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Zoology Timeline
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Certain key discoveries have greatly influenced progress in the study of zoology. This appendix presents some major landmarks in the development of biology and the individuals whose names are commonly associated with them. It is very difficult to appraise the historical development of any field of study. One investigator often gets the credit for an important discovery when many others should share in the prestige. No one individual has a monopoly on ideas; advances in science are built on the work of many minds. Especially in recent years, important discoveries have resulted from the efforts of teams of investigators. Furthermore, because knowledge of a topic accrues over a period of time, it is often difficult to decide in which year the "discovery" occurred.

In this brief outline the student may be able to see some relationships that exist between one discovery and another. Discoveries are not completely isolated, as they may sometimes appear. One may note also that fundamental discoveries in a particular branch of biology tend to be grouped fairly close together chronologically because that particular interest may have dominated the thought of biological investigators at that time.

A reader may wish to locate important discoveries in a given area without reading the entire list. Such an effort may be made easier by use of the following key symbols. Any such system of classification suffers some limitations, however. Many basic discoveries are not easily categorized because they have implications in wide areas. The list of categories must be short, or it becomes too cumbersome. Nevertheless, we hope that the classification will be useful.

[T] Taxonomy, systematics, and environmental fields (behavior, ecology, and the like)

[O] Tissue- and organ-level anatomy and physiology

[C] Cell biology

[D] Developmental biology

[G] Genetics

[E] Evolution and paleontology

[M] Of particular medical significance

Origins of Basic Concepts and Key Discoveries in Zoology

[O]  circa 450-370 b.c.: Hippocrates. Establishment of the first biomedical tradition.

This Greek physician developed an extensive body of anatomical and physiological knowledge that formed the basis of the revival of research in anatomy and physiology in the Renaissance. He is best remembered as the "Father of Medicine" who devised the code of medical ethics now administered as an oath to beginning medical practitioners.

384-322 b.c.: Aristotle. The foundation of zoology as a science.

Although this pioneer zoologist and philosopher cannot be appraised by modern standards, there is scarcely a major subdivision of zoology to which he did not make some contribution. However, Aristotle was more a philosopher and poet than scientist, and much of his biological writing is riddled with erroneous opinion.

[O]  130-200 a.d.: Galen. Development of anatomy and physiology.

This Roman investigator has been praised for his clear concept of scientific methods and blamed for passing down certain glaring errors that persisted for centuries. His influence was so great that for centuries students considered him the final authority on anatomical and physiological subjects.

1347: William of Occam. Occam's razor.

This principle of science has received its name from the fact that it is supposed to cut out unnecessary and irrelevant hypotheses in the explanation of phenomena. The gist of the principle is that, of several possible explanations, the one that is simplest, has the fewest assumptions, and is most consistent with available data is the most probable.

[O]  1543: Vesalius, Andreas. First modern interpretation of anatomical structures.

With his insight into fundamental structure, Vesalius ushered in the dawn of modern biological investigation. Many aspects of his interpretation of anatomy are just now beginning to be appreciated.

[O]  1616-1628: Harvey, William. First accurate description of blood circulation.

Harvey's classic demonstration of blood circulation was the key experiment that laid the foundation of modern physiology. He explained bodily processes in physical terms, cleared away much of the mystical interpretation, and gave an auspicious start to experimental physiology.

[O]  1627: Aselli, G. First demonstration of lacteal vessels.

This discovery, coming at the same time as Harvey's great work, supplemented the discovery of circulation.

[O]  1649: Descartes, René. Early concept of reflex action.

Descartes postulated that impulses originating at the receptors of the body were carried to the central nervous system where they activated muscles and glands by what he called "reflection."

[D]  1651: Harvey, William. Aphorism of Harvey: Omne vivum ex ovo (all life from the egg).

Although Harvey's work as an embryologist is overshadowed by his demonstration of blood circulation, his De Generatione Animalium, published in 1651, contains many sound observations on embryological processes.

[O]  1652: Bartholin, Thomas. Discovery of lymphatic system.

The significance of the thoracic duct in its relation to the circulation was determined in this investigation.

[O]  1658: Swammerdam, Jan. Description of red blood corpuscles.

This discovery, together with Swammerdam's observations on the valves of the lymphatics and the alterations in shape of muscles during contraction, represented early advancements in the microscopical study of bodily structures.

[O]  1661: Malpighi, Marcello. Demonstration of capillary circulation.

By demonstrating capillaries in the lung of a frog, Malpighi was able to complete the scheme of blood circulation. Harvey never saw capillaries and thus never included them in his description.

[C]  1665: Hooke, Robert. Discovery of cells.

Hooke's investigations were made with cork, and the term "cell" fits cork much better than it does animal cells, but by tradition the misnomer has stuck.

[C]  1672: de Graaf, R. Description of ovarian follicles.

De Graaf's name is given to the mature ovarian follicle, but he believed that follicles were the actual ova, an error later corrected by von Baer.

[C][T]  1675-1680: van Leeuwenhoek, Anthony. Discovery of protozoa.

The discoveries of this eccentric Dutch microscopist revealed a whole new world of biology.

[T]  1693: Ray, J. Concept of species.

Although Ray's work on classification was later overshadowed by that of Linnaeus, Ray was really the first to apply the species concept to a particular kind of organism and to point out the variations that exist among the members of a species.

[O]  1733: Hales, Stephen. First measurement of blood pressure.

This was further proof that bodily processes could be measured quantitatively-more than a century after Harvey's momentous demonstration.

[D]  1745: Bonnet, Charles. Discovery of natural parthenogenesis.

Although somewhat unusual in nature, this phenomenon has yielded much information about meiosis and other cytological problems.

[T]  1758: Linnaeus, Carolus. Development of binomial nomenclature system of taxonomy.

So important is this work in taxonomy that 1758 is regarded as the starting point in the determination of generic and specific names of animals. Besides the value of his binomial system, Linnaeus gave taxonomists a valuable working model of conciseness and clearness that has never been surpassed.

[D]  1759: Wolff, Kaspar F. Embryological theory of epigenesis.

This embryologist, the greatest before von Baer, did much to overthrow the preformation theory then in vogue and, despite many shortcomings, laid the basis for the modern interpretation of embryology.

[O]  1760: Hunter, John. Development of comparative investigations of animal structure.

This vigorous eighteenth-century anatomist gave a powerful impetus not only to anatomical observations but also to establishment of natural history museums.

[T]  1763: Adanson, M. Concept of empirical taxonomy.

This botanist proposed a scheme of classification that grouped individuals into taxa according to shared characteristics. A species would have the maximum number of shared characteristics according to this scheme. The concept has been revived recently by exponents of numerical taxonomy. It lacks the evaluation of the evolutionary concept and has been criticized on this account.

[G]  1763: Kölreuter, J.G. Discovery of quantitative inheritance (multiple genes).

Kölreuter, a pioneer in plant hybridization, found that certain plant hybrids had characteristics more or less intermediate between the parents in the F1 generation, but in the F2 there were many gradations from one extreme to the other. An explanation was not forthcoming until after Mendel's laws were discovered.

[T]  1768-1779: Cook, James. Influence of geographical exploration on development of biology.

This famous sea captain made possible a greater range of biological knowledge because he took able naturalists on his voyages of discovery.

[C]  1772: Priestley, J., and J. Ingenhousz. Concept of photosynthesis.

These investigators first pointed out some major aspects of this important phenomenon, such as the use of light energy for converting carbon dioxide and water into released oxygen and retained carbon.

[C]  1774: Priestley, J. Discovery of oxygen.

Discovery of this element is of great biological interest because it helped in determining the nature of oxidation and the exact role of respiration in organisms.

[C]  1778: Lavoisier, Antoine L. Nature of animal respiration demonstrated.

A basis for the chemical interpretation of the life process was given a great impetus by the careful quantitative studies of the changes during breathing made by this great investigator. His work also meant the final overthrow of the mystical phlogiston hypothesis that had held sway for so long.

[T]  1781: Abildgaard, P. First experimental life cycle of a tapeworm.

Life cycles of parasites may be very complicated, involving several hosts. That a parasitic worm could require more than one host was a revolutionary concept in Abildgaard's day and was widely disbelieved until the work of Küchenmeister over 60 years later.

[E]  1791: Smith, William. Correlation between fossils and geological strata.

By observing that certain types of fossils were peculiar to particular strata, Smith was able to work out a method for estimating geological age. He laid the basis of stratigraphic geology.

[O]  1792: Galvani, L. Animal electricity.

The lively controversy between Galvani and Volta over the twitching of frog legs led to extensive investigation of precise methods of measuring various electrical phenomena of animals.

[E]  1796: Cuvier, Georges. Development of vertebrate paleontology.

Cuvier compared the structure of fossil forms with that of living ones and concluded that there had been a succession of organisms that had become extinct and were succeeded by the creation of new ones. To account for this extinction, Cuvier held to the theory of catastrophism, or the simultaneous extinction of animal populations by natural cataclysms.

[E]  1801: de Lamarck, J.B. Evolutionary concept of use and disuse.

Lamarck gave the first clear-cut expression of a hypothesis to account for organic evolution. His assumption was that acquired characteristics were inherited; modern evolutionists have refuted this part of the hypothesis.

[O]  1802: Young, T. Hypothesis of trichromatic color vision.

Young's hypothesis suggested that the retina contained three kinds of light-sensitive substances, each having a maximum sensitivity in a different region of the spectrum and each being transmitted separately to the brain. The three substances combined produced the colors of the environment. The three pigments responsible are located in three kinds of cones. Young's explanation has been modified in certain details by other investigators.

[O]  1811: Bell, C., and F. Magendie. Discovery of the functions of dorsal and ventral roots of spinal nerves.

This demonstration was a starting point for an anatomical and functional investigation of the most complex system in the body.

[D]  1817: Pander, C.H. First description of three germ layers.

The description of three germ layers was first made on chicks, and later the concept was extended by von Baer to include all vertebrates.

[D]  1827: von Baer, Karl. Discovery of mammalian ovum.

The very tiny ova of mammals escaped de Graaf's eyes, but von Baer brought mammalian reproduction into line with that of other animals by detecting ova and their true relation to follicles.

[C]  1828: Brown, Robert. Brownian movement first described.

This interesting phenomenon is characteristic of living matter and sheds some light on the structure of cells.

[T]  1828: Thompson, J.V. Nature of plankton.

Thompson's collections of these small forms with a tow net, together with his published descriptions, are the first records of the vast community of planktonic animals. He was also the first to work out the true nature of barnacles.

[C]  1828: Wöhler, F. First to synthesize an organic compound.

Wöhler succeeded in making urea (a compound formed in the body) from the inorganic substance ammonium cyanate; thus, NH4OCN NH2CONH2. This success in producing an organic substance synthetically was the stimulus that resulted in preparation of thousands of compounds by others.

[D][E]  1830: von Baer, Karl. Biogenetic law formulated.

Von Baer's conception of this law was conservative and sounder in its implication than has been the case with many other biologists (Haeckel, for instance). Von Baer stated that embryos of higher and lower forms resemble each other more the earlier they are compared in their development, and not that the embryos of higher forms resemble the adults of lower organisms.

[E]  1830: Lyell, C. Modern concept of geology.

The influence of this concept not only did away with the catastrophic theory but also gave a logical interpretation of fossil life and the correlation between the formation of rock strata and the animal life that existed at the time these formations were laid down.

[C]  1831: Brown, Robert. First description of cell nucleus.

Others had seen nuclei, but Brown was the first to name the structure and to regard the nucleus as a general phenomenon. This description was an important preliminary to the formation of the cell theory a few years later, for Schleiden acknowledged the importance of the nucleus in the development of the cell concept.

[O]  1833: Hall, Marshall. Concept of reflex action.

Hall described the method by which a stimulus can produce a response independently of sensation or volition and coined the term "reflex action." It remained for the outstanding work of Sir Charles Sherrington in the twentieth century to explain much of the complex nature of reflexes.

[M][O]  1835: Bassi, Agostino. First demonstration of a microorganism as an infective agent.

Bassi's discovery that a certain disease of silkworms was caused by a small fungus represents the beginning of the germ theory of disease that was to prove so fruitful in the hands of Pasteur and other able investigators.

[C]  1835: Dujardin, Felix. Description of living matter (protoplasm).

Dujardin associated the jellylike substance that he found in protozoa and that he called "sarcode" with the life process. This substance was later called "protoplasm," and the sarcode idea may be considered a significant landmark in the development of the protoplasm concept.

[M][O]  1835: Owen, Richard. Discovery of Trichinella.

This versatile investigator is chiefly remembered for his researches in anatomy, but his discovery of this very common parasite in humans is an important landmark in the history of parasitology.

[C][O]  1838: von Liebig, Justus. Foundation of biochemistry.

The idea that vital activity could be explained by chemicophysical factors was an important concept for biological investigators studying the nature of life.

[C]  1838-1839: Schleiden, M.J., and T. Schwann. Formulation of the cell theory.

The cell doctrine, with its basic idea that all plants and animals were made up of similar units, represents one of the truly great landmarks in biological progress. Many biologists believe the work of Schleiden and Schwann has been rated much higher than it deserves in light of what others had done to develop the cell concept. R. Dutrochet (1824) and H. von Mohl (1831) described all tissues as being composed of cells.

[C]  1838: Mulder, G.J. Concept of the nature of proteins.

Mulder proposed the name "protéine," later "protein," for the basic constituents of protoplasmic materials.

[C]  1839-1846: Purkinje, J.E., and Hugo von Mohl. Concept of protoplasm established.

Purkinje proposed the name "protoplasm" for living matter, and von Mohl did extensive work on its nature, but it remained for Max Schultze (1861) to give a clear-cut concept of the relations of protoplasm to cells and its essential unity in all organisms.

[T]  1839: Verhulst, P.F. Logistical theory of population growth.

According to this theory, animal populations have a slow initial growth rate that gradually speeds up until it reaches a maximum and then slows down to a state of equilibrium. By plotting the logarithm of the total number of individuals against time, an S-shaped curve results that is somewhat similar for all populations.

[T][O]  1840: von Liebig, J., and F.F. Blackman. The law of minimum requirements.

Von Liebig interpreted plant growth as being dependent on essential requirements that are present in minimum quantity; some substances, even in minute quantities, were needed for normal growth. Later Blackman discovered that the rate of photosynthesis is restricted by the factor that operates at a limiting intensity (for example, light or temperature). The concept has been modified in various ways since it was formulated. We now know that a factor interaction other than the minimum ones plays a part.

[O]  1840: Müller, J. Theory of specific nerve energies.

This theory states that the kind of sensation experienced depends on the nature of the sense organ with which the stimulated nerve is connected. The optic nerve, for instance, conveys the impression of vision however it is stimulated.

[O]  1842: Bowman, William. Histological structure of the nephron (kidney unit).

Bowman's accurate description of the nephron afforded physiologists an opportunity to attack the problem of how the kidney separates waste from the blood.

[D]  1842: Steenstrup, Johann J.S. Alternation of generations described.

Metagenesis, or alternation of sexual and asexual reproduction in a life cycle, exists in many animals and plants. The concept had been introduced before this time by L.A. de Chamisso (1819).

[E]  1843: Owen, Richard. Concepts of homology and analogy.

Homology, as commonly understood, refers to similarity in embryonic origin and development, whereas analogy is the likeness between two organs in their functioning. Owen's concept of homology was merely that of the same organ in different animals under all varieties of form and function.

[O]  1844: Ludwig, C. Filtration theory of renal excretion.

About the same time that Bowman described the renal corpuscle, Ludwig showed that this unit functions as a passive filter and that the filtrate that passes through it from the blood carries into the renal tubules the waste products that are concentrated by the resorption of water as the filtrate moves down the tubules. Other investigators, Cushney, Starling, and Richards, have confirmed and extended his observations.

[O][C]  1845: von Helmholtz, H., and J.R. von Mayer. The formulation of the law of conservation of energy.

This landmark in human thinking showed that in any system, living or nonliving, the power to perform mechanical work always tends to decrease unless energy is added from without. Physiological investigation could now advance on the hypothesis that the living organism is an energy machine and obeys the law of energetics.

[G]  1848: Hofmeister, W. Discovery of chromosomes.

This investigator made sketches of bodies, later known to be chromosomes, in nuclei of pollen mother cells (Tradescantia). Schneider further described these elements in 1873, and Waldeyer named them in 1888.

[T]  1848: von Siebold, Carl T.E. Establishment of the status of protozoa.

Von Siebold emphasized the unicellular nature of protozoa, fitted them into the recently developed cell theory, and established them as the basic phylum of the animal kingdom.

[O]  1851: Bernard, Claude. Discovery of the vasomotor system.

Bernard showed how the amount of blood distributed to the various tissues by small arterioles was regulated by vasomotor nerves of the sympathetic nervous system, as he demonstrated in the ear of a white rabbit.

[D]1851: Waller, A.V. Importance of the nucleus in regeneration.

When nerve fibers are cut, the parts of the fibers peripheral to the cut degenerate in a characteristic fashion. This wallerian degeneration enables one to trace the course of fibers through the nervous system. In the regeneration process the nerve cell body (with its nucleus) is necessary for the downgrowth of the fiber from the proximal segment.

[O]  1852: von Helmholtz, Herman. Determination of rate of nervous impulse.

This landmark in nerve physiology showed that the phenomena of nervous activity could be measured experimentally and expressed numerically.

[O][C]  1852: von Kölliker, Albrecht. Establishment of histology as a science.

Many histological structures were described with marvelous insight by this great investigator, starting with the publication of the first text in histology (Handbuch der Gewebelehre).

[O]  1852: Stannius, H.F. Stannius's experiment on the heart.

By tying a ligature as a constriction between the sinus venosus and the atrium in the frog and also one around the atrioventricular groove, Stannius was able to demonstrate that the muscle tissues of the atria and ventricles have independent and spontaneous rhythms. His observations also indicated that the sinus is the pacemaker of the heartbeat.

[M][T]  1852: Küchenmeister, G.F.H. Relationship of "bladder worms" to adult tapeworms.

This was the first demonstration that "bladder worms" (cysticerci) were juveniles of taeniid tapeworms. It was followed rapidly by numerous other life-cycle studies on cestodes.

[D]  1854: Newport, G. Discovery of the entrance of spermatozoon into a frog's egg.

This was a significant step in cellular embryology, although its real meaning was not revealed until the concept of fertilization as the union of two pronuclei was formulated about 20 years later (Hertwig, 1875).

[M][O]  1855: Addison, T. Discovery of adrenal disease.

The importance of adrenals in maintaining normal body functions was shown when Addison described a syndrome of general disorders associated with the pathology of this gland.

[E]  1856: Discovery of Neanderthal fossil hominid (Homo sapiens).

Many specimens of this type of fossil hominid have been discovered (Europe, Asia, Africa) since the first one was found near Düsseldorf, Germany. Their culture was Mousterian (100,000 to 40,000 years bp), and although they were of short stature, their cranial capacity was as large as or larger than that of modern humans.

[O]  1857: Bernard, Claude. Discovery of formation of glycogen by the liver.

Bernard's demonstration that the liver forms glycogen from substances brought to it by the blood showed that the body can build up complex substances as well as tear them down.

[T]  1858: Sclater, P.L. Distribution of animals on basis of zoological regions.

This was the first serious attempt to study geographical distribution of organisms, a study that eventually led to the present science of zoogeography. A.R. Wallace worked along similar lines.

[D][C]  1858: Virchow, Rudolf. Aphorism of Virchow: Omnis cellula e cellula (every cell from a cell).

[C]  1858: Virchow, Rudolf. Formation of the concept of disease from the viewpoint of cell structure.

He laid the basis of modern pathology by stressing the role of the cell in diseased tissue.

[E]  1859: Darwin, Charles. The concept of natural selection as a factor in evolution.

Although Darwin did not originate the concept of organic evolution, no one has been more influential in development of evolutionary thought. Publication of The Origin of Species represents the greatest and most influential single landmark in the history of biology.

[O]  1860: Bernard, Claude. Concept of the constancy of the internal environment (homeostasis).

Bernard's realization that there are mechanisms in living organisms that tend to maintain internal conditions within relatively narrow limits, despite external change, is one of the most valuable generalizations in physiology.

[D]  1860: Pasteur, Louis. Aphorism of Pasteur: Omne vivum e vivo (every living thing from the living).

[D]  1860: Pasteur, Louis. Refutation of spontaneous generation.

Pasteur's experiment with the open S-shaped flask proved conclusively that fermentation or putrefaction resulted from microbes, thus ending the long-standing controversy regarding spontaneous generation.

[T]  1860: Wallace, A.R. The Wallace line of faunal delimitation.

As originally proposed by Wallace, there was a sharp boundary between Australian and Oriental faunal regions so that a geographical line drawn between certain islands of the Malay Archipelago, through the Makassar Strait between Borneo and Celebes, and between the Philippines and Sanghir Islands separated two distinct and contrasting zoological regions. On one side Australian forms predominated; on the other, Oriental ones. The validity of this division has been questioned by zoogeographers in light of more extensive knowledge of faunas of the two regions.

[C]  1861: Graham, Thomas. Colloidal states of matter.

This work on colloidal solutions has resulted in one of the most fruitful concepts regarding protoplasmic systems.

[T]  1862: Bates, H.W. Concept of mimicry.

Mimicry refers to the advantageous resemblance of one species to another for protection against predators. It involves palatable or edible species that imitate dangerous or inedible species that employ warning coloration against potential enemies.

[T]  1864: Haeckel, Ernst. Modern zoological classification.

The broad features of zoological classification as we know it today were outlined by Haeckel and others, especially R.R. Lankester, in the third quarter of the nineteenth century. B. Hatschek is another zoologist who deserves much credit for the modern scheme, which is constantly undergoing revision. Other schemes of classification in the early nineteenth century did much to resolve the difficult problem of classification, such as those of Cuvier, de Lamarck, Leuckart, Ehrenberg, Vogt, Gegenbauer, and Schimkivitch.

[C]  1864: Schultze, Max. Protoplasmic bridges between cells.

Connection of one cell to another by means of protoplasmic bridges has been demonstrated in both plants and animals. Modern techniques, including electron microscopy, have shown that many cells communicate by gap junctions, which have channels capable of passing molecules of up to 1000 daltons in molecular weight.

[G]  1866: Haeckel, Ernst. Nuclear control of inheritance.

At the time this hypothesis was formed, the view that the nucleus transmitted the inheritance of an animal had no evidence to substantiate it.

[T]  1866: Kovalevski, A. Taxonomic position of tunicates.

The great Russian embryologist showed the similarity between amphioxus and the tunicates in early stages of development and how the latter could be considered a branch of phylum Chordata.

[G]  1866: Mendel, Gregor. Formulation of the first two laws of heredity.

These first clear-cut statements of inheritance made possible an analysis of hereditary patterns with mathematical precision. Rediscovered in 1900, his paper confirmed experimental data geneticists had found at that time. Since that time Mendelian genetics has been considered the chief cornerstone of hereditary investigation.

[O]  1866: Schultze, Max. Histological analysis of the retina.

Schultze's fundamental discovery that the retina contained two types of visual cells-rods and cones-helped to explain the physiological differences of vision in high and low intensities of light.

[E][D]  1867: Kovalevski, A. Germ layers of invertebrates.

The concept of primary germ layers laid down by Pander and von Baer was extended to invertebrates by this investigator. He found the same three germ layers arose in the same fashion as those in vertebrates. Thus an important embryological unity was established for the animal kingdom.

[O]  1869: Langerhans, P. Discovery of islet cells in pancreas.

These islets were first found in rabbits, and since their discovery they have been one of the most investigated tissues in animals. The hypothesis that they have come from the transformation of pancreatic acinus cells has now given way to the belief that they originated from the embryonic tubules of the pancreatic duct.

[C]  1869: Miescher, F. Isolation of nucleoprotein.

From pus cells, a pathological product, Miescher was able to demonstrate in the nuclei certain phosphorus-rich substances, nucleic acids, which are bound to proteins to form nucleoproteins. In recent years these complex molecules have been the focal point of significant biochemical investigations on the chemical properties of genes, with the wider implications of a better understanding of growth, heredity, and evolution.

[T]  1871: Quetelet, Lambert A. Foundations of biometry.

The applications of statistics to biological problems is called biometry. By working out the distribution curve heights of soldiers, Quetelet showed biologists how the systematic study of relationships of numerical data could become a powerful tool for analyzing data in evolution, genetics, and other biological fields.

[T]  1872-1876: Challenger expedition.

Not only did this expedition establish the science of oceanography, but a vast amount of material was collected that greatly extended knowledge of the variety and range of animal life.

[T]  1872: Dohrn, Anton. Establishment of Naples Biological Station.

Establishment of this famous station marked the first of the great biological stations, and it rapidly attained international importance as a center of biological investigation.

[O]  1872: Ludwig, C., and E.F.W. Pflüger. Gas exchange of the blood.

By means of a mercurial blood pump, these investigators separated the gases from blood and thereby threw much light on the nature of gas exchange and the place where oxidation occurs (in

[E][T]  1874: Haeckel, Ernst H. Taxonomic position of phylum Chordata.

The great German evolutionist based many of his conclusions on the work of the Russian embryologist Kovalevski, who in 1866 showed that tunicates as well as amphioxus had vertebrate affinities.

[E]  1874: Haeckel, Ernst H. Gastrea hypothesis of metazoan ancestry.

According to this hypothesis, the hypothetical ancestor of all the Metazoa consisted of two layers (ectoderm and endoderm) similar to the gastrula stage in embryonic development, and endoderm arose as an invagination of the blastula. Thus the diploblastic stage of ontogeny was to be considered as the repetition of this ancestral form. This concept in modified form has had wide acceptance. It is now supported by sequence analysis of DNA.

[G][D]  1875: Hertwig, Oskar. Concept of fertilization as the conjugation of two sex cells.

The fusion of pronuclei of two gametes in the process of fertilization paved the way for the concept that nuclei contained the hereditary factors and that both maternal and paternal factors are brought together in a zygote.

[C]  1875: Strasburger, Eduard. Description of mitotic cell division.

The accurate description of the processes of cell division that Strasburger made in plants represents a great pioneer work in the rapid development of cytology during the last quarter of the nineteenth century.

[C]  1876: Pasteur, Louis. The Pasteur effect.

In his studies of fermentation processes in wine making, Pasteur discovered that cells consumed much more glucose and produced much more lactic acid in the absence of oxygen than in its presence. It is now known that the effect occurs in many different kinds of cells and is a consequence of the lower energy yield of glycolysis compared with oxidative phosphorylation.

[O]  1877: Pfeffer, Wilhelm. Concept of osmosis and osmotic pressure.

Pfeffer's experiments on osmotic pressure and the determination of the pressure in different concentrations laid the foundation for an understanding of a general phenomenon in all organisms.

[O]  1878: Balfour, Francis M. Relationship of the adrenal medulla to the sympathetic nervous system.

By showing that the adrenal medulla has the same origin as the sympathetic nervous system, Balfour really laid the foundation for the interesting concept of the similarity in the action of epinephrine and sympathetic nervous mediation.

[O][C]  1878: Kühne, Willy. Nature of enzymes.

The study of the action of chemical catalysts has steadily increased with biological advancement and now represents one of the most fundamental aspects of biochemistry.

[C]  1879: Flemming, Walther. Chromatin described and named.

Flemming shares with a few others (especially Strasburger, 1875) the description of details of mitotic cell division. The part of a nucleus that stains deeply he called chromatin (colored), which gives rise to the chromosomes.

[D]  1879: Fol, Hermann. Penetration of ovum by a spermatozoon described.

Fol was the first to describe a thin cone-like body extending outward from the egg to meet the sperm. Compare Dan's acrosome reaction (1954).

[C]  1879: Kossel, Albrecht. Isolation of nucleoprotein.

Nucleoproteins were isolated from heads of fish sperm; they make up the major part of chromatin. They are combinations of proteins with nucleic acids, and this study was one of the first investigations of a topic that interests biochemists at the present time.

Nobel Laureate (1910).

[M]  1880: Laveran, C.L.A. Protozoa as pathogenic agents.

This French investigator first demonstrated that the causative organism for malaria is a protozoan. This discovery led to other investigations that revealed the role protozoa play in causing diseases such as sleeping sickness and kala-azar. It remained for Sir Ronald Ross to discover the role of mosquitos in spreading malaria.

Nobel Laureate (1907).

[O]  1880: Ringer, S. Influence of blood ions on heart contraction.

The pioneer work of this investigator determined the inorganic ions necessary for contraction of frog hearts and made possible an evaluation of heart metabolism and replacement of body fluids.

[C]  1882: Flemming, Walther. First accurate counts of nuclear filaments (chromosomes) made.

[C]  1882: Flemming, Walther. Mitosis and spireme (thread like appearance of chromatin during prophase) named.

[M][C]  1882: Metchnikoff,Élie. Role of phagocytosis in immunity.

The theory that microbes are ingested and destroyed by certain white corpuscles (phagocytes) shares with the theory of chemical bodies (antibodies) the chief explanation for natural immunity. Metchnikoff first studied phagocytosis in cells of starfish and water fleas (Daphnia).

Nobel Laureate (1908).

[C]  1882: Strasburger, Eduard. Cytoplasm and nucleoplasm named.

[T]  1882-1924: The Albatross of the Fish Commission.

The Albatross, under the direction of the U.S. Fish Commission, was second only to the famed Challenger in advancing scientific knowledge about oceanography.

[O][C]  1883: Golgi, Camillo, and R. Cajal. Silver nitrate technique for nervous elements.

The development and refinement of this technique gave a completely new picture of the intricate relationships of neurons. Modifications of this method have yielded valuable information concern-ing a vital cellular element-the Golgi apparatus.

Nobel Laureates (1906).

[D]  1883: Hertwig, Oskar. Origin of term "mesenchyme."

This important tissue may arise embryonically from all three germ layers but chiefly from the mesoderm. It is a protoplasmic network whose meshes are filled with a fluid intercellular substance. Mesenchyme gives rise to a great variety of tissues, and both its cells and intercellular substance may be variously modified; its most common derivative is connective tissue.

[M][T]  1883: Leuckart, Rudolph, and A.P. Thomas. Life history of sheep liver flukes.

This discovery represents the first time a complete life cycle was worked out for a digenetic trematode. Working independently, these investigators found that the trematode used a snail intermediate host.

[G]  1883: Roux, Wilhelm. Allocation of hereditary functions to chromosomes.

This hypothesis could not have been much more than a guess when Roux made it, but how fruitful was the idea in the light of the enormous amount of evidence since accumulated!

[C]  1884: Flemming, W., E. Strasburger, and E. van Beneden. Demonstration that nuclear filaments (chromosomes) double in number by longitudinal division.

This concept represented a further step in understanding the precise process of cell division.

[O]  1884: Rubner, Max. Quantitative determinations of the energy value of foods.

Although Liebig and others had estimated calorie values of foods, the investigations of Rubner put their determinations on a sound basis. His work made possible a scientific explanation for metabolism and a basis for the study of comparative nutrition.

[G]  1885: Hertwig, Oskar, and E. Strasburger. Concept of the nucleus as the basis of heredity.

The development of this idea occurred before Mendel's laws of heredity were rediscovered in 1900, but it anticipated the important role the nucleus with its chromosomes was to assume in hereditary transmission.

[G]  1885: Rabl, Karl. Concept of the individuality of the chromosomes.

The view that chromosomes retain their individuality through all stages of the cell cycle is accepted by all cytologists, and much evidence has accumulated in support of the hypothesis. However, it has been virtually impossible to demonstrate chromosomal individuality through all stages.

[D]  1885: Roux, Wilhelm. Mosaic theory of development.

In the early development of a frog egg, Roux showed that the determinants for differentiations were segregated in the early cleavage stages and that each cell or groups of cells would form only certain parts of the developing embryo (mosaic or determinate development). Later, other investigators showed that in many forms blastomeres, if separated early, would give rise to whole embryos (indeterminate development).

[D][G]  1885: Weismann, August. Formulation of germ plasm theory.

Weismann's great theory of the germ plasm stresses the idea that there are two types of protoplasm-germ plasm, which gives rise to the reproductive cells or gametes, and somatoplasm, which furnishes all the other cells. Germ plasm, according to the theory, is continuous from generation to generation, whereas somatoplasm dies with each generation and does not influence germ plasm.

1886: Establishment of Woods Hole Biological Station in Massachusetts.

This station is by all odds the greatest center of its kind in the world. Many biologists in America have studied there, and the station has increasingly attracted investigators from many other countries as well. The influence of Woods Hole on the progress of biology cannot be overestimated.

[C]  1887: Fischer, Emil. Structural patterns of proteins.

The importance of proteins in biological systems has made their study the central theme of much modern biochemical work.

Nobel Laureate (1902).

[D]  1887: Haeckel, Ernst H. Concept of organic form and symmetry.

Symmetry refers to the spatial relations and arrangements of parts in such a way as to form geometrical designs. Although many others before Haeckel's time had studied and described types of animal form, Haeckel gave us our present concepts of organic symmetry, as revealed in his monograph on radiolarians collected on the Challenger expedition.

[G]  1889: Hertwig, R., and E. Maupas. True nature of conjugation in paramecium.

The process of conjugation was described (even by van Leeuwenhoek) many times and its sexual significance interpreted, but these two investigators independently showed details of the divisions before conjugation and mutual exchange of the micronuclei during the process.

[M][O]  1889: von Mering, J., and O. Minkowski. Effect of pancreatectomy.

The classic experiment of removing the pancreas stimulated research that led to the isolation of the pancreatic hormone insulin by Banting (1922).

[M]  1890: Smith, Theobald. Role of an arthropod in disease transmission.

The transmission of the sporozoan Babesia, bigemina, which is the active agent in causing Texas cattle fever, by the tick Boophilus annulatus, represented the first demonstration of an arthropod as a vector of a protozoan parasite.

[D]  1891: Driesch, Hans. Discovery of totipotent cleavage.

The discovery that each of the first several blastomeres, if separated from each other in the early cleavage of a sea urchin embryo, would develop into a complete embryo stimulated investigation on totipotent and other types of development.

[E]  1890-1891: Dubois, Eugene. Discovery of the fossil human Pithecanthropus erectus (now Homo erectus).

Although not the first fossil human to be found, the Java man represents one of the first significant primitive humans that have been discovered.

[E]  1893: Dollo, I. Concept of the irreversibility of evolution.

In general, the overall evolutionary process is one-way and irreversible insofar as a whole complex genetic system is concerned, although back mutations and restricted variations may occur over and over.

[O]  1893: His, Wilhelm. Anatomy and physiology of the atrioventricular node and bundle.

The specialized conducting tissue of the heart has given rise to many investigations, not the least of which were those of His, whose name was given to the intricate system of branches that are reflected over the inner surface of the ventricles.

[D]  1894: Driesch, Hans. Constancy of nuclear potentiality.

Driesch's view was that all nuclei of an organism were equipotential but that the activity of nuclei varied as tissues differentiated. More recent studies have emphasized the crucial importance of cytoplasm of an embryo in determining expression of the nuclear genome.

[T]  1894: Merriam, C.H. Concept of life zones in North America.

This scheme is based on temperature criteria and the importance of temperature in the distribution of plants and animals. According to this concept, animals and plants are restricted in their northward distribution by the total quantity of heat during the season of growth and reproduction, and their southward distribution is restricted by the mean temperature during the hottest part of the year.

[M][T]  1895: Bruce, D. Life cycle of protozoan blood parasite (Trypanosoma).

The relation of this parasite to the tsetse fly and to wild and domestic animal infection in Africa is an early demonstration of arthropods as vectors of disease.

[M][O]  1895: Roentgen, W. Discovery of x-rays.

This great discovery was quickly followed by its application in the interpretation of bodily structures and processes and represents one of the great tools in biological research.

Nobel Laureate (1901).

[E]  1896: Baldwin, J.M. Baldwin evolutionary effect.

It is the belief that genetic selection of genotypes will be channeled or canalized in the same direction as the adaptive modifications that were formerly nonhereditary. It is now understood that the capacity to respond to environmental conditions is itself hereditary.

[E]  1896: Russian Hydrographic Survey. Biology of Lake Baikal.

This lake in Siberia is more than 800 km long and 80 km wide and has an extreme depth of more than a mile (the deepest lake in the world). Its unique fauna is a striking example of evolutionary results from long-continued isolation. Almost all species in certain groups are endemic (found nowhere else). This remarkable fauna includes ancient freshwater animals that have become extinct in surrounding areas.

[O]  1897: Abel, J.J., and A.C. Crawford. Isolation of the first hormone

Purification and isolation of one of the active principles from adrenal medulla led to discovery of its chemical nature and naming by J. Takamine (1901) and its synthesis by F. Stolz (1904).

[C][O]  1897: Buchner, E. Discovery of zymase.

Buchner's discovery that an enzyme (a nonliving substance) manufactured by yeast cells was responsible for fermentation resolved many problems that had baffled Pasteur and other investigators. Zymase is now known to consist of a number of enzymes.

Nobel Laureate (1907).

[E]  1897: Canadian Geological Survey. Dinosaur fauna of Alberta, Canada.

Discovery and exploration of Upper Cretaceous fossil beds along the Red Deer River in Alberta revealed one of the richest dinosaur faunal finds known.

[M][O]  1897: Eijkman, Christian. Discovery of the cause of a dietary deficiency disease.

Eijkman's pioneer work on the causes of beriberi led to isolation of the antineuritic vitamin (thiamine). This work may be called the key discovery that resulted in development of the important vitamin concept.

Nobel Laureate (1929).

[M][T]  1897: Ross, Ronald. Life history of malarial parasite (Plasmodium).

This notable achievement represents a great landmark in the field of parasitology and the climax of the work of many investigators on the problem.

Nobel Laureate (1902).

[C][O]  1897: Sherrington, C.S. Concept of the synapse in the nervous system.

If the nervous system is composed of discrete units, or neurons, functional connections must exist between these units. Sherrington showed how individual nerve cells could exert integrative influences on other nerve cells by graded excitatory or inhibitory synaptic actions. The electron microscope has in recent years added much to our knowledge of synaptic structure.

Nobel Laureate (1932).

[C]  1898: Benda, C., and C. Golgi. Discovery of mitochondria and Golgi apparatus.

These interesting cytoplasmic inclusions were actually seen by various observers before this date, but they were not named in 1898, and the real study of them began at this time. W. Flemming and R. Altmann first demonstrated mitochondria. The Golgi apparatus was demonstrated by V. St. George (1867) and G. Platner (1855), but Camillo Golgi, with his silver nitrate impregnation method, gave the first clear description of the apparatus in nerve cells. Mitochondria play an important role in cell respiration and energy production in most eukaryote cells.

[E]  1898: Osborn, Henry F. Concept of adaptive radiation in evolution.

This concept states that, starting from a common ancestral type, many different forms of evolutionary adaptations may occur. In this way evolutionary divergence can take place, and the occupation of a variety of ecological niches is made possible, according to the adaptive nature of the invading species.

[E]  1900: Chamberlain, T.C. Hypothesis of the freshwater origin of vertebrates.

Evidence for this hypothesis as first proposed was based mainly on discovery of early vertebrate fossils in sediments thought to be of freshwater origin, such as Old Red Sandstone. The fossil evidence has been reevaluated by recent investigators, who interpret it to support a marine origin of the vertebrates.

[G]  1900: Correns, Karl E., Erick Tschermak von Seysenegg, and Hugo De Vries. Rediscovery of Mendel's laws of heredity.

In their genetic experiments on plants these three investigators independently obtained results similar to Mendel's, and in their survey of the literature they found that Mendel had published his now-famous laws in 1866. A few years later, W. Bateson and others found that the same laws applied to animals.

[E]  1900: Andrews, C.F. Discovery of fossil beds in the Fayum Depression region of Egypt.

Here Andrews and others discovered numerous Eocene and Oligocene fossils of protomonkeys believed to be ancestral to Old World monkeys and thus in the lineage leading to hominids.

[M][O]  1900: Landsteiner, Karl. Discovery of blood groups.

This fundamental discovery made possible successful blood transfusions and initiated intense work on the biochemistry of blood.

Nobel Laureate (1930).

[D]  1900: Loeb, Jacques. Discovery of artificial parthenogenesis.

Stimulation of embryogenesis in eggs that normally require fertilization to develop by chemical and mechanical methods has been accomplished in a number of different animals, from sea urchin and frog eggs (Loeb, 1900) to rabbit eggs (Pincus, 1936). The phenomenon has been a useful tool in studying biology of fertilization.

[G]  1901: Montgomery, T.H. Homologous pairing of maternal and paternal chromosomes in zygotes.

Montgomery showed that in synapsis before reduction division, each pair includes a maternal and a paternal chromosome. This phenomenon, verified a year later by W.S. Sutton, is of fundamental importance in segregation of hereditary factors (genes).

[E][G]  1901: De Vries, Hugo. Mutation theory of evolution.

De Vries concluded from his study of the evening primrose Oenothera lamarckiana that new characteristics appear suddenly and are inheritable. Although the variations in Oenothera were probably not mutations at all, since many of them represented hybrid combinations, the evidence that mutations are the ultimate source of all new variation has steadily mounted.

[G]  1902: McClung, Clarence E. Discovery of sex chromosomes.

The discovery in grasshoppers that a certain chromosome (X) had a synaptic mate (Y) different in appearance or else lacked a mate altogether gave rise to the theory that certain chromosomes determined sex. H. Henking actually discovered the X chromosome in 1891.

[O]  1903: Bayliss, William M., and Ernest H. Starling. Action of the hormone secretin.

Demonstration of the action of secretin, a hormone released from the mucosa of the stomach, marked the real birth of the science of endocrinology. It was the first unequivocal proof that physiological functions could be chemically integrated without participation of the nervous system.

[G]  1903: Boveri, Theodor, and W.S. Sutton. Parallelism between chromosome behavior and Mendelian segregation.

This concept states that synaptic mates in meiosis correspond to Mendelian alternative characters and that the formula of character inheritance of Mendel could be explained by behavior of chromosomes during maturation. This is therefore a cytological demonstration of Mendelian genetics.

[G]  1903: Sutton, W.S. Constitution of the diploid group of chromosomes.

Sutton related Mendelian transmission of inherited characters to cytology by showing that the diploid group of chromosomes is made up of two chromosomes of each recognizable size, one member of which is paternal and the other maternal in origin.

[O]  1904: Cannon, Walter B. Mechanics of digestion observed by means of x-ray films.

Clever application of x-rays to a study of movements and other aspects of the digestive system has revealed an enormous amount of information on physiology of the alimentary canal. Cannon first used this technique in 1898.

[O]  1904: Carlson, Anton J. Pacemaking activity of neurogenic hearts.

Heartbeats may originate in muscle (myogenic hearts) or in ganglion cells (neurogenic hearts). Carlson showed that in the arthropod Limulus the pacemaker was located in certain ganglia on the dorsal surface of the heart and that experimental alterations of these ganglia by temperature or other means altered the heart rate. Neurogenic hearts are restricted to certain invertebrates.

[T]  1904: Jennings, Herbert S. Behavior patterns in protozoa.

Careful investigations by this life-long student of behavior of these"simple" organisms led to concepts such as the trial-and-error behavior and many important concepts concerning various forms of tropisms and taxes.

[O]  1905: Haldane, John B.S., and John G. Priestley. Role of carbon dioxide in the regulation of breathing.

By their clever technique of obtaining samples of air from lung alveoli, these investigators showed how constancy of carbon dioxide concentration in alveoli and its relation to concentration in blood were the chief regulators of the mechanism of respiration.

[G]  1906: Bateson, William, and Reginald C. Punnett. Discovery of linkage of hereditary units.

Although Bateson and Punnett first discovered linkage in sweet peas, it was Morgan and associates who correctly interpreted this great genetic concept. All seven pairs of Mendel's alternative characteristics were on separate chromosomes, which simplified the problem.

[O]  1906: Einthoven, W. Mechanism of the electrocardiogram.

Invention of the string galvanometer (1903) by Einthoven supplied a precise tool for measuring bioelectrical activity of the heart and quickly led to the electrocardiogram, which gives accurate information about disturbances of a heart's rhythm.

Nobel Laureate (1924).

[O]  1906: Hopkins, Frederick G. Analysis of dietary deficiency.

Hopkins tried to explain dietary deficiency by a biochemical investigation of the lack of essential amino acids in the diet, an approach that has led to many important investigations in nutritional requirements.

Nobel Laureate (1929).

[C]  1906: Tswett, M. Principle of chromatography.

This is separation of chemical components in a mixture by differential migration of materials according to structural properties within a special porous sorptive medium. It was refined and became a widely used method 30 or 40 years later (Martin and Synge, 1941). The technique was first used by Tswett to separate pigments of plants.

[M]  1906-1913: Gorgas, William C. Control of malaria and yellow fever.

By intelligent and industrious application of knowledge that mosquitoes carry malaria and yellow fever, Gorgas saved 71,000 lives and made possible construction of the Panama Canal.

[D]  1907: Boveri, Theodor. Qualitative differences of chromosomes.

Boveri showed in his classic experiment with sea urchin eggs that chromosomes have qualitatively different effects on development. He found that only those cells that had one of each kind of chromosome developed into larvae; those cells that did not have representatives of each kind of chromosome failed to develop.

[O][C]  1907: Harrison, Ross. Tissue culture technique.

The culturing of living tissues in vitro, that is, outside the body, has given biologists an important tool for studying tissue structure and growth. Harrison overcame great technical difficulties to culture living tissues in suitable media successfully.

[O]  1907: Hopkins, Frederick G. Relationship of lactic acid to muscular contraction.

Hopkins showed that, after being formed in muscular contraction, some lactic acid is oxidized to furnish energy for resynthesis of glycogen from the remaining lactic acid. This discovery did much to clarify some metabolic reactions involved in the complicated process of muscular contraction.

Nobel Laureate (1929).

[D]  1907: Wilson, H.V. Reorganization of sponge cells.

In this classic experiment, Wilson showed that disaggregation of sponges, by squeezing them through fine silk bolting cloth so that they are separated into minute cell clumps, resulted in the surviving cells coming together and organizing themselves into small sponges.

[G]  1908: Garrod, A.E. Discovery that gene products are proteins.

Certain hereditary disorders are caused by enzyme deficiencies wherein the mutations of a single gene may be responsible for controlling the specificity of a particular enzyme in certain disorders. Garrod's work was largely ignored until 1940.

[E][G]  1908: Hardy, Godfrey H., and W. Weinberg, Hardy-Weinberg population formula.

This important theorem states that, in absence of factors (such as mutation and selection) causing change in gene frequency, frequency of a particular gene in any large population will reach an equilibrium in one generation and thereafter will remain stable regardless of whether the genes are dominant or recessive. Its mathematical expression forms the basis for the calculations of population genetics.

[O][C]  1909: Arrhenius, S., and S.P.L. Sörensen. Dissociation theory.

The sensitivity of most biological systems to acid and alkaline conditions has made pH values of the utmost importance in biological research.

Arrhenius, Nobel Laureate (1903).

[G]  1909: Castle, William E., and J.C. Philips. The inviolability of germ cells to somatic cell influences.

That germ cells are relatively free from somatic cell influences was shown by substitution of a black guinea pig ovary in a white guinea pig, which gave rise to black offspring when mated with a black male.

[E]  1909: Johannsen, W.L. Limitations of natural selection on pure lines.

This investigator found that when a hereditary group of characteristics becomes genetically homogeneous, natural selection cannot change the genetic constitution with regard to these characteristics. He showed that selection could not itself create new genotypes but was effective only in isolating genotypes already present in the group; it therefore could not effect evolutionary changes directly.

[M][T]  1909: Nicolle, Charles J.H. Body louse as vector of typhus fever.

The demonstration that typhus fever was transmitted from patient to patient by bites of body lice paved the way for the control of this dreaded epidemic disorder by using DDT to delouse populations.

Nobel Laureate (1928).

[O]  1910: Dale, Henry H. Nature of histamine.

Dale and colleagues found that an extract from ergot had the properties of histamine (-imidazolyl ethylamine), which can be produced synthetically by splitting off carbon dioxide from the amino acid histidine. It is also a constituent of all tissue cells, from which it may be released by injuries or other causes. The pronounced effect of histamine in dilating small blood vessels, contracting smooth muscle, and stimulating glands has caused it to be associated with many physiological phenomena, such as anaphylaxis, shock, and allergies.

Nobel Laureate (1936).

[M]  1910: Ehrlich, Paul. Chemotherapy in treatment of disease.

Discovery of salvarsan as a cure for syphilis represents the first great discovery in this field. Another was the dye sulfanilamide, discovered by Domagk in 1935.

Nobel Laureate (1908).

[T]  1910: Heinroth, O. Concept of imprinting as a type of behavior.

This is a special type of learning that is demonstrated by birds (and possibly other animals). It is based on observations that in many species of birds hatchlings are attracted to the first large object they see and thereafter will follow that object to the exclusion of all others.

[G]  1910: Morgan, Thomas H. Discovery of sex linkage.

Morgan and colleagues discovered that the results of a cross between a white-eyed male and a red-eyed female in Drosophila were different from those obtained from the reciprocal cross of a red-eyed male with a white-eyed female. This was a crucial experiment because it showed for the first time that how a trait behaved in heredity depended on the sex of the parent, in contrast to most Mendelian characters, which behave genetically the same way whether introduced by a male or female parent.

[G]  1910-1920: Morgan, Thomas H. Establishment of gene theory.

The extensive work of Morgan and associates on the localization of hereditary factors (by genetic experiments) on the chromosomes of the fruit fly (Drosophila) represents some of the most significant work ever performed in the field of heredity.

Nobel Laureate (1933).

[T]  1910: Murray, J., and J. Hjort. Deep-sea expedition of the Michael Sars.

Of the many expeditions for exploring depths of the oceans, the Michael Sars expedition, made in North Atlantic regions, must rank among the foremost. The expedition yielded an immense amount of information about deep-sea animals, as well as important data regarding ecological patterns of animal distribution in the sea.

[T]  1910: Pavlov, Ivan P. Concept of the conditioned reflex.

The idea that acquired reflexes play an important role in nervous reaction patterns of animals has greatly influenced the development of modern psychology.

Nobel Laureate (1904; for earlier work on the physiology of digestion).

[D]  1911: Child, Charles M. Axial gradient hypothesis.

This hypothesis attempts to explain the pattern of metabolism from the standpoint of localized regional differences along the axes of organisms. The differences in metabolic rate of different areas have made possible an understanding of certain aspects of regeneration, development, and growth.

[E]  1911: Cuénot, L. The preadaptation concept.

Preadaptation refers to a morphological or physiological characteristic that has been selected for (arisen) in one environment, but that is coincidentally adaptive in a new environment. This favorable conjunction of characteristics and suitable environment is considered an important factor in progressive evolution (opportunistic evolution).

[M]  1911: Funk, Casimer. Vitamin hypothesis.

Vitamin deficiency diseases are those in which effects can be definitely traced to the lack of some essential constituent of the diet. Thus beriberi is caused by an insufficient amount of thiamine, scurvy by a lack of vitamin C, and so on.

[D]  1911: Harvey, E.B. Cortical changes in eggs during fertilization.

In a mature egg, cortical granules gather near the egg surface, but on activation of the egg these granules, beginning at the point of sperm contact, disappear in a wavelike manner around the egg. These granules release material during their breakdown that helps form the ensuing fertilization membrane.

[C]  1911: Rutherford, Ernest. Concept of atomic nuclei.

This cornerstone of modern physics must be of equal interest to biologists in light of rapid advances in molecular biology. Rutherford also discovered (1920) protons, one of the charged particles in the atomic nucleus.

Nobel Laureate (1908).

[E]  1911: Walcott, Charles D. Discovery of Burgess shale fossils.

Discovery of a great assemblage of beautifully preserved invertebrates in the Burgess shale of British Columbia and their careful study by an American paleontologist represent a landmark in knowledge of the fossil record of invertebrates. These fossils date from the middle Cambrian age and include the striking Aysheaia, which resembles the extant Peripatus.

[O][D]  1912: Gudernatsch, J.F. Role of the thyroid gland in metamorphosis of frogs.

This investigator found that removal of the thyroid gland of tadpoles prevented metamorphosis into frogs, and also that feeding of thyroid extracts to tadpoles induced precocious metamorphosis. In 1919 W.W. Swingle showed that presence and absence of inorganic iodine would produce the same results.

[T]  1912: Wegener, Alfred L. Concept of continental drift.

This hypothesis postulates that the continents were originally joined together in one or two large masses that gradually broke up during geological time, and the fragments drifted apart to form the current landmasses. Though discounted for nearly 50 years, the theory has been amply supported by surveys of paleomagnetism, seismographic studies, tectonic plate studies, and a wealth of biological evidence, for example, the finding of amphibian fossils in Antarctic regions.

[C]  1913: Michaelis, L., and M. Menten. Enzyme-substrate complex.

On theoretical and mathematical grounds these investigators showed that an enzyme forms an intermediate compound with its substrate (enzyme-substrate complex) that subsequently decomposes to release the free enzyme and reaction products. D. Keilin of Cambridge University and B. Chance of the University of Pennsylvania later demonstrated the presence of such a complex by color changes and measurements of its rate of formation and breakdown that agree with theoretical predictions.

[E]  1913: Reck, H. Discovery of Olduvai Gorge fossil deposits.

This region in East Africa has yielded an immense number of early mammalian fossils as well as tools of Stone Age humans, such as stone axes. Among the interesting fossils discovered were elephants with lower jaw tusks, horses with three toes, an odd ungulate (chalicothere) with claws on the toes, and, more recently, several hominid fossils (see Leakey, Mary D., 1959).

[T]  1913: Shelford, Victor E. Law of ecological tolerance.

This law states that potential success of an organism in a specific environment depends on how it can adjust within the range of its toleration to the various factors to which the organism is exposed.

[G]  1913: Sturtevant, A.H. Formation of first chromosome map.

By the method of crossover percentages, it has been possible to locate genes in their relative positions on chromosomes-one of the most fruitful discoveries in genetics, for it led to extensive mapping of chromosomes in Drosophila.

[O]  1913: Tashiro, Shiro. Metabolic activity of propagated nerve impulse.

Detection of slight increases in carbon dioxide production in stimulated nerves, as compared with inactive ones, was evidence that conduction in nerves is a chemical change. Later (1926), A.V. Hill was able to measure heat given off during the passage of an impulse. Increased oxygen consumption and other metabolic changes have also been measured in excited nerves.

[O]  1914: Kendall, Edward C. Isolation of thyroxine.

Isolation of thyroxine in crystalline form was a landmark in endocrinology. It was artificially synthesized by Harington in 1927.

[D]  1914: Lillie, Frank R. Role of fertilizin in fertilization.

According to this hypothesis, the jelly coat of eggs contains a substance, fertilizin, now known to be an acid mucopolysaccharide, which combines with antifertilizin on the surface of sperm and causes sperm to clump together.

[G]  1914: Shull, George H. Concept of heterosis.

When two standardized strains or races are crossed, the resulting hybrid generation may be noticeably superior to both parents as shown by greater vigor, vitality, and resistance to unfavorable environmental conditions. First worked out in corn (maize), such hybrid vigor may also be manifested by other kinds of hybrids. Although its exact nature is still obscure, the phenomenon may be caused by the bringing together in the hybrid of many dominant genes of growth and vigor that were scattered among the two inbred parents, or it may be caused by the complementary reinforcing action of genes when brought together.

[G]  1916: Bridges, Calvin B. Discovery of nondisjunction.

Bridges explained an aberrant genetic result by a suggested formula that later he was able to confirm by cytological examination. A pair of chromosomes failed to disjoin at the reduction division so that both chromosomes passed into the same cell. It was definite proof that genes are located on chromosomes.

[T]  1917: Grinnell, Joseph. Concept of the ecological niche.

A niche is the role of an animal in relation to all of the resources in its environment, both physical and biological. C. Elton has done much to develop the concept.

[O]  1918: Krogh, August. Regulation of the motor mechanism of capillaries.

The mechanism of differential distribution of blood to various tissues has posed many problems from the days of Harvey and Malpighi, but Krogh showed that capillaries were not merely passive in this distribution but that they had the power to contract or dilate actively, according to the needs of tissues. Both nervous and chemical controls are involved.

Nobel Laureate (1920).

[T]  1918: Loeb, Jacques. Forced movements, tropisms, and animal conduct.

Regarded as the founder of a mechanist "school," Loeb opposed the generally anthropomorphic and teleological interpretation of animal behavior. While Loeb carried his mechanistic doctrine to an extreme, he did inspire more rigorous, experimental approaches in animal behavior studies.

[O]  1918: Starling, Ernest H. Law of the heart.

Within physiological limits, the more ventricles are filled with incoming blood, the greater is the force of their contraction at systole. This is an adaptive mechanism for supplying more blood to tissues when it is needed. It is now recognized that this effect varies among vertebrates; intact hearts of mammals are regulated principally by nervous and hormonal controls.

1919: Aston, Francis W. Discovery of isotopes.

Radioactive isotopes have proved of the utmost value in biological research
because they make it possible to trace the course of various elements in living

Nobel Laureate (1922).

[C]  1920: Herzog, R.O., and W. Jancke. Development of x-ray diffractometry.

When a parallel beam of x-rays is passed through crystallized biological material, the rays are spread and an image of the diffracted pattern is recorded (by rings, spots, and the like). By measurements and mathematical calculations information about structure can be obtained.

[C]  1921: Hopkins, Frederick G. Isolation of glutathione.

The discovery of this sulfur-containing compound gave a great impetus to study of the complicated nature of cellular oxidation and metabolism.

Nobel Laureate (1929).

[O]  1921: Langley, John N. Concept of a functional autonomic nervous system.

Langley's concept of functional aspects of the autonomic system dealt mainly with the mammalian type, but fundamental principles of the system have been applied with modification to other groups as well. Two divisions-sympathetic and parasympathetic-are recognized in functional interpretation of excitation and inhibition in the antagonistic nature of the two divisions.

[O]  1921: Loewi, Otto, and H.H. Dale. Isolation of acetylcholine.

This key demonstration led to the neurohumoral concept of transmission of nerve impulses to muscles.

Nobel Laureates (1936).

[O]  1921: Richards, A.N. Collection and analysis of glomerular filtrate in

This experiment was direct evidence of the role of glomeruli as mechanical filters of cell-free and protein-free fluid from the blood and was striking confirmation of the Ludwig-Cushny theory of kidney excretion.

[D]  1921: Spemann, Hans. Organizer concept in embryology.

Certain parts of developing embryos known as organizers induce specific developmental patterns in responding tissue. While many aspects of induction remain obscure, Spemann's work was important in showing that development is a sequence of programmed stages and that each stage is necessary for the next.

Nobel Laureate (1935).

[M][O]  1921, 1922: Banting, Frederick, C.H. Best, and J.J.R. Macleod. Extraction of insulin.

The great success of this hormone in relieving a distressful disease, diabetes mellitus, and the dramatic way in which active extracts were obtained have made isolation of this hormone the best known in the field of endocrinology.

Banting and Macleod, Nobel Laureates (1923).

[O]  1922: Erlanger, Joseph, and H.S. Gasser. Differential conduction of nerve impulses.

By using a cathode-ray oscillograph, these investigators found that there were several different types of mammalian nerve fibers that could be distinguished structurally and that had different rates of conducting nervous impulses according to the thickness of the nerve sheaths (most rapid in the thicker ones).

Nobel Laureates (1944).

[O]  1922: Kopec , S. Concept of neurosecretory systems.

This concept emerged from the work of many investigators. R. Cajalin (1899) discovered that nerve fibers to the neurohypophysis are extensions of neurons of hypothalamus. Kopec found that the substance responsible for metamorphosis in larvae of moths originated in the brain where certain cerebral ganglia served as glands of internal secretion. Kopec 's pioneering studies were largely ignored
by vertebrate endocrinologists until the 1950s, when through the studies of B. Scharrer, E. Scharrer, B. Hanström, G.W. Harris, and others it was recognized that vertebrates possess a neurosecretory system (hypothalamo-hypophyseal) analogous to invertebrate systems.

[T]  1922: Schjelderup-Ebbe, T. Social dominance-subordinance hierarchies.

This observer found certain types of social hierarchies among birds in which higher-ranking individuals could peck those of lower rank without being pecked in return. Those of the first rank dominated those of the second rank, who dominated those of the third, and so on. Such an organization, once formed, may be permanent.

[T]  1922: Schmidt, Johann. Life history of freshwater eels.

The long, patient work of this oceanographer in solving the mystery of eel migration from freshwater streams of Europe to their spawning grounds in the Sargasso Sea near Bermuda represents one of the most romantic achievements in natural history.

[C]  1923: de Hevesy, George. First isotopic tracer method.

Tracer methodology has proved especially useful in biochemistry and physiology. For instance, it has been possible by the use of these labeled units to determine the fate of a particular molecule in all steps of a metabolic process and the nature of many enzymatic reactions. Exact locations of many elements in the body have been traced by this method.

Nobel Laureate (1943).

[C]  1923: Warburg, Otto. Manometric methods for studying metabolism of living cells.

The Warburg apparatus has been useful in measuring gas exchange and other metabolic processes of living tissues. It proved of great value in studies of enzymatic reactions in living systems and was a standard tool in many biochemical laboratories for many years.

Nobel Laureate (1931).

[O]  1924: Cleveland, L.R. Mutualistic relationships between termites and intestinal flagellates.

This study was made on one of the most remarkable examples of mutualism known among animals. Equally important were the observations this investigator and others made of mutualism between the wood-roach (Cryptocercus) and its intestinal protozoa.

[O]  1924: Houssay, Bernardo A. Role of the pituitary gland in regulation of carbohydrate metabolism.

This investigator showed that, when a dog had been made diabetic by pancreatectomy, the resulting hyperglycemia and glucosuria could be abolished by removing the anterior pituitary gland.

Nobel Laureate (1947).

[E]  1925: Dart, Raymond. Discovery of Australopithecus africanus.

This important fossil, once referred to as the "missing link," bore many human characteristics but had a brain capacity only about one third that of humans. Most authorities place this hominid on or near the main branch of human ancestry.

[C]  1925: Mast, S.O. Nature of ameboid movement.

By studying the reversible sol-gel transformation in protoplasm of an ameba, Mast not only gave a logical interpretation of ameboid movement but also initiated many fruitful concepts about the contractile nature of cytoplasmic gel systems, such as the furrowing movements (cytokinesis) in cell divisions.

[M][O]  1925: Minot, G.R., M.W.P. Murphy, and G.H. Whipple. Liver treatment of pernicious anemia.

These investigators discovered that feeding raw liver to patients with pernicious anemia (a serious blood disorder) had a pronounced effect on their treatment. Much later investigation by numerous workers has led to understanding of antipernicious factor, vitamin B12, whose chemical name is cyanocobalamin. This complex vitamin contains, among other components, porphyrin that has a cobalt atom instead of iron or magnesium at its center.

Nobel Laureate (1934).

[T]  1925: Rowan, William. Photoperiodism hypothesis of bird migration.

Rowan demonstrated that birds subjected to artificially increased day length in winter increased the size of their gonads and showed a striking tendency to migrate out of season. Other workers, stimulated by Rowan's experiments, showed that naturally increasing day length in spring acts through the brain neurosecretory system to set in motion the migratory disposition in birds.

[C]  1926: Sumner, James B. Isolation of enzyme urease.

Isolation of the first enzyme in crystalline form was a key discovery and was followed by others that have helped unravel the complex nature of these important biological substances.

Nobel Laureate (1946).

[O]  1927: Bozler, E. Analysis of nerve net components.

Bozler's demonstration that nerve nets of cnidarians were made up of separate cells and contained synaptic junctions resolved the old problem of whether or not the plexus in this group of animals was an actual network.

[O]  1927: Eggleton, P., G.P. Eggleton, C.H. Fiske, and Y. Subbarow. Role of phosphagen (phosphocreatine) in muscular contraction.

Demonstration that phosphagen is broken down during muscular contraction and then is resynthesized during recovery gave an entirely new concept of the initial energy necessary for the contraction process. Confirmation of this discovery received a great impetus from the discovery of E. Lungsgaard (1930) that muscles poisoned with monoiodoacetic acid, which inhibits production of lactic acid from glycogen, would still contract and that the amount of phosphocreatine broken down was proportional to energy liberated. It is now known that phosphocreatine is a high-energy phosphate storage compound, readily donating its phosphate group to ADP to form ATP.

[O]  1927: Heymans, Corneille. Role of carotid and aortic reflexes in respiratory control.

The carotid sinus and aortic areas contain pressoreceptors and chemoreceptors, the former responding to mechanical stimulation, such as blood pressure, and the latter to oxygen lack. When pressoreceptors are stimulated, respiration is inhibited; when chemoreceptors are stimulated, respiratory rate increases. (A much more potent stimulator of respiration, however, is the effect of carbon dioxide on the respiratory center of the brain.)

Nobel Laureate (1938).

[G]  1927: Muller, Hermann J. Artificial induction of mutations.

By subjecting fruit flies (Drosophila) to mild doses of x-rays, Muller found that the rate of mutation could be increased 150 times over the normal rate.

Nobel Laureate (1946).

[E]  1927: Stensiö, E.A. Appraisal of cephalaspid (ostracoderm) fish fossil.

The replacement of amphioxus as a prototype of vertebrate ancestry by the ammocoete lamprey larva has to a great extent been a result of this careful fossil reconstruction. It is generally believed that living Agnatha (lampreys and hagfishes) and these ancient forms are descended from the same common ancestor.

[E]  1928: Garstang, Walter. Hypothesis of ascidian ancestry of chordates.

According to this hypothesis, primitive chordates were sessile, filter-feeding marine organisms very similar to present-day ascidians. The actively swimming prevertebrate was considered a later stage in chordate evolution. The tadpole ascidian larva, with its basic organization of a vertebrate, had evolved within the group by progressive evolution and by neoteny became sexually mature, ceased to metamorphose into a sessile, mature ascidian, and became the ancestral vertebrate.

[G][C]  1928: Griffith, F. Discovery of the transforming principle (DNA) in bacteria (genetic transduction).

By injecting living nonencapsulated bacteria and dead encapsulated bacteria into mice, it was found that the former acquired the ability to grow a capsule and that this ability was transmitted to succeeding generations. This active agent or transforming principle was isolated from the encapsulated type by other workers later and was found to consist of DNA.

F. Sanfelice (1893) had actually found the same principle when he discovered that nonpathogenic bacilli grown in a culture medium containing metabolic products of true tetanus bacilli would also produce toxins and would do so for many generations.

[C][O]  1928: Weiland, H., and A. Windaus. Structure of the cholesterol molecule.

Sterol chemistry has been a focal point in investigation of such biological products as vitamins, sex hormones, and cortisone. Cholesterol is the precursor of bile acids and steroid hormones in animals.

Nobel Laureates (1927, 1928).

[O]  1929: Berger, Hans. Demonstration of brain waves.

The science of electroencephalography, or electrical recording of brain activity, has revealed much about both the healthy and diseased brain.

[O]  1929: Butenandt, A., and E.A. Doisy. Isolation of estrone.

This discovery was the first isolation of a sex hormone and was arrived at independently by these two investigators. Estrone was found to be the urinary and transformed product of estradiol, the actual hormone. The male hormone testosterone was synthesized by Butenandt and L. Ruzicka in 1931. The second female hormone, progesterone, was isolated from corpora lutea of sow ovaries in 1934.

Doisy, Nobel Laureate (1943).

[M]  1929: Fleming, Alexander. Discovery of penicillin.

The chance discovery of this drug from molds and its development by H. Florey a few years later gave us the first of a notable line of antibiotics that have revolutionized medicine.

Nobel Laureate (1945).

[O]  1929: Heymans, Corneille. Discovery of the role of the carotid sinus and bodies in regulating the respiratory center and arterial blood pressure.

Heymans found that the carotid sinus contains pressure-sensitive receptors (baroreceptors) that, acting through a nervous reflex to the medulla, help to keep blood pressure stabilized. He also discovered oxygen-sensitive chemoreceptors in the carotid and aortic bodies. These are the origin of a reflex that responds to a drop in blood oxygen tension by increasing respiratory rate and blood pressure.

Nobel Laureate (1938).

[C]  1929: Lohmann, K., C. Fiske, and Y. Subbarow. Discovery of ATP.

Discovery of ATP (adenosine triphosphate) was the culmination of a long search for the direct source of energy in biochemical reactions of many varieties, such as muscular contraction, vitamin action, and many enzymatic systems.

[E]  1930: Fisher R.A. Statistical analysis of evolutionary variations.

With Sewall Wright and J.B.S. Haldane, Fisher analyzed mathematically the interrelationships of the factors of mutation rates, population sizes, selection values, and others in the evolutionary process. Although many of their theories are in the empirical stage, evolutionists in general agree that they have great significance in evolutionary interpretation.

[G]  1931: Stern, C., H. Creighton, and B. McClintock. Cytological demonstration of crossing over.

Proof that crossing over in genes is correlated with exchange of material by homologous chromosomes was independently obtained by Stern in Drosophila and by Creighton and McClintock in corn. By using crosses of strains that had homologous chromosomes distinguishable individually, they definitely demonstrated cytologically that genetic crossing over was accompanied by chromosomal exchange.

[O][T]  1932: Bethe, A. Concept of ectohormones (pheromones).

An organism secretes these substances out of the body, where they affect the physiology or behavior of another individual of the same species. They have been demonstrated in insects, where they may function in trail making, sex attraction, development control, and the like.

[E]  1932: Danish scientific expedition. Discovery of fossil amphibians (ichthyostegids).

These fossils were found in the upper Devonian sediments in eastern Greenland and appear to be intermediate between lobe-finned rhipidistians (Osteolepis) and early amphibians. They are among the oldest known tetrapods that can be considered amphibians. Many of their characters show primitive amphibian conditions.

[E]  1932: Lewis, G. Edward. Discovery of Ramapithecus fossil.

Ramapithecus brevirostris was a small humanlike ape of the Miocene and the earliest known hominid. Since Lewis's initial find in India, other fossil fragments of the genus have been discovered in East Africa, Greece, Turkey, and Hungary.

[E][G]  1932: Wright, Sewall. Genetic drift as a factor in evolution.

In small populations the Hardy-Weinberg formula of gene frequency may not apply because of "sampling error." If some genotypes are by chance underrepresented in matings in a small population, gene frequencies in the population may change.

[O]  1933: Goldblatt, M., and U.S. von Euler. Discovery of prostaglandins.

These compounds derived from fatty acids have been isolated from many mammalian tissues (such as seminal plasma, pancreas, seminal vesicle, brain, and kidney). They have a variety of hormonelike and pharmacological actions, such as stimulating smooth muscle contractions and relaxation, lowering blood pressure, and inhibiting enzymes and hormones.

[E]  1933, 1938: Haldane, John B.S., and A.I. Oparin. Heterotroph hypothesis of the origin of life.

This hypothesis is based on the idea that life was generated from nonliving matter under conditions that existed before appearance of life and that have not been duplicated since. The hypothesis stresses the idea that living systems at present make it impossible for any incipient life to gain a foothold as primordial life was able to do.

[G]  1933: Painter, T.S., E. Heitz, and H. Bauer. Rediscovery of giant salivary chromosomes.

These interesting chromosomes were first described by Balbiani in 1881, but their true significance was not realized until these investigators rediscovered them. It has been possible in a large measure to establish the chromosome theory of inheritance by comparing actual cytological chromosome maps of salivary chromosomes with linkage maps obtained by genetic experimentation.

[O]  1933: Wald, George. Discovery of vitamin A in the retina.

Discovery that vitamin A is a part of the visual purple molecule of rods not only gave a better understanding of an important vitamin but also showed how night blindness can occur when there is a deficiency of this vitamin in the diet.

Nobel Laureate (1967).

[O]  1934: Dam, Carl P.H., and E.A. Doisy. Identification of vitamin K.

Isolation and synthesis of this vitamin are important not merely because of the vitamin's practical value in certain forms of hemorrhage but also because of the light they throw on the physiological mechanism of blood clotting.

Nobel Laureate (1943).

[C]  1934-1935: Danielli, J.F., and H. Davson. Concept of the cell (plasma) membrane.

Danielli proposed a hypothesis that cell membranes consist of two layers of lipid molecules surrounded on the inner and outer surfaces by a layer of protein molecules. Electron microscopy reveals the plasma membrane of a thickness of 7.5 to 10 nm, consisting of two dark (protein) membranes (2.5 to 3 nm thick) separated by a light (lipid) interval membrane of 2.5 to 3 nm thickness. Recent studies confirm the Danielli-Davson model, while demonstrating a greater dynamic role for the peripheral proteins.

[O]  1934: Wigglesworth, V.B. Role of corpora allata glands in insect metamorphosis.

These small glands lie close to the brain of an insect, and it has been shown that during larval stages these gland secrete a juvenile hormone that causes larval characteristics to be retained. Metamorphosis and maturation occur as the glands secrete less and less juvenile hormone. Removal of the glands causes the larva to undergo precocious metamorphosis; grafting the glands into a mature larva will cause the latter to grow into a giant larval form. The glands were first described by A. Nabert in 1913.

[O]  1935: Hanstöm, B. Discovery of the X-organ in crustaceans.

This organ, together with the related sinus gland, constitutes an anatomical complex that has proved of great interest in understanding crustacean endocrinology. Neurosecretory cells in the X-organ (part of the brain) produce a molt-inhibiting hormone that is stored in the sinus gland of the eyestalk, while a molting hormone is produced in the Y-organ. Interrelations of these two hormones control the molting process.

[O]  1935-1936: Kendall, Edward C., and P.S. Hench. Discovery of cortisone.

Kendall had first isolated this substance, which he called compound E, from adrenal glands. Its final stages were prepared by Hench later and involved a long tedious chemical process. A hormone that controls synthesis and release of cortisone and similar steroids was
isolated in 1943 from the pituitary and was called adrenocorticotropic hormone (ACTH).

Nobel Laureates (1950).

[C]  1935: Stanley, Wendell M. Isolation of a virus in crystalline form.

This achievement of isolating a virus (tobacco mosaic) is noteworthy not only in giving information about these small agents responsible for many diseases but also in affording much speculation on the differences between living and nonliving entities.

Nobel Laureate (1946).

[O]  1936: Young, J.Z. Demonstration of giant fibers in squid.

These giant fibers are formed by fusion of axons of many neurons whose cell bodies are found in a ganglion near the head. Each fiber is really a tube, up to 1 mm in diameter, consisting of an external sheath filled with liquid axoplasm. Because of their size, they have been a very valuable system in neurophysiology.

[C]  1937: Findley, G.W.M., and F.O. MacCullum. Discovery of interferon.

These protein substances, produced by cells in response to viruses and other foreign substances, selectively inhibit virus replication and are one of the body's important defenses against viral infection. Interferon is an important cytokine in the TH-1 arm of the immune response.

[C]  1937: Krebs, Hans A. Krebs cycle (citric acid cycle tricarboxylic acid cycle).

In a brilliant example of reasoning and deduction, Krebs showed the existence of a cycle of reactions central to aerobic energy production. In the cycle, two carbon fragments from carbohydrate, fatty acids, or amino acids are oxidized to carbon dioxide. Electrons derived from oxidation reactions in the cycle are passed through a further series of reactions (electron transport system), in which energy is captured in ATP, and finally to oxygen as the final electron acceptor to produce water.

Nobel Laureate (1953).

[C][O]  1937: König, P., and A. Tiselius. Development of electrophoresis.

Electrophoresis is an extremely valuable method of separating proteins in a solution and, after numerous refinements, is currently in wide use. It depends on the differential migration of proteins on an inert carrier when an electrical field is applied.

[T]  1938: Remane, A. Discovery of the new phylum Gnathostomulida.

This marine phylum was first described by P. Ax in 1956. Members of the phylum are small wormlike forms (about 0.5 mm long) and show great diversity among different species. One of their major characteristics is their complicated jaws provided with teeth. They live in sandy substrata and are worldwide in distribution.

[O]  1938: Schoenheimer, R. Use of radioactive isotopes to demonstrate synthesis of bodily constituents.

By labeling amino acids, fats, carbohydrates, and the like with radioactive isotopes, it was possible to show how these were incorporated into the various constituents of the body. Such experiments demonstrated that parts of cells were constantly being synthesized and broken down and that an animal's body must be considered a dynamic equilibrium.

[T]  1938: Skinner, B.F. Measurement of motivation in animal behavior.

Skinner worked out a technique for measuring the rewarding effect of a stimulus, or effects of learning on voluntary behavior. His experimental animals (rats) were placed in a special box (Skinner's box) containing a lever that the animal could manipulate. When the rat pressed the lever, small pellets of food would or would not be released, according to experimental conditions.

[O][C]  1938: Svedberg, Theodor. Development of ultracentrifuge.

In biological and medical investigation this instrument has been widely used for purification of substances, determination of particle sizes in colloidal systems, relative densities of materials in living cells, production of abnormal development, and study of many problems concerned with electrolytes.

Nobel Laureate (1926).

[O]  1939: Brown, Frank A., Jr., and O. Cunningham. Demonstration of molt-inhibiting hormone in eyestalk of crustaceans.

Although C. Zeleny (1905) and others had shown that eyestalk removal shortened the intermolt period in crustaceans, Brown and Cunningham were first to present evidence to explain the effect as being caused by a molt-inhibiting hormone present in the sinus gland.

[E]  1939: Discovery of coelacanth fishes.

Collection of a living specimen of this ancient fish (Latimeria), followed later by other specimens, has brought about a complete reappraisal of this"living fossil" with reference to its ancestry of amphibians and land forms.

[D]  1939: Hörstadius, S. Analysis of the basic pattern of regulative and mosaic eggs in development.

The masterful work of this investigator has done much to resolve differences in the early development of regulative eggs (in which each of the early blastomeres can give rise to a whole embryo) and mosaic eggs (in which isolated blastomeres produce only fragments of an embryo; also called determinate cleavage).

[E][T]  1939: Huxley, Julian. Concept of the cline in evolutionary variation.

This concept refers to a gradual and continuous variation in character over an extensive area because of adjustments to changing conditions. This idea of character gradients has proved a very fruitful one in analysis of the mechanism of evolutionary processes, for such a variability helps to explain the initial stages in transformation of species.

[M][G]  1940: Landsteiner, Karl, and A.S. Wiener. Discovery of Rh blood factor.

Not only was a knowledge of the Rh factor of importance in solving a fatal disease of infancy, but it has also yielded a great deal of information about relationships between human races.

Landsteiner, Nobel Laureate (1930).

[C][G]  1941: Beadle, George W., and E.L. Tatum. Biochemical mutation.

By subjecting bread mold (Neurospora) to x-ray irradiation, they found that genes responsible for synthesis of certain vitamins and amino acids were inactivated (mutated) so that a strain of this mold carrying mutant genes could no longer grow unless these particular vitamins and amino acids were added to the medium on which the mold was growing. This discovery-that alterations in various genes resulted in loss of a corresponding biosynthetic enzyme-first revealed the precise way in which genes and enzymes are related.

Nobel Laureates (1958).

[O]  1941: Cori, Carl F., and Gerty T. Cori. Lactic acid metabolic cycle.

The regeneration of muscle glycogen reserves in mammals involves passage of lactic acid from muscles through the blood to the liver, the conversion of lactic acid there to glycogen, production of blood glucose from liver glycogen, and synthesis of muscle glycogen from the blood glucose.

Nobel Laureates (1947).

[C][O]  1941: Martin, A.J.P., and R.L.M. Synge. Development of partition chromatography.

This is a powerful method for separation of chemically similar substances in mixtures. It depends on differential solubility of a compound in stationary and moving phases of solvents. Variants of the method include column, paper, and thin-layer chromatography.

[O]  1941: Szent-Györgyi, Albert. Role of ATP in muscular contraction.

Demonstration that muscles get their energy for contraction from ATP (adenosine triphosphate) has done much to explain many aspects of muscle physiology.

Nobel Laureate (1937).

[D]  1942: McClean, D, and I.M. Rowlands. Discovery of the enzyme hyaluronidase in mammalian sperm.

This enzyme dissolves the cement substance of follicle cells that surround mammalian eggs and facilitates passage of sperm to eggs. This discovery not only aided in resolving some difficult problems of the fertilization process but also offers a logical explanation of cases of infertility in which too few sperm may not carry enough of the enzyme to afford a passage through the inhibiting follicle cells.

[C]  1943: Claude, A. Isolation of cell constituents.

By differential centrifugation, Claude found it possible to separate, in relatively pure form, particulate components, such as mitochondria, microsomes, and nuclei. These investigations led immediately to a more precise knowledge of the chemical nature of these cell constituents and aided elucidation of the structure and physiology of the mitochondria-one of the great triumphs in the biochemistry of cells.

Nobel Laureate (1974).

[D]  1943: Holtfreter, J. Tissue synthesis from dissociated cells.

By dissociating cells of embryonic tissues of amphibians (by dissolving with enzymes or other agents the intercellular cement that holds the cells together) and heaping them in a mass, he found that the cells in time coalesced and formed the type of tissue from which they had come. This is an application to vertebrates of Wilson's discovery with sponge cells. It showed that, by some mechanism, cells could recognize other cells of the same type.

[C][G]  1944: Avery, O.T.C., C.M. MacLeod, and M. McCarty. Agent responsible for bacterial transformation.

These workers were able to show that the bacterial transformation of nonencapsulated bacteria to encapsulated cells was really attributable to the DNA fraction of debris from disrupted encapsulated cells to which nonencapsulated cells were exposed. This key demonstration showed for the first time that nucleic acids and not proteins were the basic material of heredity, and initiated the study of molecular genetics. However, the profound significance of Avery's conclusions was only gradually recognized.

[C]  1945: Cori, Carl F. Hormone influence on enzyme activity.

The delicate balance that insulin and the diabetogenic hormone of the pitui-
tary exercise over activity of the enzyme hexokinase in carbohydrate metabolism has opened up a whole new field of the regulative action of hormones on enzymes.

Nobel Laureate (1947).

[T]  1945: Griffin, D., and R. Galambos. Development of the concept of echolocation.

Echolocation refers to a type of perception of objects at a distance by which echoes of sound are reflected back from obstacles and detected acoustically. These investigators found that bats generated their own ultrasonic sounds that were reflected back to their own ears so that they were able to avoid obstacles in their flight without the aid of vision. Their work climaxed an interesting series of experiments inaugurated as early as 1793 by Spallanzani, who believed that bats avoided obstacles in the dark by reflection of sound waves to their ears. Others who laid the groundwork for the novel concept were C. Jurine (1794), who proved that ears were the all-important organs in perception; H.S. Maxin (1912), who advanced the idea that the bat made use of low-frequency sounds inaudible to human ears; and H. Hartridge (1920), who proposed the hypothesis that bats emitted sounds of high frequencies and short wavelengths (ultrasonic sounds).

[C]  1945: Lipmann, Fritz A. Discovery of coenzyme A.

Discovery of this important coenzyme made possible a better understanding of catabolism of fatty acid chains and furnished important further knowledge of reactions in the tricarboxylic acid cycle.

[C]  1945: Porter, Keith R. Description of the endoplasmic reticulum.

The endoplasmic reticulum is a very complex cytoplasmic structure consisting of a lacelike network of irregular anastomosing tubules and vesicular expansions within the cytoplasmic matrix. Associated with the reticulum complex are small, dense granules of ribonucleoprotein and other granules known as microsomes that are fragments of the endoplasmic reticulum. The reticulum complex plays an important role in the synthesis of proteins.

[G]  1946: Lederberg, J., and E.L. Tatum. Sexual recombination in bacteria.

These investigators found that two different strains of bacteria (Escherichia coli) could undergo conjugation and exchange genetic material, thereby producing a hereditary strain with characteristics of the two parent strains. W. Hayes (1952) found that recombination still occurred after one parent strain was killed.

Nobel Laureates (1958).

[E]  1946: Libby, Willard F. Radiocarbon dating of fossils.

Radiocarbon age determination is based on the fact that carbon 14 in the dead organism disintegrates at the rate of one half in 5560 years, one half of the remainder in the next 5560 years, and so on. Age can be estimated if one assumes that the isotope is mixed equally through all living matter and that cosmic rays (which form the isotopes) have not varied much in periods of many thousands of years. Maximum age for carbon dating is around 40,000 years.

Nobel Laureate (1960).

[E]  1946: White, E.I. Discovery of the primitive chordate fossil Jaymoytius.

The discovery of this fossil in deposits of Silurian rock in Scotland threw some light on the early ancestry of vertebrates, specifically the origin of living Agnatha (hag fishes and lampreys). Other anapsid fossils found more recently, such as Mayomyzon, are strikingly similar to the living lampreys.

[O]  1947: Holtz, P. Discovery of norepinephrine (noradrenaline).

This hormone (vasoconstriction effects) has since been found in most vertebrates and shares with epinephrine (metabolic effects) the functions of the chromaffin part of the adrenal gland.

[E]  1947: Sprigg, R.C. Discovery of Precambrian Ediacara fossil bed.

Discovery of a rich deposit of Precambrian fossils in the Ediacara Hills of South Australia has been of particular interest because scarcity of such fossils in the past has given rise to vague and uncertain explanations about Precambrian life. It was all the more remarkable that the fossils discovered were those of soft-bodied forms, such as jellyfish, soft corals, and segmented worms, including the amazing Spriggina, which shows relationship to trilobites. The fossils are prearthropod but not preannelid.

[C]  1947: Szent-Györgyi, Albert. Concept of the contractile substance actinomyosin.

This protein complex consists of two components, actin and myosin, and is considered the source of muscular contraction when triggered by ATP. Neither actin nor myosin will contract alone.

Nobel Laureate (1937).

[G]  1947: McClintock, Barbara. Concept of mobile genetic elements.

Studying patterns of certain mutations in maize, McClintock deduced that they must be caused by movement of genetic elements ("jumping genes") within the genome. Her observations were ignored or discounted for years until mobile genetic elements were discovered in bacteria in the 1960s, then in many kinds of eukaryotes in the 1970s. We now know that transposable genes help to account for the huge diversity of antibodies in vertebrates.

Nobel Laureate (1983).

[T]  1948: von Frisch, Karl. Communication mechanisms of honey bees.

After many years of patient work, von Frisch deciphered the meaning of bee "dances," behavior patterns of individual bees returning to the hive. Dances communicate information to other bees regarding location of food and water, location and suitability of sites for a new hive, and other information.

Nobel Laureate (1973).

[T]  1948: Hess, Walter R. Localization of instinctive impulse patterns in the brain.

By inserting electrodes through the skull, fixing them in position, and allowing such holders to heal in place, it was possible to study the brain of an animal in its ordinary activities. When a rat could
automatically and at will stimulate itself by pressing a lever, it did so frequently when the electrode was inserted in the hypothalamus region of the brain, indicating a pleasure center. In this way, by placing electrodes at different centers, rats can be made to gratify such drives as thirst, sex, and hunger.

Nobel Laureate (1949).

[C]  1948: Hogeboom, G.H., W.C. Schneider, and G.E. Palade. Separation of mitochondria from the cell.

This was an important discovery in unraveling the amazing enzymatic activity of mitochondria in the tricarboxylic acid cycle. The role mitochondria play in the energy transfer of cells has earned for these rod-shaped bodies the appellation"powerhouse" of the cell.

Palade, Nobel Laureate (1974).

[C]  1949: de Duve, C. Discovery of lysosomes.

These small particles were first identified chemically, and later (1955) morphologically by electron microscopy. They contain enzymes for digestion of materials taken into cells by pinocytosis and phagocytosis and for digestion of a cell's own cytoplasm. When a cell dies, their enzymes are also released and digest the cell (autolysis).

Nobel Laureate (1974).

[M]  1949: Enders, J.F., F.C. Robbins, and T.H. Weller. Cell culture of animal viruses.

These investigators found that poliomyelitis virus could be grown in ordinary tissue cultures of nonnervous tissue instead of being restricted to host systems of laboratory animals or embryonated chick eggs.

Nobel Laureates (1954).

[O]  1949: von Euler, U.S. Role of norepinephrine as transmitter.

Von Euler isolated and identified norepinephrine as the neurotransmitter in the sympathetic nervous system (1940). Later he isolated and characterized norepinephrine storage granules in nerves and described how the substance was taken up, stored, and released by them.

Nobel Laureate (1970).

[G]  1949: Pauling, Linus. Genic control of protein structure.

Pauling and his colleagues demonstrated a direct connection between specific chemical differences in protein molecules and alterations in genotypes. Making use of hemoglobin of patients with sickle cell anemia (which is caused by a homozygous condition of an abnormal gene), Pauling was able to show an electrophoretic difference between this hemoglobin compared with that from a heterozygote or from a normal person.

Nobel Laureate (1954).

[O]  1949: Selye, Hans. Concept of a stress syndrome.

In 1937 Selye began his experiments, which led to what he called the "general adaptation syndrome." This involved chain reactions of many hormones, such as cortisone and ACTH, in meeting stress conditions faced by an organism. Whenever stress experience exceeds the limitations of these body defenses, serious degenerative disorders may result.

[C]  1950: Caspersson, T., and J. Brachet. Biosynthesis of proteins.

Investigations to solve the vital problem of protein synthesis from free amino acids have been under way since Emil Fischer's (1887) outstanding work on protein structure. Many competent research workers, such as Bergmann, Lipmann, and Schoenheimer, made contributions to an understanding of protein synthesis, but Caspersson and Brachet were the first to discover the significant role of ribonucleic acid (RNA) in the process-and most biochemical investigations of the problem since that time have been directed along this line.

[C]  1950: Chargaff, Erwin. Base composition of DNA.

Discovery that the amount of purines was equal to the amount of pyrimidines in DNA, the amount of adenine was equal to that of thymine, and the amount of cytosine was equal to that of guanine paved the way for the DNA model of Watson and Crick. The two major functions of DNA are replication and hereditary information storage.

[T]  1950: Lorenz, Konrad. Development of ethology.

Lorenz is regarded as founder of ethology, a biological approach to analyzing behavior, emphasizing a comparative method and stressing innate factors in behavior development. His classic studies on greylag geese first came to the attention of English-speaking scientists during the 1950s, though the work itself commenced in the 1930s.

Nobel Laureate (1973).

[T]  1950: von Frisch, Karl. Discovery of polarized light perception by honey bees.

Honey bees are able to detect, and navigate to, polarized sunlight reaching the earth's surface, using specialized retinular cells in a specific but small area of their compound eyes. Subsequently it has been found that some crustaceans, cephalopod molluscs, and teleost fishes, as well as many other terrestrial arthropods, can orient by polarized light.

[C]  1950s: Fischer, Edmond, and Edwin Krebs. Role of phosphorylation in enzyme activation.

Fischer and Krebs showed that glycogen phosphorylase was activated and inactivated by the reversible addition of a phosphate group. We now know that phosphorylation controls activities of hundreds of enzymes, regulating functions as diverse as hormonal responses, muscle contraction, immune responses, and cell growth and division.

Nobel Laureates (1992).

[M]  1950s-1970s: Elion, Gertrude B., and George H. Hitchings. Design of purine antimetabolites for use in chemotherapy.

Certain analogs of purines can act as antagonists of nucleic acid metabolism in rapidly dividing cells or viruses. This has led to treatments of acute leukemia, gout, herpes-virus infections, and prevention of organ transplant rejection.

Nobel Laureates (1988).

[D]  1950s-1970s: Levi-Montalcini, Rita, and Stanley Cohen. Discovery of
tissue-specific growth factors.

Levi-Montalcini and Cohen discovered and characterized nerve growth factor and epidermal growth factor, which are necessary for growth, development, and maintenance of nerve cells and epidermal cells, respectively. Since then, numerous additional growth factors that
act on many cell types have been discovered. Some oncogenes are derived from genes for growth factors or growth-factor receptors.

Nobel Laureates (1986).

[D]  1952: Briggs, Robert, and Thomas J. King. Demonstration of possible differentiated nuclear genotypes.

The belief that all cells of a particular organism have the same genetic endowment has been questioned as the result of work of these investigators who transplanted nuclei of different ages and sources from blastulas and early gastrulas into enucleated zygotes and observed variable and abnormal development.

[T]  1952: Kramer, G. Orientation of birds to positional changes of sun.

Kramer showed that birds (starlings and pigeons) can be trained to find food in accordance with the position of the sun. He found that general orientation of birds shifted at a rate (when exposed to a constant artificial sun) that could be predicted on the basis of the birds' correcting for the normal rotation of the earth. Birds were able to orient themselves in a definite direction with references to the sun, whether the light of the sun reached them directly or was reflected by mirrors. They were capable also of finding food at any time of day, indicating an ability to compensate for the sun's motion across the sky.

[C]  1952: Palade, G.E. Analysis of the fine structure of the mitochondrion.

The important role of mitochondria in enzymatic systems and cellular metabolism has focused much investigation on the structure of these cytoplasmic inclusions. Each mitochondrion is bounded by two membranes; the outer is smooth and the inner is thrown into small folds or cristae that project into a homogeneous matrix in the interior. Some modifications of this pattern are found.

Nobel Laureate (1974).

[C]  1952: Zinder, N., and J. Lederberg. Discovery of the transduction principle.

Transduction is the transfer of DNA from one bacterial cell to another by means of a phage. It occurs when an infective phage picks up from its disintegrated host a small fragment of the host's DNA and carries it to a new host where it becomes a part of the genetic equipment of the new bacterial cell.

Lederberg, Nobel Laureate (1958).

[G][C]  1953: Crick, Francis H.C., James D. Watson, and Maurice H.F. Wilkins. Chemical structure of DNA.

Based on knowledge of the chemical nature of DNA and studies of x-ray diffraction by Wilkins, Crick and Watson formulated the hypothesis that DNA molecules were made up of two chains twisted around each other in a helical structure with pairs of nitrogenous bases projecting toward each other-adenine opposite thymine and guanine opposite cytosine. Genes are considered segments of these molecules with the sequence of bases coding for amino acids in a protein. Each complementary strand acts as a model or template to form a new strand before cell division. The hypothesis has been widely accepted and is now amply confirmed.

Nobel Laureates (1962).

[C]  1953: Palade, G.D. Description of cytoplasmic ribosomes.

Description of ribonucleic acid-rich granules (usually on the endoplasmic reticulum) represents a key link in unraveling of the mechanism of protein synthesis. Ribosomes (about 25 nm in diameter) serve as the site of protein synthesis; the number of ribosomes (polysomes) involved in synthesis of a protein depends on the length of messenger RNA and the protein being synthesized.

Nobel Laureate (1974).

[E]  1953: Urey, Harold, and Stanley Miller. Demonstration of the possible primordia of life.

By exposing a mixture of water vapor, ammonia, methane, and hydrogen gas to electrical discharge (to simulate lightning) for several days, these investigators found that several complex organic substances, such as the amino acids glycine and alanine, were formed when water vapor was condensed into water. This demonstration offered a very plausible hypothesis to explain how the early beginnings of life substances could have started by the formation of organic substances from inorganic ones.

[O][M]  1953: Sperry, R.W. Independence of brain hemispheric function.

By severing the bundle of nerve fibers separating the two cortical hemispheres, Sperry developed the"split-brain" technique, which he used to show that the two brain halves govern two sets of activities. He also contributed much to developmental neurobiology.

Nobel Laureate (1981).

[C]  1954: Del Castillo, J., and B. Katz. Impulse transmission at nerve junction.

These researchers demonstrated that a chemical transmitter substance is released from presynaptic terminals in discrete multimolecular packets, or quanta, each containing several thousand molecules.

Katz, Nobel Laureate (1970).

[D]  1954: Dan, J.C. Acrosome reaction.

In echinoderms, annelids, and molluscs Dan showed that the acrosome region of a spermatozoon forms a filament and releases an unknown substance at the time of fertilization. Evidence suggests that the filament is associated with the formation of the fertilization cone. Other observers had described similar filaments before Dan made his detailed descriptions. The filament (1 to 75m long) may play an important role in entrance of sperm into cytoplasm.

[O]  1954: Du Vigneaud, V. Synthesis of pituitary hormones.

This investigator isolated the posterior pituitary hormones oxytocin and vasopressin. Both were polypeptides, and oxytocin was the first polypeptide hormone to be produced artificially. Oxytocin stimulates uterine contractions during childbirth and release of the mother's milk; vasopressin raises blood pressure and decreases urine production.

[O]  1954: Huxley, H.E., A.F. Huxley, and J. Hanson. Sliding filament model of muscular contraction.

By means of electron microscopy and x-ray diffraction studies, these investigators showed that actin and myosin were found as separate filaments that apparently produced contraction by a sliding reaction in the presence of ATP. The concept is widely accepted.

A.F. Huxley, Nobel Laureate (1963).

[C]  1954: Sanger, Frederick. Structure of insulin.

Insulin is an important hormone that regulates glucose uptake by cells and is used in the treatment of diabetes. It was the first protein for which a complete amino acid sequence was known. The molecule is made up of 17 different amino acids in 51 amino acid units. Although one of the smallest proteins, its formula contains 777 atoms.

Nobel Laureate (1958).

[C]  1955-1957: Kornberg, Arthur, and S. Ochoa. Synthesis of nucleic acids outside of cells (in vitro).

By mixing the enzyme polymerase, extracted from the bacterium Escherichia coli, with a mixture of nucleotides and a tiny amount of DNA, Kornberg was able to produce synthetic DNA. Ochoa obtained synthesis of RNA in a similar manner by using the enzyme polynucleotide phosphorylase from the bacterium Azotobacter vinelandii. This significant work reveals more insight into the mechanism of nucleic acid replication in cells.

Nobel Laureates (1959).

[D]  1955: Kettlewell, H.B.D. Natural selection in action: industrial melanism in moths.

Using field techniques, Kettlewell was able to demonstrate a selective advantage of dark (melanic) mutations in a barklike cryptic moth species in industrial areas of Great Britain, where tree trunks had been darkened by soot. This demonstration provided an evolutionary explanation for the increasing prevalence of melanism in cryptic moths that was noted throughout industrialized regions of the world and constitutes a classic example of effects of a strong selective pressure.

[O]  1956: von Békésy, Georg. The traveling wave hypothesis of hearing.

Helmholtz (1868) had proposed the resonance hypothesis of hearing on the basis that each cross fiber of the basilar membrane, which increases in width from the base to the apex of the cochlea, resonates at a different frequency; von Békésy showed that a traveling wave of vibration is set up in the basilar membrane and reaches a maximal vibration in the part of the membrane appropriate for that frequency.

Nobel Laureate (1961).

[C]  1956: Borsook, H., and P.C. Zamecnik. Site of protein synthesis.

By injecting radioactive amino acids into an animal, they found that ribosomes of endoplasmic reticulum are the locations where proteins are formed.

[G]  1956: Ingram, V.M. Nature of a mutation.

By tracing a change in one amino acid unit out of more than 300 units that make up the protein hemoglobin, Ingram was able to pinpoint the difference
between normal hemoglobin and the mutant form of hemoglobin that causes sickle cell anemia.

[C]  1956: Sutherland, Earl W., and T.W. Rall. Discovery of cyclic AMP.

An intracellular mediating agent (cyclic adenosine-3, 5-monophosphate, or cyclic AMP) is found in all living tissues, and changes in cyclic AMP levels (by effects of hormones) cause the hormones to produce different target effects depending on the type of cell in which they are found. Cyclic AMP is formed by a metabolic reaction in which the enzyme adenyl cyclase converts ATP to cyclic AMP.

Sutherland, Nobel Laureate (1971).

[G]  1956: Tjio, J.H., and A. Levan. Revision of human chromosome count.

The time-honored number of chromosomes in humans, 48 (diploid), was found by careful cytological technique to be 46 instead.

[C]  1957: Calvin, Melvin. Chemical pathways in photosynthesis.

By using radioactive carbon 14, Calvin and colleagues were able to analyze step by step the incorporation of carbon dioxide and identity of each intermediate product involved in the formation of carbohydrates and proteins by plants.

Nobel Laureate (1961).

[C]  1957: Holley, Robert W. The role of transfer RNA in protein synthesis.

Nucleotides of transfer RNAs differ from each other only in their bases. Holley also devised methods that precisely established the transfer RNAs used in the transfer of certain amino acids to the site of protein synthesis.

Nobel Laureate (1968).

[T]  1957: Ivanov, A.V. Analysis of phylum Pogonophora (beard worms).

Specimens of this phylum were collected in 1900 and represent one of the most recent animal phyla to be discovered and evaluated. They have been collected from waters of Indonesia, Okhotsk Sea, Bering Sea, and Pacific Ocean. They are found mostly in the abyssal depths. Thought originally to be deuterostomes, more recent evidence indicates that they are protostomes. At present 145 species divided into two classes have been described.

[C]  1957: Perutz, Max F., and J.C. Kendrew. Structure of hemoglobin.

Mapping of a complex globular protein molecule of 600 amino acids and 10,000 atoms arranged in a three-dimensional pattern represented one of the great triumphs in biochemistry. Myoglobin of muscle, which acts as a storehouse for oxygen and contains only one heme group instead of four (hemoglobin), was found to contain 150 amino acids.

Nobel Laureates (1962).

[T]  1957: Sauer, E. Celestial navigation by birds.

By subjecting Old World warblers to various synthetic night skies of star settings in a planetarium, Sauer was able to demonstrate that the birds made use of the stars to guide them in their migrations.

[O]  1958: Lerner, A.B. Discovery of melatonin in the pineal glands.

Lerner and associates discovered that production of melatonin in the pineal gland is increased in darkness and decreased in light. Activity of the hormone appears important in regulation of gonadal functions affected by photoperiod, and its discovery represented a breakthrough in understanding function of the pineal gland.

[C]  1958: Meselson, M., and F.W. Stahl. Confirmation "in vivo" of the duplicating mechanism in DNA.

This was really confirmation of the self-copying of DNA in accordance with Watson and Crick's scheme of the structure of DNA. These investigators found that, after producing a culture of bacterial cells labeled with heavy nitrogen 15 and then transferring these bacteria to a cultural medium of light nitrogen 14, the resulting bacteria had a DNA density intermediate between heavy and light, as would be expected on the basis of the Watson-Crick hypothesis.

[O]  1959: Burnet, F. Macfarlane. Clonal selection hypothesis of immunity.

One of the most puzzling aspects of the acquired immune response has been how to account genetically for the ability to generate specific antibodies against the enormous variety of potential antigens. N.K. Jerne suggested that the information necessary to generate antibodies was present in the host before exposure to antigens. Burnet proposed that we have a large variety of antibody-producing cells, each present in such a small number that its product cannot be detected. Upon exposure to a particular antigen, a clone of cells that can make antibody to that antigen is "selected" and multiplies rapidly, thus increasing antibody to a detectable level. A corollary to the theory is that antigens present when the organism is embryonic or very young are recognized as "self," and the immune system does not respond. This was confirmed by P. Medawar.

Burnet and Medawar, Nobel Laureates (1960); Jerne, Nobel Laureate (1984).

[G]  1959: Ford, C.E., P.A. Jacobs, and J.H. Tjio. Chromosomal basis of sex determination in humans.

By discovering that certain genetic defects were associated with an abnormal somatic chromosomal constitution, it was possible to determine that male-determining genes in humans were located on the Y chromosome. Thus a combination of XXY (47 instead of the normal 46 diploid number) produced sterile males (Klinefelter's syndrome), and those with XO combinations (45 diploid number) gave rise to Turner's syndrome or immature females.

[E]  1959: Leakey, Mary D. Discovery of Australopithecus (Zinjanthropus) boisei fossil hominid.

This fossil is a robust form within the small-brained, large-jawed genus Australopithecus, first discovered by Dart (1925). Its status is at present controversial: some believe it is a species distinct from A. africanus, whereas others believe that A. africanus and A. boisei are females and males within a single, polytypic species.

[O]  1959: Butenandt, A.F.J. Chemical identification of a pheromone.

Butenandt and associates chemically analyzed the first pheromone-the sex attractant substance of silk moths (Bombyx mori). Named bombykol, it is a doubly unsaturated fatty alcohol with 16 carbon atoms. The chemical nature of numerous other pheromones has since been determined.

[C][M]  1950s-present: Bennacerraf, B., J. Dausset, and G. Snell. Genetics and function of the major histocompatibility complex (MHC).

This complex of genes codes for cell surface antigens. These antigens are critically important in various interactions between cells, such as self/nonself recognition and in initiation of an immune response.

Nobel Laureates (1980).

Nobel Laureates (1986).

[O]  1959-1960: Yalow, Rosalyn, and S.A. Berson. Development of radioimmunoassay.

Development of this technique made it possible for the first time to measure minute quantities of a hormone directly in a complex mixture of proteins such as serum. A radioactively labeled hormone is mixed with a specific antibody to the hormone, together with a sample of the unknown. Labeled compound competes with unlabeled in formation of the antigen-antibody complex, and the amount of unknown is obtained by comparison with a standard curve prepared with known amounts of unlabeled hormone. The technique was originally described for insulin, but it has been rapidly extended to many other hormones and has revolutionized endocrinology.

Yalow, Nobel Laureate (1977).

[T]  1960: Tinbergen, Niko. Development of the concept of specific searching images in predators.

Tinbergen's studies of songbird predation in Dutch pinewoods helped to lay a foundation for the science of ethology.

Nobel Laureate (1973).

[C]  1960: Hurwitz, J., A. Stevens, and S. Weiss. Enzymatic synthesis of messenger RNA.

The exciting knowledge of the coding system of DNA and its translation to protein synthesis (ribosomes) was further elucidated when it was discovered that an enzyme, RNA polymerase, was responsible for the synthesis of RNA from a template pattern of DNA.

[C]  1960: Jacob, François, and Jacques Monod. The operon hypothesis.

The operon hypothesis is a postulated model of how enzyme synthesis is regulated in prokaryotes. The model proposes that refinement in regulation involves an inducible system for allowing structural genes to synthesize needed enzymes and a repressible system that cuts off the synthesis of unneeded enzymes.

Nobel Laureates (1965).

[C]  1960: Strell, M., and R.B. Woodward. Synthesis of chlorophyll a.

Strell and Woodward with the aid of many co-workers finally solved this problem, which had been the goal of organic chemists for generations.

Woodward, Nobel Laureate (1965).

[M]  1960s: Thomas, E. Donnall, and Joseph Murray. First successful organ and tissue transplants between unrelated donors.

Previously, organ transplantation between donors other than identical twins had been impossible because of immune tissue rejection. Discovery of methods to suppress immune rejection and tissue typing based on major histocompatibility complex (to find suitable donors) vastly increased successful transplantation rates.

Nobel Laureates (1990).

[C]  1960s-1990s: Boyer, P. D., J.E. Walker, and J. C. Skou. Mechanism of ATP synthesis and of one of ATP's most important functions.

Boyer and Walker described the molecular motor in mitochondrial membranes that catalyzes ATP synthesis, and Skou elucidated the mechanism of action of the body's biggest ATP user, the sodium-potassium pump in cell membranes.

Nobel Laureates (1997).

[C]  1961: Hurwitz, J., A. Stevens, and S.B. Weiss. Confirmation of messenger RNA.

Messenger RNA transcribes directly the genetic message of nuclear DNA and moves to the cytoplasm, where it becomes associated with a number of ribosomes or submicroscopic particles containing protein and nonspecific structural RNA. Here messenger RNA molecules serve as templates against which amino acids are arranged in the sequence corresponding to the coded instructions carried by messenger RNA.

[G][C]  1961: Jacob, François, and Jacques Monod. The role of messenger RNA in the genetic code.

Transmission of information from the DNA code in the genes to the ribosomes represents an important step in protein synthesis, and these investigators proposed certain deductions for confirmation of the hypothesis, which in general has been established by many researchers.

Nobel Laureates (1965).

[O]  1961: Miller, J.F.A. Function of the thymus gland.

Long known as a transitory organ that persists during the early growth period of animals, the thymus is now recognized as a vital processing center in development of certain lymphocytes (T cells). These cells are very important in the acquired immune response of vertebrates.

[C]  1961: Mitchell, Peter. The chemiosmotic-coupling hypothesis of ATP formation.

Although it is known that oxidation of food molecules in cells results in net synthesis of ATP from ADP and inorganic phosphate, the molecular mechanism to drive the reaction is still unclear. Current evidence supports the chemiosmotic hypothesis, which suggests that energy derived from electron transport serves to pump hydrogen ions across the inner mitochondrial membrane, actively setting up an electrochemical gradient. The gradient of hydrogen ions is then coupled with an ATPase complex in the inner membrane, providing free energy to form the high-energy phosphate bond.

[G][C]  1961: Nirenberg, Marshall W., and J.H. Matthaei. Deciphering the genetic code.

By adding a synthetic RNA composed entirely of uracil nucleotides to a mixture of amino acids, these investigators obtained a polypeptide made up solely of a single amino acid, phenylalanine. On the basis of a triplet code, it was concluded that the RNA code word for phenylaline was UUU and its DNA complement was AAA. This was thebeginning of decoding.

Nirenberg, Nobel Laureate (1968).

[O]  1962: Copp, Harold. Discovery of calcitonin.

This peptide hormone is produced by the ultimobranchial glands (non mammalian vertebrates) or their embryological derivatives, the parafollicular cells of the thyroid gland (mammals). It lowers the blood calcium and increases calcium uptake by bone cells, thus antagonizing the action of parathormone.

[C][G]  1962-1972: Arber, W., H.P. Smith, and D. Nathans. Discovery, isolation, and characterization of restriction endonucleases.

Use of these bacterial enzymes has been essential in the recent explosion of knowledge in molecular genetics and recombinant DNA technology. Arber is given credit for predicting the existence of such enzymes, Smith for isolating the first restriction endonuclease and describing its reaction, and Nathans for applying the enzymes in studies of gene regulation and organization.

Nobel Laureates (1978).

[E]  1964: Hamilton, W.D. Concepts of kin selection and inclusive fitness.

The problem of neuter castes in social insects had destroyed Lamarckian and baffled Darwinian evolutionary explanations. Hamilton, however, demonstrated that the peculiar mode of reproduction in most social insects having neuter castes (haplodiploidy, or males haploid and females diploid) resulted in a situation in which sisters would share more common genes with one another than with their own progeny. Hence, helping to rear"kin" (sisters) could be more adaptive from the point of view of one's genes (inclusive fitness) than rearing one's own young (individual fitness). These ideas have since been extended to social behaviors of many species-vertebrate as well as invertebrate-and provide a fundamental core of the emerging field of sociobiology.

[E]  1964: Hoyer, B.H., B.J. McCarthy, and E.T. Bolton. Phylogeny and DNA

These investigators presented evidence that certain homologies exist among the polynucleotide sequences in DNA of such different forms as fishes and humans. Such sequences may represent genes that have been retained with little change throughout vertebrate history. Possible phenotypic expressions may be bilateral symmetry, notochord, hemoglobin, and so on.

[C][G]  1966: Khorana, H.G. Proof of code assignments in the genetic code.

By using alternating codons (CUC and UCU) in an artificial RNA chain, Khorana was able to synthesize a polypeptide of alternating amino acids (leucine and serine) for which these codons respectively stood.

Nobel Laureate (1968).

[C]  1967: Katz, Bernard, and R. Miledi. Calcium entry at nervous synapses.

These investigators proposed that the arrival of an action potential at a presynaptic terminal causes calcium influx that facilitates binding of synaptic vesicles with the presynaptic membrane.

[T]  1967: MacArthur, Robert H., and E.O. Wilson. Theoretical ecology.

Mathematical models in conjunction with field studies form the basis of theoretical ecology. This is well shown in the Theory of Island Biogeography by MacArthur and Wilson. By methods found in their book and investigations of many other researchers, it has been possible to determine the equilibrium of species, number of extinctions, and other factors on islands. This viewpoint has been a revelation in ecological studies.

[C][G]  1967: Ptashne, M. Isolation of first repressor.

Repressors are protein substances supposedly formed by regulatory genes; they function by preventing a structural gene from making its product when not needed by the cells.

[T]  1968: Goodall, Jane. Behavior of free-living chimpanzees.

A long-term complete study of primate social behavior was done in the field, providing an impetus and stimulus for a large number of similar studies on other primates.

[C][M]  1960s-1970s: Bergström, S., B. Samuelsson, and J. Vane. Characterization of prostaglandins.

Prostaglandins are chemical transmitters of intracellular and intercellular signals. They are involved in a variety of physiological and pathological functions. Bergström is credited with isolating prostaglandins and determining their structures; Samuelsson determined their biosynthesis and metabolism; and Vane found that vascular endothelium produces a prostaglandin (prostacyclin) that inhibits platelet aggregation.

Nobel Laureates (1982).

[C]  1960s-1970s: Gilman, Alfred, and Martin Rodbell. Discovery of G

Many chemical signals (for example, hormones, growth factors, neurotransmitters) bind to specific receptors on a cell surface. The cellular effect of many such signals occurs when cyclic AMP is synthesized. Transduction of the signal is mediated by a protein that requires GTP for its action (G protein).

Nobel Laureates (1994).

[O]  1960s-1970s: Hubel, D.H., and T.N. Wiesel. Understanding of stereoscopic vision.

Analysis of processing of images in eyes and brain opened a new field in
vision physiology.

Nobel Laureates (1981).

[C]  1970: Temin, H.M., and D. Baltimore. Demonstration of DNA synthesis from an RNA template.

Many viruses carry RNA rather than DNA as a genetic material, and it was not known how an RNA virus could enter the host cell and induce the host to synthesize more RNA virus particles. Temin and Baltimore independently found an RNA-dependent DNA polymerase in RNA viruses; thus an RNA virus reproduces by entering a host cell and producing a DNA copy from the RNA template; then host cell machinery makes new virus particles from the DNA template.

Nobel Laureates (1975).

[O][C]  1970: Edelman, Gerald M, and R.R. Porter. The structure of gamma globulin.

By using myeloma tumors (which contain pure immunoglobulin proteins) these investigators were able to work out after many years a complete analysis of the large gamma globulin molecule, which is made up of 1320 amino acids and 19,996 atoms, with a molecular weight of 150,000.

Nobel Laureates (1972).

[C][M]  1970s: Doherty, P. C., and R.M. Zinkernagel. How T cells recognize when another cell is infected by a virus.

For a T cell to detect and destroy a host cell infected with a virus, two signals are necessary on the host cell membrane: MHC protein and viral peptide.

Nobel Laureate (1996).

[G][D]  1970s-1980s: Tonegawa, Susumu. Mechanisms of antibody diversity.

The immune system of a vertebrate can make enormous numbers of different antibodies against the multitude of antigens it encounters. How to account genetically for antibody diversity has been a major challenge in immunology. A system of somatic mutations, multiple copies of gene segments, and gene rearrangements all play a role in generation of antibody

Nobel Laureate (1987).

[C][G][M]  1970s-1980s: Prusiner, S. B. Discovery of prions.

Prions are proteinacous infectious particles that lack nucleic acid. They are responible for transmissible spongi-form encephalopathies (TSEs), such as Creutzfelt-Jakob disease in humans and"mad-cow" disease in cattle. Although existence of infectious particles that totally lack nucleic acid remains controversial, much evidence has accumulated.

Nobel Laureate (1997).

[C]  1971: Berg, P., D. Jackson, and R. Symons. Recombinant DNA.

A DNA molecule from both a bacterial virus and an animal tumor virus were opened with a restriction endonuclease, then spliced together. This was the first recombinant DNA from two different

Berg, Nobel Laureate (1980).

[C][O]  1971: Cheung, W.Y. Discovery of calmodulin.

The calcium-binding protein interacts reversibly with intracellular calcium to form a complex that regulates a broad spectrum of cellular activities.

[M]  1971-1973: Cormack, A.M., and G.N. Hounsfield. Invention of computer-assisted tomography (CAT scanner).

This x-ray diagnostic technique produces clear images of internal body structures. A basic problem was how to obtain accurate measurements of the x-ray attenuation coefficient for all points in the x-ray section being examined. Cormack and Hounsfield each developed mathematical solutions to the problem.

Nobel Laureates (1979).

[E]  1972: Gould, Stephen J., and N. Eldridge. Concept of punctuated equilibrium.

This hypothesis proposes that species remain virtually unchanged for long periods of time until a sudden spurt of rapid evolution produces a distinct species. Since the hypothesis is an alternative to more orthodox Darwinian gradualism, it has produced lively debate among evolutionists.

[O][C] 1972: Jerne, Niels K. Hypothesis of anti-idiotype regulation of the immune system.

After the discovery by J. Oudin and H. Kunkel that antibodies themselves bear sites (idiotypes) that stimulate production of other antibodies against them (anti-
idiotypes), Jerne proposed that regulation of the immune system was mediated by a complex network of antibodies specific for other antibodies. Binding of antibodies to each other could be stimulatory or suppressive. There is considerable evidence to support this hypothesis.

Nobel Laureate (1984).

[C]  1972: Singer, S.J., and G.L. Nicolson. Fluid-mosaic model of biological membranes.

The plasma membrane of cells contains a bimolecular leaflet of lipids with its surface interrupted by proteins. Some proteins, called extrinsic proteins, are attached to the lipid surface, whereas others, called intrinsic proteins, penetrate the bilayer and may completely span the membrane. This model remains the most widely accepted model of membrane structure.

[O]  1972: Woodward, R.B., and A. Eschenmoser. Synthesis of vitamin B12.

Vitamin B12 was the last vitamin to be synthesized. This complex molecule is not made up of polymers; new methods of organic chemistry were required before it could be synthesized. It contains the metal ion cobalt.

[T]  1973: The Endangered Species Act.

This omnibus legislation, created in 1966 and greatly strengthened in 1973, is the first United States domestic law concerned exclusively with wildlife and enacted for purely altruistic motives. Its strength resides in that portion of the act specifically prohibiting federally funded projects from jeopardizing endangered species or their habitats. Over 950 species of plants and animals have been placed on the endangered list.

[C]  1974: Brown, M., and J. Goldstein. Discovery of the LDL receptor on cell surfaces.

Cholesterol, which is an essential component of cell membranes, is taken up by body cells in association with low density lipoproteins (LDL). Discovery that the presence of a receptor for LDL on cell surfaces is essential for this process had important implications for understanding of endocytosis of other macromolecules. Brown and Goldstein also described intracellular regulation of cholesterol met-abolism, and they cloned the gene for
the LDL receptor and thus were able to work out the molecular structure of the receptor.

Nobel Laureates (1985).

[C]  1975: Miller, J., and P. Lu. Alteration of amino acid sequence.

By inserting known amino acids to replace naturally occurring amino acids in the lac repressor protein, these investigators have been able to determine which amino acids are necessary for various functions of the lac repressor.

[C][M]  1975: Milstein, Cesar, and G. Köhler. Hybridoma technique and monoclonal antibodies.

Hybridomas are cells formed by hybridizing myeloma cells (from immune system tumors) with lymphocytes. Each hybridoma produces a clone of identical daughter cells, all manufacturing identical antibodies. Monoclonal antibodies are of great value in research, are useful diagnostic tools, and have great potential in disease therapy.

Nobel Laureates (1984).

[C]  1975: Sanger, J.W. Chromosome migration on spindle fibers.

The proteins (actin and myosin) that contract muscles are involved in the migration of chromosomes along the spindle fibers. Actin bundles are present on chromosomal spindle fibers.

[C]  1975-1977: Gilbert, W., A. Maxam, and F. Sanger. Methods for determining base sequence in DNA.

Practical methods for determining the base sequence in DNA have great implications for molecular genetics and DNA technology.

Gilbert and Sanger, Nobel Laureates (1980).

[C]  1975-1990s: Blobel, G. Protein ZIP codes.

How proteins find their way, after synthesis, to sites in cells where the proteins function was a mystery for many years. Blobel and his colleagues found that proteins were initially synthesized with unique signal sequences (Zip codes), later to be trimmed away, to which"signal recognition proteins" bind in the cytoplasm. The complex is thus guided to specific receptors on ER, mitochondrion, or chloroplast, depending on function of that particular protein.

Nobel Laureate (1999).

[C]  1976-1980: Neher, Erwin, and Bert Sakmann. Development of the patch clamp.

The "patch clamp" is a technique for measuring movements of ions through very small areas of cell membrane. A patch of cell membrane is sucked onto or into a tiny pipette of 0.5m diameter, and current changes caused by individual ion channels can be monitored. This technique has revolutionized neuroscience and cell biology.

Nobel Laureates (1991).

[G][M]  1976: Bishop, J. Michael, and Harold E. Varmus. Discovery of oncogenes.

Genes that cause cancer (oncogenes) are derived from normal genes (proto-oncogenes) that have functional roles in healthy cells.

Nobel Laureates (1989).

[D][G][C]  1977: Roberts, Richard, Philip Sharp, and others. Discovery of introns and exons in DNA.

Roberts and Sharp and others in their research groups showed that genes are often interrupted by lengthy tracts of DNA that do not specify protein structure. The coding sections came to be called exons, and intervening noncoding stretches are introns.

Nobel Laureates (1993).

[D][G]  1978: Lewis, Edward B. Discovery of homeotic genes.

Lewis identified a series of control genes in Drosophila that seems to regulate activity of other genes. Later known as homeotic genes, we now know that they are highly conserved and that they play similar functions in a wide variety of organisms.

Nobel Laureate (with C. Nüsslein-Volhard and E. Wieschaus) (1995).

1979: Alvarez, W., L.W. Alvarez, F. Asaro, and H.V. Michel. Asteroid impacts cause mass extinctions observed in the fossil record.

Anomalous levels of iridium at the boundary of Cretaceous/Tertiary rocks suggest that impacts of asteroids on the earth are responsible for the mass extinction observed there. Subsequent studies of shocked quartz, soot, and spherules at the Cretaceous/Tertiary boundary throughout the world upheld predictions of the asteroid impact hypothesis. The asteroid impacts would have sent debris into the atmosphere, producing darkness and cold temperatures and eventually acid rain, wildfires, and a greenhouse effect, thereby endangering many species. The asteroid impact hypothesis may account for other mass extinctions in the fossil record, but this remains controversial.

[D][G]  1980: Nüsslein-Volhard, Christiane, and Eric Wieschaus. Discovery of genes that control activation of homeotic genes.

Groups of genes they named "gap," "pair-rule," and "polarity" genes were
discovered in Drosophila that control homeotic genes. Like homeotic genes, they are highly conserved. Thousands of researchers are now analyzing these genes and gene families in mice, chickens, zebra fish, humans, and other organisms.

Nobel Laureates (with E.B. Lewis) (1995).

[D][G][C]  1980s: Smith, Michael. Site-directed mutagenesis.

Smith worked out a technique whereby a researcher could produce a DNA with a specific mutation at a particular site coding for a certain amino acid, thus producing a customized protein. This technique is used by virtually everyone in protein engineering and molecular biology.

Nobel Laureate (with K.B. Mullis) (1993).

[C][O]  1980s: Furchgott, R. F., L.J. Ignarro, F. Murad. Cellular and biological roles of nitric oxide.

The highly reactive, unstable gas, nitric oxide (NO) has an astonishing variety of essential functions in cells. It is an important signalling molecule, and white blood cells use it to help kill parasites, bacteria, fungi, and tumor cells. Its relaxing effect on smooth muscles in walls of blood vessels led to discovery of the anti-impotency drug seldenafil.

Nobel Laureate (1998).

[C]  1981: Complete sequencing of human mitochondrial DNA.

This landmark research by a group at England's Medical Research Council revealed that the human mitochondrial genome contains 16,569 base pairs. Packed into the genome with remarkable economy are genes for making two ribosomal RNAs, 22 transfer RNAs, and 13 assorted proteins.

[E]  1982-1986: Vrba, Elisabeth, Stephen J. Gould, Niles Eldredge, and
others. The hierarchical expansion of
Darwinian evolutionary theory.

The causal explanation of evolutionary change is expanded to include selective processes acting at different levels of biological complexity (genic, organismal, species) and different scales of evolutionary time. The phenomenon of sorting (differential survival and reproduction of varying individuals) is separated conceptually from selection, a cause of sorting based on the interaction between varying individuals (genes, organisms, species) and their respective environments. This discovery refines and expands our understanding of evolutionary processes.

[C][D]  1982-1984: Altman, Sidney, and Thomas R. Cech. Discovery of RNA catalysis.

Earlier dogma held that proteins were responsible for all enzymatic activity. Discovering that RNA introns could be edited out of precursor mRNA and that some RNA had catalytic properties in the absence of protein has led to a belief that most or all RNA splicing is carried out by catalytic RNA (ribozymes).

Nobel Laureates (1989).

[T][C][G][E]  1986: Mullis, Kary B. The polymerase chain reaction.

This biochemical technique can amplify selected genes in vitro from a sample of genomic DNA. It greatly improves our ability to obtain DNA sequences for genes of interest, even from degraded DNA samples. Applications include analysis of DNA sequences preserved in fossil organisms and DNA obtained from blood samples for forensic studies.

Nobel Laureate (with M. Smith) (1993).

Books and Publications that have Greatly Influenced Development of Zoology

Aristotle. 336-323 b.c. De anima, Historia animalium, De partibus animalium, and De generatione animalium. These biological works of the Greek thinker have exerted an enormous influence on biological thinking for centuries.

Vesalius, Andreas. 1543. De fabrica corporis humani. This work is the foundation of modern anatomy and represents a break with the Galen tradition. His representations of some anatomical subjects, such as muscles, have never been surpassed. Moreover, he treated anatomy as a living whole, a viewpoint adopted by most present-day anatomists.

Fabricius of Aquapendente. 1600-1621. De formato foetu and De formatione ovi pulli. This was the first illustrated work on embryology and may be said to be the beginning of the modern study of development.

Harvey, William. 1628. Essay on the motion of the heart and the blood. This great work represents one of the first accurate explanations in physical terms of an important physiological process. It initiated an experimental method of observation that gave an impetus to research in all fields of biology.

Descartes, René. 1637. Discourse on method. This philosophical essay gave a great stimulus to a mechanistic interpretation of biological phenomena.

Buffon, Georges. 1749-1804. Histoire naturelle. This extensive work of many volumes collected together natural history facts in a popular and pleasing style. It had a great influence in stimulating a study of nature. Many eminent biological thinkers, such as Erasmus, Darwin and Lamarck, were influenced by its generalizations.

Linnaeus, Carolus. 1758. Systema naturae. This work lays the basis of classification of animals and plants. With few modifications, the taxonomic principles outlined therein have been universally adopted by biologists.

Wolff, Caspar Friedrich. 1759. Theoria generationis. The theory of epigenesis was here set forth for the first time in opposition to the preformation theory of development so widely held before Wolff's work.

von Haller, Albrecht. 1760. Elementa physiologiae. An extensive summary of various aspects of physiology that greatly influenced physiological thinking for many years. Some of the basic concepts laid down therein are still considered valid, especially those on the nervous system.

Malthus, Thomas R. 1798. Essay on population. This work stimulated evolutionary thinking among such people as Darwin and Wallace.

de Lamarck, Jean Baptiste. 1809. Philosophie zoologique. This publication was of great importance in focusing attention of biologists on the problem of the role of environment as a factor in evolution. Lamarck's belief that all species came from other species represented one of the first clear-cut statements on the mutability of species, even though his theory of use and disuse is not accepted by biologists today.

Cuvier, Georges. 1817. Le règne animal. A comprehensive biological work that dealt with classification and a comparative study of animal structures. Its plates are still of value, but the general plan of the work was marred by a disbelief in evolution and a faith in the doctrine of geological catastrophes. The book, however, exerted an enormous influence on contemporary zoological thought.

von Baer, Karl Ernst. 1828-1837. Entwickelungsgeschichte der Thiere. In this important work are laid down the fundamental principles of germ layer formation and the similarity of corresponding stages in the development of embryos that have proved to be foundation studies of modern embryology.

Audubon, John J. 1827-1938. The birds of America. The most famous of all ornithological works, it has served as the model for all monographs dealing with a specific group of animals. The plates are the work of a master artist.

Lyell, Charles. 1830-1833. Principles of geology. This great work exerted a profound influence on biological thinking, for it did away with the theory of catastrophism and prepared the way for an evolutionary interpretation of fossils and the forms that arose from them.

Beaumont, William. 1833. Experiments and observations on the gastric juice and the physiology of digestion. Beaumont's observations on various functions of the stomach and digestion were accurate and thorough. This classic work paved the way for the brilliant investigations of Pavlov, Cannon, and Carlson of later generations.

Müller, Johannes. 1834-1840. Handbook of physiology. The principles set down in this work by perhaps the greatest nineteenth century physiologist has set the pattern for the development of the science of physiology.

Darwin, Charles. 1839. Journal of researches (Voyage of the Beagle). This book reveals the training and development of the naturalist and the material that led to formulation of Darwin's concept of organic evolution.

Schwann, Theodor. 1839. Mikroskopische Untersuchungenüber die Uebereinstimmung in der Struktur und dem Wachstum der Thiere und Pflanzen. The basic principles concerning the cell doctrine are presented in this classic work.

Kölliker, Albrecht. 1852. Mikroskopische Anatomie. This was the first textbook in histology and contains contributions of the greatest importance in this field. Many of the histological descriptions Kölliker made have never needed correction. In many of his biological views he was far ahead of his time.

Maury, Matthew F. 1855. The physical geography of the sea. This work has often been called the first textbook on oceanography. This pioneer treatise stressed the integration of such knowledge as was then available about tides, winds, currents, depths, circulation, and such matters. Maury's work represents a real starting point in the fascinating study of oceans and has had a great influence in stimulating investigations in this field.

Virchow, Rudolf. 1858. Die Cellularpathologie. In this work Virchow made the first clear distinction between normal and diseased tissues and demonstrated the real nature of pathological cells. The work also represents the death knell of the old humoral pathology, which had held sway for so long.

Darwin, Charles. 1859. On the origin of species. The most influential book ever published in biology. Although built around the theme that natural selection is the most important factor in evolution, the enormous influence of the book can be attributed to the extensive array of evolutionary evidence it presented. It also stimulated constructive thinking on a subject that had been vague and confusing before Darwin's time.

Marsh, George P. 1864. Man and nature: physical geography as modified by human action. A work that had an early and important influence on the conservation movement in America.

Mendel, Gregor. 1866. Versucheüber Pflanzenhybriden. Careful, controlled pollination technique and statistical analysis gave a scientific explanation that has influenced all geneticists after the"rediscovery" in 1900 of Mendel's classic paper on the two basic laws of inheritance.

Owen, Richard. 1866. Anatomy and physiology of the vertebrates. This work contains an enormous amount of personal observation on structure and physiology of animals, and some basic concepts of structure and function, such as homolog and analog, are here defined for the first time.

Brehm, Alfred E. 1869. Tierleben. The many editions of this work over many years have indicated its importance as a general natural history.

Bronn, Heinrich G. (editor). 1873 to present. Klassen and Ordnungen des Tier-Reiches. This great work is made up of exhaustive treatises on the various groups of animals by many authorities. Its growth extends over many years, and it is one of the most valuable works ever published in zoology.

Balfour, Francis M. 1880. Comparative embryology. This is a comprehensive summary of embryological work on both vertebrates and invertebrates up to the time it was published. It is often considered the beginning of modern embryology.

Semper, Karl. 1881. Animal life as affected by the natural conditions of existence. This work first pointed out the modern ecological point of view and laid the basis for many ecological concepts of existence that have proved important in further development of this field of study.

Bütschli, Otto. 1889. Protozoen (Bronn's Klassen und Ordnungen des Tier-Reichs). This monograph has been of the utmost importance to students of protozoa. No other work on a like scale has ever been produced in this field of study.

von Hertwig, Richard. 1892. Lehrbuch der Zoologie. This text has proved to be an invaluable source of material for many generations of zoologists. Its illustrations have been widely used in other textbooks.

Weismann, August. 1892. Das Keimplasma. Weismann predicted from purely theoretical considerations the necessity of meiosis or reduction of the chromosomes in the germ cell cycle, a postulate that was quickly confirmed cytologically by others.

Hertwig, Oskar. 1893. Zelle und Gewebe. In this work a clear distinction is made between histology as the science of tissues and cytology as the science of cell structure and function. Cytology as a study in its own right dates from this time.

Korschelt, E., and K. Heider. 1893. Lehrbuch der vergleichende Entwicklungsgeschichte der wirbellosen Thiere, 4 vols. A treatise that has been a valuable tool for all workers in the difficult field of invertebrate embryology.

Wilson, Edmund B. 1896. The cell in development and heredity. This and subsequent editions represented the most outstanding work of its kind in the English language. Its influence in directing development of cytogenetics cannot be overestimated, and in summarizing the many investigations in cytology, the book has served as one of the most useful tools in the field.

Pavlov, Ivan. 1897. Le travail des glandes digestives. This work, a landmark in the study of the digestive system, describes many of Pavlov's now classic experiments, such as the gastric pouch technique and the rate of gastric secretions.

De Vries, Hugo. 1901. Die Mutationstheorie. Belief that evolution is a result of sudden changes or mutations is advanced by one who is commonly credited with initiation of this line of investigation into causes of evolution.

Sherrington, Charles. 1906. The integrative action of the nervous system. Basic concepts of neurophysiology elaborated in this book, especially the concept of the integrative action of the nervous system, remains the basis of modern neurophysiology.

Garrod, Archibald. 1909. Inborn errors of metabolism. This pioneer book showed that certain congenital diseases were caused by defective genes that failed to produce the proper enzymes for normal functioning. It laid the basis for biochemical genetics, which later received a great impetus from the work of Beadle and Tatum.

Henderson, Lawrence J. 1913. The fitness of the environment. This book pointed out in a specific way the reciprocity that exists between living and nonliving nature and how organic matter is fitted to the inorganic environment. It has exerted a considerable influence on the study of ecological aspects of adaptation.

Shelford, Victor E. 1913. Animal communities in temperate America. This work was a pioneer in the field of biotic community ecology.

Bayliss, William M. 1915. Principles of genetic physiology. If a classic book must meet the requirements of masterly analysis and synthesis of what is known in a particular discipline, then this great work must be called one.

Matthew, W.D. 1915. Climate and evolution. Matthew, in contrast to Wegener, viewed the positions of continents as permanent. He explained distribution of plants and animals by dispersal between continents across land bridges, such as the Bering bridge between Asia and Alaska and the Panamanian bridge between Central and South America. Matthew's ideas dominated biogeographical thinking until the revival of Wegener's hypotheses in the 1960s and 1970s.

Morgan, Thomas H., A.H. Sturtevant, C.B. Bridges, and H.J. Muller. 1915. The mechanism of Mendelian heredity. This book gave an analysis and synthesis of Mendelian inheritance as formulated from the epoch-making investigations of the authors. This classic work stands as a cornerstone of our modern interpretation of heredity.

Wegener, Alfred. 1915. The origin of continents and oceans. In the first (German) edition of this book, Wegener developed the idea of continental drift. Wegener's interpretation of continental history was out of favor for many decades but was substantiated by geophysical work (plate tectonics) in the 1960s and 1970s. Biogeographers now invoke Wegenerian hypotheses to explain distribution of many groups of plants and animals.

Doflein, F. 1916. Lehrbuch der Protozoenkunde, ed. 6 (revised by E. Reichenow, 1949). A standard treatise on protozoa. Its many editions have proved helpful to all workers in this field.

Thompson, D'arcy W. 1917. Growth and form. In this pioneering work the author attempted to reduce the great diversity of life into common themes and designs.

Kukenthal, W., and T. Krumbach. 1923. Handbuch der Zoologie. An extensive treatise on zoology that covers all phyla. The work has been an invaluable tool for all zoologists who are interested in the study of a particular group.

Fisher, Ronald A. 1930. Genetical basis of natural selection. This work has exerted an enormous influence on the newer synthesis of evolutionary mechanisms that emerged in the 1930s.

Dobzhansky, Theodosius. 1937. Genetics and the origin of species. The vast change in the explanation of the mechanism of evolution, which emerged about 1930, is well analyzed in this work by a master evolutionist. Other syntheses of this new biological approach to the evolutionary problems have appeared since this work was published, but none of them has surpassed the clarity and fine integration of Dobzhansky's work.

Spemann, Hans. 1938. Embryonic development and induction. In this work the author summarizes his pioneer investigations that have proved so fruitful in experimental embryology.

Hyman, Libbie H. 1940. The invertebrates: Protozoa through Ctenophora. 1951. Platyhelminthes and Rhynchocoela, The acoelomate Bilateria. 1951. Acanthocephala, Aschelminthes, and Entoprocta, the pseudocoelomate Bilateria. 1955. Echinodermata, the coelomate Bilateria. 1959. Smaller coelomate groups: Chaetognatha, Hemichordata, Pogonophora, Phoronida, Ectoprocta, Brachiopoda, Sipunculida. The coelomate Bilateria. 1967. Mollusca I. This series of volumes is a monumental work by a single author and is the only such coverage of the invertebrates in the English language. It is a benchmark in completeness, accuracy, and incisive analysis. It remains an absolutely essential reference for all teachers and investigators in invertebrate zoology.

Schrödinger, Erwin. 1945. What is life? The emphasis placed on the physical explanation of life and the popularization of the idea of a chemical genetic"codescript" provided a new point of view of biological phenomena so well expressed in the current molecular biological revolution.

Lack, David. 1947. Darwin's finches. This classic, written several years after Lack's study visit to the Galápagos Islands, introduced competition theory into animal ecology, stressed the importance of ecological isolation in speciation, and provided a cogent model for adaptive radiation.

Grassé, P.P. (editor). 1948. Traité de zoologie. This is a series of many treatises by specialists on both invertebrates and vertebrates. Since it is relatively recent and comprehensive, the work is valuable to all students who desire detailed information on the various animal groups.

Allee, W.C., A.E. Emerson, O. Park, T. Park, and K.P. Schmidt. 1949. Principles of animal ecology. The basic ecological principles laid down in this comprehensive work are a landmark in the field.

Blum, H.F. 1951. Time's arrow and evolution. In this thoughtful book, Blum explores the relation between the second law of thermodynamics ("time's arrow") and organic evolution and recognizes that mutation and natural selection have been restricted to certain channels in accordance with the law, even though these two factors appear to controvert the principle of pointing the direction of events in time.

Tinbergen, Niko. 1951. The study of instinct. The classic statement of the approaches and theoretical interpretations of early ethologists, especially K. Lorenz, is presented. This work brought ethology to the attention of American behavioral scientists, generating both controversy and collaboration.

Crick, Francis H.C., and James D. Watson. 1953. Genetic implications of the structure of deoxyribonucleic acid. The solution of the structure of the DNA molecule has served as the cornerstone for an explanation of genetic replication and control of the cell's attributes and functions.

Simpson, George G. 1953. The major features of evolution. In a comprehensive synthesis of modern evolutionary theory, the author draws on evidence from paleontology, population genetics, and systematics. This book, along with Simpson's earlier Tempo and mode in evolution, have greatly influenced our thinking about the mechanisms of evolution within the framework of natural selection.

Burnet, F. MacFarlane. 1959. The clonal selection theory of acquired immunity. This was an important new theory to explain specificity of the acquired immune response and has to a great extent replaced the template theory formulated by Haurowitz in 1930.

Carson, Rachel L. 1962. Silent spring. Though a polemic addressed to a lay audience, this book was highly valuable in increasing public awareness of the danger to the ecosystem of indiscriminate use of pesticides.

Mayr, Ernst. 1963. Animal species and evolution. This lucid and thoroughly documented landmark in evolutionary study helped to clarify and integrate the emerging synthetic theory of evolution.

Watson, James D. 1965. Molecular biology of the gene. With perhaps the clearest statement of what molecular biology is, this important book introduced the field to the new generation of investigators in molecular genetics.

Williams, George C. 1966. Adaptation and natural selection. This scholarly and insightful work, with its well-reasoned explanation of adaptation and its convincing defense of natural selection, was highly influential in clarifying the role of natural selection in evolutionary change.

MacArthur, R.H. 1972. Geographical ecology. One of the most important theoretical ecology books to have appeared in the 1970s.

Gurdon, John B. 1974. The control of gene expression in animal development. Gurdon developed an experimental system, extended from the pioneering nuclear transplantation experiments of Briggs and King, that enabled him to transfer genetic information from one animal to another. His studies, summarized in this influential work, are interpreted to mean that nuclei of embryonic cells do not undergo alterations or loss of genetic material during development.

Lewontin, Richard C. 1974. The genetic basis of evolutionary change. This book promoted the study of protein polymorphisms to measure the amount of genetic variation present in natural populations. The development of the alternative theories of neutral polymorphism versus balancing natural selection is covered in detail. The methods described in this book for the first time made possible studies on a large scale of population genetics in natural populations of animals.

Wilson, Edward O. 1975. Sociobiology: the new synthesis. The rapidly developing fields of behavioral biology, behavioral ecology, and population genetics are reviewed. Wilson attempts to provide the basis for a new biological science, utilizing concepts developed in these heretofore disparate fields, devoted to analyzing social behaviors at all phylogenetic levels.

Gould, Stephen Jay. 1977. Ontogeny and phylogeny. This book reexamined the ancient problem of relationship between organismal development and evolution and revitalized this field. Numerous studies of heterochrony-the evolutionary changes in timing of organismal development-followed publication of this book and provided most of our present knowledge about the evolution of morphology and life histories in animals.

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