Chapter 28 Chapter 15 Germ Cells

When it is said that a child has inherited a characteristic from his father or mother, some process is assumed to provide continuity from generation to generation.Indeed, continuity is the very essence of the whole concept of heredity.The ancient Greeks had vaguely understood that the union of the sexes was the key to answering the question of heredity.But how exactly is "genetic material" (as it came to be called) passed on from one generation to the next?is purely speculative (see Chapter 14).Some of the theories that have been proposed are highly improbable, because the inheritance of physical traits and behavioral traits is too fine-grained to be explained in terms of "heat," "spirit," or other forms of physical force proposed by earlier philosophers.The Hippocrates, who viewed heredity as the transmission of seed matter, seemed closest to the truth. Lucretius proposed a qualitative theory of inheritance, arguing that the properties of hair, voice, face, and other parts of the body are determined by the mixture of atoms contained in seeds passed down from ancestors.All observations of hereditary phenomena imply that some matter of a granular nature is transmitted, but whatever it is is too small to be seen by the naked eye.To meet the challenge of what the nature of hereditary material is, it was first necessary to develop a new branch of biology—cytology.The development of this new discipline was only possible after the invention of the microscope and its application to the study of cells.

It has long been apparent that eggs are necessary for the development of new individuals.The ancient Greeks also believed that sperm mattered, and even most so-called oogonists of the 17th and 18th centuries acknowledged this.However, there was no positive evidence until the 1760s.The similarity, if not identicalness, of the hybrids produced by backcrossing, as the Kerr-Luther study has shown, necessarily leads to the conclusion that the genetic contributions of both parents are the same.This insight led to a new set of questions: How could eggs and sperm (or pollen grains), so distinctly different in size and shape, be genetically identical?In which parts of the male and female bodies are the seed substances that are the transmitters of the parental traits produced?How is the seed material constituted in order to be able to pass on the complex traits of an individual to the next generation?These questions can only be answered after the cell theory is established.

The discovery that all living things (strictly speaking, only eukaryotes) are made of cells and their products was only possible after the invention of the microscope, one of the most important technological advances in the history of biology.The earliest simple microscopes were probably invented by certain Dutch opticians around 1590, until the English physicist Robert Hooke (1635-1703) in 1665 in his Micrographia. Pores and boxes in a slice of cork are only described in the book. Nehemiah Grew (1672-1682), Malpighi (1675, 1679) published more and finer microscopic sketches.All they observed with these microscopes were (cell) walls (easy to understand from the original meaning of the word "cell" or hive), and no mention was made of any biological significance of their findings.Not long after, some scholars who studied animal tissues (especially embryos) such as Swammerdam, (1737), CFWolff (1764), Meckel (1821), Oken (1805; 1839) and others described droplets or bubbles.At that time, it was not possible to determine which of the observed droplets (or globules) were true cells and which were impurities (Baker, 1948; Pickstone, 1973).In the 150 years since Hooke first described his humble microscope, no real progress has been made in the study of cells, which was made possible only by improvements in the technique of making better microscope lenses .

At the same time, many scholars (some of whom may be influenced by the atom theory in physical science) began to raise the question of what the human (one of the animals) body is ultimately composed of.According to Hippocrates' creed, the body is composed of liquids and solids, and Boer-haave and other anatomists and physiologists in the 18th century believed that these solids were composed of very thin fibers. Haller later became a major proponent of the fiber theory, which was also acknowledged by Erasmus Darwin.Although the fiber theory is wrong, its merit lies in focusing people's attention on the most basic structural matter of the body.

Since fibers, droplets, or cells were proposed by different scholars, and botanists and zoologists often seemed to contradict their findings, there was clearly a need for unity in this field of biology. Bichat has identified 21 types of animal tissues. Are they all composed of the same basic substance, and if so, what are they? Exploring the common constituents of the body seems to be of particular importance during the period of idealist morphology. In the 1820s and 1930s, microscopes began to be produced in England, France, Germany, and Austria, and soon became routine instruments in well-equipped laboratories.Improvements in new instruments have allowed microscopic (under) research to advance at an unprecedented pace.These studies not only revealed that many of the discoveries of the 18th century were adulterants, but more importantly, these studies also showed that there is more to cells than cell walls.Until then the word "cell" (as Haller and Lamarck used it) was just a name.It is seen as a structural component with a focus on the cell wall, with no mention of its function.As instruments gradually improved, researchers began to pay attention to the contents of cells.Later, it was found that living cells were not empty but filled with viscous liquid, which was called "sarcode" by French zoologist Dujardin (1835); Czech physiologist Purkinje (1839) and German The botanist Von Mohl (1845) called it "protoplasm" (translated as protoplasm).Protoplasm is much more than just a term denoting the contents of a cell (other than the nucleus).When browsing the popular literature of the period, it is widely regarded as (in a vitalistic sense) "living matter" (see Oxford English Dictionary, entry Protoplasm).It is considered to be the most basic structural substance of all living things, and has been explained for almost a hundred years or so as the real working substance of all physiological processes.

Later, when biochemistry began to "dissect" the contents of cells, it was soon discovered that there was no single substance worthy of the name protoplasm, but it was not until the use of electron microscopes after 1940 that they realized how complex the structure of cell contents was. The aggregates, its function is beyond the dream of the early protoplasm researchers. The word "protoplasm" has now virtually disappeared from the biological literature.The aggregate of cellular structures and the fluid outside the nucleus is now called the cytoplasm (in Kerr-Luther's term).The importance of the cell wall is decreasing, and finally Leydig (1857) and M. J． s. Schultze (1861) pointed out that animal cells do not contain cell walls, most of them are naked, only covered by membranes.

Another notable component of cellular inclusions is the nucleus.Although nuclei were observed in plant cells and even some animal cells in the early 18th century, the British botanist Robert Brown (1773–1858) first (1833) proposed that the nucleus was a normal component of living cells.What the function of the nucleus was was never clear, and the first explanations were completely wrong. In the 1870s, cells and protoplasm were also considered almost synonymous, and the nucleus was an unimportant component, either present or absent.Indeed, most cells do not have nuclei during part of the nuclear cycle.The above phenomenon is understandable because the spherical nucleus covered by the membrane disappears during cell division. 15.1 The Schwann-Schnedden Cell Theory

By the late 1930s, the mysteries surrounding stem cells centered on two main questions: What is the function of cells in living things?How are new cells produced?These two questions have been initially answered in the Schwann-Schnedden cell theory. "Schneiden" was the most influential cytologist at that time. With great enthusiasm, he not only persuaded Schwann to participate in cytological research, but also trained some young excellent botanists (such as Hofmeister, Nagli). He also Persuaded the young Carl Zeiss to create such an important optical instrument company and gave him pertinent advice to ensure its smooth development (Zeiss later developed many better optical instruments for biological research, especially microscopes, as a reward).

Schneiden belonged to a younger generation of German biologists who were particularly disgusted with the School of Natural Philosophy, and who tried to explain everything in a reductionist physical-chemical way (Buchdahl, 1973).In answer to "Where do new cells come from?" It was inconceivable for him to answer this question with the words "from the cells that originally existed".This is too much like preformationism, which was discredited at the time.So Schneidern applied the principle of epigeneticism to cell formation, and in 1838 he proposed the theory of free cell formation.He believed that the first step in cell formation was the formation of the nucleus from the granular material of the cell contents by crystallization.The nucleus then grows and finally forms a new cell around itself, the outer membrane of which becomes the cell wall (Schneidon has elaborated on this, 1842:191).New nuclei can form in existing cells, and can even crystallize out of shapeless bodily fluids.A major debate in the ensuing 20 years was whether such free cell formation actually occurred.The final answer is no.Although he was shown to be wrong, Sneddon did advance cytology by drawing attention to a problem and by proposing a simple, testable theory.More importantly, in the long run, he insisted that plants consist entirely of cells, and that highly differentiated plant structures are all cells or cell products.

In the classic work, "A Microscopic Study of the Uniformity of Structure and Growth in Animals and Plants" (Mikroskopische Untersuchunsen Uber dieUbberinstimmung in der Struktur unddem Wachstum der Tiers und Pflanzen, 1839), Schwann pointed out that Schnedden's conclusions also apply to animals (Okin also independently made this conclusion in 1839).By looking at animal embryonic tissues and tracing their subsequent development, Schwann succeeded in demonstrating a cellular origin even for tissues like bones (bones, when fully grown, are not at all recognizably cellular in origin).The fact that animals and plants are composed of the same basic component - cells is just another evidence of the unity of life, and is promoted as one of the famous biological theories - cell theory.This also contributed to the fleshing out of the word "biology" (co-coined by Lamarck and Treviranus), since until then it had been an unfulfilled wish.

As important as this new insight was, the shock caused by the cell theory was also somewhat puzzling.At the time, no one really understood the cell and how the nucleus and cytoplasm function.The elbow cell theory mainly refers to Schneidan's theory of free cell formation (Virchow, 1858), the idea of ​​the complete physicochemical formation (crystallization mode) of the nucleus and cells may have been found in the atmosphere of extreme physicalism and reductionism prevailing at that time Considerable attraction. A very different view comes from Brittice et al.'s view of cells as "basic organisms" (elementary organisms).His views were clearly influenced by idealist morphology.Just as Goethe "reduced" all the parts of a plant to leaves, so Britke reduced all the parts of any living thing to cells.In fact Wigand (1846) called the cells "true native plants" (eigentliche Urpflanze). Some of the above-mentioned arguments (including other scholars who have made similar remarks) have a strong atmosphere of vitalism.This caused a strong reaction among physicalists, for example Sachs (1887) claimed that cells were only secondary phenomena because formative forces pervaded organic matter.Others downplay the significance of cells because, in their view, protoplasm is the basic substance of life.Clearly, cells are incompatible with explanatory models based on the universality of "forces." E． B．In the introduction to The Cell (1896), Wilson vehemently criticized statements like Sachs's. Whatever the theory of the cell may have meant to different scholars, it did contribute to firmly establishing the unity of the biological world.In addition, it led to the conception of biological organisms as republics composed of basic living units. "The character and unity of life cannot be confined to a particular part of a highly developed organism (such as the human brain)" (Virchow, 1971 [1858]: 40); in fact, life appears in the same way in every in cells.At the time this was considered somewhat of a strong critique of vitalism.Whether Werko was influenced by similar views of Oken remains to be seen. For Schwann and Schneiden the cell was still primarily a structural component, but in the 19th century others had emphasized the physiological functions of the cell, especially developmental and nutritional functions.The meaning of the concept "cell theory" has gradually changed over time as the understanding of the cell and its components, particularly the nucleus, has grown.Schneiden's theory directly contributed to the very active research work on differentiating between animal and plant cells. In 1852, Remak (1815-1865) pointed out that frog eggs are cells, and new cells in the developing frog embryo are produced by the division of existing cells.He emphatically refuted the theory of free cell formation.On this point he was supported by Werke (1855), who pointed out that in many normal and diseased animal and human tissues, each cell divides from pre-existing cells. He asserted: "As a general principle, the development of any kind does not start from scratch, and the theory of (spontaneous) generation is therefore (must) be rejected, whether in the history of the development of individual parts or in the history of the organism as a whole" (Virchow, 1858:54 ). Kolliker and some other botanists also came to the same conclusion at the same time, however, the authority of Schneidan delayed the general acceptance of this conclusion in the botanical community.Darwin in 1868 (II: 370) was not sure whether free cell formation was even possible.Later Werke's dictum "The cell comes from the (pre-existing) cell", (omnis cellula e cellula) was finally accepted by everyone, but at that time the details of the process of cell (especially nuclear) division were not clear (see hereinafter, "mitosis"). Thanks to this new interpretation of the cell, the time is ripe to rethink the fertilization process.If everything in the body is made up of cells, are the gonads (ovaries and testes) too?What exactly is the "seed matter" of males and females?Is it also made of cells?What is the difference between male and female sex cells?Such questions, which have been conceived before, were of course not raised at the beginning, but they must be the logical consequences of the cell theory. It became increasingly apparent that a truly viable theory of genetics could not be established until the role of cells in fertilization had been elucidated.It was during these decades that the concept of germ cells came to the fore. 15.2 Significance of sex and fertilization It has been known from time immemorial that animals have two sexes, because it is inevitable by human analogy.The sex of plants was discovered much later, at least in its almost universal existence.In fact, in some dioecious plants (that is, plant species in which one individual has only male flowers and another has only female flowers), the sex is quite obvious. The ancient Assyrians used the pollen emitted by the male date palm to give the female tree This knowledge is used during insemination (see Chapter 13). After the Middle Ages, N. Grew (1672) speculated that pollen might be the agent of fertilization.However, only to R. J． After Camerarius (1665-1721) published his epistolary treatise "The Sex of Plants" (De Sexu Plantarum Epistola, 1694), the sexual reproduction of plants was clearly identified.He discovered through experiments that anthers are male organs and emphasized that pollen is necessary for fertilization. Camerarius was fully aware that sexual reproduction in plants is exactly the same as sexual reproduction in animals.He asks some very profound questions about the exact function of pollen grains in fertilization: "It would be nice if...we could find out from someone using a microscope what the contents of the pollen grains are, how well they get into the female sex organs. far, whether they reach the place where the seed (sperm) is received intact, and what is released when they break" (1694:30).This challenge was later taken up by Kerr Luther and other hybridists, but was not fully studied until Amici, Hofmeister, Pringsheim (from 1836 to 1856, see Hughes, 1959, et seq.). Camerarius also recognized the role of wind in pollination and the ability of seeds to fix in some cases despite hindered pollination.His treatise "The Sex of Plants" played an important role among his contemporaries, spurred the work of experimental plant hybridization in the 18th century, and was culminated in the writings of Linnaeus and Kerr Luther (See Chapter Fourteen and Zirkle, 1935).However, the sex of plants was still widely doubted until the 19th century. Even Kerrrudd and Timothy did not emphasize enough the ubiquity of sexual reproduction in plants and the absolute necessity of cross-pollination in most plant species.It was not generally accepted that plants with "flowers" (as understood by laymen) were all pollinated by animals. In 1795 Christian Konrad Sprengel (1750-1816) published his classic work on flower pollination by insects, which emphasized the above points, but his work went far beyond the orthodoxy and interests of the time, so it was almost completely ignored. Neglected.Most notable in this work are sprengel's detailed descriptions of the various co-adaptations between flowers and insects that facilitated cross-fertilization or made self-fertilization impossible.This was the first "Biology of Flowers" and Darwin gave it his due (:98; 1862).The obvious inference to be drawn from SPrensel's work is that in sexually reproducing species the individual indeterminate patterns (types) or Pure lines are rather members of the population, but this inference was not made until more than a hundred years later . Since the theory of the cell was established, it was evident that the question would be asked whether it would also apply to sperm and eggs. In the case of sperm, this was quickly done, and while von Baer still believed that sperm were parasitic worms present in semen, Kolliker had pointed out as early as 1841 that they were cells and could be proved by studying spermatogenesis. As far as eggs are concerned, things move much more slowly.Although von Baer discovered the mammalian egg in 1827, and Purkinje discovered the large nucleus of the ovarian egg (which he called the blastocyst) in 1830, neither of them understood the cellular nature of these structures.It was only in 1852 that Remak indicated that the frog egg was a single cell, and Gegenbaur in 1861 (by showing that the yolk material was not a cell) extended this conclusion to the eggs of all vertebrates. From modern reflection, one might think that the nature of fertilization in animals would be quickly deduced once the egg and sperm are recognized as cells.Of course, one would say that fertilization is the fusion of these two germ cells to produce a new individual.In reality, however, it took decades to achieve this understanding.The same conclusion should have been drawn for plant pollination, based on the observations of Kerr-Luther, Amici, Mendel, and others.From 1824 to 1873 one suggestive observation after another was either ignored or interpreted beyond recognition and clearly contradicted by the observation.Even as late as 1840, progressive botanists like Schneidan doubted the sex of plants.Why is the phenomenon of fertilization so difficult to explain over such a long period of time? There are many reasons for this, but perhaps the most important one is that this phenomenon belongs to both functional and evolutionary biology.Embryologists are impressed by the fact that unfertilized eggs can be inactive for long periods of time, only starting to develop after fertilization.They therefore believed that the sperm had only a mechanical effect, rather like dropping a coin into a juke box; this is true in the very rare phenomenon of pseudogamy.In contrast, scholars interested in genetics view fertilization as a process in which the genetic characteristics of the father and mother are mixed.Therefore, since there are different interpretations of the meaning of fertilization, it is natural that each adopts a completely different mode of interpretation.Fertilization has a double meaning, and both opposing interpretations are correct.These two points were not fully understood until the last 20 years of the 19th century. Since the controversy over fertilization is one of the most noteworthy developments in the history of biology and has created a situation of direct confrontation between scholars of immediate and ultimate causes, it is worthwhile to make a brief review of the competing arguments. Although differing in some details, the various theories of fertilization from ancient Greece to the early 19th century assume that the female parent provides a unit, more or less uniform substance, later called the "egg", while the male parent provides To supply some kind of power that can promote the development of eggs, including spirit, heat, or some kind of physical force or vitality.As late as 1764, Wolff still believed that pollen and animal sperm were only high-level nutrients necessary to promote the growth and development of embryos.Even von Baer's remarks (1828) have a strong Aristotelian flavor.According to Aristotle's point of view, the mother provides the substance, and the father provides the motive, the formal cause and the final cause. Bonnet discovered in 174o that aphid eggs could develop even in the absence of male aphids (parthenogenesis). This fact seems to confirm the above explanation.Evidently, the developmental potential of the egg can be induced by a certain fecundity exerted by the female itself.To Bonnet's contemporaries, the discovery was shocking, yet 19th-century research suggested that such "virgin births" were fairly common in the animal kingdom, or a seasonal phenomenon (like aphids). and rotifers), or are permanent (ChurChill, 1979). A special form of parthenogenesis, arhenotoky, was discovered in the 1840s in Hymenoptera.Unfertilized eggs in this form produce haploid male offspring.It was Mendel's contemporary, Johann Dzierzon, who discovered this particular form. He and Mendel were both from the Silesian region of Austria, and later both became Catholic priests. He was also an apiary.He fleshed out his hypothesis (1845) by confirming that androgens were formed from unfertilized eggs by inventive hybridization experiments (German peaks crossed with Italian peaks).Apomixia, which is more common in the plant kingdom and is similar to parthenogenesis, once caused a lot of confusion in the early days of genetics (see Chapter 16, Mendel's willow chrysanthemum hybridization experiment ).The special role of parthenogenesis as an evolutionary strategy has attracted widespread attention in recent years. The history of biology often sees certain problems come and go, and so did the problem of fertilization.Since Camerarius, Sprengel, Kerr Luther, etc. opened up a new situation, it appeared to be very quiet in the first 20 years of the 19th century. When it was revived in the 1830s and 1840s, it coincided with the prevalence of physicalism.According to German chemist Liebig, all chemical reactions depend on the molecular collision caused by the close contact of two substances and their constituent particles (Coleman, 1965). T． L． W． Bisc hoff applies this to the question of fertilization and puts it more clearly: "The semen acts on contact by a certain catalytic force, that is to say, it passes to the egg by an internal movement constituting a substance of a particular form... in In the egg it also causes the same or similar rearrangements of atoms" (1847). The overall effect of sperm penetration into the egg and sperm motility was not considered at the time.All phenomena are due to "molecular excitation".This explanation fits well with the mechanistic reductionist view popular in the Schwann, du Bois-Rermond, and Ludwig schools at that time and is almost universally accepted.One of the main proponents of this doctrine was the famous morphologist Wilhelm His, who demanded the reduction of all biological phenomena to chemistry, mathematics, and most importantly, mechanics. "The zygote contains the excitation which promotes growth. In this excitation is the whole content of the genetic transmission from the paternal and maternal parents. What is transmitted is not form, nor special form-forming material, but merely the The stimulation of growth to form a body is not the character itself but the beginning of the developmental process itself." (1874:152). His views greatly influenced his nephew Michel, which is a tragedy of biology and biochemistry.This is part of the reason why Michel completely missed the significance of his own discovery of nucleic acids (see Chapter 19). As late as 1899 J. Loeb was still able to write the following: "The ions, not the nuclides, in the sperm are necessary for the fertilization process." Because of the strong influence of physical explanations of fertilization, observations after observations have been ignored, even if these observations completely contradict or at least prove only part of what the reductionist explanations offer. explain the problem.Let us now review the history of some of the discoveries that finally solved the mystery of fertilization. The first question to be answered is whether it is the semen as a whole or the sperm in the semen that achieves the tranquilizing effect. As early as the 1780s, experiments conducted by L. Spallanzani should have led him to the correct answer, but they did not.He tied the male frogs to small pockets (which allow some of the semen to pass through but not the sperm), and such males were unable to fertilize the eggs of the females they mate with. In 1824 two Swiss physiologists J. L． Prevost and JB. Dumas published the results of a series of original and decisive experiments on frogs which proved beyond doubt that the spermatozoon was the element that fertilized the egg, and that the semen was only the carrier of the spermatozoa. In 1843 M． Barrx experimented with rabbits, 1851 G. Newport's experiments with frogs all pointed to the presence of sperm inside fertilized eggs, but they also failed to observe how the sperm entered the eggs and determine their subsequent whereabouts.So their observations do not shake the physics of fertilization. In 1854 Thuret discovered that the ciliated motile sperm of Fucus surrounded and entered human eggs.He was even able to use this observation to perform artificial insemination. In 1856 N. Pringsheim draws decisive conclusions about the fertilization process through observational studies of the freshwater algae Oedogonium.He actually observed the entry of the male gamete into the ovule of the female, from which he drew the correct conclusion that the first cell (zygote) of the new individual is formed by the fusion of the male gamete with the egg cell; fertilization can be accomplished by only one motile sperm.Since the sex of cryptogam was still debated at the time, Pringsheim's argument, although decisive, was ignored.When some scholars in the 1850s and 1860s emphasized that plants formed from immature embryos produced by the fertilization of many pollen grains had more vigorous vitality, the development of events was not favorable to Pringsheim's conclusion. It was Mendel (letter to Negri, July 3, 1870) who tried to refute "Darwin's view that one pollen grain is not enough to fertilize an ovum" (Darwin's view was largely due to a misunderstanding of Nao Ding's research work, the latter has actually accepted the "one pollen grain" hypothesis).Mendel experimented with Mirabilis jalappa and obtained 18 well-developed seeds fertilized by a single pollen grain. "The majority of the plants (cultivated from these seeds) have the same vigor as freely self-fertilized plants. This unquestionably solves the problem; unfortunately, since Nageli is not interested in this problem, this letter The letter was not published until 1935 (Correns, 1905). During this same period other researchers elucidated the various steps in the process of plant fertilization. In 1823 J． B． Amici observed how a free pollen grain grows a pollen tube, and in 1846 he proved that when the pollen tube arrived, the egg cell in the ovule was stimulated and developed into an embryo.Neither he nor Hofmeister (who confirmed these steps in 1849) even considered the function of pollen tubes! Botanists pioneered the study of cells in the first half of the 19th century.But roughly after 1850, thanks to proper tissue fixation methods, zoocytologists took the lead.The lack of cell walls in animal cells made it easier to focus on the nucleus and how it changes during cell division.In addition, fertilization is not complicated by the presence of pollen tubes, embryo sacs, etc. Since Kolliker and Gegenbauer proved that eggs and sperm are both cells, and cells are redefined as composed of nuclei located in the protoplasm, the question facing cytologists and biologists is: When the sperm enters the human egg , What changes have taken place in the nucleus of the egg and sperm, and the protoplasm of the egg and sperm? The two views on fertilization during the twenty-five years after 1850 may be considered reflections of the following two theories: Contact Doctrine and Fusion Doctrine.The physicalists see fertilization as the transmission of excitation, and think that the essence of fertilization is only the contact of egg and sperm; this is a reasonable explanation if only attention is paid to the beginning (that is, the recent cause) of the division of the fertilized egg.Yet to accept the contention that this mere exchange of excitations accounts for the paternal and maternal characteristics of newborn individuals requires light faith and no interest in ultimate causes.The opposite of this view (the fusion theory) gradually gained the upper hand as a result of increasingly sophisticated microscopic analyzes of the fertilization process.In the end, the physicalist theory of contact was abandoned. Although it was generally recognized at the time that spermatozoa were primarily composed of nucleoplasm, the conclusion that the nucleus was truly the key factor in fertilization was not generally accepted.The reason for this hesitation was the consensus at the time that the sperm was dissolved as soon as it entered the egg.In fact, some scholars have found two nuclei in recently fertilized eggs, and one scholar even observed the fusion of these two nuclei, but they did not know that one of them was re-transformed into a nucleus by sperm. There are two technical or methodological advances that greatly facilitate the final solution of the problem.One of them is the realization that the eggs of mammals and birds are not suitable for the study of fertilization, so zoologists experimented with eggs of many other species of organisms, and finally found that according to the problems to be solved (such as fertilization, mitosis, Chromosomal continuity) Some other species that are more suitable can be used as test materials.Another, even more important, is the rapid development of microscopy. The microscope and its lens were continuously improved, and finally in 1870, an oil immersion lens was produced.Sith invented the microtome (around 1866), and in later years newer slicers were able to prepare thinner slices.New methods of immobilizing various biological materials have also been invented.Finally, the invention of aniline dyes has produced a wide variety of stains, many of which have highly specific affinities for particular cellular components or molecules.These technological advances have improved the ability of microscopes to see fine detail by at least an order of magnitude. Butschli's (1873; 1875) and Auerbach's (1874) studies of nematodes, and Schneider's (1873) studies of a flatworm were perhaps the first to observe and understand that the nucleus of the zygote (fertilized egg) is composed of the nucleus of the egg and a nucleus from the sperm. formed after nuclear fusion, but their more or less accidental observations have not received the attention they deserve. It was Hertwick who finally demonstrated the essence of fertilization.In the spring of 1875 he studied the fertilization process of Mediterranean sea urchins (Toxopneustes lividus) using state-of-the-art equipment.The eggs of this sea urchin are very small, with very little yolk, and are transparent even when highly magnified.Both eggs and sperm are easy to store, fix and stain.Hertwick demonstrated unequivocally that the second nucleus observed in the egg immediately after fertilization was derived from the sperm.He also pointed out that only one sperm is needed for fertilization.Finally he showed that the nucleus of the sperm and the nucleus of the ovum merged into one and produced by division all the nuclei of the developing embryo.The nucleus of the zygote (zygote) never disappears, and there is complete continuity between the zygote and all the nuclei of the newly developed biological organism, as previously pointed out by Schneider, Butschli, et al.Fleming once expressed this phenomenon in a very concise language "Omnis nucleus e nucleus" (Omnis nucleus e nucleus). The momentum of cytological research in the 1970s and early 1980s was unmatched in any other field of science. "It was not uncommon for some of the leading cytologists of the time, most of them working in German laboratories, to publish seven papers in one year" (Hughes, 1959: 61).赫特维克的报告（1876）中还有某些错误因而并没有立即被研究受精作用的其他着名学者所接受（见专家文献中van Beneden与Strasburger的声明）。但是这些错误很快就被更正，赫特维克观察的正确性也由Hermann Fol（1845－1892）的卓越研究证实。 Fol正确地描述了卵细胞核的两次成熟分裂（见下）并凭藉极大的毅力观察了精子进入卵的真实过程。他完全证实了雄性核与雌性核互相融合并形成新生物有机体全部细胞的细胞核，这和赫特维克的观察完全相符。 Fol通过实验手段使一个卵同时被几个精子授精，并揭示这种过程总是引起不正常的分裂和不能生存的动体。受精作用毫无例外地总是由单个精子实现（Pol，1879）从而证实了孟德尔在植物中的观察研究结果。自此以后几乎所有研究动、植物受精作用的学者都同意细胞核的融合是这种作用的决定性因素。 这些发现彻底否定了物理主义者所声称的传递激发是受精作用的精髓的论点。自然的和由化学诱发的单性生殖确实证明了无须按精就能引起卵的分裂。然而真正的受精作用毫无例外地始终是雌、雄配子的细胞核中所含物质的互相混合。接受这一结论只不过是反对19世纪后半期物理主义信条的一种表现。对力、运动、数量的过分重视和相当起麻痹作用的先入为主偏见被对形体、性质的重要性日益深入的认识所取代。大致在同一时期在化学领域中也发生了类似的思想解放（Fruton，1972）。然而在19世纪70年代对“力”的迷信还是如此顽固以致许多细胞学家对细胞的“运动器”，星体（aster）和纺锤丝比对细胞核和染色体更加注意。另外一些细胞学家则清楚地认识到物质的混合是受精作用的真正本质，这种见解引出了一系列完全新的问题，将在下一节介绍。最重要的是，它鼓励，实际也是要求，研究细胞和细胞核的显微结构。 15．3变异和遗传的物质基础 18世纪末和19世纪初，当变异的重要意义开始被人们认识到以后，它的原因是什么的问题便提了出来。变异可能影响生物机体的各个方面，即所谓的性状，无论是形态性状还是非形态性状。必然有某种生理的或化学的因素作为引起变异的基础。起初甚至连应当提什么问题也不清楚，只是在事后才有可能将这些问题用准确的语言表达出来。 要回答的问题是：某一物种的全部性状（性状总体）是由单一、相同的物种特异性物质控制还是每个性状由可以独立起变化的个别颗粒物质控制？遗传物质是“软（式）” 的（即在个体的一生中或其世代中能逐渐发生变化）还是“硬（式）”的（即完全固定不变，只有通过骤然的激烈变换——后来称之为“突变”才能发生变化）？遗传性颗粒是怎样在体内形成的？在受精后由父本和母本提供的遗传颗粒是保持其完整性还是完全融合？ 上面这些就是19世纪后半期关于繁殖和遗传所提出的最突出的问题。在全部生物学史上某些最有才华的学者都曾为之绞尽脑汁并大大减少了可能的答案数目。他们提出了很多具有创见性的假说（其中有一些是正确的，也有很多是错误的），但他们也一再发现，他们自己面临许多看来是无法调和的矛盾。他们怎会料到，他们的这些问题的最后答案竟然会是大约一百年以后由分子生物学作出的！这个前所未有的新奇答案是，遗传物质仅仅是一份“蓝图”，一种信息指令程序，完全不是发育着的有机体的成形部分，而且在化学上也与之完全不同。但是最后取得这一答案还有很长的路要走。让我们先折回到1850年。 当时原生质还刚刚被命名并被认为是活生物的主要物质。有人主张（Brucke，1861）原生质除非是由“基本单位”（某种结构元件）构成，它就不大可能体现其功能。实际上凡是对遗传现象深思熟虑过的学者都认识到细胞作为一个整体不可能是遗传的基本成分。总之，每个配子只是一个细胞，作为一个单元，它怎么能够控制某个个体在性状上的千差万别的差异？ 从1860年到1900年关于细胞质和细胞核中结构成分的性质一直是无尽无休的臆想热点，其中绝大多数既无实验依据又不是观察结果。自斯宾塞（Spencer，1862）到魏斯曼（Weismann，1892）这段时期的纵情臆想与以前30年（1835－1864）的态度迥然不同，那段时期相当严肃，显然是对《自然哲学派》的过分臆测阶段（1800－1835）的一种反作用。在这段相当严肃的时期中，许多学者单纯描述他们最感兴趣的问题并坚决不作概括性结论，即使这些结论看来是显而易见的。 在另一个严肃阶段（1895年以后）中，摩根曾讥笑魏斯曼是“来自弗莱堡的哲学家”，并在还原论和实证论的势头上把“臆想”嘲笑得一无是处。有些批评虽然是正确的（见下文），但在这里倒想为这些臆想的学者说几句公道话，因为他们作出了一件非常宝贵的贡献：他们开始提出正确的问题，尽管他们的答案可能是错误的。如果不知道应当提出什么问题，又怎样会找到答案！错误的学说往往能给一个停滞沉寂的领域带来活力，而它们所引起的新的观察研究往往又几乎自动地导致它们本身最后被否定。 几乎所有的这些学者都假定生物的躯体，包括其细胞，由很小的颗粒构成。这些颗粒必须具有个体发生上和遗传方面的双重功能。这是他们大家都一致同意的。除此而外，在其他各个方面他们之间又有分歧。关于这些颗粒的实质、它们在发育中的作用、它们在世代之间的传递等问题上更是分歧极大。每个学者都会为这类颗粒创造一个新词并提出一种发育与遗传的新学说。 这些颗粒必须具有自我复制的能力，这一特点就是和无生物的根本区别，后者并不能自我复制。例如结晶的生长和细胞生长就按完全不同的方式进行。 最后，为了发生进化演变，这些颗粒必须或者具有不断变化的能力（“软式”遗传）或者几乎固定不变（“硬式”遗传）。完全固定不变将会使进化不可能实现，所以这些颗粒有的时候必须能够“突变”，也就是说从某种固定不变的状态转变成另一冲固定不变的状态。因此只有对这些颗粒的物理性质、它们在细胞中的位置与排列、它们的复制、突变等能够同时提供解释的传选遗传学说才是完整的。从1860年到1950年这90年间所提出的试图解答这些问题的某些遗传学说，多少是比较完整的。 第一个有关遗传和发育的概括性学说是由哲学家斯宾塞（1820－1903）完全根据演绎法提出的。它深受再生现象（如某些动物能重新长出失掉的尾巴）的影响。斯宾塞（1864）提出有某种大小介于细胞和简单有机分子之间的“生理单位” （physiclogical units）存在。这些单位被看作是能够自我复制、具有物种特异性的完全相同的单位（在某一个体内）。斯宾塞对同一物种不同个体的生理单位之间的差异作了似乎彼此矛盾的阐述。他将同胞动物之间的差异，归之于来自父本和母本的配子所含有的生理单位数目不同。生物的形体是由这些单位按预先确定的方式彼此连结起来的能力所决定，就像分子形成结晶时一样。另外，生理单位还具有对环境作出反应的能力，因而引起了获得性状遗传。 另一个重要的遗传学说是达尔文于1868年出版的《动植物在家养条件下的变异》一书中提出的泛生论（theory of Pangenesis）。德弗里于1889年正确指出，达尔文的泛生论实际上包含两部分，一部分是假定生物的遗传性是由生殖细胞中大量肉眼不可见的、各自不同的微芽（gemmules）体现的假说。这些微芽通过分裂而增殖，并在细胞分裂时由母细胞传给子细胞。 这一假说最重要的一点是，认为存在着大量不同种类的微芽（可以说是微芽种群），这和斯宾塞从本质论观点出发所设想的、在某一个体中完全相同的生理单位不同。达尔文泛生论的另一部分将在以后介绍。 在随后的15年中其他的一些学者也提出过类似的遗传微粒，例如Ellsberg（1874）和海克尔（Haeckel，1876）的“成形微粒”（Plastidules），这类微粒或者全都完全相同（和斯宾塞的生理单位相似）或者各不相同（和达尔文的微芽相仿），基本上并没有增添什么新的观点。 当时最试图说明一切而又具有纯推论性的遗传学说，是由瑞士植物学家内格里（Karl Wilhelm von nageli，1817－1891）于1884年提出的。他比前人更明确地指出生物有机体的原生质由两部分组成：普通的或营养性原生质和与生物有机体遗传成分有关的“特殊原生质”（idioplasm，一般译为异胞质）。这种区分是根据下述的观察结果作出的，即父本和母本为后代的遗传成分所作的贡献一般是相等的，虽然卵的重量或大小比精子的要高出一千多倍。因此，卵只有一小部分（大致和一个精子的重量相近）能够含有异胞质。人们可能会以为这一结论会促使内格里认定异胞质只存在于细胞核内。 奇怪的是实际并非如此；他认为异胞质是由细胞到细胞的长索状物质组成（与细胞核无关）。每股长索则由无数类群的分子团（micelles）构成，每股长索的横截面在各处都完全相同。每股各有其特殊性，由这些股合成的束来控制细胞、组织、器官的性能。生长就是这些股索的延伸，并不改变其稳定性。 内格里对异胞质活性的解释也别出心裁；他认为，这活性是由于股索中分子不同基团的激发状态不同所引起。这就是他为什么将他的推论称为“进化的机械-生理学说” s reason.他将几百页连篇累读的议论用十分矜持的语言来结束，“异胞质学说……能够对遗传的和种系的变化在自然界中得以发生（机械性地发生）作出唯一可能的说明（Nageli，1884：81）。Barthelmess（1952）说过，他之所以如此详细地介绍内格里的推测，是因为它们也许是那个时期各种臆测中最极端的例子：“今天我们对这幻想的空中楼阁当然会感到惶惑，对作者扬言只有按他的学说才能解开生物进化这个谜的自负不能不感到诧异。 ”然而也正是由于内格里对遗传和发育过程的各个可以想像得到的方面都作过推论，所以具有深远影响。事实上在此后的20年中这一研究领域内的所有文献无不以崇敬心情广泛引用他的论述。总之，内格里在他的那个时代是一位显赫的知名学者。然而，他的学说中几乎每一个细节都是根本错误的，而且几乎没有一点具有事实根据。在评价内格里的遗传学说时有一点必须注意，即他非常重视物种间的杂种，其中孟德尔的性状分离极为罕见或根本不存在。这是内格里无法理解孟德尔在豌豆中的发现的原因之一（见第十六章）。 内格里有一个观点对遗传学说真正具有十分重要的建设性影响，就是他坚持将异胞质和其余的原生质严格地区分开。正当内格里发表他的着作的同时先后有另外三位学者各自独立地得出了与内格里相同的结论并进一步推论遗传物质含于细胞核中（见下文）。 为什么内格里没有认识到细胞核是他的异胞质的所在地这个问题一直令人无法思议。因为在1884年，当内格里发表他的《进化的机械-生理学说》肘，细胞核在受精中的作用已广为人知，而且父本的和母本的异胞质处于相对平等地位（这是他作出推论的原因之一）本来也应当使内格里意识到细胞核的作用。1866年海克尔在证据很少的基础上推断，“细胞核司管可遗传性状的遗传，其周围的细胞质则负责日常生计或对环境的适应” （Haeckel，1866，I：287-288）。 动、植物受精作用的实质是父本和母本的生殖细胞（配子）互相融合，这两个配子在形成新的合子上各自作出了同样贡献，而且关键过程是两个配子的细胞核相互融合，这些观点到了1844年左右已经逐步确立并被有关学者普遍接受。人们的注意力便开始转移到细胞核上。细胞核是不是就像后生论者所设想的，仅仅是一团无定形的胚样物质、也许只是在融合时才激发了卵细胞的发育过程？或者是细胞核虽小，却具有严密结构，这肉眼不可见的显微结构是否就是受精作用之后的一切非常精确并具有特异性的发育过程的关键？如果把细胞核仅仅看作是细胞发育和细胞分裂的引发物，就会认为它在完成了这一任务后就会被溶解掉，在新的细胞分裂之前或至少是在配子形成之前再重新形成。 由于19世纪后半期的细胞学家所接受的都是生理学家或胚胎学家的教育训练，他们的侧重点是发育问题，因而用不着关心细胞核的连续性。他们很少过向性状是怎样从亲代传递到子代的遗传学问题。 1875－1880年之间由于Balbiani，van Beneden，Flemming。Schleicher，Strasburger等五位学者在细胞分裂过程中能够不断追踪其全部进程，因而“自由细胞形成”或细胞核“重新”形成这种信念的最后残余才得以完全肃清。这几位学者论证了三项重要事实： （1）在细胞分裂之前细胞核开始分裂，（2）细胞核物质的变化具有正常顺序（见下文），（3）细胞核分裂和细胞分裂的基本现象在植物界和动物界都是相同的。 越来越明显的是，细胞核的作用不单是生理性的（即纯粹物理意义上的作为细胞分裂的引发物）。它是具有严密组织的、很可能是按特定格局构成的结构。这种格局的实质此后一直是细胞学者不断关心的问题，仍然没有求得最后答案。 关于这方面研究进展的特点是分析越来越细。所涉及的步骤是从完整个体转向细胞，从整个细胞转向细胞核，现在则从完整的核转向到它的主要结构成分、染色体。 15．4染色体及其功能 在遗传学诞生（1900）之前25年，根据研究者的兴趣不同对细胞核分裂也有两种完全不同的解释。对兴趣主要在于发育问题的学者来说最重要的问题是，未分化的卵细胞通过简单的分裂怎样能产生组织学家和生理学家所确认的神经组织、腺组织、表皮等成百种组织的分化了的细胞？举例来说，这种考虑就支配了魏斯曼的学说。这一类学者主要关心的是近期原因。 后来，关心传递遗传学的少数学者提出了下面的问题：通过哪些机制使细胞核物质的分裂恰好是相等的一半传递给子代细胞？由此可以看出，两类学者提出了完全不同的问题。胚胎学家的问题是，我们怎样能将细胞分裂解释为表现型分化的机制？传递遗传学家则关心遗传型的准确延续保持，也就是说遗传问题．传递遗传学家的解释根本未触及分化问题，也可以说是留下分化问题全然没有解决；而发育遗传学家所提供的答案则又引出了一些难题，而且后来发现这些难题是在遗传传递上所无法解释的。 很明显，只有等到对细胞分裂时细胞核内部所发生的变化有了较深入的了解之后才能迈出解决矛盾的第一步。我在这里将不详细介绍细胞分裂（有丝分裂）的机制，虽然它是生物界中已知的最奇妙的过程之一。 A． Trembley（1710－1784）在18世纪40年代首次描述了原生动物的细胞分裂。 18世纪后半期在硅藻以及其他藻类中也发现了细胞分裂；19世纪30年代中，Ehrenberg对某些原生动物的细胞分裂曾进行过详细研究。自19世纪40年代以后对体细胞的分裂过程（弗莱明于1882年将之称为有丝分裂）的描述也越来越频繁（Wilson，1896；Hughes，1959）。 当细胞分裂时它的核也同时分裂，而且后来被认为是细胞分裂最重要的方面。起初人们认为核仅仅充满了颗粒状物质，当细胞分裂时，等量地分配在子细胞的细胞核中（直接细胞分裂）。然而随着光学部件质量的提高以及显微技术（如染色技术）的改进使细胞（及核）分裂的每个阶段都能更精确地加以研究，上述的简单画面就必须加以修正。在有丝分裂的某些阶段，细胞核似乎被丝、线、带充满，因为这些丝、线或带染色很深，所以被弗莱明（Flemming，1879）看作是由染色质构成。由于染色体这一名词直到1888年才由Waldeyer提出，所以在这之前每位学者都采用不同的术语和不同的描述。 Remak（1841），Nageli（1842），Derbes（1847），Reichert（1847），Hofmeistert（1848，1849）以及Krohn（1852）等所观察到的很可能就是染色体，他．们都见到分裂象（mitotic figures），有时还提供了中期板的描图。必须注意的是，他们的这些文章都是在“自由细胞形成”学说时期发表的，其中有些学者还认为细胞核在分裂过程中被溶解，两个新细胞核由细胞液重新产生。 第一位观察到细胞核改组（重新组成）的复杂性的是法国动物学家E． G． Balbiani（1825－1899）。早在1861年他非常出色地描绘了某一原生动物有丝分裂的各个阶段。 然而遗憾的是他对所观察到的作出了完全错误的判断和解释。由干他不了解原生动场只是单个的细胞，便将细胞核看作是睾丸，染色体是精子。这样一来，这一开拓性的研究对后来并没有什么影响。直到19世纪7O年代中期核的直接分裂才被大多数学者承认。 由于显微镜技术的进步，得以证实细胞核（及其染色物质）在连续的细胞分裂之间并不溶解，在静止期也以不同的形式保存着。此外，这种技术进步使得人们对有丝分裂的三个主要（以及一些次要的）阶段（分期）可以进行准确的描述；这三个阶段后来被依次称为前期、中期、后期（见图1）。 图1有丝分裂的各个时期，（a）早前期。（b）晚前期；显然在早前期中，每个染色体分解成两个染色单体。（C）中期的极面观。（d）早后期。（e）晚后期。（f）末期。（a），（b），（f）中的黑点代表核仁。 静止核（细胞分裂之间）的染色效果差，然而有迹象表明大部分核物质构成一条或几条细丝或者由丝构成的网络。当细胞分裂即将开始时，包覆细胞核的膜消失，染色质丝凝缩并且更容易被相应的染料着色。最后这些物质（染色质丝）收缩成少数着色很深的带状物，称为染色体。每一物种在正常情况下，其每个细胞都含有一定数量的染色体（人类合有46条染色体），在核分裂时这些染色体有规律地排列在细胞两极之间的赤道平面上，形成“赤道板”。正是在这一阶段（中期）每个染色体一劈为二。起初认为是横向劈开，这种错误认识引起了不少混乱与麻烦。最后才清楚地观察到（Flemming，1879）它们是纵向劈开的并且是在中期以前，也就是说当染色物质（染色质，chromatin）还处于未凝缩状态时，几乎无法观察到。到了下一阶段（后期）染色体被劈开后的两半（染色单体，chromatids）使彼此分开并移向细胞的两极。在两极处围绕着染色体束形成新的核膜，染色体又回复到丝状，而且大都处于观察不到的静止状态。 确认有丝分裂的各个阶段并对之作出正确的说明，花费了很多研究者的大量精力与时间。1873年Schneider，Butschli和Fol首次相当准确地描述了有丝分裂过程。这一过程的重要意义立刻就被人们认识到并成为一股研究热潮的主题。动物学家van Beneden和植物学家Strasburger对之作出了特别重要的贡献。8年以后一位评论家列出了1874-1878关于细胞分裂及有关问题的194篇文章（出自86位研究者）。然而其中没有一个人在准确描述和正确解释有丝分裂上赶得上弗莱明，他在1882年写了一篇关于这一领域研究现状的出色评述文章。对植物有丝分裂的观察揭示了它和动物细胞的完全相同。 这是论证动物和植物的细胞性过程一致性的又一证据（大约在半个多世纪以后才发现真核生物与原核生物在细胞分裂上的明显区别）。 每一次新的观察研究都证实了细胞分裂过程的极端复杂性。为什么必须像这样复杂？ 为什么细胞和核不像Remak所设想的那样简单地一分为二？这就是茹在1883年向他自己提出的问题。当时正是只提问近期原因的年代，并归结为内格里的机械生理学说，而茹则想要知道终极原因。他大胆地提出了为什么问题：如果简单分裂能办到的事为什么需要如此复杂的过程？他的回答是，如果细胞核物质是同质的。则核的简单直接分裂就足够了。但是，如果核物质是异质的，如果核物质是由各自具有不同遗传能力的无数颗粒组成，那么就只有一种可能的分裂方法使细胞核物质的每个颗粒都出现在两个子代细胞中。这种方法是将所有的颗粒串联起来，就像一串珍珠似的，然后将这一串纵向地劈开，“因而每一个染色质粒就分成为两半，这样一来从一串染色质粒就形成了互相紧贴着的两串（染色质粒）”（Roux，1883）。 在前此几年中曾有人一再提出（Balbiani，1881；Strasburger，1882）在静止核中一切染色质是按一条长丝的形式排列。茹的假说就是奠基于这种观察之上：“（有丝）分裂象……就是使细胞核不仅定量的而且按其质量和个别性质进行分裂的机制。核分裂的主要过程是每个母本颗粒的一分为二；所有的其他过程的目的只不过是将子代颗粒之一传送到一个子细胞的中心，将另一个子代颗粒运送至另一子细胞中心。”这一过程保证了两个子细胞无论在定量上还是定性上都完全相同。 这就是茹的19页全文的主题要旨，但是后来他却后退了。他用下面一段话表示了对不相等分裂可能性的让步：“由于（蛙卵）第二次分裂决定胚胎的前端和后端，又由于必须假定前端和后端的发育不同与物质不相等有关，所以在第二次分裂时细胞核物质很可能是分裂成性质不同的部分”。（1883：15）。这就和他的主要论点相矛盾，因为在有丝分裂的第一次与第二次分裂之间并没有任何区别。 茹的主要论点，均等分裂机制，当然恰好就是现代对有丝分裂的解释，这种解释竟然很奇怪的被在随后的年代中试图用核物质在子代细胞中的不等量分配来解释分化的学者（如魏斯曼）忽略了。然而正如威尔逊所说（1896：306），“细胞分裂中没有任何可见现象提供了哪怕是一丁点儿性质不同的分裂迹象。相反，一切事实都指陈染色质的分裂是绝对校精确均等的方式进行。” 坦白的讲茹的学说只是一种推测，然而这推测和内格里或洛布（Jacques Loeb）的推测却大不相同。茹按照哈维（Harvey）的传统提出了为什么的问题（哈维对静脉中存在瓣膜的好奇心对他发现血液循环有极大帮助）。实际上茹含蓄地问起：这一复杂过程有什么选择价值？内格里和洛布并没有提出为什么问题；而是企图按还原论者的方式，以物理和化学来解释生物学现象。他们的那种推测在当时远比茹的“目的论的”或“亚里斯多德式的”（当时就是这样称呼）研究路线更受尊重。茹的假说，和赫特维克的受精学说相仿，是生物学从纯粹物理主义者的解释中逐渐解脱出来的又一例证。 细胞核的历史描述到了1880年已经结束，因为细胞学的每一项研究都证实了弗莱明的警句：细胞核来自细胞核。自此以后注意力中心便转移到染色体上。在细胞分裂中染色体起了什么作用？ 1883年比利时细胞学家van Beneden发表了一篇非常出色的关于马蛔虫（Ascarisbivalens）受精作用的分析文章。这种蛔虫只有四个染色体，是十分难得的实验材料。 他指出马蛔虫的配子只有两个染色体，授精的雄性核并不和雌性核融合，它们的核物质也不融合在一起；但是雄核的两个染色体只和雌核的两个染色体相连结形成具有四个染色体的合子的新细胞核（他称之为染色粒）。受精卵（合子）第一次分裂时，四个染色体中的每一个染色体都纵向分裂（与其他有丝分裂相同），每个子（代）细胞接受曾参与受精作用的相同的、父本和母本的各两个染色体（见第十七章）。 虽然van Beneden观察到新个体的核物质恰好有一半来自父本，另一半来自母本，然而他并没有在他的观察结果和遗传现象之间确立任何联系。由于他不是一位理论家，所以他也没有从他那出色的细胞学论证中作出显而易见的结论。这结论几乎是在同时由四位德国生物学家各自独立地作出的，虽然Gallon（1876）又在他们四人之前。 魏斯曼在其深入分析遗传问题的着作（Weismann，1883）中断定细胞核物质就是遗传物质，并将之命名为“种质”（germ Plasm），这比内格里提出“异胞质” （idioplasm）早一年。“遗传是通过将一种具有一定化学结构、尤其是一定的分子结构的物质（种质）从一代传送到下一代而实现的。”1884年着名的动物细胞学家赫特维克和着名的植物细胞学家E．Strasburger查阅了过去10年的大量资料，最后得以论证，除了细胞核是遗传的载体而外，其他的解释都是不合理的。他们三位学者一致认为是海克尔（Haeckel）首先提出细胞核的功能。赫特微克与Kolliker（1885）更进一步断言细胞核中真正起作用的物质不是别的就是米歇尔从细胞核中分离出的他称之为核素的特殊化学物质。Kolliker强调指出它必然是遗传的物质基础。 后来甚至可以通过实验证明核是遗传物质的基地。波弗利（Boveri，1889）在一系列独创性的研究中运用强烈震动的办法将海胆卵震碎，发现没有核的卵碎片能够被形态上极不相同的其它种（和属）海胆的精子授精。即使这种单倍体杂种卵碎片只有父本染色体进入母本细胞质，它也正常发育，但这样形成的动体主要具有父本特征。通过同时用两种不同种的海胆精子授精所形成的（对照组）幼体则具有中间型形态特征。经由实验明确无误地证实了细胞核决定生物