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Practical Aspects of Vaccine
Development
This page intentionally left blank
Practical Aspects of Vaccine
Development

Edited by
Parag Kolhe
Satoshi Ohtake
Academic Press is an imprint of Elsevier
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Notices
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our understanding, changes in research methods, professional practices, or medical treatment may become
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Contents
Contributors xi
Preface xv
Acknowledgments xix

1. Introduction to vaccine development 1

Katherine E. Odneal

Vaccines: the greatest advancement of modern medicine 1

A brief historical review 2
The foundation of vaccine development 3
A summary of current strategies in vaccine development 4
Adjuvants 6
Summary 7
References 7

2. Overview of vaccine adjuvants 9

Rushit N. Lodaya, Sonia Gregory, Mansoor M. Amiji and Derek T. O’Hagan

Introduction 9
General classification of vaccine adjuvants 11
Specific types of adjuvants 13
Future considerations in the development of adjuvants 18
Conclusions 19
Trademark statement 20
References 20

v
vi Contents

3. Formulation design considerations and good practice for

live attenuated vaccine development 27
Lee C. Smith and Paul Nelson

Introduction 27
Development of products with the end in mind 29
Development by design 34
Summary 76
References 76

4. Subunit-based vaccines: challenges in developing

protein-based vaccines 79
Salvador F. Ausar, Nicholas R. Larson, Yangjie Wei, Akshay Jain and
C. Russell Middaugh

Introduction 79
Similarities of vaccine proteins to therapeutic proteins 80
Pneumococcal protein-based vaccine development 82
Pneumococcal virulence factors 83
Licensed pneumococcal vaccines 84
Recombinant pneumococcal proteins as vaccine candidates 85
Alternative approaches for pneumococcal vaccines 91
Protective immunity against Chlamydia trachomatis 92
Chlamydia trachomatis vaccine candidates 93
Ricin vaccine candidates 101
NoV vaccine candidates 108
Clostridium difficile vaccine candidates 116
Acknowledgments 124
References 124
 Contents vii

5. QbD approach to formulation development for

protein-based vaccines 137
Malte Meppen and Daniela Stranges

Scope and challenges of protein bases formulation

development 137
Quality by design as a guiding principle in vaccine
formulation development 138
Preformulation studies 143
Formulation development and optimization studies 145
Conclusion 155
Acknowledgments 155
References 155

6. pDNA and mRNA vaccines 157

Kanwal Gill, Leanne Minall and Aslin Rodriguez Nassif

Introduction 157
Basic biology of pDNA and mRNA vaccines 162
Nucleic acid vaccine development 168
Process development; scalability and manufacturability 177
The future of nucleic acid vaccines 182
References 187

7. Antigeneadjuvant formulationsdkey considerations 207

Deep Bhattacharya, Chris Wiley, Aaron Latal and Vamsi Krishna

Introduction 207
Considerations for antigeneadjuvant compatibility 209
Drug product design and considerations for dose
preparation and administration 215
viii Contents

Container closure 217

Lyophilization of antigeneadjuvant formulation considerations 219
Summary 222
References 223

8. Suspension properties and characterization of

aluminum-adjuvanted vaccines 225
Alex Langford, Michael Bruchsaler and Manish Gupta

Introduction 225
Aluminum-containing adjuvant structure 231
Principles of suspension behavior 232
Properties and characterization 237
Considerations in vaccine development 254
Conclusion 260
References 260

9. Effect of shipping stresses on suspension vaccines 267

Jianxin Guo and Parag Kolhe

Introduction 267
Interplay between particle size, charge, and settling rate 268
Effect of shipping stress on thermodynamic suspension
stability 271
Impact of individual shipping stresses on redispersion time 272
Mitigation strategy to reduce high redispersion time 276
Summary and recommendations 276
References 277
 Contents ix

10. Control strategy development guide for vaccine

drug product 279
Deep Bhattacharya and Parag Kolhe

Introduction to control strategy approach 279

Control strategy considerations 280
Application of control strategy concept 285
Raw material control strategy 293
Summary and considerations for control strategy 295
References 295

11. Lyophilized vaccine development 297

Nicole M. Payton, Rushit N. Lodaya and Adora M. Padilla

Introduction 297
Overview of lyophilization formulation and process 299
Vaccine-specific considerations 309
Considerations for lyophilization cycle scale-up 319
Summary 322
References 322

12. Conventional and nontraditional delivery methods and

routes of vaccine administration 329
Roberta Antonia Diotti, Valeria Caputo and Giuseppe Andrea Sautto

The choice: the importance of the correct delivery system

for an effective vaccination 329
Conventional delivery methods: subcutaneous and
intramuscular route 330
x Contents

Epidermis and dermis as new sites of vaccine delivery 334

Other areas of the body as targets for vaccine delivery 341
Conclusion 347
References 348

Index 357
Contributors

Mansoor M. Amiji Department of Pharmaceutical Sciences, Northeastern

University, Boston, MA, United States

Salvador F. Ausar Bioprocess Research and Development, Sanofi Pasteur, Toronto,

ON, Canada

Deep Bhattacharya BioTherapeutics Pharmaceutical Sciences, Pfizer Inc.,

Chesterfield, MO, United States

Michael Bruchsaler Pharmaceutical Research and Development, Biotherapeutics

Pharmaceutical Sciences, Pfizer Inc., Chesterfield, MO, United States

Valeria Caputo Laboratory of Medical Microbiology and Virology at “Vita-Salute”

San Raffaele University, Milan, Italy; Pomona Ricerca S.r.l., Turin, Italy

Roberta Antonia Diotti Laboratory of Medical Microbiology and Virology at

“Vita-Salute” San Raffaele University, Milan, Italy; Pomona Ricerca S.r.l., Turin, Italy

Kanwal Gill Pfizer Inc., Andover, MA, United States

Sonia Gregory GSK e Slaoui Center for Vaccines Research, Rockville, MD, United
States

Jianxin Guo Pharmaceutical R&D, Pfizer, Inc., Chesterfield, MO, United States

Manish Gupta Manufacturing Science and Technology, Global Technology and

Engineering, Pfizer Inc., Pfizer Manufacturing Belgium, Puurs, Belgium

Akshay Jain Macromolecule and Vaccine Stabilization Center, Department of

Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, United States

Parag Kolhe BioTherapeutics Pharmaceutical Sciences, Pfizer Inc., Chesterfield, MO,

United States; Pharmaceutical R&D, Pfizer, Inc., Chesterfield, MO, United States

xi
xii Contributors

Vamsi Krishna BioTherapeutics Pharmaceutical Sciences, Pfizer Inc., Chesterfield,

MO, United States

Alex Langford Pharmaceutical Research and Development, Biotherapeutics

Pharmaceutical Sciences, Pfizer Inc., Chesterfield, MO, United States

Nicholas R. Larson Macromolecule and Vaccine Stabilization Center, Department

of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, United States

Aaron Latal BioTherapeutics Pharmaceutical Sciences, Pfizer Inc., Chesterfield, MO,

United States

Rushit N. Lodaya GSK e Slaoui Center for Vaccines Research, Rockville, MD, United
States; Drug Product R&D U.S., GSK, Rockville, MD, United States

Malte Meppen GSK, Siena, Italy

C. Russell Middaugh Macromolecule and Vaccine Stabilization Center,

Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, United
States

Leanne Minalla Non-Affiliation

Paul Nelson Prism Training & Consultancy Ltd., Cambridge, United Kingdom

Derek T. O’Hagan GSK e Slaoui Center for Vaccines Research, Rockville, MD,
United States

Katherine E. Odneal Drug Product Development and Design, Pfizer Inc., New
York, NY, United States

Adora M. Padilla Drug Product R&D U.S., GSK, Rockville, MD, United States; Global
Technical Operations, AstraZeneca, Gaithersburg, MD, United States

Nicole M. Payton Drug Product R&D U.S., GSK, Rockville, MD, United States

Aslin Rodriguez Nassif Pfizer Inc., Chesterfield, MO, United States

Giuseppe Andrea Sautto Center for Vaccines and Immunology, University of

Georgia, Athens, GA, United States

a
Pfizer employee at the time the work was performed.
 Contributors xiii

Lee C. Smith GreyRigge Associates Ltd., Wokingham, United Kingdom

Daniela Stranges GSK, Siena, Italy

Yangjie Wei Macromolecule and Vaccine Stabilization Center, Department of

Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, United States;
Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, United States

Chris Wiley BioTherapeutics Pharmaceutical Sciences, Pfizer Inc., Chesterfield, MO,

United States
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Preface

Four years ago, when we embarked on the journey of editing a book focused on vaccine drug
product development, we had not imagined the spotlight, challenges, and advances we will
witness in this area underscored by the COVID-19 pandemic. The COVID-19 pandemic has
highlighted the importance of vaccines, and the social and economic impact vaccines bring.
Vaccine drug product development is complex, and there is a need for a comprehensive
review of the industry’s current state and the challenges. While formulation scientists working
in biotherapeutic development may be familiar with proteins, vaccines present unique
challenges, which include (1) the wide range of vaccine components that may comprise
proteins, polysaccharides, proteinepolysaccharide conjugates, adjuvants, etc. and (2) the
varying stability and behavior of solution- and suspension-based systems. The container
closure system may also be unique, and the product may require freezing storage or lyoph-
ilization based on the stability of the vaccine components. The vaccine delivery route is
critical for its efficiency, and depending on antigen presentation, there is a need for novel
technologies and devices. This book is structured in such a way that it addresses formulation,
process, and delivery aspects. The features discussed in this book will provide a valuable
guide for scientists on developing vaccine drug product dosage forms.
The first part of the book introduces major components of vaccines, including antigens,
adjuvants, novel and upcoming approaches, and considerations for formulation develop-
ment. Vaccine antigens and adjuvants are essential components of a vaccine. This section
introduces readers to the background on the antigens and adjuvants. It provides consider-
ations for developing major classes of antigens (live attenuated, subunit, and protein-based
vaccine and focus on DNA and RNA vaccines). Separate chapters cover antigeneadjuvant
interactions with particular focus on suspension vaccines and characterization of the same.
The second part focuses on the manufacturing process of vaccine drug products, highlighting
challenges using practical case studies. This section starts with an empirical case study of a
situation in which the vaccine is in the hands of users and how shipping affects the usability
attributes. A case study is next presented for building an effective control strategy for a
suspension vaccine, and finally the readers are guided through lyophilized vaccine devel-
opment. The last part discusses current approaches and advances in vaccine delivery
including nonconventional approaches.
The first chapter introduces the importance of vaccines and provides a historical review
and their genesis. This chapter then walks the readers through current vaccine strategies that
cover the various classes of antigens used traditionally and emerging approaches. It also
addresses the importance of adjuvants to supplement the activation of the immune system.
This chapter forms the basis of the subsequent topics covered in this book.
Chapter 2 covers the heritage of vaccine adjuvants, the current status of adjuvant
development, and future considerations for developing novel adjuvants. This chapter covers
the background of vaccine adjuvants, general classification, and specifics of adjuvants in
clinical development and commercialization. Detailed description is provided for aluminum
salts, emulsion, lipid-based adjuvants, immune potentiators, and combination adjuvants.

xv
xvi Preface

Chapter 3 provides a snapshot of live-attenuated vaccines development by imple-

menting a quality-by-design (QbD) approach combined with product and process knowledge
to define the formulation. This chapter reviews the live-attenuated vaccine landscape by
providing a historical perspective, the importance of understanding target product profile
(TPP) and critical quality attributes (CQA), and its connection to formulation development. It
provides an excellent articulation of the formulation development approach by applying QbD
and DoE (design of experiments).
Chapter 4 touches upon the challenges of developing subunit-based recombinant
protein vaccines with the example of current clinical vaccines of this genre. The chapter starts
with a discussion on the similarity and differences between vaccine proteins and therapeutic
proteins. Furthermore, this chapter sheds light on the diversity of protein vaccine types and
delivery systems and illustrates the challenges associated with their development. It covers
five vaccines currently under clinical evaluation to highlight the science, complexity, and
development approaches. These vaccines include pneumococcal vaccine, Chlamydia tra-
chomatis, ricin, norovirus, and Clostridium difficile vaccine candidate development.
Chapter 5 builds on the theme of protein-based vaccine development and provides the
application of the QbD paradigm as a guiding principle for preformulation and formulation
approaches. It provides illustrative examples to highlight systematic ways of assessing the
formulation by utilizing QbD principles. Understanding various liabilities is critical for a given
vaccine candidate and constitutes the framework for preformulation and formulation
development by considering multiple interdependencies. The chapter provides a compre-
hensive discussion on the development of vaccine dosage forms, container closure aspects,
and challenges associated with adjuvanted vaccine systems.
Chapter 6 introduces the exciting world of DNA- and RNA-based vaccines. It covers
background on the technology, biology of plasmid DNA (pDND), messenger RNA (mRNA),
and pharmacology aspects. Formulation approaches for these vaccines, challenges in delivery
systems, and current advances are comprehensively covered. Processing and scale-up are
critical for this new technologydauthors touch upon the current process development ap-
proaches and manufacturing process. The authoring of this chapter took place when this
technology was under development. It is noteworthy that this technology is part of the
leading vaccines approved for emergency use in various countries for the COVID pandemic.
Designing a drug product formulation containing adjuvant is a complex challenge, and
our existing knowledge base needs to be improved. Chapter 7 provides a brief overview of
adjuvants and dwells deeper on antigeneadjuvant compatibility considerations. An adjuvant
is a critical part of vaccines and hence needs to be understood in conjunction with antigens. It
also captures considerations for crucial classes of adjuvant and their formulation with anti-
gen(s). This chapter provides practical advice on drug product design and container closure
considerations and also touches upon the lyophilization of vaccines containing adjuvants.
Chapter 8 focuses on suspension vaccines with emphasis on aluminum-based vaccines.
It provides a comprehensive review of bulk suspension properties of aluminum-adjuvanted
vaccines, such as particle size, surface charge, sedimentation rate, and techniques used to
characterize these properties. These physical properties provide an in-depth look at the
factors that can affect the flocculation state of the suspension and its impact on the
manufacturing process. The interplay between the colloidal properties and formulation is
critical and needs to be understood to enable the development of proper commercial
manufacturing process and product.
Combining formulation development and shipping logistics can profoundly impact how
users experience suspension vaccines in terms of redispersion. Chapter 9 provides a compre-
hensive case study illustrating the effect of shipping stress on suspension vaccine, mechanism
of suspension settling with shipping stress, and impact of particle size, settling rate, and charge.
 Preface xvii

Chapter 10 provides a comprehensive summary of the control strategy for vaccine

development. It articulates the control strategy concepts and provides an example using
concentration as a quality attribute. The chapter provides the guidance and considerations
for developing a holistic control strategy by walking the users through a case study.
Vaccine antigens can be challenging from a formulation development perspective and
should be stable for increased shelf life. Lyophilization of vaccine antigens can improve
stability during shipment and storage, although it can also expose the antigens to process
stresses during lyophilization. Hence, it is critical to understand the impact of each pro-
cessing step during lyophilization through in-depth characterization. Chapter 11 provides a
detailed overview of the impact of various stresses and considerations for various antigen
types (multivalent conjugates, live-attenuated, subunit, and inactivated), antigen/adjuvant
system, and lyophilization process scale-up.
Vaccine delivery defines the success of the vaccine’s effectiveness. Chapter 12 covers
important considerations for vaccine delivery and provides an in-depth view of conventional
and nonconventional delivery methods and recent advances. It explores traditional delivery
methodsdsubcutaneous and intramuscular routes. The chapter provides an excellent dis-
cussion on seven nonconventional delivery methods to overcome the corneum stratum
barrier, such as the mucosal and the nasal administration route.
Given the importance of vaccines and their pivotal role in eradicating many infectious
diseases over the centuries, it is crucial to understand the challenges and opportunities in
vaccine drug product development. Vaccine formulation development is similar to protein
formulation development in some respect and vastly differs in others due to the complexity of
multivalent systems and adjuvants. The content covered in this book was designed to guide
scientists working on vaccine formulation and drug product development, whether new or
experienced in the field. While technologies continue to evolve to better address unmet
needs, our expectation is that the fundamentals and practical considerations covered in this
book will serve as a foundation for future vaccine development.
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dint of pleading and main force he is induced slowly to retire, seeking
to cover the rear of the fleeing. And well it was, for a longer stay
would have proved fatal. But for the eagerness of the Mexicans to
secure as prisoner so magnificent a prize, they could easily have
despatched him. Aztecs made it a point to obtain as many prisoners
as possible, particularly chiefs and nobles, and white men, who
ranked even above these, in order to do honor to the war-god. This
effort was prompted by a deep religious obligation as well as by
warrior spirit.
Not far from the disastrous channel a horse was brought, upon
which Cortés was mounted, though wounded in the leg. Shortly
before, his chamberlain, Cristóbal de Guzman, a great favorite, had
ridden up with a charger to the relief of his master, only to be
surrounded with warriors and cut down, together with the animal,
[1166] while another rider was obliged to retreat with a lance-thrust in
the throat. On retiring from the section of causeway assigned to the
horse, another animal was killed and a third narrowly escaped.
Finally the troops reached the broader Tlacopan road, and now
Cortés, with the nine horsemen left in his division, was able to take a
firm stand against the enemy. Checked in their pursuit, and made
timid in their charges by the presence of the bold line of horses and
lances, they flung their missiles and insults with increased energy.
Suddenly two or three Spanish heads were cast before the
horsemen, with the cry: “Tonatiuh!” “Sandoval!” The meaning could
not be misunderstood, and as the Spaniards gazed on the gory and
disfigured faces a sickening fear crept over them. Could it be that
these beloved leaders had fallen! There was no time for deliberation.
Finding his own party now comparatively secure, Cortés hurriedly
sent messengers to recall the other divisions under Alderete and
Tápia.
There was hardly need for this message. The triumphant shouts
of the Mexicans in pursuit of the troops of Cortés and the increased
attack on their own had already warned these leaders. Still they
persevered, although their men manifested some discouragement. It
was not long, however, before two or three mutilated, bearded heads
were cast before them with the cry, “Malinche is dead!” “Tonatiuh and
all their men have fallen!” The leaders saw that farther advance was
useless, especially since the Mexicans now attacked with great fury.
The leaders kept their men in good order, and were already retiring
when the order of recall reached them. The streets there being wider
and easier, and the channels all filled, they found no trouble in
rejoining their general. Now jointly they retreated through the plaza
and down the Iztapalapan road, furiously pursued by the warriors,
who showed themselves more reckless than usual on seeing their
prey escape. The central temple was filling with a vast throng to
watch the onslaught, and on the summit the priests were already
burning incense and chanting in honor of victory, while the rabble
railed at the humiliated children of the sun.
Alvarado had meanwhile advanced along the road to Tlatelulco
from his causeway, leaving Sandoval to coöperate along the flank
and to direct the movements of the brigantines and the filling of the
channels. The advance was fiercely resisted by the Mexicans from
roofs, cross-lanes, and barricades, and hundreds had been severely
wounded, chiefly Tlascaltecs, only too many fatally, yet he
persevered. He was already near the market, the aim of all efforts,
when the drum and trumpet came to startle his men and to
encourage the Mexicans to greater resistance. Progress was now
almost checked, and soon came the cry, “Malinche is dead!”
“Sandoval and the other captains are dead!” “Behold their faces!”
And therewith several heads with gory beards were cast before
them. “This shall be your fate!”
Alvarado’s men were white with dismay, and but for the intrepid
courage of their leader the rout of Cortés’ party might have been
repeated. Making a bold stand with his Spaniards, he ordered the
Tlascaltecs to fall back and leave the retreat open. They needed no
second instructions to this end, for the bleeding heads lent wings to
their haste. Then grew the onslaught fiercer than ever, for the retreat
of Cortés’ forces enabled a larger number of enemies to turn against
Alvarado and Sandoval. The latter also received his cast of bloody
heads with a new string of prominent names, all calculated to inspire
terror. “By this time they had us all killed,” adds Bernal Diaz, “but, in
truth, we were all wounded, and filled with anguish concerning the
fate of our chief. Without God’s aid we could never have escaped
from the swords and clutches of the Mexicans.” Some pious
chroniclers, indeed, assert as usual that the virgin appeared in
person, together with perennial Santiago, to save the Spaniards from
their greatest peril.[1167]
Encouraged by the victories on land, the Mexicans had ventured
forth also in their canoes to harass the vessels which were occupied
in protecting the retreat of the armies. Unable in some instances to
leave their position, or impeded in their movement by stakes and
other obstacles, many of the brigantines were severely pressed, and
one, commanded by Briones, in Alvarado’s division, was actually
captured, with the loss of four men, one being taken alive. Jaramillo
came to the relief of the vessel, however, drove forth the enemy, and
kept them at bay.[1168] By this time both the forces of Alvarado and
Sandoval had reached the causeway, pursued by a great host,
reckless in their endeavor to inflict all the injury possible ere the
Spaniards escaped. Some delay occurred in crossing the only partly
filled channel to the causeway, and a number of soldiers were
detained waist-deep in water, seeking to lift a brigantine over the
stakes, for the auxiliaries were already away from the front; and all
this time the cavalry were compelled to remain before the causeway
to cover the infantry and bear the brunt of the terrible onslaught.
Charge after charge they made to keep back the advancing foe,
through the shower of blinding missiles, against the line of bristling
lances, amidst the whirling swords and clubs, until not a rider but felt
his arm droop and his body grow faint with loss of blood. Sandoval
himself had a number of wounds. “For God’s sake make haste and
retire,” he cried to his foot-soldiers, “or we shall all be lost!”
Finally the passage was clear, and they fell back along the
causeway, still fighting, and now exposed to the canoe sallies. On
reaching his quarters, Alvarado turned two cannon against the
swarm which sought to scale the camp, and this with the fusillade
procured a much needed respite.[1169] It was time, for the increasing
darkness would soon have added fresh dangers to the retreat.
Sandoval had already hurried away with a solitary companion to
seek the camp of Cortés and calm his fears.[1170] With a similar
object Andrés de Tápia had been sent with three horsemen from Fort
Xoloc to Alvarado’s camp, where he arrived with some scars from
marauding stragglers. Not wishing to discourage the soldiers, he
reduced the losses of his party to quite a small number, and made
light of the matter.
By this time the enemy had retired, but from the city rose their
shouts of triumph, and every temple was ablaze with fires to
celebrate the victory. The summit of the Tlatelulco pyramid, the
highest of them all, was the scene of great commotion, and soon the
sombre notes of the melancholy drum called it to attention. A number
of instruments now added their discordant notes, in clash and blast,
and a procession with torches, swinging censers, and religious
paraphernalia circled round with imposing ceremony. Then a space
was cleared, and a long file of naked men stood revealed. A cry of
horror burst from the gazing soldiers. There could be no mistake.
Distant as was the temple, the glare of fire clearly revealed the white
hue and bearded faces of their comrades, bound for sacrifice, and
plumed. Now they were made to march forward, and with blows to
dance before the idol to whom they had been consecrated. Ah, to be
a helpless looker-on at such a time! Again they formed in line
exhausted, and then one was seized by several priests and borne
struggling to the stone of sacrifice. He was thrown on his back and
held down by the limbs while the high-priest with ceremonious
flourish raised the glittering blade. The gazing soldiers clutched each
other’s hands in agony, as their eyes followed the instrument and
saw it plunged into the breast of the victim. They seemed to hear his
stifled cry, to feel the knife in their own heart, and realizing that they
were still safe they thanked heaven for their escape.[1171]
Victim after victim was carried to the stone, some with frantic
struggles, others resigned, and still others weighed down in helpless
fear of what they had beheld. Heart after heart was torn from the
gaping breasts and held before the idol, while the bodies were cast
down the steps. The skin, particularly of the head and upper body,
was removed and used as a dress for festive occasion, and the flesh
was hacked to pieces, the limbs for the banquet table, the trunk for
the beasts. After a while came darker-hued victims, and now the
Tlascaltecs and other allies shuddered. To them the sacrifices were
not so terrifying as to the Spaniards, but they could not unmoved
behold the cruel death of their countrymen. Then came more
processions, music, and idolatrous rites, followed by fresh
companies for the sacrifice, white and dark; and so passed the night,
until the horror palled on the gazers, and many expressed the
opinion that the priests were pretending sacrifice by producing the
same bodies upon the stone several times so as to inspire greater
fear. This belief was strengthened when they observed similar
ceremonies take place on other minor temples, and by the
continuance of the sacrifices for several days. The offering at the
minor temples consisted chiefly of the lower class of allies. All the
pyramids, however, received a quota of heads from Spanish, leading
native, and equine victims, wherewith to decorate their summits.
[1172]
 Aware that the sight of the sacrifice, purposely intensified for
Spanish edification, must have stirred deeply the breasts of the
survivors, the Mexicans took advantage of this to attack the camp of
Alvarado during the night. “Behold the fate in store for you all!” they
cried, casting in half-roasted pieces of flesh from white and dusky
bodies. “Eat, for we are satiated!” The Spaniards were too well
prepared to suffer from the assault, but it added to their sorrows. The
lesson had been costly, for about sixty men were lost, with six
horses, one gun, and a number of small-arms, while the ranks of the
allies had been diminished by from one to two thousand, and this
without reckoning the vast number of wounded.[1173]
When Sandoval reached Camp Xoloc and learned the news he
burst forth, “Señor Capitan, what is this? Where are the fine
counsels and warlike skill which you are wont to exhibit?” With tears
springing to his eyes, Cortés replied: “Sandoval, my son, my sins I
admit, but I am not so guilty in this matter as I appear. The officer
whom I charged to fill the channel failed to obey.” He further
intimated that Alvarado might be led by his daring into difficulties,
and bade Sandoval watch carefully over the safety of the western
and northern camps, particularly for the present, while Cortés was
restrained by his wounds.[1174] The injunction was needful in view of
the reoccupation by the Mexicans of the channels from which they
had lately been driven, and their harassing attacks, chiefly by night,
against the camps and fleets. Alvarado’s camp, as the nearest to the
city, was the most exposed, and Sandoval with his tried prudence
could be best relied on to counteract the recklessness of its
commander in repelling these attacks. Knowing the signal for the
sallies, usually a shot, the enemy were warned in time to retire, or to
form some trap or combination; so that the charge of the soldiers
carried little advantage.
On one occasion, it is related, a shield-bearer named Peinado
stepped outside the camp gate and found himself surrounded by a
horde of marauders. Escape was cut off. In this dilemma he began to
rattle his shield and sword, and shout, looking at the same time
toward the camp. The enemy assumed at once that he was
signalling to some party in ambush, and beat a hasty retreat.[1175]
For several days[1176] the Spaniards remained inactive. During this
time the Mexicans continued their daily sacrifice of captives, with
conspicuous rites and loud demonstrations.
As usual amidst trying scenes, there were here examples of the
devotedness of woman. In one of the encounters on the causeway to
drive back the prowling Mexicans, Beatriz Bermudez de Velasco,
wife of Francisco de Olmos, accompanied the soldiers, in cotton
armor, and with sword and shield. Such was the pressure of the
enemy that the troops were thrown into disorder and began to turn in
flight. With raised sword she planted herself in their path and cried,
“Shame upon you, Castilians! turn at once against this vile rabble, for
I will kill any man who attempts to pass this way.” So abashed were
the men by this resolute demeanor that they again fell upon the
Mexicans and defeated them.[1177] Other women of less valor did
equally good service as sisters of mercy, to tend and cheer the many
disabled. One, named Isabel de Rodriguez, attained quite a
reputation in curing wounds, a success attributed chiefly to her holy
invocation, for in applying the bandage she invariably uttered the
formula, “In the name of the father, the son, and the holy ghost, one
true God; may he cure and restore thee!”[1178]
Cortés found it absolutely necessary to resume operations in
order to prevent the utter demoralization of his men, although they
could advance no farther than the last canal on the Iztapalapan road,
which was strongly fortified to protect the plaza. On the Tlatelulco
side the channel separating the city from the causeway had been
reopened as a barrier. No serious effort was made to pass these
points, and the movements were effected with the greatest prudence
possible.
For this caution several reasons existed, based on momentous
consequences of the late defeat. In their exultation the Mexicans had
imprudently published the oracular utterance that within eight days
the Spaniards would be destroyed, though many Aztecs would also
perish.[1179] Care was taken that this divine proclamation should be
known in the Spanish camps, with the intent of disheartening the
allies and procuring their desertion. This main object accomplished,
it was hoped that neighboring districts might be again persuaded to
join in hostile operations, or at least assume a neutral attitude
against the isolated Spaniards. Severely harassed by all the strength
of the capital and its allies, the Spaniards would be unable to
maintain the siege or even to sustain their own position, particularly if
supplies were cut off, and so be obliged to retreat. Many indeed
looked upon the Spaniards as doomed, and tired besides of the long
siege, so contrary to native ideas of warfare, corps after corps of
their allies disappeared, in secret retreat to their homes. Others were
sufficiently shaken in their belief to lose all ardor, the more so when
they recalled the prophecy of disaster uttered by the hanged
Xicotencatl. Cortés and his officers did all they could to counteract
this influence by referring to previous failures of oracles, to the
comparatively small percentage of the late losses, the critical
condition of the besieged, and their efforts to gain advantages by
spreading lies. Let the allies but abide till the end of the term
mentioned by the oracle and they would be convinced of its falsity.
The last argument was perhaps the strongest that could be offered
under the circumstances, and it was decided to take no risks that
might imperil the proof.[1180]
These precautions were imperative in view of the effect of Aztec
machinations in the lake districts and outlying provinces. The lake
towns last to join the Spaniards relapsed into a frigid neutrality, and
might have risen but for the imposing proximity of the fleet and army.
Remoter districts assumed a more decided attitude, and from
Quauhnahuac came an urgent appeal for help against the attacks of
the Malinalcas and Cohuixcas, prompted by Mexico. Immediately
after the late victory Quauhtemotzin had sent envoys to these and
other provinces, in every direction, bearing heads or flayed skins of
Spaniards and horses, and other tokens, wherewith to impress their
story that more than half of the white besiegers were slain, and that
the remainder would soon perish, as declared by the oracle. It
behooved them, therefore, to decide at once whether they would join
for a share in the spoils, or be forever excluded from all favor at the
hands of victorious Mexico. Thus, while many were frightened into
severing their connection with the invaders, secretly or openly, more
aggressive provinces like Malinalco hastened to profit by the state of
affairs.
To detach troops under the circumstances was not agreeable,
and many officers objected, but Cortés considered that it would be
far more dangerous to Spanish prestige and prospects to encourage
such hostile movements by a passive demeanor. “It was now more
necessary than ever,” he writes, “to exhibit prowess and spirit, so as
to hide our weakness both from friends and foes.” Andrés de Tápia
was accordingly despatched with ten horse and eighty foot, together
with a considerable force of allies.[1181] In order to calm the many
remonstrances against the expedition, he was instructed to return
within ten days. Tápia found the enemy awaiting him in large force
near a hamlet not far from Malinalco, and at once prepared to attack,
assisted by the Quauhnahuacs. The ground being level, the horses
proved of great service, and the hostile army was presently in flight
toward Malinalco. This place was strongly situated on a height, well
supplied with water, so that Tápia considered it useless to attempt an
assault, much less a siege when so short a term had been allowed
him, and he accordingly returned.
 The complaint from Quauhnahuac was followed by a deeper wail
from Toluca and adjoining Otomí settlements in the mountain region
west of the lake. The Matlalzincas, devoted adherents of
Quauhtemotzin, had been induced to openly declare for him and to
invade their districts, preparatory to advancing against the
Spaniards. This intention had been already vauntingly proclaimed by
the Aztecs, and since the Matlaltzincas were both powerful and
warlike, the necessity for prompt measures became even more
apparent in this case. The tried Sandoval was intrusted with the
expedition, composed of eighteen cavalry, one hundred infantry, and
a large force of allies chiefly Otomís, which soon grew to about
seventy thousand. After a quick march he came to the smoking ruins
of some settlements and startled into flight a band of marauders,
who left behind them a quantity of plunder and provisions, including
some tender children still roasting on the spit. He pursued the
raiders, and after crossing a river[1182] came upon a larger force,
which turned as he approached, to seek safety within the town of
Matlaltzinco, over two leagues distant. The cavalry made terrible
havoc among them, and the infantry following in their wake, killed
more than two thousand. Those who escaped made a stand at the
town to cover the conveyance of families and effects to a fortified hill
close by. This was pretty well accomplished before the infantry came
up to assist in capturing the town. The defenders now fled, and the
place was entered and burned, after being rifled of what remained to
take. Since it was late, the assault on the hill was deferred till the
morning. There the natives maintained a loud uproar until some time
after midnight, when all became quiet. With early dawn the
Spaniards prepared to storm the hill only to learn that it had been
abandoned. A number of people were seen in the field, however, and
eagerly the soldiers revived the fading expectation for a fray. In a
twinkling they were among the rabble, and a number were slain
before the explanation gained ears that these people belonged to the
friendly Otomís. Sandoval now advanced on another fortified town,
whose cacique threw open the gates on beholding the hosts before
him, and not only offered his own submission, but promised to effect
the submission of the allied caciques and those of Malinalco and
Cohuixco. Regardless of the insinuations of the Otomís that such
promises could not be relied on, Sandoval returned to Mexico, and
four days later appeared there the caciques of all these provinces to
tender allegiance and aid for the siege.[1183]
Meanwhile the portentous eighth day had dawned on the
Spanish camps. Hardly less concerned than the natives, the soldiers
could not control their trepidation as they thought of the oracle,
although striving to appear indifferent. Nor were they without tangible
reasons for their fears. With a daily growing desertion among the
much needed allies, and fading enthusiasm among those who
remained; with supplies greatly reduced owing to the neutral attitude
assumed by surrounding districts; with fresh wars upon their hands,
which demanded not only more hardships but a division of their
weakened forces; with constant vigils and alarms amid the harassing
attacks of a triumphant foe; with a large number of wounded
deprived of needful care and comforts, and above all the ghastly
spectacle of a daily sacrifice of late comrades, attended by wild and
imposing celebrations—with all this gloom and distress it required
stout hearts indeed to remain steadfast. Yet they were firm; they
believed in the strength and justice of their cause, and in their
ultimate triumph, though momentarily dismayed, prayer afforded
them relief. It dissipated fear and infused fresh courage.
Thus passed the day, amidst fear and hope, and the Spaniards
still existed. The Mexicans do not appear to have made any special
effort to support the oracle by a determined attack. Nor had they
been able to open any effective communication with the mainland;
for although the lake towns had withdrawn their canoe fleet, they
offered no aid to the besieged, while the brigantines maintained too
strict a guard to permit many boats to gain the capital with supplies.
 The ninth day came, and now it was the turn of the Spaniards to
exult, for not only did they feel inspired with the belief that
providence was protecting them—and nobly the friars helped Cortés
to impart that stirring idea—but they were cheered with revived
animation among the allies and the early return of most of the
deserters. From Tezcuco, indeed, came additional troops under the
command of some Spaniards there stationed.[1184] Cortés greeted
the returning corps with rather cold forgiveness. He showed them
that besides carrying on the siege without their aid he had
undertaken victorious campaigns, and needed not their assistance.
Nevertheless, since they had served so zealously before, he would
not only overlook the grave crime of desertion, due partly to
ignorance of Spanish laws, but let them again share in the final
reduction of the city, and thus gain both revenge and riches. Cortés
could adopt no other course, for the siege could not be carried on
without the allies.
Under Spanish training the latter had besides grown very
efficient, as the following instance will illustrate: No sooner had the
eight portentous days passed by than Chichimecatl, the leading
Tlascaltec captain serving under Alvarado, disgusted with the idle
fears which had unmanned his people, and eager to retrieve them in
the eyes of the Spaniards, resolved to show both them and the
Aztecs what he could do. With the aid of the soldiers the first fortified
channel was captured, and the chief advanced into the city with his
own people only, the flower of his warriors, after leaving several
hundred archers near the passage to keep the route clear for retreat.
With unwavering columns he advanced along the main street and
captured the next canal passage after a fierce struggle. Then he
passed onward to the next, maintaining a sharp contest all the day.
Finally came the hour for returning, and the Aztecs bore down with
doubled fury on his flank and rear. The retreat was performed in
good order, partly owing to the foresight of leaving a rear body; and
Chichimecatl came back a lauded hero.[1185]
Messengers had been sent to the allies far and wide to
encourage them with the news of the non-fulfilment of the oracle.
Ojeda and Marquez went in person to Tlascala, partly also with the
object of procuring certain supplies. They left Alvarado’s camp at
midnight with only a few natives, and when about half-way to
Tepeyacac they perceived a train of men descending from the hills
with heavy burdens, which they deposited in a number of canoes.
Information was at once sent to Alvarado, who placed a guard along
the shore to check this smuggling that had evidently escaped the
cruisers.[1186] Ojeda’s party proceeded to Tlascala and brought a
large train of provisions.[1187] In addition to this the camps were
cheered by the arrival of a party of recruits with quite a mass of war
material, chiefly powder and cross-bows, relics of Ponce de Leon’s
Florida expedition.[1188] The war stores were particularly valuable; so
low had run the actual stock that Cortés was preparing more
Chinantec pikes to cover the deficiency in weapons.
Everything was again ready for a serious revival of hostilities.
Over six weeks had passed since the siege began, and the end
seemed little nearer than before. On the day of the defeat three
fourths of the city might be said to have been reduced; but nearly all
this advantage had been lost, owing chiefly to the narrow streets,
encompassed by houses which served both for attack and retreat,
and the numerous traps in the form of canals and channels. So long
as these obstacles remained the progress must not only be slow,
ever slower as advance was made, but the troops would be
constantly exposed to fresh disaster. One more defeat might ruin all,
and Cortés resolved to avoid risks. He would tear down every
building as he advanced on both sides of the streets, and fill up
every channel; “not take one step in advance without leaving all
desolated behind, and convert water into firm land, regardless of the
delay.” So writes the general, and yet he expresses regret for this
destruction of the city, “the most beautiful in the world.”[1189] In
pursuance of this plan he asked the allied chiefs to summon
additional forces of laborers with the necessary implements. They
eagerly consented, and within a few days the men stood prepared.

FOOTNOTES
[1143] ‘Eran esclavos del señor de Tenuxtitan,’ is Cortés’ definition of their
vassalage to Mexico. Cartas, 220.

[1144] A service which employed 20,000 carriers, 1000 canoes, and 32,000
convoy warriors, all at the expense of Tezcuco, says Ixtlilxochitl, Relaciones, 314.

[1145] His biographer admits to a certain extent the truth of the invectives, but
eager to please his Spanish masters he seeks rather to extol the self-sacrifice and
loyalty of his kinsman. He claims that with this reënforcement the Tezcucan
auxiliaries reached the improbable number of 250,000 men, of whom 5000
wounded were now sent home. ‘Next to God, Cortés owed to Tezcucan aid the
conquest and the planting of the faith.’ He further assumes that Ixtlilxochitl was
already king, and had been with Cortés since the fleet set sail, while his brother
Ahuaxpictzoctzin remained at Tezcuco to provide supplies. Hor. Crueldades, 21-
33. He contradicts himself on several points in his Relaciones, 314 et seq. Duran
also, as may be expected from a compiler of native records, extols the hero, ‘à
quien dió una espada dorada que Don Hernando Cortes traia y una rodela.’ Hist.
Ind., MS., ii. 493. With Ixtlilxochitl came half a dozen out of his hundred brothers.
Gomara, Hist. Mex., 198; Chimalpain, Hist. Conq., ii. 55. Torquemada, i. 548,
sends Cohuanacoch as general of the forces, while Clavigero allows King
Fernando Ixtlilxochitl to send his brother Cárlos Ixtlilxochitl. Storia Mess., iii. 202.
He is evidently confused with respect to the surname.

[1146] Sahagun, Hist. Conq. (ed. 1840), 177-8. Torquemada places the incident
earlier, i. 547. Cortés admits no losses of Spaniards this day.

[1147] Cartas, 222-3. ‘Los combidauan a çena, mostrando les piernas y braços.’
Gomara, Hist. Mex., 199.
[1148] Bernal Diaz speaks of a bridge attack which cost the lives of four
Spaniards, besides numerous wounded. Hist. Verdad., 145.

[1149] He enumerates also the cities of Mexicalcinco and Vitzilopuchtli. Hist. Mex.,
202. Herrera adds Mizquic. dec. iii. lib. i. cap. xix.

[1150] Mazeoatzi, as Sahagun calls the cacique, sacrificed four chiefs,

Quauhtemotzin four more; the rest fell by the hands of priests. Hist. Conq. (ed.
1840), 187. He does not speak of a premeditated plan like Torquemada, i. 551-2,
and since the account comes from native sources it may be merely an
exaggerated version of a flotilla raid.

[1151] This was the lieutenant of Velazquez at Habana, who joined Cortés during
the Tepeaca campaign. Portillo was a soldier from the Italian wars. Bernal Diaz
adds that one brig was captured, but this is doubtful. Hist. Verdad., 143; Clavigero,
Storia Mess., iii. 214; Sahagun, Hist. Conq., 46.

[1152] Bernal Diaz, Hist. Verdad., 144-5.

[1153] Cortés exultantly claims that three fourths of the city is now captured.
Cartas, 227; Sahagun, Hist. Conq. (ed. 1840), 181; Torquemada, i. 550.

[1154] ‘No se hartauan de pescado, que tuuierõ pocos dias: y demas de la

hambre con q̄ peleauan, el sol, y el frio no les dio pequeño trabajo.’ Herrera, dec.
iii. lib. i. cap. xix.

[1155] ‘Soliti sunt hostes in prælio cadentes intra suos ventres sepelire,’ explains
Peter Martyr, dec. v. cap. viii., and with some truth.

[1156] Forty soldiers watched till midnight, when a similar number relieved them,
and they again were relieved two hours before dawn; all three divisions camping
on the spot. Often every man was kept awake by alarms. Bernal Diaz, Hist.
Verdad., 142-3. The old soldier waxes eloquent over the hardships, for he served
at this camp.

[1157] The Spaniards tried in vain to despatch him. Sahagun states that during
these attacks fifteen soldiers were captured, and shortly after eighteen more, who
were sacrificed in a temple of Tlacuchcalco ward, ‘donde agora es la iglesia de
Santa Ana.’ Hist. Conq., 183, ed. 1840, 188-9. One repulse took place in
Coyonacazco ward. Torquemada, i. 550-2. Spanish versions indicate no such
losses, and they may probably belong to the later great defeat.

[1158] Such is in main the version of Bernal Diaz; the other accounts differ greatly.
This author states that five Spaniards were captured, nearly all the men wounded,
and two rowers killed, for the brigantines in seeking to aid had become fast on
stakes and exposed to attack. Had the Mexicans not been so frightened by the
horsemen the loss would have been very great. Hist. Verdad., 143-4. Cortés
allows three or four captured. Cartas, 228; Clavigero, Storia Mess., iii. 196. Duran
places the scene where rose afterward the San Hipólito hermitage. Hist. Ind., MS.,
ii. 500. But for Quauhtlizcatzin, the prince who led the Tezcucan auxiliaries, all the
Spaniards would have been lost, exclaims Ixtlilxochitl, Hor. Crueldades, 36.
Herrera assumes that the fault lay with Alvarado for neglecting to fill the channel.
dec. iii. lib. i. cap. xx.

[1159] ‘No solo no le culpo, mas loole.’ Gomara, Hist. Mex., 203.

[1160] The most serious attacks took place on June 24th and 25th, as if oracles
had impelled the Mexicans to seek the destruction of the Spaniards on the
anniversary of their reëntry into the city after the Alvarado massacre. The
Tlacopan camp lost ten soldiers and had a dozen severely wounded, including
Alvarado. Bernal Diaz, Hist. Verdad., 142, 145.

[1161] Bernal Diaz seeks to convey the idea that he or his camp were opposed to
the attempt, Id., 146, but had it succeeded, he would probably have declared the
truth, that Cortés was urged on all sides to make the effort, as stated in Gomara,
Hist. Mex., 203, Herrera, dec. iii. lib. i. cap. xx., and Cortés, Cartas, 228-9.
Perhaps the general made objections chiefly to cover his responsibility in case of
failure.

[1162] Alderete’s party consisted of 70 infantry, 7 or 8 horsemen, and 15,000 to

20,000 allies, besides a force of laborers to tear down and to fill up; Tápia’s of 80
men and over 10,000 allies, and Cortés’ of 8 horsemen, 100 infantry, and an
immense number of allies. Cortés, Cartas, 230-1. Gomara and Herrera differ
slightly. Ixtlilxochitl says that his namesake followed Cortés with 8000 Tezcucans.
Hor. Crueldades, 37. This insignificant number makes it difficult to account for the
250,000 Tezcucans which he lately introduced into the camps. Chimalpain names
the three streets Cuahuecatitlan, Tecontlanamacoya, and the later Santa Ana.
Hist. Conq., ii. 62.

[1163] See Native Races, ii. 303; iii. 293 et seq.

[1164] He crossed the channel with fifteen soldiers to sustain the fugitives, says
Torquemada, i. 554; but this seems incorrect.

[1165] The claims to the honor of rescuing the general are conflicting. Gomara,
followed by Herrera and Torquemada, names ‘Francisco’ de Olea. Bernal Diaz,
who states that this soldier slew four of the captains holding Cortés, lets Lerma
dispose of the remainder. After this came other soldiers and Quiñones. Cristóbal
de Olea was quite young, 26 years of age, a native of Medina del Campo,
muscular, and skilled in arms, and a general favorite. Bernal Diaz adds other
particulars. Hist. Verdad., 146, 246. Ixtlilxochitl, on the other hand, claims for his
namesake the credit of having done what Spaniards claim for Olea, aided by his
Tezcucans, who kept the enemy at bay. This, he adds, is proved by a painting on
the gate of the monastery of Santiago Tlatelulco. Hor. Crueldades, 38-9. Herrera
briefly alludes to Ixtlilxochitl as coming up after Olea, and then relates with some
detail that at the same time came the Tlascaltec, Tamaxautzin he calls him, a
native of Hueyotlipan. He was afterward baptized as Antonio or Bautista, and
became a good Christian, the first native to receive extreme unction. dec. iii. lib. i.
cap. xx. Torquemada, i. 555, copies, but calls the man Teamacatzin. Both
evidently prefer Tlascaltec to Tezcucan records. In fact, Ixtlilxochitl adds certain
incredible particulars about the prowess of his wounded hero in pursuing the
Mexican general into a temple, although such pursuit could not have taken place
under the circumstances. See also Duran, Hist. Ind., MS., ii. 503, and Camargo,
Hist. Tlax., 130. Cortés writes that he would have been lost but for Quiñones, and
one of his men who lost his life to save him. Cartas, 233. A small chapel was
erected in the convent de la Concepcion to commemorate the escape. See
Saavedra, Indio Peregrino, canto 20.

[1166] Bernal Diaz assumes that Guzman rode up after Cortés was mounted, and
fell captive into Aztec hands. Hist. Verdad., 147.

[1167] ‘Como lo hallarán pintado en la Yglesia de Tlatilulco, los cuales Indios

confiesan haberle visto.’ Duran, Hist. Ind., MS., ii. 512. Why these patrons did not
give their aid before is a question to which Bernal Diaz answers ‘porque Nuestro
Señor Iesu Christo lo permitiò.’ Hist. Verdad., 146.

[1168] Herrera relates how two captains, Flores and Mota, advanced with their
vessels up a narrow channel. Flores was severely pressed at one time, and the
latter had to sally on the street to relieve him and enable the brigantines to gain
more open water. Flores died within a week of his wounds. dec. iii. lib. i. cap. xx.
Torquemada says that Briones’ vessel was lifted through a breach in the
causeway. i. 555. Bernal Diaz speaks of several such narrow escapes. loc. cit.

[1169] The artillerists being all disabled or dead, Pedro Moreno de Medrano,
afterward a settler at Puebla, took their place. Id.

[1170] Bernal Diaz writes as if Sandoval gained the camp at an early hour, rode
over to Fort Xoloc, and came back in time to aid in Alvarado’s retreat. But he
would never have ventured to leave his command and his comrade in their
danger; nor does it seem likely that he could have ridden the long distance to
Xoloc and back in time to join in Alvarado’s conflict, even if Cortés’ defeat took
place before ‘misa mayor,’ as he assumes. Hist. Verdad., 146-8. This author is
here very confused, assuming, for instance, that Sandoval was fighting from his
own camp instead of coöperating near Alvarado.

[1171] So deeply affected was Bernal Diaz, among others, by the sight, and by the
fear of himself falling captive—twice had he narrowly escaped—that he ever after
had an oppressive feeling before battle. He then had recourse to prayer, and this
invariably fortified him for the fight, so that he always maintained his reputation as
a good soldier. He enumerates several incidents to prove that he was esteemed a
brave man. Hist. Verdad., 157. Oviedo, referring to human sacrifices among the
Romans, observes that they could not have been half so fearful. iii. 515.

[1172] ‘Sacrificados los Nuestros, en el Momoztli, y Templo de su Maior Dios,’

observes Torquemada, i. 553, among other points, though all are not exactly true.
Huitzilopochtli’s image had been brought with the retreating Mexicans to
Tlatelulco. ‘Immediatamente sacrificati,’ says Clavigero, Storia Mess., iii. 212,
probably on authority of Gomara; but Bernal Diaz states that the sacrifices lasted
ten days, Hist. Verdad., 150; others write eight; one victim is said to have been
kept eighteen days. See also Sahagun, Hist. Conq., 192. Ixtlilxochitl states that
three victims were burned. Hor. Crueldades, 39.

[1173] A count revealed the loss of 62 men and 6 horses, says Bernal Diaz, Hist.
Verdad., 146, 152, 241, though he in one place leaves the impression that the
men were all captured alive. This could hardly be the case, for a ‘count’ would
reveal only the missing; none could tell how many fell captive. Yet Prescott boldly
assumes this number to have been taken, besides those who fell. Vetancurt
divides the figures into 40 captives and 20 dead, Teatro Mex., pt. iii. 162, and
Clavigero also includes dead and captive in that number, while raising the dead
horses to 7. Storia Mess., iii. 212. Solis writes that over 40 Spaniards were carried
off alive, and that Alvarado and Sandoval lost 20. Hist. Mex., ii. 410. Bernal Diaz
acknowledges only a third of such loss between these two captains. Gomara gives
40 captives, several killed, 3 or 4 horses lost, and over 30 wounded. Hist. Mex.,
205-6. Ixtlilxochitl raises the allied loss to over 2000. Hor. Crueldades, 37-9. Fifty-
three Spaniards, says Sahagun, Hist. Conq., 192. In the cédula of March 7, 1525,
granting a coat-of-arms to Cortés, 50 are mentioned, but in his letter to the
sovereign the general acknowledges only 35 to 40 and over 1000 allies. Herrera
and Torquemada adopt these figures. Oviedo, iii. 516, lowers the number to 30.
Duran, who confounds the late repulse of Alvarado with the Sorrowful Night and
this defeat, allows 4 banners to be captured. Hist. Ind., MS., ii. 501-4, 508.

[1174] Bernal Diaz gives this conversation with some detail, and names Treasurer
Alderete as the guilty officer who neglected to fill the channel, intimating that
Cortés had been heedlessly allured onward by the Mexicans, leaving Alderete to
attend to the filling. He even allows the treasurer to retort to the charge, in
Sandoval’s presence, that Cortés’ eagerness had been the cause of the neglect.
This is probably an invented account, based on Gomara’s statement that the
‘treasurer,’ no name being given, neglected to fill a channel on his route. Informed
of this, Cortés hastened thither to remedy the fault, only to meet the fleeing.
Herrera adopts this version, as do most writers, including Prescott; but it is
evidently wrong, for Cortés writes clearly that the misfortune occurred on his own
route, some distance above its junction with the Tlacopan road, to which they soon
retreated. On reaching this road he sent to recall the ‘treasurer and comptroller,’
who were leading their division victoriously at the farther end of it. Owing to their
care in filling channels ‘they received no injury in retreating.’ Cartas, 233-4. There
can be little doubt about this statement, since Cortés would have been only too
glad to cast the blame on any other division than his own. He does not even claim
to have been at the front, but in the rear, and near the spot where the neglect
occurred. The only question then is, who was the guilty officer? The ‘treasurer’
commanded the centre division, and although there were several treasurers, the
royal, late and new, and he who acted for the army, yet the new royal treasurer is
undoubtedly meant, and this appears to have been Alderete, according to the
statement of several authorities. Hence the accusation against Alderete must be
wrong; anything besides this must be conjecture.

[1175] ‘Bolviò à la grita, Andrés de Tapia [the captain of his party] matò mas de
sesenta Mexicanos,’ adds Torquemada, i. 558-9.

[1176] ‘Esto no fue sino cinco dias.’ Bernal Diaz, Hist. Verdad., 149.

[1177] Similar women of courage were María de Estrada, the heroine of Otumba,
Beatriz de Escobar, Juana Martin, and Beatriz de Palacios. Herrera, dec. iii. lib. ii.
cap. i.

[1178] Oil was the chief remedy. Torquemada, i. 558-60. Bernal Diaz speaks of a
soldier named Juan Catalan who performed cures with the sign of the cross and
psalm-singing. The Tlascaltecs also besieged the man for his attentions. ‘Y
verdaderamente digo, que hallauamos que Nuestro Señor Iesu Christo era
servido de darnos esfuerço, ... y de presto sanauan.’ Not twenty of Alvarado’s
men were free from wounds at this time. Hist. Verdad., 142. Solis allows this
wonderful healing power to be attributed to no woman. Hist. Mex., ii. 412. But then
he was a strict priest, who saw woman chiefly as a feeble and adoring supplicant.

[1179] ‘Que de ai a ocho dias no auia de quedar ninguno de nosotros a vida,

porque assi se lo auian prometido la noche antes sus Dioses.’ Bernal Diaz, Hist.
Verdad., 149.

[1180] Solis, Hist. Mex., ii. 415, states, and Prescott hastily affirms, that nearly all
the allies deserted, and Bernal Diaz enumerates the mere handful that remained;
but this must be erroneous, as shown by the course of the narratives in general.
Two expeditions were sent forth about this time, and the large number of allies
which joined therein may account in part for the gaps which gave rise to the above
exaggeration. Cortés, indeed, alludes very indirectly to any defection.

[1181] Forty thousand, says Ixtlilxochitl, obtained chiefly from Quauhnahuac and
other towns subject to Tezcuco. Hor. Crueldades, 40. Herrera and others mention
no auxiliaries from the camp. Bernal Diaz is confused.

[1182] The Chicuhnauhtla, Ixtlilxochitl calls it.

[1183] ‘Y ellos le siruieron muy biẽ en el cerco.’ Gomara, Hist. Mex., 207.
Ixtlilxochitl claims of course that his Tezcucans formed the chief auxiliaries of
Sandoval. Bernal Diaz wrongly gives Tápia this expedition, which Cortés intimates
to have been sent about three days after the return of the Quauhnahuac party.
Cartas, 237.

[1184] Farfan and Villareal came, says Bernal Diaz, and Tecapaneca, cacique of
Topeyanco, led the returning Tlascaltecs. Hist. Verdad., 151.

[1185] Cortés leaves the impression that this incident took place during the days
when the Spaniards were making desultory entries into the city; but since he does
not speak of the oracle or the defection the affair is undecided. Torquemada, i.
557, intimates that Chichimecatl served under Sandoval, but this is wrong.

[1186] Ojeda magnifies the train of men to 4000 and the canoes to 3000. Herrera,
dec. iii. lib. i. cap. xxii.

[1187] Fifteen hundred loads maize, 1000 loads fowl, 300 sides venison, besides
other effects, including Xicotencatl’s confiscated property and women. Id.

[1188] Herrera intimates that the material may have been a consignment to Leon,
for which the disappointed owner sought a market. A vessel of Aillon’s fleet, says
Bernal Diaz, Hist. Verdad., 153.

[1189] Some time before he had expressed the same intention, and the fear that
little or no treasure would be recovered. Cartas, 222, 241. Ixtlilxochitl claims that
his namesake provided 100,000 men for the task, Hor. Crueldades, 42, and Bernal
Diaz states that this prince proposed purely a strict blockade as a safe and sure
plan. Hist. Verdad., 150. The result proves that this would have been the best and
as speedy as the one adopted, while the city would have been saved from
destruction. That the plan was ever seriously suggested among this impatient
crew is affirmed by no other authority.