with the discovery of something that is often likened to a “genetic tool kit.”

      ©2016 by Tim Forsell            15 May 2016

[1] The term was coined by Julian Huxley (1887–1975), brother of Aldous, grandson of Thomas (“Darwin’s bulldog”) and early proponent of the modern synthesis.
[2] Isotopes are forms of elements with different atomic weights; they share the same number of protons and electrons but have differing numbers of neutrons in the nucleus. Some isotopes are inherently unstable (radioactive) and spontaneously decay at known rates, thus altering—through passing time—the minute quantities naturally found in rock, water, ice, or gases. Certain radioactive isotopes occur in various types of rocks and organic substances, making possible the radiometric dating methods that have proven invaluable for establishing absolute ages of geologic formations and carbon-bearing historic artifacts.
[3] Less than half the current figure of 4.54 billion years. Creationists, of course, deny the validity of radiometric dating methods and still cite Lord Kelvin as the leading authority on Earth’s age.
[4] From a Latin word meaning “to leap.”
[5] Bateson is perhaps best known among modern geneticists for having the works of Mendel translated and introducing them to English-speaking scientists. He coined the term genetics in 1905 (before Swedish botanist Wilhelm Johannsen introduced the word gene in 1909). Bateson is also considered “the father of population genetics.” 
[6] Darwin proposed sexual selection as a way to explain many conspicuous features of animals (typically males) that couldn’t be attributed to natural selection as he envisioned it. These are characteristics more likely to reduce rather than enhance an animal’s chances of survival. The classic example is a male peacock’s extravagant nuptial train: while being attractive to potential mates and thus possibly helping pass on the male’s genes, it makes the bird much more vulnerable to predators.
[7] Many researchers unexpectedly developed a genuine fondness for their tiny subjects and practically lived with them in the cramped space. An early photo shows a typical crowded lab, shelves lined with scores of glass beakers (containing the flies) and other equipment…with an enormous bunch of bananas hanging prominently on one wall.
[8] In that era, plants and animals with severe mutations were typically called either “sports” or “monstrosities.” 
[9] The paper, entitled “Punctuated Equilibria: An Alternative to Phyletic Gradualism,” was first presented at the Annual Meeting of the Geological Society of America in 1971.
[10] A reappraisal of the fossil record in recent times has vindicated the claims made by Eldredge and Gould in this regard. (As one example, see Lyne & Howe, in Harris, p 73: “[R]e-analysis of existing fossil data has shown…that Eldredge and Gould were correct in identifying periods of evolutionary stasis which are interrupted by much shorter periods of evolutionary change.”)