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 BASIC PRINCIPLES OF DRUG
DISCOVERY AND DEVELOPMENT
 BASIC PRINCIPLES OF
DRUG DISCOVERY AND
DEVELOPMENT

SECOND EDITION

BENJAMIN E. BLASS
Temple University School of Pharmacy, Department of Pharmaceutical Sciences,
Moulder Center for Drug Discovery Research, Philadelphia, PA, United States
Academic Press is an imprint of Elsevier
125 London Wall, London EC2Y 5AS, United Kingdom
525 B Street, Suite 1650, San Diego, CA 92101, United States
50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States
The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom
Copyright © 2021 Elsevier Inc. All rights reserved.
No part of this publication may be reproduced or transmitted in any form or by any means,
electronic or mechanical, including photocopying, recording, or any information storage and
retrieval system, without permission in writing from the publisher. Details on how to seek
permission, further information about the Publisher’s permissions policies and our arrangements
with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency,
can be found at our website: www.elsevier.com/permissions.
This book and the individual contributions contained in it are protected under copyright by the
Publisher (other than as may be noted herein).
Notices
Knowledge and best practice in this field are constantly changing. As new research and experience
broaden our understanding, changes in research methods, professional practices, or medical
treatment may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in
evaluating and using any information, methods, compounds, or experiments described herein. In
using such information or methods they should be mindful of their own safety and the safety of
others, including parties for whom they have a professional responsibility.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors,
assume any liability for any injury and/or damage to persons or property as a matter of products
liability, negligence or otherwise, or from any use or operation of any methods, products,
instructions, or ideas contained in the material herein.

British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library
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A catalog record for this book is available from the Library of Congress

ISBN: 978-0-12-817214-8

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visit our website at https://www.elsevier.com/books-and-journals

Publisher: Susan Dennis

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Typeset by MPS Limited, Chennai, India
 Dedication

Sir Isaac Newton, one of the greatest scientists of his time, wrote “If I
have seen further it is by standing on the shoulders of Giants.”
Although he was almost certainly referring to his scientific achieve-
ments, the underling concept of learning from our forbearer is true in
any endeavor. Indeed, this concept can be further extended to include
those who are there in the present day, supporting the activities of an
individual as he or she attempts to accomplish that which they view as
important. With this thought in mind, I have dedicated this book to the
scientists who came before me, those who mentored me, and those who
work with me on a daily basis. In addition, and perhaps more impor-
tantly, this text is dedicated to the loving and supportive family that
has helped me become the person that I am today. Special thanks are
offered to my mother, father, sister, brother, my three children, and of
course, my wife Kathleen. These are the giants on whose shoulders I
have stood upon.
 Contents

Foreword xv

1. Drug discovery and development: An overview of modern

methods and principles 1
Drug discovery and development from 20,000 Feet 11
Target selection: the first step forward 15
Hit identification: finding a starting point 19
Identify a clinical candidate: juggling the properties 25
Questions 31
References 31

2. The drug discovery process: From ancient times to the

present day 43
The age of botanicals: pre-industrial drug discovery 44
Early biotherapeutics: before the biotechnology revolution 48
Paul Ehrlich: the father of modern drug discovery 51
Milestones in drug discovery 53
Milestones in animal models: breeding a better model 54
The Wistar rat 54
Immunocompromised mice 55
Transgenic animal models 56
Knockout animal models 58
Milestones in molecular science 60
X-ray crystallography 60
Molecular modeling and computational chemistry 63
High-throughput technology: chemical synthesis and screening science 64
Milestones in biotechnology 70
Recombinant DNA and transfection technology 72
Polymerase chain reaction technology 75
DNA Sequencing and genomics 76
Proteomics 80
Monoclonal antibody and hybridoma technology 83
The rise of biologics and macromolecular therapeutics 86
Societal and governmental impacts 87
The Pure Food and Drug Act of 1906 88
The Elixir of Sulfanilamide Disaster of 1937 89
The Thalidomide story 91
Regulatory milestones 93

vii
viii CONTENTS

Durham-Humphrey Amendment of 1951 94

Kefauver-Harris Amendment of 1962 95
Hatch-Waxman Act of 1984 96
Biologics Price Competition and Innovation Act of 2009 97
Future developments in drug discovery 99
Questions 99
References 100

3. Classical targets in drug discovery 111

Protein structure 113
Enzymes 119
Inhibition of enzymes 125
G-protein-coupled receptors 130
G-protein-dependent signaling pathways 133
Cyclic adenosine monophosphate signaling 134
IP3 signaling 136
β-Arrestin pathways 138
G-protein-coupled receptor signaling pathways 140
Modulating G-protein-coupled receptor signaling 141
Ion channels 143
Gating mechanisms 149
Ligand-gated channels 149
Voltage-gated channels 152
Other gating mechanisms 155
Membrane transport proteins (transporters) 156
Nuclear receptors 164
Nuclear receptor signaling pathways 167
Modulating nuclear receptor activity 169
Biomolecular interactions: protein/protein, protein/DNA, and protein/RNA
interfaces 170
Types of “hot spots” in biomolecular interactions 172
Stabilizing biomolecular interactions 174
Questions 176
References 176

4. In vitro screening systems 185

The language of screening: basic terms 186
Concentration response curves and IC50s 187
Dissociation constants (Kd) and inhibition constants (Ki) 188
Efficacy versus binding: EC50s 190
Agonist, partial agonist, antagonist, allosteric modulators, and inverse agonists 191
Agonists and partial agonists 192
Antagonists 193
Basal activity and inverse agonist 193
Receptor reserve 193
Allosteric modulation 194
 CONTENTS ix

Streptavidin and biotin 195

Biochemical versus cellular assays 196
Assay systems and methods of detection 198
Radioligand systems 199
Scintillation proximity assay 201
Enzyme-linked immunosorbent assay 204
Fluorescence-based assay systems 206
Fluorescence polarization 207
Fluorescence resonance energy transfer 210
Time-resolved fluorescence resonance energy transfer 214
Amplified luminescent proximity homogeneous assay (AlphaScreent) 217
Fluorescent detection of calcium flux 220
Reporter gene assays 223
Chloramphenicol acetyltransferase 224
β-Lactamase reporter assays 224
Luciferase reporter assays 226
Bioluminescence resonance energy transfer assays 228
Kinetic fluorescent measurement systems 230
Label-free assay systems 231
Cellular dielectric spectroscopy 232
Optical biosensors 233
Surface plasmon resonance technology 236
Electrophysiological patch clamp 237
Thermal shift assay 240
High content screening 243
General consideration for all screening methods 245
Questions 248
References 248

5. Medicinal chemistry 257

Structure activity relationships and structure property relationships 258
The role of chirality 263
Push and pull in structure activity relationships 266
Quantitative structure activity relationships 267
The pharmacophore 272
Developing an structure activity relationship data set 276
The structure activity relationship cycle 287
Bioisosterism 288
Structure activity relationship, selectivity, and physicochemical properties 294
“Drug-like” guidelines 295
Questions 297
References 298

6. In vitro ADME and in vivo pharmacokinetics 305

Absorption 309
Solubility 310
Permeability 315
x CONTENTS

Distribution 324
Permeability 326
Transporters 328
Plasma protein binding 330
Elimination pathways 332
Metabolism 333
Excretion 345
In vitro ADME model systems 348
In Vivo pharmacokinetics 351
Volume of distribution 353
Clearance 355
Half-life 356
Bioavailability 359
Species selection 362
Questions 362
References 364

7. Animal models of disease states 371

Sources of animal models 373
Validity of animal models 376
Species selection 377
Number of animals 378
Exemplary animal models by disease category 378
Animal models in neuroscience 379
The forced swimming test: A model of depression 379
The elevated plus maze: A measure of anxiety 380
The novel object recognition test: A model of memory and cognition 381
Contextual fear conditioning model: A model of contextual learning 382
The Morris water maze: A model of spatial learning and memory 383
Animal models of neurodegeneration 384
The SOD1G93A mouse of amyotrophic lateral sclerosis (ALS) 384
The MPTP model of Parkinson’s disease 386
Animal models of cardiovascular disease 387
Models of hypertension 387
Models of hyperlipidemia and high cholesterol 389
Models of atrial fibrillation 391
Models of heart failure 393
Animal models of infectious disease 396
Murine thigh infection model 397
Murine model of systemic infection 397
Mouse model of influenza virus infection 398
Limitations of animal models of infection 399
Animal models of oncology 400
Mouse xenograft tumor model 400
Mouse allograft tumor model 401
Genetically engineered mouse models of cancer 402
 CONTENTS xi

Animal models of pain 403

The Von Frey test 404
The Ramdall-Selitto test 405
Heat based models 406
Inflammation based models 408
Surgical models 409
General consideration for pain models 409
Animal models of diabetes 409
Animal models of drug addiction 411
Conclusion 413
Questions 414
References 414

8. Safety and toxicology 421

Sources of toxicity 423
Acute versus chronic toxicity 430
Cytotoxicity 430
Carcinogenicity, genotoxicity, and mutagenicity 432
Drug drug interactions 436
Cardiovascular safety and toxicology studies 438
Central nervous system safety and toxicology studies 445
Immune system-mediated safety issues 447
Teratogenicity 450
In vivo toxicity and safety studies 451
Questions 453
References 453

9. Antibody-drug discovery 459

IgG structure and function 461
Antibody therapy drug discovery 463
Hybridoma technology 463
Antibody phage display 469
Modified monoclonal antibodies 473
General considerations 476
Conclusion 478
Questions 478
References 478

10. Basics of clinical trials 483

Before the clinic 486
Drug supply 486
Delivery methods 489
Formulation 491
Investigational new drug application 502
Phase 1 clinical trials 504
xii CONTENTS

Phase 2 clinical trials 506

Phase 3 clinical trials 510
Phase 4 clinical trials 515
Adaptive clinical trial design 516
Meta-analysis of clinical trial data 517
Questions 519
References 519

11. Translational medicine and biomarkers 523

Definition of a biomarker and their classification 526
Characteristics and impact of biomarkers 529
Biomarkers versus surrogate endpoints 531
Imaging technologies 533
The practical application of biomarkers 540
Dipeptidyl peptidase IV inhibitors (Januvia) 541
Physiological measurements as biomarkers: Orexin antagonists 543
FDG PET imaging agent 545
The neurokinin 1 receptor, depression, and PET imaging:
The Aprepitant story 546
Cancer biomarkers 548
Conclusion 553
Questions 553
References 554

12. Organizational consideration and trends in the

pharmaceutical industry 561
Organizational structures of pharmaceutical companies 562
Business divisions interactions 562
The discovery project team evolutionary cycle 563
The business climate 567
Mergers and acquisitions 567
Contract research organizations 573
Academic drug discovery 575
Funding issues 581
Conclusion 584
Questions 584
Appendix 1 585
References 591

13. Intellectual property and patents in drug discovery 595

Patentable subject matter 597
Inherent properties and patentability 601
Novelty and the prior art 603
Obviousness and the prior art 604
Inventorship 607
 CONTENTS xiii

Assignment and ownership 609

Classification of patents and patent applications 611
Impact of overlapping patents 612
Patent applications and their contents 612
Contents of a patent application 617
Conclusion 621
Questions 622
References 622

14. Case studies in drug discovery 625

Tamiflu: From mechanism of action to marketed drug 625
Histone deacylase inhibitors: Physicochemical optimization via structural change 630
HIV protease inhibitors: Chemically complex miracle drugs 632
Nitrofurantoin: A surprisingly successful drug 637
Seldanes (Terfenadine) vs Allegras (Fexofenadine): Metabolism matters: Safety 639
Claritins (Loratadine) versus Clarinexs (Desloratadine): Metabolism matters:
Pharmacokinetics 642
MPTP: Parkinson’s disease in a bottle 644
Bupropion and Methylphenidate: Improving performance via formulation
changes 647
Selective inhibition of COX-2: The impact of an inadequate written description 651
Antibiotic resistant bacteria and the development of β-lactamase inhibitors 652
Association for Molecular Pathology vs Myriad Genetics: The validity of gene
patents 655
Conclusion 658
Questions 659
References 659

Answers to questions in textbook by chapter 665

Subject Index 693

Drug Index 713
 Foreword

The last several decades have witnessed a revolution in the drug dis-
covery and development process. Medicinal chemistry and in vitro
screening that were once major bottlenecks in the process of identifying
novel therapeutics have been dramatically accelerated through the
incorporation of automation and the development of enabling technolo-
gies such as recombinant DNA and transfection technology. High-
throughput screening, parallel synthesis, and combinatorial chemistry
have facilitated the synthesis and biological evaluation of large numbers
of potentially useful compounds. These activities, in turn, have gener-
ated vast amounts of data that can be analyzed to develop structure
activity relationships and structure property relationships useful for the
optimization of lead compounds. At the same time, new techniques,
technological advances, and a greater understanding of the importance
of pharmacokinetics, animal models, and safety studies have dramati-
cally altered how new molecules are selected for clinical study. Clinical
trial design strategies, biomarkers, translational medicine, the regulatory
landscape, intellectual property rights, and the business environment
have also changed dramatically over the course of the last 40 years.
The complexities of the drug discovery and development process
cannot be overstated, nor can the wide range of expertise required for
the successful development of new, marketable therapeutics. In order to
thrive in this very changing landscape, individuals interested in a career
in the pharmaceutical industry or related fields must be more than sim-
ply experts in their chosen field of study. They must also have an
understanding of the numerous, overlapping fields of their colleagues.
Basic Principles in Drug Discovery and Development has captured the criti-
cal information on the disparate processes, technologies, and expertise
required for modern drug discovery and development and presents it
in a logical and concise manner for students, practicing scientists, and
nonscientist with an interest in the pharmaceutical industry. Dr.
Benjamin E. Blass, an experienced educator and scientist with founda-
tional knowledge in medicinal chemistry, drug design, biological tar-
gets, and over 25 years of experience in industrial and academic drug
discovery and development, provides a comprehensive account of the
many functions involved in drug discovery and development, from

xv
xvi Foreword

initial medicinal chemistry conceptualization and in vitro biological

evaluation to clinical trials and beyond.
There are many aspects of this book that will help practicing scien-
tists, graduate students, and future drug researchers to develop a strong
foundation in the concepts that govern the multidisciplinary process of
drug discovery. Through this unique text, they will acquire an under-
standing of key aspects of drug discovery and development. The organi-
zation of the subject material was chosen to allow the readers to
incrementally increase their knowledge in the wide range of disciplines
required to identify new, marketable therapeutic agents. The book is
thoroughly written and includes 14 chapters with more than 300
figures and 900 references. Throughout the text the reader will become
familiar with more than 100 drugs and clinical candidates that exem-
plify important theories and practices.
Each chapter contains examples of drugs pertaining to the material in
the chapter. The opening chapter provides an overview of drug discov-
ery and development. This serves as the foundation for the following 12
chapters that describe the various functions involved in drug discovery
and development. The early phases of drug discovery are described in
detail through the discussions of important topics such as target identi-
fication, target validation, lead identification, multidimensional lead
optimization, pharmacokinetics, preclinical pharmacodynamics, and
early toxicology. This is followed by discussions of preclinical activities,
clinical trial design, biomarkers, and translational medicine. Each chap-
ter builds on the previous chapters and this approach provides the
readers with an integrated view of the various multidisciplinary func-
tions required for the drug discovery and development process.
Chapter 12, Organizational Consideration and Trends in the
Pharmaceutical Industry, and Chapter 13, Intellectual Property and
Patents in Drug Discovery, describe two important topics essential for
running an effective pharmaceutical R&D business, organizational
structure and patent protection. These chapters give the reader a true
understanding of the organizational structure required for the success-
ful management of research and development organizations and the
importance of protecting intellectual property to ensure a good return
on investment. Patent protection is the life blood of the pharmaceutical
and biotech industries, and at the same time a source of innovation for
new discoveries. Patents ensure the sharing of discoveries and innova-
tions that might otherwise be kept as trade secrets. In the final chapter,
case studies demonstrating the practical application of the concepts and
principles described in the previous chapters are provided. These vign-
ettes also describe important lessons learned in each case, some of
which changed the way modern drug-discovery research and develop-
ment programs are executed.
 Foreword xvii

Although there are numerous textbooks that discuss various aspects

of the drug discovery and development process, none of them provides
a comprehensive view of the process. Basic Principles in Drug Discovery
and Development is unique in its comprehensive approach to this com-
plex endeavor. In writing this textbook, Dr. Blass has provided an
important new tool for the education of the next generation and a valu-
able resource for people with a vested interest in the identification and
commercialization of novel medications.

Magid Abou-Gharbia, PhD, FRSC

Laura H. Carnell Professor
Director Moulder Center for Drug Discovery Research
School of Pharmacy, Temple University
Philadelphia, PA, United States
Another random document with
no related content on Scribd:
The Project Gutenberg eBook of Honeymoon in
bedlam
This ebook is for the use of anyone anywhere in the United States
and most other parts of the world at no cost and with almost no
restrictions whatsoever. You may copy it, give it away or re-use it
under the terms of the Project Gutenberg License included with this
ebook or online at www.gutenberg.org. If you are not located in the
United States, you will have to check the laws of the country where
you are located before using this eBook.

Title: Honeymoon in bedlam

Author: Nelson S. Bond

Illustrator: Henry del Campo

Release date: July 11, 2024 [eBook #74019]

Language: English

Original publication: New York, NY: Weird Tales, 1940

Credits: Greg Weeks, Mary Meehan and the Online Distributed

Proofreading Team at http://www.pgdp.net

*** START OF THE PROJECT GUTENBERG EBOOK HONEYMOON IN

BEDLAM ***
 Honeymoon in Bedlam

By NELSON S. BOND

Gigantic webs of doom—miles

in extent, hundreds of feet deep.

[Transcriber's Note: This etext was produced from

Weird Tales January 1941.
Extensive research did not uncover any evidence that
the U.S. copyright on this publication was renewed.]
I remember the preacher saying, "I now pronounce you man and
wife—," and I remember the sweet smile on Lorraine Bowman's face
and the dazed smirk on Johnny Larkin's, and the clank of sabers as
we walked up the aisle through an arch of gleaming steel. I
remember asking to kiss the bride. Then I remember something
about a banquet, with somebody passing out drinks, and I
remember demanding to kiss the bride again.
Then there was another bottle or three, and it must have been
powerful juice because I remember Johnny Larkin frowning when I
insisted on kissing the bride. Then I felt sorry for myself and started
to cry, and Captain Bowman roared something about, "Take that
boiled son-of-a-spacehawk home and pour him into bed," and I
looked around, wondering who was tanked, and by golly, they all
were but me! Which I tried to explain, standing on a table so I could
get their attention, but somebody pulled the table out from under
me.
And that's all I remember until I woke up the next morning with my
mouth tasting like the inside of a birdcage, and Lt. Sam Evans,
Second Mate of the Pegasus, was standing at my bedside grinning at
me. Sunbeams were bouncing up and down on my counterpane like
elephants. I moaned and said, "Get 'em out of here, Sam!"
He said, "Them? Who?"
"Those little purple men. They're making faces at me."
He said, "Shoo! Go away, little purple men!" and they disappeared.
"You," he said, "sure collected yourself a snootful last night."
"Who?" I demanded, holding the top of my head on. "Me? I don't
know what you're talking about. Can I help it if I was suddenly taken
sick?"
"You were suddenly taken," he chortled, "drunk! I thought I'd die
when you picked Cap Bowman up piggy-back and started sliding
down banisters with him. You said you were a space vacuole looking
for some place to happen. And when you told the crowd about the
time you swiped the skipper's winter drawers and ran 'em up the
flagpole—"
"Did I," I shuddered, "tell them that?"
"You sure did. You also had a lot to say about some girl at Mars
Central spaceport. You said you called her 'Ginger,' because she was
a snap—"
"Go 'way!" I moaned. "Go 'way and let me explode in peace."
Evans grinned. "No can do, Sparks. Bowman sent me down to get
you. All brevetmen are to report to the control turret immediately. So
grab some breakfast, and—"
"Don't!" I howled.

But I had some breakfast while I dressed: an aspirin, a cup of

coffee, and two more aspirins. And I finally reached the control
turret of our space-going scow, there to find my shipmates standing
around looking very what-the-hell? The skipper scowled at me as I
wobbled in.
"Well! So you made it? Darby, there's limits to everything, and you
exceeded 'em last night—"
"Look, Skipper," I said, "I can explain everything. It was this way—"
"Best man!" he snorted. "If you was the best man at that weddin',
I'm a grampus' tonsils. You was a disgrace to yourself, the Pegasus,
an' mankind in general—Ah! The top of the mornin' to you, son."
Enter the bridegroom, Johnny Larkin, preceded by a sheepish grin.
He said, "Good morning, folks. Lovely day, isn't it?" Then, to the Old
Man, curiously, "I thought they were Earthdocking us for three
weeks, Skipper? Why the conference?"
"Your guess is as good as mine. I got a call from G. H. Q. first thing
this mornin'. All leaves to be cancelled, they said. We're to have a
visitor in a few—There! That must be him now."
It was. Colonel Ira Brophy, one of the igbay otshays of the IPS, the
corporation that pays us our monthly insufficient. He bustled in all
grins, grunts and glamor, pump-handled the skipper and beamed on
us like an overgrown sunbeam.
"A fine looking body of men, Captain Bowman! Yup, yup! And
believe me, sir, the IPS is justly proud of this ship and its officers.
Yup!"
At my side, Johnny Larkin muttered something that sounded like "—
donae ferentes—" But Captain Bowman fell for it, hook, line and
sinker. He said, "Thank you, Colonel. And we, in turn, are proud to
be privileged to do our little part for the Corporation. Any thing, any
time—that's the way we feel about it—"
Brophy pounced gleefully.
"Wonderful, Captain! Marvelous! Yup, yup, yup! I told my associates
that would be your attitude. 'The men of the Pegasus,' I told them,
'will be delighted to undertake this mission. Even though it may
mean the curtailment of a certain amount of personal liberty and
pleasure—'"
Bowman's chin hit his wishbone. A pint-sized Aurora Borealis played
over his gills. "M-mission?" he gargled.
"Yes, Captain. It is my pleasure to inform you that to the Pegasus
has been allotted the honor of investigating our recent cosmic visitor,
Caltech VI. Yup, yup!
"You will be equipped with motion-picture, meteorological and
analytical devices, and will lift gravs at 19.03 Solar Constant Time
tomorrow. I need not assure you that with you go the best wishes of
our great organization—"
I didn't hear the rest. I was too busy stifling an impulse to wham
Brophy over the conk with a blunt instrument. I glimpsed the pans
of Larkin, Evans, Weir, and the rest of the boys, and knew I wasn't
alone in my reaction.
This was a hellbuster of an assignment! Caltech VI was the latest
addition to Sol's family, a space-wandering planet that, from God-
knows-where, had recently swum within the gravitational attraction
of our sun—and taken up residence between Mars and the asteroids.
From the beginning it had been a trouble-maker. I needn't tell even
the ground-grippingest Earthlubber of you that the solar system is
weighed on such a hair-trigger balance that any considerable outside
influence will throw it haywire. Caltech VI—named after the old,
200-inch platter that had spotted it—had raised a terrific rumpus
settling into an orbit. It had caused howling storms on Mars, ionic
disturbances on mighty Jupiter, and blasted a half hundred
planetoids clear out of existence.
Astronomers agreed the newcomer could not last very long. A couple
thousand years at the most. Inevitably it would be torn to pieces by
the titanic tug-o'-war eternally waged by Jupiter and the Sun. But in
the meantime, according to the Fraunhofer analysis, there were
valuable ores on the interloper. Somebody, the first person or group,
who set claim-stakes on Caltech's soil, would clean up big.
Fine, hush? Swell! I should have been joyful at the prospect of
dipping into this celestial gravy, eh? But maybe I forgot to mention
that already three expeditions had gone out from Earth and one
from Venus. All of them had reported successful landings on the
planet, then—silence!
Cap Bowman had gathered up his scattered wits, now, and began
volleying protests like a skeet-chucker.
"But, Colonel!" he howled, "The Pegasus isn't good enough for that
sort of job. We're a freighter! Our plates are worn, our hypatomics
old-fashioned—"
"Yup," said Brophy agreeably. "We know. But your space record is
enviable. You have served the Corporation faithfully and well—"
What he meant was, we could be spared. Johnny Larkin said wryly,
"I should think those would be arguments for not sending the
Pegasus."
Brophy glowered at him from behind glinting pince-nez. "And who
might this be?"
The skipper said nervously, "Lt. Larkin, sir. My First Mate." He added
proudly, "Him an' my daughter had a military weddin' last night."
"That's too bad, Captain," harumphed Brophy. "But to return to the
subject—"
"Military!" bellowed the skipper. "Not 'shotgun!'" Then a sudden idea
struck him; he adopted a wheedling tone. "Look Colonel—if we gotta
go, we gotta go. But I c'n excuse Lt. Larkin from duty, can't I? After
all, he's on his furlough. This is his honeymoon—"
Brophy shook his head decisively.
"I'm sorry, Captain. All furloughs are cancelled. All men must report
for duty on this special assignment. I might add, though, that if your
venture is successful, the Corporation will fittingly reward all
participants—"
"An' if it ain't?" asked the Old Man.
"They'll bury us," I piped up, "by remote control. With honors. See
you later, boys. I've got to see a carpenter about a coffin." And I
left.

So that was that. You don't argue with the I. P. S. The next day
found the Pegasus loaded to the gunwales with all sorts of
equipment. Cameras, spectroscopes, interferometers, gadgets and
junk, the very names of most of which were just so much Sanskrit to
me. That's where Johnny Larkin came in. He was not only our First
Mate; he was our technological expert.
But the Corporation also had the almighty viscera to fill one freight
hold with cargo! "Concentrate of zymase," said the lading
superintendent. "For deposit at Mars Central on the return trip. Get a
receipt from the Medical Officer, Captain."
"What's his name?" demanded the skipper gloomily. "Saint Peter?
Oh, hello, son. Sorry I couldn't get you out of this mess. Where's
Lorraine?"
"That's all right," said Larkin. "Maybe everything will be all right.
She's home. She wanted to come along but I wouldn't let her. Space
is no place for a woman."
Bowman growled, "This is a hell of a honeymoon for you, boy! An'
for her, too. Well, we might as well lift gravs. Sparks, get clearance
from the port."
I said, "Aye, sir!" and did. At 19.03 on the nose we blasted hell-for-
Thursday out of Long Island Port, for'rd tubes pointed at a
mysterious new dot in the heavens that had already killed more men
than a Central American rebellion.
That was at 19.03. At 22.00 sharp, Slops boomed the gong for the
late watch mess. And at 22.07, the door of the mess hall opened and
in walked—Lorraine Larkin, nee Bowman!

Cap Bowman had a mouthful of tomato juice when he laid eyes on

her. Two seconds later, his mouth was open in a roar and the
tablecloth had a mouthful of tomato juice.
"Lorraine! What in the name of the seven sacred satellites are you
doing aboard? Don't you know—?"
"Now, Daddy!" She smiled, and my heart did tricks. You've never
been smiled at till you've been out in front of one of those extra-
special de luxe Lorraine Larkin jobs. She was sugar and spice and
everything nice, and don't some guys have all the luck? "Now,
Daddy, remember your blood pressure."
"Blood pressure be damned!" frothed Bowman. "You git right off'n
this barge an' go back to Earth where you belong!"
"It's cold out there," said Lorraine. "Remember? And besides, this is
where I belong—isn't it, honey?"
She looked at Johnny Larkin, who was suddenly having trouble with
his epi-brothers, dermis and glottis. The first was scarlet, the second
was charging up and down in his throat like a berserk elevator. He
managed to get a few words out.
"You," he gulped, "shouldn't be here!"
"And where else would a girl be," demanded Lorraine coolly, "than at
her husband's side? Especially on her honeymoon?" She plumped
herself down beside him. "Bring one more plate, Slops. There's
company for dinner."
The skipper rose.
"Enough," he declared, "is too much. I wasn't hot on this trip from
the start. Now I'm an Eskimo. Sparks, take a message to Long
Island Spaceport. Tell 'em—"
"Tell them," interrupted Lorraine Larkin, "that the captain and crew
of the Pegasus are on their way to find out what happened to those
other poor fellows who tried to land on Caltech VI. And tell them we
will find out, because we're the toughest, smartest, space-lickingest
gang of etherhounds who ever lifted gravs. And there's nothing
between here and Procyon that can scare us. Mmmm! What
delicious soup—"
That stopped them. That stopped them cold. Bowman looked
thoughtful, one gnarled hand caressed his jowls. Larkin stopped
trying to talk, a curious look came into his eyes. Tom Anderson's
shoulders stiffened; old MacPhee, the Chief Engineer, dragged out a
filthy, oil-smeared handkerchief, blew his nose viciously and said,
"Grrrumph!"
Me, I was stunned speechless, too. Oh, not because she had
reminded me we had a moral obligation to find out what had
happened to the previous explorers. It wasn't that she'd roused in
me any latent spark of pride in the Pegasus, either. What got me
was her calling the soup 'delicious'! Good golly, that stuff? Delicious?

So we went on, and Lorraine Larkin went with us. I don't have to tell
you about the trip; you can get that from the log book. It was
sixteen days to the Mars ecliptic, but Mars wasn't there, of course.
It was sky-hooting along four weeks to sta-board. Little things
happened, none important. The outstanding thing about the trip was
the dopey way our one time sane and sensible first mate, Johnny
Larkin, was behaving.
He had apparently reconciled himself to the idea of Lorraine's being
with us. Reconciled? Whoops! He was closer to his bride than twelve
o'clock sharp. Everywhere you saw Lorraine, there was Johnny, and
vice versa.
Then we hit the highroad between Mars and the asteroids, the great
open spaces in which Caltech had taken squatters' rights. Bob Weir
punched keys on the astrocalculator and figured it would take us a
week and a half to reach our destination. I wasn't sure I could last
that long.
For why? One guess. Lt. and Mrs. J. Larkin. Their billing and cooing
was enough to make a Martian canal-pussie blush green. Every time
you saw Johnny he was playing octopus with Lorraine's hand. He
had dawn and soft breezes in his eyes when he looked at her, and
the glances she heaved back weren't exactly typhoons at midnight.
The worst part is, they didn't seem to have a bit of shame! They
didn't care whether anybody saw them acting like melted cheese
sandwiches or not. And oh! what they said! He called her "Lovums";
she called him "Cutsie," which was all wrong, "Bugsie," which was
one hundred per cent right, and a lot of other names too nauseating
to mention.
But somehow we survived. And finally came the time when the
skipper came busting into my turret and bawled, "Git y'r feet off'n
the desk, Sparks. Take a message to—"
"I know," I told him. "I already sent it. To Joe Marlowe at Lunar III.
Caltech VI is oh-oh under the nose. The Pegasus is preparing to
land, and the situation is—"
"Ain't you the smart little numbskull?" snorted the skipper. "Remind
me to use your brain for mattress stuffin'. No, dimwit, we ain't
landin'. I ain't goin' to set down on this here outlaw planet till I learn
what I'm landin' on. The Pegasus ain't goin' to be number four on
the missin' list." He beamed complacently. "Me, I'm smart, I am."

Well, so is sunburn. But who loves it. Anyway, I said, "Well, if we're
not going to land on Caltech, what's that big thing looming in the
visiplate? Green cheese?"
Bowman took one squint through the perilens and let loose a howl
that frightened its own echoes. "He's landin'! The damn fool's settin'
us down!"
He made a dive for the door. I grabbed his flying coat-tails long
enough to squawk, "Who?" and the answer came Dopplering back,
"Larkin! The space-crazy idiot!"
I moved, too. Sheer suction pulled me along as we hit the ramp,
charged through the corridors, scrambled up the Jacob's-ladder and
bore down on the control room. At the door I managed to pant,
"Who—who's in there with him?"
"Who do you think?"
"That's what I thought. What is this? A spaceship or a mushroom?"
Then we were inside, and it was just like I thought it would be.
Larkin was seated in the pilot's chair, pushing the buttons that eased
the Pegasus to terra firma, and hovering over him like a halo around
a saint's occipital was his ever-loving bride.
Bowman screamed, "Larkin! Wait!" and Lorraine turned, smiling.
"Isn't he clever, Daddy? He's the best pilot in the whole, wide
universe—aren't you, peachie?"
"Now, sweet—" protested Johnny modestly.
"Wait!" squalled the skipper. "Wait!"
"Weight, sir?" said Johnny, lifting out of his daze for a moment. "Aye,
sir. If you think best—" And he punched the grav plugs. My knees
buckled suddenly as the plates took hold. Bowman stumbled;
Lorraine gasped. Over the intercommunicating audio came voices, a
dozen irate queries from various parts of the ship. Bowman spoke
with an effort.
"Not weight, you double-blasted lunatic! Wait! Till we see what we're
gettin' into—"
But he spoke too late. The grip of the grav plates had done it. Our
nose jets spluttered, the ship lurched and slithered, there came a
sharp bump, surprisingly yielding and bouncy considering the speed
at which we had grounded, and—here we were. On Caltech.
Motionless, after weeks of travel.
No, not motionless! For then I felt it. Bowman and Larkin felt it. A
squidgy sort of sinking sensation, a sort of wobbling insecurity, as
though the ground were opening to let us drop through. The skipper,
an incredible mauve color, roared, "Lift 'er up, Johnny! We're gettin'
into something!"
Larkin made desperate passes at the control board. The rockets
flared and hissed, turning the control room into a bedlam. But
nothing happened. I saw why. I yelled,
"We ain't getting—we've got! Look!"
They all stared, like me, at the quartzite forward panes. Blue sky
should have been visible through them, warm sunlight should have
been flooding the turret. The terrain of Caltech should have
stretched before our gaze. But guess again. All we could see was a
gooey splatter of stuff oozing up the sides of the Pegasus. A strange,
viscous, colorless matter that surged up and about our ship with
weird, tentacular writhings. It covered the entire pane, gulped and
burbled sloppily as it engulfed the top of the ship. We continued to
experience that sinking feeling—
"Sweet whispering stars!" gasped the skipper. "Am I off my gravs?
Do you see what I see? The ground melted an' come up an' et us!"
And I knew, suddenly, what had happened to those who had landed
before us on mysterious Caltech. Like us they had been swallowed
beneath the soggy, flypaper crust of the alien planet.

Well, everything happened at once, then. I guess I'm just a bug-

pounder at heart, after all. My first thought was composed of dots
and dashes. I made a bee-line for the radio room, powered the
tubes and began CQ-ing up and down the wavelengths like a
longhair at the Steinway.
Which was just so much wasted time. I couldn't draw a hum out of
the audio. Even the more delicate earphones failed to bring in the
powerful Mars-Ceres beam. And if I couldn't get a message in, it's a
damn sure thing I couldn't get one out. My transmission was blanked
out.
So I hung a sign on my door, OUT TO LUNCH, and went back to the
control turret. It looked like the bleacher entrance to Terra Stadium
on the opening day of the Interplanetary Series. Everybody and his
brother was there. Officers, engineers, blasters, stewards. Even
Slops had come up, armed with a rolling pin, to find out what had
happened.
As I entered, Johnny Larkin was turning off the hypatomic power,
swiveling around to face the skipper.
"No go, Captain. I've tried anti-grav, neg potential and reverse
rockets. We can't get loose. We seem to be in something akin to
quicksand. Every move we make digs us in a little deeper."
Bowman growled savagely, "If you hadda used common sense
instead o' makin' billy-doos with y'r eyes—but this ain't no time to
talk about truffles. What do you think? Is this here planet somethin'
like Jupiter? Low specific, so we keep fallin' toward the center?"
Johnny said, "I don't believe so. The material about us is peculiar. It
seems to be organic. And it has a certain type of inherent energy—"
"Energy?" I yelled. "Hey, then maybe our Ampie can eat us out of
here? That little critter can gobble its way through an H-layer. This
dish of planetary junket—"
Larkin glanced up sharply. "And just how would you plan to get the
Ampie out of the ship, Sparks?"
"Why, through the lug-sail vent, of course."
"No. Don't try that. I have a feeling—"
He stopped. He didn't say what his feeling was. To tell you the truth,
the sharpness of his tone made me just a little bit sore. After all, I'm
not the dumbest guy afloat in space. I said stiffly, "Then what do we
do to get out of here? Or are we number four on the flit parade?"
Johnny swallowed hard. He said, "I'm the tech man on this freighter.
All of you clear out of here. I'll find some way—"
His words dwindled into silence. Lorraine looked at him proudly,
patted his cheek. She said, "That's right, Cuddlums. You'll get us out,
won't you?"
The skipper said, "Gug!" The crowd broke up and began drifting
away. Johnny started fussing with instruments and gadgets. Lorraine
soothed his brow by tying strands of his hair into lovers'-knots. I got
sick at the stomach looking at them after a while, so I left. Cap
Bowman beat me to the bar by three drinks—

It must have been an hour later that we felt it. A jarring whoomp
beneath our keel. The upset-tummy-in-an-elevator sensation
stopped. Bowman looked at me and said, "Larkin? He done
somethin', maybe?" and we went back to the bridge.
Larkin had not caused the settling, but he was beaming triumphantly
anyway. As we charged in, demanding information, he said, "Why,
it's very simple. We have finally come to rest on the surface of
Caltech."
"Sue me if I'm wrong," said the skipper, "but somehow I got the
impression we landed on this overgrowed custard an hour an' a half
ago? Or what's that I see out the ports? A bowl of taffy?"
"No, skipper. We didn't land on the surface before. We landed on a
particular kind of matter which is, so far as I have been able to
figure out, allied with the peculiar life-form inhabiting this planet."
"Life-form? You mean that stuff's alive?"
"Not exactly. That's the point I haven't been able to solve yet. I've
made a careful analysis of the stuff. It seems to be a highly complex
carbohydrate. Its formula is C6—"
"This ain't no time," I broke in, "to discuss mal-demer. What I want
to know is, do we or don't we try my idea about putting out the
Ampie? Johnny, maybe—"
"No!" he said.
"Well, why not? What have we got to lose?"
"No!" he said again. Oh, all right. I guess he was preoccupied and
didn't mean to be curt. But his tone rekindled my anger, and I didn't
feel any better when Lorraine said, "Please, Sparks, don't bother
Johnny when he's trying to figure this out. Go ahead, sugar-plum."
So sugar-plum went ahead, and I stalked out of the room. I went to
my own turret and tried to read a magazine, but I couldn't get
interested in the hokey adventures of a Patrolman on Io when I was
buried alive in cosmic goo myself. So I fiddled with the dials again
for a while. No soap. So pretty soon I got up and looked in my
auxiliary cabinet. My Ampie was curled in inside, pale blue and shot
full of tiny red sparks, sucking contentedly on an old-flashlight
battery. I put on my rubber gloves. I went down to the engine loft.
Ampies live on energy. And Larkin had said the gelatinous mass
engulfing us was at least partially composed of energy. Which made
what I did seem, to me, quite logical. I pressed the button that
extends the lug-sails of a freighter, heard the machinery creak into
motion, lifted my Ampie out of its lead-foil container, and shoved it
through the widening vent. Then I waited for things to happen.

They did happen! But not what I had expected. I had expected to
see the Ampie gnaw a hole through that dough like a St. Bernard
working out on a T-bone, rare. But instead, the Ampie touched one
shimmering feeler to the mass of gray matter, hummed, sparked,
and rolled backward across the room!
I said, "Aw, damn! He was right!" and started to close the lug-vent.
But—
It wouldn't close! Because the writhing stickiness was welling into
the ship with incredible, fluid swiftness. A heavy, saccharine stench
was in the air. Gray streamers fingered toward me. I yelped,
slammed tight the engine loft door, and raced for the control turret.
In the middle of the control turret I waited for my breath to catch up
with me. Larkin spoke subconsciously from the depths of a deep
ponder. "Shh!" he said.
"Shh!" repeated Lorraine. "He's thinking."
"Then tell him to think about pancakes!" I howled. "Because there's
a shipful of gray molasses following me up the corridor!"
Larkin started. "What's that?"
I told him. "—it looked like a good idea," I finished, "only it wasn't.
Now the stuff's in, and I can't get it out again. It'll fill the whole
damned ship—"
But Cap Bowman is no dope. He had already sprung to the audio,
was barking orders to other parts of the Pegasus.
"Seal port and loft sections of the ship immediately. Lock emergency
doors! Get all men into safe sectors!"
Lorraine looked at me worriedly.
"What—what is it, Sparks?"
"Nothing much," I told her grimly, "except that I've just about killed
us all. That stuff will ooze through every crack and crevice in the
ship, swallow everything just like it swallowed the ship. That's
probably what happened to those other explorers. There must have
been one dope like me aboard each of them. With a bright idea that
—I'm sorry, Mrs. Larkin. I've sure put the final touch on your happy
honeymoon."
She was Cap Bowman's daughter; she was the bride of Johnny
Larkin. A gal doesn't get to be both of those things without having
more innard-stuffings than a sofa-cushion. My words heaved her
back on her heels, but only for a fraction of a second. Then, smiling,
she turned to Johnny.
"We're not afraid, are we, honey? But you'll have to hurry now."
Larkin pawed his hair frantically.
"I'm doing my best. I've got all the facts. But I still can't quite
understand—"
Voices rasped in over the audio. Anderson reported from the
sleeping quarters, "All men evacuated, sir. Standing by for further
orders." MacPhee snarled defiance from the engine deck, "We've
plugged all doors, sirrr! We'll hold this position to the last posseeble
minute!"
"It's a form of carbohydrate," mused Larkin aloud. "Plastic. Semi-
fluid. But why? Why?"
"Think hard, sugar!" pleaded Lorraine. Larkin said mechanically,
"Yes, honey—" Then he stiffened. "Honey!" he said.
I groaned. "This is no time for lovey-dove talk, Johnny!" I cried.
"Keep scratching at those gray cells—"
And over the audio, the voice of super-cargo Freddy Harkness. "Am
abandoning holds, Captain. The invading—er—substance has already
covered the aft bins and is moving forward rapidly."
"Seal the safety door, Harkness—" began Bowman.
Then Larkin was at his side, suddenly frantic, eager.
"No, Skipper! Tell him to keep them open a minute! I'll be right
there. I need three men!"
He lit out for the door. Bowman cried, "No, son—come back! You'll
be killed. Come—"
But he was talking to empty air. Johnny was pounding down the
runway. Lorraine sniffed once. Then her jaw hardened. She said,
"I'm going after him."
Bowman pushed her into a chair—but hard. He said, "You're waiting
here! With us. You'll only be in his way. Johnny's the tech man on
this ship. If anybody can save us, he's the one." But as her head
lowered, his eyes met mine. And the words were written there, "Not
this time—"
Still, we had to do something. We couldn't just sit there and take it
blind. We had to know what was going on. So we cut in the visiplate
to the corridor outside the storage bins. It was a dismal scene that
appeared before us.
The long corridor was deserted save for a thin sliver of something
oozing out of an adjacent chamber. As we watched, this sliver turned
to a bulky, rolling mass; became the doughy body of the mysterious
matter in which the Pegasus was caught. Like a ponderous wave it
surged up the corridor, straining into every crack and crevice,
engulfing everything it met.
We saw a tiny, gray ship mouse scurry from under a doorway,
hesitate as one pink foot slipped into the sluggish excrescence.
It tugged, trying to get free. But it was like a fly snared on flypaper.
It couldn't move. In a few seconds it disappeared. Lorraine began
crying softly. I turned away, too sickened to condemn myself again
for having loosed this thing amongst us.
Then there were bright gleams in the visiplate, and Johnny,
accompanied by three or four not-at-all eager sailors, entered the
corridor. As he passed the visiplate, he looked up and grinned at us,
nodded encouragingly. Then he ducked into one of the storage bins.
He came out staggering under the load of a heavy, wooden crate.
He began ripping the top off this frantically, motioned his assistants
to get other similar boxes from the bin and open them. They did so,
but one look at their pans told us they didn't like this business
nohow!
Finally he had the box open. He tore out a portion of the contents.
And—
"Has he gone nuts?" raged Bowman. "That's only that medical junk
for Mars! That zy-something extract!"
Johnny made it perfectly clear what he was trying to do. He
wrenched the cap off one bottle—and deliberately poured the
contents into the nearest pseudopod of the matter now approaching
within scant feet of him. Then another bottle; tossed into the mass
this time. And another. And another.
Lorraine screamed suddenly, "Daddy, look! He's trapped! Behind
him!"
She was right. From another cross-corridor had rolled more of the
Caltechian effluvium. It formed a solid barrier through which Johnny
and his co-workers could not now escape. They could move neither
forward nor backward. In a few minutes the two sluggish tentacles
of the syrupy monster would meet. And then—
I said, "Skipper, you'd better turn off the plate."
Bowman nodded. He reached toward the button. Closer and closer,
now. In seconds the two walls of matter would coalesce. The sailors
had seen their peril. We couldn't hear their voices, but they were
apparently pleading with Johnny to let them take refuge in the one,
so far untouched, storage vault; seal that door. And he had refused.
He was forcing them to hold their ground. All four of them, like
himself, were desperately ripping corks from bottles, scattering the
medical export into the substance closing in on them.
And then one man slipped! His foot flew from under him, was avidly
seized by a tentacle of that slimy mass. His eyes and mouth opened
wide; I knew he was screaming.
Larkin stepped forward to grasp his shoulders. The skipper hoarsed,
"Look out, son! Behind you!"
It happened all at once. One minute there were two towering walls
of fleshy matter surging inexorably down upon the trapped quintet,
and the next instant—
The walls collapsed! Just like that! Collapsed into running streams of
blotched liquid scum. The sailor's leg slipped free. Johnny toppled
over backward into the slippery puddle. A foolish look spread over
his face. A look that was mirrored in the faces of his associates. His
eyes rolled. He goggled up into the visiplate, kissed his fingers to us,
and—and hiccuped! His lips formed a syllable. The syllable was,
"Wheeee!"
Bowman's shaking fingers sought his jowls. He cried, "My God, he—
he's—"
"He's what, Daddy? What?"
"He's as boiled," roared Bowman, "as an owl!"

Some time later—about twelve hours, to be exact—I dragged him

back into the control turret. He was still a little blue from the cold
shower. But the fog was out of his brain, and that was what was
most necessary. For all of us were dying of curiosity.
Bowman said, "Well, your plan worked, son. We got the ship empty,
and like you said we would, we pulled out of the goo we was in.
Now we're on our way back to tell Earth about Caltech, and—" he
added proudly, "—collect that bonus. 'Cause under that scum is a
fortune in ores. But what was the scum? An' how did you know you
could bust it up with that there zy—zy—"
"—mase," grinned Johnny. "Zymase, Skipper. Why, it wasn't difficult,
once Lorraine supplied the key. You might say I was slow in figuring
it out mainly because the disaccharose existed on such a gigantic
scale that I could net comprehend it."
"The di—which?" I said.
"Sugar," said Johnny, "to you. Or, more accurately, a form of treacle.
Honey-gum.
"Here's what I figure. Subsequent investigation may prove me
wrong, of course, but my theory must be fundamentally sound or we
wouldn't have escaped.
"Caltech VI is apparently inhabited by some sort of gigantic insect,
which may be of the bee, the spider, or the ant family. Each of these
insects, as you know, possesses the power of secreting fluids which
it adapts to its private needs. The ant seals nests and wraps larvae
in his, the bee builds hives and makes honey, the spider spins
threads wherein to trap its prey.
"We were captured in a gigantic 'trap' built by one of these insects,
that's all. From what we saw, I judge that most of Caltech's surface
must be covered by these gigantic webs. Miles in extent, hundreds
of feet deep. Webs of doom for the unwary. Being highly tensile,
gummy, irradiated with a rather unusual form of inherent energy,
these traps cannot be damaged by rocket blasts." He shook his head
soberly. "I can't help thinking of those poor devils who died there.
Like human flies in a monster's viscous web—"
"I can't help thinking of the poor devils who died there. Like
human flies in a monstrous viscous web."

I prodded, "Lieutenant, the zymase?"

"Oh, yes. Of course. Well, you know what zymase is, don't you?"
"No," I told him. "Do you?"
"Naturally. A nitrogenous substance. A freshly expressed concentrate
of yeast juice. Its action on sugar is to speed up, terrifically, the
ordinary process that transpires when sugar and yeast are brought
together. In short—fermentation!
"As soon as we emptied the zymase concentrate into the flood of
honey—for it was that, though I might never have guessed it in time
had it not been for you, dear!"
Here he beamed at Lorraine. "—the natural sugar was broken down
into carbon dioxide, glycerin, succinic acid, and—er—"
"Urr?" repeated Bowman curiously. "What's that? A new element?
Never heard of it."
"And—er—" said Johnny sheepishly, "alcohol! You see, that's why the
sailors and I were a trifle—confused—by the atmosphere
surrounding us—"
"Confused your hat!" I told him. "You were stewed! But it all makes
sense now. The fermentation naturally continued. It loosened up the
sticky goo, our blasts dragged us out of the trap. But, say! That alky
odor is still all through the ship. We can't air the joint while we're
traveling through space. Do you think—?"
But he didn't hear me. For this, after all, was the honeymoon trip of
Johnny Larkin. And now, the danger over, he had reverted to type.
He and Lorraine looked like a brace of intertwined pretzels.
The skipper coughed. He said, "Sparks? Maybe we—"
I gasped, "Gosh, yes! This red on my face ain't sunburn!"

So, folks, that was that. Oh—one thing more. I was right. That alky
odor didn't leave the ship. Don't ask me how we ever got back to
Long Island Spaceport.
They told me later we zig-zagged in by way of Mercury and Luna. I
wouldn't know. It was just one, long, delirious dream to me. I was
two weeks coming out of it.
What a headache! What a hangover! What a honeymoon!
 *** END OF THE PROJECT GUTENBERG EBOOK HONEYMOON IN
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