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Physical Biology From Atoms to Medicine 1st Edition
Ahmed Zewail Digital Instant Download
Author(s): Ahmed Zewail
ISBN(s): 9781848162006, 1848162006
Edition: 1
File Details: PDF, 107.31 MB
Year: 2008
Language: english
 PHYSICAL BIOLOGY
From Atoms to Medicine

P559tp.indd 1 4/9/08 3:17:55 PM

This page intentionally left blank
 PHYUSICAL BIOLOGY
From Atoms to Medicine

BALTIMORE . BUSTAMANTE . DOBSON . HOOD . HUSH

KOCH . KORNBERG . MACKINNON . MCCAMMON
MILLER . PARRINELLO . PHILLIPS . QUAKE . REES . THOMAS
TIRRELL . VARSHAVSKY . WHITESIDES . WOLYNES

Ahmed H. Zewail
California Institute of Technology, USA

Imperial College Press

ICP

P559tp.indd 2 4/9/08 3:17:55 PM

 Published by
Imperial College Press
57 Shelton Street
Covent Garden
London WC2H 9HE

Distributed by
World Scientific Publishing Co. Pte. Ltd.
5 Toh Tuck Link, Singapore 596224
USA office: 27 Warren Street, Suite 401-402, Hackensack, NJ 07601
UK office: 57 Shelton Street, Covent Garden, London WC2H 9HE

Library of Congress Cataloging-in-Publication Data

Physical biology : from atoms to medicine / editor, Ahmed H. Zewail.
p. cm.
Includes bibliographical references.
ISBN-13: 978-1-84816-199-3 (hardcover : alk. paper)
ISBN-10: 1-84816-199-9 (hardcover : alk. paper)
ISBN-13: 978-1-84816-200-6 (pbk. : alk. paper)
ISBN-10: 1-84816-200-6 (pbk. : alk. paper)
1. Biophysics. 2. Biochemistry. 3. Molecular biology. I. Zewail, Ahmed H.
QH505.P457 2008
570--dc22
2008009371

British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library.

Copyright © 2008 by Imperial College Press

All rights reserved. This book, or parts thereof, may not be reproduced in any form or by any means,
electronic or mechanical, including photocopying, recording or any information storage and retrieval
system now known or to be invented, without written permission from the Publisher.

For photocopying of material in this volume, please pay a copying fee through the Copyright
Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, USA. In this case permission to
photocopy is not required from the publisher.

Printed in Singapore.

SC - Physical Biology.pmd 1 4/2/2008, 1:50 PM

00a_Group photo.indd 5

Front row (left to right): Peter J. Wolynes, J. Andrew McCammon, John Meurig Thomas, David Baltimore, Ahmed H. Zewail, Leroy
4/7/2008 3:12:23 PM

Hood, Roderick MacKinnon, Carlos J. Bustamante. Back row (left to right): Christof Koch, Douglas C. Rees, Michele Parrinello,
David A. Tirrell, Christopher M. Dobson, George M. Whitesides, Stephen R. Quake, Rob Phillips, Roger D. Kornberg.
 This page intentionally left blank

00a_Group photo.indd 6 4/7/2008 3:12:23 PM

 Contents

Prologue by Ahmed H. Zewail xi

Chapter 1 The Preoccupations of Twenty-First-Century Biology 1

David Baltimore

Chapter 2 The World as Physics, Mathematics and Nothing Else 7

Alexander Varshavsky

Chapter 3 Physical Biology: 4D Visualization of Complexity 23

Ahmed H. Zewail

Chapter 4 Revolutionary Developments from Atomic to

Extended Structural Imaging 51
John Meurig Thomas

Chapter 5 Physical Biology at the Crossroads 115

Carlos J. Bustamante

Chapter 6 The Challenge of Quasi-Regular Structures in Biology 137

Roger D. Kornberg

Chapter 7 The Future of Biological X-Ray Analysis 145

Douglas C. Rees

Chapter 8 Reinterpreting the Genetic Code: Implications for

Macromolecular Design, Evolution and Analysis 165
David A. Tirrell

vii

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 Contents

Chapter 9 Designing Ligands to Bind Tightly to Proteins 189

George M. Whitesides, Phillip W. Snyder,
Demetri T. Moustakas, and Katherine A. Mirica

Chapter 10 Biology by the Numbers 217

Rob Phillips

Chapter 11 Eppur si muove 247

Michele Parrinello

Chapter 12 Protein Folding and Beyond: Energy Landscapes

and the Organization of Living Matter in
Time and Space 267
Peter G. Wolynes

Chapter 13 Protein Folding and Misfolding: From Atoms to

Organisms 289
Christopher M. Dobson

Chapter 14 A Systems Approach to Medicine Will Transform

Healthcare 337
Leroy Hood

Chapter 15 The Neurobiology of Consciousness 367

Christof Koch and Florian Mormann

Chapter 16 Computer-Aided Drug Discovery: Physics-based

Simulations from the Molecular to the Cellular Level 401
J. Andrew McCammon

Chapter 17 Precision Measurements in Biology 411

Stephen R. Quake

viii

00b_TOC.indd 8 4/7/2008 3:09:42 PM

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someone ought to look out for her. As we brought her to life we’re
responsible.”
“Come along with you,” cried Grampa recklessly. So away through the
wizard’s garden marched this strange little army, the patched flag of
Ragbad fluttering from the top of Tatters’ red umbrella and the little
flower maiden falling out of line every few minutes to dance gaily round
a tree or skip merrily through a fountain.
She fairly seemed to float above the flowers that blossomed along
the way, as her dainty feet slipped from daisy to daisy. Prince Tatters
could hardly keep his eyes away from Urtha as she danced along the
way. And Grampa smiled happily at the delight of the two happy young
people.
 CHAPTER 7

The Winding Stairway

It was twilight in the wizard’s garden. All the lanterns burned low and
the birds twittered drowsily in the tree tops. Grampa and Tatters sat
wearily upon a golden bench—for after a whole day’s march they were
no nearer the Emerald City than before. Indeed, there seemed no way
out of the enchanted garden. They had lunched satisfactorily on the
fruit of a bread and butter bush, and Grampa’s knapsack was full of
nicely spread slices, but for all that each one of them felt tired and
downhearted.
Urtha, on the contrary, was as fresh and merry as in the morning
and, seated under a willow tree, was weaving a daisy chain for Bill.
“She is certainly a fairy,” mused Grampa and absently pulling a
blossom from a near-by bush he popped it into his mouth. “We’ll take
her back to Ragbad, my boy, and won’t she liven up the old castle! I tell
you, now—” Suddenly Grampa stopped speaking and clapped his hand
to his belt. His eyes grew rounder and rounder and Tatters, turning to
see why he did not finish his sentence, gave a little scream of fright.
“Help!” called the Prince of Ragbad in an agonized voice. “Help!
Help!” Urtha was beside him in an instant, while Bill circled wildly
overhead.
“He’s growing,” breathed the little flower maid softly.
“Yes,” groaned Tatters distractedly, “he’s growing a chimney!” And
Tatters was quite right. Not only was the old soldier growing a chimney,
but a bay window as well. The chimney had knocked off his cap and
grown brick by brick as the horrified Prince looked on. The bay window,
of fancy wood-work and glass, jutted out at least three feet beyond
Grampa’s waist line. (The old soldier had always been proud of his slim
figure.)
“Give me my pipe,” panted Grampa in a choked voice. He had no idea
what was happening, but felt too terribly dreadful for words. Tatters
sank on one knee, snatched the pipe from its place in his game leg and
lit it with trembling fingers. Then it was that he caught sight of the sign
on the bush beside Grampa. “House plants,” said the sign distinctly.
“Oh!” wailed the Prince, suddenly remembering that Grampa had
eaten one of the blossoms, “you’ve eaten a house plant and there’s a
chimney sticking out of your head.”
“There is!” roared Grampa, puffing away at his pipe in great
agitation. “Well, that’s what comes of this pesky magic. A chim-nee!
Well, I’ll try to bear it like a soldier,” he finished grimly. A perfect cloud
of smoke rose from the chimney at these valiant words. Too overcome
for speech, Tatters covered his face.
“Don’t you care!” cried Urtha, flinging her arms ’round Grampa’s
neck. “It’s a sweet little chimney, and so becoming!”
“The wind is blowing North,” crowed Bill, disconsolately following the
direction of the smoke as it curled up Grampa’s chimney. “If I see this
wizard I’ll fall on his head. I’ll give him a peck in the eye, five pecks, but
say!” Bill paused in his circling and swooped down upon the old soldier.
“How about the medicine?” Grampa and Tatters had forgotten all about
the wizard’s green bottle, but at Bill’s words the old soldier drew it
quickly from his pocket.
 “I don’t believe there’s any cure for chimneys,” puffed Grampa,
running his finger anxiously down the list. He was so nervous that his
hands shook. To tell the truth he expected to grow a flight of steps or a
veranda any minute.
“Here, let me look,” begged Tatters, snatching the bottle from
Grampa. But though there was everything on the green label from ear
ache to lumbago, no mention was made of chimneys or bay windows at
all.
“But it says ‘cure for everything,’” insisted Bill, perching stubbornly on
Grampa’s shoulder.
“This is worse than a battle!” moaned Grampa, rolling up his eyes.
“I’m poisoned, that’s what I am.”
“Poisoned!” cried Bill triumphantly. “Then find the cure for poison.”
Hurriedly Tatters consulted the label. “For poison of any nature, two
drops on the head,” directed the bottle. So while Urtha and Bill watched
nervously, Tatters uncorked the bottle and let two drops of the magic
liquid fall down Grampa’s chimney. There was a slight sizzle. Tatters
rubbed his eyes and Bill gave a crow of delight. The chimney had
melted and the bay window was gone and the gallant old soldier quite
himself again. Urtha was so happy that she danced all the way round
the golden bench and Grampa jumped up and ran to look at himself in a
little pond.
 “No worse for it,” mused the old soldier, stroking the top of his head
tenderly and patting his belt with great satisfaction, “but that’s the last
bite I’ll take in this garden.” As Grampa turned to go, a particularly
bright little flower bed caught his attention. The flowers grew right
before his eyes, dropped off their stems and were immediately
succeeded by other ones. Even in the dim lantern light the old soldier
could see that they were spelling out messages.
“Gorba will return to the garden at twelve o’clock.” This
announcement bloomed gaily in red tulips, and while the old soldier was
still staring at it in astonishment, the tulips faded away and another
sentence formed in the bed:
Who stays all night shall leave here never,
He’ll be a lantern tree forever!
In yellow daffodils, the sentence danced before Grampa’s eyes. “A life
sentence!” panted the old soldier wildly, and without waiting for more
he plunged across the garden.
“Tatters! Bill! Urtha!” shouted Grampa, his own voice hoarse with
excitement. “The wizard’s coming back and we’ve got to get out of this
garden or be lantern trees forever!”
 “Forever!” gasped the Prince of Ragbad, who had scarcely recovered
from the chimney business. As fast as he could, Grampa told of the
flower messages, and when they hurried back to the bed, a pansy
sentence had already grown there.
“Good-night,” said the pansies politely, then fluttering off their stems,
blew like gay little butterflies across the lawn.
“Good night!” choked Grampa bitterly. “It’s the worst night I ever
heard of. I won’t be rooted to the spot, nor a tree for any old wizard
wizzing. Come on! Company ’tenshun!”
“Here I come by the name of Bill,” crowed the weather cock, hurling
into the air.
“But what are we coming to?” panted Tatters, shouldering his red
umbrella dutifully, while Urtha kept anxiously beside him.
“We’re going back to those stepping stones,” puffed Grampa,
stumping along determinedly. The lanterns winked lower and lower and
soon it was so dark and shadowy they lost the path entirely. Smothering
his alarm, Grampa marched doggedly on, bumping into benches and
trees, but never once pausing.
“They ought to be here some place,” wheezed the old soldier and
then stopped with a grunt, for he had run plump into an iron railing in
the dark.
“What is it?” whispered Tatters, straining his eyes in the gathering
gloom.
“Why, it’s a flight of steps,” cried Grampa in the next breath. Feeling
for the gate, he entered the little enclosure and struck a match. By the
flickering light, he saw six circular golden steps and on the top one in
jewelled letters were just three words: “Gorba’s Winding Stairway.” Then
the match sputtered and went out.
“Winding stairway,” puffed the old soldier joyfully. “Why, this must be
the way out. They wind up, I’ll bet a gum drop! Get aboard everybody.
Hurry! Here Loveliness!” Taking Urtha’s hand, Grampa guided her up the
first step. Tatters stood on the second with Bill on his shoulder. Grampa
mounted quickly to the top and striking another match looked anxiously
for directions. There were no more inscriptions, but under Gorba’s name
was a tiny gold handle. The match was burning lower and lower and
just as it went out Grampa seized the handle and turned it sharply to
the left. Then—“Great Gollywockers!” gasped the old soldier, clutching
at the rail. “It’s winding down!”
Poor Grampa, in his hurry, had turned the handle the wrong way, and
next instant the brave little company were whirling down the wizard’s
winding stairway, ’round and ’round, down and down, ’round and down,
down and ’round, until they were too dizzy to know where they were
going.
“Hold on!” called Grampa wildly. “Hold on! Hold on! Hold on!” And
hold on was about all they could do.
 CHAPTER 8

Strange Happenings in Perhaps City

On the same bright morning that Grampa and Tatters started from
Ragbad, the Peer of Perhaps City sat cozily breakfasting with Percy
Vere. Percy was a poet and attended to all the guess work in Perhaps
City. True he was a terribly forgetful poet, but he did the best he could
and was a prime favorite with the old mountain monarch. Perhaps City
itself is a tall, towered city of gold set high in the Maybe Mountains of
Oz. So steep and craggy are its peaks that none of the dwellers in the
city ever descend into the valleys below. Indeed there is little need of it,
for life in Perhaps City, owing to the jolly nature and good management
of old Peer Haps, is so delightfully entertaining that the people have no
desire to leave. The Happsies themselves are of the light-hearted and
old-fashioned race of Winkies, who in olden Oz times, settled all the
countries of the East. The only one who ever left the city at all was
Abrog, the High Sky prophet of the realm, and to his goings and
comings no one paid much attention, for he was a queer, silent old
man, who spoke but once a year and only then to prophesy as to the
weather, crops and important events that would take place in the town.
So far these events had all been happy and fortunate ones, and on
this sunshiny morning, old Peer Haps, buttering his muffins in his cozy
breakfast room, felt so well pleased and content with his lot that he
fairly beamed upon Percy Vere.
For his part, Percy Vere always was happy and, beaming back at the
king, he shook his long locks out of his eye and laughed merrily at old
Peer. Percy Vere always felt that his patron enjoyed his breakfast
particularly if Percy opened the proceedings with a verse, so he sang, as
breakfast was served, this ditty:
“Oh, muffins mellow light and clear,
Fit diet for a mountaineer;
Oh, muffins pale and yellow!
Oh, muffins sweet to sniff and eat,
How you refresh a—a—”
The poet’s merry blue eyes grew round and puzzled, as they always
did when he forgot a word.
“Fellow!” chuckled the Peer, taking a sip of coffee. “Percy, my child,
you are ridiculish!”
“I am ridiculish, I know it;
A young, a poor forgetful—er”
“Poet!” spluttered Peer Haps, with another chuckle.
“Thanks old Nutmeg!” sighed Percy, helping himself to another
muffin. “You always know what I mean.”
“Nut Meg!” roared Peer Haps. He never got over being amused at
Percy’s informal way of addressing him. “Nut Meg! Well, I’ll be grated!”
And immediately he was, for at that very moment, the folding doors
flew open and in rushed Abrog the prophet.
“Greater than all other Rulers in Oz, great of the greatest!” began the
old man, salaaming before Peer Haps, “a great misfortune threatens,
approaches, is about to take place.”
 “What?” cried the Peer, choking on the last bit of his muffin. It was
strange enough to have Abrog speak at all when it was not the day for
prophecy, but to have him speak in this foreboding fashion was simply
too terrible.
“Speak out! Speak up!” cried the Forgetful Poet, leaping to his feet:
“Speak out, speak up
And then get hence,
We cannot stand this dire—
this dire, this dire—”
“Suspense,” finished Peer Haps automatically. “Yes, speak up, fellow!”
he cried anxiously.
“In four days, a monster will marry the Princess!” wailed Abrog,
pulling his peaked cap down over his eyes. “In four days, four days,
four days!” And having said this, he began to gallop ’round the
breakfast table, Peer Haps and the Forgetful Poet right after him. You,
yourself, can imagine the effect of such a message on the merry old
Peer of Perhaps City. Why, he prized the little Princess above all his
possessions, yes, even above his yellow hen who was a brick layer and
laid gold bricks instead of eggs. Indeed, she had done more than
anyone else to lay the foundation of his fortune.
“What kind of a m-monster?” stuttered the Forgetful Poet, waving his
muffin.
“Where is my daughter now?” demanded Peer Haps, seizing Abrog by
the whiskers, for there seemed no other way of stopping him. Abrog
waved feebly toward the window and, rushing across the room, the
Peer and the poet stared out into the garden where the sweetest little
Princess in all the countries of the East was gathering roses. She waved
gaily to the two in the window, and, with a shudder, Peer Haps turned
back to Abrog.
“Let me see the prophecy,” he demanded, holding out his hand.
Abrog produced a crumpled parchment and after one glance the old
Peer covered his face and sank groaning into his enormous arm chair.
The Forgetful Poet had read over his shoulder and instantly burst into
all the melancholy poems he knew. “Oh, hush!” begged the old
monarch at last, “and you,” he waved wildly at the prophet, “can you do
nothing but run ’round that table like a merry-go-round goat?”
“I could marry the Princess myself,” rasped Abrog, coming to a
sudden standstill before the Peer. “If she were already married to me, a
monster could not marry her,” he leered triumphantly.
“To you!” shrieked Percy Vere, crushing his muffin to a pulp.
“You weazened, wild, old, whiskered dunce,
Be off! Be gone! Get out, at—at—at—at—”
Percy began hopping about on one foot groaning, “What’s the word,
what’s the word?”
“Once!” finished Peer Haps, mopping his forehead and glaring at
Abrog, for he was stunned at the old man’s suggestion. “It wouldn’t do
at all,” he muttered gloomily. “Why, you’re a thousand years old if you’re
a day, and she’s the only daughter I’ve got.”
“Well, you won’t have her long,” sneered Abrog, gathering his robe
about him. His black eyes gleamed wickedly from beneath their bushy
brows. He was furiously angry, but quickly hiding his feelings he began
to move slowly toward the door. Halfway there he paused. “Since you
refuse my first solution of the difficulty, I will endeavor to think of
another one. I used to know a little magic,” he wheezed craftily. “I will
retire to my tower to think.”
Peer Haps nodded absently. He was too dazed to think himself and
could only mutter over and over, “A monster! A monster! My daughter!
A monster!”
“The fellow’s a fool!” choked Percy Vere. “He’s as full of ideas as a
dish pan. Why he’s a monster himself!”
“But there’s something in what he says,” groaned the old Peer
unhappily. “If my daughter were already married when this monster
came, he could not carry her off. I have it! Percy, we’ll marry the
Princess at once, to the likeliest lad in Perhaps City.”
“To me!” cried the Forgetful Poet, tossing back his long locks and
sticking out his chest complacently.
“Well—er,” the old monarch looked a trifle embarrassed, “you’re
hardly the man to marry and settle down to a humdrum royal existence.
I was thinking of young Perix.”
 “You’re right,” agreed Percy, mollified at once. “Marriage would
interfere with my career, O Peer. Shall I fetch our pretty little Princess?”
“Yes, call her at once,” begged Peer Haps, clasping and unclasping
his hands, “but don’t frighten her, Percy my boy, no talk of marriage or
monsters!” Percy felt that the only thing he could do, under the
circumstances, was to lapse into verse.
“I go, I go, on heel and toe
To fetch the sweetest girl I know,
The Princess of Perhaps City,
As sweet as sugar full of tea!”
caroled the Forgetful Poet, bounding through the door into the garden.
Peer Haps smiled faintly, then remembering the monster, frowned and
began drumming nervously on the arm of his chair. He did not even look
up when the yellow hen hopped into the room, and, with a self-
conscious cluck, laid a gold brick on the mantel.

“What’s the matter?” asked the hen sulkily.

“Everything!” groaned Peer Haps, straining his eyes for the first sign
of Percy and the Princess. “Everything!” At that instant Percy rushed
back.
 “The Princess is lost, gone, mislaid!” cried the Forgetful Poet, crossing
his eyes in his extreme agitation.
“You speak as if she were an egg,” clucked the yellow hen, but no
one paid any attention to her and in a huff the spoiled creature flew out
the window and dropped a gold brick on the head of the chief gardener.
But no one, except the chief gardener, paid any attention to this either,
for Peer Haps had raised such a clamor over the disappearance of his
daughter that the whole castle was in an uproar. Indeed in five minutes
more every woman, man and child in Perhaps City had joined in the
search for the missing Princess. After they had searched high and low,
and everywhere else for that matter, Percy suddenly bethought himself
of the prophet and, rushing up the fifty steps to his tower, thumped
hard upon the door. There was no answer. Percy flung the door open
and there was no prophet. Abrog was gone too!
In the face of this new calamity the dreadful prophecy about the
monster was almost forgotten. Peer Haps sank down upon his throne
and in spite of his sixty years and three hundred pounds wept like a
baby.
“He’s perfectly perfidious!” exclaimed Percy Vere, who was entirely
out of breath from the steps. All the courtiers solemnly shook their
heads.
“A villain old and hideous,
And perfectly perfidious,
Has run off with our daughter.
What shall be done to him, O Peer,
This prophesighing profiteer
Deserves both death and—and—”
“Slaughter,” sobbed Peer Haps convulsively. Then mopping his face
he sat up. “Someone must follow him at once and bring her back!”
thundered the old monarch. “A thousand gold bricks to the man who
brings her back. A thousand gold bricks and the Princess’ hand in
marriage!” At this there was a great shuffling of feet and the young men
of Perhaps City began to exchange uneasy glances.
“Down the mountain?” asked Perix faintly.
 “Where else?” demanded Peer Haps, glaring angrily at the young
nobleman whom he had intended for his daughter.
“But we might be dashed to pieces. It is terribly unsafe,” stuttered
Perix unhappily. All the other Happsies began to shake their heads and
murmur sadly, “Unsafe, very unsafe!”
“Well, how about my daughter?” roared the poor monarch, puffing
out his cheeks. “Will no one go after my daughter?” There was more
shuffling of feet, but not a voice was raised. We must not be too hard
on these young Happsies, remembering that in all their lives and in the
lives of their fathers and grandfathers no one had ever descended
Maybe Mountain excepting Abrog the old prophet.

“I’ll go myself!” spluttered Peer Haps explosively. But as he arose

with a great groan, the Forgetful Poet rushed forward and embraced as
much of the Peer as his arms would circle.
“You’d be broken to bits!” cried Percy distractedly. “Suppose you
stumbled. I, I will go and find the Princess and this meddling, miserable
prophet.”
“You! Why you’ll forget what you’re after before you start,” sneered
Perix disagreeably.
“As to that,” said Percy, snapping his fingers under the young fellow’s
nose, “I may forget a word now and then, but I don’t forget how to act
when my King is in trouble!”
 “Hurrah!” shouted the gardener, throwing up his hat. He had
recovered from the shock of the gold brick. “Hurrah for Percy Vere; he’s
the bravest of the lot!”
“But how will you go?” quavered Peer Haps. He was torn between
relief at Percy’s brave offer and sorrow at the thought of losing his
prime and favorite companion.
“Here’s how,” cried the valiant Poet. Rushing down the golden steps
of the palace, Percy leaped over the gate and plunged recklessly down
the steep mountain side. Percy was well accustomed to hill-climbing and
met with no mishap as he plunged downward.
 CHAPTER 9

Dorothy Meets a New Celebrity

Dorothy had been to see the Tin Woodman and now, with Toto, her
small shaggy dog, running at her side, was skipping merrily down one
of the wide Winkie Lanes.
“I think Nick Chopper looks very well, don’t you Toto?” said Dorothy,
tickling his ear with a long feathery weed.
“Woof!” barked Toto reproachfully. Toto—like all other dogs in Oz—
could talk if he wanted to, but Toto, being originally from Kansas,
preferred his own language. Just then, seeing a lively baconfly, Toto
gave another bark and dashed across a daisy field. Away fluttered the
baconfly, and you have no idea how fast these little rascals can flutter,
and away, his ears flapping with excitement, pounded Toto, and away
after Toto ran Dorothy, for she was always in fear of losing her reckless
little pet. Up and down, here and there, ’round and ’round, darted the
mischievous baconfly, until Toto’s tongue hung out and he simply
panted with exhaustion. Then with a spiteful sputter, the baconfly
disappeared under a rhinestone, and after scratching and whining and
even growling a little, Toto gave up the chase and trotted rather
sheepishly back to Dorothy.
“That was really too bad of you Toto,” panted the little girl
reprovingly. “You wouldn’t eat a poor little baconfly, would you?”
“Woof, gr-rr woof!” sulked Toto, which was Kansas for “You bet I
would!” Pretending not to understand this last remark, Dorothy fanned
herself with her broad straw hat and started slowly back toward the
lane. But the baconfly had led them such a roundabout chase that when
she did come to the lane she turned in exactly the opposite direction
from the way she had intended, and instead of walking toward the
Emerald City she began walking away from it. But as neither she nor
Toto was aware of this fact, they progressed most cheerfully, Dorothy
carrying on a one-sided conversation with the saucy little bow-wow.
Occasionally Toto would bark or wag his tail, but most of the time he
listened in superior silence to the little girl’s chatter of the fun they had
had in Nick Chopper’s tin castle.
Now how Nick Chopper came to have a castle is a story in itself, for
Nick has, in the course of his strange and interesting life, risen from a
wood-chopper to Emperor of all the Winkies and from an ordinary blood
and bone man to a real celebrity of tin. Yes, Nick is entirely a man of
tin, as you can see by referring to any of the histories of Oz. In these
same histories it is recorded how a wicked witch enchanted Nick’s ax, so
that first it cut off his legs, then his arms and finally his body and head.
But you cannot kill a good Ozman like Nick Chopper and after each
accident he hied him to a tin-smith for repairs. First the tin-smith made
him tin legs, then tin arms, next a tin body and at last a tin head, so
that he was completely a man of tin. And this same little Dorothy, on
her first trip to Oz, had discovered the Tin Woodman, rusting in a forest,
had oiled up his joints and taken him to the Emerald City itself. There
the Wizard of Oz had given him a warm, red plush heart, which he still
has and since then Nick has been in almost every important adventure
that has happened in the wonderful Land of Oz. Ozma, the little fairy
ruler of Oz, finding Nick so dependable and so unusual, has made him
Emperor of the East, and the loyal little Winkies have built him a
splendid tin castle in the center of their pleasant yellow country.
 Dorothy herself was first blown to Oz in a Kansas cyclone and after a
great many visits to this delightful country, determined to stay for good.
Ozma, with the help of her magic belt, transported Dorothy and Uncle
Henry and Aunt Em and Toto to the Land of Oz. Uncle Henry and Aunt
Em have a comfortable little farm just outside of the Emerald City, but
Dorothy and Toto have a cunning apartment in the Emerald Palace
itself, for Ozma cannot bear to have Dorothy far away. The two girls—
for Ozma herself is only a little girl fairy—have been through so many
adventures together that they are almost inseparable, and to show her
love and affection for this little girl from the United States Ozma has
made Dorothy a Royal Princess of Oz.
But through all her honors and adventures Dorothy has remained the
same jolly little girl she was in Kansas. Every now and then she puts
aside her silk court frocks, slips into an old gingham dress and steals off
for a visit to some of her friends in the country.
“We’ll soon be at the Scarecrow’s, Toto; shall you like that?” she
asked, after skipping along for five whole minutes without speaking.
“Perhaps he’ll have corn muffins and honey and—Whatever’s that?”
“Little girl! Little girl!” A voice came echoing high and clear down the
sunlit lane. Toto pricked up his ears, and Dorothy, shading her eyes,
turned in the direction of the voice. Running toward her was a young
man clothed all in buff—an extremely excited and agitated young man—
and by the time he reached Dorothy and Toto he was perfectly
breathless.
“Well—” began Dorothy, hardly knowing what else to say.
“Not very well, thank you,” puffed the young man, slapping at his
face with a yellow silk handkerchief. On closer inspection Dorothy saw
that his handsome suit was torn and muddied and the young man
himself exceedingly scratched and weary.
“I am most unhappy,” he continued, regarding her mournfully. “At
least, when I can remember to be. It is hard to be unhappy in a lovely
country like this.”
“Then why do you try to remember to be?” asked Dorothy with a
little laugh, while Toto made a playful dash at the stranger’s heels.
“A great deal depends on my remembering,” explained the young
man eagerly. “If I forget to be unhappy I may forget why I fell down
the mountain and why I am wandering in this strange country without
friends or food.”
“Well, why are you?” Dorothy could control her curiosity no longer.
“I am seeking a Princess,” replied the youth solemnly.
“A Princess! Well, will I do?” Dorothy smiled mischievously and while
the stranger stared at her, round-eyed, she made him her prettiest court
bow. The result was extremely funny. The Forgetful Poet—for of course
you have guessed all along that it was he—extended his arms toward
Toto and cried accusingly:
“I looked the maiden in the eye,
I looked her up and down,
She says she is a Princess,
But, she hasn’t any—any—?”
Toto barked indignantly at this limping poetry.
“I suppose you mean crown,” giggled Dorothy. “Yes I have too, but
it’s at home, in Ozma’s castle.”
“The crown is in the castle,
The castle’s in the town;
The town is in the land of Oz,
But how about her—her—”
He stared helplessly at Dorothy’s gingham dress and, with another
little scream of laughter, Dorothy finished his verse. “Gown!” spluttered
the little girl. “Do you always talk like that?”
“Pretty often,” admitted Percy Vere apologetically. “You see, I am a
poet. And I know who you are now. You’re Princess Dorothy herself!”
He smiled so charmingly as he said this that Dorothy could not help
smiling back.
“I’ve read all about you in Peer Haps’ history books,” confided Percy
triumphantly. “Shall I address you as Princess?” As he asked this
question the troubled expression returned to his eyes. “You haven’t
seen a Princess anywhere around here have you?” he added anxiously.
Dorothy shook her head and Toto began sniffing under all the bushes as
if he expected to find a Princess in any one of them.
 “A little Princess,
Passing fair,
With rosy cheeks
And yellow—yellow—”
“Hair,” put in Dorothy quickly. “Who is she? Who are you and how did
she get lost? Let’s sit down and then you can tell me all about it.”

“He’s exactly like a puzzle,” thought Dorothy, with an amused little

sniff. So Percy Vere sat down beside her under a spreading jelly tree
and as quickly as he could he told of the strange happenings in Perhaps
City, of the prophecy about the monster, of the strange conduct of old
Abrog, the Prophet, and finally of the disappearance of both the
Princess and the Prophet.
Percy himself had fallen down the steep craggy sides of Maybe
Mountain, arriving in a scratched and bruised heap at the bottom. All
morning he had been wandering through the fields and lanes of the
Winkle land and Dorothy was the first person he had encountered.
“Well, I think you were just splendid,” breathed the little girl, as the
Forgetful Poet finished his story. Percy had tried to gloss over the young
men’s refusal to go in search of the Princess, but Dorothy had guessed
quite correctly what had happened.
“I’ll bet that old prophet carried her off himself,” she declared
positively.
“I think so two,
I think so three,
I think so four,
Where can they—?”
Percy mopped his brow and looked appealingly at the little girl.
“Be,” supplied Dorothy obligingly. “I’m sure I don’t know, but we can
soon find out. You just come to the Emerald City with me and we’ll look
in Ozma’s magic picture.”
“Why you are wise
As you are pretty;
Let’s hasten to
The Emerald City!”
Smiling all over because he had actually finished his own verse, the
Forgetful Poet helped Dorothy to her feet and both started gaily down
the lane, Dorothy telling the poet all about the interesting folk in the
capitol and Percy Vere telling Dorothy all about the City of Gold on
Maybe Mountain. Dorothy’s idea of looking in Ozma’s picture, like all of
her other ideas, was a mighty good one, for this picture has a magical
power enabling a person to see whomever he wishes, so that one look
would disclose the whereabouts of the lost Princess of Perhaps City. But
at every step, they were putting a longer distance between themselves
and that look. For at every step, thanks to that little baconfly, they were
going farther and farther away from the Emerald City of Oz.
They had eaten the lunch the Tin Woodman had thoughtfully put up
for Dorothy, and now, as the afternoon shadows began to lengthen, the
little girl looked anxiously ahead for familiar landmarks. But instead the
lane—which should have led straight to the Scarecrow’s tower, which is
halfway between the Tin Woodman’s Palace and the Emerald City—the
lane suddenly came to a stop in a scraggly little woods.
“That’s funny!” mused Dorothy, looking around in surprise.
 “Are we lost?” asked Percy, leaning wearily against a tree.
“Hello! Hello, why here’s a sign
Tacked up upon this prickly—prickly—”
Without bothering to finish the verse, Dorothy hurried over to the
pine.
“Look out for the Runaway,” advised the sign, in large red letters.
“Runaway!” cried Dorothy, snatching Toto up in her arms. “Good
gracious! I wonder what kind of a runaway it is?” They were not long
left in doubt, for while Percy was still staring nervously all ’round, there
came a hiss and a snap and ’round a big rock shot the runaway itself,
scooping up the two travellers before they had time to even wink a
single eyelash.
“This is p-perfectly preposterous,” blustered the Forgetful Poet. Both
he and Dorothy were sitting in the middle of the runaway and Percy
Vere hastily slipped his arm around the little girl to keep her from falling
off. The runaway road itself was humping along like some dreadful sort
of serpent, jouncing and bouncing them so terribly that talking was
almost impossible.
“Wonder where it’s running!” gasped Dorothy, hugging Toto so tight
he began to growl a little. From somewhere ahead a gritty voice
answered her.
 “I’m running straight to a pepper mine,” roared the runaway, “and
you’ll make a handsome pair of pepper diggers.”
“P-pepper diggers!” groaned Percy Vere.
“Pepper diggers, not that please,
The very idea makes me, makes me—”
“Ha-ha-ka kachoo,” sneezed Percy miserably.
“Pepper doesn’t grow in mines. It’s a plant,” shouted Dorothy
indignantly.
“Well, this pepper mine of mine was planted,” replied the road,
twisting ’round to stare at Dorothy with its stony eyes. Neither Dorothy
nor the Forgetful Poet answered this time, for the bumping and
bouncing had grown so much worse that it was all they could do to hold
on to each other and keep from biting their tongues off. Nothing like
this had ever happened to the Forgetful Poet before. He was simply
stunned. But Dorothy had been in so many strange adventures and had
had so many odd experiences in the land of Oz, that she was already
planning to outwit the runaway.
“It wouldn’t be safe to jump off,” thought the little girl, “for we’d
probably be broken to bits, but—” Her eyes travelled upward to the
trees and bushes that were flashing past as the runaway flung itself
recklessly through the forest—“If we caught hold of a low branch the
old road would go on without us,” she reflected triumphantly.
As well as she could, for bumps and bounces, she whispered her plan
to Percy Vere. He nodded enthusiastically and transferred Toto to his
blouse, so that Dorothy would have both hands free. Then, when a
huge tree loomed up ahead, they both began to count, and as its
branches stretched over the runaway, they hurled themselves upward
and held on for dear life. Beneath slithered the road and not until the
last yellow length of it had flashed by did Dorothy and Percy Vere let go.
Percy dropped to the ground first, gently lifted Dorothy down, and took
the frightened, wiggling little Toto out of his blouse.
“Whew!” breathed Dorothy, leaning dizzily against Percy, “that’s the
worst ride I’ve had for a long time. Wonder where we are?”
“Do—we—do—this—often?” panted the Forgetful Poet, looking at
Dorothy with round eyes. “I’m perfectly pulverized!”
 “Well, I never met a runaway before,” confessed Dorothy, “but you
never can tell what’s going to happen in Oz, so first thing we’d better do
is to find out where we are!”
“We’re in a forest dark and deep,
I hope the bears are all—are all—”
 “Asleep! So do I!” sighed Dorothy, and began tip-toeing along under
the great lonesome trees, Toto keeping close at her side and Percy Vere
treading softly behind her.
 CHAPTER 10

Prince Forge John of Fire Island

Before Grampa and his little company had recovered from the shock
of winding down instead of up, the strange stairway gathered itself
together, and, with a sudden jerk, shook them all off.
“Break ranks!” roared the old soldier, kicking out wildly with his game
leg.
“I don’t want to break my ranks,” said Bill crossly. Tatters and Urtha
were too startled to say anything and for a few seconds they simply fell
in surprised silence. The hollow down which they were tumbling was
wide and dimly lighted with a soft, spooky glow. The air was thick and
heavy and they were falling much slower than Grampa and Tatters had
fallen down the hollow tree. First fell Urtha, her flowery skirts fluttering
gracefully around her; then fell Tatters, clinging to Bill with one arm and
his red umbrella with the other; then the old soldier, his gun, drum,
sword and knapsack rattling like a box full of marbles.
 “I feel exactly like a butterfly. Are we flying, dear Mr Soldier?”
laughed the flower maiden presently.
“No, my poor child,” puffed Grampa, staring down at her anxiously.
“We’re falling!”
“Falling asleep?” asked Urtha contentedly.
“Depends on how we land,” groaned the old soldier, and suddenly
remembering his last landing he snatched the wizard’s medicine bottle
from his pocket.
“Is there anything on the label about falling?” panted Tatters, who
was close enough to notice the old soldier’s action. Grampa held the
bottle close to his eyes, and though reading while falling is one of the
hardest things I know of to do, after a deal of squinting the old soldier
read out the following: “For falling hairs, one drop in full glass of water!”
“But we’re not hares,” wheezed Bill indignantly.
“And if our hair stopped falling and we fell on, we’d be scalped!”
puffed Grampa hoarsely. “Besides there isn’t any water, so there’s
nothing to do but fall!”
“Stormy weather! Stormy weather!” predicted Bill gloomily. “Look out
below, look out, look out, look out!” As the weather cock came to his
last look out, the air grew suddenly lighter, the speed of the four fallers
increased and next thing, with a great splash and splutter, they had
plunged into a deep underground lake. Blowing like a porpoise, Grampa
rose to the surface.
“One drop in water,” choked the old soldier and, treading water
furiously, he began to look around for his little army. In the dim green
light he could see Urtha floating like a tiny island of flowers on the top
of the water—her fine spray of hair spread out ’round her lovely little
face. A short distance away Tatters was making frantic efforts to keep
afloat but, with the iron weather cock and the enormous umbrella, it
was a difficult business and every few minutes the poor Prince of
Ragbad would disappear under the waves. Grampa himself,
handicapped as he was by a game leg and so many weapons, found
swimming a dreadful exertion and by the time he reached Tatters he
was completely exhausted. He still grasped the wizard’s bottle in one
hand.
 “Wet—very wet!” The head of Bill appeared above the water and then
went under, as Tatters took another dive toward the bottom.
“Grampa, I’m drowning!” gulped the poor Prince, reappearing for a
second on the surface. It never occurred to the Prince to drop Bill or his
father’s umbrella. Grampa himself had shipped so much water he had
no breath to speak, but he flung his hand out desperately toward the
Prince and, as luck would have it, it was the hand holding the wizard’s
medicine.
“D—don’t drown!” begged Grampa, his eye fixed desperately on the
green label. “Wait, there’s a cure for it.” Treading water again, he
clutched Tatters by the hair and pressed the bottle to his lips. “One
swallow and you’ll swim like a fish,” promised Grampa.
 “My head’s swimming already,” muttered Tatters weakly. It was all the
Prince could do to get the stuff down, for he had swallowed quarts of
the lake already. Grampa was so interested in watching the effects of
the dose that he forgot to move his feet and went down himself. But
just as the water closed over his head he put the wizard’s bottle to his
own lips, took a hasty mouthful and jammed in the cork. Immediately
he bobbed to the surface and, with a great sigh of relief, saw Tatters
floating on top of the waves, Bill perched precariously upon his chest.
Grampa felt as buoyant as a cork and, using his gun as an oar, steered
toward Tatters and Urtha and soon all three were bobbing along side by
side.
“This medicine’s the only good thing that wizard ever invented,” said
Grampa, sticking the bottle through his belt. “Feeling better, old boy?”
Tatters shook his head feebly. He could not help thinking how far out
of their way they had fallen, and how very far they were from the
Emerald City and even from Ragbad itself. He blinked hastily at the
thought of Mrs Sew-and-Sew and the cozy red castle on the hill, and he
hoped Pudge had remembered to feed his pigeons. Tatters himself
never expected to see them again. Only Urtha seemed really to be
enjoying the adventure. Her little flower face was wreathed in smiles
and her lovely flower frock fairly sparkled with freshness.
“Isn’t this fun!” she kept repeating merrily. “Isn’t this fun?” Grampa
nodded, but not very enthusiastically.
“Do you think we’ll ever get back on top again?” asked Tatters
gloomily.
 “Of course,” spluttered Grampa. “We’ve fallen down about as far as
we can fall and from now on things will take an upward turn, you see.
Hello, this water’s kinda hot! Great swordfish, what’s that noise?”
“The fortune! The fortune!” shrieked Bill, jumping up and down upon
Tatters’ thin chest and ducking the Prince at every jump. “The fortune!”
With a great effort, Grampa sat up in the water, which was already
beginning to steam, and then fell backward with a terrific splash.
“Halt!” commanded Grampa, trying to push against the current with
his sword. “Stop! Halt!” A great roaring was in their ears and the green
light had changed to a red hot glow. Now Tatters sat up. Then he, too,
began to kick wildly about in an effort to stop himself. And no wonder!
They were being carried straight toward a roaring red island of fire!
“The fortune! The fortune!” screeched Bill, more excited than ever.
“Fortune!” groaned Grampa, reaching out to catch Urtha, who was
floating rapidly past. “Misfortune! Halt! Stop! Everybody back!”
“Better stop backing and look on that bottle,” gulped the Prince of
Ragbad. “Better see if there’s any cure for—for this!” He waved
desperately ahead. And Grampa, with a little choke of fright, pulled out
the wizard’s medicine. “Burns, scalds and heat strokes,” faltered
Grampa. “Well, we’d better take the cure for all three. A teaspoonful
was prescribed in each case and with trembling hands the old soldier
measured out the doses. Bill could not swallow, so the old soldier
dashed the medicine over his head.”
“I think you’re a fairy,” puffed Grampa, throwing a dose in the face of
the surprised little flower girl, “but if anything should happen I’d never
forgive myself.” Tatters came next and by this time the water was so hot
that Grampa himself began to groan with discomfort. So he hastily
swallowed his three spoonfuls, corked the bottle and prepared for the
worst. But immediately everything grew better. The waves of heat from
the island seemed only pleasant breezes now and the steaming water
did not even feel hot. Before they had time to wonder at all this, they
were washed up on the burning sands of Fire Island itself.
“Is it the fortune?” asked Bill, hopping out of Tatters’ arms. “You said
land—or gold, and this is a golden land.”
Grampa was too dazed to answer. Finding himself completely fire
proof was strange enough, but actually walking on an island of fire
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