MCB 142
MAJOR ADVANCES IN UNDERSTANDING EVOLUTION AND HEREDITY
FALL 2015
WEEK 3 SEPTEMBER 22 AND 24
SEPTEMBER 22: THE CELL THEORY I. ALL CELLS FROM CELLS. PRIMACY OF THE NUCLEUS.
Development of the microscope. Brown's description of the nucleus. Scheiden and Schwann's findings
that plant and animal tissues are composed of cells. Remak's observation of cell division. Virchow's
dictum "omni cellula e cellulula". Hertwig's evidence that egg and sperm nuclei fuse during fertilization.
SEPTEMBER 24: THE CELL THEORY II. CHROMOSOMES AND MITOSIS. EVIDENCE FOR A REDUCTION
DIVISION. FUNCTIONAL INDIVIDUALITY OF CHROMOSOMES.
Flemming's description of mitosis. Roux's interpretation of mitosis. Van Beneden's observation that
sperm and egg chromosomes have half the number of chromosomes present in the zygote and the
somatic cells. Weismann's germ plasm hypothesis. Boveri's evidence for functional individuality of
chromosomes.
Readings to be discussed on Tuesday, September 22

Introduction, from Edmund Wilson, The Cell in Development and Inheritance, 2nd edition (London:
1900).
Read pages 1-15.

English translations of Theodor Schwann, Microscopical Researches into the Accordance in the
Structure and Growth of Animals and Plants (1839) and of Matthias Schleiden, Contributions to
Phytogenesis (1838). Printed together for the Sydenham Society, London, 1847.
Read The parts indicated by penciled brackets in the posted excerpts from Schwann and from
Schleiden.
Inspect Schleiden’s Plate I and its legend at pp 265-267, particularly the five succesive stages of
“free cell formation” in the embryo sac of the New World palm Chamaedorea schiedeana depicted
in Figure 1, a through e.
If you would like to see the entire book it may be found at:
http://books.google.com/books?id=m9kHAAAAIAAJ&printsec=frontcover&source=gbs_ge_summa
ry_r&cad=0#v=onepage&q&f=false
In order to navigate to particular regions of the book click on the small black triangle at the top right
of the screen immediately to the right of “front cover” (not the triangle farther to the right).

Oskar Hertwig (1875) Contribution to knowledge of the formation, fertilization and division of the
animal egg. Morphologisches Jahrbuch 1: 347- 434.
Read posted excerpts.
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Readings to be discussed Thursday, September 24

Edmund Wilson, The Cell in Development and Heredity, 3rd edition (New York: 1928) Chapter XII,
Heredity and the Chromosomes.
Read posted excerpt.

Walther Flemming (1879) Contributions to the knowledge of the cell and its life appearance. Arkiv
für Mikroskpsiche Anatomie, 16: 302-406.
Read posted excerpt.

Excerpt from Wilhelm Roux (1883) On the significance of nuclear division figures. A hypothetical
discussion. Gesammelte Abhandlungen über Entwickelungsmechanik der Organismen, 2: 125-143
(Leipzig: 1895).
Read posted excerpt.

Excerpt from Edouard van Beneden (1883) Researches on the maturation of the egg and fertilization.
From Archives de Biologie 4: 265-640.
Read posted excerpt.
 Theodor Boveri (1902) Über mehrpolige Mitosen als Mittel zur Analzyse des Zellkerns.
Verhandlungen der physicalisch-medizinischen Gesselschaft zu Würzburg. Neu Folge 35: 67-90 in
Chapter 7: Blocks to Polyspermy: On Multipolar Mitosis as a Means of Analysis of the Cell
Nucleus.
Read the article.
Study Questions
Please hand in Tuesday September 22
1.
As described by Wilson in 1899, what at the time, were (i) the generally accepted views and (ii)
the continuing controversies regarding each of the following questions?
a) Are all plants and animals are made up of cells and the products of cells?
b) Can cells arise both by division of pre-existing cells and also by what Wilson on page 9 calls
“free cell formation”?
c) What part of the cell is the vehicle of heredity?
d) Is a sperm ("spermatozoön") a cell? Is fertilization of the egg normally accomplished by a
single sperm?
e) Can acquired characters be inherited?
2.
What are the essential attributes of what Schwann calls "Zellenkeimstoff" (cell germ substance)?
3.
According to Schleiden, where are new cells formed? What misconception about the origin of
cells is evident in Figure 1 of Plate I of Schleiden?
4.
What evidence does Hertwig present in support of his conclusion that the sperm nucleus (i)
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enters the egg and then (ii) fuses with the egg nucleus in the course of fertilization?
5.
What two observations does Flemming cite in support of his conclusion that the "threads" divide
longitudinally?
6.
What evidence does Flemming present that his description of the longitudinal division of nuclear
"threads" (chromosomes) in salamander is not based on an artifact of the picric and chromic acid
fixatives he used?
7.
After asking "What, after all, does this mean", Flemming presents an hypothesis. What is his
hypothesis?
8.
a) What reason does Roux give for believing that the function of nuclear division is the
equipartition of qualities rather than the equipartition of mass?
b) Describe each of the mechanisms discussed by Roux that might ensure that a cell containing a
large number of “mother granules” of different “qualities” contributes to each daughter cell a
daughter granule from the division of each mother granule.
c) What arguments does Roux present for and against each mechanism?
10.
To what fundamental questions do the observations of van Beneden provide answers? What are
the corresponding observations?
Some terms used by Schwann and/or Schleiden
"intussusception" means taking up from outside, referring to the growth of a cell by taking up material
from outside itself.
"quartum non datur" means there is no fourth possibility, referring to the three places where new cells
might form: inside, at the surface, or outside of existing cells.
"Zellenkeimstoff" means cell germ substance, the structurless fluid in which Schwann asserts new cells
are formed. Synonymous with "cytoblastema".
Some Background
Edmund Beecher Wilson
1856-1939
Edmund Beecher Wilson, professor at Bryn Mawr and then at Columbia, was one
of the most influential cell biologists of the period just before and just after the
"rediscovery" of Mendel’s 1866 paper. Wilson wrote three editions of his famous
textbook, The Cell in Development and Inheritance (or The Cell in Development and
Heredity, depending on the edition). The first reading this week is from the second
edition, which was completed only months before the rediscovery, in 1900, of
Mendel's 1866 paper. We read it for its lucid overview of cell biology of the time.
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The conclusion that all animals and plants are made up of cells and cell
products, put forward already by Lamarck in his "Philosophie Zoologique"
(1809) and subsequently supported by the observations of several others,
became firmly established with the work of the botanist Matthias
Schleiden in Belgium and the zoologist Theodor Schwann in Germany in
the late 1830s, based on their microscopic examination of a wide variety
of plant and animal tissues, using the presence of a nucleus as a criterion
Theodor Schwann
1810-1882
for defining a cell. Nevertheless, both men failed to realize that new cells
arise by division of pre-existing cells and thought instead that cells arise
de novo from a liquid or gel (“schleim”) between or within cells, the so-called “free cell
formation.”
It appears to have been the Polish cytologist Robert Remak working in Berlin who,
skeptical of free cell formation because of its resemblance to the discredited idea of
spontaneous generation of life, proposed in 1841 on the basis of his observations of cell
division in chicken erythrocytes, that cells arise by the binary division of existing cells.
The conclusion was famously encapsulated in 1855 in the dictum Omnis cellula e cellula
("All cells come from cells") by the German biologist and pathologist Rudolf Virchow.
Leopold Auerbach
1828-1897
Herman Fol
1845-1892
Mathias Schleiden
1804-1881
Robert Remak
1815-1865
In 1874 Leopold Auerbach in Germany published camera lucida drawings of the nuclei at
successive stages of fertilization of the egg of the parasitic nematode, Ascaris equorum (the
horse thread-worm). He depicted two nuclei inside the egg approaching each other and
finally fusing but did not identify them as the pre-existing nuclei of egg and sperm,
concluding instead that the two nuclei he saw had formed de novo from substances
contributed by the sperm and egg.
After reading Leopold Auerbach’s paper, the German zoologist Oskar Hertwig,
decided to investigate fertilization in sea urchin eggs, a particularly favorable system,
owing to their transparency and large size. Hertwig was able to see in living material
a few minutes after the sperm attaches to the egg that a nucleus appears inside the
egg, approaching and then fusing with the egg nucleus. Although he did not see the
sperm nucleus actually entering the egg he assumed, correctly, that the nucleus he
saw approaching and then fusing with the egg nucleus had come from the sperm.
Almost simultaneously, the Swiss zoologist Hermann Fol, observing fertilization in
the starfish, actually saw the sperm nucleus enter the egg. The important conclusion
that fertilization involves the fusion of the egg nucleus with a single sperm nucleus
was published by Hertwig in 1875 and by Fol in 1876.
Oskar Hertwig
1849-1922
Walther Flemming, Professor of Anatomy in Kiel, Germany, in 1879 published remarkably
clear drawings of mitosis in cells of salamander larvae, the chromosomes of which are
particularly large and thick and therefore visible even in live material, dispensing with the
use of fixatives that could cause artifacts. Using the newly developed aniline dyes that
preferentially stain chromatin (a term coined by Flemming) he showed that during nuclear
Walther Flemming
1843-1905
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division each “thread” (chromosome) splits longitudinally into two “half threads” (sister chromosomes)
and that these then move apart in apparently equal numbers to the two daughter nuclei. Owing to the
large number of chromosomes (2n=24) in the salamander, Flemming could not follow the movements of
individual sister chromasomes but speculated that the strict longitudinal division that he observed served
the function of providing each of the two daughter nuclei a daughter of each initial chromosome. In a
subsequent publication, Flemming coined the term “mitosis” (Greek mitos, thread) for the process of
nuclear division.
Although Flemming realized that the longitudinal splitting of the chromosomes
provided a mechanism for partitioning them to daughter nuclei, it was Wilhelm Roux
(1850-1924) in Germany who in 1883 provided a brilliant interpretation of the
meaning of mitosis. In particular, Roux assumed that the hereditary material of the
nucleus was composed of a large number of granules, discrete hereditary qualities. He
realized that the partitioning into two parts of a mixture composed of many different
kinds of individual components so as to assure the presence of each kind of element in
each part could not be achieved by simply mixing them and dividing the resulting mass
in two unless there are very many copies of each component and the components do
Wilhelm Roux
1850-1924
not preferentially aggregate or otherwise interact. That would be like dividing a
mixture of two molecular species, say a mixture of two salts, in which case the vast
number of ions of each type would assure the presence of some of each type in both parts.
Alternatively, if there is only a rather small number of each kind of “bit” or “granule”, then, as Roux
argued, no such simple halving of the mixture can ensure that a representative of each and every kind
will be present in both halves. After considering and rejecting arrangements of the bits in twodimensional arrays, this line of reasoning led him to propose that a linear array including one of each
kind of granule would, upon longitudinal division, provide an
excellent means for exact partitioning. By such reasoning,
Roux showed how the problem of equal partitioning could be
solved and offered it as an explanation for the behavior of
Flemming’s “threads” in mitosis.
In 1883, Edouard van Beneden, in Belgium, examining
fertilization in the horse thread worm Ascaris maglocephala
Edouard van Beneden
(modern
name parascaris equorum) made the important
1846-1910
discovery that sperm and egg nuclei each contribute two
chromosomes to the zygote, a finding that demanded a reduction of the
chromosome number somewhere in the lineage leading to sperms and eggs.
August Weismann
1834-1914
As we discussed last week, August Weismann, the German naturalist, embryologist
and the leading biological theorist of the period between Darwin and Mendel strongly
supported the Darwin-Wallace theory of evolution by natural selection of heritable
variation but decisively refuted the previously general belief in the inheritance of
acquired characteristics. Initially accepting Darwin’s explanation of the source of
variation as being “conditions of life”, including heritable effects of "use and disuse",
Weismann starting in 1882-83 advanced a number of powerful arguments to the
contrary: (i) that it could not account for the adaptations of insects that do not
reproduce, such as warrior ants and termites; (ii) that the germ cells are set aside from
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the soma early in animal development; (iii) that all claims of inheritance of acquired characteristics
could be given alternative explanations and (iv) in analogy with a telegram sent in English being
received in Chinese, that information from the soma could not be deciphered in the germline. And, as we
have read, Weismann conducted his own extensive test of the possible heritable effects of cutting off the
tails of mice, both parents for 20 generations, with entirely negative results. Therefore rejecting any
participation of the soma in heredity, Weismann postulated the existence in the germ cells of a material
carrier of heredity, the “germ plasm”. Moreover, accepting the theoretical argument of Roux that the
behavior of chromosomes in mitosis must constitute a mechanism for exactly equal partitioning of
diverse "qualities" between sister cells, Weismann concluded that the germ plasm resided in the
chromosomes. Assuming that such qualities were in fact the determinants of heredity and that, as Van
Beneden had shown, both parental gametes contribute an equal number of chromosomes during
fertilization, Weismann further concluded that in each generation there must be a special cell division
the function of which was to reduce the number of qualities (and chromosomes) by half. It was known
that the last two cell divisions leading to egg production, the "maturation divisions" were unusual in
several respects, including, in oogenesis, the production of polar bodies. Weismann argued that the
second of these two divisions was the predicted "reducing division" and that in both sexes "there must
be a form of nuclear division in which the ancestral germplasms contained in the nucleus are distributed
to the daughter-nuclei in such a way that each of them receives only half the number contained in the
original nucleus." Initially thinking that such reduction was accomplished by the expulsion of the polar
bodies in oogenesis, this view became untenable when it was later established that there are no polar
bodies in spermatogenesis. (From your knowledge of meiosis, how is the reduction in chromosome
number accomplished in gametogenesis?) Although we do not read any of Weismann's somewhat prolix
writings on his germ plasm proposal and his speculations regarding the role of the chromosomes in
heredity, his germ plasm proposal was a major advance in unerstanding heredity.
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