Coleman-Cell, Nucleus, and Inheritance: An Historical Study

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Cell, Nucleus, and Inheritance: An Historical Study

Author(s): William ColemanSource: Proceedings of the American Philosophical Society, Vol. 109, No. 3 (Jun. 15, 1965), pp.124-158Published by: American Philosophical Society

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CELL, NUCLEUS, AND

INHERITANCE: AN

HISTORICAL

STUDY*

WILLIAM

COLEMAN

Department ofthe Historyof

Science,

The

Johns

Hopkins University

T.

HEREDITY

AND VARIATION

TilEr transmutation

of biological species

by

means

of natural

selection

Charles

Darwin re-

garded

as wholly

dependent

upon

the occurrence

of variations

in the structure,

behavior,

and

vital

processes

of animals

and plants.

Variation

was an

established

fact of natural

history

and no

mere

hypothetical

necessity.

"No

one supposes,"

Dar-

win justifiably

laimed,

"

that all the

individuals

of

the same species

are

cast in the

very

same

mould."

1

It

was

just these

individual

differences

between organisms

which

provided

the

raw ma-

terial

for the

accumulative action

of

natural

selection. The latter agency brought forth the

divergence

of specific

character,

a change

pre-

sumably representing

the origination

of

new

and distinct species.

A

matter

so important

as

variation

invited

further

and more exact

inquiry,

particularly

with

regard to problems

of

causation

and

trans-

mission. The

cause

of

any

particular

variation,

Darwin realized,

was

still beyond

comprehension.

In

such

circumstances

one spoke

as if variations

were

due to

chance. Erroneously

believing,

however, that

the

amount

of variation was

signifi-

cantly greater among groups of domesticated

animals

and

plants

than it

was

in

any

natural,

untamed population,

Darwin

concluded

that

the

conditions

of

ife under

domestication

were

in

some

way responsible

for

inducing

variation.

The

reproductive

system

was

rendered

more

plastic

and

the

"male

and

female

elements

[seemed]

to

be

affected

before

that

union

takes

place

which

is to

form

a new being."

2

Variation,

therefore,

was

an

organism's

response

to the influence

of

external

agents.

Use

and disuse

of various

parts

as

well

as correlative changes

of different truc-

tures were also thought to contributeto organic

*

I thank

MM.

F.

L.

Holmes,

E.

Mayr,

C.

P.

Swanson

and

C.

Zirkle

for

their criticism

of an

earlier

draft

of

this

paper.

G. Uschmann

kindly provided

details

con-

cerning

0.

Hertwig's

teaching

activity.

1

C.

Darwin,

On

the

Origin

of

Species

by

Means of

Natural

Selection.

A facsimile

of the

first

dition.

With

an

Introduction

by E. Mayr (Cambridge,

Mass.,

1964),

p.

45.

2

Ibid.,

p.

132.

variability.

Darwin's

position

was

ambivalent

although t appearsnot self-contradictory. hen

natural

election

eemed

nsufficient

e introduced

external or

Lamarckian

factors

to account

for

specific

change.

Moreover,

environmental

n-

fluences

e urged

as the

cause of variation

tself,

variation

which, in

strict

selection

theory,

was

admitted

ut (wisely)

not explained.

Variation

was obviously

ssential

othe

evolutionary

rocess,

whether

onceived

n Lamarckian

or

selectionist

terms,but

what

was the

nature and

origin

of

variation?

To this

admittedly

entral

uestion

f

evolution

theory

neither

Darwin nor

his

con-

temporaries ffered consistent r satisfactory

answer.

On the

one hand,

the

arguments

f the

Origin

f

Species developed

he dea that

variation

was

a fundamentalttribute

f

all living

beings.

On the other

hand,

no mechanism

ither

morpho-

logical

or physiological

was proposed

to

account

for

his

fact.

Variation

was assumed

nd

described

but

not explained.

Darwin

in 1859

had already

pointed

to

the

sexual elements

s the bearers

during

generation

of

the

hereditary

endencies

f the

organism.

The

egg

and

sperm

rovided

continuity

f generations

and alonemadepossibletheperpetuation,s well

as the

variation,

f the

manifold

orms

of

life.

Although

not discussed

n

detail,the

germ prod-

ucts

seemed the

crucial

intermediaries

etween

any two

generations.

Evolution

theory

s es-

sentially istorical.

It

considers he

changes

and

presumed

causes

of the

diverse

manifestations

of

lifewhich

have populated

nd

still occupy

the

surface

of

the

globe.

Evolution by

natural

selection postulates

that change

occurs

only

through

he

gradual

accumulation

f small

vari-

ations.

For

this

to

be true, t

is essential

that

an inviolable ontinuityf generations e estab-

lished.

The connecting

ink

urely

must ie

in

the

egg

and

the sperm.

What was

the

nature

f the

germinal

lements?

Was it their

ross

substance,

hat

s,

matter

lone,

or

their

molecular xcitations,

he

actionof

this

matter,

which

nitiated

new

generation?

How

could the simplegerm

cells

control,

s

they

must,

the

complex

processes

of

embryonic

rowth

nd

PROCEEDINGS

OF

THE

AMERICAN

PHILOSOPHICAL

SOCIETY,

VOL.

109,

NO.

3,

JUNE,

1965

124

This content downloaded from 168.176.5.118 on Tue, 27 Jan 2015 18:16:48 PMAll use subject to JSTOR Terms and Conditions






VOL. 109,

NO. 3,

19651

CELL,

NUCLEUS, AND INHERITANCE

125

differentiation

How

could

the

egg

and

sperm

account

for the

origin

and transmission

f

in-

heritance

and, at the

same

time,

serve

as

the

basis

of variation?

Heredity

nd variation

were

themselves

efinite

roblems

nd,

in

association

with evolutionand ontogeny,helped to draw

attention o the structural

nd

functional

meaning

,of oth ell and nucleus.

During

the late nineteenth entury he

terms

"heredity"

nd "variation"were ess casual descrip-

tive

words than titles for forces

believed

ntrin-

sic to the

organicrealm.

"Heredity"

was

ideally

a

conservative orcewhose

perfect

ction ensured

that the

offspring ould always closely resemble

their

parents. The

resemblance, owever,

was

never xact. Deviations rom

truerepresentation

of

the parent

were noted

as

variations

nd

were

attributedto

a

force

directly antagonistic to

heredity, force designated"variation." In a

discussion of

then (1885) current theories of

inheritance, harles van

Bambeke, Belgian cy-

tologist, ave excellent xpression

o these

deas:

Toutefoisa ressemblancees

procrees

vec es pro-

cr6ateurs

'est

amais absolue.

Car

l'heredite

u

la

force

onservatricee trouve ontinuellementn lutte

avec une

autre orce, reatrice elle-la, a

variabilite.

Pendant

'herediteravaille maintenires formes r-

ganiques ans es limites e leurs

speces, faire ue

la

descendance essemble ux ancetres, produire

toujours

es

generationsoujours

rappees

la

meme

effigie,

a

variabilite,lle,poursuit n butdiametrale-

ment ppos6. Elle tend onstammentmodifieres

caracteres

pecifiques, infirmereurconstance,eur

immutabilite.

'est a la lutte

ou plutot l'action

combinee e ces

deux forces ue toutes es especes

vegetales

t animales ui peuplente globe doivent

leur

rigine.3

In

effect, an Bambeke

only elaborates upon

long-familiardeas. Darwin's suggestion hat no

two individuals

are ever

quite alike

is based

upon

similar

reasoning.4

Between

1859

and

1885

a

major advance was

made

n

the tudy f heredity

nd variation. First

the cell and then the nucleus were recognized

as

the vehicle of inheritance.

Darwin himself

was

neither

histologist or a cytologist nd only

in

1868 did

he publish brief tatement elating

heredity

nd

cell theory.

Other, less myopic

biologists, owever,

ad

seen

that ertain enerali-

zations

of cell

theorywere

directly pplicable to

3

C.

van

Bambeke

"Pourquoi

nous

ressemblons a nos

parents,"

Bull. de

l'A

cad.

roy.

de

Belgique, s. 3,

10

(1885):

pp.

901-902.

4

See C.

Darwin,

The

Variation

of Animnals

nd

Plants

uinder

Domestication

(2 v.,

London,

1868)

2: pp.

3-4.

the problem

of

generation.

By

the 1860's

they

had proved that the spermatozoonwas essential

to fertilization,hat

the

male

element

penetrated

into the egg,

and

that

both

male and female

germproducts

were derived

rom

issues

nd

were

therefore rue cells. But what eventor events

really constituted he essence of fertilization

e-

mainedthe object

of curious

speculation

nd was

subject to littleprecise

nvestigation.

Those

who

studied he cell were obsessed withthe

novelty

f

the upposed ife-substance,he

viscous

lbuminoid

called protoplasm. The nucleuswas

at best

con-

sidered only a persistent rtifact

aving

no

real

importance. It seemed more ikely o be

a

mere

aggregate

of

refringent articleswhose

presence

could only rregularly e demonstrated.Review-

ing the work of this epoch,

M. Verworn

recalled

that

no

one

knewwhat

to

do

with

he nucleus."

Early in the 1870's therewere discoveredwithin

the cell

certain singular

and

extremely egular

transformations

f

the

nuclear ubstance. Further

study elucidated the phenomena of "indirect"

nuclear division (mitosis).

These were soon

found o be characteristic

henomena ccompany-

ing

all normal

ell division.

The cell nucleusnow became an object worthy

of

careful nvestigation.

Attention urned wiftly

to

the

constitution

nd

behavior of

the

nuclei

contained

n

the egg and

the sperm. By 1885

the

story

was

complete,

nd

to the ong-established

axiom ofthe continuityf all cell generations as

joined theparallel xiom of

the ontinuity,hrough

the

ntermediary

f

mitotic

ivision,

f

all

nuclear

stages

and

hence

all

nuclei. Most importantly,

the

close

structural

nd

chemical

similarity

f

the male

and

female

nuclei

and

the fact

of

the

hereditary quivalence of the two parents, re-

peatedly

onfirmed

y means

of

reciprocal rosses,

led

to the idea that the cell

nucleus,or the sub-

stance of

which it seemed to be composed, the

idioplasm, was the true

vehicle of inheritance.

Realizing that here one finally ouched au

cceur

de la question,"van Bambeke could rightly on-

clude that

.

.

.le

noyaude l'aeuf t le

noyaudes cellules n

general ont e veritable iege de l'idioplasma. Le

noyau doit etre considere

omme 'organe repro-

ducteur e

la

cellule. .

Dans l'aeuffeconde,a

masse

ilamentaire,otammenta partie usceptiblee

coloration

nucle'ine),

epre'sente

'idioplasma;

lle

est

e

vraie

iege

des

propriete'se'reditaires.6

5

M.

Verworn,

General

Physiology,

trans. F.

S. Lee

(London,

1899),

p.

505.

6

Bambeke,

1885 (note

3): pp.

918, 922.







126

WILLIAM

COLEMAN

[PROC. AMER. PHIL.

SOC.

The physical

asis

of the

transmission

f

heredity

and variation

tood

revealed. Only n the

decades

following

1885

would a

greater understanding

of

the causes of

variation nd

an appreciation

f

the ntricate

mechanisms

nderlying

uclear

rans-

formationse acquired. The identificationfthe

nucleus

nd its enclosed

ubstances

s

thevehicle

of inheritance,

he

subject

of the present

essay,

formed

he necessary

prelude

to these

later re-

searches.

The central

role of

the nucleus

was disclosed

by numerous

ndfrequently

uite

different

etsof

evidence. At

no time after

the appearance

of

the Origin

of Species

could

the problems

of

heredity

nd variation

be

separated

from the

prevailing

iscussion

of thecourse

and forces

of

plant

and

animal phylogeny.

Heredity,

more-

over,

mplied iterally

he

production

nd not an

abrupt reappearancefrom the germ of a new

generation.

Morphologists

insisted

that any

hereditary

chemamust

provide

some plausible

directivemechanism

or

embryonic

evelopment.

On

thevisible

evel,

t least,

ontogenywas

under-

stood to be

strictly

pigenetic.

The substance

and

hypothetical

molecular

arrangement

f the

hereditary

nit(s) was

held responsible

or this

process.

Evolution,

mbryology,

nd cytology

ecame

he

common

oncern

fa number

f eading

biologists.

Essays

published

n 1884-1885

by Oscar

Hertwig,

Edouard Strasburger, nd August Weismann

developed

at

length these

several

themes

and

offered vidence

and

decisive

argument

hat

the

nucleus was

the fundamental

ellular

element,

at once ensuring

eredity,

llowing

variation

nd

directing

ntogeny.

For

Hertwig

nd

Strasburger

the

nucleus

was an

internal

omponent

ut

one

to

some

degree

till

subject

to external nfluences,

while Weismann

looked to the

nucleus

as the

exclusive

factor

n

heredity

nd

variation.

These

essays

represent

turning

oint

in the

study

of

evolution

nd

ontogeny

nd

in

the

early

analysis

ofthe problems f nheritance.To E. B. Wilson,

one

of

the

greatest

f all

cytologists,

he

"identifi-

cation

of

the

cell-nucleus

s the

vehicleof

inheri-

tance"

marked heessential

dvancewhich

ecured

the

integration

f

two

of

the

principal

general-

izations

of nineteenth-centuryiology,

ell

theory

and evolution

by

means

of natural

selection.7

7E. B.

Wilson,

The Cell

in

Development

and

Inheri-

tance

(2nd

ed.,

New

York,

1900),

pp. 6-7.

See

also

J. W. Wilson,

"Biology

Attains

Maturity

in

the

Nine-

teenth

Century,"

Critical

Problems

in the

History

of

Sci-

ence,

ed.

M. Clagett (Madison,

Wis.,

1959),

p.

416.

II.

CELL,

PROTOPLASM

AND

NUCLEUS

The theory

f

natural election

nd a

rigorous

interpretation

f

cellular

continuity

were

made

public

simultaneously

1858).

While

Darwin

and A.

R. Wallace

were

presenting heir

pre-

liminary ssays in evolution heory,R. Virchow

published

he

mature

statement

f his

views

on

the cell.

The famous

dictum

omnis

cellula

e

cellula seems

Vichow's

alone,

but

the idea it

ex-

presses

was already

ppreciated

n theearly

1850's.

Cell theory

rom he

beginning

was

concerned

with

the form

and structure

f

the cell and

of

its complex

derivative

tissues. Essential

also

to

the enunciation

f the

theory

was the

prob-

lematical

origin

of these

elementary

tructures.8

M. J.

Schleiden's

hypothesis

f cellular

formation

in plants

by means

of intracellular

oagulation

f

mucous substance about granular aggregates

(endogeny)

was

appliedby

T. Schwann

o

animal

cell formation.

According

o Schwann,

he

medium

(cytoblastema)

urrounding

ertain

ranules

alled

nuclei

and nucleoli

coagulated

or precipitated

o

formcells.

These events,

however,

seemed

al-

ways to

be external

o existing

ells (exogeny).

The

notionof

cell origin

by

precipitation.

t

the

outset

a fruitful

onception,

ecame

part

of the

dogma

of early

cell

theory

nd required

great

effort

or

ts

final xtirpation.

Careful

attention

to the

mode

of

multiplication

f

the

unicellular

organisms nd the filamentouslgae did suggest

direct

ellular

division,hence

cell

continuity,

nd

denied precipitation

r

de

novo cell

formation.

Furthermore,

s

early

s

1824, J.

L. Prevost

and

J.

B. Dumas

had noted

the repeated

urface

r-

regularities

fthe

blastula

or "raspberry"

tage

of

the

early

frog

mbryo.

In the

1840's the

work

of

C.

von

Siebold,

M.

Barry,

H.

Bagge,

and

C.

Bergmann

howed that

these

irregularities

ere

cleavage products

of the

fertilized gg.

They

were

cells

and had

been

derived

from

preexisting

cells.

No

less

a

histologist

han

A.

von

Kolliker

was convertedby these

discoveriesto

the

new

idea that

all

of

the

dividing

masses

represented

by

thecleavage

of the

zygote

were

really

cells

in

the

process

of formation.

From the fertilized

gg

to the

large,

highly

differentiated

dult

body

existed

an

unfailing

ontinuity

f

cells.

In 1852

Robert

Remak

brought ogether

he

scattered

pieces

of evidence

and declared

firmly

against

Schwann's

hypothesis

f the

exogenous

8

See

J.

R.

Baker,

"The Cell-theory:

A

Restatement,

History

and Critique.

Part

IV.

The

Multiplication

of

Cells,"

Quart.

Jour.

Micro.

Sci.

94

(1953)

:

pp.

407-440.







VOL. 109, NO. 3,

1965]

CELL, NUCLEUS,

AND

INHERITANCE

127

formation

f animal cells.9

Calling upon the

botanists,

Remak showed that

they

too, despite

their onfusion f the

division

f the cell wall

and

of cell

contents,

were advocates

of cell

division.

All

daughter

ells received

heir

ubstance

pro-

toplasm)onlyfrom he mother ell. Remakwas

uncertain bout

the earliest

mbryonic

ell

stages

and

allowed for some

endogenous

ell

formation.

His

essay,

nevertheless,

s well as his

greatest

work,

Untersuchungen

iber die

Entwicklung

er

Wirbelthiere,

which

systematically

nterpreted

the

whole realm

of

descriptive

ertebrate

mbryol-

ogy

in

termsof

cell

theory,

emonstrated orce-

fully hat the

origin of cells occurs

normally y

division

alone

and

only

exceptionally y

other

means.

While

Remak,

a

Jew,

endured the miserable

disregard of a bigoted Prussian Ministry of

Education,

Virchow

returned to Berlin

after

youthful

dventures nd

became

one

of

the

aca-

demic

ornamentsof the

great age of

German

biology. His

teaching and

writings

made him

the

leading exponent f the

new ideas

regarding

cellular

ontinuity.

n

an early

tatement1855)

he

spoke of

the continuity

f cells

but only of

cells

in

a

pathological

ondition. By

1858 he

had

enlargedhis view

to include ll

cells, normal

or

physiological s

well as

pathological.

"Wher-

ever a

cell

originates,"he now

declared,

"in

that

place there

must have been

a cell before

(omnis cellula e cellula), just as an animal can

only

originate rom n

animal and

a plant from

a

plant."

10

The

demonstration

f the

continuity f multi-

plying

ells made

possible the later

establishment

of

the role of

the cell

and nucleus

in hereditary

transmission.

The

Schleiden-Schwann

ypotheses

had

left pen

the door to

equivocalor

spontaneous

generation f

cells and

nuclei. If

such elements

could

spring

forth from

anything other

than

previously xisting

cells and

nuclei, therecould

never be any

certainty

hat the cell

with its

enclosednucleus was the unique connection e-

tween

each and

every

generation. The

spontane-

ous generation

f cells or

nuclei, by

whatever

9

R.

Remak,

"tber

extracellulare

Entstehung

hierischer

Zellen

und

iiber

Vermehrung

derselben

durch

Theilung,"

.4rch.

Anat.

Physiol.

u.

wiss.

Med.

1852:

pp.

47-57.

See

B.

Kisch,

"Forgotten

Leaders in

Modern

Medicine.

III.

Robert

Remak,

1815-1865,"

Trans. Amer.

Philos.

Soc. 44

(1954)

:

pp. 227-296.

10

R.

Virchow,

Cellular

Pathology as

Based

upon

Phys-

iological

and

Pathological

Histology,

trans.

F.

Chance

(New

York,

1860),

p. 54.

means

proposed,

ould

only

be a

constant

denial

of

the necessary

nd exclusive

generative

gency

assigned

o

these structured

arts.

The

intensive tudy

f

the cell

was

accompanied

by

a

generalneglect

f the nucleus.

M.

Schultze,

attempting o reduce the often dissident cell

doctrines of the botanists

and

zoologists

to

a

common

definition,

as

clearly

disinterestedn

the cell nucleus.

What

must we call a

cell

he asked. The old view

represented

he

cell

as

any

"blaschenf6rmige ebilde

mit

Membran,

n-

halt, und Kern."

'1

Schultze

feltthat there

was

needed

only a critical examination f

prevailing

views and that from

his

could be extracted he

true

essence

or

definition

f

the cell. But

there

were

many

kinds

of cells

(his essay

was devoted

to

muscle ells) and one had to seek out the most

important ypes. These Schultze found in the

relatively imple

early embryonic

issues whose

cells

represented"die

Zukunft eines ganzen

Organismus."

They

were the

"wahre Urbild"

of all

later

cell generations.

Their structure

was not

complicated.

A

nu-

cleus,

barrel-shapednd

homogeneous ave for a

few

bright

points,

was

often

present,

and the

protoplasm, lear and

containing iverse formed

elements,was never

absent. "Eine

Zelle,"

he

concluded,

"ist ein

Kliimpchen

Protoplasma,

in

dessen

Innerem ein Kern

liegt. Der Kern

sowohl als

das

Protoplasma sind

Theilproducte

dergleichenBestandtheileineranderenZelle."12

Schultze

received

greatest

acclaim for

having

eliminated

from

the cell definition

ny consid-

eration of

a

membrane.

This

set aside many a

long-standing

uarrelbetween otanist

nd zoolo-

gist.

The sarcode,proposed

by F. Dujardin and

favoredby the

zoologists, nd

protoplasm, ro-

posed by H. von

Mohl and

supported by the

botanists,

were interpreteds

being one and the

same

substance, he

life-substance,nd together

given the

old name,

protoplasm.

For

Schultze the nucleus

enjoyed at best a

quasi-equivalencewith the protoplasm. The nu-

clear

role

may

have been significant

ut it was

whollyunknown.

Schultze's

views (enlarged n

an

essay

of

1863) were

extendedby the work of

E.

Brucke (1861),

who saw even less

need for

the

nucleus and

showed

greatest concern for

protoplasmic ifferentiation,

ndeed seeking here

11

M.

Schultze, "Ueber

Muskelkorperchen

und

das,

was man

eine

Zelle zu

nennen

habe,"

Arch.

Anat.

Phvsiol.

u.

wiss. Med.

1861:

p.

8.

12Ibid.,

p.

11.







128

WILLIAM

COLEMAN [PROC.

AMER. PHIL. SOC.

rather

complex

"organelles."

Their

writings

gave

shape

to

a

new

orthodoxy

which

looked

almost

exclusively

to

protoplasm

as

the

basic

vital

substance.

The

decade

of

the 1860's

was

a heyday

or

peculation

pon

the

nature

f

proto-

plasmandfor hecelebrationf tsamazing

prop-

erties.

Few wrote

more boldly

on this

theme

than

Haeckel

and T.

H.

Huxley.

Haeckel

in 1868

undertook

o classify

what

he

supposed

to

be

a newly

recognized

roup

of

ani-

mals,

the

monera.

These,

he believed,

were

cer-

tainly

he

simplest

nd therefore

hylogenetically

the

most primitive

f all organisms.

They

were

but

a

mere

nonnucleate

lobule

of

protoplasm;

in Haeckel's

expressive

phrase,

"ein

einfaches

Kugelchen

von

Urschleim."

3

This

phrase

Haeckel

used

to

describe

he

post-fertilization

gg

of

the

human.

He

shared

the

prevalent

mis-

apprehensionhat, t the momentf either uclear

division

or fertilization,

he

nucleus

first

dis-

appeared

and

only

ater

reappeared.

This

belief,

doubtlessly

ue to

the

technical

nadequacies

of

microscopic

bservation,

would

infinitely

mbar-

rass

contemporary

fforts

o

demonstrate

he

direct hysical

ontinuity

fthe

nucleus.

Haeckel

himself

was

delighted

to

find

that even

man,

long

placed

at

the

apex

of

creation,

exhibited

during

his development

cell stage

which

united

him to

the

lowest

of

all

forms,

he

monera.

A

purely

rotoplasmic

tage

was therefore

common

feature fhigherndlowerforms f ife. Haeckel,

it

will

be seen,

in

no

sense entirely

isregarded

the

nucleus,

ut

his

characterization

f the

monera

allows

no

doubt

as to the preponderant

ole

assigned

to the

protoplasm.

Die

einfachsten

on

llenOrganismen,

ie wir

kennen,

[he

maintained]

nd

ugleich

ie denkbar

infachsten

Organism

ind

die

Moneren,

meistens

mikroskopisch

kleine

ormlose

6rperchen,

ie

aus

einerhomogenen

Substanz,

einer

eiweissartigen

der

schleimigen

weichen

Masse

bestehen,

6rperchen

hne

Structur,

ohne

Zusammensetzung

us verschiedenen

rganen

und doch

mit allen

Lebenseigenschaften

es

Or-

ganismus egabt. Sie bewegen ich, rnahrenich,

und

pflanzen

ichdurch

heilung

ort.14

Haeckel's

opinions

regarding

he cell

and

nu-

cleus

have special

mportance.

At the

University

of

Wurzburg

he had

studied

under

two

of

the

creators

f

the

reformed

ell

theory,

irchow

and

K6lliker.

He

saw

little

interest

n

Virchow's

lectures

on

pathology,

ave

for the

fact that

all

13 E.

Haeckel,

Anthropogenie,

oder

Entwicklungsge-

schichte

des Menschen

(2nd

ed., Leipzig,

1874),

p.

142.

14 Ibid.

phenomena

were

reduced

to

a

cellular

basis.

Kolliker

llowed

him o

pursue

ndependent

icro-

scopical

nvestigations.

To

his parents

he

wrote

in 1853

that

there

s nothing

more nteresting

han

hetheory

f

cells.... In reality,hisgenesis f cells s something

that

closely

oncerns

verybody,

orall of

us,

like

plants

nd

animals,

onsist

f

and have

our

origin

in cells.

.

. .

Vivant

cellulae

Vivat

micro-

scopia 5

Haeckel's

enthusiasm

was

infectious

nd

passed

within

decade

to two

of

his celebrated

tudents,

Hertwig

and

Strasburger.

Haeckel

thus

forms

an

important

ink

between

the

masters

of

early

histology

nd

the eaders

of ater

ytology.

The

first

pparent

onfirmation

f the

monera

hypothesis

ame

from

Huxley,

always

partial

to

protoplasm.

Sticky

mud

dredged

n

1857

from

NorthAtlanticdepthsand brought o England

for study

was

seen

by

Huxley

to

contain

certain

lumps

of

a "transparent

elatinous

substance"

within

which

were

found

numerous

ranules

nd

coccoliths

but

no

"nucleus."

Huxley

perceived

here

bit

of

Urschleim

nd,

creating

new

species

and genus

of monera,

baptized

it Bathybius

haeckelii.

This

unfortunate

reature

r creation,

for

creature

t certainly

was not,

was often

de-

nounced

during

he

1870's.

Huxley

finally

on-

ceded

(1879)

that

he

was

in error,

greeing

hat

Bathybius

was probably

precipitate

nducedby

the pplication fchemical reservativeso organic

substances

aken

from he

ocean

floor.

Haeckel,

unregenerate,

as

less

willing

to see his

name-

sake

read

out

of

existence."6

Bathybius

merely

reinforced

Huxley's

earlier

interest

n

the

physical

basis

of

life. The cell,

he

had

argued

n

1853,

was

notthe owest

ommon

denominator

f

living

things.

It was

only

an

indicator

which

revealed

"where

the vital

tides

have been,

and

how

they

have acted."

7

These

vital

tides

were

of

material

rigin:

"

'vital'

forces

are

molecular

orces."

Here

already

s stated

he

themeof Huxley's decisive Protoplasmaddress

15

E.

Haeckel,

The Story

of

the

Developmnent

f

a

Youth.

Letters to

His

Parents,

1852-1856,

trans.

G.

B.

Gifford

New

York,

1923),

pp.

182-183,

187.

16T.

H.

Huxley,

"On Some

Organisms

Living

at

Great Depths

in

the

North

Atlantic

Ocean,"

Quart.

Jour.

Micro.

Sci.

8

(1868):

pp.

202-212.

See

The

Life

and

Letters

of Thomas

Henry

Huxley,

ed.

L.

Huxley

(3

vol.

ed.,

London,

1903)

2: pp. 268-270;

E.

Haeckel,

"Bathybius

und

die

Moneren,"

Kosmos

1

(1877):

pp.

293-305.

17

T.

H. Huxley,

"The

Cell-theory

[1853],"

The

Sci-

entific

Memoirs

of

Thomas Henry

Huxley,

ed.

M.

Foster

and

E.

R.

Lankester

(4

v.,

London,

1898)

1:

pp.

277-278.







VOL. 109, NO. 3, 1965]

CELL, NUCLEUS, AND INHERITANCE

129

of

1868.18 All

organisms,

oth animal and

veg-

etable, were

"fundamentally

ne." Their

modes

of action,form

nd

elementaryomposition

ere,

on

the

microscopicalevel,

astonishinglyimilar.

Their chemical

onstitution-basically roteinace-

ous and

subject to

heat

coagulation-betrayedcellular catholicity f assimilation." Huxley was

nmore

oncernedwith

the cell and

its contents

as units f

functionhan

with hecellular

tructure

of

the

body. His was a

truly

physiological p-

proaclh.

Subserving ll vital

functionswas

the

protoplasm. Huxley

conceded,as had

Schultze

and

others, hat

rdinarilyhecell was

a

nucleated

mass of

protoplasm. But it

was the

protoplasm,

and not

the nucleus,

to

which

he

gave prime

importance.

After all, there

had just been dis-

covered

minute

ivingforms

(monera)

without

nuclei.

The

protoplasm

ndifferentlyould be

"'simple" r "nucleated" ndstillremain hephysi-

cal

basis

of

life.L9

Even

Schultze

and

Brucke,

however,

had

felt

that he

protoplasm

ould notbe

absolutely eature-

less. From

about 1865 a

search began for

the

formal

tructure

f

the

protoplasm.20

he enquiry

ultimately ed to

remarkable nd

sometimes

bi-

zarre

notions

of

protoplasmic

tructure

ut,

in

so

doing,

t pointed o

the stable

formal lements

within

the cell.

The nucleus

could not be dis-

regarded. J.

Heitzmann

1873) described s

the

true

iving ubstance

f

the

cell

the

nuclei,

bodies

withinthe nucleus and othercytoplasmic truc-

tures. All

of

these

parts existed mmersed n a

nonlixvingthat

is,

noncontractile) iscous

fluid.

Others,

ncluding trasburger,

. Arnold, nd

S.

Freud,

continued he analysis

of the

protoplasm

and

its

parts. By the

early 1870's it

was evident

thatthe cell was

anything ut

a

mass of

formally

simple

although

chemically omplex

protoplasm.

Within the

protoplasm

were

located various dis-

tinctive

tructures.

Rods,

threads,

membranes,

vacuoles,

and

pigment

bodies were

found in

abundance and

diversity.

So, too, were

nuclei

and thedemonstrablend now-appreciatedntra-

nuclear

elements.

A

new era in

the study of

the cell and

the

18

T. H.

Huxley,

"On

the

Physical Basis

of

Life

[1868],"

MIethod

and

Results

(New

York,

1893), pp.

130-165.

19

bid.,

pp.

139-142. See

F. L.

Holmes,

"The

Milieu

Int6rieur

and

the Cell

Theory,"

Bull.

Hist.

Med. 37

(1963):

pp.

315-335.

20

See W.

Flemming,

Zellsubstanz, Kern und Zellthei-

lung

(Leipzig,

1882), pp.

10-21;

A.

Hughes,

A

History

of

Cytology

(London, 1959),

pp.

112-130.

understanding

f

heredity pens

with the

recog-

nition

of

the ubiquity

f

the

cell nucleus and the

discovery

f

the extraordinary

eans

provided or

the

regular

division of

this

body.

In the

minds

of

cytologists

he

nucleus

rapidly cquired parity

with

and even

supremacy

ver

the

much admired

protoplasm. Hertwig, ookingback at thisperiod

when

he was still

a

young

student

n

Haeckel's

laboratory,

eclared with

obvious

satisfaction:

Wieder

sind zahlreiche

rscheinungen

es

organi-

schen

Lebens

unter

inheitliche

esichtspiunktee-

bracht

nd unserem

erstandnis ahergeriuckt

or-

den....

Nachdem rkannt

st,

dass

Protoplasma

nd

Kern die beidenHauptbestandtheileer Zellen sind,

bleibtdas Wechselverhiltnisieserbeiden, ie Art

undWeise,wie Kern

und

Protoplasma

m

Leben

der

Zelle

wirksam

ind,

durchweitereUntersuchungen

aufzudecken.Auf diesemGebiete rangen ich uns

taglich

eue

Rathsel

uf....21

Between

1873

and

1883 one of the greatest

of these riddles

would be resolved.

A decade

of

major

technical

nnovation, ersistent

nd

thor-

ough microscopical bservation

nd

imaginative

reflection ade known he sequence nd detailsof

normal nuclear division. The efficiency, eg-

ularity, nd precision

of

mitoticphenomena

n-

duced cytologistso searchbeyond heir mmediate

data

for the meaning of this singular process.

Soon

they

ealized

hathere was the

deal mecha-

nism for

the even distribution f the hereditary

substance.

III.

CONTINUITY OF THE NUCLEUS

Two great optical difficulties-chromaticnd

spherical berration-had ong prevented he pre-

cise

microscopicalresolution

of

small objects.

By

the late

eighteenth entury ombinations

f

lenses,

each

of whichwas composed f a different

kind of glass and had therefore different e-

fractivendex,were constructed,nd these llowed

the

elimination

f much of

the chromatic

ber-

ration.22The systemsworked,however, nly at

relativelyow magnifications. rom 1830 onwards

theoretical

onsiderations nduced J. J. Lister,

J.

B.

Amici,

and

others o devise new systems f

carefully round lenses which, when assembled

together, elped

eliminate

part

of the

spherical

aberration. Minor improvementsolloweduntil,

in

1886, the famousZeiss Jena glass, made with

boron and

phosphorus,was introduced. The

21

0.

Hertwig, "Die

Geschichte der

Zellenlehre,"

Deutsche

Rundschau

20

(1879):

p. 429.

22

Hughes,

1959 (note

20): pp.

1-28.







130

WILLIAM COLEMAN

[PROC. AMER. PHIL.

SOC.

apochromatic

ens

systems

reated

from

his

ma-

terial

removed

virtually

ll serious spherical

nd

chromatic

berrations.

Apochromatic

enses

rep-

resent

the

culmination

f

efforts

o improve

he

optical

system

f the lightmicroscope.

It is

not

fortuitoushat

following

he

production

f

these

lenses

cytological

nalysis eached n to evermore

minute

elements

f

the

cell. Microscopes

made

with

these

lenses,

when

used

with

immersion

techniques,

llowed

magnifications

f

up to

2,500

diameters

nd

a resolving

ower

of ca.

1

micron.

In the

hands

of

T.

Boveri,

E.

B. Wilson,

L.

Guignard,

nd

innumerable

thercytologists,

he

new

instrument

ltimately

disclosed

the

finer

details

of

number,

structure,

nd behavior

of

chromosomes.

The

demonstration

f

the

nucleus

s the

vehicle

of nheritance

as

made

at

just

the

moment

when

these importanttechnical improvementswere

becoming

vailable.

The

latter

were

not,

there-

fore,

n

their

final

form necessary

ondition

or

the

former.

Water,

glycerine,

nd, finally,

il

immersion

techniques,

introduced

during

the

1870's,

were

sufficient,

ven

when

used

with

the

olderoptical

ystems,

o

reveal

the

major

features

of the

nucleus

and its

constituents.

Moreover,

refinements

n

the

techniques

f

cytological

rep-

aration-alcohol,

cetic

cid,

and osmic

acid

tissue

fixation

nd

bold

and

extensive

use

of

staining,

especially

with

the

aniline

dyes-permitted

the

discernmentnd preservation f extremely ine

cellular

detail.

The

researches

f

W.

Flemming

and E.

Strasburger,

arried

ut

in the ate

1870's

and

absolutely

ssential

to

the

establishment

f

the

new

view

of the

nucleus,

were

dependent

upon

the

pecial

echniques

f

fixation

nd

staining.

Early

observers

of the

nucleus

lacked

these

means

and their

descriptions

f this body

were

confused.

Some

believed

t to

be a

mere

bladder

filled

with

fluids

and

a

few

scattered

granules,

while

otherspictured

t as

a

homogeneous

lump

of

solid particles.23

In

the 1860's

cytologists

observedwithinthe nucleus the frequentper-

sistence

of

bright

pots

or refractive

oints.

V.

Hensen suggested

hat

these were end-points

f

the

nerve

fibers,

hich

he thought

ould

be

traced

into

the

cell.

In 1865

C. Fromann,

examining

cells

from

the

spinal

cord,

epithelium

nd

con-

nective

issue,

believed

he had found

real

nuclear

structures.

"Skeins

and rods"

(Strdnge

und

Faden)

were

present

n such numbers

nd

their

ramifications

ere

so

complex

hat hey

ould

not

23

Flemming,

1882

(note

20):

pp.

178-190.

reasonably

e considered

arts

of the nerve

fiber,

but

must

pertain

peculiarly

o the nucleus.

Fro-

mann,

nfortunately,

ollowed

hese

bodies

beyond

thenucleus

nd into ll parts

of the

cells.

Others,

including

lemming

imself,

. van Beneden

and

0.

Biistchli,

lso

identified

hese

elements

and

restrictedhem o thenucleus.

These

discoveries

were

finallygeneralized

n

1876

by

Richard

Hertwig,

younger

brother

of

0.

Hertwig.24

Hertwig

concluded

hat

the

most

important

nd

characteristic

art

of the

nucleus

was the

Kernsubstanz,

an albuminoid

having

certain

features

n common

with

the

surrounding

medium.

The

latter,

he

Kernsaft,

was

a formless

fluid

mass

while

the

Kernsubstanz

was

particu-

larly

notable

or

ts

structure.

n primitive

orms

the

nucleus

might

e naked

and

in

some

creatures

protoplasmic

trands

might

ccasionally

enetrate

its bounds,but the typicalnucleuswas distinct

from

the

protoplasm

nd

presented

n

obvious

separation

f the

two

nuclear components.

The

Kernsubstanz

ppeared

to

divide

with

some

reg-

ularity

nd

to exhibit

specific

hemical

eaction.

That

the

nucleus

did

divide

and

multiply

ad

long

been

evident.

But

to

comprehend

ully

he

phenomena

ccompanying

his

division

required

deep

knowledge

of

"that

which

was

divided,"

that

s,

of

the

structure

f the nucleus.

By

1850

division

was

generally

ccepted

as the

normal

means

of

nuclear

multiplication,

lthough

some

nucleiwere stillbelievedto originate y precipi-

tation

or

aggregation

n

the

surrounding

luids

(either

within

or without

the

cell).25

Nuclear

division

was

at this

time

regarded

as

literally

"direct."

An

indentation

as

seen

to appear

on

the

nuclear

surface

nd

to

penetrate

more

deeply

until the

nucleus quite

simply

had

been

sheared

into

two parts.

There

was

no

question

here

of

the

elaborate

rrangements

hich

ed

to

lnuclear

multiplication

y

"indirect,"

r mitotic,

i-vision.

Direct

nuclear

ivision

was accepted

nd

adv-ocated

by

both

Remak

and

Virchow

and remained

ntil

ca.

1875theprevailingonceptionftheprocess.26

All possibility

f

precise

division

was

excluded.

Nuclear

masses

were

furrowed

nd

then

eparated

24

R.

Hertwig,

"Beitraige

zu

einer

einheitlichen

Auffas-

sung

der verschiedenen

Kernformen,"

Morph.

Jahrb.

2

(1876)

:

pp.

63-82.

25

See

J.

R.

Baker,

"The

Cell-theory:

A

Restatement,

History

and Critique.

Part

V.

The

Multiplication

of

Nuclei,"

Quart.

Jour.

Micro.

Sci.

96

(1955):

pp.

449-481.

26

R.

Remak,

Untersuchungen

iber

die

Entwickelung

der

Wirbelthiere

(Berlin,

1855),

pp. 174-175;

Virchow,

1860

(note

10):

pp.

345-349.







VOL.

109, NO. 3, 1965]

CELL, NUCLEUS, AND

INHERITANCE

131

and there eemed

to be

no

rules

for

what

course

these

cleavages

might ollow.

Furtherconfusionwas

introduced

y

the

ap-

parent

disappearance

and

reappearance

of the

nucleus

at each

division.

An

existing

nucleus

was perceivedslowly to dissolve itself nto the

protoplasm

fthe

mother ell and

then,

s division

came

to

completion, wo

wholly

new nuclei were

reconstituted

t opposite

poles of

the cell. The

daughter nuclei

exhibited

no

necessary

or

de-

monstrable

onnection

with the

mothernucleus.

A

not

too careful

crutiny f

living

ells

(neither

fixednor

stained)

was

responsible or this

inter-

pretation.

This

conception f

nuclear ransforma-

tion

was

widely accepted.

It

was,

for

example,

illustrated n

greatdetail

by L.

Auerbach,whose

Organologische Studien

(1874)

was the im-

mediate

cause of

0. Hertwig'srevolutionaryn-vestigationsof the behavior of nuclei

during

fertilization

nd

cell

multiplication.

That the

disappearance-reappearance

uclear

cycle

was apparent

nly seems

first o have been

demonstrated

1873)

in

a

little-known

eport

by

A.

Schnieder.27

Schniederwas

studying

post-

fertilization

vents

in

the

summer eggs of the

free-living

latyhelminthin

orm,

Mesostomum

ehrenbergii.

The

preparations

were fixed with

acetic

acid but

were

not stained.

Schnieder's

views on

fertilization

erewholly

rroneous,

ut

his

account of

the fate of

the

newly

formed

nucleus that s, the ygote ffirst leavagenucleus

formed

y the unionof

the

sperm nd

egg

nuclei)

refuted

he notion

that the

nucleus

disappeared

during

multiplication. He

observed

that "der

ganze

Kern

hat sich

in

einen Haufen

feiner,

lockig

gekriimmter, ur

auf

Zusatz von

Es-

sigsaure

sichtbar

werdener aiden

verwandelt."

8

From

these

threads

arose heavier

rods.

The

latter ssumed

a roseate

form nd

oriented

hem-

selves

about

the

equatorial

plane of

the ovum

(Aequatorialebene), hus

forming

regular

divi-

sional

figure.

Schniederwas

describing

hemiddle

stage of mitosis, Flemming's metakinesis and

Strasburger's

metaphase, he term

till

n

use. A

polarity

f

the cell

then

became manifest

nd the

nuclear

lements

Kornchen) separatedfrom

ne

another

anaphase).

Finally, wo

new nuclei

were

formed

t

opposite

poles

of

the egg

and a

cleavage

of

the cell

occurred

between

them.

Schnieder

27

A.

Schnieder,

Untersuchungen

iber

Plathelminthen,"

VierzeAnterBericht

der

Oberhess.

Gesell.

fir

Natur-

ui.

Heilkunzde

873:

pp. 69-140.

28

Ibid.,

p.

114.

understood

he

mportance

f

his

discoveries. The

regular

occurrence f definite

tages in the

divi-

sion of

the nucleus

convincedhim

thatthis

body

did not disappear

t any

moment n the ife

of the

normal

cell.

Nuclear division

was

the meta-

morphosis,not the loss and recreation,of a

persistent

ell

component. His

discoveries,he

felt,

evealed

.

.

.

zum erstenmal

deutlich,

welche

umstandliche

Metamorphose er Kern

(das

Keimblaschen) bei der

Zelltheilung

ingehenkann.

Diese

Metamorphose st

offenbar

icht

bei

jeder

Zelltheilung

othwendig,ber

sehr

wahrscheinlich ritt ie

immerdannin, wenn

der

Kern

scheinbar

verschwindet. Waire

hier der Kern

nicht zufallig

gross und die

Zelle

durchsichtig, o

wiirde

wahrscheinlich

uch annehmen,dass

wie

in

anderen

Faillen

der

Kern

verschwindet.29

Schnieder's observations

did

not extend

to

other

organisms but already investigators were studying

similar

phenomena

in

the

various divisions of

the animal

kingdom.

Researches by Biitschli

on

the

nematode

worm

(Cucullanus),

mollusca and

the

infusorians and by

van Beneden on

the

rabbit

disclosed the common

occurrence of the

process

in

the

major

animal

groups.

They

also described

the

broad

pattern

of

mitosis:

the

formation

of

the

nonstaining

achromatic) bundle of

threadsplaced,

like two cones

with their

bases in contact,

per-

pendicularly to the

equatorial

plane; the

appear-

ance on

the

latter

plane

of

the

now

familiar

deeply-staining rods; and the cleavage of the

equatorial

mass

producing

two

daughter

nuclei.

Strasburger reported

(with

reservations)

the

occurrence of much

the same

sequence

in

other

forms, bove all

in

a

great

variety of plant

species.30

He

introduced,

furthermore, capital

error, be-

lieving that the central

event of

mitosis

was a

rude,

transverse, and

strictly

quantitative division

of

nuclear

masses

lying perpendicular

( ) to the

equatorial

plane.

Flemming began

in

1878 to

correct

these

misapprehensions;

Strasburger

him-

self

was

converted to the

new ideas

only

in

1884.

The nuclear mass refers of course primarily

to

those elements

which reacted

strongly

to

stains,

carmine

being

used at

first but

later

supplanted

by haemotoxylin

and

the vast series of

synthetic

(aniline)

dyes.31 Because

of

this

affinity

for

stains,

Flemming (1879)

introduced the

term

29 Ibid.

30

E.

Strasburger,

Zellbildung und

Zelltheilung (1st

ed., Jena,1875).

31

See

M.

C.

Leikind,

"Aniline

Dyes-Their

Impact

on

Biology and

Medicine,"

Smithsonian Report for

.19.57

(Washington, 1958), pp.

429-444.







132

WILLIAM

COLEMAN

[PROC. AMER.

PHIL.

SOC.

chromatin.,

eaning

hereby

he

well-colored

ody

or bodies

within

he

nucleus.

After

decade

of

extraordinary

rogress

n the resolution

f

the

nuclear

onstituents,

. Waldeyer

oined

(1888)

the

felicitous

erm

chromosome.

Perhaps

the

earliest bservationfchromosomes

ad

been

made

by

the

botanist

C.

von Nageli (1842: Lilium,

Tradescantia)

.32

From

this

time onwards

fre-

quent

reports

f these

bodies

were

made. C.

B.

Reichart,

W.

Hofmeister,

J.

Henle,

and

even

Virchow

detected

these

common

nuclear

con-

stituents.

Nevertheless,

the

chromosomes

re-

mained

unnamed,

were

totally

misunderstood

and

attracted

minimal

ttention.

Beginning

nly

with

A. Kowalevsky's

publication

1871)

of pic-

tures

of

chromnic

cid

preparations

f

nuclei

of

the

lumbricid

worm

Rhynchelmis

were

"kornige

Anhaufungen,"

r chromosome

roups,

noted

with

regularity.Schnieder's bservations,ollowed y

the

data

of Biitschli,

van Beneden,

and

Stras-

burger,

ncontrovertibly

stablished

he

persistence

of these

formed

uclear

elements,

most

of which

doubtlessly

ere

composed

f R.

Hertwig's

Kern-

substanz.

The

chromosome

heory

f

nheritance

ould

be

the

ultimate

ffspring

f

these

discoveries.

First,

however,

here

ame

the

nuclear

heory

f

heredity.

The

critical

esearches

f

Flemming

1878-1882)

and van

Beneden

(1883)

obviously

oncerned

he

chromosomes.

While

their

work

represents

he

brilliant ommencementf a wholenew realmof

investigation,

hat

of the

structure

nd

behavior

of

the

chromosomes,

enceforth

onsidered

the

principal

onstituents

f

the

nucleus,

t also

marks

the

climax

of all those inquiries

which

were

pointing

towards

the

suspected

hereditary

ole

of the

nucleus

n

toto.

A

knowledge

f the

bodies

later

called

chromosomes

nd

of their

behavior

during

division

was

indispensable

o the

formu-

lation

of the

nuclear

theory

f

inheritance,

ut

a

discussion

f

the

role

of the nucleus

n

inheritance

need

introduce

he

chromosome

heories

nly

in

so far as theypertain o the nucleusas a whole.

Flemming

provided

the conclusive

demonstra-

tion

of the

regular

division

of

the

nucleus

and

thereby pened

the

way

to

the

conception

f

an

equable

distribution

f

the

hereditary

nits.

He

studied

rimarily

he

epithelial

ells

of the

urodele

amphibian

alamandra

maculosa.

These

flattened

cells

contained arge

nuclei

rich

n

chromatin

nd

32

See

Baker,

1955 (note

25):

p.

459;

M. J.

Sirks,

"The

Earliest

Illustrations

of

Chromosomes,"

Genetica

26

(1952):

pp.

65-76.

only

a

scanty

upply

of

protoplasm.

They

were

relatively

ransparent

nd easily ccessible

o

elabo-

rate

fixing

nd

staining

rocedures.

Flemming

e-

scribed

with

great exactitude

he various

trans-

formations

which

carried

the nucleus

from

one

generation

Mutterkern)

to the next

(Tochter-

kerne)33

Fromthe pre-divisionr resting tage

of the

nucleus,

haracterized

t best

by

a

diffuse,

irregular,

nd

highly

divided chromatic

mesh-

work

(Geriist),

there

arose

a twisted

but

very

distinct

nd

deeply

olored

tructure,

he

"knauel-

formiger

Bau"

or

"Spirem."

The

achromatic

figure

ppeared

and

the

spireme,

now

located

on

the equatorial

plane

of the

cell, broke

tip

into

a

frequently

haracteristic

umber

f pieces

(Faden-

segmente

or

Schleifen).

Following

this

stage

(metaphase)

came

the

expected

eparation

f

the

mother

ucleus

nto

wo parts

anaphase).

At

the

oppositepoles of the cell the nuclearfragments

rejoined

end

to end

and

reproduced

first

the

Kniuelforrn

tages

(since

there

were

now

two

nuclei,

this

was

called

the

Dispirern)

and

finally

the resting

tages

of the

daughter

nuclei.

In

spite

of

the

mistaken

observation

of the

fragmentation

f

the

spireme,

no

more

powerful

demonstration

ould

have

been

made

of the

con-

tinuity

uring

eneration

f the

cell

nucleus.

The

progressive

rganization

f

the

nuclear

elements

at the

onset

of

mitosis

nd

the

inverse

process

of

growing

diffuseness

s

the

daughter

nuclei

took

shape showed that the nucleus,or at least its

constituents,

ever

disappeared.

Not only

had

Flemming

onfirmed

arlier

observations

f

vari-

ous

mitotic

tages:

he

also

described

series

of

metamorphoses

hich

included

all stages

of

the

process

and

had

determined

he

normal

order

of

their appearance.

But this

was

not

the

end

of

his

contributions

o

cytology.

In 1878

he

had

noted

that

the

chromatic

lements ying

on

the

equatorial

late

were double,

hat s,

t

appeared

s

if each

nuclear

thread

had been

split

down

its

length

o

as to

form

joined

pair.

The

following

yearherepeated hese bservationsnddrewfrom

them

the

notable

conclusion

that

here,

finally,

was

the

means by

which

truly

xact

division

f

the

nucleus

was

possible.34

Following

carefully

the

fate

of each

of the members

of

a

pair

of

33

W.

Flemming,

"Beitrage

zur

Kenntnis

der

Zelle

und

ihrer

Lebenserscheinungen.

Theil

I,"

Arch.

wlikro.

Anat.

16

(1878):

pp.

302-436.

34

W.

Flemming,

"Ueber

das

Verhalten

des

Kerns

bei

der

Zelltheilung

und

uiber

die

Bedeutung

mehrkerniger

Zellen,"

Arch.

fiur

path.

Anat.

u.

Physiol.

77

(1879):

pp.

1-29.







VOL.

109, NO. 3, 1965]

CELL, NUCLEUS,

AND INHERITANCE

133

stained

lements,

e ascertained

eyond

ny

doubt

that one member

went to one

daughternucleus

and the

other member

was sent to the

other

daughternucleus. The elementsof the

mother

nucleuswere

thereby

qually

distributed.

Because

of theirsimilarorigin,due to the longitudinal

(and

not

transversal)

plitting

f

only

one

mother

element,

ach

pair-member

r

daughternucleus

element

was

with reason

presumed

to

be

very

much f

not

exactly

ike the other

member

f

the

same

pair.

Extending

his vision

from one

cell

to

many,

lemming

erived he

nucleiof

all

verte-

brate

body

cells from

re-existing

uclei,

nd

this

always

by the

unique means

of

mitotic

ivision.35

Strasburger,

he

recognized

leader

in

plant

cytology,

was

at

first

cepticalof

the

persistence

of

the

nuclear

elements

throughout he meta-

morphoses

f

indirect

ivision. In

the

first

wo

editions fhisZellbildung ndZelltheilung1875,

1876) he

derived

he

formed

lements f

nuclear

division

from

he

relatively

omogeneous

esting

nucleus.

He

then

followed hem

o

the

equatorial

plane

and

to the

two

daughter

nuclei

where

they

disappeared, gain

producing

esting

nuclei.

He

agreed

to

a

continuity

f

the

nucleus as

a

whole,

but would

not

allow a

strict

continuity

f

the

individual

nuclear

elements.

Somewhat

later,

however, he

announced his

conversion

to

the

doctrine f

nuclear

continuity:

Im Pflanzenreichassen sich, in allen bekannten,

Faillen,

neu

auftretende

ellkerne

uf

friiher

or-

handene

uriickfiihren.

ie

neuen

Kerne

ehen

urch

Theilung us

alteren

hervor.

Die

friuhere

uffas-

sung,

der

zufolge

er

Mutterzellkern

ufgel6st,

ie

Tochterkerne

eugebildet

erden

ollten,

hat

sich

als

unrichtig

rwiesen.36

In

1884,

immediately

riorto

the

publication f

his

essay on

the

nucleus

s the

bearer

of

heredity,

Strasburger

inally

yielded

completely

o Flem-

ming's

evidence

and

accepted

the

main

themes

developed

by the

zoologist.

Most

significantlye

agreed hat

longitudinal

plitting

fthe

chromatic

threads ccurred, hereupononceding he mpor-

tance of

these

elements.

This fact,

nd

the

read-

ing

of

W.

Roux's

speculative

essay on

nuclear

division

(see

below), led

him

to

admit

that

Die

Bedeutung,

elche er

complicirten

erntheilung

zukommt,

uirft

unachst

arin

iegen,

en

Zellkern

n

zwei

vollig

gleiche

Halftenzu

zerlegen .

.

so

wurde

die

Langsspaltunger

Segmente

leichzeitig

35Flemming,

1882

note

20)

: pp.

252-256.

36

E.

Strasburger,

ellbildung

und

Zelltheilung

(3rd

ed.,

Jena,

880),

p.

321.

das sicheresteMittel

sein,

um

diese

Substanzen

gleichmassig

uf die beiden Tochterkerne

u

ver-

theilen.37

It

was

now

proved that the

normal

mode

of

nuclear

multiplication

as

by

means

of

indirect

division r mitosis. The entire abric f thebody

was

composed

of

cells

each

containing nucleus

and

all

of

these

nuclei

were

genetically

elated.

By

simple nd

obvious

reasoning

ne

tracedback

within

ver-narrowing

imits

henumber f

denti-

cal

nuclei

until

finally

was

reached

the

earliest

stage

in

the

life

of

the

organism,

he

fertilized

ovum. From

whence

did

its

nucleus

arise? It

was

the one

nucleus

within

he body

which

had

not

arisen

by

division.

It

was,

in

fact,

uspected

by

some

that he

zygote

r

"cleavage"

nucleus

was

produced

by

the

fusion of

other

nuclei.

The

uncertainties

urrounding

he

phenomena

f

fertili-

zationwere no less numerous han thosewhich

had

obscured

the

details of

nuclear

multiplica-

tion.

While

mitotic

division

assured

the

trans-

mission of

the

hereditary

ubstance

across the

innumerable

ell

generations f

any

given

organ-

ism,

the

means which

guaranteed

he

transferal

of

this same

material

rom

ne

generation

o

the

next

was

still

unsettled.

IV.

FERTILIZATION THE

UNION OF

NUCLEI

For

three

decades the

prevailing

iew of

fecun-

dation rested upon physico-chemical nalogy.

Largely

through

he

influence

f

J. von

Liebig

it

was

believed

hat ll

chemical

ctivity

epended

upon

molecular

agitations

nduced by

the

close

contact of

two

substances

and

their

constituent

particles.38

The

idea of

contagious

molecular

excitation

was

extended

y

K6lliker

nd

especially-

T. L.

W.

Bischoff

o

include he

eventsof

fertili-

zation.39

Bishoff,

nable

o

observe

he

penetration

of

the

sperm nto

the

egg,

suggested

nstead

direct

sperm

ction,

hat s,

fertilization

s

the

resultof

mere

close

proximity

f

sperm

nd

egg.

No

law

in

nature

being

more

general

han

that

excitations

are transmitted rom one contiguousbody to

another,

ertainly

ertilization

must

result

from

egg-sperm

contact.

"Der

Saamen

wirkt

beim

Contact,"

he

declared,

37

E.

Strasburger,

"Die

Controversen

der

indirecten

Kerntheilung,"

Arch.

mikro.

Anat. 23

(1884):

p. 301.

38J. von

Liebig,

"Sur

les

phenomenes de la

fermenta-

tion,"

Ann. de

chim.et

de

phys.

71

(1839): pp.

147-195.

Dr.

F.

L.

Holmes

provided

this

reference.

39

T.

L.

W.

Bischoff,

"Theorie

der

Befruchtung

und

uiberdie

Rolle,

welche

die

Spermatozoiden

dabei

spielen,"

Arch.

Anat.

Physiol.

u.

wiss.

Med

1847:

pp.

422-442.







134

WILLIAM

COLEMAN

[PROC. AMER.

PHIL. SOC.

bei Beruhung,

durch

katalytische

Kraft,

d. h.,

er

konstituirt

ine in einer

bestimmten

orm

der

Um-

setzung

und inneren

Bewegung

begriffene

Materie,

welche Bewegung

sich

einer

anderen

Materie,

dem

Eie, die

ihr nur

einen hochst

geringen

Widerstand

entgegensetzt,

der,

wie wir

auch sagen

konnen,

n

demZustande der

grossten

Spannung

oder der

gros-

stenNeigung zu einergleichenund ahnlichenBewe-

gung

und Umsetzung

sich

befindet,

mittheilt, nd

in

ihr eine gleiche

und

ahnliche

Lagerungsweise

der

Atome hervorruft.40

Bischoff explicitly

denied that

excitation

was

due

to the gross

movements

of the

spermatozoon.

Rather,

it was

the consequence

of internal

and

undetectable

molecular

motions.

The

proponents

of the

new

hypothesis

were

numerous

and influential.

R. Wagner

and

R.

Leuckart, two

of the foremost

students

of

genera-

tion,

were

persuaded

that

Bischoff's

notion,

albeit

imperfect,

asily surpassed

the

nonsense suggested

by K. F.

Burdach

(the spermatozoa

were really

unicellular

infusorians

and had

nothing

to do

with

fecundation)

or the

unsatisfactory

peculations

of

R.

Valentin

(movements

of the spermatozoa

maintained the

proper

mixture

of the true

fecun-

dating

substance,

the

seminal fluid).41

Wagner

and Leuckart,

like

many

others, accepted

the

contact

theory

of fertilization

because

there

existed

no

plausible

alternative.

The contact

theory,

moreover,

could be and

was

claimed

as a

triumph

of new

physiological

ideals.

In opposition to the traditional mode of physio-

logical

inquiry,

relying

principally

upon

anatomi-

cal

description

and refined

vivisectional techniques,

there

was

heard from about

the late 1840's

a

loud

clamor

demanding

that physiology

strive

henceforth

to

reduce

all vital

processes

to

more

elementaryand, presumably,

primary

phenomena.

Only

chemistry, physics

and

the

mathematical

spirit

would

satisfy

these

demands. Said

Carl

Ludwig

in

a classical

statement

of the

reductionist

position:

So oftnuneineZergliederung er thierischen orpers

geschah,

so

oft stiess man schliesslich

auf

eine

begrenzte

Zahl

chemischer

Atome

und auf

Erschei-

nungen,

die

durch

die Annahme

des

Lichtathers

und

der

Electricitaiten

rklirlich

ind.

Dieser

Erfahrung

entsprechend

ieht

man den

Schluss,

dass alle

von

thierischen

orper

usgehenden

eistungen

ine

Folge

der

einfachenAnziehungen

und

Abstossungen

sein

m6chten,

welche

bei

einem

Zusammentreffen

ener

40Ibid.,

p.435.

41

R.

Wagner

and

R. Leuckart,

"Semen,"

The

Cyclo-

pedia

of

Anatomy

and PhysMiology,

d.

R. B.

Todd

(6

v.,

London,

1847-1849)

4,

1:

pp.

472-508.

elementaren

Wesen

beobachtet

werden. Diese Folge-

rung wird unumst6sslich, enn

es gelingtmit mathe-

matischer

chairfe

achzuweisen, s seien die

erwahn-

ten elementaren edingungen

ach Richtung, eit und

Masse im

thierischen

K6rper derartiggeordnet,

ass

aus ihren Gegenwirkungen

mit Nothwendigkeit lle

Leistungen

des lebenden und todten Organismus

herfliessen.42

At mid-century

t was, of course, markedly

pre-

mature to anticipate a rapid

realization of these

ambitions.

Except in limitedareas (for

example,

electrophysiology

and muscular heat production)

proclaimed ideals far exceeded

available means.

The contact

theory of fertilizationreflects

both

the claims and the shortcomings

at this time of

the reductionist point of

view. The theory was,

at

its

creation, strictly up-to-date

and, until the

1870's, it was not seriously

challenged. In 1874,

two years before the publication of Hertwig's

revolutionary

paper on the process of fertilization,

W.

His

argued passionately

in favor of

a "Theorie

der ubertragenen Bewegung."

His, an outstand-

ing embryologist,was thoroughly

persuaded that

chemistry,mathematics, and,

above all, mechanics

were the only

sound foundation for the study

of

organic

development. Growth,

the develop-

mentalmanifestation

f

the

vital processes,

seemed

but

the net effect of a great

series

of

motive

phenomena

(B ewegungsvorgdnge)

founded

in

the

intimate

molecular structure

of

the

organism.

The starting point for all growth was the egg

which, benefiting

from

the

stimulus

of the

male

and

not

from its substance,

was

made

ready

for

development.

Fertilization

meant

(molecular)

stimulation

and

not

a substantial

transfer.

"Das

befruchtete

Ei,"

said

His,

traigt

n sich die

Erregung

zum

Wachtsum.

...

In

der Wachstumerregung

aber

liegt

.

.

.

der

ge-

sammte Inhalt

erblicher

Uebertragung

von

vater-

licher sowohl,

als

von

miitterlicher

eite.

Nicht

die

Form

ist

es, die

sich

iubertraigt,

och

der

specifisch

formbildende

toff,

onderndie

Erregung

zum

form-

erzeugenden Wachstum, nicht die Eigenschaften

sondern

der

Beginn

eines

gleichartigen

Entwicke-

lungsprocesses.43

These words

no more than

restate

the basic

prin-

ciples

of

Bischoff's

contact

theory.

As director of

42

C. Ludwig,

Lehrbuch

der

Physiologie

des

Menschen

(2nd

ed.,

Heidelberg,

1858)

1: p. 2.

See K.

Rothschuh,

"Johannes

Muller

und

Carl

Ludwig.

Ihre

Bedeutung

fiurdie

Entwicklung

der

modernen

Physiologie,"

Deuts.

wed.

Wochschr.

78

(1953)

: pp.

71-74.

43

W. His,

Unsere

Korperform

und

das

physiologische

Problem

ihrer

Entstehung

(Leipzig,

1874),

p.

152.







VOL. 109, NO. 3, 1965]

CELL, NUCLEUS, AND INHERITANCE 135

the Anatomisches nstitut

t

Leipzig

and a

col-

league

and

friend f

Ludwig, His had

long been

exposed to

the

reductionist octrine. He felthe

had succeeded n

reducing eneration

o

no

more

than

"eine Fonction von

Raum und von

Zeit,"

space and

time being

the essential

reductionist

conditions f any naturalprocess.44

The

views expressed

y His and others

directly

contradicted he central

thesis of Hertwig's so-

called

"fertilization

heory." According

to the

latter, ertilization

as nothing ess

thanthe com-

plete fusion r

at least the

apposition f the nuclei

contained within

the uniting

germ products.

The argument

required of the

egg and sperm

cells

the transmission

rom arent o

offspringf

a

substance,

presumably

substance of definite

molecular

onstitution.

While thecontact

heory

conceded that

the peculiar

fertilizing xcitation

was in some mannerusually, f not always, as-

sociated with the

spermatozoa,

Hertwig's theory

demanded

bsolutely he direct

physical

union

of

the

egg

and

sperm.

L.

Spallanzani

in

the

1780's reported

xperi-

mentswhich

mighthave

shown conclusively

hat

the

presence

f

spermatozoa

nd

their

uninhibited

access

to the

egg were

essential

for

fecundation.

Despite

his

evidence,however, pallanzani

chose

to

disregard

the

spermatozoa

of

the

frog

and

to

maintain

hat the seminal fluid

n

which the

spermatozoawere

found

was

the true fecundat-

ing agent. Spallanzani's peculiar bias appears

to

have

been due to his

strict

dherence o

pre-

formationist

hinking.

An

ovist,he saw

no

need

for the

male.45

Almost

half-centuryater

these

experiments

were

repeated

in

Geneva

by

two

physiologists, .

L.

Prevost

and

J. B. Dumas.

Their data

demonstrated eyond

any reasonable

doubt thatthe formed

lements

n

the

semen,

he

spermatozoa,

were

the active

fecundatinggency;

the seminal fluidwas a

passive vehicle.

In

the

most

dramatic

f their

xperiments,hey

showed

that the

fecundating power"

of

the semen

was

progressivelyost as thisfluidwas drawnthrough

a series

of

five ilica-covered

ilters.46

pallanzani

44Ibid.,

p. 153.

45

J.

Rostand,

Les Origines de la

biologie

experimentale

et

l'abbe Spallanzani

(Paris,

1951), pp. 180-186.

But see

P.

C. Ritterbush, Overtures to

Biology. The

Specula-

tions of

Eighteenth-century

Naturalists

(New Haven,

1964), p. 106.

46

J.

L. Prevost

and J. B.

Dumas,

"Deuxieme

memoire

sur

la

generation.

Rapport

de

l'oeuf

avec

la

liqueur

fecondante.

Phenomenes

appreciables resultant

de

leur

action

mutuelle.

Developpement

de

l'oeuf des

Batrachi-

ens,"

Ann. des sci.

nat.

2

(1824)

rpp. 142-143.

had

performedmuch the

same experiment nd

had acquired many

of the same data. He

never-

theless

nterpretedhem

n a

wholly pposed man-

ner.

Prevost

and

Dumas were

convinced epi-

geneticists-the

ommencementf cleavage of

the

egg was

used

as

the criterion f successful

ertili-

zation-and they elt hatonlythe unionof sperm

and

egg effected

truegeneration.

M.

Barry

in

1843 recorded

the presence

of

spermatozoa

within he fertilized

gg (the yolk,

and

not merely he

vitelline nvelopes).

His

dis-

covery

was notgreatly

emarked nd it remained

for

George Newport,

in

a

series of splendid

monographs n the

generative arts of

the frog

and other

animals, to show

that this was the

normal ondition f

fertilization.47 either

Barry

nor

Newport, orany other

nvestigator,itnessed

the

actual

penetration

f

the

egg by the sperm.

Furthermore,t proved impossibleto trace the

fate of

the contained

permatozoon. Apparently

it was dissolved in

the egg mass and

lost all

identity. As a

consequenceof

these discoveries

even Bischoff

1854)

was

convinced that the

sperm ould

and

did

enter he

egg,but what effect

it

might

have there was

in

no

way clarified.48

Material

contact etween

gg

and

sperm

was now

indisputable. Whether here

henresulted

n

ex-

change

of

materials

or

whether

he

sperm

still

exerted a

purely excitatory

ower

could

not be

decided.

H.

Milne-Edwards,

eeking

the most

general statement f the fundamentalonditions

of

fecundation,

ould

offer

nly the

ambiguous

"action

directe de la

liqueur seminale sur

cet

ceuf,phenomene ui

n'a lieu

que par l'effect

u

contactmutueldu

sperme et de ce corps

repro-

ducteur."

9

Interpretations

f

the

physiology

f

sexual

generationhad

become

exceedingly

on-

fused. The contact

heory

f

excitationwas not

wholly

discredited

y

the

supposition

f

the

pene-

tration

of

sperm and

its

included

material. A.

Thomsen

suggested hat

inthe ct of fecundationheproducts f theoriginalcells that s, sperm nd

eggsderived

rom

heir

rigi-

nal

tissue sources]

meet and combine r

mutually

influence

ach other. The

germ-cells,hen, re the

links in

the

chain of

organic connection etween

47G.

Newport, "On the

Impregnation

of

the Ovum

in

the

Amphibia.

First

series," Phil.

Trans.

Roy.

Soc.

Lond. 141

(1851): pp.

169-242,

etc.

See

Hughes,

1959

(note

20):

pp.

60-61.

48

See H.

Milne-Edwards,

LeCons

sur

la

physiologie

et

l'anatomie

compare'ede

l'homme et

des animaux

(14 v.,

Paris,

1863)

8: pp.

359-364.

49

Ibid., p.

338.







136

WILLIAM

COLEMAN

[PROC.

AMER.

PHIL.

SOC.

either r

both heparents

nd theprogeny

apable

f

beingdeveloped

rom he

fecundated

vum.50

While admitting

he essentiality

f the germ

prod-

ucts as

the links between

uccessive

generations,

Thomsenwas

unable to

choose between

combi-

nationor mutual nfluence. The respective ole

in fecundation

f the

egg and sperm

and

also

that of their

parts would

remain

unknownuntil

the cytological

esearches

f

Hertwig and

Fol.

The

confusion

exhibited

by the alternative

theories

f fertilization

y contact

or penetration

is

suggestive

f the difficulties

hich

beset

the

entire tudy

f the nucleus

nd disturb

hose

who

mightwrite

ts history.

One is often

ompelled

to speak

of "errors" or

"mistakes."

To utter

such

udgements

s

clearly o violate

hehistorian's

wise rule

never to press

present

understanding

into past circumstances.But, when judged by

later

work of the

same decade, Schnieder's

views

on fertilization

ere truly

rroneous

nd so

too

was

Strasburger's

ision

of the transverse

ivi-

sion of the chromatic

mass

lyingon the

nuclear

equator.

To

speak

here

of "error,"

therefore,

will

be

assumed

to be legitimate,

or these

are

questions

having

at least

some tangible

nd

re-

peatable

basis

of

reference,

he relevant

ell prep-

arations.

"Error"

or "mistake"will

henceforth

refer o

observations

ased on

material repared

y

inadequate

r inappropriate

ytological

echniques

(as judged by lateror modern tandards) or to

observations

taken

from recalcitrant

materials.

"Error"

n

the

conceptual

ense

s

another

nd less

simple

matter.

Mere

reference

o

later

discoveries

or

interpretation

s here unsatisfactory

nd

il-

legitimate,

nd

can serve

no

useful

purpose.

Present

disagreement

ith

the views

of

Hertwig,

Strasburger,

eismann,

nd others

may

mean

that

these

will

be labeled

"erroneous"

but this

can

only

be

accepted

as

a

figure

f

speech

and

not

as

a definitive

stimate

f the meritsor

failings

of their

opinions.

To completethe cellularcycle

of

generations

it

was

necessary

only

to

derive the

sperm

and

the

egg

fromthe

parent

tissues. The

study

of

mitosis

proved

the

continuity

f cell

and

nucleus

from he

first

ody cell,

the

fertilized

gg,

to

the

final

orm

f the

organism.

Fertilization

nvolved

either

ontact

r union of

two cellular

derivatives

of

the

parent rganism.

A. von

K6lliker

described

the

derivation

f the

spermatozoa

rom he

tissues

of

the

male

organ.

His classic treatise

on

50A. Thomsen,

"Ovum,"

Todd's

Cyclopedia

(note

41)

5

[Suppl.

1859]:

p.

138.

spermatogenesis

as

based on researches

arried

out on a great

variety

f North

Sea invertebrate

species, specially

hecrustacea.5'

It won

general

approval

and its

conclusions

were

confirmed

y

studies

on

numerous

other animal

groups.

By

1865 cytologists uch as A. von la Vallette St.

George and

H. Schweiger-Seidel

lready

were

seeking he

nnerdetail

of the

spermatozoon,

ow

definitely

egarded

s a cell.52

C. Gegenbaur

rought

ogether

vidence stab-

lishing

he cellular

nature

of the

egg. Drawing

upon

Schultze's

new definition

f

the cell

(pub-

lished n the

same

volume of

the same

journal)

Gegenbaur

decided

that "jede

Zelle

bestande

sonach

aus einem

Quantum

lebender

Substanz,

namlich em

Protoplasma

nd

demKerne.

der in

letzerem

eingebettet

st."

3

The egg was

just

such a vital quantum

and

it was

so because

it

was

the

product

of living ovarian tissues.

The decisive

dvance

n the tudy

ffertilization

was made by

Oscar

Hertwig.

Afteryears

of

attention

o

theprotoplasm,

ertwig

ecalled,

here

appeared

a

treatise

n which

the nucleus

received

major

consideration.

This

work,

Heft

2 of

Auer-

bach's Organologische

tudien (1874)

induced

Hertwig

to

look more closely

to

the

nuclear

phenomena

f fertilization.54

uerbach

had ex-

amined

unstained

reparations

rom he

nematode

worms,

Ascaris

nigrovenosa

nd

Strongyluis

uric-

ularis.

He

had

noted

a

peculiar

sequence

of

events lwaysfollowed ertilization.55Within he

egg

there ppeared

two

nuclei.

These

nuclei

ap-

proached

ne

another ndfinally

used.

The

single

resulting

ucleus

then

diminished

n

size,

became

elongate

and

finally

ssumed

a

dumbbell-shaped

form,

with

broadened

ends and

a

narrow

waist.

At

the

rounded

ends

of

the dumbbell

"rays"

appeared

which

penetrated

nto the

surrounding

51

A.

von

K6lliker,

Beitrage

zur

Kenntnis

der

Gesch-

lechtsverhdltnisse

nd der

Samenfliissigkeit

wirbelloser

Tiere,

nebst

eine Versuche

iiber

das

Wesent

und

die

Bedeutung

der

sogenannten

Samentiere

(Berlin,

1841).

Not seenby author.

52 Hughes,

1959 (note

20):

pp.

19-24.

53

C. Gegenbaur,

"Ueber

den

Bau

und

die

Entwickelung

der

Wirbelthier-Eier

mit

partieller

Dottertheilung,"

Arch.

Anat.

Physiol.

u. wiss.

Med.

1861:

p.

502.

54

0.

Hertwig,

"Beitraige

zur

Kenntniss

der

Bildung,

Befruchtung

und Theilung

der

thierischenEies,"

Morph.

Jahrb.

1

(1876):

p. 340.

See

B.

Kisch,

"Forgotten

Leaders

in

Modern

Medicine.

IV.

Leopold

Auerbach,

1828-1897,"

Trans.

Amer.

Philos.

Soc.

44(1954):

pp.

297-313.

55

See

E.

L.

Mark,

"Maturation,

Fecundation

and

Seg-

mentation

of

Limax

campestris,"

Bull.

Mus.

Cornp.

Zool.

6 (1881):

pp.

263-264.







VOL.

109,

NO.

3, 1965]

CELL, NUCLEUS,

AND

INHERITANCE

137

protoplasm. These, Auerbach

believed, were

formed y the nuclear

fluids s they eft

he nu-

cleus.

The nucleuswas

disappearing, issolving

itself nto

the protoplasm. The

old nucleus

be-

came invisible, he yolkmass

began

to cleave

and,

moments ater, two new nuclei appeared,one in

each of the

new cells

or

blastomers. Auerbach's

descriptioneems

no

morethan

repetition

f

the

common

notion of

nuclear

disappearance-reap-

pearance. His

fundamental iscovery,

however,

was

the presence f a

second

nucleus

qua nucleus

in

the

fertilized gg. The

binucleate tage

had

already

briefly

een

described

y

Biitschli;

t

had

been overlooked by

Schnieder.56 Auerbach's

descriptionwas

more complete

and, moreover,

was

part

of a

discussionof

segmentation. But-

schli's

discovery f

the binucleate tage had

been

incidental o

his

principal bjective, he

descriptive

anatomy nd taxonomy f the free-living ema-

todes.

Neither Auerbach

nor

Biitschlihad

any

conception

f the origin of the

second nucleus.

After

fertilizationne saw two

nuclei appear at

opposite nds of the

egg; it seemed hat hey

were

products

f the egg protoplasm.

No connection

was

made between

one

of

these nuclei and the

fertilizing

permatozoon.

In

the spring f

1875 Hertwigwas

investigating

the marine

fauna at

Villefranche n the

French

Riviera. He was

seekingan

organism suitable

for

the

study of

nuclear transformations.

An

almostperfectubjectwas found n theMediter-

ranean

ea-urchin, oxopneustes

ividus.57 t was

everywhere vailable and

was

sexually

mature

throughout

ost f

the

year.

The

male

and

female

animals were

separate and

artificial ertilization

was

therefore

asily practicable. The

eggs

were

small,

acked

noticeable

membrane,nd

contained

a

finely ivided

yolk. They werethus

ransparent,

even

at

high magnifications.

Finally,

both

egg

and

sperm emained iable

n

laboratory

ea

water

and

were

also

simple

to

preserve, ix,

and

stain.

Using

stained

preparationsHertwig

first

fol-

lowed the fate of the egg or "female"nucleus,

and fell into

error. He

studied the

by-then-

familiar

events

of

the

"retrogressivemetamor-

phosis"

of the

egg nucleus, hat s,

nuclear hanges

occurring

ust prior to

fertilization. His con-

clusion was

that,

while

a

major

part

of the

nu-

cleus

did

disintegrate,ne

constituent

lement, he

56

0.

Biitschli,

"Beitrage

zur

Kenntnissder

freilebenden

Nematoden,"

Nova

acta Acad.

caes.

Leop.-Carol. 36

(1873):

pp. 1-144,

esp. Tafel X

(XXVI),

61d: i-xi.

57

0.

Hertwig,

"Dokumente

zur

Geschichte der

Zeu-

gungslehre,"Arch.

mikro.

Anat.

90

(1918):

pp. 31-32.

Keimfieck,

did

persist.58

This

deeply staining

body,

he nucleolus

r

Wagner's

spot,

thereby

s-

sured

thecontinuity

f

thefemale

nucleus nd

was

the

"morphological"

lementwith

which

he

perm

or

"male" nucleuswould

unite.

Spermatozoa were added to a sea-watersus-

pensionof

ripening

ggs. Always within

fifteen

minutes nd

usually

within five to ten

minutes

Hertwig discerned

the

commencement

f

the

familiar

phenomena

f

indirectnuclear division.

Prior to thisevent,

however, e had

observed wo

nuclei within the

egg. They

migrated owards

one

another, ame

into

contact

nd then

ppeared

to fuse

completely.

This

was the

moment

of

fertilization:

wo

nuclei united to

produce

the

first

nucleus of a

new generation.

The impor-

tant fact was

established,

aid

Hertwig, hat

der unmittelbaror der Furchung n der Eizelle

vorhandeneinfache

ern,

um welclien ie Dotter-

k6rnchenn

Radien

ngeordnetind, us der

Copu-

lation

weierKerne

hervorgegangenst.59

Hertwighadnot

actually een the

male element

(spermatozoon), which

presumablywould

carry

the

male nucleus,

enter the egg.

He

could

only

infer hat

the second

nucleus within he

egg had

come

from

he male

parent.

In

spite

of

this,he

felt

that

the

evidence was

conclusive. He re-

corded the

earliest

appearance of the

second

nucleus at

exactly hat

pointon the egg's

surface

where the spermatozoontselfwas last seen and

he

described he

thin traceof a

line

in

the yolk

which

he

believed had

resultedfrom he

passage

of

the

male nucleus on

its way

towardsthe egg's

center nd

union

with the

femalenucleus. Most

importantly,e did

nothesitate o

statethat one

and

only one sperm or

male

nucleus appeared

in

the

egg and

therefore,

y extension,

ut

one

sperm

nd

no

more was

required o

effect

ormal

fertilization.60

In

the

cleavage of

the egg

subsequent o fertili-

zation

the

nuclei,

Hertwig maintained,

never

disappeared. All nucleiwerederivatives,hrough

mitotic

ivision, f

the original

cleavagenucleus

(Furchungskern).

The nuclei

were therefore

absolutely

ontinuous;

that is, the nuclei

of the

germmother ells of

generation gave

rise to the

nuclei

of

that

generation's ametes

egg, sperm),

the latter

nuclei

united

to formthe

first cell

nucleusof

generation

and from hiscell

nucleus

arose

generation

's germ ell

nucleiwhichwould

58

Hertwig,

1876

(note

54):

pp. 357-358,

378.

59

Ibid.,

.

383.

60

Ibid.,

.

384.







138

WILLIAM

COLEMAN

[PROC. AMER. PHIL.

SOC.

later

unite

o

produce

he

ygote

ucleus

f

genera-

tion C,

and

so

on ad

infinitum.

Evidently

the

nucleus

was

a body

of

great

physiological

mpor-

tance,

ein

in der Zelle bestehendes

utomatisches

Kraftcentrum."

1 Beyond

this general

and

in-

conclusive tatement,owever, ertwigwouldnot

speculate.

Challenged

lmost

mmediately

n

various

points

of detail

and

interpretation,

ertwig

hastened

o

gather

more comprehensive

orroborative

vi-

dence.62

In 1877

he

repeated

his

experiments

n

Toxopneustes

nd

examined

also

the

process

of

fertilization

mong

the

Hirudinea

nd

in the

frog.

The

following

ear,

working

t

Messina,

he ex-

tended

his researches

o

include

various

coelenter-

ates,

marine

worms,

chinoderms,

nd

molluscs.63

In all

cases,

his

earlier

observations

nd

con-

clusionswere confirmed.

The greatest

resistance

o

the Hertwig

fertili-

zation

theory

was

offered

y

Strasburger

nd van

Beneden.

The latter

had in

1875

published

a

report

on the

maturation,

ecundation,

nd

first

cleavage

events

of the

rabbit gg;

this

essay

was

reviewed

n an expanded

eport

f 1876.64

Several

points

n

the

memoir

greed

nicely

with

Hertwig's

later

discoveries.

The peripheral

lear

spot (the

second

or male

nucleus),

ts central

migration

nd

the

final

nion

of the

maleand female

pronuclei"

(van

Beneden's

term

for the egg

and sperm

nuclei) were recordedby both observers. But

van

Beneden

refused

o

derive the

mature

female

pronucleus

rom

he

nucleus

f the

pre-fertilization

egg.

Not only

did

he

reject

Hertwig's

rroneous

derivation

rom he

Keimfleck

ut he denied

any

female

nucleus-pronucleus

ontinuity

hatsoever:

"the

central

[female]

pronucleus

which

appears

after

fecundation

s

an element

of new

for-

mation.

65

Seeking

a more suitable

subject

for

study

han

the

rabbit,

an Beneden

turned

o

the

sea.

At

Ostende

Oil

the

English

Channel

he

found

the

sea

star,

Asteracanthion ubens,

in

abundance.

It

possessed

many

of

the same

ad-

vantagesexhibitedby Toxopnetstes. From the

study

f ts

germ

products,

owever,

an

Beneden

61

bid.,

p. 418.

62

Hertwig,

1918

(note

57):

pp.

15-30.

63

0.

Hertwig,

"Beitrage

zur

Kenntniss

der

Bildung,

etc.:

Zweiter

Theil,"

Morph.

Jahrb.

3

(1877):

pp.

1-86;

"Weitere

Beitrage,"

ibid.,

pp. 271-279;

"Dritter

Theil,

Erste

Abtheilung,"

bid.,

4

( 1878):

pp.

156-175;

"Dritter

Theil,

II. Abschnitt,"

bid.,

pp.

177-213.

64 E. van Beneden,

"Contributions

o

the

History

of

the

Germinal

Vesicle

and

of

the

First

Embryonic

Nucleus,"

Quart.

Jour.

Micro.

Sci.

16 (1876)

: pp.

153-182.

65 Ibid.,

p.

156.

came

to

singularly

nexact

conclusions.

More

vigorously

hanbefore

he denied

the

contribution

of the

egg

nucleus

to

the

femalepronucleus,

e-

claring

that

there

was

"no genetic

bond"

of

any

sort

between

he

two.

Of equal importance,

e

deniedthatthe secondnucleuswithin he ferti-

lized

egg

(male pronucleus)

was derived

or

in

any

sense

related

to the spermatozoon

nd

its

nucleus.

Quite

simply,

"clear

spot"

appeared

de novo

in the

cortex

of

the

egg

and

this

clear

spot

(really,

small,

circular,

ess opaque

region

of

the

yolk)

then

became

the male

pronucleus.66

Van

Beneden

lso stressed

Hertwig's

ailure

o

see

actual

sperm

penetration.

This essay

reveals

more

the deficiency

f

van

Benden's

early

cytological

technique

than

it

refuted

he

sperm's

contribution

o

fertilization.

To accept t facevaluehisconclusionswouldhave

meant

to

discount

any

materialcontribution

y

the

male parent

to the offspring.

According

to

his theory,

he

sperm

played

little

or

no

role

in fecundation

nd

the

egg

nucleus

was

a

new

formation.

Fertilization

was

in effect

enied

all

reality.

It was

Hermann

Fol

who

produced

the

most

persuasive

evidence

of

the correctness

of

the

Hertwig

theory.*

Fol rectified

number

of

Hertwig's

observational

rrorsbut,

unfortunately,

added

several

of his

own. Like

van

Beneden

he

chose

the

common

ea

star,

Asterias

glacialis

(=Asteracanthion), for the investigationof

fertilization.

This work

was carried

out

at

Mes-

sina

in

early

1876

and was

completely

ndependent

of Hertwig's

earlier

researches.67

Fol

traced

the

two rapid

divisions (maturation

r

meiotic

divisions)

which preceded

fertilization

nd

ob-

served

that upon

their

completion

there

was

left

n

the

egg

but

one

nucleus.

This

nucleus

was

the

direct

product

of

a

series

of

divisions

(whose

precise

nature

Fol

did not

discover)

which

had

begun

with

the

undisturbed

ucleus

of the egg.

The

whole

female pronucleus

was

thereforeeneticallyonnected o theeggnucleus.

66 Ibid.,

.

179.

*

Hermann

Fol

(1845-1892).

Studied

zoology

at

Geneva

and Jena (student

of

E.

Claparede,

C.

Gegenbaur,

and

E.

Haeckel);

Professor

of

Comparative

Embryology

and Teratology,

Geneva

(1878-1886).

Devoted

to

the

study

of

all

aspects

of the

marine

fauna

and

especially

microanatomy.

A

founder

and

later

sub-director

of

the

marine

station

at Villefranche.

See

M.

Bedot,

"Hermann

Fol.

Sa

vie

et

ses

travaux [with

bibliog.

of

F.],"

Rev.

suisse

de

zool.

2

(1894):

pp.

1-21.

67

One

must

beware

of

Hertwig's

(esp.

1918,

note

57)

often

minute

attention

o

priorities.







VOL. 109, NO. 3, 1965]


139

This pronucleuswas derived

from

nucleus

and

not from

the

Keimfieck,

as

Hertwig

had

main-

tained. These

eventsoccurred

near the

surface

of the

egg where,

ccording

o

Fol,

D'autres

aches laires

pparaissent

ur es

c6tes

de

la premierevec aquelle lles e soudent leur our;

et de la sorte a

tache

ugmente

apidement,

out

n

marchant

ers e

centre

u

vitellus,

t se

change

n

un

veritable

oyau

muni

'un ou deux

nucleoles.

La

suite

du

developpement

ontre

ue

ce

noyau doit

encore

ecevoir

n

element

male;

nous

pouvons

onc,

avec E.

van

Beneden,

ui

donner e nom

de

pro-

nuclMus

emelle.68

On

the female

side,

continuity

f

the

whole

nucleus, nd

not

merely

f

one of

its

ephemeral

parts,

was

established.

Fol,

Hertwig,

nd

others

were

studying

oth

iving

nd

fixed-stained

rep-

arations and,

lacking a

standardized

vocabulary,

theywere not alwaysclear in their dentification

of

those

parts which

were

deemed

continuous.

One

of

the

greatest

riumphs f

the ater

chromo-

some

theory

would

be the

simple

recognition f

the

chromosomes

s

the

persistentnuclear

ele-

ments.

Fol

referredo

"refringent

odies" within

the

pronuclei,which

are

probably our

chromo-

somes, but

he

preferred o

speak

of

fertilization

as

the

union

of

"bodies"

or

"pronuclei."

Showing

tremendous

enacity, ol

was

finally

able

to

present

la

preuve

directe"

of

the

pene-

trationof

the

egg

by

the

sperm.

He

observed

theprocess of theactual spermentrancentothe

egg and

then

traced

to

the

centerof

the

egg

the

"tache

claire"

producedby

the

spermatozoon.

The

egg

presented

slight

bosse or

protuberance

(fertilization

one) to

the

first

permatozoon

o

reach its

surface.

The tail

of the

spermatozoon

slowed, ts

body

became

longated

nd

more

diffuse

and

finally

t was

seen

within the

egg.

"Ce

pronucleus

male,"

said

Fol,

"traverse e

vitellus

pour se

meler

ntimement

u

pronucleus

emelle.

...

De

la

fusion e

ces

deux

pronucleus

esulte e

nucleus

de

l'ceuf qui

se

fractionne

nsuite."

9

Normally,

o

more

han

one

spermatozoonnteredtheegg. Fol experimentallynduced

polyspermic

fertilization

nd

showed hat

his

condition

lways

led

to

aberrant

cleavage

and

monstrous

forms.

Fertilization

y

more

than

one

spermatozoon

as

68

H.

Fol,

"Sur le

commencement

e

1'henogenie

chez

divers

animaux,"

Arch.

zool.

exper. et

gen.

6

(1877)

p.

154.

This

paper

is an

advance

summaryof

Fol's

prin-

cipal

contribution

to

the

study of

fertilization:

"Re-

cherches

sur

la

fecondation

et le

commencement

de

l'henogenie

chez

divers

animaux,"

Metm.

de

la

Soc. de

Phys.

et

d'Hist.

Nat.

de

Gene've 26

(1879):

pp.

89-397.

69

Fol,

1877

(note

68),

p.

158.

obviously

bnormal.

These

splendid

xperiments

not

only confirmed he

directly

bserved fact

of

normal

monospermic

ertilization,

ut introduced

a

flexible

echnique

or

the

study

of

the

chromo-

somal

constitution f

the

nucleus,

a

technique

later brilliantly tilized by Boveri and others.

Fol

would

now,

presumably,

raw the

con-

clusion

which

today

seems

nevitable:

he essence

of

fertilizations

the union of

the male and

female

pronuclei

and of

no

other

parts.

This,

how-

ever,

he

could

not

do,

for

he had

previously

compromised

he

integrity

f

each of

these

ele-

ments.70

Both,

he

believed,

were

complexes

of

true

nuclear substance

and of

egg

protoplasm,

the

atter

ntering

nto the

formation f the

male

pronucleus rom

he

disintegrating

permatozoon.

While

nuclear

continuity

was

reaffirmed,

he

purity

of

the

fundamental

nuclear

componentswas denied.

Through

the

work of Fol

and

Hertwig

the

"physiological"

onception f

fertilization

as

re-

placed by an

increasingly

morphological"

on-

ception

of

the

process.

Fertilization

was

recog-

nized as

the

union

of

two

formal

constituents

of

the

organism, he

nuclei of

the

unitinggerm

cells.

The

new

theory,

ccording

o

V.

Hensen,

who was

generally

ympathetico

Hertwig's nter-

pretation,

... vertieftnsere

Kenntniss

on

dem

Befruchtungs-

vorgang,ndem ie zu denbishernur in Betrachtgezogenen

hemischen

nd

physikalischen

omenten

noch

hinzufuigtas

fur

den

Leberserscheinungen

(und

Vererbung)

so

bedeutsame

morphologische

Moment,

ass

naimlich ie

Materie in

bestimter

Formung

mitwirkt. . es

liegt eine

materielle

Vereinigunger

Geschlechtsstoffeem

Vorgang er

Befruchtung

u

Grunde.71

The

units of

fertilization

nd of

heredity,

what-

ever

else

they

might

ppear

to be,

were

presumed

to

have

a

definite

tructure

r

morphology,o

be

of a

specific

hemical

omposition nd

molecular

arrangement.

That

the

nuclei

ould be

hereditary

unitsat all seemedto Hertwig,Strasburger,nd

Weismann

to

depend

upon this

fact.

It

is

singular

that in

none

of

the

papers dis-

cussed

above

will

there be

found

an

explicit

statement

relating

the

newly

established

facts

of

nuclear

continuity

hrough

mitosis nd

fertili-

zation

to

the

general

problems

of

heredity

nd

70

Ibid.,

p.

169;

Fol

1879

(note

68),

p.

250.

See

Hert-

wig

1918

(note

57),

pp.

42-43.

71

V.

Hensen,

"Physiologie

der

Zeugung,"

Handbuch

der

Physiologie,

ed.

L.

Hermann

(6

v.,

Leipzig,

1881)

6,

zweiter

Theil,

pp.

126,

114.







140

WILLIAM COLEMAN [PROC. AMER.

PHJL.

SOC.

variation.

Hertwig, or

xample,

was bold

enough

to suggest

thatto this

data "eine

fundamentale

Bedeutung

eigemessen

erden

muss." 2

But

he

made

no reference

t this

time to

heredity, or

would he

do so until

1884.

Available evidence

was yet inconclusive. The new understanding

of fertilization,

uggestive

thoughit may

have

been, still

could not

demonstrate

ecurely

that

the

nucleus was

the unique

or principal

vehicle

of inheritance.

No

sooner,

however,

had van

Beneden

published

his researches

on

the origin

and fate

of

the

pronuclear

lements

of Ascaris

and

von

Nageli

had

issued

his great

essay

of

synthesis

and speculation

on

the mechanical

principles

f the

theory f

descent han

the situa-

tion was

transformed.

hese two

works

nduced

Hertwig,

Strasburger,

nd

Weismann

within

he

year independentlyo conclude that

the

nucleus

beyond

all question

was the material bearer of

heredity.

V.

EQUABLE

DIVISION

AND

IDIOPLASMA

The advance

of cytology

was due

as

much to

thestudy

f

new

animals

and

plants

as to

optical

improvements

nd the introduction

f new

tech-

niques.

The

discoveries

of

Hertwig

and

Fol

were

made

possible

by

the transparency

nd

ease

of

study

of

the

eggs

of

Toxopneustes

nd

Asterias. No less certainwas van Beneden's

success

in

1883

owing

to the

investigation

f

a

peculiarly

suitable

organism,

the

horse-thread

worm,

Ascaris

megalocephala

[var.

bivalens],

a common arasitic

nematode.*

Ascaris

attracted

van Beneden's

attention

because

of

its

large,

clear germ

cells.

The

large

spermatozoa

were

especially

elpful,

ince

t was

difficult

o

examine

72

Hertwig,

1878:

"Dritter

Theil,

II.

Abschnitt,"

note

63),

p.

177.

*

Edouard

van

Beneden

(1846-1912).

Educated

in

Belgium;

Professor

of

Zoology,

Liege

(1874),

his

only

academic position. A warm advocate of the new descent

theory,

but

principally

interested

in the

study

of

the

cellular

basis

of

life.

Described

the

phenomena

of

matura-

tion

and fertilization,

emonstrated independently

f

C.

Rabl

and

T. Boveri)

chromosomal continuity

nd

the

characteristic

hromosome

number

of

various

species

and

was

among

the

first

o

trace

cell-lineages

in

the

develop-

ing

embryo.

A

true

specialist,

he wrote

no

comprehensive

treatises

and

few

general

essays

and

devoted

himself

to

careful

and scrupulously

thorough

microscopical

inquiry.

See

A.

Brachet,

"Notice

sur

Edouard

van

Beneden

[with

bibliog.

of v. B.],"

Annuaire

de

l'Acad. roy.

de

Belg.

89'

annee,

pp. 167-242;

C.

Rabl,

"Edouard

van

Beneden

und

der

gegenwairtige

tand

der

wichtigsten

on

ihm

behandel-

ten

Probleme,"

Arch.

mikro.

Anat.

88

(1915):

pp.

1-470.

in

detail

the

transformations

f the very

small

male

product

f

the

sea-star

or sea-urchin.

The

arrangement

f

the female

reproductive

rgans

and

the

reproductive

ycle

of

Ascaris

also

were

advantageous.

At each stage

of

development

here

appeared n theoviduct housands f eggs in the

same

condition

nd the degree

of development

f

each

egg

was related

o its position

n the

oviduct.

Van

Benden

attempted

o trace

all events

pre-

ceding,

ccompanying,

nd

following

ertilization.3

Of

fundamental

mportance

was his

account,

based

on observations

f

living

nd stained

prep-

arations,

of the

fate

of

the

nuclear

components

during

fertilization

nd

the first

mbryonic

ivi-

sion

of the

nucleus.

In

modern

terms,

van

Beneden

discovered

hat

in the

variety

bivalens,

whose

somatic

hromosome

umber

was

4,

there

were

delivered

y the

sperm

o

the egg

2

chromo-

somes. These came into the proximity f, but

neither

disintegrated

or

fused

with,

two

chro-

mosomes

derived

from

the

female

pronucleus.

At the

first

embryonic

nuclear

division

each

daughter

ell

received

from

he

fertilized

ucleus

an equivalent

et

of

parental

chromosomes.

Van

Beneden,

of

course,

does not

use

the

term

hromosome.

According

o

his

observations

the

two pronuclei

within

he

fertilized

gg

each

exhibited

irst generalized

hromatic

eticulum.

This body

was

then

transformed

nto

a distinct

strand

(cordon),

deeply

staining

with

carmine.

The nuclearmembranelso disappeared. Finally

the

cordon was

divided

transversely

nd there

were produced

two

well-defined

hromatic

oops

(anses

chromatiques)

these

would

be the

chromo-

somes.74

In

order

that

the

normal,

or

somatic,

number

of

anses

be

reduced

from

four

(body

tissues)

to

two

(germinal

issue:

the

pronuclei)

van Beneden

proposed

that

the

formation

f

polar

bodies

was

really

the

expulsion

from

the

yet

immature egg

of one-half

of the

nuclear

substance.

His

views

on

the maturation

ivi-

sions

were

confused,

t

seems,by

a

belief

that

thefertilizedgg and all bodycellswere literally

hermaphroditic.

t

was

necessary

hat

he

egg get

rid

of its

male

elements

prior

to fertilization;

an

analogous

process

was

proposed

for

spermato-

genesis.

Fertilization

was therefore

he

recon-

stitution

f

the

hermaphroditic

ondition.75

73

E.

van

Beneden,

"Recherches

sur

la

maturation

de

l'oeuf,

a fecondation

et

la

division

cellulaire,"

Arch.

de

biol.

4 (1883,

publ.

1884):

pp.

265/640.

74

Ibid.,

pp.

532-534.

75

Ibid.,

pp.

527,

611.

On

maturation

division

(meio-

sis),

see Hughes,

1959 (note

20)

:

pp.

67-73;

Wilson,

1900

(note

7):

pp.

233-288.







VOL. 109, NO. 3, 1965] CELL, NUCLEUS,

AND INHERITANCE

141

When

the

two

pronuclei

met

at the

center

of

the egg there

was

never a

blending

of

their

substance

utalways

a

conjugaison,

n

apposition

of

their parts. Here

was a

capital

discovery.

The male

and

female contributions o the

first

embryonic ucleus, howevertheymightbe de-

scribed or

whatever

they

might

be

called,

re-

mained

physically ndependent

f

one

another.

They did

not blend,

hey

did

not fuse. ". . .

les

deux

pronucleusne se

confondent

amais....

il ne se

produit," aid

van Beneden,

"ni

avant,

ni

pendant la

karyokinese, ucune

fusion,

tout

au moins

en ce qui

concerne es elements

hro-

matiques es

pronucleus."6

This

discovery tood

in

opposition,

nd

correction, o the defective

idea of Hertwig

that

fertilizationesulted

from

the

"Verschmelzung er zwei

geschlechtlich

if-

ferenzirten

erne, des

Ei-

und

Spermakerns."

Once locatedupon the equatorialplane of the

fertilized

gg

the anses

(as

far

s observed

lways

four

n

number)

divided each

along

its

length

n

the

manner

previously

described by

Flemming.

At the

onset of the

separationof the

chromatic

mass

lying

on

the

equatorial plane

there were

thus

eight

elements, divided into four

pairs.

The parent anse

for two

pairs came from

the

father,

he parent anse

for the

remaining airs

came from he

mother. The

longitudinal

plitting

of

each

anse appeared to

produce

exactly quiva-

lent, lthough maller

ilaments.This fact

greatly

iinpressed an Beneden:

Ce

qui

frappe,'est

a

symetriearfaite

es filaments

marginaux; es

deux filaments

ont dentiques

ntre

eux.

Chaque grain

hromatiquee l'un a

[sic]

son

semblable

ans l'autre t

l'on ne

distingue as dans

l'un des

filamentsa

moindre

articuliariteui ne se

retrouve

xactement

dentique ans son

congenere.78

Following the splitting

f the four

anses, one

filament

nly from ach

pair was

drawn to each

pole

of

the egg.

These events

were strictly

om-

parable

to

those of

mitosis and

from the first

nucleuswere

derived, lways n

thesame

manner,

all of the cells of the organism.

These

discoveries

evealed he

means by which

a

discrete

morphological

lement f the

nucleus,

the anse

chromatique

r

chromosome,

as trans-

mitted

withunvarying

xactitude nd

regularity

from ne

generation o

the next.

Every normal

daughter

ell

without

xceptionwas

guaranteed

a

full

set

of

the

chromatic lements

elivered o

the

egg by the

spermand

receivedas

well a

76van

Beneden,

1883

(note

73)

:

p. 526.

77

Hertwig,

1877:

"Zweiter

Theil"

(note

63), p.

83.

78van

Beneden,

1883 (note

73)

:

p. 541.

full

set

of

those contained

by

the

ripe

egg

itself.

The

nucleus of

every

cell

was

composed

of

a

given

number

of elements,

one-half

of

which

were

paternal

nd one-half

maternal. "Le

present

memoire,"

an Beneden

ustly

claimed,

renfermea demonstratione ce faitcapitalque les

pronucleus ale

et

femelle

nterviennent

egalite

de

titres,

n fournissanthacun

eux nses

chromatiques

a la

plaque

nucleaire,

ans la

constitution

e

cette

plaque;

chaquenoyau ille

eqoit

u

disque quatorial

deux anses secondaires

males et deux

anses

sec-

ondaires

emelles.

De la

la

notion

'hermaphrodisme

nucleaire

read, besides

van Beneden's

nterpreta-

tion, the

equivalent arental ontributions

o

each

nucleus]

t

par consequentellulaire.79

In

August of

1883, an

avowedly

hypothetical

consideration" f

the problems f

nucleardivision

was

published.80

n

it a number f van

Beneden's

conclusions found independentsupport. The

author,W.

Roux, could not

agree,

however, hat

mitotic

division was

"quantitative"

alone and

not also

"qualitative."

Repeated

equivalentdivi-

sion of

the

nucleus ould

not,he

believed, rovide

the

diversity

f

chromatic

ubstancewhich was

deemednecessary

or he

xplication f

embryolog-

ical

differentiation.Roux

noted that

indirect

nuclear

division had

almost

entirely

replaced

direct division n

the favor of

cytologists.

But,

when

considered rom

strictly

mechanical oint

of

view and

with

regard

only to

structure,

ime,

and minimalenergy, he nucleus should divide

as Remak

had

suggested, hat s,

by directmass

cleavage.

What, Roux

then

demanded, ould

be

the

significance

or

biological

processes of

the

complex

and

physically

ess

efficient

ndirect

division

?

1

He

concluded

that

the purpose of

mitotic

division

was

to ensure

an

equal

distribution f

nuclear

quantity nd a

differential

istribution

f

hereditary

ualities.

The nuclear

substance

was

not, he

argued,a

mere

homogeneousmass

but

an

aggregate

f

bodies

Korner)

which

doubtlessly

represented he characters Qualitiiten) of the

organism.

If

these

bodies or

qualities did

not

form

aggregates and

were

scattered t

random

within

he

nucleus

there

ould

be

no

assuranceof

their

equable division.

The

aggregate, alled

by

Roux

an

einreihige

Anordnungor

Faden, was

thus

that

component f

the

nucleus

whichwas

79Ibid., p.

598.

80W.

Roux, Ueber

die

Bedeutung

der

Kerntheilungs-

figuren. Eine

hypothetische

rorterung

[1883]:

Gesam-

melte

Abhandlungen

iuber

Entwickelungsmechanik

der

Organismen

(2 v.,

Leipzig,

1895)

2:

pp.

125-143.

81

Ibid.,

p.

128.







142

WILLIAM COLEMAN

[PROC. AMER.

PHIL.

SOC.

distributed

o

daughter

nuclei.

Glancing

briefly

at the

available

cytological

nd

chemical

vidence

Roux

proposed

to identify

he Faden

with

the

chromatic

substance.82

Knowing

that

the

quali-

ties

were

secure

n

Faden the purpose

(Zweck)

of indirect ivision ould thenbe defined:

Die

Kerntheilungsfiguren,

ie Gestaltungen

er

in-

directen

Kerntheilung,

ind

Mechanismen,

elche

[wenn

ie

in

Thatigkeit

esetzt

werden]

s

"erm6gli-

chen,"

enKern

nicht

los einer

Masse

sondern

uch

der

Masse

undBesehaffenheit

einer inzelnen

uali-

taten

nach

["gleich"

oder

in bestimmter

Weise

"ungleich"]

zu

theilen.

Der wesenthliche

ern-

theilungsvorgang

st

die

"Halbirung"

der

Mutter-

k6rner;

lle

uibrigen

organge

haben

den

Zweck,

vonder

durch

iese

Theilung

ntstandenen

ochter-

k6rnen

esselben

utterkornes

mmer

e eines

n

das

Centrum

er

einen,

as

andere

n das Centrum

er

anderen

ochterzelle

icher

iberzufiihren.83

On the one hand this interpretation ould

accord

fully

with

van

Beneden's

views

and

those

f

a

majority

of contemporary

ytologists.

The

equal

distribution

"gleiche

Vertheilung")

of

Roux

harmonizes

fully

with

the

common

con-

ception

that

mitotic

division

ensured

an

equal

allotment

f

all

nuclear-chromatic

ubstance

to

every

daughter

ell.

On

the

other

hand,

Roux's

special

hypothesis

of

an unequal

distribution

("ungleiche

Vertheilung")

f the

nuclear

ualities

was

received

only

reluctantly.

Weismann

alone

would

accept

he

dea

and

bring

o

life ts

broadest

implications.

Whereas

van Beneden's

memoir

was

empirical

in

the

narrowest

nd

best

sense

of the

term,

Roux's

little

pamphlet

was

the

product

of

re-

markable

peculative

enius.

Roux's

essay

con-

tributed

o anatomical

novelties

but

it

did

serve

to

force

attention

o

the apparently

undamental

nuclear

components,

he

Fadden

or

anses

chro-

matiques.

Roux

returned

epeatedly

o

speculation

on the

nature

of

these

bodies.

Merely

because

their

ntimate

tructure

as inaccessible

o optical

examination

was,

to his

way

of

thinking,

no

reasonnot toconsider ll nuclear vents s chemi-

cal

and

physical

n

nature,

view strictly

n

keep-

ing

with

his

extreme

eductionist hilosophy.

The

nucleus

must

have

a

Metastructur.

"Es

muss,"

Roux felt,

aus den complicirten

errich-

tungen

es

scheinbar

omogenen

rganischen

ub-

strates

mit Sicherheit

ine

complicirte

tructur

gefolgert

erden."

4

Since

the

mode

of

division

82 Ibid.,

p. 133, 39.

83

Ibid.,

pp.

138-139.

Bracketed

phrases

added

by

Roux

in 1895.

84 Ibid.,

pp. 142-143.

of

the

nucleus

was

more

elaborate

hanthat

of

the

surrounding

ytoplasm,

he nucleus

was

evidently

a

complex

structure

nd because

of this

was

more

important

or the

vital processes

of

re-

generation,

evelopment

nd,

of

course,

reproduc-

tion. The chemicophysicalases of the nucleus

necessarily

ould

always

assume

a

definite

truct-

ural arrangement;

tendency

owards

a

firm

nuclear

morphology

as indicated.

Roux's

com-

plex

Fdden

would

have

provided

n

ideal

vehicle,

however

peculative,

or

the

hereditary

haracter-

istics

of

the

organism.

By implication,

ertainly,

Roux,

discussing

the

determination

f

bodily

Qualitaiten,

uggested

his

possibility.

However,

like so

many

others

before

him,

the issues

of

heredity

remained

a

submerged

theme.

They

would

only be

brought

nto

view

and related

to

the

various

cellular

components

y

the

botanist,

Carl

von Nageli.

Nageli

approached

broadly

the

whole

complex

of hereditary

roblems.*

His

bias

was

that

of

the physiologist

nd

not the cytologist.

He

was

seeking

above

all a "mechanical"

explanation

f

organic

evolution,

n

explanation

which

would

eliminate

he

uncertainties

f

Darwinian

natural

selection.

There

once

was

a

time,

Nageli

ad-

mitted,

when

descriptive

atural

history

ad

been

useful

but

that day

now had passed.

Only

"necessary"

knowledge

ould

be

of value

to

the

naturalist;

causal

laws

henceforth

were

alone

sufficient.Die Erkenntnissst beendigt,"Nageli

proclaimed,

wenn

es

als

die nothwendige

olge

bestimmter

rsachen

sich nachweisen

isst."

85

Nageli's

indictment

f natural

selection

con-

tained

several

counts.86

The selectionist

nquired

only

into

the

uses of

parts

and

characters

nd

never

of their

causes.

Useful

variations

eemed

*

Carl

Wilhelm

von

Nageli

(1817-1891).

Studied

zoology

with

L.

Oken

at

Zurich,

botany

at

Geneva

with

A.

P.

de

Candolle,

and

further

botanical

work

at

Berlin

and

with

M.

J.

Schleiden

at

Jena;

Privatdozent

at

Zurich,

Professor

of botany

at

Freiburg

i.

B.

(1852),

Zurich

Polytechnical nstitute 1855) and finallyMunich (1857).

One

of

the

most

versatile

and

influential

otanists

of

the

nineteenth

entury.

Student

of

apical

growth

and

other

problems

of

plant physiology,

n

early

and

eloquent

ex-

ponent

of

the

cell

doctrine,

a

supporter

of

the

descent

theory

but

not

Darwinian

natural

selection,

nd

proponent

of

the

micellar

hypothesis.

See

D.

H.

Scott,

"Carl

Wil-

helm

von

Nageli,"

Nature

44

(1891):

pp.

580-583;

K. Cramer,

Leben

und

Wirken

von

C.

W.

v,oni

Nageli

(Zurich,

1896).

85

C.

W.

von Nageli,

Mechanisch-physiologische

The-

orie

der

Abstammungslehre

(Munich-Leipzig,

1884),

pp.

8-9.

86

Ibid.,

pp.

284-337.







VOL. 109, NO. 3, 1965] CELL, NUCLEUS, AND

INHERITANCE

143

but

minor

in

nature and

offered

no

grasp

for

natural

selection.

Selection,

moreover, could

not explain

the obvious

breaks

in

the

organic

series. All

of these

rguments,

nd several

others

besides, were the common

baggage

of

Darwin's

scientificritics. So, too,was Nageli's principal

complaint.

According

to selection

theory

the

evolutionof

organisms

could

only

be "die

un-

bestimmter

Wirkung

unbestimmter

raschen."

But

Nageli

demanded

"stetiger

hylogenetische

Fortschritt u einer

corplicirteren

Organisa-

tion."

7

Here is

the crux of

Naigeli's

criticism

of

Darwin's

hypothesis. He

regarded

he entire

historical

evelopment

f

ife s an

obviously ro-

gressive

affair. The

course of

evolution was

always

positive,

pwards, owards

ncreasing er-

fection

(Vervollkommnung), perfection

being

measured

by greater structural

omplexity

nd

greater nd moreefficienthysiological iversity.

Directing

phylogeny

was the

"perfecting

orce"

(Vervollkonmnungstrieb)

nherent

n each

or-

ganism.

Natural

selection was

distinctly

un-

creative:

.

. .

nach

Darwin

st die

Verainderungas

triebende

Moment, ie

Selection

as

richtende

nd

ordnende;

nach

meiner

Ansicht st

die

Veranderung

ugleich

das

treibende

nd

das

richtende

Moment. Nach

Darwin

stdas

Selection

othwendig;

hne ie

konnte

eine

Verollkommnung

icht

tattfindennd

wiirden

die

Sippen

n

dem

naimlichem

ustande

eharren,

n

welchen

sie sich einmalbefinden.Nach meinerAnsicht eseitigt ie Concurrenzlossweniger x-

istenzfahige;ber

sie ist

gainzlich

hne

Einfluss uf

das

Zustandekommen

lles

Vollkommneren

nd

besser

Angepassten.88

The

burden of

Nageli's

inquirynow

lay in

dis-

covering the

locus,

nature

and

mode of

action

of

the

Vervollkomnungstrieb.

The

proposed

substance,

hefamous

dioplasma,

was then

found

to

control

both

ontogeny

nd

phylogeny

nd, in

fact,

o

be

slowly

modified y

the

latter. It

was

also

the

bearer of

heredity nd

the

determiner f

variation.

The idioplasm, hecreation fan extraordinary

reflective

ancy,

was

described s

a

proteinaceous

substance

f

very

peculiar

tructure.89

n a

rude

inorganic

olution

aggregatesof

molecules were

formed

nd

were

closely

covered

with a

filmof

water.

Under

appropriate

onditions hese

groups

(micellae)

might

spontaneously o

react as

to

87

Ibid.,

p.

290.

88

Ibid.,

p.

285.

89

bid.,

pp.

83-129.

See

J. S.

Wilkie,

"Nageli's

work

on

the

fine

structure of

living

matter.

I.,

II.,"

Ann.

of

Sci. 16

(1960,

publ.

1962):

pp.

11-42,

171-207.

form

protein.

The

production

of

protein,

a

characteristic

f

life,

meant that

primitive

nd

exceedingly

imple

organisms

might

rise

spon-

taneously.

In

these

forms

the

ever-present

u-

tritivematerials

and

the

proteinaceous

micellae

were thoroughlymixed. Under the influence f

molecular

orces,

however, he micellae

began to

acquire a definite

rientation.

The new

structure,

composed

mainly

of

proteinaceousmicellae

and

having

a low water

content,

was

highly

stable.

It

was the

idioplasm. From

an

original

single

micellargroup,

the

idioplasm,

during

the

course

of

evolutionary

hange,

was transformednto

a

highly

complex

structure

ontaining

numerous

parallel

strands. At

any

given

time

any

cross-

section of

the

same

idioplasmic tructurewould

everywhere

resent he same

pattern

f

strands.

It

was the

cross

sectionwhichdefined henatureofanyparticulardioplasm. The form,

magnitude,

and

arrangement

f

the

dioplasmicmicellae

were

really he

essenceof

the

organism,

or

theydeter-

mined

precisely

ow the

organism

would

develop,

how

it would

react

to

external

conditions nd

how these

propertieswould

be

transmittedo

the

offspring.

The

Idioplasma was the

substantial

basis of

the

Vervollkommnungstriebnd

thebearer

of

the

hereditary

ualities.

"Bei der

Fortpflanzung,"

ageli

claimed, ver-

erbt der

Organismus die

Gesammtheit

einer

Eigenschaften

ls

Idioplasma.

In

der

Keimzelle

sind die Merkmalealler Vorfahren ls Anlagen

eingeschlossen."

0

Naigeli

riumphantly

egarded

his

hypothesis s

an

indication

hat

evolutionary

biology

was

at

last

entering

the

"molecular-

physiologische

ebiet,"

with

the

idioplasm pro-

viding

complexly

atterned,table

physical

asis

for

heredity.

Although

by

naturebeyond

direct

confirmation

r

refutation

he

idioplasm

theory

was an

exceptionally ertile

nstance f

speculative

construction. To

the

idioplasm

Nageli

assigned

control

of

the

occasional

appearance of

"latent"?

characteristics,he

correlation

nd

exclusion

of

variouscharacter ombinationsnd thereinforce--

ment

or

diminution

f any

particular

haracter.

By

doing

o

he

not

only

uggested

pecial

qualities.

of

the

idioplasmbut

introduced

o the

searchfor

the

material

basis of

heredity he

evidence

to be

drawn from

plant

and

animal

breeding.

Decisive

was

the

well-known act

of

hybridiza-

tion

that,

n

most

reciprocal

rosses,

he

maternal

and

paternal

contributions

ere

equivalent.

A

female

of

variety

A

fecundatedby a

male

of

90

Nageli,

1884

note

85):

p.

24.







144

WILLIAM

COLEMAN

[PROC. AMER. PHIL.

SOC.

variety

B would

commonly

ive rise

to the

same

manifestation

f a particular

haracteristic

n

the

progeny

s a cross

between

female

of variety

B and

a male of

variety

A.

This

facthad

been

frequently

onfirmed

y

many different

reeders,

although t appeared to be dependentupon a

sufficientlylose

degree

f relationship

etween

he

two

crossedvarieties.91

he

equivalent

ereditary

contributions

f

the male

and female

gametes

suggested

o Naigeli

hat under

no circumstances

could

one equate

the contributions

f

the total

mass

or volume

of the egg

and sperm.

There

had to

be some esser

hereditary

ommon

enomi-

nator since

"die vaterliche

nd

mutterliche

rb-

schaft

ist ungefaihr

leich

gross, obleich

der

Vater

zur befruchteten

izelle bloss

denhunderd-

sten oder tausendsten

Theil beigetragen

at."

2

For Nageli this

common

denominator

was the

idioplasm includedin the egg and sperm; the

great

mass

of nutritive

material n

theovum

was

hereditarily

ndifferent.

he

idioplasm,

because

of its stable

arrangement

Anordnung),

had

the

furtherdvantage

hat

t retained

ts morphological

integritynd

would

not blend

with other

idio-

plasms.

In

the

process

of fertilization,

herefore,

two

different

dioplasms

nited

nd

produced

hat

of

the

following

eneration.93

Recalling

Naigeli's

insistence n

the equivalence

f male and

female

roles

in heredity

nd his

suggestion

that this

equivalence

was

due

to more

or less

equal

heredi-

tarymasses,bothHertwigand Strasburgerub-

stituted he

nucleus

for

the

idioplasm

nd

looked

to the

former

s thetrue

vehicle

f nheritance.

Nageli

had not confined

he

idioplasm

to

the

nucleus.

In

order

to account

for the

events

of

ontogeny

nd

regeneration

t

had seemed

essential

that

every

cell

of

the

body

have its

own

portion

of

the

idioplasm.

He

proposed

therefore

hat

during

bodily growth

the

idioplasmic

strands

also

enlarged,

ot

n cross

section,

ut

n

length.94

An

idioplasmic

eticulum

enetrated

ll

parts

of

the

body,

he

dioplasm

ommunicating

reely

nd

without nterruptioncross protoplasm, ucleus,

and

organ.

The

nucleus and

the

idioplasm

were

in

no sense

coextensive.

The

idioplasm

was not

entirely

ecure

from

modification

y

external

nfluences.

Naigeli

are-

91

See

C.

Naudin,

"Nouvelles

recherches

sur

i'hy-

bridite

dans

les

vegetaux,"

Ann.

des.

sci.

nat.,

Bot.,

s.

4,

9

(1863):

p.

189;

G.

Mendel, Experiments

in plant

hy-

bridisation

[1865],

trans.

Roy. Hort.

Soc.

(Cambridge,

Mass.,

1960),

p.

8.

92

Naigeli,

1884

(note

85)

:

p.

24.

93

Ibid.,

p.

141.

94

Ibid.,

p.

41.

fully

outlined

"eine ganze

Reihe

aufeinander

folgender

olecularer

ewegungen"

nduced n

the

nutritive

lasm Erndhrungsplasma)

ythe

action

of light,

cold,

dryness,

excessive

food and

so

forth.95

n order

for these

forces

o be

effective,

that s, to produce definitehange n themicellar

constitution

f

the idioplasm,

they had to

be

steady

in action

and

of long

duration.

To

be

hereditary

he

changes

had to

affect

he dioplasm.

The acquisition

f a new

hereditary

haracteristic

as a

consequence

f external

gents

was

therefore

not

excluded,

but such

an

eventwas

considered

to

be

neither

requent

or easy.

In support

f

this conclusion

Naigeli

ntroduced

earlier observations

nd experiments,

ncluding

muchof

hisown

work,

n thehawkweed

Hiera-

cium),

an extremely

iverse

genus

and

one

we

now

know

to be

unsuited

for simple

genetic

analyses.96Transportingnd cultivatingifferent

species

of the

hawkweed

n

various

regions

of

Europe

where

markedly

different

emperature,

light,

nd soil

conditions

would

be expected

had

led to temporary

morphological

iversity

nly.

Upon

the

return

f more

normal

original)

con-

ditions

the

normal (original)

plant

form

reap-

peared.

"Acquired"

characters

ad

not

really

een

acquired.

These

investigations

were prompted

by

evolutionary

onsiderations.

Nageli,

like the

great

majority

of

post-Darwinian

plant

and

animal breeders,

was

testing

he effectiveness

f

hybridizations a possiblecause of speciestrans-

mutation.

His regard

was

on the

wholeorganism,

the

species

and

the genus;

he was uninterested

n

the breeding

behavior

of individual

character-

istics.

It seems

not surprising,

herefore,

hat

he

should regard

Mendel's

precise

analysis

of

the

breeding

ratios

of

individual

characteristics

f

Pisum

sativum

as

"only

empirical,

ecause

they

can not

be

proved

rational"

nd should

then

suc-

cessfully

enlist

Mendel's

aid

in the

study

of

Hieracium.97

For

Naigeli

"rational"

xplanation

f

heredity

could only be one foundedupon mechanical r

causal

modes

of

explanation.

It is

regrettable

that

he failed

to remark

the stress

placed

by

Mendel

himself

on

the

required

physical

basis

95Ibid.,

p.

140.

96

Ibid.,

p.

107.

See

H.

F.

Roberts,

Plant

Hybridiza-

tion

before

Mendel

(Princeton,

1929),

pp.

183-204.

97

Naigeli

to

Mendel,

31

December

1866:

"The

Birth

of

Genetics,"

trans.

L.

K.

and

G.

Piternik,

Genetics

35

(Suppl.)

(1950)

: p.

5.

See

A.

Weinstein,

"The

re-

ception

of Mendel's

paper

by

his

contemporaries,"

A

ctes

du

xe Cong.

int. d'Hist.

des Sci. (2 v., Paris,

1964)

2:

pp.

997-1001.







VOL.

109,

NO.

3,

19651

CELL,

NUCLEUS,

AND

INHERITANCE

145

of

the

segregatingharacteristics.

Mendel's

state-

ment

reveals how

fully

he

appreciated

he

recent

advances

of

cell

theory

and

their relevance

to

hereditary roblems:

With

Pisum

t

was

shown

by

experiment

hat

the

hybrids ormegg and pollen cells of

different

inds,

and that herein ies the reason of

the

variabilityof

their

offspring.

...

In the

opinion

of

renowned

physiologists

esp. G.

Thuret,

1854;

N.

Pringsheim,

1855-1856], for

the

purpose

of

propagation one

pollen cell

and

one

egg

cell unite in

Phanerogams

into a

singlecell,

which

s

capable

by

assimilation

nd

formation f

new

cells to become an

independent r-

ganism.

This

development

ollows a

constant

aw,

which

s

founded

n

the material

composition nd ar-

rangement f the

elements

which

meet

in

the

[fertil-

ized

egg] cell in

a

vivifying nion.98

When

Nageli,

twentyyears

later,

finallypresented

his own

scheme of

the "inner

causes" of

heredity

and

variation

(Idioplasma), he

had

apparently

forgotten

oth

Mendel and his

suggestions.

What

perhaps

should have

caught Nageli's

eye,

quite

apart from

the

breeding ratios

themselves, was

the brief

but

definite assertion

that

the basis

of

heredity

and

variation

was to

be

sought in the

substance and

pattern of

the

cellular

elements.

Mendel, of

course,

looked

not to the

nucleus

but

rather

vaguely to the

cell as

the bearer

of

heredity,

a

position,

as

has

been

seen,

wholly typical

of

the

1860's.

VI. THE NUCLEUS AND INHERITANCE

Nageli's

distinction

between

Idio

plasma and

Erndhrutngsplasma

was of

major

importance

in

the

subsequent evolution of

the

problems of

in-

heritance

and

ontogeny.

The

Idioplasma, being

structurally

table,

became

the basis

for

hereditary

transmission, and,

because

of

its

molecular

com-

plexity,

served

to

control

the

endlessly

complicated

processes of

embryonic

growth and

differentiation.

The

distinction

emphasized the

active

role of the

Idioplaswiia

and the

passivity

of the

Ernihrungs-

plasmia. Despite the patent lack of concrete

supporting

evidence

Hertwig and

Strasburger and,

later,

Weismann,

looked to

Nageli's

hypothesis

as

both

suggestion

and

security for

their

conviction

that

the

nucleus

was

the

vehicle of

inheritance.

In

1884

Hertwig

finally

onverted

the

Befruch-

tungstheorie

nto a

genuine

Vererbungstheorie.*

98

Mendel,

[1865]

(note

91):

pp.

35-36.

Footnote

deleted.

*

Oscar

Hertwig

(1849-1922).

Studied

zoology at

Jena

and

Bonn

(student

of

E.

Haeckel,

C.

Gegenbaur,

and

M.

Schultze);

ord.

Professor

of

Anatomy,

Jena

(1881-1888)

and

Berlin

(from

1888).

Made

studies

of

His

essay,

bearing he

same date

(October,

1884)

as

that

by

Strasburger,

ecordedno

newly dis-

covered

vidence

but

presented

nstead

thought-

ful

review

of

established acts

nd a

full

develop-

ment of

arguments

upporting

he nuclear

basis

of inheritance.99 he fertilizationaperof 1875,

he

believed,was

the

essential

tep

towards

under-

standing

hereditary

ransmission,

or

in

it were

established

hat the

nucleus

alone,

and

not

the

protoplasm, as

the

fecundating

gent

and,

most

importantly,

hat

fertilization

was a

"morpho-

logical"

process, hat

s, a

union of

two

structural

elements, he

egg

and

sperm

nuclei.

There

could

be no

other

conclusion

than

that these

nuclei

were

the

connection

between

generations

nd,

because of

the

singular

facts

regarding their

behavior

iscovered

ince

1875,

he

unique bearers

of

heredity.

Hertwig

and

Strasburger

were

doubtlessly l-

erted

during heir

Jena

yearsto

the

potentialities

of

investigating

he

nucleus. Both

had

been

students

nd

were

warm

friends nd

colleagues

of

Haeckel.

Strasburgerwas

attracted

o

Jena

(1864) by

the

distinguished

otanist nd

student

of

reproduction

n

the

Phanerogams,

N.

Pring-

sheim,

but,

taking

minor

subjects

in

chemistry

and

zoology,

he

soon

came

under

Haeckel's

influence.

By

Haeckel

he

was

converted

o the

new

transmutation

octrine. Of

his

examinations,

passed

summacum

aude, Haeckel

recalled

Stras-

burger's intensiv ndgleichextensiv usgezeich-

neten

Kenntnissen"

and

gave

him

"nur

das

h6chste

Lob."

Strasburger

n

later

years

wrote

to

Haeckel "des

massgebenden

Einflusses,

den

Du

auf

meine

geistige

Entwicklung

ibtest."

00

The

relationship

etween

Hertwig

and

Haeckel

was

apparently

ess cordial

but no

less

significant.

The

Hertwigs

came

to

Jena

but

two

years

after

all

aspects

of

microscopical

anatomy,

especially

fertiliza-

tion,

heredity,

nd

germ-cell

maturation.

Later

became

a

sharp

critic

of the

chromosome

theory

of

inheritance.

Supporter of descent theorybut opponent of natural se-

lection.

With

brother,

Richard

Hertwig,

co-author

of

coelom

theory

of

development.

With

his

children,

Gunther

and

Paula

Hertwig,

introduced the

use

of

radiation

damage

as a

tool

for

investigating

develop-

mental

processes.

See

R.

Weissenberg,

Oscar

Hertwig,

1849-1922.

Leben

und

Werk

eines

deutschen

Biologen

[Deut.

Akad.

Naturf.

Leop.,

Lebensdartellungen

eutscher

Naturforscher,

nr.

7]

(Leipzig,

1959).

99

0.

Hertwig,

"Das

Problem

der

Befruchtung

und

der

Isotropie des

Eies, eine

Theorie

der

Vererbung,"

Jena

Ztschr.

fur

Naturwiss. 18

(1885): pp.

276-318.

100

G.

Uschmann,

Geschichte

der

Zoologie und

der

zoologischen

Anstalten in

Jena,

1779-1919

(Jena,

1959),

pp. 67-68.







146

WILLIAM

COLEMAN

[PROC.

AMER.

PHIL.

SOC.

the

publication

f Haeckel's

remarkable

volution-

ary synthesis,

he

Generelle

Morphologie

1866).

Although

only

Richard

studied

directly

with

Haeckel

(Oscar

enrolled

n

the medical

faculty)

both

were

his constant

ssociates

nd

it was

while

returningfrom a zoological expedition with

Haeckel

to

Corsica

that

Hertwig

undertook

he

fertilization

esearches

at

Villefranche.

In

the

Habilitation

defense

of

the fertilization

ssay

he

was

called

upon

to evaluate

the

claim

that

"die

Eizelle

durchliuft

n ihrer

Entwicklung

ein

Monerenstadium,"

statement

learly

proposed,

and

opposed,

by

Haeckel

and

one with

obvious

bearing

n

the

presumed

ructifying

nd

hereditary

role

of

the

nucleus.101

In the

Generelle

Morphologie

Haeckel

had

sought

o

explain

he

greatdiversity

f

animal

form

in terms f theevolutionaryransformationf

the

basic

structural

units.

The

latter

he

called

"plastids."

02 "Cytodes"

were plastids

without

nuclei

and

could

arise

either spontaneously

r

by

division.

The

Monera

were

cytodes

nd

so,

too,

were

all

cells

at the

moment

hey

underwent

division

ince,

at

that

stage,

the

old

nucleus

dis-

appeared

and

a

new

one

was formed.

"Cells"

were

also plastids

but

arose

only

by

division

nd,

except

during

division,

possessed

a

nucleus.

Haeckel

could

give

few

details

as

to

nuclear

structure.

Like Schultze

nd

contemporary

istol-

ogists

he

knew that

the

nucleus

was

varied

in

form,containedperhaps smaller bodies within

itself

and

was

probably

composed

of

some

al-

buminous

ubstance.103

No

more

than

this

would

he suggest.

But

as to the physiological

role

of the

nucleus

Haeckel

had

no doubts

and,

un-

fortunately,

o

real

evidence.

The

nucleus

was

the

bearer

of

heredity.

One has

the

impression

that

Haeckel

admired

most

the ogic

or

symmetry

of

his

scheme:

while

the

protoplasm

was

pliable

and

subject

to

external

conditions

the

nucleus

remained

nviolate

nd

guarded

the integrity

f

the

species.

In a

justly

famous

passage,

referred

to by all of the authorsof 1884-1885, Haeckel

set

forth

his views

on

the roles

of

nucleus

and

protoplasm,

he

one

hereditary,

he other

"adap-

tive":

Wenn

wir

.

.

die Form

e

des

Organismus

ls

das

Product

us

zwei

verschiedendene

actoren,

amlich

aus

den

ererbten igenschaften

einer

Materie

und

101

Ibid.,

pp.

90-93.

102

E.

Haeckel,

Generelle

Morphologie

der

Organismnen

(2

v.,

Berlin,

1866)

2:

pp.

113-117.

103

Ibid.

1:

pp.

278-279.

aus

der

Anpassung

an die Verhaltnisse

der

Aussen-

welt

zu betrachten

aben,

o

miissen

wir

dieses

Gesetz

auch

auf

die

Beurtheilung

er

Elementarorganismen,

der

Plastiden

anwenden

k6nnen.

Hier scheinen

nun

die

beiden

Functionen

der

Erblichkeit

und

der

An-

passung

.

.

.

bei

der

kernfuhrenden

ellen

in

der

Weise

auf

die

beiden

heterogenen

activen

Sub-

stanzenderZelle vertheilt ind,dass der innereKern

die

Vererbung

der

erblichen

Charactere,

das

aussere

Plasma

dagegen

die Anpassung,

die

Accomodation

oder

Adaptation

n

die

Verhaltnisse

der

Aussenwelt

zu

besorgen

hat.104

This scheme

is strikingly

imilar

to

that

developed

by

Naigeli.

The

idioplasm

replaces

the

nucleus,

but the

protoplasm

continues

its essential

role

as

mediator

with

the

external

world.

Naigeli,

when

creating

the

Idioplasma,

failed

to refer

o

Haeckel's

proposal

but

by

this

time

it was

probably

unneces-

sary.

Strasburger,

giving Haeckel

his

due,

never-

theless noted that the nucleus-protoplasmdistinc-

tion

by

1884

had

become

such

a

commonplace

that

scarcely

anyone

bothered

to

recall

its

origin.105

In a

brief

historical

review

of nucleus

and

fertilization

studies

Hertwig,

too,

referred

to

Haeckel's

conception.

While

applauding

the

hypothesis,

however,

he

lamented

the

absence

of

detail.

Hertwig

set

about

to

correct

this

de-

ficiency.

As usual,

ontogeny,

fertilization,

and

heredity

could

not

be separated.

The

commence-

ment

of

development,

as

signaled

by

the

first

cleavage

of

the

zygote,

was

still

the

prime

indi-

cator of successful fertilization nd, since growth

and

differentiation

lone

led to

the

formation

of

the

characteristic

specific

form,

they

could

safely

be

considered

the

most

evident

manifestations

of

heredity

(in

case

of

developmental

change

or

aberration,

of

variation

also). Ontogeny

was

thus

the

expression

of

heredity

and variation.

Of

course,

any

of the

numerous hypotheses

which

proposed

certain

environmental

influences

upon

development

or,

worse yet,

upon

the germ

would

grandly

confuse

the

whole

matter.

The

first

piece

of

evidence

offered

by

Hertwig

concerned

the penetrationof the sperm into the egg. Pene-

tration

alone

was

not fertilization,

for

cleavage

did

not

ensue.

As Auerbach

had shown

in

1874

the

two

nuclei

(of

unknown

origin)

witlhin

the

egg

must

fuse

(verschmelzen)

if the egg

is

to

develop.

Clearly,

then,

it was the nucleus

and

not the

protoplasm

which

controlled

developml-ent.

104 Ibid.

2:

pp.

287-288.

105

E.

Strasburger,

Neue

Untersuchungent

ibcr

den

Befruchtungsvorgang

ei

der

Phanerogamen

a/s

Grutnd-

lage

fir

eine

Theorie

der

Zeugung

(Jena,

1884)

:

p.

111.

See

Nageli

1884 (note

85),

pp.

21-29.







VOL.

109, NO. 3, 1965]

CELL, NUCLEUS, AND

INHERITANCE

147

This

was further

uggested

by

the

increasing

indications

hat the

egg

nucleus must

prepare

itself

for

fertilization.

t must become

mature.

The

reductiondivisions

appeared

to

guide

this

process.

No

longer was

there the least

doubt

thatthe ripe egg nucleuswas derived,probably

exclusively,

from

the

preexisting

egg nucleus.

Moreover,

t was

the nucleus

withinthe

sperm

head and

not the

sperm s

a

whole

which

provided

the

second

nucleus

n

the

fertilized

gg

and

which

then

unitedwith

he

ripe

egg

nucleus

to

yield

the

first

ell

nucleus

of

thenew

organism.

Hertwig

looked o

the

spermnucleus s

the

most

mportant

or,

at

least,

the

only relevant

onstitutentf the

spermatozoon ith

regard

o

fertilization. t

was,

after

all,

the

only direct

productof

the

nuclei

of

the

permmother

ells. The

sperm

rotoplasm,

flagellum,r

other

rotoplasmic

erivatives

layed

no part n fertilization.One spermatozoon lone

was

the

necessary

nd

sufficient

ause of

ferti-

lization

and

polyspermy,

s Fol

had

shown,

ed

always to

defective

evelopnient.106

It

was

essential

that

Hertwig

be able

to

establish

he

equivalence f

the

two

uniting

uclei.

He

must

reconcile

he facts

hat

no

matterwhere

one

looked

the

male and

female

gametes were

strikingly

ifferentn

form

nd

size

and

yet the

contribution

f

each to

the

offspring

as

strictly

comparable.

Hertwig

merely

pursued

Nageli's

argument nd

followed t

to the

separation

f the

hereditarymaterial and the remainingcellular

components.

But

Nageli, said

Hertwig,

spoke

only

from

the

imagination

nd

not from

facts.

Add

now

these

latter,he

continued,

nd

it will

be

shown

"dass

die

Kerne

der

Sexualproducte

den

Anforderungen,

welche

die

Nageli'sche

Hypothese

tellt,

ollkommen

enugen."

07

The

Idioplasma

gave

way to

the

nucleus.

To this

supposition

was

joined

perhaps

the

most

convinc-

ing

demonstration

f

nuclear

equivalence,

that

offered

by van

Beneden's

studies

on

Ascaris.

Hertwig

briefly

ecalled

the

contribution

o the

zygote ucleus ffour nseschromatiquesSchlei-

fen), two

from

he

egg

and two

from

he

sperm.

Every cell

therefore

would

have

two

masculine

and

two

feminine

lements.

Van

Beneden's

re-

searches

roved

hat

not only

the

cleavage

nucleus

but ll

the

nuclei f

an

organismn

ere

the

products

106

Hertwig,

1885

(note

99):

pp.

286,

296-298,

302-304.

See

W.

Flemming,

"Beitrage zur

Kenntniss

der

Zelle

und

ihrer

Lebenserscheinungen.

Theil

II,"

Arch.

mikro.

Anat.

18

(1880) :

pp.

233-250.

107

Hertwig,

1885

(note

99): p.

286.

of

the

union in

fertilization f two

equivalent

nuclei.108

It

was

evident

o

Hertwig hat

fertilization,he

union

of

equivalent

parental

nuclei,

must

be

the

basis of

the

equivalence

of

the

products

of

re-

ciprocal rosses. Hertwig,no hybridizer,earned

of

this

phenomenon rom

Naigeli

and

with

it

introduced

he

pivotal

chapter

of his

essay,

"Die

befruchtende

ubstanz ist

zugleich

auch

Trager

der

Eigenschaften,

welche von

den Eltern

auf

ihre

Nachkommen

ererbt

werden."

09

The evi-

dence

summarized

bove was then

marshalled

o

support this

declaration.

Again

it was

Nageli who had

insisted

pon the

morphological

ature of

the

hereditary

material.

This

became

a

central

theme

n

Hertwig's

argu-

ment.

He did

not

propose, s

Nageli had

done,

to describethe structure f the hereditaryub-

stance

but was

content o

stress the

fact

that

it

definitelywas

structured.

During

fertilization

some

substance,

probably

nucleine,passed from

the

nuclei

of

the

egg

and

sperm to

the

newly

formed

nucleus

and did

so

without

ever

losing

its

identity.

This,

the

"morphological"

oncep-

tion, was

opposed

by

Hertwig to

the

"physio-

logical"

hypothesis.

"Physiological"

fecundation

either

represented

he

contact

heory f

Bischoff,

embellished

y

His,

or

the

chemical

notion,by

which a

union

of

two

substances

ccurs

but the

substances

re

necessarily

n

solution.

The

latter

viewwas favored y E. Pfluigernd, n his earlier

work,

by

Strasburger.

It meant

that there

were

no

formed

lements

which

tookpart

in

fertiliza-

tion,

that

nuclear

union

was

really

a

mixing

of

two

dissolved

chemical

masses

derived,

it

appeared,

from

the

disintegration

roducts of

the

egg and

sperm

nuclei. In

reply

Hertwig

pointed o

the

massive

cytological

vidence

gath-

ered

by

Flemming,

.

Selenka

and,

after

1882,

Strasburger

nd

concluded

hat das

Nuclein

vor,

wzvhrend,

nd

nach

der

Befruchtung n

einem

organisirten

Zustand

befindet."

10

While

not

directly tated by Hertwig it is clear that he,

like

Naigeli,

ooked

to

the

formal

molecular

on-

stitution f

the

nuclear

substance

s

the

basis of

heredity

recisely

because of

its

structural

om-

plexity.

Only nuclear

complexity

eemed

able

to

account for

growth

nd

differentiation,

ut

how

it

did

so

was

absolutely

unknown.

The

physiological

elationship

etween

he

nu-

108

Ibid.,

p.

288.

109

Ibid.,

p.

283.

110

Ibid.,

p.

291.







148

WILLIAM

COLEMAN

[PROC.

AMER.

PHIL.

SOC.

cleus

and

the

protoplasm

was

a constant

ource

of puzzlement.

Since

the

organism

was

composed

principally

f

protoplasm

nd,

in

the

first

ell

(the

fertilized

gg), protoplasm

ar

outweighed

nuclear

ubstances,

here

was

always

a

temptation

to ascribe the direction f development o this

homogeneous,

iscous

substance

nd to allow

the

nucleus

ittle

rno

part

nthe

process.

Ifthis

were

true,

t would

become

necessary

lso

to

attribute

to the

protoplasm

t

large

the control

of

inheri-

tance.

Such

a plan

was

proposed

by His

in

1874.

A

decade

later

Hertwig,

relying

n

ex-

periments

made by

Pfluger,

evoted

pecial

effort

to

destroying

his

scheme

nd thereby

eassuring

the hereditary

rimacy

of

the

nucleus.

His

had suggested

hat

the

protoplasm

f

the

egg

was

prearranged

or development.

He

did

not

imply

that

the

egg

was

preformed

n

a

morphologicalense but onlythatits everypart

enjoyed

a

peculiar

molecular

predisposition

o

develop

long

very

definite

ines.

The egg

there-

fore

had its

own

special coordinates,

t

was

"-tropic."

This notion

of organbildene

Keim-

bezirke

(germinal

localization:

Wilson)

tended

to

eliminate

ll nuclear

control

of

development

(and

inheritance)."'

Pfluger's

xperiments,

ow-

ever,

hallenged

o comfortable

proposal.

His's

basic

idea

that

there

existed

n the

egg

a spatial

orientation

pened

heway

to experimental

anip-

ulation

because

any

disturbance,

ven

artificial,

would bringabout some change in the develop-

mental

rocess.

Pfluger's

work,

n fact,

s

among

the

earliest

essays

in

rigorous

experimental

embryology.

Gently

grasping

a

fertilized

rog's

egg

in

a

compression

lide,

Pfluiger

howed

that no

matter

to

what

position

ne

rotated

he

egg ("direction"

being

indicatedby

the

egg

axis,

running

from

animal

to

vegetable

poles),

thus changing

its

polar

orientation

n the earth'sgravitational

ield,

the

first

leavage

divisionalways

came

in

ver-

tically,

hat

s, parallel

to the

plane

of

gravitation.

From his experimentPfluger concluded, and

Hertwig

nthusiastically

greed,

hat

he

egg

pro-

toplasm's

wn orientation

polarity)

or

"germinal

location"

was

irrelevant

o the course

of

devel-

opment.112

In other

words,

here

was

no internal,

111

His,

1874

(note

43):

pp.

18-31.

112E.

Pfluiger,

Ueber

den

Einfluss

der

Schwerkraft

auf

die

Theilung

der

Zellen

und auf

die

Entwicklung

des

Embryo,"

Arch.

furd.

ges.

Physiol.

23

(1883):

pp.

1-79.

See

Wilson,

1900

(note

7), pp. 397-401;

H. Spemann,

Embryonic

Development

and

Induction (New

Haven,

1938),

pp. 14-21.

protoplasmic

ontrol

of

egg

development.

The

fertilized

gg lacked

all

special coordinates;

it

was

"isotropic."

Pfluger adopted

the

extreme

position

hat

gravitation,

n external

gent,

ould

alone direct

embryonic

hanges.

Hertwig,

of

course, stopped far short

of this

conclusion.

Pfluger's

experiments,

e believed,

had fairly

demolished

the notion

of

germinal

ocalization

but

they had

in no way

touched the

supremacy

of the

nucleus.

It was

the protoplasnm

hich

was presumed

o

be polarized,

not the

nucleus.

By

thus eliminating

major

protoplasmic

ffects

(Hertwig

would

not

deny the

protoplasm

ome

role n development)

he

experiments

econfirmed

the directive

ole of

the nuclear

elements.

His,

Hertwig

believed,

was

guilty on

all counts:

he

uncritically

ccepted

heold

idea of the

protoplasm

as the ssential

ellular

onstituent,

e

refused

ven

to consider the nucleus and he slippeddanger-

ously

near

to

undisguised reformationist

hink-

ing

113

ig.ll

The nucleus

had

become the

effective

gent

of

development

nd

was

therefore

he

indisputable

vehicle of

inheritance.

Hertwig

resolved

the

question

of nuclear-protoplasmic

nteraction

n

a

mannerremarkably

imilar

to both

Haeckel

and

Nageli:

Das

Protoplasma

ermittelt

en Verkehrmit

der

Aussenwelt,

ndem

sich

in ihm die Ernahungs-

processe

abspielen

und

es

zur Gewebebildung

n

Beziehungteht; er Kern dagegen rscheintls das

Organ

der Fortpflanzung

nd Vererbung;

as

Nu-

clein st

eine Substanz,

elche

ie

Eigenschaften

er

Eltern uf

die

Kinder

ibertragt

nd

wahrend

er

Entwicklung

elbst

von

Zelle

auf

Zelle iibertragen

wird.114

Hertwig

seems

to

state

the

distinction etween

the

daptive

rotoplasm

nd the

hereditary

ucleus

rather

more sharply

han

did Nageli.

At stake

was

an

important

ssue:

Is

the

hereditary

ubstance

protected

nd stable, perhaps

permanently

o ?

If it were

not

and were

immediately

ubject

to

forces

emanating

from

a

changed

surrounding

protoplasm,hen ts guarantee fhereditywould

lose

much

in

value. Variation

could

rapidly

or

slowly

(Naigeli)

come to be

predominant

nd

external forces,

the

entire environment.

would

assume

ascendancy

ver

inner

forces,

focused

at

the

nucleus.

Hertwig's

brief

tatement

asts

little

light

on

the

tangled

subject

of

the

inheritance

of

acquired

haracters

nd it was

left o

Weismann

to

pursue

this

problem

o

its

logical

conclusion.

113

Hertwig,

885

note

99): pp.

304-309.

114

Ibid.,

p.

310.







VOL. 109, NO. 3,

19651

CELL, NUCLEUS,

AND INHERITANCE

149

The greatest

ccomplishment

f

Hertwig's ssay

was

to bring

ogether

nd

systematically

o

inter-

pret the vast

abundance of data

pertaining

o

nuclear

structure nd

behavior,

nd

all

with

re-

gard

to

the possible

role in

heredity

f the

struc-

ture. Cytology, xperimentalmbryologynd, n-

directly, lant

and animal

breeding

each contri-

butedto

the

task.

For

Hertwig

t

became

almost

self-evident

hat

heredity as

not an

abstract orce

but

was

founded on a

material

basis. This

substance was located

in

the

cell

nucleus

and,

most

significantly,ssumed there

a

definite nd

steady

molecular

rrangement. Als

die

Anlagen,"

Hertwig

summarized,

von

complicirter

olecularer

tructur,

welche

die

mutterlichen

nd

vaiterlichenigenschaften

iber-

traigen 6nnenwir die

Kerne

betrachten, elche

n

den

Geschlechtsproducten

ich

ls

die

einzigen

inan-

deraiquivalentenheileergeben,n welchenwir bei

dem

Befruchtungsactllein

ausserordentlich

edeut-

same Vorgange

eobachtennd

von denenwir allein

den Nachweis

fiihren

6nnen,

ass

von

ihnen

der

Austoss ur

Entwickelung

usgeht.1'5

Strasburger's progress

towards the nuclear

theory

f

inheritance

as

far

ess

direct han that

of

Hertwig.* He had

firstof all to

persuade

himself

hat

fertilization as

the union of two

formed

ubstances nd that,

because of this, the

nucleus ould control

heredity. Years of

arduous

labor

preceded

final conversion

nd conviction.

Already n his earliestdiscussion f theproblem,

Strasburgermaintained

hat

in

fertilizationdie

Substanz

der

Spermatozoiden

urch die

Eihiille

diffundire

nd

in den Dotter

eindringend ich

zum

Spermakern

ammle . .

es aber nicht um

die Kern der

Spermatozoiden ls

morphologische

Elemente,

ondernum die

Substanz dieser Kerne

als

physiologische

lement zu thun

sei."

16

At

first

nclined o view

fertilizations the

osmotic

passage of

a

thoroughly issolved and

diffused

115

Ibid.,

p.

302.

*

Edouard

Strasburger

1884-1912).

Studied

botany

at Paris, Bonn, and Jena (studentof Pringsheim,

H4eckel);

Ph.D., Jena

(1866);

Professor

a.o.

of

Botany

nd

Director

fthe

Botanic

Garden, ena

1869-

1881);

ord.

Professor

of

Botany, Bonn

(1881-1912).

Research

in

general

plant

physiology

conduction f

fluids,

ollination)

nd

plant

microanatomy.

master

cytologist; tudied

mitosis, eduction

ivision,

ertiliza-

tion, nd

chromosome

umbers.

Author

f

standard

arly

manual

of

phytocytology,

ellbildung

und

Zelltheilung

(Jena, d.

1:1875, d.

3

1880). See

G.

Tischler,

Edouard

Strasburger

with

bibliog.

of

S.],

Arch.

f.

Zellen-

forschung

(1913):

pp. 1-40.

116

E.

Strasburger,

Zellbildung und

Zelltheilung

(2nd

ed.,

Jena,

876),

pp.

307-308.

male generativenucleus across

the

membrane

f

the

pollen

tube

and then into

the

egg (where

fusion

occurred)

Strasburger

would

but

slowly

convince

himself

f

the

errorof

this

view.

Only

in

1882

did he

finally

gree

to the

Hertwig-Fol

conception f.nuclearunion,but he did so in a

most

ambiguousmanner.

Long

believing

hat

f

anythingoined at

fertilization

t was the cell

and

all of

its

constituents,

e was

delighted

when

F. Schmitz

(1879)

showed that

in the

uniting

parts of the

alga

Spirogyra

the nuclei

were

greatly

enlargedand the

protoplasmmuch di-

minished.

There

was

really

nothing

eftto fuse

but

the

nuclei and

Strasburger

accepted

this

fact

s

one of

great

but

unexplained

mportance.1"7

Later

in

the same

year,

however,

he

suggested

that fertilization

eant the union of

two

distinct

material

lements,die

morphologischls

Zellkerne

zu bezeichnen ind, ganz abgesehendavon, wie

ihr

physiologischer

egensatz sich

verhalt" and

thereby roclaimed

his

espousal of

the new

hy-

pothesis."18

Earlier

errors,

trasburger

onceded,

had

been

due

to

faulty

method.

He had

studied

either

living or

inadequately tained

specimens.

Now,

through

he

use

of

new

techniques nd

different

stains

(Picrocarmine,

Boraxcarmine),

he

could

undertake

he

difficult

ut

conclusive

xamination

of

fertilization n

the

angiosperms

(flowering

plants).

The

data thus

obtained ed

Strasburger

"Stellungzu denneuerenTheorieenderZeugung

zu

nehmen

und

selbst

die

Begrundung

einer

solchen

Theoriezu

versuchen."

19

The

particular

datum

which

Strasburger

oughtand

found

was

the

ntegral

assage

of

the

male

generative

ucleus

qua

nucleus from

pollen

tube to

egg.

In the

latter

the two

nuclei

were

seen to

unite.

This;

sequence

was

especially

evident n

Orchis

lati-

folia.120

He was

then

convinced,

as

Hertwig

had

been, that

an

absolute

continuity f

the

nucleus

existed

across the

generations,

nucleus

reconstitutedt

fertilization

nd

everywhere

er-

petuatedbymitosis.

In

one

sense

Strasburger's

thought

seemed

more

rigorous

than

that of

Hertwig.

While

Hertwig

demanded

"morphological"

nterpreta-

tion

of

fertilization, is

imprecise

terms

(sich

verschmelzen,

urchdringen)

uggested

nuclear

117

E.

Strasburger, Uber

den

Bau

und

das

Wachstum

der

Zellhaute

(Jena,

1882),

pp.

250-252.

118

E.

Strasburger,

tYber

die

Befruchtung,"

.

B.

niederrh.

Ges. in

Bonn,

39

(1882):

pp. 188-189.

119

Strasburger,

884

note

105):

p.

iii.

120

Ibid.,

p.

67;

Tafel

I,

Figuren

1-77.







150

WILLIAM COLEMAN [PROC.

AMER. PHIL. SOC.

blending

possible

only

if the nuclei

were

in

at

least

a semi-fluid

tate

r if

the

ndividual

lements

were

joined

together,

erhaps

nd

to end.

Stras-

burger,

ike

van Beneden,

nsisted strongly

hat

"morphological"

uclei

as

such should

not

blend

orfuse. "Sie durchdringenichnicht egenseitig,"

he

maintained,

sondern

egen

sich

nur an

ein-

ander.

Es

findet

omit

nicht

in

Vermischen

er

beiden

Kernfaden

tatt,

die beiden

Geruistwerke

treten

ielmehr ur

in Contact

ohne

thatsachlich

zu

verschmelzen."

21 The

nuclear

fluids id

mix,

and

therefore

layed

no significant

art

in

ferti-

lization.

Only

the nucleus,

lone

a

structure

f

structural

ifferentiation,

articipated

n

this

event

and

consequently

n

heredity.

Ich

glaube,"

Stras-

burger

ater

concluded,

in

dieser

Arbeit

definitiv

en

Beweis

erbracht

u

haben, assdieBefruchtungun ufderVereiningung

der

Zellkerne

eruht

nd

dass

bei

vorgeschrittener

Geschlechtsdifferenzirung

us

dem

vaterlichen

r-

ganismus

ur

ein

Spermakern

n

das

Ei eingefuihrt

zu werden

raucht

nd

oft uch

allein

nur ingefiihrt

wird.

Da das

Kind

somit

urdurch

Vermittlung

es

Zellkerns

ie

Eigenschaften

on

dem

Vater

erbt,

o

muissen

n

dem

Eigenschaften

er

Zellkerne

die

specifischen

haraktere

es

Organisnmus

egriindet

sein.122

But this

fundamental

onclusion

brought

o

a

close only

the first

tage of

the

proposed

nquiry.

It was

Strasburger's

leasure

to speculate,

ften

in a manner ecallinghis teacher,Haeckel, upon

the

exact

relations

between

he nucleus

and

the

phenomena

of development

nd

heredity.

Pre-

sumably

it was the

formed

nuclear

substance

(Nucleo-Hyaloplasma)

and

not

the

more

homo-

geneous

and

changing

Cyto-Hyaloplasma

which

controlled

all metabolic

activity.

The former,

stable

and

hereditary,

nd the latter,plastic

and

adaptive,

are

of

course

only

derivations

from

Naigeli's

dioplasma

and

Erndhrungsplasma.

t

-appeared

hat

the

nucleus

directed

he

nutrition

and growth

of

the

protoplasm

nd

thereby

m-

printedupon the latter

the

character

of

the

species.

In return,

the

protoplasm

subserved

-nuclear

utrition

nd was

charged

with

he

division

of this

body.

It was

also

possible

that

n

certain

cases

the

maternal

nd

paternal

nuclear

contri-

-butions

o the

zygote

were

not

of

exactly

the

same Quantitat

and

in other

cases

excessive

maternal rotoplasm

might

ause deviations

rom

the

usual

hereditary

patterns.

These

factors

helped

to

explain,

Strasburger

believed,

those

121

Ibid.,

p.

85.

122

Ibid.,

p.

104.

instances

where

the

equivalence

of reciprocal

crosses

failed.123

The

details of the scheme

were

necessarily

ague

but

it is beyond

question

that

this

plan

was

adopted

because

it appeared

to

be

mechanistic

r causal.

All vital processes

were

interrelatedby unexplained "moleculare Er-

regungen"

nd every

tage

of

a developing

rgan-

ism

necessarily

ollowed

rom

he topography

nd

dynamics

f

the

preceding

tage.

These

general

notions

Strasburger

ad acquired

from

he

plant

physiologist,

J.

von

Sachs,

perhaps

the

type

specimen

of

the

maturephysiological

eduction-

ist.124

Sachs,

and Strasburger,

aw

in

"Stoff

und

Form"

a

sufficient

xplanation

of many

a

complex

biological

problem,

nd

the initial,

basic

material

nd

form

f an

organism

was

found

n

the

nucleus.

Using

the

biogenetic

aw

("ontogeny

recapitu-

latesphylogeny")n a dynamic enseStrasburger

explained,

s

Haeckel

and

F.

Muller

had

done,

thegrowth

nddifferentiation

f anygiven

organ-

ism as

the

retracing

f

its evolutionary

istory.125

Since

no

one

was

contentwith

having

no

explana-

tion

at

all

of

development,

robably

his

notion

was

no more

fanciful

r erroneous

han

a

host

of othersproposed

t

this

time.

It suggested

o

Strasburger,

owever,

hat

perhaps

during

ntog-

eny

and as

a consequence

of the

vital

flow

of

mutual

excitations

etween

the

nucleus

and

the

protoplasm

he

former

ody

was

altered

n con-

stitution. f thiswereso,then t was necessary o

restore,

prior

to

the

formation

f

the

mature

sexual

cells, the

pristine

condition

of

nucleus.

Heredity

could not

be

founded

on

a

constantly

changing

nucleus.

By

a

process

of

germinal

return

(Ruckkehr

des

Idioplasma)

Strasburger

uggested

that

the

altered

ondition

f the

nuclei

could

be

converted

and the original

nuclear

state

once

again

ob-

tained.126

How

these

events

took

place

quite

escaped

comprehension,

ut

Nageli's

suggestion

that the

flowers,

r

reproductive

arts,

seem

to

appear last in the developingplant was given

serious

attention.

Strasburger

lso

left the

im-

pression

that

reduction

division

or

maturation

may

have something

o

do with

germinal

eturn.

The presupposition

ehind

this elaborate

rea-

soning

was

one

common

to

Hertwig

and

Weis-

mann

as well

as

to

Strasburger.

Heredity

was

123 Ibid.,

pp. 163-164.

124

Ibid., pp.

113-114.

Cf. J.

von

Sachs,

Vorlesungen

fiber

Pflanzen-Physiologie

(Leipzig,

1882),

pp.

11-14.

125

Strasburger,

884 (note

105):

p. 114.

126 Ibid.,

pp.126-133.







VOL. 109, NO. 3,

19651


151

thetransmissionrom

arent

o

offspring

f

similar

form

nd

function, hese

becoming

manifest

nly

during

development.Everymember f a

species

was to

pass through he same

embryonic

tages,

from he

simpleovum to

the highly

ifferentiated

adult. It was necessary,therefore, hat each

individual

have the same

starting

oint,

that

is,

the same

material,nternal

onstitution,

nd

this

was

its

nucleus.

If

the nucleus

changed

during

ontogeny

t

was

imperative

hat it

return

o

its

initial

ondition

rior o

generation. Only

in

this

way

could

heredity

e assured

and

major

formal

or

functional eviations

be avoided.127

But whether

he

restQred

ucleus

was

precisely

like the original

nucleus

was

a

matter

of

some

doubt.

Strasburger o

more than

Nageli would

tolerate

phemeral orces

permanently

modifying

the

hereditary

ubstance.

Prolonged ction,

how-

ever, might erywell provoke uchmodifications.

All of

thenuclear

hanges

during erminal

eturn,

nevertheless, ere

internally onditioned

y

the

idioplasm

tself. The

acquisition f

new character-

istics

was

therefore

ossible but

never

easy

or

frequent. During

maturation

divisions,

more-

over,

some of

these

changes

could be

eliminated

from he

nucleus nd thus

rendered

onhereditary.

Finally,

the

purpose of

fertilization

eemed,

in

addition

to

generating new

organism,

o

be to

eliminiate

ariations and

thereby preserve

the

species

character a

view

diametricallypposed

to

modernhinking)

128

Strasburger

llowed

the nuclear

substance,

he

bearerof

heredity, great but not absolute

meas-

ure

of

independence

from

external

conditions.

The continued

discussion of

possible nuclear-

environmental

nteractions,

ediated

y

the

proto-

plasm, would

lead at

least one

author to the

perhaps nevitable onclusion

hat he

nucleus

tood

not

only supremewithin

he cell

but was

wholly

and

permanently

nresponsive o

external gents

of

change. August

Weismann's

germ-plasm

hypothesis

presentsthe

definitive

tatement f

nuclear hegemony. It also offerspossibly the

finest

xample of

the

transformation

ince 1860

of

the

conception

of

the

cell, then

a mass of

protoplasm

ommonly

ontaining nucleus,

now

a

nucleus

of

complex nd

singular

nature n vary-

ing

degrees

surroundedby

protoplasm.

Two

interrelated

hemes

among

Weismann's

innumerable

nd always

thoughtful

uggestions

127

Cf.

E.

S.

Russell,

The

Interpretation

of

Develop-

nmentnd

Heredity

(Oxford,

1930),

pp. 47-48.

128

Strasburger,

1884

(note

105):

pp.

137-140.

were of

central

importance

o

the

doctrine

of

nuclear

inheritance: he

germ-plasm

hypothesis

and

the

notion

of

nuclear

disaggregation

uring

development.*

Weismann

seems

first to

have

used the

famous

erm,

erm-plasm,

n

1883. The

conceptionrepresented revolution n his own

thinking

n the

problemsf

heredity

nd

evolution.

In

1863

his

eyesight

failed him

and, forced

to

abandon

microscopical

research,

he

turned

to

considering he

broader ssues

of the

new

theory

of

evolution

by

natural

selection.

From

the

outset

he was a

Darwinist.

Particularlyoncerned

with

the forces f

evolution,

e

agreed

fully

with

Darwin

that

these

were natural

election,

orrela-

tive

variation nd

"the

transformingnfluence f

direct

ction,

s

upheld

by

Lamarck."

29

This

is

an

astonishing

tatement, or

Weismann

is

commonly

egarded

s the

arch-opponent f

the

transformationfspeciesby meansofLamarckian,

or

acquired,

haracteristics.

On

questionsof

he-

redity,

Weismann

spoke

with

two

voices,

the

second

and familiar

one

becomingevident

only

after

1883.

In his

earlier

writings

e

attempted

to

deny

s

evolutionary

orces

ny

nternal

actors.

His reaction

was

againstthe

proposal

by

several

philosophers

nd

biologists f

independent

emi-

metaphysical,

nternal

perfecting

"drives"

or

"forces"

which

purported

o

eliminate

he

need

for

natural

selection,an

external,

mechanical

and,

to

their

minds,

unfounded

assumption.

Among those whom Weismann challengedwas

Nageli,

already ong at

work on

his

Vervollkom-

mnungstrieb. t

seemed o

Weismann

hat

hered-

ity

was a

conservative

rinciple

nd

that,

when

unaffected

y

foreign

agencies, it

could

only

generate

more of

the same

organism, ither

at

*

August

Weismann

(1834-1914).

Studied

chemistry

and

histologyat

Gottingen

(student of

Wohler,

Henle);

M.D.,

Frankfurt

.M.; later

studied at

Paris and

Giessen

with

I.

Geoffroy

t.-Hilaire, Milne

Edwards,

Serres and

Leuckart;

Professor

a.o. of

Zoology

(1865-1873), ord.

Professor

(1873-1914),

Freiburg

i. B.

Original

work

in

insect mimicry, limnology, and invertebrate histology

and

development. An

imaginative

interpreter

f

general

problems of

evolutionary

theory,

impassioned

apologist

for the

efficacy f

natural

selection,and

admirable

stu-

dent

of

heredity and

variation.

Author of

lucid

and

highly

influential

ssays

and a

leading

popular

advocate

of

Darwinism.

See

W.

Schleip,

"August

Weismanns

Bedeutung

fur die

Entwicklungder

Zoologie

und

allge-

meinen

Biologie,"

Naturwiss.

22

(1934): pp.

33-41;

E.

Gaupp,

August

Weismann. Sein Leben und

sein

Werk

(Jena,

1917).

129

A.

Weismann,

"Preface

to the

English

Edition

[1881],"

Studies in

the

Theory of

Descent,

trans. R.

Meldola

(2

v.,

London,

1882)

1:

p.

xvii.







152

WILLIAM

COLEMAN

[PROC.

AMER. PHIL.

SOC.

generation r during

ell multiplication.

Whence,

then, the cause

of variation or developmental

differentiation?

Weismann

replied:

If we could bsolutely

uspend hechange f the

ex-

ternal onditions

f life, xisting pecies

would re-

main stationary.The actionof external xciting

causes,

n

thewidest

ense ftheword, s

alone able

to produce

modifications;nd

even the never-failing

"individual

ariations,"ogether

ith the inherited

dissimilarityf constitution,

ppear o me

to depend

upon

unlike xternalnfluences,

he nheritedonsti-

tution tself eing

dissimilarecause he

ndividuals

have been t all times

xposed o somewhat

arying

externalnfluences.

A

change

rising rom urely

nternalauses eems

to me above all

quite untenable,ecause

cannot

imagine

ow the amematerial

ubstratumf physi-

cal constitution

fa species anbe transferred

o the

succeeding

enerations two

opposing endencies.

Yet this

mustbe the case

if the directionf de-

velopmentransferredy hereditys to be regarded

as theultimate round

oth fthe imilarity

nd dis-

similarity

o the ancestors.

All changes,

rom he

least to

the greatest, ppear

to me to

dependulti-

mately n only xternal

nfluences:hey

re the re-

sponse

of the organism o external

nciting auses.

It

is

evident

hat his esponse

must e differenthen

a

physicalonstitution

f differentature

s affected

by the

same nciting ause, nd

upon his, ccording

to

my view, depends

he

great mportance

f

these

constitutional

ifferences.130

To

internal

factors, he physical

constitution,s

allowed

t

least

the

role of determining

he organ-

isms' differing

eactions to external

changes.

Weismann's focus is

upon

variation and not

heredity.

Even at this

arlydate,

however, e

had

brought

together

wo

of

the

basic

tenets

of the

germ-

plasm

hypothesis.

".

.

.

that

the

germ

of the

organism

by

its chemico-physical omposition

together

with

its

molecularstructure ad

com-

municated o

it [the progeny]

a fixed

direction

of

development"

seemed

incontestable.'13

Weis-

mann ommitted

imself o

seeking

nly special-

ized material

asis

of

inheritance,deally

reduced

to

physics

and

chemistry,

matter

and

motion

(Helmholtz is cited withapproval). Moreover,

the

problem

f

heredity

ecame

nseparable

rom

that

f

development.

When

Weismann

iscovered

how

he

could

preserve

he

material

asisof

nherit-

ance

and

at

the

same

time look to it as

the

guide

of a

changing

nd not a "fixeddirection

f

development"

e was

prepared

o devise a

com-

prehensive

heory

of

inheritance.

130

A.

Weismann,

"On

the

Seasonal

Dimorphism

of

Butterflies

1875],"

ibid.

1:

pp.

114-115.

131

A. Weismann,

"On

the

Mechanical

Conception

of

Nature

[1876],"

ibid.

2:

p.

667.

More than

either

Hertwig

or

Strasburger,

Weismann combined

the points

of view of

the

microscopical

natomist,

the

embryologist,

nd

the evolutionist.

Flemming,

for example,

had

never reached

beyond

the

limited

realm of

the

exact and exhaustiveexaminationof the con-

struction

f cell

and nucleus.

His, the

embryolo-

gist,

cast unceasing

regard

on

the course

and

causes

of individual

development.

The

temporal

history f

the living

world

as well as

the

micro-

scopical

refinements

f its ultimate

structures

werepassed

over n

favor

f a mechanicochemical

hypothesis

fontogeny.

The evolutionist,

aeckel,

emphasized

the

historical

element

n all

living

things.

His experience

n the field

ssured

sound

judgement

on numerous

oological

matters,

ut

the haste

and prejudice

with

which

he assaulted

obscure

problems

nevitably

roduced

outrageous

generalizationsnd endlessunsupportedupposi-

tion. Flemming,

His,

and

Haeckel

represent

diverse

and

often ntertwined

hemes

found

in

post-Darwinian

biology.

The

evolutionist,

he

cytologist,

he

embryologist

nd

the physiologist

saw different

acetsof

life and

only

occasionally

did a consensus

of opinion

emerge

on

any

par-

ticular et

of

problems.

Biology

as the

ntegrated

study

of the

phenomena

f

life was

viewed

not

with one but

with many

eyes

and

rare

was the

individual

whose

experience

nd

inclination

pened

to

him

the

broader spects

of his

science. Weis-

mann, n spiteof his penchant or peculationnd

theerror

nd misinterpretation

hich

hisfostered,

was one

of these

rare

individuals,

and

it

is

perhaps

his

greatest

ontribution

hat

he

attempted

to erect

a consistent

nd

complete

system

of

evolutionary

iology,

a

system

wherein

embry-

ology

nd

physiology

ccupied

heirnecessary

nd

important

laces

and the

transmutation

f

species,

then

the

primary

utstanding

ssue,

served as

a

uniting theme.

It may

have

been

Roux's

essay

of 1883

which

gave Weismann

the

clue

he

had been

seeking.

In this essay, cited by Weismann only in a

second

memoir

f

1885,

Roux

had

suggested

hat

mitotic

division

was

at

once

quantitative

nd

qualitative.132

The

former nsured

the

equable

distribution

f

the

nuclear

mass

(chromatic

ub-

stance),

while

the

latter

presented

sorting

ut

of the

qualities

presumably

ssociated with

this

material.

No

more

deal

hypothesis

ould

Weis-

132

A.

Weismann,

"On

the

Number

of

Polar

Bodies

and

Their

Significance

in

Heredity

[1885],"

Essays

upon

Heredity

and Kindred

Biological

Problems,

trans.

E.

B.

Poulton

et

al.

(2

v., 2nd

ed., Oxford,

1891)

1:

p.

370.







VOL. 109, NO.

3, 19651 CELL, NUCLEUS, AND

INHERITANCE

153

mann

have

desired.

With

each

nuclear

division

following

ertilization

he

original

omplete hro-

matic

constitution

was

unequally

distributed

o

the

daughter

nuclei:

If

therefore

he

first

egmentation ucleus

contains,

in its molecularstructure,hewhole of the inherited

tendencies

f

development,

t

must follow

that

during

segmentation

nd

subsequent

ell-division,

he

nucleo-

plasm

will

enter

upon

definite

nd

varied

changes

which

must cause

the differences

ppearing

in

the

cells

which

are

produced;

for

identical

cell-bodies

depend,

ceteris

paribus, upon identical

nucleoplasm,

and

conversely

ifferent

ells

depend

upon differences

in

the

nucleoplasm.133

By a

process

of

continued

nuclear

disaggrega-

tion

each

cell in

the

adult

organism

ultimately

received

just

that

quality

which

was

destined

to

determine ts

(the

cell's)

structure

nd

function.

The original hereditarymass, representativeofthe

species,

was in

its final

form

scattered

through-

out

the

fabric

of

the

developing

body.

The

hereditary

qualities

were

nothing

but

hereditary-

embryological

determinants.

Although

some ex-

perimental

evidence,

later

refuted,was

introduced

in

support

of

this

scheme, it

did

not

gain

general

acceptance.

Known

as

the

Roux-Weismann

hy-

pothesis

of

development

it

was

used

to

explain,

in

terms

of

heredity

and

the

nuclear

control

of

physiological

events, the

several

fascinating

cases

of

mosaic

development

which

became of

foremost

concern to embryologists in the closing decades

of

the

century.

Fallacious

though

the

hypothesis

was,

it

provided

in

its

time

a

remarkable

stimulus

to

research

and

raised

problems

of a

"quite

new

order."

134

The

Roux-Weismann

hypothesis ap-

parently

explained

development,

but,

in so

doing,

it

seemed

to

eliminate

any

possibility of

exact

hereditary

transmission of

the

total

features

of

the

organism.

In the

adult,

sexually

mature

body,

presumably all

or

almost all

of

the

hereditary

qualities

had

been

distributed

to

the

separate

parts.

How,

therefore,

ould

the

organism

trans-

mit

during

reproduction

the complete species

character?

Since

he

had

explicitly

rejected

Stras-

burger's

dream

of

germinal

return,

there

remained

for

Weismann

but

one

solution.

Somewhere

in

the

organism

there

had

to

persist

unchanged

some

portion

at

least

of

the

original

germ

mass.

The

continuity f

the

germ-plasm

must

be

assured.

In

1883

the

germ-plasm

was

first

defined

as the

133

A.

Weismann, "The

Continuityof

the

Germ-plasm

as

the

Foundation

of a

Theory

of

Heredity

[1885],"

ibid.

1: p.

188.

134

Spemann,

1938

(note

112);

p. 37.

See

Wilson, 1900

(note

7):

pp.

404-413.

"substance

of

the

germ-cells."

35

In

support

of

this

notion

Weismann

ffered

he unusual

circum-

stancesof

gametogenesis

mong

certain

hydroids,

where

the direct

ancestors of

the

germ cells

appeared

to be

spatially

et

apart

from

he

future

somatic ells before nytissuedifferentiationad

commenced.

he entire

erm

ell

therefore

eemed

an

entity apart from

the

organic

body

which

carried t.

Its

sole

functionwas

to

remain

un-

changed

or

"continuous"

nd

thereby

uarantee

at

generation

he

species

character.

The

narrow

foundation,

esting

on

only

one

animal

group,

f

Weismann's

dea was

immediately

assaulted and

shown

to

be

inadequate. Stras-

burger, or

xample,

roduced

numerous

nstances

among

he

plants,

specially

egonia,

where

issues

with

obvious

capacity

for

normal

sexual

genera-

tion had arisen frommature nd evenspecialized

parts.

Plants

developed

from

rhizomes,

roots,

branches nd

even

leaves

could

not

in

any

way

be

considered

art

of a

continuous

erm

ine

and

yet

they

were

all

quite

capable

of

sexually

re-

producing

y

the

unionof

typical erm

cells.136

Reacting

to his

critics,Weismann

revised

the

hypothesis nd

restricted he

germ-plasm ot

to

the

entire ell

but

only

to its

central

lement,

he

nucleus.137

Henceforth, he

continuity f

the

germ-plasm

would

imply the

continuity f the

nucleus,

lthough

he

germ-plasm

nd

the

nucleus

werenotcoextensive. "The natureof heredity,"

he

claimed,

"is

based

upon

the

transmission f

nuclear

substancewith

a

specific

molecular

on-

stitution.

This

substance

s

the

specific

nucleo-

plasm

of

the

germ-cell,

o

which

have

given

the

name

of

germ-plasm."38

The

nucleoplasm

as

not

synonymouswith

Nageli's

Idioplasma,

not

even

when

this

substancehad

been

confined

y

Hertwig

and

Strasburger

o the

nucleus.

The

idioplasm

was

everywhere

he

same,

at

least

in

cross

section,

nd

penetrated

ll

partsof

the

body.

Only

in

the

germ-line,

owever,

was

nucleoplasm,

here

true

germ-plasm,

ncluded

withinthe idio-plasm,forthe Weismanniannotion

of

ontogeny

depended

upon

the

general

disaggregationf

the

somatic

nuclei

as

differentiation

roceeded.

By

removing

he

germ-plasm

rom

he cell

at

large and

assigning

t to

the

nucleus,

Weismann

reversed

his

earlier

views

and

turned

to ex-

clusively

nternal

auses

of

development,

eredity,

135

A.

Weismann,

On

Heredity

1883],"

1891

(note

132):

1:

p.

105.

136

Strasburger,

884

note

105):

pp.129-131.

137

Weismann,

1885]

1891

note

132):

1:

pp.

175-176.

138

Ibid.,

p.

182.







154

WILLIAM

COLEMAN

[PROC.

AMER. PHIL.

SOC.

and

variation.

For

all

of

these

phenomena

he

germ-plasm

was

held responsible

nd,

as

far

as

regards

the

generative

issues,

germ-plasm

nd

nuclei

were

one

and

the

same

thing.

No

less

than

Hertwig

nd Strasburger,

Weismann

ooked

tovan Beneden's ytologicalesearches n Ascaris

as decisive

for

he

new

view

that

male and

female

contributions

o

the offspring

ere equivalent

nd

that

there

were contributed

nly

definite

uclear

components.139

he

only

ignificant

ew

evidence

bearing

n the

supremacy

f

the

nucleus

reported

by

Weismann

was

that

dealing

with

regeneration

in the

ciliated

protozoa

(Infusoria).

Extensive

experiments

erformed

y A. Gruber

and

M.

Nussbaum

had

shown

thatenucleate

ragments

f

a divided

nfusorian

sually

perished.

These

same

fragments,

oreover,

ailed

to

regenerate

new

organism,

while

those

pieces

which

had

retained

someportion f theoriginalnucleusdid produce

new,

f smaller,

orms.

Here

was

"conclusive

nd

important

onfirmation"

hat

the

nucleus

mpres-

ses

its

specific

haracter

pon

the

cell."

40

Weis-

mann

would

later

have great

difficulty

ith

the

argument

from

regeneration,

articularly

when

dealing

with

multicellular

rganisms,

ut

at

the

moment

of

creating

the

germ-plasm

hypothesis

he could

findno better

upport

orhis

view.

By

virtue

of

its

central

physiological

ole,

the

nucleus

and

the

included

germ-plasm

ssumed

direction

f

all

important

ital

activities.

The

germ-plasm as definedya complex, egular,nd

highly

table

structure.

It

was,

for all

practical

purposes,

beyond

themodifying

nfluence

f

any

external

gent;

hence,

ts value

n

heredity.

Char-

acteristics,

hen

and

if

nduced

by

environmental

conditions,

were

gained

but temporarily.

They

did not

affect

hegerm-plasm

nd

therefore

ere

irrelevant

o

heredity.

In

the

firstplace,

new

characteristics

ere

difficult

o

acquire

and,

in

the

second place,

if

acquired

would

not reappear

n

the

progeny.

The continuity

f thegerm-plasm

y

definition

xcluded

the fact

and possibility

f

the

inheritanceof acquired characteristics. Vari-

ation

could

not

be

induceddirectly

rom

he

ex-

terior

ut

required

n internal

ource.

Seeking

he

latter Weismann

ultimately

eveloped

the

idea

of amphimixous,

ccording

to

which

deviations

from

trict

heredity

were

caused

by

the

recombi-

nation

during eneration

f the different

aternal

and

paternal

hereditary

lements

onstituting

he

139

Ibid.,pp.

180-181.

140

Ibid., p.

188.

See

T.

H.

Morgan,

Regenteration

(New

York,

1901), pp.

65-68.

germ-plasm.

Weismann

thus

escaped

from

the

demands

of

his

early

environmentalism

nd

de-

veloped

nto

ne ofthemost

nthusiastic

hampions

of pure

selection

theory,

where heredity

and

variation

were

always

the ffair

f nternal

actors.

Deliberately,Weismann

became

the

orthodox

selectionist

while

Darwin knowingly riftednto

seeming-Lamarckian

eresies.

The story

of

the

germ-plasm

nd

what

came

to

be called

Weis-

mannism

s

inseparable

rom

he

history

f

evolu-

tion

heory

n

the

post-Darwinian

poch

nd

needs

no further

iscussion

here.141

VII.

NUCLEAR

CHEMISTRY

By

1885

t was

commonly

dmitted

hat

heredity

depended

upon

what

Weismann

had

identified

as a

"nuclear

substance

with

a specific

molecular

constitution."Hertwig and Strasburger greed

that

this

substance,

nucleine,"

was

undoubtedly

of great

mportance

ut,

not being

chemists,

hey

could

add

little to

the

discussion.

K6lliker,

again

no chemist,

as

more

nsistent

nd

declared

emphatically

hat

he

peculiar

material

irst

denti-

fied by

Miescher

and given

by

him

the

name

Nuclein

was

"der

in

erster

inie

wirksame

toff"

and

presumably

must

be

the

material

basis

of

inheritance.142

The researches

f

F.

Miescher

established

u-

clear

chemistry.143

student

t

Basel

of His,

at Tubingen f Hoppe-Seyler nd finallyt Leip-

zig with

Ludwig,

Miescher

had

been

exposed

without

relief

to the

reductionist

onception

of

physiology.

Hoppe-Seyler

directed

his

interests

towardsphysiological

hemistry

s

a

consequence

of which

Miescher

ndertook

hechemical nalysis

of

the

cell nucleus.

Amassing

pus

cells

adhering

to bandages

discardedby

the

Tiubingen

ospitals

Miescher gathered

research

materials.

Analysis

of

pus-cell

nuclei

led

him

to conclude

(1871)

that

the

principal

nuclear

material

was

both

unique

and extraordinarily

omplex.

The

follow-

ing yearhe beganworkon the spermnuclei

of

141

See,

e.g.,

E.

B.

Poulton,

"The

Bearing

of

the

Study

of

Insects

upon

the

Question

'Are Acquired

Characters

Hereditary?'

[1905],"

Essays

in Evolution.

1889-1907

(Oxford,

1908),

pp. 139-172;

G. J. Romanes,

An

Exami-

nation

of Weisnmannism

Chicago,

1893),

pp.

86-116.

142

A.

von

Kolliker,

"Die

Bedeutung

der

Zellenkerne

fur

die

Vorgange

der Vererbung,"

Zeits.

fur

wiss.

Zool.

42

(1885):

p. 42. Cf. Hertwig,

1885

(note

99):

p.

290;

Strasburger,

1884

(note

105):

pp.

106-107.

143

See

J.

P.

Greenstein,

"Friedrich

Miescher,

1884-

1895.

Founder

of

Nuclear

Chemistry,"

ci.

Monthly

57

(1943):

pp.

523-532.







VOL.

109,

NO. 3,

19651

CELL, NUCLEUS,

AND INHERITANCE

155

the

Rhine salmon.

In both

cases his

results

were the same: the

new

substance,

Nuclein,was

insoluble

n dilutemineral

cids,

soluble

n

caustic

alkali

solutions and,

for

an

organic compound,

possessed an

uncommonlyhigh proportion

of

phosphorus. RatherhopefullyMiescher ssigned

it

the empirical ormula,

29H49N9P3022.

It was not Miescher, owever,

ut E. Zacharias

who

succeeded

in

identifying

ucleine as

the

fundamental onstituent

f the

formed nuclear

elements. Miescher

had

worked with whole

nuclei;

Zacharias

applied microchemical ech-

niques.

Working with plants

(Tradescantia,

Ranunculus) Zachariasattempted

o

discriminate

clhemicallyetween he various

ntranuclear

truc-

tures.

In

the resting nucleus he found the

characteristic

ucleine reaction fairly well

dis-

persed throughouthe nucleus. In the dividing

nucleus,however,

he nucleinewas

concentrated

in

the elements

athering n the equatorialplane

of the cell.

The nuclear threadswere

composed

of

nucleine. These were

the

same

structures

whose

substance,because

of

its

great avidity

for

stains, Flemminghad

called chromatin nd

Waldeyer

chromosomes. Chromatin

nd nuclein

were

thus the

same chemical

substance.144

A

regular

distribution f chromatinduring

ferti-

lization nd

mitotic ivisionwas equally a

regular

distribution f Miescher's

nucleine. Nucleine, a

peculiar if still far from understood chemical

material, was

the "nuclear substance

with a

specificmolecular

onstitution" hich

determined

heredity nd variation.

With the

study of the

atonmicomposition f

nucleine

came

an

emphasis

upon its necessarily

elaborate

molecular

structure. Identification

f

mere

chemical

lementswas but a first tep,

ince

it

seemed obvious that any

substancebearing

such

great

responsibilities-the ontrolof

hered-

ity,

variation

and

ontogeny-must itself be of

unprecedented

rchitecturalomplexity.

Sachs in

particular tressedthis conclusion:

... es verschiedene

rten on

Nuclein ebenmiisse,

die

vielleicht

hemisch

icht u

unterschiedenind,

die

aber, ahnlich

wie

die

Weinsaure nd

Antiwein-

saure,

wie

rechts- nd

linksdrehenderucker sich

unterschieden

nd gegen aussere

physikalische

in-

fliisse

verschieden

reagiren.145

144

E.

Zacharias,

"Ueber

die

chemische

Bechaffenheit

des

Zellkerns,"

Bot.

Ztg.

39

(1881):

pp.

169-176.

145

J. von

Sachs,

"II.

Stoff und

Form

der

Pflanzenor-

gane

[1882]," Arb.

des

Bot.

Inst. in

Wiirzburg

(2

v.,

Leipzig,

1882) 2:

p.

718.

Ambition, f

course,

far exceeded means and

a

structural esolution

f

the

nucleic

cids

has

been

approached

only

in recent

years.

The

claim

of the structural

deal

on

the

biologists

of

the

1870's

and

1880's was further

nfluenced,

f

not

actuallycaused, by the contemporaryuccesses

of structural

rganic

hemistry.

Beginning

n

the

late 1850's

with the assumption

y

A. F.

Kekule

and,

independently,

.

S.

Couper

of the

quadri-

valency

of the carbon

atom, organic

chemistry

turned to the

study

of carbon chains and

as-

sociated

molecular

omplexes.146

rom

the

quad-

rivalentcarbon atom

arose vast

possibilities f

structural

iversity

hile

atomic

composition

as

almost

exactly preserved.

Undoubtedly

uch

a

geometrical r

morphological onception

f mo-

lecular

onstruction ould appeal

to the

naturalist,

himselfprimarily nterestedn formalarrange-

ments.

Naigeli's Idioplasma

is a geometrico-

morphological

onstruct nd

Weismann's germ-

plasm,

especially n its mature form

(1892),

is

really

nothing lse. To

these men, and

perhaps

even to

the more cautious

Hertwig

and

Stras-

burger,

t

seemed obvious

that

complex external

phenomena

such

as

growth and

differentiation

required

eterminingactors f

at least comparable

complexity.

Nothing was less

difficulthan to

locate these factors

n

an

intricate

patial

frame-

work.

That the

molecular

ubstratewas

beyond

visualapprehensionn no way reduced onfidence

in

the

nference.

VIII. INNER

FACTORS

SUPREME IN

HEREDITY

The

identificationf the

nucleus as the

vehicle

of

inheritance

ed

to

a

clarification f

issues;

a

solution

o the more

elementaryf the

problems

posed would come

only

n

the

twentieth entury.

A

physical

body such as the

nucleus offered

he

possibility hat

the control of

inheritance

might

be

effectively

solatedfrom

hechanging

nviron-

ment. Darwinhad neverrested omfortably ith

the

unsolved

uestion

f

the

cause(s)

of

variation.

He

finallywas

reduced,

perhaps n spite of

him-

self,

o a

thorough-going

nvironmentalism.

ec-

tions of

the

heavily-revised ifth

dition of the

Origin of

Species (1869)

constitute

patently

Lamarckian

ract nd in

the

hypothesis f

pangene-

sis,

Darwin's

confessed beloved child,"

was pro-

146

See A.

Findlay,

A

Hundred

Years

of

Chemistry

(2nd

ed.,

London,

1948), pp.

21-39; J. R.

Partington,

A

Short

History

of

Chemistry

(2nd

ed.,

London,

1951),

pp.

284-293.







156

WILLIAM COLEMAN

[PROC.

AMER. PHIL.

SOC.

posed

the

cellular

mechanism

y which

external

influences

might

ct

upon

the

germinal

ubstance.

It

now

seems

clear

that

the

idea

of

pangenesis

was

developed

well

before

the sharp

attack

of

F.

Jenkin

1867).

It

may be, therefore,

hat

the hypothesiswas framedby Darwin

while

investigating

he

possible

causes

of variation

of

which

the

formation

f

the

pangenic

gemmules

was

one) and

that

t was not

ntended

s a

reply

or

rebuttal

f

Jenkin's

ontentions

egarding

he

presumed

swamping

effect

f cross

breeding.147

According

to

the

"provisional

hypothesis

f

pangenesis"

the

cells

of

the generative

organs

very

rarely

nd

of

the

body

parts

quite

commonly

reacted

o

novel,

xternal

orces

y producing

iny

particles

alled

gemmules.

The

"minute

granules

or

atoms,"

Darwin

suggested,

circulate

freely"

throughout

he

body

and ultimately

developed

into ells ike hosefromwhich heywerederived."

Most

importantly,

they

re

supposed

o be

trans-

mitted

from

the

parents

to

the offspring."

48

Only

by

this

means,

Darwin

believed,

ould

there

be

explained

such

occurrences

s the

induced

inheritance

f

gout

in

intemperate

amilies,

he

changes

n

size

and

age

of

maturity

fdomesticated

animals

and even

the

alteration

rom

wild

type

of the

wing

and

legbone

proportions

of

the

domestic

duck.149

Changes

in the

environment,

urely

external

factors,

ould

cause

variation.

Even

the

use

or

disuse of a part,a processwhichalso produced

new

gemmules,

ould

in

this

sense

be

considered

an

external

factor

ince

the

crucial point

of

the

pangenesis

hypothesis

as

the

aggregation

n

the

sexual products

f

a

representative

opulation

f

the

species

gemmules.

Those gemmules

f

recent

origin

n

the

great

majority

f cases

were

pro-

duced

outside

of

the germ

cells

and

only

second-

arily

were

transported

here. In

his later

words,

therefore,

arwin

tended

o

stress

the efficacy

f

external

nfluences

pon

the creation

f

variations

(however

much

this

might

confound

he

action

of natural selection) and to diminishthe role

played

by

intrinsic

factors.

That

this was

a

tendency

nly,

nd not

a

dogma,

hould

be

noted;

forDarwin,

ike

Scripture,

an

be cited n support

of

all

manner

of

interpretation.

He

was

admit-

147

C. Darwin,

On

the

Origin

of

Species

by

Means

of

Natural

Selection

(5th

ed., London,

1869),

pp.

165

ff.

Cf.

R.

C.

Olby,

"Charles

Darwin's

Manuscript

of

Pangenesis,"

Brit.

Jour.

Hist.

Sci.

1

(1963):

pp.

251-263;

P. Vorzimmer,

"Charles

Darwin

and

Blending

Inheri-

tance,"

Isis

54 (1963):

pp.

371-390.

148 Darwin,

1868

(note

4)

2: p.

374.

149 Ibid.,

p.

371.

tedly

eeking

ome

way

to

account

for

variation,

and

pangenesis

was

deliberately

ut

a

"provisional

hypothesis."

He confessed

o A.

R. Wallace

that

it

was

truly

a relief o have

some feasible

ex-

planation

of the

various

facts, which

can

be

given

up

as

soon

as

any better

hypothesis

s

found."

50

These words, ntroducednto a dis-

cussion

of the

causes

of variation,

were

written

less

than

a

month

after

the publication

f

the

hypothesis

f

pangenesis.

Darwin's

conception

nvited experiment

nd

abundant

speculation.

F. Galton's

vain

efforts

to transfer

emmules

rom

ne rabbit

o

another

by

means

of

blood

transfusions

nduced,

over

Darwin's

loud

protest,

considerable

scepticism

regarding

he

proposed

asy

transporation

f

these

particles

from

their

cellular

point

of

origin

to

the reproductive

lands,

nd thence

n to

follow-

ing generations.'5' In general,Darwin's com-

mentators

were

inclined

o

be critical

f

the

new

idea.

Yet there

were

some

naturalists

ho,

while

not agreeing

with

the

hypothesis,

egarded

it

as the opening

tep

in the early

modern,

hat

s,

pre-1900,

study

of

inheritance.

Somewhat

un-

generously

Hertwig

remarked:

"Den

Reigen

moderner

ypothesen

r6ffnet

arwins

Pangene-

sis."

Weismann,

more courteous,

felt

that

the

pangenesis

hypothesis,

lthough

almost

wholly

erroneous,

has

been

one of

those

ndirect

oads

along

which

cience

had

been

compelled

o

travel

in orderto arrive t thetruth." Hensen,stating

in his great

review

of

the

problems

f

generation

that

the hypothesis

was

patently

ncorrect,

till

allowed

that

"die

Untersuchung

er

Gesetze

der

Erblichkeit,

on jeher

sehr wichtig,

st

durch

die

Arbeiten

arwin's

zur Nothwendigkeit

ewor-

den."

52

The

hypothesis

f

pangenesis

irected

ttention

more losely

o

the

general

problem

f

nheritance.

Haeckel's

brief uggestion

n 1866

of the role

of

the

nucleus

n

inheritance

eems

to have

deflected

the

naturalists'

bias towards

a

predominantly

150

Darwin

to

Wallace,

27

February

1868:

The

Life

and

Letters

of Charles

Darwin,

ed.

F.

Darwin

(3

v.,

London,

1888)

3: p.

80.

151

F.

Galton,

"Experiments

in

Pangenesis

by

Breeding

from

Rabbits

of

a

Pure

Variety,

into

Whose

Circu-

lation

Blood

Taken

from

Other

Varieties

Had

Been

Largely

Transfused,"

Proc.

Roy.

Soc. Lond.

19

(1871):

pp.

394-410.

See

the

Galton-Darwin

correspondence

n

The

Life,

Letters

and

Laboutrs

of

Francis

Galton,

ed.

K.

Pearson

(4

v.,

Cambridge,

1924)

2:

pp.

156-202.

152

0.

Hertwig,

Das

Werden

der Organismen

(Jena,

1916),

p.

523;

Weismann,

[1885]

1891

(note

132)

1:

p.

168;

Hensen,

1881

(note

71):

p.

198.







VOL.

109, NO. 3,

19651

CELL,

NUCLEUS, AND

INHERITANCE

157

internal

ontrolof

heredity nd

variation. This

presupposition

ame

to

underlie

he

greatest

art

of

the

subsequent

development

f

genetics.

The

source

of

Haeckel's

idea

cannotbe

identified

ith

certainty.

Haeckel

himself

ites

L.

S.

Beale, but

Beale's distinction etween"formed" and "un-

formed"

ellular

material

does

not

correspond o

nucleus

and

cytoplasm.'53

Surely

the

bare

idea

of

nuclear

upremacy

ntedates

Beale's

superficial

inquiry;

vague

anticipations f

Haeckel's

notion

had been

expressed

by

R.

Owen.'54

The

most

likely

possibility,

however,

is

that

Haeckel's

interest

n

the

nucleus

was

inspired

y

his

teacher,

Virchow.

During just

those

years

(1852-1856)

when

Haeckel

was

following

is

master's

Wiirz-

burg

lectures,

Virchow

was

converted

rom

the

contact

theory f

fertilization

o

the new

sperm

penetration

doctrine of Newport.155 Withoutdirect

reference

ither to

variation or

heredity

Virchow

regarded

the

nucleus as an

element

principally

onnected

with

the

"maintenance

nd

multiplication"

f

the

cell

"as a

living

part."

Without the

nucleus

the cell

had

no

more than

a

"transitory

xistence."

56

As

has

been

seen

the

later

elaborations

upon

nucleus and

heredity

owe

much

to

Haeckel's

almost

passing

reference.

The

nuclear-proto-

plasmic

distinction

was

essential

to a

compre-

hensive

tatementf

the

theory f

the

continuity

of

the

germ-plasm,157

nd

it

was

Weismann's

reflections pon the natureand activityof the

germ-plasm

which

brought

more

sharply

into

focus

the

relative

roles of

internal

nd

external

factors

s

the

sourcesof

biological

ariation.

Any

scheme

for

the

inheritance

f

acquired

charac-

teristics

aspiring

to

scientific

igor

necessarily

would

need

to

consider

he

mechanism

y

which

these

changes could

be

passed

from

the

site of

the

alteration

o

the

unique

agentsof

propagation,

the

germ

cells and

their

nuclei.

The

conclusions

153

See L.

S.

Beale,

Protoplasm;

or,

Matter

and

Life

(3rd ed., London, 1874), pp. 187-198.

154

R.

Owen,

On

Parthenogenesis, or

the

Successive

Production

of

Procreating

Individuals From

a

Single

Ovum

(London,

1849),

pp.

5-6.

155

R.

Virchow,

Gesammelte

Abhandlungen

zur

wissen-

schaftlichen

Medizin

(Frankfurt a.

M.,

1856),

pp.

51-52.

See

C.

Posner, "Rudolf

Virchow

und

das

Vererbungs-

problem,"

Arch.

fir

Frauenk. u.

Eugen.

8

(1922): pp.

14-23.

156

Virchow,

1860

(note

10): p.

37.

157

Weismann

neglects

Haeckel's

contribution: The

Germ-Plasm.

A

Theory

of

Heredity,

trans.

W.

N.

Parker

and H.

Ronnfeldt

New

York,

1893), pp.

198-202.

See

P.

Geddes and

J. A.

Thomson,

The

Evolution

of Sex

(New

York,

1890),

pp.

81-96.

drawn in

1884-1885

with

regard

to

the

nucleus

and

inheritance

made

the

acceptance of

such

bodily

ransport nd

inter-generation

ransmission

exceedingly

difficult.

Vague and

once

verbally

satisfactory

otions

were

replaced

by

a

very

definiteonception fthephysicalbasis ofhered-

itary

transmission.

The

nucleus

was

the

vehicle of

inheritance.

Within

t was located

most

peculiar

nd

specific

substance,

ucleine.

A

heavy

molecule f

complex

yet

constant

architecture,

ucleine

presumably

was

resistant o

change.

How,

then,

ould

forces

whose action

commonly

ffected

arts

very de-

cidedly

emote rom

he

gametogenic

issue,

bring

about

changes in

the

hereditary

ature of

the

species?

What

conceivable

hysiological

rocess

could,

for

example,

predispose

the

hereditary

substance towards the productionof epileptic

progeny

rom

parent

whose

spinal

cord

hadbeen

partially

evered?

58

It

was

here

that

the

new

conception

f

strictly

nuclear

nheritance

larified

ssues.

The

efficacy

of

external

actorsn

producing

eritable

nutations

could

not,

and

cannot,

be

disproved a

priori

(radiation

and

chemical

mutagens

re

factors f

a

quite

different

ature from

those

suggested

during

the

1880's).

Then, as

now,

each

case

required

ndividual

xamination.

But

that

force

so

generalized

as

"environmental

onditions"

or eventhemorespecific actors,ight, empera-

ture,

nutrition, nd

so

forth, ould

cause

quite

definite

hanges

n

the

stable

hereditary

ubstance

taxed

the

imagination.

For

those

who

believed

in

the

inheritance f

acquired

characteristics

new

and,

to

many

observers,

n

insurmountable

obstacle

had

been

erected

which

precluded

even

partial

acceptance of

direct

environmental r

external

nfluences n

heredity.

Variation

and

particularly

ariation

n

an

abundance nd

magni-

tude

ufficient

or

he

operation f

natural

election

would

have to

be

sought

elsewhere.

In less thanhalfa century,oughly 840-1885,

the

first

tage

in

an

understanding f

the

broad

problem

of

generation

had

been

attained.

The

continuity

f

life, nce as

great a

mystery s

any

in

biology,had

been

traced

first o

the

cell

and

ultimately

o

the

nucleus and

its

contents.

No

summary f

the

synthesis f

thought

chieved

n

1884-1885 on

the

problems of

inheritance

an

excel

that

presented

y

K6lliker, himself

ne of

the

participants:

158

See

J. M.

D.

Olmsted,

Charles-Edouard

Brown-

Sequard

(Baltimore,

1946),

pp.

172-177.







158

WILLIAM

COLEMAN

[PROC.

AMER.

PHIL.

SOC.

1) Die Vorgaingeder Vererbung ind einzig und al-

lein aus den bei der Zeugung stattfinden

rscheinun-

gen zu begreifen. 2) Genauer bezeichnet,

ubertragen

die

zeugenden Organismen

auf den

erzeugten eine

morphologisch

bestimmte Substanz von

typischer

Zusammensetzung, on deren Leistungen die Ganze

Gestaltung des Erzeugten abhingt. 3) Dieser

VererbungsstoffIdioplasma, C. Naigeli) ist in den

Keimblaschen

der

Eier

und in den Samenfaden

enthalten,welche beide die Bedeutung von Kernen

haben, und wird

chemisch

wahrscheinlich urch das

sogenannteNuclein

charakterisirt....

4) Durch den

Zusammentritte eines dieser mannlichenund wei-

blichenKerngebilde ntsteht er erste Kern des neuen

Gesch6pfes, der somit

als

eine hermaphroditische

Bildung anzusehen ist und als Trager mainnlicher

und weiblicherCharaktere

rscheint.

5) Von diesem

ersten

embryonalen

Kern stammen alle

Kerne

des

vollendeten Gesch6pfes

n

ununterbrochener

orm-

folge ab und sind dieselben somit ebenfallsVertreter

beider zeugendenOrganismen.159

159

Kolliker,

885 note

142):

pp.

39-40.

The nucleus

ppeared o stand, f not absolutely

inviolate, t least well beyond

the easy reach of

manifold and fortuitous xternal

agents, from

the protoplasm

tself n to the total environment.

The nucleus,whose normal

metamorphoses ere

strictly egular, nd the nucleine,with apposite

form nd stability,

eemed alone responsible

or

heredity,

ereditytself eing

a conservative

orce

tending always towards

ensuringthat like will

produce like. Interpreting

ariation as an ex-

ception rdeviation

f

esser

orgreatermagnitude

of heredity, t too

could be assigned to the

nucleus.

Through heredity and variation

the

nucleus ppeared o guide all

of the phenomena

f

inheritance,

ncludingontogeny

nd the

diverse

metabolicprocesses

relating thereto.

Heredity,

dependent pon

a

chemical

molecule,

had

become

as much a physiological uestionas it had long

been

an issue for the

naturalist.

Documents

Coleman-Cell, Nucleus, and Inheritance: An Historical Study