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 Protocells
Bridging Nonliving and Living Matter

Mark A. Bedau,
Liaohai Chen,
David Deamer,
David C. Krakauer,
Norman H. Packard,
and Peter F. Stadler
Protocells
Protocells
Bridging Nonliving and Living Matter

edited by Steen Rasmussen, Mark A. Bedau, Liaohai Chen, David Deamer,

David C. Krakauer, Norman H. Packard, and Peter F. Stadler

The MIT Press

Cambridge, Massachusetts
London, England
6 2009 Massachusetts Institute of Technology

All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical
means (including photocopying, recording, or information storage and retrieval) without permission in
writing from the publisher.

For information about special quantity discounts, please email special [email protected]

This book was set in Times New Roman and Syntax on 3B2 by Asco Typesetters, Hong Kong.
Printed and bound in the United States of America.

Library of Congress Cataloging in Publication Data

Protocells : bridging nonliving and living matter / edited by Steen Rasmussen . . . [et al.].
p. ; cm.
Includes bibliographical references and index.
ISBN 978 0 262 18268 3 (hardcover : alk. paper) 1. Artificial cells. 2. Life (Biology) I. Rasmussen,
Steen.
[DNLM: 1. Cells. 2. Biogenesis. 3. Cell Physiology. 4. Models, Biological. QU 300 P967 2008]
QH501.P76 2008
576.8 0 3 dc22 2007049243

10 9 8 7 6 5 4 3 2 1
Contents

Preface ix
Acknowledgments xi
Introduction xiii

I Overview: Bridging Nonliving and Living Matter 1

1 The Early History of Protocells: The Search for the Recipe of Life 3
Martin M. Hanczyc

2 Experimental Approaches to Fabricating Artificial Cellular Life 19

David Deamer

3 Semisynthetic Minimal Cells: New Advancements and Perspectives 39

Pasquale Stano, Giovanni Murtas, and Pier Luigi Luisi

4 A Roadmap to Protocells 71
Steen Rasmussen, Mark A. Bedau, John S. McCaskill, and Norman H. Packard

II Integration 101

5 Steps Toward a Synthetic Protocell 107

Martin M. Hanczyc, Irene A. Chen, Peter Sazani, and Jack W. Szostak

6 Assembly of a Minimal Protocell 125

Steen Rasmussen, James Bailey, James Boncella, Liaohai Chen, Gavin Collis,
Stirling Colgate, Michael DeClue, Harold Fellermann, Goran Goranović, Yi Jiang,
Chad Knutson, Pierre-Alain Monnard, Fouzi Mouffouk, Peter E. Nielsen, Anjana Sen,
Andy Shreve, Arvydas Tamulis, Bryan Travis, Pawel Weronski, William H. Woodruff,
Jinsuo Zhang, Xin Zhou, and Hans Ziock
vi Contents

7 Population Analysis of Liposomes with Protein Synthesis and a Cascading Genetic

Network 157
Takeshi Sunami, Kanetomo Sato, Keitaro Ishikawa, and Tetsuya Yomo

8 Constructive Approach to Protocells: Theory and Experiments 169

Kunihiko Kaneko

9 Origin of Life and Lattice Artificial Chemistry 197

Naoaki Ono, Duraid Madina, and Takashi Ikegami

10 Models of Protocell Replication 213

Ricard V. Solé, Javier Macı́a, Harold Fellermann, Andreea Munteanu, Josep Sardanyés,
and Sergi Valverde

11 Compositional Lipid Protocells: Reproduction without Polynucleotides 233

Doron Lancet and Barak Shenhav

12 Evolutionary Microfluidic Complementation Toward Artificial Cells 253

John S. McCaskill

III Components 295

13 Self-Replication and Autocatalysis 299

Volker Patzke and Günter von Kiedrowski

14 Replicator Dynamics in Protocells 317

Peter F. Stadler and Bärbel M. R. Stadler

15 Peptide Nucleic Acids as Prebiotic and Abiotic Genetic Material 337

Peter E. Nielsen

16 The Core of a Minimal Gene Set: Insights from Natural Reduced Genomes 347
Toni Gabaldón, Rosario Gil, Juli Peretó, Amparo Latorre, and Andrés Moya

17 Parasitism and Protocells: Tragedy of the Molecular Commons 367

Jeffrey J. Tabor, Matthew Levy, Zachary Booth Simpson, and Andrew D. Ellington

18 Forming the Essential Template for Life: The Physics of Lipid Self-Assembly 385
Ole G. Mouritsen and Ask F. Jakobsen

19 Numerical Methods for Protocell Simulations 407

Yi Jiang, Bryan Travis, Chad Knutson, Jinsuo Zhang, and Pawel Weronski
Contents vii

20 Core Metabolism as a Self-Organized System 433

Eric Smith, Harold J. Morowitz, and Shelley D. Copley

21 Energetics, Energy Flow, and Scaling in Life 461

William H. Woodruff

IV Broader Context 475

22 Gánti’s Chemoton Model and Life Criteria 481

James Griesemer and Eörs Szathmáry

23 Viral Individuality and Limitations of the Life Concept 513

David C. Krakauer and Paolo Zanotto

24 Nonlinear Chemical Dynamics and the Origin of Life: The Inorganic-Physical Chemist
Point of View 537
Jerzy Maselko and Maciej Maselko

25 Early Ancestors of Existing Cells 563

Andrew Pohorille

26 Prebiotic Chemistry, the Primordial Replicator, and Modern Protocells 583

Henderson James Cleaves II

27 Cell-like Entities: Scientific Challenges and Future Applications 615

John M. Frazier, Nancy Kelley-Loughnane, Sandra Trott, Oleg Paliy, Mauricio
Rodriguez Rodriguez, Leamon Viveros, and Melanie Tomczak

28 Social and Ethical Issues Concerning Protocells 641

Mark A. Bedau and Emily C. Parke

Glossary 655
About the Authors 667
Index 679
Preface

The idea for this book grew out of two international protocell workshops in Sep-
tember 2003. One meeting, at Los Alamos National Laboratory and the Santa Fe
Institute, was organized by Steen Rasmussen, Liaohai Chen, David Deamer, David
Krakauer, Norman Packard, and Peter Stadler. The other meeting, at the European
Conference on Artificial Life (ECAL) in Dortmund, Germany, was organized by
Steen Rasmussen and Mark Bedau. We published a short summary of the state of
the art of protocell research as reflected in those workshops in early 2004 (Rasmussen
et al., 2004), and we planned to collect more details about this research in a longer
volume. That plan was the seed for this book. But a series of events intervened,
changing and delaying the book.
Those events grew out of the Seventh Artificial Life Conference in Portland, Ore-
gon, organized by Mark Bedau, John McCaskill, Norman Packard, and Steen Ras-
mussen in August 2000. Coinciding with the millennium, the conference aimed to
take stock of the young field of artificial life. Out of the Oregon meeting came a com-
munity consensus of specific grand challenges in artificial life. One of these challenges
is to create wet artificial life from scratch.
Over the next three years, our activities were a portfolio of projects, most involv-
ing, in one way or another, the creation of life from scratch. In 2001 we coined the
term living technology as an umbrella for our activities. The next year we realized
how computer-controlled microfluidics could act as life support for the evolution of
minimal chemical systems, and two months later we started creating a new roadmap
to protocells. Our meetings led to a proposal for a new Center for Living Technology
at which scientific developments in this area could be nurtured and developed along
the way to producing practical applications.
The European Commission’s program on complex systems funded the first phase
of these plans. Just before the first protocell workshops in 2003, we learned that our
EC proposal on Programmable Artificial Cell Evolution (PACE) was funded. John
McCaskill led the PACE project, which consisted of fourteen European and U.S.
partners and included plans for a European Center for Living Technology in Venice.
x Preface

One of the members of the PACE consortium was the new startup company, Proto-
Life Srl., of which Norman Packard and Mark Bedau became CEO and COO. Soon
afterwards Los Alamos National Laboratory awarded a complementary grant for a
project on Protocell Assembly, led by Steen Rasmussen. While these new activities
absorbed our time for a couple of years, this book was on the back burner.
In 2005 Emily Parke agreed to manage the editorial process of producing the
book. Our vision of the book had grown in the intervening years, so we solicited
chapters from many who had missed the original workshops.
Though it had a convoluted gestation, we hope this book will be both a resource
and an inspiration for the exciting and important quest to create life from scratch.

Mark Bedau
Norman Packard
Steen Rasmussen
Venice, Italy, June 2007

Reference

Rasmussen, S., Chen, L., Deamer, D., Krakauer, D., Packard, N., Stadler, P., & Bedau, M. (2004). Tran
sitions between nonliving and living matter. Science, 303, 963.
Acknowledgments

This book has been produced only because of the time and energy of a large group of
people. The editors are extremely grateful for the various kinds of help provided, and
we are pleased to have the opportunity here to acknowledge them.

Editorial Manager: Emily C. Parke

Editorial Board
James Bailey Doron Lancet
James Boncella Pierre-Alain Monnard
James Cleaves Harold Morowitz
Stirling Colgate Ole Mouritsen
Gavin Collis Andreea Munteanu
Michael DeClue Peter Nielsen
Andrew Ellington Andrew Shreve
Goran Goranović Eric Smith
Martin M. Hanczyc Ricard Solé
Takeshi Ikegami Pasquale Stano
Martin Nilsson Jacobi Eörs Szathmáry
Yi Jiang Bryan Travis
Günter von Kiedrowski Woody Woodru¤
Chad Knutson Hanz Ziock
Natalio Krasnegor Jinsuo Zhang
James La Clair
xii Acknowledgments

First, we want to convey special thanks to Emily Parke. As editorial manager,

Emily coordinated and oversaw the complex process of soliciting chapters, coordi-
nating reviews of the chapters, checking revisions, copy editing the final manuscripts,
and generally keeping the project on track. None of the editors wants even to imag-
ine what producing this book would have been like without Emily’s unflagging ex-
pert assistance.
We are also especially grateful to the thoughtful critical attention devoted to early
drafts of the chapters by our Editorial Board.
We want to single out John McCaskill for thanks. John has been a key intellectual
partner and friend in the creation of the diverse portfolio of protocell-related activ-
ities, especially the European Commission’s Programmable Artificial Cell Evolution
(PACE) project, the Los Alamos Protocell Assembly project, the European Center
for Living Technology, and ProtoLife Srl. All of those projects, and so indirectly
this book, show the benefit of John’s wit, intelligence, and vision.
We would also like to thank the MIT Press for critical early support that helped
launch this project and critical later patience when the timeline slipped. We thank
the Santa Fe Institute and the European Center for Living Technology for hospital-
ity while some of the work on this volume was completed. For financial support for
some of this work, we thank EU-supported PACE integrated project, EC-FP6-IST-
FET-IP-002035, and the Los Alamos National Laboratory LDRD-DR Protocell As-
sembly project.
Introduction

I.1 What Are Protocells?

All life forms are composed of molecules that are not themselves alive. But how
exactly do living and nonliving matter di¤er? Is there a fundamental di¤erence at
all? How could we possibly turn a collection of nonliving materials into something
that is, at least operationally speaking, alive? This book is a compendium of the state
of the art on attempts to answer these questions by building bridges between non-
living chemistry and emergent living states of matter. It focuses on attempts to create
very simple life forms in the laboratory. These new forms of life might be quite
unfamiliar.
In this book a living system is operationally defined as a system that integrates
three critical functionalities (figure I.1, outer ring): First, it maintains an identity
over time by localizing all its components. Second, it uses free energy from its envi-
ronment to digest environmental resources in order to maintain itself, grow, and
ultimately reproduce. Third, these processes are under the control of inheritable in-
formation that can be modified during reproduction. These properties enable selec-
tion and thus evolution as part of the reproduction process. Living systems are
sometimes said to include various further essential properties, such as autonomous
information processing, sensitivity to the environment, self-organization, and pur-
poseful behavior. We agree that these are central properties of living systems, but
we hold that they are derivative in the sense that they are e¤ectively implied by the
functionally integrated triad described previously.
This book aims to provide a very general understanding of how one could obtain
entities with these lifelike properties from experiments that begin with nonliving
materials. The book generally reflects the perspective that chemical instances of
such forms of life must embody the three operational functionalities in three inte-
grated chemical systems: a metabolism that extracts usable energy and resources
from the environment, genes that chemically realize informational control of liv-
ing functionalities, and a container that keeps them all together (see figure I.1, inner
xiv Introduction

Figure I.1
The three essential operational functionalities of living systems (outer circle), together with the correspond
ing realizations of these functionalities in protocell architectures (inner triangle).

triangle). We will use the term protocell to refer to any realization of these three func-
tional components. Our usage is close to the engineering word prototype, that is, an
artificial structure that represents the first simple working model of a designed sys-
tem. The importance of cooperative structures for minimal life was initially stressed
in Eigen’s hypercycle concept (Eigen, 1971), which focused on the cooperation be-
tween informational structures (genes). Gánti (1975) first identified the minimal co-
operative structure capable of forming a cell as the triad of genes, metabolism, and
container.
We use the terms container, metabolism, and gene quite generally, with minimal
presupposition concerning their chemical details. In most contexts, the container
will be an amphiphilic structure such as a vesicle or micelle, but immobilizing chem-
icals on a surface can also achieve the required spatial localization. Similarly, metab-
olism could harvest redox energy or light, it could work with more or less complex
material precursors, and it might or might not use adenosine triphosphate (ATP)
and complex enzymes. Furthermore, genes might achieve informational control
and inheritance with some nucleotide other than DNA, or even without using any
biopolymers.
Introduction xv

Figure I.2
The bottom up approach focuses on assembling a minimal protocell from simple inorganic and organic
components. The top down approach focuses on the simplification of modern cells. Eventually these two
approaches will meet in the middle.

One way to produce a protocell is to combine an appropriate mix of nonliving

molecules and then let them react and self-assemble into a living protocell. This
process begins with molecular constituents and so may be considered a bottom-up
approach to protocells. Most of the work in this book falls within this bottom-up
approach. Complementing this is a top-down approach based on the recent success
of genomic research. The top-down approach begins with an existing contemporary
living cell, typically a very simple one, and reduces its genome by successive removal
of genes, to arrive at a minimal cell with just enough genes to maintain itself and
reproduce (Hutchison et al., 1999). One long-range aim of this top-down research is
to make an artificial cell by destroying a cell’s original genome and inserting a new
minimal genome that is synthesized externally from nucleotides using genomic tech-
nology (Glass et al., 2006). A spectrum of intermediate levels of functional organiza-
tion is spanned by top-down approaches beginning with living matter (contemporary
cells) and bottom-up approaches beginning with nonliving matter, as illustrated in
figure I.2.
Once a population of protocells exists, their functional e¤ectiveness might cause
some to be selected over others. If there is a combinatorially large family of possible
forms of informational control, and if information inheritance is neither too perfect
xvi Introduction

nor too imperfect, then the process of evolution might be able to improve those func-
tionalities over time. Evolvability is often thought to be an essential property of life
(e.g., Maynard Smith, 1975), but it remains elusive in existing protocell realizations.
In fact, it is an open question under which conditions such a system will be able to
exhibit open-ended evolution, by which we mean a system’s ability to create new
properties in an open-ended manner over time as a result of selection and environ-
mental pressures (Bedau et al., 2000). Statistical analysis of evolutionary systems,
including artificial life models, indicates that the only systems known to exhibit
open-ended evolution are natural life (the biosphere) and human technology, which
is itself generated by living entities (Bedau et al., 1997; Skusa and Bedau, 2002). One
key to achieving open-ended evolvability is the ability of evolving systems to gener-
ate novel properties. Novel properties in molecular systems can be obtained not only
by genetic rearrangement but also by aggregation of existing systems. For example,
combining a lipid membrane system with a photosynthesizer might produce a simple
light-driven metabolic system. Aggregation-generated novelty could be as important
as genetic variation in the evolution of protocells.
Most of the protocell architectures presented in this book rely crucially on the pro-
cess of self-assembly. This means that the resulting protocell objects are not designed
or constructed piece by piece, as happens with the products of traditional engineer-
ing; rather, the requisite materials are brought together under the appropriate labo-
ratory conditions and the protocells spontaneously form. Protocells are themselves
emergent structures, so designing them and controlling their functionality will require
the development of new techniques of emergent engineering.

I.2 Scientific Roots of Protocell Research

Contemporary protocell research has a number of scientific roots. One is the long
tradition of work on the origin of life. The question of how life might be obtained
from nonliving materials is similar to that of how contemporary life originated, since
contemporary life presumably arose from nonliving materials, but these two ques-
tions lead us in very di¤erent directions. The methods and conditions used to make
protocells might be radically unlike those actually involved in life’s origins, and it is
an entirely open question whether such new forms of life would or could ever evolve
into anything like naturally existing life-forms. The understanding of life obtained
from making protocells, however, should contribute to research on the origin of life
as well as benefit from it.
Research on the origin of life naturally spawned several of the research threads
that comprise current protocell e¤orts. A particularly important thread is the concept
of the RNA world, which concentrates on RNA as the primary element in origin of
life scenarios (see, e.g., Gilbert, 1986; Orgel, 1994). The connection with protocell re-
Introduction xvii

search comes when RNA chemistry is integrated with container structures (cf. Szos-
tak, Bartel, and Luisi, 2001; see also chapters 2 and 5).
Protocell research may also be seen as an endeavor within the field of artificial life.
The phrase ‘‘artificial life’’ is much broader and refers to any attempt to synthesize
the essential features of living systems. Artificial life traditionally falls into three
branches, corresponding to three synthesis methods. ‘‘Soft’’ artificial life creates com-
puter simulations or other purely digital constructions that exhibit lifelike behavior.
‘‘Hard’’ artificial life produces hardware implementations of lifelike systems, usually
in robotics. ‘‘Wet’’ artificial life involves the creation of lifelike systems in a wet lab,
in most cases based on carbon chemistry in water. The holy grail of wet artificial life
is the construction of protocells, which is the focus of this volume.
Another strand of human activity that produces living cells that are not found in
nature is represented by the recent success of synthetic biology e¤orts to alter meta-
bolic pathways of existing contemporary cells by genetic manipulation (for an over-
view see Baker et al., 2006). These techniques may produce a range of more or less
artificial cells, depending on the extent of genetic modification and the resulting dis-
tance from naturally existing life. If synthetic biology is characterized as the attempt
to engineer new biological systems, then protocell research can be viewed as a branch
of synthetic biology (see the introduction to part IV).
Astrobiology is concerned with the search for life elsewhere in the universe, so it
and protocell research share an interest in the fundamental properties of living sys-
tems. While the artificial life community asks what is minimal life and how can it be
useful, the astrobiology community asks where life comes from and whether it exists
only on the Earth. In contrast with astrobiology, protocell research does not need to
justify the cosmological or geochemical origins of its starting materials. However, the
possibility of detecting alien life on other planets or moons adds many intriguing
questions, some of which we will touch on in the last section of this book.

I.3 Purposes and Organization of This Book

This volume is a comprehensive general resource on protocell research intended to

serve a number of functions. The first, of course, is simply to convey the state of the
art in contemporary protocell research. Doing this comprehensively involves a rich
multiplicity of perspectives: di¤erent disciplines (e.g., physics, chemistry, biology,
biochemistry, geochemistry, materials science, computer science, biophysics, evolu-
tionary theory, engineering, philosophy), di¤erent approaches to creating protocells,
the employment of di¤erent scientific methods (observation, experiment, simulation,
theory), and the understanding of processes happening on di¤erent spatial and tem-
poral scales. A resource that collects key protocell research in one place can promote
mutually beneficial crosstalk with related and overlapping scientific and engineering
xviii Introduction

projects, such as studies of the origin of life and extraterrestrial life, e¤orts in syn-
thetic and systems biology, investigations in material science and nanotechnology,
as well as the study of artificial life and artificial chemistry in general.
This snapshot of protocell research today can also promote, inform, and construc-
tively focus future work in this area in at least two ways: by enhancing synergies
among the various perspectives and approaches currently being pursued within pro-
tocell research, and by identifying and calling attention to milestones that represent
the key tractable open questions that will most likely propel scientific progress.
Finally, being able to bridge the gap between the nonliving and the living will raise
a number of new practical issues for society to face. The capacity to engineer truly
living technology will galvanize a wealth of practical projects and surely spawn a
diverse ecology of revolutionary applications. But in the wrong hands, or with the
wrong designs, protocell technology could generate new kinds of risks to human
health and the environment. In addition, the practice of creating novel forms of life
from scratch could shock existing cultural norms, with the potential to fundamen-
tally reshape our sense of who we are and where we come from. A comprehensive
compendium on protocells could help those whether scientists, journalists, public
o‰cials, or the general public interested in gaining a scientifically informed per-
spective on this rapidly expanding new field.
These purposes for this volume have informed its overall organization. Part I con-
tains four overviews of protocell science. These range from histories of experimen-
tal e¤orts to a conceptual framework for comparing experimental and theoretical
protocell achievements and proposals. Together the chapters provide complemen-
tary views on how to evaluate and categorize the field. The eight chapters in part II
present some of the leading approaches to integrating the core complementary func-
tionalities of containment, metabolism, and informational control and transfer (genet-
ics) into a fully functioning protocell. The work presented here includes experimental
e¤orts, simulation of theoretical schemes, attempts to combine both approaches, and
a method of achieving integration with the help of computer-controlled microfluidic
and microelectrical devices.
Part III focuses on the foundational functional components of protocells provided
by containment, metabolism, and genetics. These nine chapters dive into experimen-
tal and simulation details of replicating informational molecules, lipid membranes
and compartments, and metabolic processes as well as energetics. This section also
includes a chapter on protocell simulation methods.
Part IV situates protocell science in the broader contexts of theories of life, mini-
mal forms of life, the related scientific investigation into the origin of life, and inves-
tigations of some practical applications and social and ethical implications. The book
closes with a glossary of technical terms found in the chapters.
Introduction xix

I.4 Why Now?

Modern studies of simple protocells began to appear in the 1980s, typically in the
context of origin of life research. (For a historical account of earlier work, see chap-
ter 1.) This modern research was inspired by the discovery of Bangham and co-
workers in (1965) that phospholipids could not only assemble into the vesicular
structures now called liposomes, but also could trap concentration gradients of ions
and other solutes. From this work it immediately became apparent that the lipid
bilayer was the primary permeability barrier to the free di¤usion of ions and metab-
olites, and that specialized proteins must be present in the bilayer in the form of
channels and pumps to allow communication between the intracellular volume and
the external environment.
In the 1990s, other laboratories began to investigate encapsulated systems of mac-
romolecules. The early goals were to develop e‰cient encapsulation methods, design
lipid compositions and techniques that would permit external substrates to supply
encapsulated enzymes, establish conditions in which lipid vesicles could undergo
growth and division, and demonstrate catalyzed synthesis of polymers such as RNA,
DNA, and peptides within the liposome volume. As these goals were achieved and
reported in the literature, other laboratories began to think seriously about develop-
ing a variety of further protocell systems.
Much of the theoretical research on minimal life has its intellectual origin from the
ideas presented by the experimentalist Manfred Eigen back in 1971, when the notions
of quasispecies and hypercycle were created (Eigen, 1971). Cooperative structures
that provide mutual support of genes, metabolism, and containers can be seen as
generalizations of Eigen’s ideas. Also, Ilya Prigogine’s creation of the concept of dis-
sipative structures in the late 1970s gripped the imagination of many theorists trying
to understand the origins of life. The notion from the late 1980s of the RNA world
inspired both theoretical and experimental investigations of minimal life, and even
today this concept is probably still the most prevalent hypothesis about the bridge
between early minimal life and contemporary life.
With the turn of the millennium, ever-increasing numbers of publications explicitly
related to functional protocells began to appear. An Internet search in 2006 for the
terms protocell and artificial cell produced approximately 50,000 references to each
term. A similar search in the scientific literature revealed 435 citations for protocell
and 1,310 citations for artificial cell. These numbers reveal exploding interest in these
topics since the first modern publications about 25 years ago.
What might have given rise to this remarkable increase? First, of course, is the in-
trinsic interest in bridging the gap between nonliving and living matter. To truly un-
derstand what it would take to create a minimal living cell, the obvious challenge is
xx Introduction

to verify this understanding by assembling a minimal cell from its parts list. The first
fabrication of a functioning protocell will be a major scientific breakthrough. It is
also clear that protocell technology will have significant applications, particularly in
the biotechnology, material science, computer and information technology, and envi-
ronmental science industries.
All of these considerations make this book timely and of real use to the increasing
number of investigators who see research on protocells as their primary scientific
quest. We expect that this book will serve as a focus for such activity, calling atten-
tion to the progress that has been made so far, and identifying milestones to guide
future research and development.
In an environment in which basic scientific research su¤ers from decreasing re-
sources, society owes great thanks for the foresight and vision of national funding
sources, such as the Department of Energy’s support for Los Alamos National Lab-
oratory and NASA programs in Astrobiology and Exobiology, as well as for the Eu-
ropean Commission’s program on Future and Emerging Technologies, the United
Kingdom’s Engineering and Physical Sciences Research Council, the Japan Society
for the Promotion of Science, and the Japanese Minister of Education, Culture,
Sports, Science, and Technology, all of which have provided significant financial sup-
port for protocell research well in advance of any proven applications. Without these
kinds of resources, the research reported in this book would have been impossible.
The eventual applications of protocell research will come through the flowering of
living technology. Living technology is one of the first concrete realizations of what
the U.S. National Science Foundation (NSF) and the European Commission (EC)
have termed convergent technologies. Convergent technologies are the emerging syn-
theses of nano-bio-info-cognitive (NBIC) knowledge production, and the NSF and
EC both believe that convergent technologies will have a very large socioeconomic
impact in the next 25 years. We hope that this volume will help forge an interna-
tional community of interested stakeholders working with protocell scientists to ex-
plore the broader global opportunities and challenges of protocell research and the
emergence of living technology.

References

Baker, D., Church, G., Collins, J., Endy, D., Jacobson, J., Keasling, J., & Modrich, P. (2006). Engineering
life: Building a fab for biology. Scientific American, 294, 44 51.
Bangham, A. D., Standish, M. M., & Watkins, J. C. (1965). Di¤usion of univalent ions across the lamellae
of swollen phospholipids. Journal of Molecular Biology, 13, 238 252.
Bedau, M. A., McCaskill, J. S., Packard, N. H., Rasmussen, S., Adami, C., Green, D. G., et al. (2000).
Open problems in artificial life. Artificial Life, 6, 363 376.
Bedau, M. A., Snyder, E., Brown, C. T., & Packard, N. H. (1997). A comparison of evolutionary activity
in artificial evolving systems and the biosphere. In P. Husbands & I. Harvey (Eds.), Proceedings of the
fourth European conference on artificial life, ECAL97 (pp. 125 134). Cambridge, MA: MIT Press.
Introduction xxi

Eigen, M. (1971). Self organization of matter and the evolution of biological macromolecules. Naturwis
senschaften, 58, 465 523.
Gánti, T. (1975). Organization of chemical reactions into dividing and metabolizing units: The chemotons.
Biosystems, 7, 15 21.
Gilbert, W. (1986). The RNA world. Nature, 319, 618.
Glass, J. I., Smith, H. O., Hutchinson III, C. A., Alperovich, N. Y., & Assad Garcia, N. (2007). Minimal
bacterial genome. U.S. Patent Application Publication 2007/0122826.
Hutchison, C. A. III, Peterson, S. N., Gill, S. R., Cline, R. T., White, O., Fraser, C. M., et al. (1999).
Global transposon mutagenesis and a minimal mycoplasma genome. Nature, 286, 2165 2169.
Maynard Smith, J. (1975). The theory of evolution, 3rd ed. New York: Penguin.
Orgel, L. E. (1994). The origin of life on the Earth. Scientific American, 271, 76 83.
Skusa, A., & Bedau, M. A. (2002). Towards a comparison of evolutionary creativity in biological and cul
tural evolution. In R. Standish, M. A. Bedau, & H. A. Abbass (Eds.), Artificial life VIII (pp. 233 242).
Cambridge, MA: MIT Press.
Szostak, J. W., Bartel, D. P., & Luisi, P. L. (2001). Synthesizing life. Nature, 409, 387 390.
I OVERVIEW: BRIDGING NONLIVING AND LIVING MATTER
1 The Early History of Protocells: The Search for the Recipe of Life

Martin M. Hanczyc

1.1 Introduction

Vitalism is an old ideology that makes a clear distinction between chemicals compris-
ing a living organism and chemicals from inanimate matter. The synthesis of urea by
Friedrich Wöhler (1828) challenged the philosophical distinction between nonliving
and living matter by demonstrating that a biological organic molecule can be synthe-
sized in a laboratory from nonliving chemical precursors. Further development of
organic chemistry demonstrated how most of the organic molecules that comprise a
cell could be synthesized in a laboratory under detailed reaction conditions. Subse-
quent experiments such as the Buchner brothers’ fermentation of sugar into ethanol
(a biological process) by the nonliving yeast extracts in 1897 opened the door further
to exploration of the conceptual gray space between chemistry and biology (Fried-
mann, 1997). The following brief historical introduction recounts the principal exper-
imental endeavors to create a protocell that began more than 100 years ago.

1.2 The First ‘‘Cell Models’’

The first studies from the latter half of the nineteenth century that reported lifelike
behaviors from nonliving systems were not based on cells or even cell extracts. Begin-
ning in 1867, Moritz Traube described a system that demonstrated the formation and
growth of semipermeable membranes composed of copper ferrocyanide surrounding
a seed crystal of copper sulfate. Such an artificial membrane superficially resembled a
cell membrane in that it exhibited selective permeability to di¤erent solutes and
responded to osmotic pressure (Traube, 1867). In 1892, Bütschli described structures
with an amoebalike movement formed by combining olive oil and potash. The dy-
namic structures appeared to form pseudopodia and engulf other particles, behaviors
seen with living amoebae (Bütschli, 1892). Leduc (1907) also produced ‘‘osmotic
cells’’ similar to Traube’s by placing a seed crystal of calcium chloride in a saturated
4 Martin M. Hanczyc

potassium salt solution. As the crystal dissolved, a membrane of calcium phosphate

appeared and formed a structure similar in morphological appearance to a cell. He
reported the shape change of the cell-like structures in response to environmental
changes in osmotic pressure that presumably modulated the surface of the structures.
These early cell models showed that simple, nonliving materials such as salt solutions
could organize into structures at least superficially resembling living cells (Oparin,
1965a). Even though the relevance of such models to actual living cells was not
clearly established at that time, the tendency of nonliving matter to adopt some char-
acteristics of life fascinated researchers interested in not only the origin of but also
the synthesis of life.

1.3 Herrera’s Sulphobes

In 1897 Alfonzo L. Herrera published a book, Recueil des lois de ta Biologie Generale
(Collection of Laws of General Biology), in which he introduced the idea that the
functions and structures of living cells can be attributed to physicochemical laws
(Negrón-Mendoza, 1994). In 1904, Herrera founded a new branch of science, plas-
mogeny, which he defined as the study of the origin of protoplasm as an experimen-
tal science. Protoplasm was a term used to describe the living material inside a cell. It
had the observable properties of flow and movement, was the site of metabolism, and
was able to self-replicate. Herrera began to explore how such properties could be the
result of physicochemical forces acting and interacting within living cells. His ap-
proach was to reconstitute such properties using nonbiological chemicals. By mixing
substances with di¤erent chemical potentials and di¤erent phases, he observed life-
like patterns emerging. He is most famous for producing ‘‘sulphobes’’ by exposing
thin films of formaldehyde in water to fumes of ammonium sulfide (Herrera, 1942).
Through microscopy (figure 1.1), Herrera observed populations of many diverse
structures reminiscent of protoplasm, including structures that appeared to undergo
mitotic division (Herrera, 1912). Apparently Herrera’s sulphobes were so lifelike that
when presented to an ‘‘eminent microscopist,’’ they were determined to be living
creatures and were then classified as such (Young 1965, p. 357).
Plasmogeny o¤ered a view of biology seen through the eyes of a synthetic chemist.
With his sulphobes, Herrera demonstrated that the superficial structure and organi-
zation of the protoplasm could be recapitulated through purely chemical means. Fur-
thermore, such structures produced chemistry that resulted in the fortuitous synthesis
of two amino acids and dyes. Therefore the sulphobes not only resembled lifelike
structures but also were capable of limited biologically relevant synthesis. Most nota-
bly Herrera’s synthesis of protoplasm-like properties in the laboratory was demon-
strated starting from simple, nonbiological constituents.
The Early History of Protocells 5

Figure 1.1
Sample micrographs from the work of Herrera showing various cell like morphologies (800 magnifica
tion) from Herrera (1912).

1.4 Bungenberg de Jong’s Coacervates

Although Herrera began an extensive experimental research program to recapitulate

and understand protoplasm through chemistry, the origin of the idea that the proto-
plasm is made up of chemicals subject to physicochemical laws can be found in early
research on colloidal systems. Thomas Graham (1805 1869), an English chemist,
studied the di¤usion of nonbiological materials and biological extracts such as
starch, gum, and gelatin. He termed the class of substances with very low di¤usion
rates colloids. In 1861, he wrote that the plastic parts of the animal body also behave
like colloids (Graham, 1861).
The Dutch biochemist H. G. Bungenberg de Jong (1893 1977) coined the term
coacervate as a special from of colloid. When certain organic substances such as gel-
atin and gum arabic are mixed with an aqueous solution, the fluids separate into two
distinct phases. Upon agitation, the bottom, organic-rich layer breaks up into a pop-
ulation of small microscopic spherical structures or coacervates (see figure 1.2). These
structures of a few microns in diameter do not readily dissolve because of a tight
layer of water molecules that interacts with the charged organics at the surface sur-
rounding the coacervate. This in e¤ect delays the di¤usion of concentrated material
in the coacervate sphere into the surrounding media. Bungenberg de Jong (1932)
noted the similarities between coacervates and living protoplasm, and like Graham
before, held the idea that the physical conditions that produced coacervates may
also explain something about the organization of the protoplasm.
6 Martin M. Hanczyc

Figure 1.2
Coacervates containing bacterial polynucleotide phosphorylase enzyme able to synthesize RNA polymers,
from Oparin, 1965b (magnification not specified).

Coacervates are interesting as model systems of simple cells in that they form
spontaneously, are rich in organic material (as opposed to the aqueous environment
around the coacervate), and provide a locally segregated environment with bounda-
ries that allow selective absorption of exogenous organic molecules. Coacervates are
most stable when formed from a mixture of positively and negatively charged sub-
stances resulting from an interplay of hydration and electrostatic forces. As a result,
coacervates are dynamic, can respond to external manipulation, and at the same
time are quite unstable, especially when the conditions under which they form are
changed. As a result of such investigations into colloidal and coacervate systems, it
was thought that living protoplasm consisted of di¤erent coacervate systems acting
and interacting together to produce the various dynamical properties observed in liv-
ing cells.

1.5 Crile’s Autosynthetic Cells

At the Cleveland Clinic Foundation in the 1930s, Doctor George Crile and col-
leagues experimented with the reconstitution of artificial cells from living material.
Two fractions were prepared from animal brain: one containing the lipid (lipoid) ma-
The Early History of Protocells 7

Figure 1.3
Crile’s autosynthetic cells (400 magnification; reproduced from Crile, Telkes, and Rowland, 1932).

terial and another containing sterilized protein material. When these fractions were
mixed together with a salt solution representing the salinity found in the animal
brain, structures resembling cells self-assembled. These structures, typically 50 to
150 microns in diameter, were termed autosynthetic cells (Crile, Telkes, and Row-
land, 1932) (figure 1.3) and were scrutinized for lifelike behavior. Beyond their mor-
phological similarities to living protozoa, Crile determined that the autocatalytic cell
preparations consumed a certain amount of oxygen and produced carbon dioxide (in
comparison with controls), and concluded that a certain amount of metabolism was
taking place. However, it was never shown what this metabolism-like activity was, or
if it was localized to the cell-like structures. In addition, they observed budding and
division of the structures by microscopy. The autosynthetic cells could be maintained
for months by feeding the structures with the sterile protein fraction, or destroyed by
heat, poisons, radiation, lack of oxygen, or lack of food.
Crile and colleagues relied heavily on self-organized processes in living matter to
reconstitute some of the properties of life from biological extracts. They then used
currently available techniques to test for signs of life. The work of Noireaux and Lib-
chaber (2004) recreated a similar approach of artificially reconstituting cells from
extracts under more controlled conditions and using modern techniques.

1.6 Oparin and Coacervates

Although A. I. Oparin’s interests were focused on understanding the origin of life, he

made many contributions to the field of protocell research, primarily by introducing
metabolism to coacervates. Oparin and colleagues continued the pioneering work of
Bungenberg de Jong and made coacervates from gum arabic (an extract from the
8 Martin M. Hanczyc

Acacia tree, a complex and variable mixture of arabinogalactan oligosaccharides,

polysaccharides, and glycoproteins) and gelatin (a protein product formed by partial
hydrolysis of collagen extracted from animal skin, bones, cartilage, and ligaments).
Such coacervates were prepared containing phosphorylase enzymes capable of poly-
merizing the substrate glucose-1-phosphate into starch. Once the coacervates con-
taining the enzyme were prepared, the substrate was added to the external medium
and adsorbed by the coacervates. It was found under such conditions that starch pro-
duction proceeded within the coacervate. Taking this experimental design a step fur-
ther, Oparin prepared coacervates containing two di¤erent enzymes, phosphorylase
and b-amylase, which together could form a simple two-step enzymatic pathway.
When the substrate glucose-1-phosphate was added exogenously, it was found that
not only did starch form in the coacervate droplet but also maltose, the product of
b-amylase acting on the starch, was found in the external media (figure 1.4). Report-
edly Oparin and colleagues succeeded in encapsulating polyadenine synthesis (see
figure 1.2), NAD oxidative-reductive reactions, and ascorbic acid oxidation within
coacervates (Oparin, 1966). Oparin also understood that the rates of reaction for
each step determine whether the coacervate assembly would grow by incorporating
and converting the incoming substrates into retainable products or diminish by con-
verting all available molecules into highly di¤usible product (Oparin, 1965b).
This work with coacervates demonstrated a few essential points. First, structures
with a superficial semblance to living protoplasm can be formed in the laboratory
from organic material. Such structures can trap functional molecules such as
enzymes. Molecules added to the external media can be absorbed by the coacervate
structure. The absorption is selective and depends on the composition of the coacer-
vate. Once absorbed, the molecules can be acted on by the trapped enzymes and the
product accrues within the structure. Finally, the products of the reaction can also
di¤use out of the structure into the environment. The essential role of selective per-
meability is clearly demonstrated. As Young stated in 1965, ‘‘It [a selectively perme-
able barrier] permits the cell to create its own internal environment necessary for its
metabolic and reproductive activities’’ (Young 1965, p. 348). On the importance of
metabolism, Oparin stated that ‘‘individual chemical reactions in living beings are
strictly coordinated and proceed in a certain sequence, which as a whole forms a
network of biological metabolism directed toward the perpetual self-preservation,
growth, and self-reproduction of the entire system under the given environmental
conditions’’ (Oparin 1965b, p. 331).
By engineering supramolecular structures capable of housing a simple metabolic
pathway, Oparin demonstrated that the reconstitution of a population of structures
with simple lifelike metabolism was possible. Although Oparin’s main objective for
this work was to understand fundamental processes related to chemical evolution
and the origin of cellular life, his work with coacervates followed an approach more
The Early History of Protocells 9

Figure 1.4
(A) Representation of molecules involved in the coacervate enzymatic pathway. (B) Schematic of the
encapsulated enzymatic pathway. The enzymes, phosphorylase and b amylase, are entrapped within
the coacervate structure. The substrate, glucose 1 phosphate, is supplied exogenously and absorbed by the
coacervate. The substrate is converted to starch within the coacervate droplet by phosphorylase. Then
the b amylase converts the starch to maltose, which di¤uses out of the coacervate structure (Crile, Telkes,
and Rowland, 1932).
10 Martin M. Hanczyc

akin to synthetic biology. This is because his work was based on organic molecules
and enzymes extracted and purified from already living matter. (In contrast, Her-
rera’s work involved the generation of structures directly from nonbiological chemi-
cals.) Because of his success in reconstituting lifelike microscale structures in the
1950s and 1960s, Oparin inspired many to pursue the fundamental questions of the
origin of life and to understand the basic physicochemical forces that underlie cellu-
lar life.

1.7 Jeewanu

In the 1960s Krishna Bahadur from the Department of Chemistry at the University
of Allahabad reported on the synthesis of protocells called Jeewanu (Bahadur, 1966).
The name given to these structures, Jeewanu, comes from a Sanskrit work for par-
ticles of life. Jeewanu were made using various protocols and components. Some
were made by combining peptides, ascorbic acid, ammonium molybdate, and inor-
ganic minerals. Others were made by mixing paraformaldehyde, molybdic acid, and
ferric chloride in water and then placing this mixture on a nutrient-rich agar. After
some time (hours to weeks) under exposure to a source of light (sunlight or artificial
ultraviolet light), globular structures of about 0.5 to 15 microns in diameter ap-
peared. Bahadur claimed that the Jeewanu had a similar morphology to living cells,
grew over time, possessed weak metabolic activity, and could reproduce by budding.
He also made the claim that Jeewanu were living cells. The creation of Jeewanu was
an attempt to synthesize actual living cells using simple precursors with the goal of
understanding the origin of life. The inadequate detail provided in his publications
led to criticisms (see Caren and Ponnamperuma, 1967) and doubt was cast on his
claims.

1.8 Fox’s Microspheres

With the development of molecular biology in the 1950s through the 1970s, the fun-
damental role of self-organization or self-assembly in biological systems became in-
creasingly apparent (Fox, 1968; Wald, 1954). It is this type of interaction among
molecules that gives rise to higher-order structures of complexity in modern-day cells
and is a main factor in the formation of sulphobes, autosynthetic cells, Jeewanu, and
coacervates as described earlier. In addition, self-organization provides a tool that
can be used to construct protocells without relying excessively on precise and often
untenable manipulation on the molecular level.
In the 1960s and 1970s, Sidney Fox (1912 1998) and colleagues contributed to the
pursuit of the synthesis of life by creating populations of peptide-based spherical
structures in the laboratory. Specifically, by heating amino acids, mixing in water or
The Early History of Protocells 11

Figure 1.5
Microspheres of proteinoid in water from Young, 1965 (900 magnification).

salt solution, and then allowing the solution to cool slowly, Fox found that spherical
structures formed spontaneously (figure 1.5). These structures were similar in diame-
ter (typically a few microns), with each microsphere containing an estimated 10 10
proteinoid molecules. The proteinoid material formed during the heating step by
linking and crosslinking of the amino acid monomers to form more elaborate and
complex peptides. These peptides would then interact and self-assemble within
minutes into larger macromolecular structures called microspheres (Fox and Dose,
1972). Fox’s microspheres were found to be generally more stable than coacervates.
Fox extensively characterized the dynamics of his microspheres, reporting that he
observed many interesting phenomena including di¤usion of material from the inside
of the sphere to the outside, partial fission (due to dissolution of proteinoid and
change in surface tension), generation of double-layer membrane, shrinkage or swell-
ing resulting from osmotic changes, sensitivity to pH (depending on amino acid com-
position), selective permeation of polysaccharides and monosaccharides, motility
(with zinc and ATP), budding, growth by accretion, and formation of junctions
between microspheres. In addition, Fox and his colleagues reported some weak
enzymelike activity in the proteinoid products (Fox, 1965, 1968). It is not clear
whether microspheres exhibiting such behaviors were common or the conclusions
were based on a few rare events in the population.
Like Oparin, Fox was searching for abiotic processes that could have led to the
formation of cellular life. In much the same way, microspheres showed encapsulated
metabolism and supramolecular dynamics. One fundamental di¤erence between
12 Martin M. Hanczyc

coacervates and microspheres is that Fox demonstrated the self-assembly of a popu-

lation of complex microstructures from simple precursors.

1.9 Toward the Modern Concept of the Protoplasm

The cell model systems presented here were simplistic conceptualizations of biologi-
cal cells and may not have been accurate representations of the important forces that
define a living cell. Concurrent research into properties of living cells painted a di¤er-
ent picture of the vital physicochemical properties of life. Although coacervates and
microspheres were shown to have some type of selectively permeable barriers, other
research has shown that all natural living cells use a particular kind of barrier com-
posed of a lipid membrane. In 1900, Charles E. Overton showed that nonpolar, oily
chemical substances were selectively absorbed by plant cells. He hypothesized that
the cell membrane barrier is similar in some way to olive oil and is lipoid in com-
position (Overton, 1900). Further investigation into the physicochemical nature of
lipids by Irving Langmuir (1917) led to the idea that fatty acid molecules form a
monolayer at the air-water interface with the fatty hydrocarbon chains oriented
away from the water. Gorter and Grendel (1925) then performed experiments similar
to Langmuir’s, but with lipid extracts from erythrocytes. They were able to calculate
that enough lipid was present to cover approximately twice the surface area of the
cells, concluding that the cells were covered in a layer of lipids ‘‘two molecules
thick.’’ This research may have inspired Crile and colleagues to use two fractions to
construct their autosynthetic cells: the protein fraction to reconstitute the cytosol and
the lipoid fraction to reconstitute the membrane.
Danielli and Davson (1935) proposed a bilayer model of lipid cell membrane in
which lipids were arranged such that the hydrocarbon chains formed the interior of
the membrane sandwich, and proteins covered the lipid headgroups on both sides
of the membrane. This hypothetical structure was further supported by electron mi-
croscopy studies in the 1950s, and renamed the unit membrane model (Robertson,
1957). Further evolution in the conceptualization of the cell membrane led to the cur-
rent fluid mosaic model of the cell membrane (Singer and Nicholson, 1972). In this
model the cell is enclosed in a bilayer of lipids as before, but now the lipids as well as
integral proteins move within the membrane. The fluid mosaic model allows for a
detailed understanding of processes in real cells such as osmotic response, selective
permeability, and specific cell-cell and cell-environment communication. Bangham
demonstrated in 1965 that dispersions of phospholipid extracts self-assemble into
spherical structures reminiscent of cell membranes, and these ‘‘liposomes’’ like cell
membranes are osmotically active (Bangham, Standish, and Watkins, 1965). This
provided the first in vitro model of a real cell membrane. Since then, liposomes have
The Early History of Protocells 13

been developed extensively as models of natural cell membranes and used in con-
structing protocells.
In sulphobes, autosynthetic cells, coacervates, Jeewanu, and microspheres, the
morphology of the structures bears a superficial resemblance to living cells. The elec-
trostatic forces of interacting polymers and the crosslinking of peptides may explain
their shape and consistency. However, the real structure of the cytoplasm is of a
much di¤erent complexity. While Graham, Bungenberg de Jong, and others were
investigating the properties of coacervates, other contemporaneous models of the
protoplasm were being developed. One included a view in which the internal contents
of the cell are physically organized in three dimensions by a protein network of
fibers. In the eighteenth and nineteenth centuries, an intracellular fiber network was
proposed to explain contraction of animal muscles (see Frixione, 2000). Sigmund
Freud, the father of psychoanalysis, was one of the original proponents of the fibril-
lary theory of protoplasm structure as it applied to his research into nerve cells
(Freud, 1882; Triarhou and Del Cerro, 1987). During the early part of the twentieth
century, similar conceptualizations were applied to explain the intracellular organiza-
tion and movement in many types of animal cells. Such hypotheses were supported in
the 1950s through the visualization of protein fiber networks by electron microscopy.
Today, we understand that the consistency of the eukaryotic cytoplasm is not due to
colloidal properties of the constituents after all, but rather to an elaborate protein
cytoskeleton that is responsible for the cell shape as well as internal organization
and cell movement. Evidence also exists for similar protein networks in bacteria (see
Carballido-Lopez, 2006).
Returning now to the attempts to synthesize protocells, those cell models did not,
after all, represent the true complexity of living protoplasm beyond superficial mor-
phological similarity. Nevertheless, the early research into the recipe of life has
shown that much simpler aggregate constructions can exhibit some lifelike behaviors.
Furthermore, some structures have been engineered to contain primitive metabo-
lisms. So although such works may not have successfully explained the physico-
chemical forces of cellular life, they can be seen as useful attempts to synthesize a
simplistic form of artificial life.

1.10 Summary

The ideology of vitalism has been challenged, and its once-defined lines blurred by
the research programs that ambitiously tried to synthesize life and lifelike behavior
from nonliving components. These early attempts at synthesizing life from nonlife fu-
eled the debate about what life essentially is. Such research projects attracted the in-
terest of many researchers and thinkers from a wide range of disciplines, and also of
14 Martin M. Hanczyc

religious leaders. Indeed, Sidney Fox was invited on multiple occasions to the Vati-
can for discussions about the origin and synthesis of life with the Pope and his scien-
tists (Fox, 1997). Self-organization of structure, response to environmental changes,
uptake of nutrients, internal metabolism, expulsion of waste, movement, and self-
replication: These concepts persist in modern-day attempts to synthesize protocells,
as described in the following chapters of this book. Although these early attempts
did not satisfactorily represent the real physicochemical forces that shape a modern
living cell, they did show the tendency of matter, under the proper conditions, to or-
ganize itself into structures possessing similar qualities to living cells. And in that
way, they imply that there may be many paths toward synthesizing primitive life.
In 1966, at the national meeting of the American Chemical Society (ACS), a sym-
posium on the synthesis of living systems was held to present the major steps in the
developing field of molecular biology. The topics ranged from the laboratory synthe-
sis of bovine insulin and other proteins to the synthesis and replication of nucleic
acids. The symposium prompted the publication of a paper in 1967 suggesting that
‘‘[i]t is the accomplishments of the past decade and the confidence in the creative
powers of scientists which have led to speculation that these accomplishments may
lead, before the end of the century to the synthesis of new types of rudimentary living
systems’’ (Price, 1967, p. 144).
In an earlier optimistic view published in Science in 1960, Simpson noted that ‘‘[a]t
a recent meeting in Chicago, a highly distinguished international panel of experts was
polled. All considered the experimental production of life in the laboratory immi-
nent, and one maintained that this has already been done . . .’’ (Simpson 1960, p.
969).
Despite predictions, most researchers would agree that the goal of a synthetic cell
has not yet been achieved. The question remains: When will science create synthetic
life? This is di‰cult to answer. Recently, Jack Szostak remarked that $20 million dol-
lars and three more years of research would produce a living and evolving protocell
(Zimmer, 2004). Indeed, a well-funded, consistent research program may reach the
desired goal in a relatively short time. Protocell history captured in manuscripts and
texts over the past hundred years shows us that progress in chemistry, physics, biol-
ogy, biochemistry, and other areas inspires an enthusiasm that makes the goal of a
synthetic cell seem closer. Descriptive and exploratory research in many fields, along
with technological advancements, is intimately linked with the vision of turning our
knowledge of life toward the synthesis of life.
Looking back over the history of protocell development, we can see that there are
many often related avenues that one can take to create a living cell through chemis-
try. We need not only a fundamental knowledge of a variety of subjects, but also our
creativity. A few scientists spent a career exploring the benefits and limitations of the
The Early History of Protocells 15

chosen path described here. In the end, none of these e¤orts has produced a living
cell. But they all asked the important questions, highlighted the challenges, and
shaped our thinking. These attempts to synthesize living cells from chemistry show
that a viable experimental model of a living cell will depend on more than the co-
localization of various essential characters such as the type of molecule, source of in-
formation, and functional metabolism. Higher-order interactive networks must also
be in place to coordinate the form and function of all components in a living cell
with high reliance on the self-organizing properties of the system.
The creation of a self-replicating protocell is only one step toward the synthesis of
life. Our predecessors were interested in not only creation of a self-replicating proto-
cell through chemistry and physics but also the synthesis of a ‘‘protoplasm’’ capable
of evolving into a diverse array of cell types and a communal network of living enti-
ties. Although current e¤orts often focus on the creation of a single synthetic cell, our
history envisions an even larger goal of an interwoven community of synthetic struc-
tures acting and interacting to produce a rich environment suitable not only for the
creation but for the evolution of synthetic life.

Acknowledgments

My sincere thanks and gratitude to Christopher Barbour, Coordinator of Special

Collections, at the Tisch Library Special Collections of Tufts University, and Patricia
Killiard, Head of Electronic Services and Systems, of the Cambridge University
Library, for their assistance in acquiring many of the older references cited in this
chapter.

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of swollen phospholipids. Journal of Molecular Biology, 13, 238 252.
Bungenberg de Jong, von H. G. (1932). Die koazervation und ihre bedeutung fur die biologie. Proto
plasma, 15, 110 176.
Butschli, O. (1892). Untersuchungen über microscopische Schäume und das Protoplasma. Leipzig:
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Carballido Lopez, R. (2006). The bacterial actin like cytoskeleton. Microbiology and Molecular Biology
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Caren, L. D., & Ponnamperuma, C. (1967). A review of some experiments on the synthesis of ‘‘Jeewanu’’
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2 Experimental Approaches to Fabricating Artificial Cellular Life

David Deamer

2.1 Introduction

Recent scientific advances suggest that it may be possible to fabricate an artificial cell
(i.e., a protocell) with most, if not all, of the properties associated with the living
state. At first glance, this might seem to be an impossible task, but life appears to
have arisen spontaneously on the early Earth, so perhaps we can be optimistic. Yet
life did not spring into existence with a full complement of genes, ribosomes, mem-
brane transport systems, metabolism and the DNA ! RNA ! protein information
transfer that dominates all life today. There must have been something simpler, a
kind of sca¤old-life that was left behind in the evolutionary rubble. Can we repro-
duce that sca¤old? One possible approach is to incorporate one or a few genes into
artificial vesicles to produce molecular systems that display the properties of life. The
properties of the system may then provide clues to the process by which life began in
a natural setting of the early Earth, and perhaps lead to a second origin of life, but
this time in a laboratory setting.
What would such a system do? We can answer this question by listing the basic
functions that would be required of artificial cellular life:
 Self-assembled lipidlike molecules form membrane-bounded compartments that en-
capsulate internal molecular machinery.
Macromolecules are encapsulated, but smaller nutrient molecules cross the mem-
brane barrier by di¤usion or through polymer pores.
Energy is captured by a pigment system (light energy), or from chemical energy or
oxidation-reduction reactions.
 A primitive version of metabolism is initiated within the boundary membrane.
 The energy is coupled to the synthesis of activated monomers, and macromolecules
grow by polymerization of the monomers.
20 David Deamer

The membrane-bounded compartment grows by addition of amphiphilic

molecules.
Macromolecular catalysts speed the growth process, and primitive regulatory
mechanisms evolve to control metabolism and polymerization processes.
 Information is captured in the sequence of monomers in one set of polymers, and
used to direct the synthesis of a second set of catalytic polymers, thereby reproducing
the catalysts during growth.
 The membrane-bounded system of macromolecules can divide into smaller
structures.
 Genetic information is passed between generations by duplicating the informa-
tional polymers and sharing them between daughter cells.
 Occasional mistakes (mutations) are made during replication or transmission of in-
formation so that the system can evolve through natural selection.
Looking at this list, one is struck by the complexity of even the simplest form of
cellular life. This is why it has been so di‰cult to ‘‘define’’ life in the usual sense of
a definition, that is, boiled down to a few sentences in a dictionary. Cellular life is a
complex system that cannot be captured in a few sentences, so perhaps listing its
observed properties is the best we can ever hope to do. Despite the apparent com-
plexity, it is also significant that most of the functions have been reproduced in the
laboratory. We can now describe how this set of functions might be integrated into
artificial cellular life.

2.2 Self-Assembly Processes in Cellular Life

All modern cellular life incorporates two processes, which we will refer to as self-
assembly and directed assembly. Spontaneous self-assembly occurs when certain
compounds associate through noncovalent hydrogen bonds, electrostatic forces, and
nonpolar interactions that stabilize orderly arrangements of small and large mole-
cules. A classic example is the manner by which amphiphilic molecules in aqueous
phases form micelles and bimolecular structures (figure 2.1, top panel). Another ver-
sion of self-assembly requires the formation of covalent bonds between similar mo-
lecular species, such as the random polymers of amino acids that can be produced
by energy-dependent condensation reactions (figure 2.1, center). In contrast, the
directed assembly processes characteristic of today involve the formation of covalent
bonds by energy-dependent synthetic reactions, but also require that a coded se-
quence in one type of polymer in some way directs the sequence of monomer addi-
tion in a second polymeric species (figure 2.1, lower panel).
Experimental Approaches to Fabricating Artificial Cellular Life 21

Figure 2.1
Cellular life today uses both self assembly and directed assembly processes to grow. Self assembly (upper
panel) is essential for synthesis and stability of membrane structures and protein folding, whereas directed
assembly (lower panel) underlies the synthesis of proteins according to the base sequences in DNA and
mRNA. We assume that on the early Earth, random polymers similar to peptides and nucleic acids were
produced by a yet unknown synthetic pathway (center). The random polymers, if capable of growth in
a membrane bounded microenvironment, would be subjected to selection and thereby begin biological
evolution.

Spontaneous self-assembly of organic compounds in aqueous phases was presum-

ably common on the prebiotic Earth, and likely involved certain compounds that can
form closed membrane-bound microenvironments. Such boundary structures, and
the compartments they produce, have the potential to make energy available in the
form of ion gradients, and can provide a selective inward transport of nutrients. Fur-
thermore, membranous compartments, in principle, are capable of containing unique
systems of macromolecules. If a yet unknown macromolecular replicating system of
polymers could be encapsulated within a membrane-bounded compartment, the
components of the system would share the same microenvironment (figure 2.2) and
the result would be a major step toward cellularity, speciation, and true cellular func-
tion (Cavalier-Smith, 1987; Conde-Frieboes and Blochliger, 2001; Deamer et al.,
2002; Dyson, 1999; Hutchison et al., 1999; Kock and Schmidt, 1991; Morowitz,
22 David Deamer

Figure 2.2
A protocell would have a minimal set of functional properties, including self assembly of boundary mem
branes, transport of monomers, capture of energy to drive polymerization reactions, and encapsulation of
polymer systems capable of growth.

1992; Ourisson and Nakatani, 1994; Segré, Deamer, and Lancet, 2001; Szostak, Bar-
tel, and Luisi, 2001).

2.2.1 Self-Assembly Processes in Organic Mixtures

What physical properties are required for a molecule to become incorporated into a
stable bilayer? All bilayer-forming molecules are amphiphiles, with a hydrophilic
‘‘head’’ and a hydrophobic ‘‘tail’’ on the same molecule. If amphiphilic molecules
were present in the mixture of organic compounds available on the early Earth, it is
not di‰cult to imagine that their self-assembly into molecular aggregates was a com-
mon process.
It is reasonable to conclude that a variety of simpler amphiphilic molecules can
participate in the formation of membrane structures. The long-chain fatty acids and
alcohols that contribute the amphiphilic property of contemporary membrane lipids
are possible components. Significantly, such simple amphiphiles readily form vesicles
(Apel, Deamer, and Mautner, 2002; Monnard et al., 2002). Stability of the vesicles is
strongly dependent on chain length, pH, ionic strength, amphiphile composition
and concentration, temperature, and head group characteristics. For example, even
a 9-carbon monocarboxylic acid nonanoic acid can form vesicles at concen-
trations of 85 mM and pH 7.0, which is the pK of the acid in bilayers. At this pH,
half of the carboxylic acid groups are protonated, half are anions, and hydrogen
bonding between the protonated and anionic head groups stabilizes the bilayer con-
figuration. Addition of small amounts of a nonanol can also stabilize the bilayers
as a result of hydrogen bonding between the alcohol and acid head groups, so
that vesicles form at lower concentrations (@20 mM) over a pH range from 7 to
Another Random Scribd Document
with Unrelated Content
and in perfect accord with the physical wants and moral necessities
of the race.
But the mere covering of the head, or the mere protection of the
brain, is not all that distinguishes the different races in these
respects. The beard is equally radical and universal, though not so
palpable a specialty as color, and in some respects it may be said to
be a more important one. The Caucasian alone has a beard, for
though all others approximate to it in this respect, it is the only
bearded race, and some writers on ethnology have been so impressed
with this imposing and striking distinction that they have sought to
make it the basis of a classification of races. And there certainly is no
physical or outward quality that so imposingly impresses itself on the
senses as a mark of superiority, or evidence of supremacy, as a full
and flowing beard. Color, when in repose, or when it does not give
expression to the inner nature, does not, in reality, constitute a
distinction at all, but the beard is an evidence of superiority, that,
however varied the action or whatever the circumstances, is equally
distinct and universal as an attribute of supremacy. This is
sufficiently illustrated in our own race and our every day experience.
The youth is beardless, and pari passu as he approaches to the
maturity of manhood there is a corresponding development of beard.
The intellect—the mental strength—the moral beauty, all the
qualities of the inner being, as well as those outward attributes
tangible to the sense, harmonize perfectly with the growth of the
beard, and when that has reached its full development, it is both the
signal and the proof of mature manhood—an exact admeasurement
and absolute proof of the maturity of the individual as well as the
type and standard of the race. This is equally true when applied to
different races. The Caucasian is the only bearded race, but all others
approximate in this respect, and the negro is furthest removed of all,
for the tropical woolly-haired African or negro, except a little tuft on
the chin and sometimes on the upper lip, has nothing that can be
confounded with a beard. People sometimes see negroes with
considerable hair on their faces, and hence conclude that they are as
likely to have beards as white men; but they forget that all in our
society who are not whites are considered negroes, and therefore
those bearded negroes have a large infusion, and doubtless
sometimes a vastly predominating infusion of Caucasian blood. The
beard symbolizes our highest conceptions of manhood—it is the
outward evidence of mature development—of complete growth,
mental as well as physical—of strength, wisdom and manly grace,
and the full, flowing, and majestic beard of the Caucasian, in contrast
with the negro or other subordinate races, is as striking and
imposing as the mane of the lion when compared with the meaner
beasts of the animal world. Like color or any other of the great
fundamental facts separating races, the beard is sufficient to
determine their specific character and their specific relations to each
other, and we have only to apply our every day experience as regards
this outward symbol of inner manhood to measure the relative
inferiority of the negro. The Abolitionists demand that the “equal
manhood” of the negro shall be recognized, and complain bitterly of
a government that refuses to respond to their wishes in this respect,
but if this “equal manhood” was actually revealed to them in the
person of the negro as it is in the persons of white men, and as God
has alone provided and ordained or permitted it to be revealed, they
would be overwhelmed with astonishment or convulsed with
laughter. A negro with a full and flowing beard, with this symbol of
perfect manhood or with this outward manifestation of the inner
(Caucasian) being, would be a ludicrous monstrosity, as impossible,
of course, as the Caliban of Shakespeare; but if such a supernatural
being should suddenly make his appearance in an Abolition
conventicle, the “friends of humanity” would be as much astonished
as if an inhabitant of another world had come among them. A youth,
with the majestic and flowing beard of adult life, if the monstrosity
did not shock and disgust us, would be irresistibly comical, and
equally so in the case of the childish and romping negro. Thus, were
the leaders of the “anti-slavery enterprise” busily engaged in
discussing the “equal manhood” of the negro, and in earnestly
denouncing those who, unable to see it, decline to admit such a
thing, and a negro should enter the room with the actual proof of its
existence—with the full, flowing beard of the Caucasian, and
therefore the outward symbol of an “equal manhood,” as the hand of
the Eternal has revealed it in the person of the former—the whole
Abolition congregation, if not paralyzed with horror, would burst
into uncontrollable laughter. The wrongs of the “slave,” the cruelties
of the master, the “hopes of humanity,” the most doleful stories and
the saddest tales of the suffering “bondmen,” would be interrupted
by screams of laughter at such a ludicrous spectacle as a negro with
the majestic and flowing beard of the white man. This outward
symbol of complete manhood, or this external indication which
typifies the high nature and lofty qualities of the Caucasian, is no
more impossible, however, to the negro than that “equal manhood”
which is demanded for him, and therefore were the “friends of
humanity” to vary their programme and demand an “equal” beard, or
that we shall grant the negro the full and flowing beard of the
Caucasian, they would render their performances more interesting
without giving up any of their “principles,” as the absurdity is exactly
the same in either case.
 CHAPTER VIII.
THE FEATURES.

The features reflect the inner nature, the faculties or specific

qualities, and they are distinct or indistinct, developed or
undeveloped, as we ascend or descend in the scale of being. In the
simpler forms of animal existence, there is close resemblance to
vegetable life in this respect; but ascending to the vertebrata, and
especially the mammalia, there is a broad distinction between the
head and body, and instead of an undefined uniformity pervading
the whole exterior surface, the face becomes a centre in which the
essential character of the creature is written by the hand of Nature. It
is true, that the general form of the body is significant of the grosser
qualities. The muscular and motive forces of the horse are evidently
designed for swiftness; those of the lion, and the felinæ generally, are
designed both for strength and swiftness; while that of the ox and
other mammalia is adapted to a negative kind of strength which
results from a combination of all the physical forces, and not, as in
the former case, from an excessive muscular development. But the
higher qualities, even in animals, are legibly written in the face or
features. In the human creation, of course, this external reflection of
the inner nature in the features becomes vastly more distinct and
real, and in our own race not unfrequently does the face become a
very window of the soul, where may be read the sweetest and most
exquisite emotions of a sensitive and delicate nature, or, as
sometimes happens, the gross and sensual thoughts of a depraved
and perverted one. There are, indeed, countless and innumerable
variations in our own race in this respect. The white or Caucasian
men of Asia, of Africa, Europe, and America, are so modified by
climate, habits, government, religion, etc., that those ethnologists
who are not anatomists have sometimes confounded them, and
classed them as distinct species. Even on the same continent, in the
same country, sometimes the same family, these variations are so
marked that they always seem to belong to different species. The
globular head, broad forehead, oval cheeks, straight nose, and
distinct, well-defined lips and mouth, however, whatever may be the
expression, always remain the same, and can never be confounded
with any other race of men. And these modifications in the Caucasian
are not confined to the face, but pervade the whole surface. White,
black, and red hair, white skin and brown ones, blondes and
brunettes, are often found in the same family. It is even so in regard
to size—some are short and others tall—some pigmies while others
are giants—and not unfrequently in the same household, while the
same nation exhibits every possible variety in this respect. The
Caucasian race alone presents these variations—the other races great
uniformity; and the negro, lowest in the scale, presents an almost
absolute resemblance to each other. Of all the millions that have
existed on the earth, their hair not only in color but in form has been
absolutely the same, and such a being as a different-colored or
straight-haired, or long-haired negro never existed. On visiting a
plantation at the South, one sees a thousand negroes so nearly alike,
that except where wide differences of age exist, they are all alike, and
even in size rarely depart from that standard uniformity that nature
has stamped upon the race. The entire external surface, as well as his
interior organism, differs radically from the Caucasian. His muscles,
the form of the limbs, his feet, hands, pelvis, skeleton, all the organs
of locomotion, give him an outward attitude that, while radically
different from the Caucasian, approaches an almost absolute
uniformity of character in the negro. His longitudinal head, narrow
and receding forehead, flat nose, enormous lips and protuberant
jaws, in short, his flat, shapeless and indistinct features strikingly
approximate to the animal creation, and they are as utterly incapable
of reflecting certain emotions as so much flesh and blood of any
other portion of his body. The Almighty and All-Wise Creator has
made all things perfect, and adapted the negro features, as well as
those of the white man, to the inner nature, but if it were true that
the negro had certain qualities with which ignorance and delusion
would endow him, then it would be quite evident that the Almighty
Creator had made a fatal blunder in this case, for it is clearly a matter
of physical demonstration that the negro features cannot reflect
these qualities. The features of the animal are made to express its
wants, to reflect the nature God has given it. We witness this every
day among our domestic animals—the cat, the dog, the horse, all
exhibit their qualities, their wants, their moods, at different times
their anger, suffering, and affection, all that their natures are capable
of, are reflected in their faces, and we understand them. In our own
race, the transparent skin, the deeply cut and distinct features
become often a perfect mirror of the inner nature, and reflect the
nicest shades of feeling as well as the deepest emotions of the soul.
Envy, anger, pride, shame, scowling hate and malignant fear, as well
as gentle affection and the most exalted love, are written as legibly in
the face as if they were things of physical form, and their
innumerable modifications and variations are witnessed all about us,
and every day of our lives. How grandly this is displayed in the case
of the orator! This must have been apparent to those who heard Mr.
Clay in the Senate, and saw those wonderful changes of feature—one
moment convulsed with anger, then lit up with genius, or with pride
and pomp of conscious power, and in another reflecting, perhaps, all
a woman’s sweetness or a child’s gentleness. Color, of course, is
essential to this, for a display of the passions and emotions on the
dark ground-work of the negro skin would be as impossible as a
rainbow at midnight, but without the deeply cut and distinctly
marked features of the Caucasian, color would be comparatively
useless in reflecting the grander emotions of the soul. Any one
referring to his own experience for a moment will see how
impossible, as a mere physical matter, that the negro face can reflect
the qualities attributed to him by those who are ignorant of his real
nature. The narrow and receding forehead, the shallow eyes, flat
nose, almost on a level with the cheeks, the protruding and
enormous lips,—the only thing that really can be said to be distinct in
the negro face,—the tout ensemble without form or meaning when
contrasted with the white man, is, in connection with the color, the
dark ground of the negro skin, clearly incapable of reflecting certain
qualities of our own race. The negro has, of course, moral emotions,
as have all human creatures, and his face, like that of the Caucasian,
is capable of reflecting all his wants, his likes and dislikes, his hopes
and fears, but every one who has seen him must know that the
higher qualities of the Caucasian cannot find expression in the negro
features, and therefore he does not possess those qualities, or, as has
been said, the All-Wise and Almighty Creator of all has committed a
fatal mistake, and unjustly endowed him with qualities which he is
forever forbidden to express!
 CHAPTER IX.
LANGUAGE.

A few years since, an eminent historian, in a public lecture,

discussed the probabilities of a universal language as an instrument
of universal history, and as means for the universal civilization of
mankind! Another public lecturer discussing this subject, and on a
professedly scientific basis, held that language had a miraculous
origin, though the period when this supernatural gift was conferred
on man was left wholly to the imagination of his audience. Others,
and among them Buffon, Pritchard, and even several ethnologists,
have scarcely risen above this nonsense, while their uses or
application of this faculty have been vastly more injurious to science
than even their original misconceptions on the general subject.
Language is naturally divided into two distinct and widely
separated portions, having no necessary connection, though at
certain points or stages uniting and combining together. First, is that
universal capacity of expressing itself—its wants, its sufferings, and
its enjoyments—which God has given to all His creatures, from the
insect at our feet to the Caucasian man standing at the head of this
vast and innumerable host of living beings. In the second place, in its
structure and arrangement into parts or portions of speech; in short,
its grammatical construction. With the former it is alone or mainly
proposed to deal in this place, though it will be necessary
occasionally to refer to the latter. As has been said, all living or rather
all animal beings have the faculty of expressing their wants, and they
have a vocal organism in exact correspondence with these wants and
the purposes for which they are designed by the common Creator of
all. Except to a few laborious and enthusiastic students of natural
history, the vast world of insect life is a terra incognita, but each one
of these myriad of beings is adapted to some specific purpose and
beneficently designed by the Almighty Master of Life for the same
universal enjoyment which is so distinctly revealed as the end of
their existence in the more elaborately organized and higher
endowed classes of animal being. And millions of these minute and
often unseen creatures are daily and hourly singing praises to the
Almighty Creator for His infinite goodness, rendering the fields and
forests vocal with the music of their gratitude and the exuberance of
their enjoyment. As we ascend in the scale of animated existence, the
vocal faculty or language becomes still more distinctly revealed, with
a vocal apparatus or organism in exact correspondence with the
function or faculty that God has given to the being in question. The
pigeon, of course, cannot give us the notes of the canary bird, nor the
owl sing the songs of the nightingale. The serpent cannot exchange
his hiss for the growl of the tiger, nor the ass abandon its uncouth
utterances for the mighty roar or the majestic voice of the lion. Each
is permitted to express its wants, its sufferings, and its joys, and each
is provided with a vocal organism specific and peculiar to itself and
to its kind, and in accord with the universal law of adaptation which
inseparably unites organism with function. This, then, in its
elementary form, is language—a faculty common to the animal
world, and a necessity of animal existence. It differs in no essential
respect in regard to human beings, or it varies no more from that of
the animal world than other functions or faculties of the human
being. There is, it is true, a point of departure or divergence where
the analogies of the animal world are no longer applicable to human
beings, or where animal beings cannot furnish parallels for those
endowed with a moral nature and destined for immortality; but a
vocal organism with its corresponding faculty or function is
essentially the same thing in both, and differs only in form and
degree among the innumerable beings that compose or are
comprised within the vast world of animated existence. While
language, therefore, the voice or faculty by which animals as well as
human beings express their wants, is universal and only varied as the
structure and nature are varied, and while the vocal organism is in
exact harmony with the faculty or function in all cases and in every
phase of animated existence, there is also, and of necessity, a specific
modification of this faculty in the case of the several human races or
species. The vocal organs of the negro differ widely from those of the
white man, and of course there is a corresponding difference in the
language. The specific or the most essential feature of the negro
nature is his imitative instincts, or his capacity for imitating the
qualities and for acquiring the habitudes of the white man. This, of
course, is limited to his actual juxtaposition with the superior race,
for aside from that organic necessity which utterly forbids its being
otherwise, there is no historical fact better attested than that which
shows him invariably relapsing into savageism whenever he is left
without the restraining support of the former. But for wise and
beneficent purposes, God has endowed him with a capacity of
imitation, and he is enabled to apply it to such an extent that those
ignorant of the negro nature actually offer it as a proof of his equal
capacity! But with all his power to thus imitate the habits and to copy
the language of the white man, it is not possible that a single example
can be furnished of his success in regard to the latter. With us, and
especially at the North, all are negroes who are tainted with negro
blood, and thus many persons will imagine that they have seen
negroes who were as competent to speak our language as white men
themselves. But no actual or typical negro will be able—no matter
what pains have been taken to “educate” him—to speak the language
of the white man with absolute correctness. European ethnologists
have, notwithstanding, sought to make language the means for
tracing the history and determining the character of races, the
worthlessness and indeed the absurdity of which only needs a single
illustration to expose it. The negroes of Hayti have imitated or copied
the language of their former masters, the French, therefore they are
of the same race, and the future ethnologists would pronounce them
Frenchmen! As the negro cannot preserve anything that he copies
from the Caucasian beyond a certain period, the negroes of that
island are rapidly losing all that they obtained from their former
masters, and though the educated portion on the coasts, and
especially the mongrels, yet retain the French language, those in the
interior are rapidly relapsing into their native African tongue. And a
century or two hence, when the French is entirely extinct and the
existing negro population speak an African dialect, or what is far
more probable, speak our own, the ethnological enquirer would
decide that those led by Touissant and Christophe in the war of
“Independence” were Frenchmen instead of Negroes, because,
forsooth, the public documents of the time showed they spoke the
French language! Thus, while language is an important means for
tracing nationalities or varieties of our own race, as, for example, the
modern Spanish, French, Italian, etc., in connection with the great
Latin family of southern Europe, it is simply absurd to apply it to
distinct species like Caucasians and negroes. Each race or each
species, as each and every other form of life, is in perfect harmony
with itself, and therefore the voice of the negro, both in its tones and
its structure, varies just as widely from that of the white man as any
other feature or faculty of the negro being. Any one accustomed to
negroes would distinguish the negro voice at night among any
number of those of white men by its tones alone, and without regard
to his peculiar utterances. Tones or mere sounds are of course
indescribable, and therefore no comparison in this respect is
possible, but all those familiar with the tones of the negro voice know
that it is never musical or capable of those soft and sweet inflections
or modulations common to our own race. Music is to the negro an
impossible art, and therefore such a thing as a negro singer is
unknown. It is true that, a few years since, certain amiable people,
both at the North and in England, believed for a time that they had
secured a prodigy of this kind in the person of the “Black Swan,” but
after a careful and patient trial, it was found to be a mistake. She was
not even a negress, though perhaps of predominating negro blood,
and was aided and encouraged by every possible means, especially in
England, where she was actually placed under the care of Queen
Victoria’s music master, but without avail—Nature was superior to
art—the laws of God more potent than those of human invention—
and the “Black Swan” finally disappeared from public view. The
negro is fond of music, as are all other beings, and indeed all animal
beings of the more elevated classes, but music is to him merely a
thing of the senses. With the white race music is perceived as well as
felt—an intellectual as well as sensuous thing—and though it by no
means follows that intellectual persons, with minds above the
common average, should also have musical powers, that sensitive
and exquisite organization which is necessary to a musical genius
must be united with a brain of corresponding complexity. The brain
and the nerves constitute a whole—a system—however widely
portions of the latter may diverge in their especial functions, and it is
as impossible that the musical temperament, or that the elaborate
and exquisitely sensuous system of the Caucasian could be united
with the brain of the negro, as it would be to unite the color of the
former with the negro structure. The negro, therefore, neither
perceives nor can he give expression to music—he has neither the
brain nor the delicacy of nerve nor the vocal organism that is
essential to this faculty—all that is possible to him is a certain
approximation through his wonderful powers of imitation, but which
is less available to him in this respect perhaps than any other. His
brain is much smaller, but his nerves are much larger, and his senses
are consequently much more acute, and here is the cause of that
“musical power” with which ignorant and mistaken persons have
endowed him. Music is felt by the nerves rather than perceived by
the brain, in his feet as much as in his head, and with an intensity
unknown and unfelt by whites. His imitative instinct enables him to
rapidly acquire the language of his master, but he also loses it with
similar rapidity. The negroes imported to the West India Islands,
though living on large plantations, soon acquired the language of the
few whites, so far as words were concerned, but an organic necessity
compelled them to retain the structure of their original tongue. Thus,
those in British islands spoke English, in French islands, French,
etc., but the general structure remained the same in all, and now,
when the external force applied by the several European
governments has removed the control and guidance of the superior
race, they are rapidly losing the words of their former masters, and in
this as well as every other respect returning to their native
Africanism. In Hayti, where the imitative capacity has little or
nothing to stimulate it, this process is very rapid indeed, and could
they be entirely isolated, the utter extinction of the French language
would doubtless occur within the present century.
 CHAPTER X.
THE SENSES.

The senses are those special organisms that connect us with the
outer world through which external impressions are received and
transmitted to the brain—the great sensorium or centre of the
nervous system. They are popularly designated as sight, hearing,
smelling, touch, and taste, each having its own peculiar organism;
some, as sight, exceedingly elaborate, and others, like taste, quite
simple, being little more than a delicate expansion of nervous matter
spread upon the tongue and lining the inner surface of the mouth.
The nervous system includes the brain and the nerves, but is, in fact,
an indivisible whole, of which the brain forms the centre, and the
nerves the circumference, in exact proportion as we ascend in the
scale of being. The centre of the nervous system is increased and the
circumference diminished as the brain becomes larger and the
nerves smaller. Among quadrupeds—the horse, for example—the
nerves are enormously large in comparison with the brain of that
animal; and this holds good throughout, so that an intelligent
physiologist might determine the possible capabilities of any of the
higher order of animals by a simple comparison of the brain and
nerves. And in the human creation a single skull of a Mongol, or
Malay, or Negro, and especially of the latter, should be quite
sufficient to enable a physiologist to comprehend the essential
character of the race to which it belonged. True, he might, as has
often happened, mistake it for an abnormal specimen of the
Caucasian, and thus display a vast amount of learned nonsense of the
Gall-Spurzheim order, but if he knew it to be an actual negro skull,
and then compared it with that of the Caucasian, he should be able
not only to determine the intellectual inferiority, but the vastly
preponderating sensualism of the former. He would see that the
relatively small cerebrum, and the large cerebellum, must be united
with a corresponding development of the senses, and a
comparatively dominating sensualism. The mere organism of the
senses, of sight, hearing, etc., though of course differing widely from
those of the Caucasian, it is not necessary to describe, for even in
animals of the higher class there is a certain resemblance, and the
student of anatomy studies the mechanism of the eye in the ox or
horse as satisfactorily as in that of the human creature.
The organisms while thus, in a sense, similar—of the eye, for
example—in whites and negroes, is more elaborately and delicately
constituted in the case of the former, and therefore it is also vastly
more liable to disease, to congenital defects, to strabismus, etc., and
especially short-sightedness. The negro, on the contrary, rarely
suffers from these things, or even from inflammation of the eyes, so
common among white people, and though, in keeping with the
imitative instinct of the race, the negro “preacher” dons spectacles as
well as white neck-cloth, it may be doubted if there ever was a case of
near-sightedness in the typical negro. Though in extreme old age
they doubtless lose the power of vision common to their youth, it is
rare that negroes need spectacles at any age. The organism is
supplied with a larger portion of nervous matter than in the case of
the whites, and the function or sense is thus endowed with a strength
and acuteness vastly greater than are the senses of the Caucasian.
Travelers and others mingling among savages, Indians, negroes, etc.,
have observed the extraordinary power and acuteness of the external
senses, and have supposed that this was a result of their savage
condition, which, calling for a constant exercise of these faculties,
gave them an extraordinary development. And Pritchard, carrying
this theory or notion to an extreme, inferred that men were originally
created negroes, for the exigencies of savage life demanded, as he
supposed, a black color as well as acuteness of the senses! Doubtless
the civilized negro of America ordinarily displays less strength and
acuteness of sense than his wild brother of Africa, but he is born with
the same faculties, and were the surrounding circumstances changed
so as to call them into more active exercise, he would exhibit similar
characteristics.
The Almighty Creator, with infinite wisdom, has adapted all His
creatures to the ends or purposes of their creation. The Caucasian or
white man, with his large brain and elevated reasoning powers, is
thus provided with all that is necessary to guard his safety and to
increase his happiness. Inferior races, with smaller brains and
feebler mental powers are endowed with strength and acuteness of
the external senses which enable them to contend specifically with
surrounding circumstances and to provide for their safety. This is
strikingly manifest in the North American Indian who marks or
makes a trail in the forest which he follows with unerring confidence,
though the eye of the white man sees nothing whatever. The
descriptions of Indian character in Cooper’s novels are in these
respects perfectly correct and true to nature, as are all those of the
Indianized white man, Leather-Stocking, Hawkeye, etc. The one
depends upon his senses—his sight, hearing, etc., the other on his
powers of reasoning or reflection, which in the end enable him to
“sarcumvent” his Huron enemies and to win the victory. Each,
according to his “gifts,” is able to fulfil the purposes of his creation,
and while the superior intelligence of the Caucasian is spreading that
race, with its benign and civilizing consequences, over the whole
northern continent, the strength and acuteness of his senses have
enabled the Indian to resist to a degree all these mighty forces for
three hundred years.
Some historians have advanced the notion that Rome was overrun
by northern barbarians, similar to our North American Indians, but
if the mighty hordes led by Alaric and Genseric to the conquest of
Italy, had been Indians, not one would have escaped to tell the tale of
their destruction. A high civilization, rotten at heart, falls an easy
conquest to ruder and more simple communities of the same race—
thus, the effete and corrupt Roman aristocracy fell before the simple
and rude populations of Northern Europe, as the polished and
scholastic Greeks had succumbed to the Romans, when the latter
practised the simple and hardy virtues of their earlier history. In our
own times we have seen Spain, long ruled over by an effete and
worn-out aristocracy, sink from a first class to a fourth rate power,
while France, relieved from the dead weight of “nobility,” has in half
a century become the leading power of the world. And if the English
masses have not sufficient vitality to cast off the mighty pressure of a
diseased and effete aristocracy by an internal reform like that which
the French passed through in 1789, then it is certain that, at no
distant day, the nation will fall a conquest to some external power
that has greater vitality than itself, however deficient it may be in
wealth and learning, and those refinements that pass for high
civilization. But while nations ruled over by privileged classes thus
carry within them the seeds of their own destruction, and sooner or
later fall a conquest to ruder and simpler societies, the intellectual
superiority of the white man always enables him to conquer inferior
races, whatever may be the disparity of numbers, and Clive with
three thousand Europeans, attacking the Hindoo horde of one
hundred thousand, or Cortez invading Mexico with five hundred
followers, amply illustrates the natural supremacy of the Caucasian
race. But, on the contrary, if the Aztecs had had the intellectual
capacity of the Caucasian superadded to their own specific qualities
—the strength and acuteness of the senses—common to the native
race, not alone would Cortez have failed to conquer them, but it may
be doubted if all Europe, combined together for that purpose, could
have accomplished it.
There are no examples for testing the capabilities of negroes in
these respects, for there is no instance in history where they have
contested the supremacy of the white man, the insurrection in Hayti
having been the work of the “colored people” and mulattoes, and the
negroes only forced into it by their fears after the outbreak was
complete. But we have the actual physical facts as well as our every-
day experience of the negro qualities, and therefore can arrive at
positive truth when comparing him with the superior race. The large
distribution of nervous matter to the organs of sense and consequent
dominating sensualism (not mere animalism), is the direct cause of
that extreme sloth and indolence universal with the race. The small
brain and limited reasoning power of the negro render him incapable
of comprehending the wants of the future, while the sloth dependent
on the dominating sensualism, together with strong animal appetites
impelling him always to gross self-indulgence, render a master guide
or protector essential to his own welfare. Indeed it may be matter of
doubt which is the paramount cause of the negro’s inability to
provide for future necessities—his limited reasoning power or his
indolence—his small brain or his dominating sensualism. It is a
statistical fact that “free” negroes do not produce sufficient for their
support, and consequently that they tend perpetually to extinction,
and when it is remembered that the small brain and feeble
intellectual power render them incapable of reasoning on the future
rewards of self-denial, and that the large distribution of nervous
matter in the organs of sense, and the consequent sensualism impels
them to gross indulgence of the present, and moreover that they are
in juxtaposition, and must contend with white people, then it is plain
enough to see that it could not be otherwise, and that the total
extinction of these unfortunate beings is necessarily a question of
time alone.
But it is not the mere predominance of the senses, or the strength
and acuteness of the sense which so broadly and radically separates
whites and negroes. They are entirely different in the manifestations
of these qualities. As has been observed, there are few if any near-
sighted negroes, or negroes with other defects of vision, and the
sense of smell in negroes permits them to discriminate and to
indicate the presence of the rattle snake, or other venomous
serpents. And in respect to the sense of touch or feeling, the
peculiarity of the negro nature is perhaps most remarkable of all.
This sense in the white person, though universal of course, is mainly
located in the hand and fingers. Sir Charles Bell, an eminent English
surgeon, has written an interesting work—one of the Bridgewater
treatises—on the flexibility and adaptation of the human hand, and
other volumes might be given to the world without exhausting the
subject. The universal law of adaptation, indeed, demands that the
sense of touch, the flexibility of the hand, the delicacy of the fingers,
should be in accord with the large brain and commanding intellect,
otherwise the world itself would long since have come to a stand-still,
and human invention ended with the antediluvians. It is true the
structure—the arrangement of the bones, muscles, tendons, etc., in
short, the mere mechanism of the hand, is essential, but without the
sense of feeling, or that delicacy of touch found only in the fingers of
the Caucasian, the mechanical perfections of the hand would be
comparatively useless.
All the nice manipulations in surgery, in the arts, in painting,
statuary, and the thousands of delicate fabrics seen every day and all
about us, demand both intellect and delicacy of hand, and these, too,
in that complete perfection found alone in the Caucasian. The sense
of touch, on the contrary, in the negro is not in the hand or fingers,
or only partially so, but spreads all over the surface and envelops the
entire person. The hand itself, in its mere mechanism, is
incompatible with delicate manipulation. The coarse, blunt, webbed
fingers of the negress, for example, even if we could imagine delicacy
of touch and intellect to direct, could not in any length of time or
millions of years be brought to produce those delicate fabrics or work
those exquisite embroideries which constitute the pursuits or make
up the amusements of the Caucasian female. The mechanism of the
negro hand, the absence or rather the obtuseness of the sense of
touch in the fingers, and the limited negro intellect, therefore, utterly
forbid that negroes shall be mechanics, except it be in those grosser
trades, such as coopers, blacksmiths, etc., which need little more
than muscular strength and industry to practice them. But the sense
of touch, though feeble in the hand or fingers, is none the less largely
developed as are the other senses of the negro, and spreads over the
whole surface of the body. This is witnessed every day at the South,
where whipping, as with Northern children, is the ordinary
punishment of negroes. As in all other foolish notions that spring
from the one great misconception—that negroes have the same
nature as white people, the “anti-slavery” people of the North and of
Europe labor under a ludicrous mistake in respect to this matter.
They take their notions of flogging from the practice of the British
army and the Russian knout, where strong men are cut to pieces by
the “cat” or beaten to death by clubs, and they suppose that precisely
similar barbarity is practiced on the “poor slave.” And the runaway
negro has doubtless added to these notions, perhaps, without
meaning it. At Abolition conventicles he is expected, of course, to
horrify the crowd with awful tales of his sufferings, but having always
had plenty to eat and never overworked, he has really nothing to fall
back on but the “cruel whippings,” which the imaginations of the
former readily transform into their own notions, but which, in fact,
correspond to that which they deal out to their own children without
a moment’s compunction. The sensibility of the negro skin closely
resembles that of childhood, and while there are doubtless cases of
great barbarity in these respects, as we all know there are in cases of
children, the ordinary flogging of negroes is much the same as that
which parents, guardians, teachers, etc., deal out to white children,
and the “terrible lash” so dolefully gloated over by the ignorant and
deluded usually dwindles down into a petty switch in reality. But it is
painful to the negro, perhaps more so than hanging would be, for
while the local susceptibility of the skin makes him feel the slightest
punishment in this respect, the obtuse sensibility of the brain and
nervous system generally would enable him, as is often manifest, to
bear hanging very well. Those who can remember being flogged in
childhood will also remember the great pain that it gave them,
though now in their adult age they would laugh at such a thing. The
negro is a child forever, a child in many respects in his physical as
well as his mental nature, and the flogging of the negro of fifty does
not differ much, if any, from the flogging of a child of ten, and while
the British soldier or Russian would receive his three hundred lashes
without wincing, the big burly negro will yell more furiously than a
school-boy when he receives a dozen cuts with an ordinary switch.
 CHAPTER XI.
THE BRAIN.

The brain is the seat or the centre of the intellect, in short, the
mental organism. The “school men” believed that mind, intellect, the
reasoning faculty, whatever we may term it, had no locality or
organism, but, on the contrary, was some impalpable, shadowy,
unfixed principle that existed as much in the feet or hands as in any
other portion of the body. And even Locke and Bacon, while they
promulgated the great truths of inductive philosophy, were not
sufficiently grounded in its elementary principles to understand
clearly the foundation of their own doctrines. Nor did Dugald Stuart,
Dr. Brown, or even the great Kant, of more modern times,
understand any better the fixed truths on which rest the vast and
imperfect systems of philosophy which they labored so assiduously
to build up in their day. It remained for Gall, Spurzheim, and their
followers to do this—to demonstrate certain great elementary truths
which form a foundation, eternal as time itself—for the mental
phenomena to rest upon, and whatever advance may be made
hereafter in the study of these phenomena, its basis is immovable.
Metaphysicians were wont to shut themselves up in their libraries
and to analyze their own emotions, etc., which when noted down,
became afterwards the material for ponderous lectures or the still
more ponderous volumes inflicted on society. Rarely, perhaps, were
these speculations connected with the brain—indeed it is a rare thing
to find a physiologist indulging in metaphysical speculation, while
the most famous among the “philosophers” were profoundly
ignorant of that organ, though they fancied they knew all about its
functions! The man that should undertake to write a treatise on
respiration, and at the same time was utterly ignorant of the
structure of the lungs, or to give a lecture on the circulation, while he
knew nothing of the blood vessels, would certainly be laughed at, and
yet innumerable volumes have been written, and continue to be
written, on the functions of the brain or on “moral and mental
philosophy,” by men who never saw a human brain in all their lives!
Gall and Spurzheim did, therefore, a great good to the world when
they began their investigations of the laws of the mind, by the study
of the brain itself as the first and absolutely essential step to be taken
in these investigations. It is true, they, and especially their followers,
sought to set up a fancy science under the name of Phrenology, and
the former thus, to a great extent, neutralized a reputation which
otherwise would have secured the respect of the scientific world. And
it is also true that others before them had recognized the same truths
with more or less distinctness, but it is certain that Gall and
Spurzheim demonstrated and placed beyond doubt the great, vital,
and essential truth that the brain is the organ of the mind, and that
the mental capacity, other things being equal, is in exact proportion
to the size of the brain relatively with the body. This truth holds good
throughout the animal world, and the intelligence of any given
animal or species of animal, is always in keeping with the size of the
brain when compared with the size of the body.
The brain is composed of anterior and posterior portions—of the
cerebrum and the cerebellum—the first the centre of intelligence, the
latter of sensation, or the first the seat of the intellect, and the latter
of the animal instincts, and the proportions they bear to each other
determines the character. As the anterior portion is enlarged and the
posterior diminished the creature ascends, or as the anterior portion
is diminished and the posterior portion enlarged it descends, in the
scale of being. These are the general laws governing men and
animals. There is intelligence in proportion to the size of the brain
compared with that of the body, and in the former there is
intellectual capacity—latent or real—in proportion to the enlarged
cerebrum and diminished cerebellum. It is true we see every day
seeming contradictions to the laws in question, but they are not so,
not even exceptions, for they are not general but universal. Every day
we meet people with small heads and great intelligence, with large
heads and large stupidities, but a closer examination may disclose
the truth that the seemingly small head is all brain, all cerebrum, all
in front of the ears, while the large one is all behind, and only reveals
a largely developed animalism. And even when this is not sufficient
to explain the seeming anomaly, there is a vast and inexhaustible
field for conjecture—of accident—where misapplied or undeveloped
powers have been the sport of circumstances. A man may have a
large brain, great natural powers, in truth, genius of the most
glorious kind, and the world remain in total ignorance of the fact,
and among the countless millions of Europe doomed generation after
generation to a profound animalism, there doubtless have been
many “mute inglorious Miltons,” who have lived and died and made
no sign of the Divinity within. On the contrary, there have been men
of much distinction—of great usefulness to their fellows and to the
generations after them, who, naturally considered, were on the dead
level of the race, but by their industry, perseverance, and energy have
left undying names to posterity. Then, again, circumstances have
made men great. An epoch in the annals of a nation—great and
stirring events in the life of a people—stimulate and call into exercise
qualities and capacities that make men famous, who otherwise would
not be heard of. Our own great revolutionary period furnished
examples of this, and still later, we have Jackson, Webster, Clay,
Calhoun, and their senatorial cotemporaries, who many doubtless
think will never be equalled, though their equals in fact are in the
senate now, and only need similar circumstances to manifest that
equality.
The organism of the race—the species—whether human or animal,
never changes or varies from that eternal type fixed from the
beginning by the hand of God; and men, therefore, are now, in their
natural capacities what they always have been and always will be,
whatever the external circumstances that may control or modify the
development of these capacities. And the brain being the organ or
organism of the mind, as the eye is of the sight or the ear of the sense
of hearing, it may be measured and tested, and its capabilities
determined, with as entire accuracy as any other function or faculty.
Not, it is true, as the phrenologists or craniologists contend, that the
brain reveals the character of individuals of the same species, but the
character of the species itself, and its relative capabilities when
contrasted with other races or species of men. This is beyond doubt
or question, or will be beyond doubt or question with all those who
understand it, and taking the Caucasian as the standard or test, the
capabilities of the Mongol, the Malay, the Aboriginal American, or
negro, may be determined with as absolute certainty as the color of
their skins or any other mere physical quality. The brain of the
Caucasian averages ninety-two cubic inches, that of the negro
seventy-five to eighty-five inches, while the bodily proportions can
scarcely be said to vary. There are great variations among whites as
to size—there are giants as well as dwarfs, and quite as great variety
in the form,—from the “lean and hungry Cassius,” to the rounded
proportions of a Falstaff or Daniel Lambert. But on a Southern
plantation of a thousand negroes, sex and age are the only difference
or the principal difference that one sees, and a stranger would find
some trouble to recognize any other, or at all events to distinguish
faces. The brain of the negro corresponds in this respect with the
body, and though there are doubtless cases where there is some
slight difference, there seems to be none of those wide departures
witnessed in these respects among whites.
The material, the fibre or texture of the brain itself is little
understood, and though it is quite likely that what we call genius is
attended by a corresponding delicacy or fineness of texture in the
nervous mass, and future exploration in this abstruse matter may
reveal to us important truths, at this time little is known in regard to
the brain except the great fundamental and universal law that, in
proportion to its size relatively with that of the body is there
intellectual power, actual or latent. Many, doubtless, fancy that there
are immense differences in men in this respect—that a Webster, or
Clay, or Bonaparte are vastly superior to common men—but they
have only to remember that the brain is the organ of the intellect, to
see its fallacy. The notion has sprung from the habitudes of
European society, where a man clothed in the pomp and parade of
high rank is supposed to be vastly and immeasurably superior to his
fellows, while, in truth, most of these, or, at all events many of these
are absolutely (naturally) inferior to the base multitudes that
prostrate themselves in the dust at their feet. Nevertheless, there are
striking differences in these respects; not more so, however, than in
strength of body, beauty of features, difference of hair, complexion,
etc. But in the case of the negro there is an eternal sameness, a
perpetual oneness, the same color, the same hair, the same features,
same size of the body, and the same volume of brain. All the physical
and moral facts that make up the negro being irresistibly lead to the
conclusion that the Almighty Creator designed him for juxtaposition
with the superior white man, and therefore such a thing as a negro
genius—a poet, inventor, or one having any originality of any kind
whatever—is totally unnecessary, as they are totally unknown in the
experience of mankind. Some, with more or less white blood, have
exhibited more or less talent, possibly even have shown eccentric
indications of genius, but among a million of adult typical negroes,
there probably would not be a single brain that would vary from the
others sufficiently to be detected by the eye, and therefore not an
individual negro whose natural capacities were so much greater than
those of his fellows as to be recognized by the reason.
Such are briefly the leading and fundamental facts that constitute
the mental organism and distinguish the intellectual character of
races, that separate white men and negroes by an interval broader
and deeper than in any other forms of humanity, and render an
attempted social equality not merely a great folly but a gross impiety.
As has been stated, in exact proportion to the volume of brain,
relatively with the size of body in men and animals, there is
intelligence, and as the cerebrum or anterior portion predominates
over the cerebellum or posterior portion, there is a corresponding
predominance of intellectualism over animalism in the human races.
The negro brain in its totality is ten to fifteen per cent. less than that
of the Caucasian, while in its relations—the relatively large
cerebellum and small cerebrum—the inferiority of the mental
organism is still more decided; thus, while in mere volume, and
therefore in the sum total of mental power, the negro is vastly
inferior to the white man, the relative proportion of the brain and of
the animal and intellectual natures adds still more to the Caucasian
superiority, while it opens up before us abundant explanations of the
diversified forms in which that superiority is continually manifested.
There are no terms or mere words that enable us to express the
absolute scientific superiority of the white man. We can only
measure it, or indeed comprehend it, by comparison, but this will be
sufficiently intelligible when it is said that the past history and
present condition of both races correspond exactly with the size and
form of the brain in each. The science, the literature, the progress,
enlightenment and intellectual grandeur of the Caucasian from the
beginning of authentic history to this moment, and which have
accompanied him from the banks of the Nile to those of the
Mississippi, are all fitting revelations of the Caucasian brain, while
the utter absence of all these things—the long night of darkness that
enshrouds the negro being, and which is only broken in upon when
in juxtaposition and permitted to imitate his master, is the result or
necessity of his mental organism.
There being nothing superior to the Caucasian, it may be said that
he is endowed with unlimited powers; that is, while the mental
organism remains the same, his powers of acquisition and the
increase of his knowledge have no limit. A generation in the exercise
of its faculties acquires a certain amount of knowledge; this is
transmitted to the next; it, in turn, adds its proportion, and so on,
each generation in its turn accepting the knowledge of its progenitors
and transmitting with its own acquisitions the sum total to its
successors. This is called civilization, and we can suppose no limit to
it, except it be in the destruction of the existing order and a new
creation. On the contrary, the negro brain is incapable of grasping
ideas, or what we call abstract truths, as absolutely so as the white
child, indeed as necessarily incapable of such a thing as for a person
to see without eyes, or hear without ears. In contact with, and
permitted to imitate the white man, the negro learns to read, to
write, to make speeches, to preach, to edit newspapers, etc., but all
this is like that of the boy of ten or twelve who debates à la Webster
or declaims from Demosthenes. People ignorant of the negro mistake
this borrowed for real knowledge, as one ignorant of metals may
have a brass watch imposed on him for a golden one. The negro is
therefore incapable of progress, a single generation being capable of
all that millions of generations are, and those populations in Africa
isolated from white men are exactly now as they were when the
Hebrews escaped from Egypt, and where they must be millions of
years hence, if left to themselves. Of course this is no mere opinion or
conjecture of the author. It is a necessity of the negro being—a
consequence of the negro structure—a fixed and eternally
inseparable result of the mental organism, which without a re-
creation—another brain—could no more be otherwise than water
could run up hill, or a reversal of the law of gravitation in any respect
could be possible. But people, ignorant of the elementary principles
of science as well as of the nature of the negro, fancy that this is quite
possible; that, however inferior the organism of the negro in these
respects, it is the result of many centuries of savagery and “slavery,”
and therefore if he were made “free,” given the same rights with the
same chances for mental cultivation, that the brain might gradually
alter and become like that of the white man! This involves gross
impiety, if it were not the offspring of ignorance and folly, for it
supposes that chance and human forces are more potent than the
Almighty Creator, whose work is thus the sport of circumstances.
They would seek by stimulating the mind to add ten per cent. to the
negro brain—then to add to the cerebrum while they diminished the
cerebellum—certainly a work of much greater magnitude than
changing the color of the negro skin; but even the most ignorant or
the most impious among these people would scarcely undertake the
latter operation. If reason could at all enter into the matter, it would
surely be more reasonable to suppose that mind might be changed by
acting on matter, rather than the reverse, and therefore it would be
better to change the color of the skin, as the first, as it would also be
the most practicable, step to be taken in this grand undertaking of
setting aside the Creator and re-creating the negro. But, after all,
their labors would fail—after they had changed the color, after they
had increased the volume of the brain and duly modified its relations
as well as altered its texture—in short, when they had turned him
into a white man, then all would be in vain, for such a brain could no
more be born of a negress than an elephant could be!
 CHAPTER XII.
GENERAL SUMMARY.

In the several preceding chapters, those outward characteristics

that specifically distinguish the negro have been briefly considered.
It has been shown that color, the hair, the figure, the brain, etc., are
simply facts out of many millions of facts that separate the races; that
each and all of them are original, invariable, and everlasting, and the
exception, or the absence of any of them, or of any of the associated
facts not enumerated, at any time, in the case of a single individual
or any generation, or under any possible circumstances of time,
climate, or external agencies whatever, is, or would be, necessarily
impossible. Nature is always true to herself, and even in those
abnormal specimens sometimes presented to our observation—those
so-called monstrosities—there is, properly speaking, no departure
from her original designs, or from those fixed and eternal laws that
govern organic life. We sometimes see Albinos, but except a certain
tinge to the color, itself totally unlike any color in other races, the
absolute negro, that is the millions of facts that constitute the negro
being, are untouched. We witness all kinds of abnormal development
in our own race, in animals, in the vegetable world, in all the
innumerable beings and things that surround us. For example—let
any one spend an autumn day in the forest, and turn his attention to
the strange and often ludicrous sights that surround him. It often
seems as if nature delighted herself in creating odd and uncouth
shapes, as if intended for relaxation and relief from her graver and
grander labors. But even here there is no violation of the higher law—
the order of nature though very often interrupted by accident, is
never contradicted—the abnormal development, the most uncouth
and monstrous consequences are still pervaded by the eternal decree
stamped upon the whole universe, that forbids forever any change in
the minutest atom of this mighty mass of life. The Albino, the
deformed or monstrous Negro, the seemingly wide departure from
the normal standard, still obeys the higher law. All the peculiarities
that distinguish him from his race are sui generis, without any
approximation or resemblance to the white man. So, too, with the
latter, and so, too, with all monstrosities in the lower animals. The
things that constitute the monstrosity, that separate the creature, or
seem to do so, from his own kind, separate him also from other
species, whether of men or animals. The eternal gulf, the impassable
barrier, the decreed limits fixed by the Creator himself, are never
passed. A negro, with the color, or the hair, or the language, or the
brain, or the sense of touch, or taste, or sight of the Caucasian, would
not be a monstrosity but an impossibility. He might differ very
widely from his own race in any one of these things, as we actually
witness in the case of Albinos, in fact might retain scarcely any
outward resemblance to his kind, and yet exist; but none has ever
had, or ever will have, an existence that has any thing in common
with the white man, for that would contradict the universal order of
God himself.
Such being the fact, all that is external or tangible to the sense
being thus widely, immeasurably, and indestructibly different from
the Caucasian or white man, it is obvious that, in all beyond the outer
surface, the same relative differences must exist. It was originally
intended to demonstrate this in detail—to show the actual
anatomical facts and structural differences in the organs, the tissues,
the systems, down to the minutest atom of the bodily structure. It
was designed to present the reader with numerous plates, showing
all this—the minutest particle, the single globule of blood, even,
painted after the employment of the microscope, being sufficiently
palpable to the sense, to show that the primordial atoms of the negro
structure are as specifically, and relatively as widely, different from
the white man’s as the color, the hair, or any of those outward
qualities that confront us daily in the streets. But this would have
added so much to the expense of the work, as to often place it out of
the reach of the day laborer and working man, those who alone, or
mainly, need to understand the great “anti-slavery” imposture of our
times, and the world-wide conspiracy against their freedom,
manhood and happiness, which has so long held them in abject
submission to its clamorous pretences of philanthropy and
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