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 Fitzpatrick’s
Dermatology

Kang_DIGM-FM_Vol-I.indd 1 08/12/18 5:30 pm

 SEWON KANG, MD, MPH
Noxell Professor and Chair
Department of Dermatology
Johns Hopkins School of Medicine
Dermatologist-in-Chief
Johns Hopkins Hospital
Baltimore, Maryland

MASAYUKI AMAGAI, MD, PhD

Professor and Chair
Department of Dermatology
Keio University School of Medicine
Tokyo, Japan

ANNA L. BRUCKNER, MD, MSCS

Associate Professor of Dermatology and Pediatrics
University of Colorado School of Medicine
Section Head, Pediatric Dermatology
Children’s Hospital Colorado
Aurora, Colorado

ALEXANDER H. ENK, MD
Professor and Chair
Department of Dermatology
University of Heidelberg
Heidelberg, Germany

DAVID J. MARGOLIS, MD, PhD

Professor of Dermatology and Epidemiology
Department of Dermatology
Department of Biostatistics and Epidemiology
University of Pennsylvania Perelman School of Medicine
Philadelphia, Pennsylvania

AMY J. McMICHAEL, MD
Professor and Chair
Department of Dermatology
Wake Forest University School of Medicine
Winston-Salem, North Carolina

JEFFREY S. ORRINGER, MD
Professor and Chief
Division of Cosmetic Dermatology
Department of Dermatology
University of Michigan
Ann Arbor, Michigan

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 Fitzpatrick’s
Dermatology
Ninth Edition

EDITORS
SEWON KANG, MD, MPH
MASAYUKI AMAGAI, MD, PhD
ANNA L. BRUCKNER, MD, MSCS
ALEXANDER H. ENK, MD
DAVID J. MARGOLIS, MD, PhD
AMY J. McMICHAEL, MD
JEFFREY S. ORRINGER, MD

VOLUME I

New York Chicago San Francisco Athens London Madrid Mexico City
Milan New Delhi Singapore Sydney Toronto

Kang_DIGM-FM_Vol-I.indd 3 08/12/18 5:31 pm

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 CONTENTS

Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii 10 The Immunological Structure of the Skin . . . . . .130

Georg Stingl & Marie-Charlotte Brüggen
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxix

Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxxi 11 Cellular Components of the Cutaneous

Immune System . . . . . . . . . . . . . . . . . . . . . . . . . . . .143
Johann E. Gudjonsson & Robert L. Modlin

Volume One 12 Soluble Mediators of the Cutaneous

Immune System . . . . . . . . . . . . . . . . . . . . . . . . . . . .159
Allen W. Ho & Thomas S. Kupper

PART 1 FOUNDATIONS OF CLINICAL 13 Basic Principles of Immunologic Diseases

DERMATOLOGY in Skin (Pathophysiology of Immunologic/
Inflammatory Skin Diseases) . . . . . . . . . . . . . . . . .192
1 Fundamentals of Clinical Dermatology: Keisuke Nagao & Mark C. Udey
Morphology and Special Clinical
Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 14 Skin Barrier . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .206
Erin H. Amerson, Susan Burgin, & Kanade Shinkai Akiharu Kubo & Masayuki Amagai

2 Pathology of Skin Lesions . . . . . . . . . . . . . . . . . . . .18 15 Epidermal and Dermal Adhesion. . . . . . . . . . . . .232

Rosalie Elenitsas & Emily Y. Chu Leena Bruckner-Tuderman & Aimee S. Payne

3 Epidemiology and Public Health 16 Microbiome of the Skin. . . . . . . . . . . . . . . . . . . . . .253

in Dermatology . . . . . . . . . . . . . . . . . . . . . . . . . . . . .40 Heidi H. Kong
Junko Takeshita & David J. Margolis
17 Cutaneous Photobiology . . . . . . . . . . . . . . . . . . . .265
Thomas M. Rünger

PART 2 STRUCTURE AND FUNCTION 18 Genetics in Relation to the Skin . . . . . . . . . . . . . .289

Etienne C. E. Wang, John A. McGrath,
OF SKIN & Angela M. Christiano
4 Developmental Biology of the Skin . . . . . . . . . . . .49
Luis Garza 19 Carcinogenesis and Skin. . . . . . . . . . . . . . . . . . . . .310
Kenneth Y. Tsai & Andrzej A. Dlugosz
5 Growth and Differentiation of the Epidermis . . . .62
Terry Lechler 20 Pigmentation and Melanocyte Biology . . . . . . . .328
Stephen M. Ostrowski & David E. Fisher
6 Skin Glands: Sebaceous, Eccrine, and
Apocrine Glands . . . . . . . . . . . . . . . . . . . . . . . . . . . .70 21 Neurobiology of the Skin . . . . . . . . . . . . . . . . . . . .351
Christos C. Zouboulis Sonja Ständer, Manuel P. Pereira,
& Thomas A. Luger
7 Biology of Hair Follicles . . . . . . . . . . . . . . . . . . . . . .89
George Cotsarelis & Vladimir Botchkarev

8 Nail . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .106
PART 3 DERMATITIS
Krzysztof Kobielak
22 Atopic Dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . .363
Eric L. Simpson, Donald Y. M. Leung,
9 Cutaneous Vasculature . . . . . . . . . . . . . . . . . . . . . . 116
Lawrence F. Eichenfield, & Mark Boguniewicz
Peter Petzelbauer, Robert Loewe, & Jordan S. Pober

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 23 Nummular Eczema, Lichen Simplex 38 Subcorneal Pustular Dermatosis
Chronicus, and Prurigo Nodularis . . . . . . . . . . . .385 (Sneddon-Wilkinson Disease) . . . . . . . . . . . . . . . .617
Jonathan I. Silverberg Franz Trautinger & Herbert Hönigsmann

24 Allergic Contact Dermatitis . . . . . . . . . . . . . . . . . .395 39 Autoinflammatory Disorders . . . . . . . . . . . . . . . .621

Jake E. Turrentine, Michael P. Sheehan, Takashi K. Satoh & Lars E. French
& Ponciano D. Cruz, Jr.
40 Eosinophilic Diseases . . . . . . . . . . . . . . . . . . . . . . .649
25 Irritant Dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . .414 Hideyuki Ujiie & Hiroshi Shimizu
Susan T. Nedorost
41 Urticaria and Angioedema. . . . . . . . . . . . . . . . . . .684
26 Seborrheic Dermatitis . . . . . . . . . . . . . . . . . . . . . . .428 Michihiro Hide, Shunsuke Takahagi,
Dae Hun Suh & Takaaki Hiragun

27 Occupational Skin Diseases . . . . . . . . . . . . . . . . . .438 42 Mastocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .710

Contents

Andy Chern, Casey M. Chern, & Boris D. Lushniak Michael D. Tharp

PART 4 PSORIASIFORM DISORDERS PART 7 REACTIVE ERYTHEMAS

28 Psoriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .457 43 Erythema Multiforme . . . . . . . . . . . . . . . . . . . . . . .723
Johann E. Gudjonsson & James T. Elder Jean-Claude Roujeau & Maja Mockenhaupt

29 Pityriasis Rubra Pilaris . . . . . . . . . . . . . . . . . . . . . .498 44 Epidermal Necrolysis (Stevens-Johnson

Knut Schäkel Syndrome and Toxic Epidermal Necrolysis) . . . .733
Maja Mockenhaupt & Jean-Claude Roujeau
30 Parapsoriasis and Pityriasis Lichenoides . . . . . .505
Stefan M. Schieke & Gary S. Wood 45 Cutaneous Reactions to Drugs . . . . . . . . . . . . . . .749
Kara Heelan, Cathryn Sibbald, & Neil H. Shear
31 Pityriasis Rosea . . . . . . . . . . . . . . . . . . . . . . . . . . . .518
Matthew Clark & Johann E. Gudjonsson 46 Erythema Annulare Centrifugum and Other
Figurate Erythemas . . . . . . . . . . . . . . . . . . . . . . . . .765
Christine S. Ahn & William W. Huang

PART 5 LICHENOID AND

GRANULOMATOUS DISORDERS
PART 8 DISORDERS OF CORNIFICATION
32 Lichen Planus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .527
Aaron R. Mangold & Mark R. Pittelkow 47 The Ichthyoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . .775
Keith A. Choate & Leonard M. Milstone
33 Lichen Nitidus and Lichen Striatus . . . . . . . . . . .554
Aaron R. Mangold & Mark R. Pittelkow 48 Inherited Palmoplantar Keratodermas . . . . . . . .816
Liat Samuelov & Eli Sprecher
34 Granuloma Annulare . . . . . . . . . . . . . . . . . . . . . . .564
Julie S. Prendiville 49 Keratosis Pilaris and Other Follicular
Keratotic Disorders . . . . . . . . . . . . . . . . . . . . . . . . .867
35 Sarcoidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .572 Anna L. Bruckner
Richard Marchell
50 Acantholytic Disorders of the Skin . . . . . . . . . . . .877
Alain Hovnanian

PART 6 NEUTROPHILIC, EOSINOPHILIC, 51 Porokeratosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .901

Cathal O’Connor, Grainne M. O’Regan,
AND MAST CELL DISORDERS & Alan D. Irvine
36 Sweet Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . .587
Philip R. Cohen & Razelle Kurzrock
PART 9 VESICULOBULLOUS DISORDERS
37 Pyoderma Gangrenosum . . . . . . . . . . . . . . . . . . . .605
Natanel Jourabchi & Gerald S. Lazarus 52 Pemphigus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .909
vi Aimee S. Payne & John R. Stanley

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 53 Paraneoplastic Pemphigus. . . . . . . . . . . . . . . . . . .934 69 Relapsing Polychondritis . . . . . . . . . . . . . . . . . . . 1186
Grant J. Anhalt & Daniel Mimouni Camille Francès

54 Bullous Pemphigoid . . . . . . . . . . . . . . . . . . . . . . . .944

Donna A. Culton, Zhi Liu, & Luis A. Diaz
PART 11 DERMAL CONNECTIVE
55 Mucous Membrane Pemphigoid . . . . . . . . . . . . .960 TISSUE DISORDERS
Kim B. Yancey
70 Anetoderma and Other Atrophic Disorders
56 Epidermolysis Bullosa Acquisita . . . . . . . . . . . . .971 of the Skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1193
David T. Woodley & Mei Chen Catherine Maari & Julie Powell

57 Intercellular Immunoglobulin (Ig) 71 Acquired Perforating Disorders . . . . . . . . . . . . .1203

A Dermatosis (IgA Pemphigus) . . . . . . . . . . . . . .981 Garrett T. Desman & Raymond L. Barnhill

Contents
Takashi Hashimoto
72 Genetic Disorders Affecting Dermal
58 Linear Immunoglobulin A Dermatosis and Connective Tissue . . . . . . . . . . . . . . . . . . . . . . . . .1212
Chronic Bullous Disease of Childhood . . . . . . . .992 Jonathan A. Dyer
Matilda W. Nicholas, Caroline L. Rao,
& Russell P. Hall III

59 Dermatitis Herpetiformis . . . . . . . . . . . . . . . . . . .1002 PART 12 SUBCUTANEOUS TISSUE

Stephen I. Katz
DISORDERS
60 Inherited Epidermolysis Bullosa. . . . . . . . . . . . . 1011
73 Panniculitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1251
M. Peter Marinkovich
Eden Pappo Lake, Sophie M. Worobec,
& Iris K. Aronson

74 Lipodystrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . .1295
PART 10 AUTOIMMUNE Abhimanyu Garg
CONNECTIVE TISSUE AND
RHEUMATOLOGIC DISORDERS
61 Lupus Erythematosus . . . . . . . . . . . . . . . . . . . . . .1037 PART 13 MELANOCYTIC DISORDERS
Clayton J. Sontheimer, Melissa I. Costner,
& Richard D. Sontheimer 75 Albinism and Other Genetic Disorders
of Pigmentation . . . . . . . . . . . . . . . . . . . . . . . . . . .1309
62 Dermatomyositis . . . . . . . . . . . . . . . . . . . . . . . . . .1061 Masahiro Hayashi & Tamio Suzuki
Matthew Lewis & David Fiorentino
76 Vitiligo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1330
63 Systemic Sclerosis . . . . . . . . . . . . . . . . . . . . . . . . .1086 Khaled Ezzedine & John E. Harris
Pia Moinzadeh, Christopher P. Denton,
Carol M. Black, & Thomas Krieg 77 Hypermelanoses . . . . . . . . . . . . . . . . . . . . . . . . . .1351
Michelle Rodrigues & Amit G. Pandya
64 Morphea and Lichen Sclerosus . . . . . . . . . . . . . . 1106
Nika Cyrus & Heidi T. Jacobe

65 Psoriatic Arthritis and Reactive Arthritis . . . . . 1127 PART 14 ACNEIFORM DISORDERS

Ana-Maria Orbai & John A. Flynn
78 Acne Vulgaris . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1391
Carolyn Goh, Carol Cheng, George Agak,
66 Rheumatoid Arthritis, Juvenile Idiopathic
Andrea L. Zaenglein, Emmy M. Graber,
Arthritis, Adult-Onset Still Disease, and
Diane M. Thiboutot, & Jenny Kim
Rheumatic Fever . . . . . . . . . . . . . . . . . . . . . . . . . . 1146
Warren W. Piette
79 Rosacea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1419
Martin Steinhoff & Jörg Buddenkotte
67 Scleredema and Scleromyxedema . . . . . . . . . . . 1163
Roger H. Weenig & Mark R. Pittelkow
80 Acne Variants and Acneiform Eruptions. . . . . .1448
Andrea L. Zaenglein, Emmy M. Graber,
68 Sjögren Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . 1170
& Diane M. Thiboutot
Akiko Tanikawa
vii

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 96 Solar Urticaria. . . . . . . . . . . . . . . . . . . . . . . . . . . . .1650
PART 15 DISORDERS OF ECCRINE Marcus Maurer, Joachim W. Fluhr, & Karsten Weller
AND APOCRINE SWEAT GLANDS
97 Phototoxicity and Photoallergy. . . . . . . . . . . . . .1657
81 Hyperhidrosis and Anhidrosis . . . . . . . . . . . . . .1459 Henry W. Lim
Anastasia O. Kurta & Dee Anna Glaser
98 Cold Injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1666
82 Bromhidrosis and Chromhidrosis . . . . . . . . . . .1469 Ashley N. Millard, Clayton B. Green,
Christos C. Zouboulis & Erik J. Stratman

83 Fox-Fordyce Disease . . . . . . . . . . . . . . . . . . . . . . .1475 99 Burns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1679

Powell Perng & Inbal Sander Benjamin Levi & Stewart Wang

84 Hidradenitis Suppurativa . . . . . . . . . . . . . . . . . .1480

Ginette A. Okoye
Contents

PART 18 PSYCHOSOCIAL SKIN DISEASE

100 Delusional, Obsessive-Compulsive, and
PART 16 DISORDERS OF THE HAIR Factitious Skin Diseases . . . . . . . . . . . . . . . . . . . .1693
Mio Nakamura, Josie Howard, & John Y. M. Koo
AND NAILS
85 Androgenetic Alopecia . . . . . . . . . . . . . . . . . . . . .1495 101 Drug Abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1705
Ulrike Blume-Peytavi & Varvara Kanti Nicholas Frank, Cara Hennings, & Jami L. Miller

86 Telogen Effluvium . . . . . . . . . . . . . . . . . . . . . . . . .1507 102 Physical Abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . .1717

Manabu Ohyama Kelly M. MacArthur & Annie Grossberg

87 Alopecia Areata . . . . . . . . . . . . . . . . . . . . . . . . . . .1517

Nina Otberg & Jerry Shapiro
PART 19 SKIN CHANGES ACROSS
88 Cicatricial Alopecias . . . . . . . . . . . . . . . . . . . . . . .1524 THE SPAN OF LIFE
Nina Otberg & Jerry Shapiro
103 Neonatal Dermatology . . . . . . . . . . . . . . . . . . . . .1727
89 Hair Shaft Disorders . . . . . . . . . . . . . . . . . . . . . . .1537 Raegan Hunt, Mary Wu Chang, & Kara N. Shah
Leslie Castelo-Soccio & Deepa Patel
104 Pediatric and Adolescent Dermatology. . . . . . .1750
90 Hirsutism and Hypertrichosis. . . . . . . . . . . . . . .1555 Mary Wu Chang
Thusanth Thuraisingam & Amy J. McMichael
105 Skin Changes and Diseases in Pregnancy . . . . .1765
91 Nail Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . .1568 Lauren E. Wiznia & Miriam Keltz Pomeranz
Eckart Haneke
106 Skin Aging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1779
Michelle L. Kerns, Anna L. Chien, & Sewon Kang

PART 17 DISORDERS DUE TO THE 107 Caring for LGBT Persons in Dermatology . . . .1792
Howa Yeung, Matthew D. Mansh,
ENVIRONMENT
Suephy C. Chen, & Kenneth A. Katz
92 Polymorphic Light Eruption . . . . . . . . . . . . . . . . 1611
Alexandra Gruber-Wackernagel
& Peter Wolf
PART 20 NEOPLASIA
93 Actinic Prurigo . . . . . . . . . . . . . . . . . . . . . . . . . . . .1628
108 Benign Epithelial Tumors, Hamartomas,
Travis Vandergriff
and Hyperplasias. . . . . . . . . . . . . . . . . . . . . . . . . .1799
Jonathan D. Cuda, Sophia Rangwala,
94 Hydroa Vacciniforme . . . . . . . . . . . . . . . . . . . . . .1634
& Janis M. Taube
Travis Vandergriff
109 Appendage Tumors of the Skin . . . . . . . . . . . . .1820
95 Actinic Dermatitis . . . . . . . . . . . . . . . . . . . . . . . . .1639
Ruth K. Foreman & Lyn McDivitt Duncan
Robert S. Dawe
110 Epithelial Precancerous Lesions . . . . . . . . . . . . .1857
viii Markus V. Heppt, Gabriel Schlager, & Carola Berking

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 111 Basal Cell Carcinoma and Basal Cell 127 Fabry Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2292
Nevus Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . .1884 Atul B. Mehta & Catherine H. Orteu
Jean Y. Tang, Ervin H. Epstein, Jr., &
Anthony E. Oro 128 Calcium and Other Mineral Deposition
Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2307
112 Squamous Cell Carcinoma and Janet A. Fairley & Adam B. Aronson
Keratoacanthoma. . . . . . . . . . . . . . . . . . . . . . . . . .1901
Anke S. Lonsdorf & Eva N. Hadaschik 129 Graft-Versus-Host Disease . . . . . . . . . . . . . . . . . .2320
Kathryn J. Martires & Edward W. Cowen
113 Merkel Cell Carcinoma . . . . . . . . . . . . . . . . . . . . .1920
Aubriana McEvoy & Paul Nghiem 130 Hereditary Disorders of Genome Instability
and DNA Repair . . . . . . . . . . . . . . . . . . . . . . . . . .2342
114 Paget’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . .1934 John J. DiGiovanna, Thomas M. Rünger, &
Conroy Chow, Isaac M. Neuhaus, & Roy C. Grekin Kenneth H. Kraemer

Contents
115 Melanocytic Nevi . . . . . . . . . . . . . . . . . . . . . . . . . .1944 131 Ectodermal Dysplasias . . . . . . . . . . . . . . . . . . . . .2372
Jonathan D. Cuda, Robert F. Moore, & Klaus J. Busam Elizabeth L. Nieman & Dorothy Katherine Grange

116 Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1982 132 Genetic Immunodeficiency Diseases . . . . . . . . .2394

Jessica C. Hassel & Alexander H. Enk Ramsay L. Fuleihan & Amy S. Paller

117 Histiocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2018 133 Skin Manifestations of Internal

Astrid Schmieder, Sergij Goerdt, & Jochen Utikal
118 Vascular Tumors . . . . . . . . . . . . . . . . . . . . . . . . . .2042
Kelly M. MacArthur & Katherine Püttgen
119 Cutaneous Lymphoma . . . . . . . . . . . . . . . . . . . . .2072
Martine Bagot & Rudolf Stadler
120 Cutaneous Pseudolymphoma . . . . . . . . . . . . . . .2108
Werner Kempf, Rudolf Stadler, & Martine Bagot
121 Neoplasias and Hyperplasias of
Muscular and Neural Origin . . . . . . . . . . . . . . . .2130
Hansgeorg Müller & Heinz Kutzner
Organ Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . .2425
Amy K. Forrestel & Robert G. Micheletti
134 Cutaneous Paraneoplastic Syndromes . . . . . . .2441
Manasmon Chairatchaneeboon & Ellen J. Kim
135 The Neurofibromatoses . . . . . . . . . . . . . . . . . . . .2465
Robert Listernick & Joel Charrow
136 Tuberous Sclerosis Complex . . . . . . . . . . . . . . . .2480
Thomas N. Darling
137 Diabetes and Other Endocrine Diseases . . . . . .2493
April Schachtel & Andrea Kalus

122 Lipogenic Neoplasms . . . . . . . . . . . . . . . . . . . . . .2172

Thomas Mentzel & Thomas Brenn
PART 22 VASCULAR DISEASES
Volume Two 138 Cutaneous Necrotizing Venulitis . . . . . . . . . . . .2527
Nicholas A. Soter

PART 21 METABOLIC, GENETIC, AND 139 Systemic Necrotizing Arteritis . . . . . . . . . . . . . .2539

Peter A. Merkel & Paul A. Monach
SYSTEMIC DISEASES
123 Cutaneous Changes in Nutritional 140 Erythema Elevatum Diutinum . . . . . . . . . . . . . .2562
Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2199 Theodore J. Alkousakis & Whitney A. High
Albert C. Yan
141 Adamantiades–Behçet Disease . . . . . . . . . . . . . .2567
124 The Porphyrias . . . . . . . . . . . . . . . . . . . . . . . . . . . .2234 Christos C. Zouboulis
Eric W. Gou & Karl E. Anderson
142 Kawasaki Disease . . . . . . . . . . . . . . . . . . . . . . . . .2580
125 Amyloidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2258 Anne H. Rowley
Peter D. Gorevic & Robert G. Phelps
143 Pigmented Purpuric Dermatoses . . . . . . . . . . . .2590
126 Xanthomas and Lipoprotein Disorders . . . . . . .2273 Alexandra Haden & David H. Peng
Vasanth Sathiyakumar, Steven R. Jones, &
Seth S. Martin 144 Cryoglobulinemia and
Cryofibrinogenemia . . . . . . . . . . . . . . . . . . . . . . .2599
Julio C. Sartori-Valinotti & Mark D. P. Davis ix

Kang_DIGM-FM_Vol-I.indd 9 08/12/18 5:31 pm

 145 Raynaud Phenomenon . . . . . . . . . . . . . . . . . . . . .2613
Drew Kurtzman & Ruth Ann Vleugels PART 24 FUNGAL DISEASES
160 Superficial Fungal Infection . . . . . . . . . . . . . . . . .2925
146 Malignant Atrophic Papulosis
Lauren N. Craddock & Stefan M. Schieke
(Degos Disease) . . . . . . . . . . . . . . . . . . . . . . . . . . .2630
Dan Lipsker
161 Yeast Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . .2952
Iris Ahronowitz & Kieron Leslie
147 Vascular Malformations . . . . . . . . . . . . . . . . . . .2636
Laurence M. Boon, Fanny Ballieux,
162 Deep Fungal Infections . . . . . . . . . . . . . . . . . . . . .2965
& Miikka Vikkula
Roderick J. Hay
148 Cutaneous Changes in Arterial, Venous, and
Lymphatic Dysfunction . . . . . . . . . . . . . . . . . . . .2669
Sabrina A. Newman
PART 25 VIRAL DISEASES
Contents

149 Wound Healing . . . . . . . . . . . . . . . . . . . . . . . . . . .2700 163 Exanthematous Viral Diseases . . . . . . . . . . . . . .2989

Afsaneh Alavi & Robert S. Kirsner Vikash S. Oza & Erin F. D. Mathes

164 Herpes Simplex . . . . . . . . . . . . . . . . . . . . . . . . . . .3021

Jeffrey I. Cohen
PART 23 BACTERIAL DISEASES
165 Varicella and Herpes Zoster. . . . . . . . . . . . . . . . .3035
150 Superficial Cutaneous Infections and
Myron J. Levin, Kenneth E. Schmader,
Pyodermas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2719
& Michael N. Oxman
Lloyd S. Miller
166 Poxvirus Infections . . . . . . . . . . . . . . . . . . . . . . . .3065
151 Cellulitis and Erysipelas . . . . . . . . . . . . . . . . . . . .2746
Ellen S. Haddock & Sheila Fallon Friedlander
David R. Pearson & David J. Margolis
167 Human Papillomavirus Infections . . . . . . . . . . .3095
152 Gram-Positive Infections Associated with
Jane C. Sterling
Toxin Production . . . . . . . . . . . . . . . . . . . . . . . . . .2757
Jeffrey B. Travers
168 Cutaneous Manifestations of HIV
and Human T-Lymphotropic Virus . . . . . . . . . .3107
153 Necrotizing Fasciitis, Necrotizing Cellulitis,
Adam D. Lipworth, Esther E. Freeman,
and Myonecrosis . . . . . . . . . . . . . . . . . . . . . . . . . .2770
& Arturo P. Saavedra
Avery LaChance & Daniela Kroshinksy
169 Mosquito-Borne Viral Diseases . . . . . . . . . . . . .3135
154 Gram-Negative Coccal and
Edwin J. Asturias & J. David Beckham
Bacillary Infections . . . . . . . . . . . . . . . . . . . . . . . .2782
Breanne Mordorski & Adam J. Friedman

155 The Skin in Infective Endocarditis, Sepsis,

Septic Shock, and Disseminated
Intravascular Coagulation . . . . . . . . . . . . . . . . . .2815
Joseph C. English III & Misha Rosenbach
156 Miscellaneous Bacterial Infections with
Cutaneous Manifestations . . . . . . . . . . . . . . . . . .2827
Scott A. Norton & Michael A. Cardis
157 Tuberculosis and Infections with Atypical
Mycobacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2858
Aisha Sethi
158 Actinomycosis, Nocardiosis, and
Actinomycetoma . . . . . . . . . . . . . . . . . . . . . . . . . .2876
Francisco G. Bravo, Roberto Arenas,
& Daniel Asz Sigall
159 Leprosy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2892
Claudio Guedes Salgado, Arival Cardoso de Brito,
x Ubirajara Imbiriba Salgado, & John Stewart Spencer
PART 26 SEXUALLY TRANSMITTED
DISEASES
170 Syphilis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3145
Susan A. Tuddenham & Jonathan M. Zenilman
171 Endemic (Nonvenereal) Treponematoses . . . . .3173
Francisco G. Bravo, Carolina Talhari,
& Khaled Ezzedine
172 Chancroid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3186
Stephan Lautenschlager & Norbert H. Brockmeyer
173 Lymphogranuloma Venereum . . . . . . . . . . . . . .3193
Norbert H. Brockmeyer & Stephan Lautenschlager
174 Granuloma Inguinale . . . . . . . . . . . . . . . . . . . . . .3202
Melissa B. Hoffman & Rita O. Pichardo

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 175 Gonorrhea, Mycoplasma, and Vaginosis. . . . . .3207 189 Antihistamines . . . . . . . . . . . . . . . . . . . . . . . . . . . .3451
Lindsay C. Strowd, Sean McGregor, & Rita O. Pichardo Michael D. Tharp

190 Cytotoxic and Antimetabolic Agents . . . . . . . . .3463

Jeremy S. Honaker & Neil J. Korman
PART 27 INFESTATIONS, BITES,
AND STINGS 191 Antiviral Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . .3493
Zeena Y. Nawas, Quynh-Giao Nguyen,
176 Leishmaniasis and Other Protozoan Khaled S. Sanber, & Stephen K. Tyring
Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3223
Esther von Stebut 192 Immunosuppressive and
Immunomodulatory Drugs . . . . . . . . . . . . . . . . .3517
177 Helminthic Infections . . . . . . . . . . . . . . . . . . . . . .3251 Drew Kurtzman, Ruth Ann Vleugels, & Jeffrey Callen
Kathryn N. Suh & Jay S. Keystone
193 Immunobiologics: Targeted Therapy Against

Contents
178 Scabies, Other Mites, and Pediculosis . . . . . . . .3274 Cytokines, Cytokine Receptors, and Growth
Chikoti M. Wheat, Craig N. Burkhart, Factors in Dermatology . . . . . . . . . . . . . . . . . . . .3531
Craig G. Burkhart, & Bernard A. Cohen Andrew Johnston, Yoshikazu Takada, & Sam T. Hwang

179 Lyme Borreliosis. . . . . . . . . . . . . . . . . . . . . . . . . . .3287 194 Molecular Targeted Therapies . . . . . . . . . . . . . . .3558

Roger Clark & Linden Hu David Michael Miller, Bobby Y. Reddy, & Hensin Tsao

180 The Rickettsioses, Ehrlichioses, and 195 Antiangiogenic Agents . . . . . . . . . . . . . . . . . . . . .3590

Anaplasmoses . . . . . . . . . . . . . . . . . . . . . . . . . . . .3306 Adilson da Costa, Michael Y. Bonner,
Maryam Liaqat, Analisa V. Halpern, Justin J. Green, & Jack L. Arbiser
& Warren R. Heymann
196 Other Topical Medications . . . . . . . . . . . . . . . . . .3610
181 Arthropod Bites and Stings . . . . . . . . . . . . . . . . .3324 Shawn G. Kwatra & Manisha Loss
Robert A. Schwartz & Christopher J. Steen
197 Photoprotection . . . . . . . . . . . . . . . . . . . . . . . . . . .3623
182 Bites and Stings of Terrestrial and Jin Ho Chung
Aquatic Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3338
Camila K. Janniger, Robert A. Schwartz,
Jennifer S. Daly, & Mark Jordan Scharf
PART 29 PHYSICAL TREATMENTS
198 Phototherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3635
PART 28 TOPICAL AND SYSTEMIC Tarannum Jaleel, Brian P. Pollack, & Craig A. Elmets

TREATMENTS 199 Photochemotherapy and Photodynamic

Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3664
183 Principles of Topical Therapy . . . . . . . . . . . . . . .3363
Herbert Hönigsmann, Rolf-Markus Szeimies,
Mohammed D. Saleem,
& Robert Knobler
Howard I. Maibach, & Steven R. Feldman
200 Radiotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3687
184 Glucocorticoids . . . . . . . . . . . . . . . . . . . . . . . . . . .3382
Roy H. Decker & Lynn D. Wilson
Avrom Caplan, Nicole Fett, & Victoria Werth

185 Retinoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3395

Anna L. Chien, Anders Vahlquist, PART 30 DERMATOLOGIC SURGERY
Jean-Hilaire Saurat, John J. Voorhees, & Sewon Kang
201 Cutaneous Surgical Anatomy . . . . . . . . . . . . . . .3697
186 Systemic and Topical Antibiotics . . . . . . . . . . . .3407 Arif Aslam & Sumaira Z. Aasi
Sean C. Condon, Carlos M. Isada,
& Kenneth J. Tomecki 202 Perioperative Considerations in
Dermatologic Surgery . . . . . . . . . . . . . . . . . . . . . .3706
187 Dapsone. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3423 Noah Smith, Kelly B. Cha, & Christopher Bichakjian
Chee Leok Goh & Jiun Yit Pan
203 Excisional Surgery and Repair,
188 Antifungals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3436 Flaps, and Grafts . . . . . . . . . . . . . . . . . . . . . . . . . .3726
Mahmoud Ghannoum, Iman Salem, Adele Haimovic, Jessica M. Sheehan,
& Luisa Christensen & Thomas E. Rohrer xi

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 204 Mohs Micrographic Surgery . . . . . . . . . . . . . . . .3761 211 Noninvasive Body Contouring . . . . . . . . . . . . . .3857
Sean R. Christensen & David J. Leffell Murad Alam

205 Nail Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3774 212 Treatment of Varicose Veins and

Robert Baran & Olivier Cogrel Telangiectatic Lower-Extremity Vessels. . . . . . .3871
Daniel P. Friedmann, Vineet Mishra,
206 Cryosurgery and Electrosurgery. . . . . . . . . . . . .3791 & Jeffrey T. S. Hsu
Justin J. Vujevich & Leonard H. Goldberg
213 Chemical Peels and Dermabrasion. . . . . . . . . . .3895
Gary Monheit & Bailey Tayebi

PART 31 COSMETIC DERMATOLOGY 214 Liposuction Using Tumescent

Local Anesthesia . . . . . . . . . . . . . . . . . . . . . . . . . .3906
207 Cosmeceuticals and Skin Care C. William Hanke, Cheryl J. Gustafson,
in Dermatology . . . . . . . . . . . . . . . . . . . . . . . . . . .3803
Contents

William G. Stebbins, & Aimee L. Leonard

Leslie Baumann
215 Soft-Tissue Augmentation . . . . . . . . . . . . . . . . . . 3911
208 Fundamentals of Laser and Lisa M. Donofrio & Dana L. Ellis
Light-Based Treatments . . . . . . . . . . . . . . . . . . . .3820
Omer Ibrahim & Jeffrey S. Dover 216 Botulinum Toxin . . . . . . . . . . . . . . . . . . . . . . . . . .3921
Richard G. Glogau
209 Laser Skin Resurfacing: Cosmetic
and Medical Applications . . . . . . . . . . . . . . . . . .3834 217 Hair Transplantation . . . . . . . . . . . . . . . . . . . . . . .3931
Bridget E. McIlwee & Tina S. Alster Robin H. Unger & Walter P. Unger

210 Nonablative Laser and Light-Based Therapy: Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3951

Cosmetic and Medical Indications . . . . . . . . . . .3846
Jeffrey S. Orringer

Videos can be accessed via the following link: mhprofessional.com/fitzderm9evideos

Chapter Number: Title Video Number: Title

Chapter 159: Leprosy Video 159-1: Sensitivity Test Monofilament

Video 159-2: Drop Foot
Video 159-3: Walking Impairment
Chapter 205: Nail Surgery Video 205-1: Lateral Longitudinal Biopsy
Video 205-2: Biopsy of the Distal Matrix
Video 205-3: Tangential Shave Excision
Video 205-4: Biopsy of Onychopapilloma

xii

Kang_DIGM-FM_Vol-I.indd 12 08/12/18 5:31 pm


Sumaira Z. Aasi, MD
Clinical Professor, Dermatology,
Clinical Professor (By Courtesy),
Surgery–Plastic and Reconstructive
Surgery, Dermatology–North
Campus, Stanford University,
Redwood City, California [201]
George Agak, PhD
Research Scientist, Dermatology/
Medicine, David Geffen School of
Medicine at UCLA, Los Angeles,
California [78]
Christine S. Ahn, MD
Resident Physician, Wake Forest
School of Medicine, Winston Salem,
North Carolina [46]
Iris Ahronowitz, MD
Assistant Professor of Clinical
Dermatology, Keck School
of Medicine, University of
Southern California, Los Angeles,
California [161]
Murad Alam, MD, MSCI, MBA
Professor of Dermatology,
Otolaryngology, and Surgery,
Vice-Chair, Department of
Dermatology, Chief, Section of
Cutaneous and Aesthetic Surgery,
Director, Micrographic Surgery and
Dermatologic Oncology Fellowship,
Northwestern University, Chicago,
Illinois [211]
Afsaneh Alavi, MSc, MD, FRCPC
Assistant Professor of Dermatology,
Women’s College Hospital,
University of Toronto, Toronto,
Ontario, Canada [149]
Theodore J. Alkousakis, MD
Assistant Clinical Professor,
University of Colorado School of
Medicine, Medical Director, Adult
Dermatology, Aurora, Colorado [140]
Tina S. Alster, MD
Director, Washington Institute
of Dermatologic Laser Surgery,
Clinical Professor of Dermatology,
Georgetown University Medical
Center, Washington, DC [209]
Kang_DIGM-FM_Vol-I.indd 13
CONTRIBUTORS
Masayuki Amagai, MD, PhD
Professor and Chair, Department
of Dermatology, Keio University
School of Medicine, Tokyo,
Japan [14]
Erin H. Amerson, MD
Associate Professor, University
of California, San Francisco,
Department of Dermatology,
San Francisco, California [1]
Karl E. Anderson, MD, FACP
Departments of Preventive
Medicine and Community Health,
and Internal Medicine (Division of
Gastroenterology and Hepatology),
University of Texas Medical Branch,
Galveston, Texas [124]
Grant J. Anhalt, MD
Professor of Dermatology and
Pathology, Department of
Dermatology, Johns Hopkins
Hospital, Baltimore, Maryland [53]
Jack L. Arbiser, MD, PhD
Emory University School
of Medicine, Department of
Dermatology, Atlanta Veterans
Affairs Medical Center, Atlanta,
Georgia [195]
Roberto Arenas, MD
Mycology Section, Dr. Manuel Gea
Gonzalez General Hospital, Mexico
City, Mexico [158]
Adam B. Aronson, MD
Resident Physician, Dermatology,
University of Iowa Carver College
of Medicine, Iowa City, Iowa [128]
Iris K. Aronson, MD
University of Illinois at Chicago,
Chicago, Illinois [73]
Arif Aslam, MBChB, MRCP (UK),
MRCGP, MRCP (Dermatology)
Consultant Dermatologist and Mohs
Surgeon, St Helens and Knowsley
Teachings Hospitals NHS Trust,
St Helens, United Kingdom [201]
Edwin J. Asturias, MD
The Jules Amer Chair in
Community Pediatrics, Children’s
Hospital Colorado, Associate
Professor of Pediatrics and
Epidemiology, Division of Pediatric
Infectious Diseases, University
of Colorado School of Medicine,
Center for Global Health, Colorado
School of Public Health, Aurora,
Colorado [169]
Martine Bagot, MD, PhD
Department of Dermatology,
Hôpital Saint-Louis, Paris,
France [119, 120]
Fanny Ballieux, MD
Resident, Center for Vascular
Anomalies, Division of Plastic
Surgery, Cliniques Universitaires
St Luc and University of Louvain,
Brussels, Belgium [147]
Robert Baran, MD
Honorary Professor, Nail Disease
Center, Cannes, France [205]
Raymond L. Barnhill, MD
Professor, Department of Pathology,
Institut Curie, and University of
Paris Descartes Faculty of Medicine,
Paris, France, Department of
Pathology, Paris, France [71]
Leslie Baumann, MD
Board Certified Dermatologist,
Baumann Cosmetic and Research
Institute, Miami, Florida [207]
J. David Beckham, MD
Associate Professor, Director of
the Infectious Disease Fellowship
Training Program, Division of Adult
Infectious Diseases, University
of Colorado School of Medicine,
Denver, Colorado [169]
Carola Berking, MD
Department of Dermatology,
University Hospital Munich,
Ludwig-Maximilian University
(LMU), Munich, Germany [110]
08/12/18 5:31 pm
 Christopher Bichakjian, MD
Department of Dermatology,
University of Michigan Health
System, Ann Arbor, Michigan [202]
Carol M. Black, MD, FRCP
Centre for Rheumatology and
Connective Tissue Diseases, UCL
Medical School, Royal Free Hospital,
London, United Kingdom [63]
Ulrike Blume-Peytavi, MD
Department of Dermatology and
Allergy, Charité-Universitätsmedizin,
Berlin, Germany [85]
Contributors
Mark Boguniewicz, MD
Professor, Division of Allergy
and Immunology, Department of
Pediatrics, National Jewish Health
and University of Colorado School
of Medicine, Denver, Colorado [22]
Michael Y. Bonner, BA
Emory University School
of Medicine, Department of
Dermatology, Atlanta, Georgia [195]
Laurence M. Boon, MD, PhD
Coordinator of the Center for
vascular Anomalies, Division
of Plastic Surgery, Cliniques
Universitaires St Luc and Human
Molecular Genetics, de Duve
Institute, University of Louvain,
Brussels, Belgium [147]
Vladimir Botchkarev, MD,
PhD, FRSB
Professor and Deputy Director,
Centre for Skin Sciences, University
of Bradford, United Kingdom,
Adjunct Professor, Department of
Dermatology, Boston University
School of Medicine, Boston,
Massachusetts [7]
Francisco G. Bravo, MD
Associate Professor of Dermatology
and Pathology, Universidad
Peruana Cayetano Heredia, Lima,
Peru [158, 171]
Thomas Brenn, MD, PhD
Consultant Dermatopathologist
and Honorary Senior Lecturer,
Department of Pathology NHS
Lothian University Hospitals Trust
and the University of Edinburgh,
Edinburgh, United Kingdom [122]
Norbert H. Brockmeyer
Walk In Ruhr (WIR) Center for
Sexual Health and Medicine,
Department of Dermatology,
Venerology and Allergology,
xiv Ruhr-Universität Bochum, Bochum,
Germany [172, 173]
Kang_DIGM-FM_Vol-I.indd 14
Anna L. Bruckner, MD, MSCS
Associate Professor of Dermatology
and Pediatrics, University of
Colorado School of Medicine,
Section Head, Pediatric
Dermatology, Children’s Hospital
Colorado, Aurora, Colorado [49]
Leena Bruckner-Tuderman,
MD, PhD
Professor and Chair of Dermatology,
Medical Center-University of
Freiburg, Freiburg, Germany [15]
Marie-Charlotte Brüggen,
MD, PhD
Department of Dermatology,
University Hospital Zurich, Zurich,
Switzerland [10]
Jörg Buddenkotte, MD, PhD
Academic Research Scientist,
Department of Dermatology and
Venereology, Hamad Medical
Corporation, Doha, Qatar [79]
Susan Burgin, MD
Assistant Professor, Beth Israel
Deaconness Medical Center,
Harvard Medical School,
Department of Dermatology, Boston,
Massachusetts [1]
Craig G. Burkhart, MD
Sylvania, Ohio [178]
Craig N. Burkhart, MD
The University of North Carolina
at Chapel Hill, Chapel Hill, North
Carolina [178]
Klaus J. Busam, MD
Professor of Pathology and
Laboratory Medicine, Weill Medical
College of Cornell University,
Department of Dermatopathology
and Pathology, Memorial Sloan
Kettering Cancer Center, New York,
New York [115]
Jeffrey Callen, MD
Professor of Medicine
(Dermatology), University
of Louisville, Chief, Division
of Dermatology, Louisville,
Kentucky [192]
Avrom Caplan, MD
Department of Dermatology,
Hospital of the University of
Pennsylvania, Philadelphia,
Pennsylvania [184]
Michael A. Cardis, MD
Department of Dermatology,
Washington Hospital Center/
Georgetown University,
Washington, DC [156]
Arival Cardoso de Brito,
MD, PhD
Full Professor, Dermatology, Pará
Federal University, Belém, Pará,
Brazil [159]
Leslie Castelo-Soccio,
MD, PhD
Assistant Professor of Pediatrics
and Dermatology, The Children’s
Hospital of Philadelphia and
University of Pennsylvania Perlman
School of Medicine, Philadelphia,
Pennsylvania [89]
Kelly B. Cha, MD, PhD
Department of Dermatology,
University of Michigan Health
System, Ann Arbor, Michigan [202]
Manasmon
Chairatchaneeboon, MD
Clinical Instructor in Dermatology,
Department of Dermatology,
Faculty of Medicine Siriraj Hospital,
Mahidol University, Bangkok,
Thailand [134]
Mary Wu Chang, MD
Clinical Professor of Dermatology
and Pediatrics, University of
Connecticut School of Medicine,
Farmington, Connecticut [103, 104]
Joel Charrow, MD
Professor of Pediatrics, Feinberg
School of Medicine, Northwestern
University, Ann and Robert H.
Lurie Children’s Hospital of
Chicago, Division of Genetics, Birth
Defects and Metabolism, Chicago,
Illinois [135]
Mei Chen, PhD
Director, USC Laboratories for
Investigative Dermatology, The
Keck School of Medicine, University
of Southern California, Los Angeles,
California [56]
Suephy C. Chen, MD, MS
Vice Chair and Associate Professor
of Dermatology, Emory University
School of Medicine, Atlanta,
Georgia [107]
Carol Cheng, MD
Assistant Clinical Professor of
Dermatology/Medicine, David
Geffen School of Medicine at UCLA,
Los Angeles, California [78]
08/12/18 5:31 pm
 Andy Chern, MD, MPH
Captain, Medical Corps, United
States Army, Associate Program
Director, Occupational and
Environmental Medicine Residency
Program, Uniformed Services
University of the Health Sciences, F.
Edward Hébert School of Medicine,
Department of Preventive Medicine
and Biostatistics, Bethesda,
Maryland [27]
Casey M. Chern, MD
Captain, Medical Corps, United
States Army, Dermatology Resident,
National Capital Consortium
Dermatology Residency Program,
Walter Reed National Military
Medical Center, Bethesda,
Maryland [27]
Anna L. Chien, MD
Assistant Professor, Department
of Dermatology, Johns Hopkins
School of Medicine, Baltimore,
Maryland [106, 185]
Keith A. Choate, MD, PhD
Professor of Dermatology, Genetics
and Pathology, Yale University
School of Medicine, New Haven,
Connecticut [47]
Conroy Chow, MD
Assistant Professor, Department
of Dermatology, Loma Linda
University, Loma Linda,
California [114]
Luisa Christensen, MD
Center for Medical Mycology,
University Hospitals Cleveland
Medical Center, Case Western
Reserve University, Cleveland,
Ohio [188]
Sean R. Christensen, MD, PhD
Assistant Professor of Dermatology,
Section of Dermatologic Surgery,
Yale University School of Medicine,
New Haven, Connecticut [204]
Angela M. Christiano, PhD
Department of Dermatology,
Department of Genetics and
Development, Columbia University,
New York, New York [18]
Emily Y. Chu, MD, PhD
Assistant Professor of Dermatology,
Hospital of the University of
Pennsylvania, Perelman School
of Medicine, Philadelphia,
Pennsylvania [2]
Kang_DIGM-FM_Vol-I.indd 15
Jin Ho Chung, MD, PhD
Professor and Chairman,
Department of Dermatology, Seoul
National University College of
Medicine, Seoul, Korea [197]
Matthew Clark, MD
Dermatology Resident, University
of Michigan Department of
Dermatology, Ann Arbor,
Michigan [31]
Roger Clark, DO
Assistant Professor of Medicine,
Tufts Medical Center, Brigham and
Women’s Faulkner Hospital, Boston,
Massachusetts [179]
Olivier Cogrel, MD
Dermatologic Surgery and Laser
Unit, Dermatology Department,
CHU Bordeaux, Hôpital Saint-
André, Bordeaux, France [205]
Bernard A. Cohen, MD
Johns Hopkins Hospital Baltimore,
Maryland [178]
Jeffrey I. Cohen, MD
Chief, Laboratory of Infectious
Diseases, National Institute of
Allergy and Infectious Diseases,
National Institutes of Health,
Bethesda, Maryland [164]
Philip R. Cohen, MD
Professor of Dermatology,
University of California San Diego
School of Medicine, San Diego,
California [36]
Sean C. Condon, MD
Department of Dermatology,
Cleveland Clinic, Cleveland,
Ohio [186]
Melissa I. Costner, MD
Associate Clinical Professor,
Dermatology, UT Southwestern
Medical School, North Dallas
Dermatology Associates, Dallas,
Texas [61]
George Cotsarelis, MD
Milton B. Hartzell Professor and
Chair, Department of Dermatology,
Perelman School of Medicine
University of Pennsylvania,
Director, Program on Epithelial
Regeneration and Stem Cells,
University of Pennsylvania
Institute for Regenerative Medicine,
Philadelphia, Pennsylvania [7]
Edward W. Cowen, MD
Head, Dermatology Consultation
Service, Dermatology Branch,
Center for Cancer Research,
National Cancer Institute, National
Institutes of Health, Bethesda,
Maryland [129]
Lauren N. Craddock, MD
Department of Dermatology,
University of Wisconsin-Madison,
Madison, Wisconsin [160]
Ponciano D. Cruz, Jr., MD
Distinguished Professor, Paul
Bergstresser Endowed Chair in
Contributors
Dermatology, Department of
Dermatology, The University of
Texas, Chief of Dermatology, North
Texas Veterans Affairs Medical
Center, Dallas, Texas [24]
Jonathan D. Cuda, MD
Assistant Professor of Dermatology,
Johns Hopkins School of Medicine,
Baltimore, Maryland [108, 115]
Donna A. Culton, MD, PhD
Department of Dermatology,
University of North Carolina at
Chapel Hill, Chapel Hill, North
Carolina [54]
Nika Cyrus, MD
Department of Dermatology,
Parkland Health and Hospital
System, Dallas, Texas [64]
Adilson da Costa, MD
Emory University School
of Medicine, Department of
Dermatology, Atlanta, Georgia [195]
Jennifer S. Daly, MD
Clinical Chief, Infectious Diseases
and Immunology, Professor of
Medicine, Microbiology and
Physiological Systems, University
of Massachusetts Medical School,
Worcester, Massachusetts [182]
Thomas N. Darling, MD, PhD
Professor and Chair of Dermatology,
Uniformed Services University
of the Health Sciences, Bethesda,
Maryland [136]
Mark D. P. Davis, MD
Professor of Dermatology, Mayo
Clinic College of Medicine,
Department of Dermatology,
Rochester, Minnesota [144]
xv
08/12/18 5:31 pm
 Robert S. Dawe, MBChB,
MD(Glasg), FRCP(Edin)
Consultant Dermatologist and
Honorary Reader in Dermatology,
Department of Dermatology and
Photobiology Unit, NHS Tayside
and University of Dundee, Dundee,
Scotland [95]
Roy H. Decker, MD, PhD
Associate Professor, Vice Chair
and Director of Clinical Research,
Department of Therapeutic
Radiology, Yale School of Medicine,
New Haven, Connecticut [200]
Contributors
Christopher P. Denton, PhD,
FRCP
Centre for Rheumatology and
Connective Tissue Diseases, UCL
Medical School, Royal Free Hospital,
London, United Kingdom [63]
Garrett T. Desman, MD
Assistant Professor of Pathology
and Dermatology, Icahn School of
Medicine at Mount Sinai, New York,
New York [71]
Luis A. Diaz, MD
Department of Dermatology,
University of North Carolina at
Chapel Hill, Chapel Hill, North
Carolina [54]
John J. DiGiovanna, MD
Senior Research Physician, DNA
Repair Section, Dermatology
Branch, Center for Cancer Research,
National Cancer Institute, National
Institutes of Health, Bethesda,
Maryland [130]
Andrzej A. Dlugosz, MD
Poth Professor of Cutaneous
Oncology, Departments of
Dermatology and Cell and
Developmental Biology, University
of Michigan Medical School, Ann
Arbor, Michigan [19]
Lisa M. Donofrio, MD
Associate Clinical Professor,
Department of Dermatology, Yale
School of Medicine, Yale University,
New Haven, Connecticut [215]
Jeffrey S. Dover, MD, FRCPC
SkinCare Physicians, Chestnut Hill,
Massachusetts [208]
Lyn McDivitt Duncan, MD
Professor of Pathology,
Harvard Medical School,
Chief, Dermatopathology Unit,
Department of Pathology,
xvi Massachusetts General Hospital,
Boston, Massachusetts [109]
Kang_DIGM-FM_Vol-I.indd 16
Jonathan A. Dyer, MD
Associate Professor of Dermatology
and Child Health, Departments of
Dermatology and Child Health,
University of Missouri, Columbia,
Missouri [72]
Lawrence F. Eichenfield, MD
Chief, Pediatric and Adolescent
Dermatology, Professor of
Dermatology and Pediatrics, Vice
Chair, Department of Dermatology,
University of California, San Diego
School of Medicine, San Diego,
California [22]
James T. Elder, MD, PhD
Kirk D. Wuepper Professor of
Molecular Genetic Dermatology,
Department of Dermatology,
University of Michigan, Ann Arbor,
Ann Arbor, Michigan [28]
Rosalie Elenitsas, MD
Professor of Dermatology, Director
of Dermatopathology, Hospital of
the University of Pennsylvania,
Perelman School of Medicine,
Philadelphia, Pennsylvania [2]
Dana L. Ellis, MD
Clinical Instructor, Department
of Dermatology, Yale School of
Medicine, Yale University,
New Haven, Connecticut [215]
Craig A. Elmets, MD
Professor and Emeritus Chair,
Department of Dermatology,
University of Alabama at
Birmingham, The Birmingham
VA Medical Center, Birmingham,
Alabama [198]
Joseph C. English III, MD
Professor of Dermatology,
University of Pittsburgh,
Department of Dermatology, UPMC
North Hills Dermatology, Wexford,
Pennsylvania [155]
Alexander H. Enk, MD
Professor and Chair,
Department of Dermatology,
University of Heidelberg,
Heidelberg, Germany [116]
Ervin H. Epstein, Jr., MD
Children’s Hospital of Oakland
Research Institute, UCSF, Oakland,
California [111]
Khaled Ezzedine, MD, PhD
Professor, Department of
Dermatology, Hôpital Henri
Mondor, EA EpiDermE
(Epidémiologie en Dermatologie
et Evaluation des Thérapeutiques),
UPEC-Université Paris-Est Créteil,
Créteil, France [76, 171]
Janet A. Fairley, MD
John S. Strauss Professor and
Chair, Department of Dermatology,
University of Iowa Carver College
of Medicine, Iowa City, Iowa [128]
Steven R. Feldman, MD, PhD
Department of Dermatology,
Wake Forest University School of
Medicine, Winston-Salem, North
Carolina [183]
Nicole Fett, MD, MSCE
Associate Professor of Dermatology,
Department of Dermatology,
Oregon Health and Science
University, Portland, Oregon [184]
David Fiorentino, MD, PhD
Professor in the Department of
Dermatology and the Department
of Immunology and Rheumatology
at Stanford University School
of Medicine, Redwood City,
California [62]
David E. Fisher, MD, PhD
Edward Wigglesworth Professor
and Chairman, Department of
Dermatology, Harvard Medical
School, Director, Melanoma
Program MGH Cancer Center,
Director, Cutaneous Biology
Research Center, Massachusetts
General Hospital, Boston,
Massachusetts [20]
Joachim W. Fluhr, MD
Oberarzt, Charité-
Universitätsmedizin Berlin, Klinik
für Dermatologie, Venerologie und
Allergologie, Berlin, Germany [96]
John A. Flynn, MD, MBA, MEd
Professor and Associate Dean of
Medicine, Johns Hopkins University,
Baltimore, Maryland [65]
Ruth K. Foreman, MD, PhD
Instructor of Pathology, Harvard
Medical School, Dermatopathology
Unit, Department of Pathology,
Massachusetts General Hospital,
Boston, Massachusetts [109]
08/12/18 5:31 pm
 Amy K. Forrestel, MD
University of Pennsylvania,
Department of Dermatology,
Philadelphia, Pennsylvania [133]
Camille Francès, MD
AP-HP, Hôpital Tenon, Université
Paris VI, Service de Dermatologie-
Allergologie, Paris, France [69]
Nicholas Frank, MD
Dermatology Resident, Vanderbilt
University Medical Center,
Department of Internal Medicine,
Division of Dermatology, Nashville,
Tennessee [101]
Esther E. Freeman, MD, PhD
Assistant Professor of Dermatology,
Harvard University Medical
School, Director, Global Health
Dermatology, Massachusetts
General Hospital, Department
of Dermatology, Boston,
Massachusetts [168]
Lars E. French, MD
Professor and Chairman,
Department of Dermatology,
University of Zurich, Zurich,
Switzerland [39]
Sheila Fallon Friedlander, MD
Professor of Dermatology and
Pediatrics, University of California,
San Diego School of Medicine, Rady
Children’s Hospital, San Diego,
San Diego, California [166]
Adam J. Friedman, MD
Associate Professor of Dermatology,
Director of Translational Research,
Residency Program Director,
Department of Dermatology, George
Washington School of Medicine
and Health Sciences, Washington,
DC [154]
Daniel P. Friedmann, MD
Westlake Dermatology Clinical
Research Center, Westlake
Dermatology and Cosmetic Surgery,
Austin, Texas [212]
Ramsay L. Fuleihan, MD
Professor of Pediatrics,
Northwestern University Feinberg
School of Medicine, Chicago,
Illinois [132]
Abhimanyu Garg, MD
Professor of Internal Medicine,
Chief, Division of Nutrition and
Metabolic Diseases, Department of
Internal Medicine and the Center
for Human Nutrition, Distinguished
Chair in Human Nutrition Research,
Dallas, Texas [74]
Kang_DIGM-FM_Vol-I.indd 17
Luis Garza, MD, PhD
Associate Professor, Department
of Dermatology, Johns Hopkins
School of Medicine, Baltimore,
Maryland [4]
Mahmoud Ghannoum,
PhD, EMBA
Center for Medical Mycology,
University Hospitals Cleveland
Medical Center, Case Western
Reserve University, Cleveland,
Ohio [188]
Dee Anna Glaser, MD
Interim Chair and Professor,
Director Cosmetic and Laser
Surgery, Director of Clinical
Research, Department of
Dermatology, Saint Louis University
School of Medicine, St. Louis,
Missouri [81]
Richard G. Glogau, MD
Clinical Professor of Dermatology,
University of California,
San Francisco, San Francisco,
California [216]
Sergij Goerdt, MD
Professor of Dermatology, Chair
of Dermatology, Department
of Dermatology, Venereology
and Allergology, University
Medical Center and Medical
Faculty Mannheim, University
of Heidelberg, Mannheim,
Germany [117]
Carolyn Goh, MD
Assistant Clinical Professor of
Dermatology/Medicine, David
Geffen School of Medicine at UCLA,
Los Angeles, California [78]
Chee Leok Goh, MD, MBBS,
M. Med (Int. Med), MRCP (UK),
FRCP (Edin), Hon FACD, FAMS
(Dermatology)
Clinical Professor, National Skin
Centre, Singapore [187]
Leonard H. Goldberg, MD
DermSurgery Associates, Houston,
Texas [206]
Peter D. Gorevic, MD
Professor of Medicine, Division
of Rheumatology, Icahn School of
Medicine at Mount Sinai, New York,
New York [125]
Eric W. Gou, MD
Department of Internal Medicine,
Division of Gastroenterology
and Hepatology, University of
Texas Medical Branch, Galveston,
Texas [124]
Emmy M. Graber, MD, MBA
Dermatologist, The Dermatology
Institute of Boston, Boston,
Massachusetts [78, 80]
Dorothy Katherine Grange, MD
Professor of Pediatrics, Division of
Genetics and Genomic Medicine,
Department of Pediatrics,
Washington University School of
Medicine, St. Louis, Missouri [131]
Clayton B. Green MD, PhD
The Marshfield Clinic, Marshfield,
Wisconsin [98]
Contributors
Justin J. Green, MD
Division of Dermatology, Cooper
Medical School of Rowan
University, Camden,
New Jersey [180]
Roy C. Grekin, MD
Professor of Dermatology, Director,
Dermatologic Surgery and Laser
Center, University of California,
San Francisco, San Francisco,
California [114]
Annie Grossberg, MD
Associate Director, Dermatology
Residency Program, Assistant
Professor, Departments of
Dermatology and Pediatrics, Johns
Hopkins University, Baltimore,
Maryland [102]
Alexandra Gruber-
Wackernagel, MD
Medical University of Graz,
Research Unit for Photodermatology,
Department of Dermatology,
Medical University of Graz, Graz,
Austria [92]
Johann E. Gudjonsson,
MD, PhD
Assistant Professor, Department of
Dermatology, Frances and Kenneth
Eisenberg Emerging Scholar of
the Taubman Medical Research
Institute, University of Michigan,
Ann Arbor, Michigan [11, 28, 31]
Cheryl J. Gustafson, MD
St. Vincent Carmel Medical Center,
Carmel, Indiana [214]
Eva N. Hadaschik, MD
Department of Dermatology,
University Hospital Heidelberg,
Heidelberg, Germany [112]
Ellen S. Haddock, AB, MBA
University of California, San
Diego School of Medicine, La Jolla,
California [166] xvii
08/12/18 5:31 pm
 Alexandra Haden, MD
Assistant Professor of Clinical
Dermatology, Department of
Dermatology, University of
Southern California, Los Angeles,
California [143]
Adele Haimovic, MD
SkinCare Physicians, Chestnut Hill,
Massachusetts [203]
Russell P. Hall III, MD
J. Lamar Callaway Professor,
Department of Dermatology, Duke
University Medical Center, Durham,
North Carolina [58]
Contributors
Analisa V. Halpern, MD
Division of Dermatology, Cooper
Medical School of Rowan
University, Camden, New
Jersey [180]
Eckart Haneke, MD, PhD
Clinical Professor (em) of
Dermatology, Department of
Dermatology, Inselspital, University
of Berne, Bern, Switzerland [91]
C. William Hanke, MD,
MPH, FACP
St. Vincent Carmel Medical Center,
Carmel, Indiana [214]
John E. Harris, MD, PhD
Associate Professor, University
of Massachusetts Medical School,
Worcester, Massachusetts [76]
Takashi Hashimoto, MD
Professor and Director, Kurume
University Institute of Cutaneous
Cell Biology, Kurume, Fukuoka,
Japan [57]
Jessica C. Hassel, MD
Section Head, DermatoOncology,
Department of Dermatology and
National Center for Tumor Diseases,
University Hospital Heidelberg,
Heidelberg, Germany [116]
Roderick J. Hay, DM, FRCP,
FRCPath, FMedSci
Professor, Department of
Dermatology, Kings College
Hospital, Denmark Hill, London,
United Kingdom [162]
Masahiro Hayashi, MD, PhD
Associate Professor of Dermatology,
Yamagata University Faculty of
Medicine, Yamagata, Japan [75]
xviii
Kang_DIGM-FM_Vol-I.indd 18
Kara Heelan, MB BCh, BAO
Dermatology Department,
University College London
Hospitals, London, United
Kingdom [45]
Cara Hennings, MD
University of Tennessee/Erlanger
Medical Center, Chattanooga,
Tennessee [101]
Markus V. Heppt, MD
Department of Dermatology,
University Hospital Munich,
Ludwig-Maximilian University,
Munich, Germany [110]
Warren R. Heymann, MD
Division of Dermatology, Cooper
Medical School of Rowan
University, Camden,
New Jersey [180]
Michihiro Hide, MD, PhD
Department of Dermatology,
Institute of Biomedical and Health
Sciences, Hiroshima University,
Hiroshima, Japan [41]
Whitney A. High, MD, JD, MEng
Associate Professor of Dermatology
and Pathology, University of
Colorado School of Medicine,
Director of Dermatopathology
(Dermatology), Aurora,
Colorado [140]
Takaaki Hiragun, MD, PhD
Department of Dermatology,
Institute of Biomedical and Health
Sciences, Hiroshima University,
Hiroshima, Japan [41]
Allen W. Ho, MD, PhD
Resident Physician, Department
of Dermatology, Harvard Medical
School, Boston, Massachusetts [12]
Melissa B. Hoffman, MD
Resident, Dermatology, Wake Forest
School of Medicine, Winston Salem,
North Carolina [174]
Jeremy S. Honaker, CNP, PhD
Assistant Professor, Department of
Dermatology, Case Western Reserve
University, Cleveland, Ohio [190]
Herbert Hönigsmann, MD
Professor of Dermatology,
Emeritus Chairman, Department of
Dermatology, Medical University of
Vienna, Vienna, Austria [38, 199]
Alain Hovnanian, MD, PhD
Professor of Genetics, Department
of Genetics, Imagine Institute for
Genetic Diseases, Necker Hospital
for Sick Children, University Paris
Descartes-Sorbonne Paris Cité,
Paris, France [50]
Josie Howard, MD
Clinical Faculty, Departments
of Psychiatry and Dermatology,
University of California, San
Francisco, San Francisco,
California [100]
Jeffrey T. S. Hsu, MD
Clinical Assistant Professor,
Department of Dermatology,
University of Illinois College of
Medicine at Chicago, Co-Director
of Dermatologic, Laser and
Cosmetic Surgery, The Dermatology
Institute of DuPage Medical Group,
Naperville, Illinois [212]
Linden Hu, MD
Professor of Microbiology and
Medicine, Tufts University
School of Medicine, Boston,
Massachusetts [179]
William W. Huang, MD, MPH
Associate Professor of Dermatology,
Residency Program Director, Wake
Forest School of Medicine, Winston
Salem, North Carolina [46]
Raegan Hunt, MD, PhD
Assistant Professor of Dermatology
and Pediatrics, Texas Children’s
Hospital, Baylor College of
Medicine, Houston, Texas [103]
Sam T. Hwang, MD, PhD
Department of Dermatology,
University of California Davis
School of Medicine, Sacramento,
California [193]
Omer Ibrahim, MD
SkinCare Physicians, Chestnut Hill,
Massachusetts [208]
Alan D. Irvine, MD, DSc
Paediatric Dermatology and
National Children’s Research
Centre, Our Lady’s Children’s
Hospital Crumlin, Dublin, Clinical
Medicine, Trinity College, Dublin,
Ireland [51]
Carlos M. Isada, MD
Department of Infectious Disease,
Cleveland Clinic, Cleveland,
Ohio [186]
08/12/18 5:31 pm
Another random document with
no related content on Scribd:
genus Globigerina (one of the Foraminifera), some modern species
of which are identical with those found in the Cretaceous. To quote
the words of the Protozoologist, Charles A. Kofoid: “The Protozoa
are found in the oldest fossiliferous rocks and the genera of
Radiolaria therein conform rather closely to genera living today, while
the fossil Dinoflagellata of the flints of Delitzsch are scarcely
distinguishable from species living in the modern seas. The striking
similarities of the most ancient fossil Protozoa to recent ones afford
some ground for the inference that the Protozoa living today differ
but little from those when life was young.” (Science, April 6, 1923, p.
397.)
The Metazoa offer similar examples of persistence. Among the
Cœlenterata, we have the genus Springopora, whose
representatives from the Carboniferous limestones closely resemble
some of the present-day reef builders of the East Indies. Species of
the brachiopod genera Lingula and Crania occurring in the Cambrian
rocks are indistinguishable from species living today, while two other
modern genera of the Brachiopoda, namely, Rhynchonella and
Discina, are represented among the fossils found in Mesozoic
formations. Terebratulina striata, a fossil species of brachiopod
occurring in the rocks belonging to the Cretaceous system, is
identical with our modern species Terebratulina caput serpentis.
Among the Mollusca such genera as Arca, Nucula, Lucina, Astarte,
and Nautilus have had a continuous existence since the Silurian,
while the genera Lima and Pecten can be traced to the Permian.
One genus Pleurotomaria goes back to pre-Cambrian times. As to
Tertiary fossils, Woods informs us that “in some of the later
Cainozoic formations as many as 90 per cent of the species of
mollusks are still living.” (“Palæontology,” 1st ed., p. 2.) Among the
Echinodermata, two genera, Cidaris (a sea urchin) and Pentacrinus
(a crinoid) may be mentioned as being persistent since the Triassic
(“oldest” system of the Mesozoic group). Among the Arthropoda, the
horseshoe crab Limulus polyphemus has had a continuous
existence since the Lias (i.e. the lowest series of the Jurassic
system). Even among the Vertebrata we have instances of
persistence. The extant Australian genus Ceratodus, a Dipnoan, has
been in existence since the Triassic. Among the fossils of the
Jurassic (middle system of the Mesozoic group), Sharks, Rays, and
Chimaeroids occur in practically modern forms, while some of the
so-called “ganoids” are extremely similar to our present sturgeons
and gar pikes—“Some of the Jurassic fishes approximate the
teleosts so closely that it seems arbitrary to call them ganoids.”
(Scott.)
The instances of persistence enumerated above are those
acknowledged by evolutionary palæontologists themselves. This list
could be extended somewhat by the addition of several other
examples, but even so, it would still be small and insufficient to tip
the scales decisively in favor of fixism. On the other hand, we must
not forget that the paucity of this list is due in large measure to the
fact that our present method of classifying fossiliferous strata was
deliberately framed with a view to excluding formations containing
modern types from the category of “ancient” beds. Moreover,
orthodox palæontology has minimized the facts of persistence to an
extent unwarranted even by its own premises. As the following
considerations indicate, the actual number of persistent types is far
greater, even according to the evolutionary time-scale, than the
figure commonly assigned.
First of all, we must take into account the deplorable, if not
absolutely dishonest, practice, which is in vogue, of inventing new
names for the fossil duplicates of modern species, in order to mask
or obscure an identity which conflicts with evolutionary
preconceptions. When a given formation fails to fit into the accepted
scheme by reason of its fossil anachronisms, or when, to quote the
words of Price, “species are found in kinds of rock where they are
not at all expected, and where, according to the prevailing theories, it
is quite incredible that they should be found ... the not very
honorable expedient is resorted to of inventing a new name, specific
or even generic, to disguise and gloss over the strange similarity
between them and the others which have already been assigned to
wholly different formations.” (“The New Geology,” p. 291.) The same
observation is made by Heilprin. “It is practically certain,” says the
latter, “that numerous forms of life, exhibiting no distinctive
characters of their own, are constituted into distinct species for no
other reason than that they occur in formations widely separated
from those holding their nearest kin.” (“Geographical and Geological
Distribution of Animals,” pp. 183, 184.) An instance of this practice
occurs in the foregoing list, where a fossil brachiopod identical with a
modern species receives the new specific name “striata.” Its
influence is also manifest in the previously quoted apology of Scott
for calling teleost-like fish “ganoids.”
We must also take into account the imperfection of the fossil
record, which is proved by the fact that most of the acknowledged
“persistent types” listed above “skip” whole systems and even
groups of “later” rocks (which are said to represent enormous
intervals of time), only to reappear, at last, in modern times. It is
evident that their existence has been continuous, and yet they are
not represented in the intervening strata. Clearly, then, the fossil
record is imperfect, and we must conclude that many of our modern
types actually did exist in the remote past, without, however, leaving
behind any vestige of their former presence.
Again, we must frankly confess our profound ignorance with
respect to the total number and kinds of species living in our modern
seas. Hence our conventional distinction between “extinct” and
“extant” species has only a provisory value. Future discoveries will
unquestionably force us to admit that many of the species now
classed as “extinct” are in reality living forms, which must be added
to our list of “persistent types.” “It is by no means improbable,” says
Heilprin, “that many of the older genera, now recognized as distinct
by reason of our imperfect knowledge concerning their true
relationships, have in reality representatives in the modern sea.”
(Op. cit. pp. 203, 204.)
Finally, the whole of our present taxonomy of plants and animals,
both living and fossil, stands badly in need of revision. Systematists,
as we have seen in the second chapter, base their classifications
mainly on what they regard as basic or homologous structures, in
contradistinction to superficial or adaptive characters. Both kinds of
structure, however, are purely somatic, and somatic characters, as
previously observed, are not, by themselves, a safe criterion for
discriminating between varieties and species. In the light of recent
genetical research, we cannot avoid recognizing that there has been
far too much “splitting” of organic groups on the basis of differences
that are purely fluctuational, or, at most, mutational. Moreover, the
distinction between homologous and adaptive structures is often
arbitrary and largely a matter of personal opinion, especially when
numerous specimens are not available. What the “Cambridge
Natural History” says in allusion to the Asteroidea is of general
application. “While there is considerable agreement,” we read,
“amongst authorities as to the number of families, or minor divisions
of unequivocal relationship, to be found in the class Asteroidea,
there has been great uncertainty both as to the number and limits of
the orders into which the class should be divided, and also as to the
limits of the various species. The difficulty about the species is by no
means confined to the group Echinodermata; in all cases where the
attempt is made to determine species by an examination of a few
specimens of unknown age there is bound to be uncertainty; the
more so, as it becomes increasingly evident that there is no sharp
line to be drawn between local varieties and species. In
Echinodermata, however, there is the additional difficulty that the
acquisition of ripe genital cells does not necessarily mark the
termination of growth; the animals can continue to grow and at the
same time slightly alter their characters. For this reason many of the
species described may be merely immature forms....
“The disputes, however, as to the number of orders included in the
Asteroidea proceed from a different cause. The attempt to construct
detailed phylogenies involves the assumption that one set of
structures, which we take as the mark of the class, has remained
constant, whilst the others which are regarded as adaptive, may
have developed twice or thrice. As the two sets of structures are
about of equal importance it will be seen to what an enormous extent
the personal equation enters in the determination of these
questions.” (Op. cit., vol. I, pp. 459, 460.)
In dealing with fossil forms, these difficulties of the taxonomist are
intensified: (1) by the sparse, badly-preserved, and fragmentary
character of fossil remains; (2) by the fact that here breeding
experiments are impossible, and hence the diagnosis based on
external characters cannot be supplemented by a diagnosis of the
germinal factors. Fossil taxonomy is, in consequence, extremely
arbitrary and unreliable. Many fossil forms classed as distinct
species, or even as distinct genera, may be nothing more than
fluctuants, mutants, hybrids, or immature stages of well-known
species living today. Again, many fossils mistaken for distinct
species are but different stages in the life-history of a single species,
a mistake, which is unavoidable, when specimens are few and the
age of the specimens unknown. The great confusion engendered in
the classification of the hydrozoa by nineteenth-century ignorance of
the alternation of hydroid and medusoid generations is a standing
example of the danger of classifying forms without a complete
knowledge of the entire life-cycle. When due allowance is made for
mutation, hybridization, metagenesis, polymorphism, age and
metamorphosis, the number of distinct fossil species will undergo
considerable shrinkage. Nor must we overlook the possibility of
environmentally-induced modifications. Many organisms, such as
mollusks, undergo profound alteration as a result of some important,
and, perhaps, relatively permanent, change in their environmental
conditions, though such alterations affect only the phenotype, and do
not involve a corresponding change in the specific genotype, i.e. the
germinal constitution of the race.
In the degree that these considerations are taken into account the
number of “extinct” fossil species will diminish and the number of
“persistent” species will increase. This is a consummation devoutly
to be wished for, but it means that hundreds of thousands of
described species must needs be reviewed for the purpose of
weeding out the duplicates, and who will have the knowledge, the
courage, or even the span of life, necessary to accomplish so
gigantic a task?
But so far as the practical purposes of our argument are
concerned, the accepted list of persistent types needs no
amplification. It suffices, as it stands, to establish the central fact
(which, for the rest, is admitted by everyone) that some generic and
even specific types have remained unchanged throughout the
enormous lapse of time which has intervened between the
deposition of the oldest strata and the advent of the present age. Our
current theories, far from diminishing the significance of this fact,
tend to intensify it by computing the duration of such persistence in
millions, rather than in thousands, of years. Now, whatever one’s
views may be on the subject of transformism, this prolonged
permanence of certain genera and species is an indubitable fact,
which is utterly irreconcilable with a universal law of organic
evolution. The theory of transformism is impotent to explain an
exception so palpable as this; for persistence and transmutation
cannot be subsumed under one and the same principle. That which
accounts for change cannot account for unchange. Yet unchange is
an observed fact, while the change, in this case, is an inferred
hypothesis. Hence, even if we accept the principle of transformism,
there will always be scope for the principle of permanence. The
extraordinary tenacity of type manifested by persistent genera and
species is a phenomenon deserving of far more careful study and
investigation than the evolutionally-minded scientist of today deigns
to bestow upon it. To the latter it may seem of little consequence,
but, to the genuine scientist, the actual persistence of types should
be of no less interest than their possible variability.
With these reflections, our criticism of the palæontological
argument terminates. The enumeration of its various deficiencies
was not intended as a refutation. To disprove the theory of organic
evolution is a feat beyond our power to accomplish. We can only
adduce negative evidence, whose scope is to show that the various
evolutionary arguments are inconsequential or inconclusive. We
cannot rob the theory of its intrinsic possibility, and sheer justice
compels us to confess that certain facts, like those of symbiotic
preadaptation, lend themselves more readily to a transformistic, than
to a fixistic, interpretation. On the other hand, nothing is gained by
ignoring flaws so obvious and glaring as those which mar the
cogency of palæontological “evidence.” The man who would gloss
them over is no true friend either of Science or of the scientific theory
of Evolution! They represent so many real problems to be frankly
faced and fully solved, before the palæontological argument can
become a genuine demonstration. But until such time as a
demonstration of this sort is forthcoming, the evolutionist must not
presume to cram his unsubstantiated theory down our reasonably
reluctant throats. To accept as certain what remains unproved, is to
compromise our intellectual sincerity. True certainty, which rests on
the recognition of objective necessity, will never be attainable so long
as difficulties that sap the very base of evolutionary argumentation
are left unanswered; and, as for those who, in the teeth of discordant
factual evidence, profess, nevertheless, to have certainty regarding
the “fact” of evolution, we can only say that such persons cannot
have a very high or exacting conception of what scientific certainty
really means.
For the rest, it cannot even be said that the palæontological record
furnishes good circumstantial evidence that our globe has been the
scene of a process of organic evolution. In fact, so utterly at variance
with this view is the total impression conveyed by the visible portion
of the geological column, that the modern geologist proposes, as we
have seen, to probe depths beneath its lowest strata for traces of
that alleged transmutation, which higher horizons do not reveal.
There are six to eight thick terranes below the Cambrian, we are
told, and igneous masses that were formerly supposed to be basal
have turned out to be intrusions into sedimentary accumulations, all
of which, of course, is fortunate for the theory of organic evolution,
as furnishing it with a sadly needed new court of appeal. The bottom,
so to speak, has dropped out of the geological column, and Prof. T.
C. Chamberlin announces the fact as follows: “The sharp division
into two parts, a lifeless igneous base and a sedimentary
fossiliferous superstructure, has given place to the general concept
of continuity with merely minor oscillations in times and regions of
major activity. Life has been traced much below the Cambrian, but its
record is very imperfect. The recent discoveries of more ample and
varied life in the lower Palæozoic, particularly the Cambrian, implies,
under current evolutional philosophy, a very great downward
extension of life. In the judgment of some biologists and geologists,
this extension probably reaches below all the pre-Cambrian terranes
as yet recognized, though this pre-Cambrian extension is great. The
‘Azoic’ bottom has retired to depths unknown. This profoundly
changes the life aspect of the ‘column.’” (Science, Feb. 8, 1924, p.
128.) All this is doubtless true, but such an appeal, from the known
to the unknown, from the actual to the possible, is not far-removed
from a confession of scientific insolvency. Life must, of course, have
had an earlier history than that recorded in the pre-Cambrian rocks.
But even supposing that some portion of an earlier record should
become accessible to us, it could not be expected to throw much
light on the problem of organic origins. Most of the primordial
sediments have long since been sapped and engulfed by fiery
magmas, while terranes less deep have, in all probability, been so
metamorphosed that every trace of their fossil contents has
perished. The sub-Archæan beginnings of life will thus remain
shrouded forever in a mystery, which we have no prospect of
penetrating. Hence it is the exposed portion of the geological column
which continues and will continue to be our sole source of
information, and it is preëminently on this basis that the evolutionary
issue will have to be decided.
Yet what could be more enigmatic than the rock record as it
stands? For in nature it possesses none of that idealized integrity
and coherence, with which geology has invested it for the purpose of
making it understandable. Rather it is a mighty chaos of scattered
and fragmentary fossiliferous formations, whose baffling complexity,
discontinuity, and ambiguity tax the ingenuity of the most sagacious
interpreters. Transformism is the key to one possible synthesis,
which might serve to unify that intricate mass of facts, but it is idle to
pretend that this theory is the unique and necessary corollary of the
facts as we find them. The palæontological argument is simply a
theoretical construction which presupposes evolution instead of
proving it. Its classic pedigrees of the horse, the camel, and the
elephant are only credible when we have assumed the “fact” of
evolution, and even then, solely upon condition that they claim to
approximate, rather than assign, the actual ancestry of the animals
in question. In palæontology, as in the field of zoölogy, evolution is
not a conclusion, but an interpretation. In palæontology, otherwise
than in the field of genetics, evolution is not amenable to the check
of experimental tests, because here it deals not with that which is,
but with that which was. Here the sole objective basis is the
mutilated and partially obliterated record of a march of events, which
no one has observed and which will never be repeated. These
obscure and fragmentary vestiges of a vanished past, by reason of
their very incompleteness, lend themselves quite readily to all sorts
of theories and all sorts of speculations. Of the “Stone Book of the
Universe” we may say with truth that which Oliver Wendell Holmes
says of the privately-interpreted Bible, namely, that its readers take
from it the same views which they had previously brought to it. “I am,
however, thoroughly persuaded,” say the late Yves Delage, “that one
is or is not a transformist, not so much for reasons deduced from
natural history, as for motives based on personal philosophic
opinions. If there existed some other scientific hypothesis besides
that of descent to explain the origin of species, many transformists
would abandon their present opinion as not being sufficiently
demonstrated.... If one takes his stand upon the exclusive ground of
the facts, it must be acknowledged that the formation of one species
from another species has not been demonstrated at all.” (“L’herédité
et les grands problèmes de la biologie générale,” Paris, 1903, pp.
204, 322.)
 II
THE PROBLEM OF ORIGINS
 CHAPTER I
THE ORIGIN OF LIFE

§ 1. The Theory of Spontaneous Generation

Strictly speaking, the theory of Transformism is not concerned with
the initial production of organic species, but rather with the
subsequent differentiation and multiplication of such species by
transmutation of the original forms. This technical sense, however, is
embalmed only in the term transformism and not in its synonym
evolution. The signification of the latter term is less definite. It may
be used to denote any sort of development or origination of one thing
from another. Hence the problem of the formation of organic species
is frequently merged with the problem of the transformation of
species under the common title of evolution.
This extension of the evolutionary concept, in its widest sense, to
the problem of the origin of life on our globe is known as the
hypothesis of abiogenesis or spontaneous generation. It regards
inorganic matter as the source of organic life not merely in the sense
of a passive cause, out of which the primordial forms of life were
produced, but in the sense of an active cause inasmuch as it
ascribes the origin of life to the exclusive agency of dynamic
principles inherent in inorganic matter, namely, the physicochemical
energies that are native to mineral matter. Life, in other words, is
assumed to have arisen spontaneously, that is, by means of a
synthesis and convergence of forces resident in inorganic matter,
and not through the intervention of any exterior agency.
The protagonists of spontaneous generation, therefore, assert not
merely a passive, but an active, evolution of living, from lifeless
matter. As to the fact of the origin of the primal organisms from
inorganic matter, there is no controversy whatever. All agree that, at
some time or other, the primordial plants and animals emanated from
inorganic matter. The sole point of dispute is whether they arose
from inorganic matter by active evolution or simply by passive
evolution. The passive evolution of mineral matter into plants and
animals is an everyday occurrence. The grass assimilates the
nitrates of the soil, and is, in turn, assimilated by the sheep, whose
flesh becomes the food of man, and mineral substance is thus finally
transformed into human substance. In the course of metabolic
processes, the inorganic molecule may doff its mineral type and don,
in succession, the specificities of plant, animal, and human
protoplasm; and this transition from lower to higher degrees of
perfection may be termed an evolution. It is an ascent of matter from
the lowermost grade of an inert substance, through the intermediate
grades of vegetative and animal life, up to the culminating and
ultimate term of material perfection, in the partial constitution of a
human nature and personality, in the concurrence as a coagent in
vegetative and sensile functions, and in the indirect participation, as
instrument, in the higher psychic functions of rational thought and
volition.
At the present time, the inorganic world is clearly the exclusive
source of all the matter found in living beings. All living beings
construct their bodies out of inorganic substances in the process of
nutrition, and render back to the inorganic world, by dissimilation and
death, whatever they have taken from it. We must conclude,
therefore, the matter of the primordial organisms was likewise
derived from the inorganic world. But we are not warranted in
concluding that this process of derivation was an active evolution.
On the contrary, all evidence is against the supposition that brute
matter is able to evolve of itself into living matter. It can, indeed, be
transformed into plants, animals, and men through the action of an
appropriate external agent (i.e. solely through the agency of the
living organism), but it cannot acquire the perfections of living matter
by means of its own inherent powers. It cannot vitalize, or sensitize,
itself through the unaided activity of its own physicochemical
energies. Only when it comes under the superior influence of
preëxistent life can it ascend to higher degrees of entitive perfection.
It does not become of itself life, sensibility, and intelligence. It must
first be drawn into communion with what is already alive, before it
can acquire life and sensibility, or share indirectly in the honors of
intelligence (as the substrate of the cerebral imagery whence the
human mind abstracts its conceptual thought). Apart from this unique
influence, inorganic matter is impotent to raise itself in the scale of
existence, but, if captured, molded, and transmuted by a living being,
it may progress to the point of forming with the human soul one
single nature, one single substance, one single person. The
evolution of matter exemplified in organic metabolism is obviously
passive, and such an evolution of the primal organisms out of non-
living matter even the opponents of the hypothesis of spontaneous
generation concede. But spontaneous generation implies an active
evolution of the living from the lifeless, and this is the point around
which the controversy wages. It would, of course, be utterly irrational
to deny to the Supreme Lord and Author of Life the power of vivifying
matter previously inanimate and inert, and hence the origin of
organic life from inorganic matter by a formative (not creative) act of
the Creator is the conclusion to which the denial of abiogenesis
logically leads.
The hypothesis of spontaneous generation is far older than the
theory of transformism. It goes back to the Greek predecessors of
Aristotle, at least, and may be of far greater antiquity. It was based,
as is well known, upon an erroneous interpretation of natural facts,
which was universally accepted up to the close of the 17th century.
As we can do no more than recount a few outstanding incidents of its
long and interesting history here, the reader is referred to the VII
chapter of Wasmann’s “Modern Biology” and the VIII chapter of
Windle’s “Vitalism and Scholasticism” for the details which we are
obliged to omit.

§ 2. The Law of Genetic Continuity—

From time immemorial the sudden appearance of maggots in
putrescent meat had been a matter of common knowledge, and the
ancients were misled into regarding the phenomenon as an instance
of a de novo origin of life from dead matter. The error in question
persisted until the year 1698, when it was decisively disproved by a
simple experiment of the Italian physician Francesco Redi. He
protected the meat from flies by means of gauze. Under these
conditions, no maggots appeared in the meat, while the flies, unable
to reach the meat, deposited their eggs on the gauze. Thus it
became apparent that the maggots were larval flies, which emerged
from fertilized eggs previously deposited in decaying meat by female
flies. Antonio Vallisnieri, another Italian, showed that the fruit-fly had
a similar life-history. As a result of these discoveries, Redi rejected
the theory of spontaneous generation and formulated the first article
of the Law of Genetic Vital Continuity: Omne vivum ex vivo.
Meanwhile, the first researches conducted by means of the newly
invented compound microscope disclosed what appeared to be fresh
evidence in favor of the discarded hypothesis. The unicellular
organisms known as infusoria were found to appear suddenly in hay
infusions, and their abrupt appearance was ascribed to spontaneous
generation. Towards the end of the 18th century, however, a Catholic
priest named Lazzaro Spallanzani refuted this new argument by
sterilizing the infusions with heat and by sealing the containers as
protection against contamination by floating spores or cysts. After
the infusions had been boiled for a sufficient time and then sealed,
no organisms could be found in them, no matter how long they were
kept. We now know that protozoa and protophytes do not originate
de novo in infusions. Their sudden appearance in cultures is due to
the deposition of spores or cysts from the air, etc.
The possibility that the non-germination of life in sterilized
infusions kept in sealed containers might be due to the absence of
oxygen, removed by boiling and excluded by sealing, left open a
single loophole, of which the 19th century defenders of abiogenesis
proceeded to avail themselves. Pasteur, however, by employing
sterilized cultures, which he aerated with filtered air exclusively,
succeeded in depriving his opponents of this final refuge, and
thereby completely demolished the last piece of evidence in favor of
spontaneous generation. Prof. Wm. Sydney Thayer, in an address
delivered at the Sorbonne, May 22, 1923, gives the following
account of Pasteur’s experiments in this field: “Then, naturally (1860-
1876) came the famous studies on spontaneous generation
undertaken against the advice of his doubting masters, Biot and
Dumas. On the basis of careful and well-conceived experiments he
demonstrated the universal presence of bacteria in air, water, dust;
he showed the variation in different regions of the bacterial content
of the air; he demonstrated the permanent sterility of media
protected from contamination, and he insisted on the inevitable
derivation of every living organism from one of its kind. ‘No,’ he said,
‘there is no circumstance known today which justifies us in affirming
that microscopic organisms have come into the world, without
parents like themselves. Those who made this assertion have been
the playthings of illusions or ill-made experiments invalidated by
errors which they have not been able to appreciate or to avoid.’ In
the course of these experiments he demonstrated the necessity of
reliable methods of sterilization for instruments or culture media, of
exposure for half an hour to moist heat at 120° or to dry air at 180°.
And behold! our modern procedures of sterilization and the basis of
antiseptic surgery.” (Science, Dec. 14, 1923, p. 477.) Pasteur
brought to a successful completion the work of Redi and
Spallanzani. Henceforth spontaneous generation was deprived of all
countenance in the realm of biological fact.
Meanwhile, the cytologists and embryologists of the last century
were adding article after article to the law of genetic cellular
continuity, thus forging link by link the fatal chain of severance that
inexorably debars abiogenesis from the domain of natural science.
With the formulation of the great Cell Theory by Schleiden and
Schwann (1838-1839), it became clear that the cell is the
fundamental unit of organization in the world of living matter. It has
proved to be, at once, the simplest organism capable of independent
existence and the basic unit of structure and function in all the more
complex forms of life. The protists (unicellular protozoans and
protophytes) consist each of a single cell, and no simpler type of
organism is known to science. The cell is the building brick out of
which the higher organisms or metists (i.e. the multicellular and
tissued metazoans and metaphytes) are constructed, and all
multicellular organisms are, at one time or other in their career,
reduced to the simplicity of a single cell (v.g. in the zygote and spore
stages). The somatic or tissue cells, which are associated in the
metists to form one organic whole, are of the same essential type as
germ cells and unicellular organisms, although the parallelism is
more close between the unicellular organism and the germ cell. The
germ cell, like the protist, is equipped with all the potentialities of life,
whereas tissue cells are specialized for one function rather than
another. The protist is a generalized and physiologically-balanced
cell, one which performs all the vital functions, and in which the
suppression of one function leads to the destruction of all the rest;
while the tissue cell is a specialized and physiologically-unbalanced
cell limited to a single function, with the other vital functions in
abeyance (though capable of manifesting themselves under certain
circumstances). Normally, therefore, the tissue cell is functionally
incomplete, a part and not a whole, whereas the protist is an
independent individual, being, at once, the highest type of cell and
the lowest type of organism.
According to the classic definition of Franz Leydig and Max
Schultze, the cell is a mass of protoplasm containing a nucleus, both
protoplasm and nucleus arising through division of the corresponding
elements of a preëxistent cell. In this form the definition is quite
general and applies to all cells, whether tissue cells, germ cells, or
unicellular organisms. Moreover, it embodies two principles which
still further determine the law of genetic cellular continuity, namely:
Omnis cellula ex cellula, enunciated by Virchow in 1855, and
Flemming’s principle: Omnis nucleus ex nucleo, proclaimed in 1882.
In this way, Cytology supplemented Redi’s formula that every living
being is from a preëxistent living being, by adding two more articles,
namely, that every living cell is from a preëxistent cell, and every
new cellular nucleus is derived by division from a preëxistent cellular
nucleus. Now neither the nucleus nor the cell-body (the cytoplasm or
extranuclear area of the cell) is capable of an independent existence.
The cytoplasm of the severed nerve fibre, when it fails to reëstablish
its connection with the neuron nucleus, degenerates. The enucleated
amœba, though capable of such vital functions as depend upon
destructive metabolism, can do nothing which involves constructive
metabolism, and is, therefore, doomed to perish. The sperm cell,
which is a nucleus that has sloughed off most of its cytoplasm,
disintegrates, unless it regains a haven in the cytoplasm of the egg.
Life, accordingly, cannot subsist in a unit more simply organized than
the cell. No organism lives which is simpler than the cell, and the
origin of all higher forms of life is reducible, as we shall see, to the
origin of the cell. Consequently, new life can originate in no other
way than by a process of cell-division. All generation or reproduction
of new life is dependent upon the division of the cell-body and
nucleus of a preëxistent living cell.
Haeckel, it is true, has attempted to question the status of the cell
as the simplest of organisms, by alleging the existence of cytodes
(non-nucleated cells) among the bacteria and the blue-green algæ.
Further study, however, has shown that bacteria and blue-green
algæ have a distributed nucleus, like that of certain ciliates, such as
Dileptus gigas and Trachelocerca. In such forms the entire cell body
is filled with scattered granules of chromatin called chromioles, and
this diffuse type of nucleus seems to be the counterpart of the
concentrated nuclei found in the generality of cells. At any rate, there
is a temporary aggregation of the chromioles at critical stages in the
life-cycle (such as cell-division), and these scattered chromatin
granules undergo division, although their distribution to the daughter-
cells is not as regular as that obtaining in mitosis. All this is strongly
suggestive of their nuclear nature, and cells with distributed nuclei
cannot, therefore, be classified as cytodes. In fact, the polynuclear
condition is by no means uncommon. Paramœcium aurelia, for
example, has a macronucleus and a micronucleus, and the
Uroleptus mobilis has eight macronuclei and from two to four
micronuclei. The difference between the polynuclear and diffuse
condition seems to be relatively unimportant. In fact, the distributed
nucleus differs from the morphological nucleus mainly in the
absence of a confining membrane. From the functional standpoint,
the two structures are identical. Hence the possession of a nucleus
or its equivalent is, to all appearances, a universal characteristic of
cells. Haeckel’s “cytodes” have proved to be purely imaginary
entities. The verdict of modern cytologists is that Shultze’s definition
of the cell must stand, and that the status of the cell as the simplest
of organic units capable of independent existence is established
beyond the possibility of prudent doubt.
With the progressive refinement of microscopic technique, it has
become apparent that the law of genetic continuity applies not
merely to the cell as a whole and to its major parts, the nucleus and
the cell-body, but also to the minor components or organelles, which
are seen to be individually self-perpetuating by means of growth and
division. The typical cell nucleus, as is well known, is a spherical
vesicle containing a semisolid, diphasic network of basichromatin
(formerly “chromatin”) and oxychromatin (linin) suspended in more
fluid medium or ground called nuclear sap. When the cell is about to
divide, the basichromatin resolves itself into a definite number of
short threads called chromosomes. Now, Boveri found that, in the
normal process of cell-division known as mitosis, these nuclear
threads or chromosomes are each split lengthwise and divided into
two exactly equivalent halves, the resulting halves being distributed
in equal number to the two daughter-cells produced by the division of
the original cell. Hence, in the year 1903, Boveri added a fourth
article to the law of genetic vital continuity, namely: Omne
chromosoma ex chromosomate.
But the law in question applies to cytoplasmic as well as nuclear
components. In physical appearance, the cell-body or cytoplasm
resembles an emulsion with a clear semiliquid external phase called
hyaloplasm and an internal phase consisting mainly of large spheres
called macrosomes and minute particles called microsomes, all of
which, together with numerous other formed bodies, are suspended
in the clear hyaloplasm (hyaline ground-substance). Now certain of
these cytoplasmic components have long been known to be self-
perpetuating by means of growth and division, maintaining their
continuity from cell to cell. The plastids of plant cells, for example,
divide at the time of cell-division, although their distribution to the
daughter-cells does not appear to be as definite and regular as that
which obtains in the case of the chromosomes. Similarly, the
centrioles or division-foci of animal cells are self-propagating by
division, but here the distribution to the daughter-cells is exactly
equivalent and not at random as in the case of plastids. In the light of
recent research it looks as though two other types of cytoplasmic
organelles must be added to the list of cellular components, which
are individually self-perpetuating by growth and division, namely, the
chondriosomes and the Golgi bodies—“both mitochondria and Golgi
bodies are able to assimilate, grow, and divide in the cytoplasm.”
(Gatenby.) Wilson is of opinion that the law of genetic continuity may
have to be extended even to those minute granules and particles of
the cytosome, which were formerly thought to arise de novo in the
apparently structureless hyaloplasm. Speaking of the emulsified
appearance of the starfish and sea urchin eggs, he tells us that their
protoplasm shows “a structure somewhat like that of an emulsion,
consisting of innumerable spheroidal bodies suspended in a clear
continuous basis or hyaloplasm. These bodies are of two general
orders of magnitude, namely: larger spheres or macrosomes rather
closely crowded and fairly uniform in size, and much smaller
microsomes irregularly scattered between the macrosomes, and
among these are still smaller granules that graduate in size down to
the limit of vision with any power (i.e. of microscope) we may
employ.” (Science, March 9, 1923, p. 282.) Now, the limit of
microscopic vision by the use of the highest-power oil-immersion
objectives is one-half the length of the shortest waves of visible light,
that is, about 200 submicrons (the submicron being one millionth of a
millimeter). Particles whose diameter is less than this cannot reflect
a wave of light, and are, therefore, invisible so far as the microscope
is concerned. By the aid of the ultramicroscope, however, we are
enabled to see the halos formed by particles not more than four
submicrons in diameter, which, however, represents the limit of the
ultramicroscope, and is the diameter hypothetically assigned to the
protein multimolecule. Since, therefore, we find the particles in the
protoplasm of the cell body graduating all the way down to the limit
of this latter instrument, and since on the very limit of microscopic
vision we find such minute particles as the centrioles “capable of
self-perpetuation by growth and division, and of enlargement to form
much larger bodies,” we cannot ignore the possibility that the
ultramicroscopic particles may have the same powers and may be
the sources or “formative foci” of the larger formed bodies, which
were hitherto thought to arise de novo.
 Certainly, pathology, as we shall see, tells us of ultramicroscopic
disease-germs, which are capable of reproduction and maintenance
of a specific type, and experimental genetics makes us aware of a
linear alignment of submicroscopic genes in the nuclear
chromosomes, each gene undergoing periodic division and
perpetual transmission from generation to generation. The cytologist,
therefore, to quote the words of Wilson, “cannot resist the evidence
that the appearance of a simple homogeneous colloidal substance is
deceptive; that it is in reality a complex, heterogeneous, or
polyphasic system. He finds it difficult to escape the conclusion,
therefore, that the visible and the invisible components of the
protoplasmic system differ only in their size and degree of
dispersion; that they belong to a single continuous series, and that
the visible structure of protoplasm may give us a rough magnified
picture of the invisible.” (Ibidem, p. 283.)
It would seem, therefore, that we must restore to honor, as the fifth
article of the law of cellular continuity, the formula, which Richard
Altmann enunciated on purely speculative grounds in 1892, but
which the latest research is beginning to place on a solid factual
basis, namely: Omne granulum ex granulo. “For my part,” says the
great cytologist, Wilson, “I am disposed to accept the probability that
many of these particles, as if they were submicroscopical plastids,
may have a persistent identity, perpetuating themselves by growth
and multiplication without loss of their specific individual type.” And
he adds that the facts revealed by experimental embryology (e.g.,
the existence of differentiated zones of specific composition in the
cytoplasm of certain eggs) “drive us to the conclusion that the
submicroscopical components of the hyaloplasm are segregated and
distributed according to an ordered system.” (Ibidem, p. 283.) The
structure of the cell has often been likened to a heterogeneous
solution, that is, to a complex polyphasic colloidal system, but this
power of perpetual division and orderly assortment possessed by the
cell as a whole and by its single components is the unique property
of the living protoplasmic system, and is never found in any of the
colloidal systems known to physical chemistry, be they organic or
inorganic.