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Biodrug Delivery Systems Fundamentals Applications and
Clinical Development Drugs and the Pharmaceutical
Sciences 1st Edition Mariko Morishita Digital Instant
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Author(s): Mariko Morishita, Kinam Park
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Biodrug Delivery
Systems
 DRUGS AND THE PHARMACEUTICAL SCIENCES
A Series of Textbooks and Monographs

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150. Laboratory Auditing for Quality and Regulatory Compliance, Donald
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152. Preclinical Drug Development, edited by Mark C. Rogge and David R. Taft
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Biodrug Delivery
Systems
Fundamentals, Applications
and Clinical Development

edited by
Mariko Morishita
Hoshi University
Tokyo, Japan

Kinam Park
Purdue University
West Lafayette, Indiana, USA
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Biodrug delivery systems : fundamentals, applications, and clinical development /

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 Preface

Drugs have been essential in modern medicine. It is hard to imagine what our
daily lives would look like without all those drugs treating various diseases.
Drug discovery in old days was relatively easy as a large number of drugs were
waiting to be discovered. In the 21st century, however, drug discovery has
become much more difficult, not just in a relative sense as compared with the
old days but also even after the inflation in difficulties is adjusted. This is
because the nature of drugs in the 21st century has shifted from low to high
molecular weight drugs. Drug discovery in the 21st century is now focused on
biotechnology-based drugs (biodrugs) that include peptides and proteins,
antibodies, and siRNAs. There is no doubt that biodrugs will occupy a signifi-
cant portion of the drugs in the near future.
Biodrugs have several advantageous properties. Their clinical efficacy is
exquisite, and even a minute amount of the drug is highly effective. Because of
their high specificity, the side effects of biodrugs are usually low. The use of
biodrugs is not limited to symptomatic therapy, and they can be used to cure
diseases. Furthermore, on the basis of the diversity of their characteristics, bio-
drugs have wide applicability in drug development. Usually the target for a
biodrug is well defined, and thus, their effectiveness and safety surpass those of
low molecular weight drugs. For example, antibody can be used as a drug and
also as a vehicle for drug delivery to the target tissues and cells. Antibodies have
been used quite effectively as a homing device for delivery of nanoparticulate
systems containing various drugs. Biodrugs, like any other drugs, also suffer
from certain limitations. These, in general, have low stability because of their
proteinaceous nature. This requires careful handling of biodrugs during pro-
duction, supply, and storage. Moreover, the high molecular weight of biodrugs
limits the selection of their administration routes and, thus, formulation designs.
It is also well known that biodrugs are rapidly cleared from the body, and thus,
they have to be administered quite frequently. Various difficulties and limi-
tations of developing biodrugs require sophisticated drug delivery technologies
for improvement in absorption, control of their in vivo metabolism, and their in
vivo distribution, that is, delivery to target tissues. Simply put, development of
the future biodrugs requires advanced drug delivery technologies, such as smart
drug delivery systems and nanotechnology-based delivery vehicles.
This book is intended to provide timely information that is critical for
development of various biodrug formulations. Part I of the book deals with
fundamental aspects of biodrugs. It begins with an overview and issues asso-
ciated with the development of biodrug delivery systems. Recent understanding
on pharmacokinetic considerations for biodrug delivery is covered in detail. Part
II deals with specific routes of delivery, ranging from parenteral to oral routes,
and covers most routes available in the body for biodrug delivery. Such an
overview of administration routes will be useful to beginners who are new to
biodrug delivery as well as experts with years of experience who have been

vii
viii Preface

focusing on the specific field of drug delivery. Readers will gain a fundamental
understanding of the mechanisms of biodrug absorption and possibilities for
biodrug delivery via alternative routes. Part III deals with modern strategies for
biodrug delivery. It presents recent advances in biodrug delivery systems and
associated techniques in sufficient detail for readers to understand and utilize
the techniques in their own studies. The delivery systems discussed are bio-
adhesives, modified release systems, nanoparticles, lipid-based systems,
implantables, reversible lipidization, and noncondensing gelatin systems. Also
included in part III is in vivo–in vitro correlation for biodrugs. Part IV of the
book focuses on case studies of the development of clinical formulations, some
of which are currently available on the market for treating patients. This section
starts with perspectives on the regulation of biodrug development, followed by
formulations for leuprorelin acetate, atrial natriuretic peptide, Sandostatin,
interferon-a, vaccines, tumor necrosis factor-a, and antibodies. As more and
more biodrugs are developed, the issue of delivery becomes more important.
‘‘Delivery’’ of biodrugs will remain one of the main issues in the development of
clinically successful formulations for the foreseeable future.
We sincerely hope that this book will serve as a comprehensive guide for
those who are engaged in the development of biodrug delivery systems. We also
hope that this book not only provides important information on biodrugs but
also stimulates scientists in various stages of their careers to develop new,
innovative delivery systems. Finally, we would like to send our deepest
appreciation to all the authors who submitted their high-quality chapters in a
timely manner, and the editorial staff at Informa Healthcare who believed in this
book and provided endless supports.
Mariko Morishita
Kinam Park
 Contents

Preface . . . . vii
Contributors . . . . xiii

Part 1: Fundamentals
1. Overview of Biodrug Delivery Systems: Disease Fundamentals, Delivery
Problems, and Strategic Approaches 1
Justin P. Shofner and Nicholas A. Peppas

2. Issues in Development of Biodrug Delivery Systems 13

Lene Jørgensen, Sven Frokjaer, and Hanne Mørck Nielsen

3. Pharmacokinetic Consideration of Biodrugs 26

Kazuya Maeda, Motohiro Kato, and Yuichi Sugiyama

4. Pharmacokinetic Consideration of Biodrugs: Targeting 40

Yoshinobu Takakura

Part 2: Routes of Delivery

5. Parenteral Delivery of Peptides and Proteins 50
Archana Rawat and Diane J. Burgess

6. Pulmonary Delivery Systems 69

Hirokazu Okamoto

7. Transdermal Delivery Systems 87

Heather A. E. Benson

8. Nasal Delivery Systems 104

Takahiro Morita and Hiroshi Yamahara

9. Buccal Delivery Systems 119

Joseph A. Nicolazzo and Janne Mannila

10. Colon-Targeted Delivery Systems 138

Efrat Abutbul and Abraham Rubinstein

ix
x Contents

11. Oral Delivery Systems 172

Mariko Morishita, El-Sayed Khafagy, Justin P. Shofner, and Nicholas A. Peppas

12. Ocular Delivery Systems: Transscleral Drug Delivery to the Posterior Eye
Segment 187
Arto Urtti

13. Cellular Delivery Systems 194

Greg Russell-Jones

Part 3: Modern Delivery Strategies

14. Bioadhesive Delivery Systems 218
Anja Vetter and Andreas Bernkop-Schnürch

15. Modified Release Delivery Systems 234

Mark M. Bailey and Cory J. Berkland

16. Nanoparticle Delivery Systems 248

Greg Russell-Jones

17. Lipid-Based Delivery Systems: Liposomes and Lipid-Core

Micelles—Properties and Applications 260
Tiziana Musacchio and Vladimir P. Torchilin

18. Implantable Delivery Systems 293

Moon Suk Kim, Jae Ho Kim, Byoung Hyun Min, Kinam Park, and Hai Bang Lee

19. Modifying the Physicochemical Nature of Biodrugs by Reversible

Lipidization 309
Jennica L. Zaro, Wei-Chiang Shen, and Jeffrey Wang

20. Gelatin-Based DNA Delivery Systems 323

Luis Brito, Sandra Chadwick, and Mansoor Amiji

21. In Vitro–In Vivo Correlation: Application to Biotech Product

Development 341
Jean-Michel Cardot

Part 4: Development of Clinical Formulations

22. Perspectives on the Regulation of Biodrug Development 357
Takao Hayakawa

23. Depot Injectable Microcapsules of Leuprorelin Acetate (Lupron

Depot) 370
Hiroaki Okada
Contents xi

24. Development of Novel Formulation for Atrial Natriuretic Peptide

(ANP) 384
Yasushi Kanai, Mayumi Furuya, and Yujiro Hayashi

25. Clinical Significance of the Long-Acting Formulation

Sandostatin LAR 394
Nobutaka Demura

26. Interferon-Alpha: Sustained Release Type Injection 402

Shunji Nagahara, Akihiko Sano, and Keiji Fujioka

27. Vaccine Delivery Systems 412

Terry L. Bowersock and Sunil Narishetty

28. PEGylated Tumor Necrosis Factor-Alpha and Its Muteins 425

Yasuhiro Abe, Shin-ichi Tsunoda, and Yasuo Tsutsumi

29. Delivery and Effector Function of Antibody Therapeutics in Human

Solid Tumor 436
Yutaka Kanda, Akifumi Kato, Harue Imai-Nishiya, and Mitsuo Satoh

Index . . . . 451
 Contributors

Yasuhiro Abe Laboratory of Pharmaceutical Proteomics, National Institute of

Biomedical Innovation, Ibaraki, Osaka, Japan

Efrat Abutbul Faculty of Medicine, The School of Pharmacy Institute of Drug

Research, The Hebrew University of Jerusalem, Jerusalem, Israel

Mansoor Amiji Department of Pharmaceutical Sciences, School of Pharmacy,

Northeastern University, Boston, Massachusetts, U.S.A.

Mark M. Bailey Department of Chemical and Petroleum Engineering,

The University of Kansas, Lawrence, Kansas, U.S.A.

Heather A. E. Benson Curtin Health Innovation Research Institute, School of

Pharmacy, Curtin University, Perth, Western Australia

Cory J. Berkland Departments of Chemical and Petroleum Engineering and

Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas, U.S.A.

Andreas Bernkop-Schnürch Department of Pharmaceutical Technology,

Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innsbruck,
Austria

Terry L. Bowersock Pfizer Animal Health, Kalamazoo, Michigan, U.S.A.

Luis Brito Department of Pharmaceutical Sciences, School of Pharmacy,

Northeastern University, Boston, Massachusetts, U.S.A.

Diane J. Burgess School of Pharmacy, University of Connecticut, Storrs,

Connecticut, U.S.A.

Jean-Michel Cardot UFR Pharmacie, ERT-CIDAM, Univ Clermont 1,

Clermont-Ferrand, France

Sandra Chadwick Department of Pharmaceutical Sciences, School of

Pharmacy, Northeastern University, Boston, Massachusetts, U.S.A.

Nobutaka Demura Translational Sciences Department, Development

Division, Novartis Pharma KK, Tokyo, Japan

Sven Frokjaer Department of Pharmaceutics and Analytical Chemistry,

University of Copenhagen, Copenhagen, Denmark

xiii
xiv Contributors

Keiji Fujioka Technology Research and Development, Dainippon Sumitomo

Pharma Co., Ltd., Chuo-ku, Osaka, Japan

Mayumi Furuya Biomedical Research Laboratories, Asubio Pharma Co., Ltd,

Osaka, Japan

Takao Hayakawa Pharmaceutical Research and Technology Institute, Kinki

University, Higashi-Osaka City, Japan

Yujiro Hayashi Biopharma Center, Asubio Pharma Co., Ltd, Gunma, Japan

Harue Imai-Nishiya Antibody Research Laboratories, Kyowa Hakko Kirin

Co., Ltd., Tokyo, Japan

Lene Jørgensen Department of Pharmaceutics and Analytical Chemistry,

University of Copenhagen, Copenhagen, Denmark

Yasushi Kanai Biopharma Center, Asubio Pharma Co., Ltd, Gunma, Japan

Yutaka Kanda Antibody Research Laboratories, Kyowa Hakko Kirin Co., Ltd.,
Tokyo, Japan

Akifumi Kato Antibody Research Laboratories, Kyowa Hakko Kirin Co., Ltd.,
Tokyo, Japan

Motohiro Kato Chugai Pharmaceutical Co. Ltd., Gotemba, Shizuoka, Japan

El-Sayed Khafagy Department of Pharmaceutics, Hoshi University,

Shinagawa, Tokyo, Japan

Moon Suk Kim Department of Molecular Science and Technology, Ajou

University, Suwon, Korea

Jae Ho Kim Department of Molecular Science and Technology, Ajou

University, Suwon, Korea

Hai Bang Lee Department of Molecular Science and Technology, Ajou

University, Suwon, Korea

Kazuya Maeda Department of Molecular Pharmacokinetics, Graduate School

of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

Janne Mannila Drug Delivery, Disposition and Dynamics, Monash Institute of

Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia

Byoung Hyun Min Department of Molecular Science and Technology and

Department of Orthopedic Surgery, Ajou University, Suwon, Korea

Mariko Morishita Department of Pharmaceutics, Hoshi University,

Shinagawa, Tokyo, Japan
Contributors xv

Takahiro Morita Mitsubishi Tanabe Pharma Corporation, Osaka, Japan

Tiziana Musacchio Center for Pharmaceutical Biotechnology and

Nanomedicine, Northeastern University, Boston, Massachusetts, U.S.A.

Shunji Nagahara Technology Research and Development, Dainippon

Sumitomo Pharma Co., Ltd., Chuo-ku, Osaka, Japan

Sunil Narishetty Pfizer Animal Health, Kalamazoo, Michigan, U.S.A.

Joseph A. Nicolazzo Drug Delivery, Disposition and Dynamics, Monash

Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria,
Australia

Hanne Mørck Nielsen Department of Pharmaceutics and Analytical

Chemistry, University of Copenhagen, Copenhagen, Denmark

Hiroaki Okada Department of Pharmaceutical Science, School of Pharmacy,

Tokyo University of Pharmacy and Life Sciences, Horinouchi, Hachioji, Tokyo,
Japan

Hirokazu Okamoto Faculty of Pharmacy, Meijo University, Nagoya, Japan

Kinam Park Departments of Biomedical Engineering and Pharmaceutics,

Purdue University, West Lafayette, Indiana, U.S.A.

Nicholas A. Peppas Departments of Chemical Engineering and Biomedical

Engineering, and College of Pharmacy, The University of Texas at Austin,
Austin, Texas, U.S.A.

Archana Rawat School of Pharmacy, University of Connecticut, Storrs,

Connecticut, U.S.A.

Abraham Rubinstein Faculty of Medicine, The School of Pharmacy Institute of

Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel

Greg Russell-Jones Mentor Pharmaceutical Consulting Pty Ltd, New South

Wales, Australia

Akihiko Sano Technology Research and Development, Dainippon Sumitomo

Pharma Co., Ltd., Chuo-ku, Osaka, Japan

Mitsuo Satoh Antibody Research Laboratories, Kyowa Hakko Kirin Co., Ltd.,
Tokyo, Japan

Wei-Chiang Shen Department of Pharmacology and Pharmaceutical Sciences,

School of Pharmacy, University of Southern California, Los Angeles, California,
U.S.A.
xvi Contributors

Justin P. Shofner Department of Chemical Engineering, The University of

Texas at Austin, Austin, Texas, U.S.A.

Yuichi Sugiyama Department of Molecular Pharmacokinetics, Graduate

School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo,
Japan

Yoshinobu Takakura Department of Biopharmaceutics and Drug Metabolism,

Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku,
Kyoto, Japan

Vladimir P. Torchilin Center for Pharmaceutical Biotechnology and

Nanomedicine, Northeastern University, Boston, Massachusetts, U.S.A.

Shin-ichi Tsunoda Laboratory of Pharmaceutical Proteomics, National

Institute of Biomedical Innovation, Ibaraki, Osaka, Japan

Yasuo Tsutsumi Laboratory of Pharmaceutical Proteomics, National Institute

of Biomedical Innovation, Ibaraki, and Department of Toxicology, Graduate
School of Pharmaceutical Sciences, Osaka University, Osaka, Japan

Arto Urtti Centre for Drug Research, University of Helsinki, Helsinki, Finland

Anja Vetter Department of Pharmaceutical Technology, Institute of

Pharmacy, Leopold-Franzens-University Innsbruck, Innsbruck, Austria

Jeffrey Wang Department of Pharmaceutical Sciences, College of Pharmacy,

Western University of Health Sciences, Pomona, California, U.S.A.

Hiroshi Yamahara Mitsubishi Tanabe Pharma Corporation, Osaka, Japan

Jennica L. Zaro Department of Pharmacology and Pharmaceutical Sciences,

School of Pharmacy, University of Southern California, Los Angeles, California,
U.S.A.
 1 Overview of Biodrug Delivery Systems:
Disease Fundamentals, Delivery Problems,
and Strategic Approaches
Justin P. Shofner
Department of Chemical Engineering, The University of Texas at Austin, Austin,
Texas, U.S.A.

Nicholas A. Peppas
Departments of Chemical Engineering and Biomedical Engineering, and College of
Pharmacy, The University of Texas at Austin, Austin, Texas, U.S.A.

INTRODUCTION
Recent advances in the field of biotechnology have led to increased usage of
pharmaceutical formulations involving therapeutic proteins. There is a wide
variety of therapeutic proteins that are used to treat a wide variety of illnesses.
One of the most prevalent therapeutic proteins based on medical need is insulin,
which is used to treat diabetes. Another prevalent therapeutic protein is calcitonin,
which is administered to treat Paget disease, bone metastases, hypercalcemia, and
postmenopausal osteoporosis.
Here a number of common diseases requiring therapeutic protein treatment
are discussed. Also, several alternative routes of administration of injections for
the delivery of proteins are explored such as oral, transdermal, and pulmonary
delivery. Oral protein delivery is discussed in detail and is presented with respect
to its benefits and challenges as well as strategies to circumvent the natural
biological barriers that are present in the body.

DISEASE FUNDAMENTALS
Diabetes Mellitus
Diabetes is an illness in which the body cannot produce or properly use insulin.
Specifically, diabetes mellitus refers to a group of diseases that are characterized
by chronic hypoglycemia and abnormal metabolism due to a deficiency in the
overall effect of insulin in the body (1). Over 16 million people in the United
States are estimated to have diabetes mellitus (2); many of whom are unaware
that they have the disease. Globally, the number of diabetics is predicted to
double from 150 million to over 300 million worldwide in the next 30 years (3).
The most alarming fact is that diabetes is already the fourth to fifth leading
cause of death in developed countries and is quickly rising in developing
countries (4). The combination of the death toll from diabetes and the expected
increase of diabetics to over 300 million by 2030 suggests that diabetes will
become a worldwide epidemic in the upcoming decades.
There are several types of diabetes mellitus. Type I diabetes is often
referred to as autoimmune diabetes mellitus because of the autoimmune attack
of insulin-secreting b cells, leading to insulin deficiency. The autoimmune attack
is mediated by T cells and occurs in b cells in the pancreatic islets of Langerhans.
Generally, no preventative measures can be taken against type I diabetes.

1
2 Shofner and Peppas

However, some options for preservation of b cells are being investigated. Apart
from possible technologies resulting from recent research, type I diabetics are
generally dependent on insulin therapy to maintain proper blood glucose levels.
Regular and controlled insulin dosage is required for the survival of type I
diabetics. Improper insulin dosage can result in extremely high blood glucose
levels and ketoacidosis, a condition in which the body undergoes abnormal
metabolism and releases dangerous amounts of ketone bodies into the blood-
stream (5). If ketoacidosis is not recognized and treated immediately, it can
result in a coma or even death of the patient.
Type II diabetes is the most common form of diabetes mellitus and gener-
ally develops as a result of the combination effect of an increased insulin resis-
tance as well as a decrease in insulin secretion. The exact cause of type II diabetes
is unknown, but obesity, high carbohydrate intake, and lack of physical activity
have been shown to increase insulin resistance in the body (6). Many patients at
risk for developing type II diabetes, or those with prediabetes, have the possibility
of preventing or at least delaying the onset of type II diabetes by adopting healthy
eating habits, being regularly active, and maintaining a healthy body weight (7).
Once a patient has developed type II diabetes, the level of insulin dependence can
vary over a wide range. Diabetics in the early stages of type II diabetes often do
not require therapeutic insulin, but the transition into insulin therapy is typically
inevitable due to the progressive nature of the disease (8). Noncompliance of
insulin-dependent diabetics, either by skipping needed injections or by mis-
calculating the amount of insulin, is a point of emphasis in diabetes education and
can lead to serious complications if repeated over prolonged periods (9).
Pregestational diabetes mellitus (PDM) and gestational diabetes mellitus
(GDM) are two of the less common forms of diabetes and only affect a small
percentage of all pregnancies. Gestational diabetes is typically characterized by an
elevated blood glucose level in the later months of the pregnancy due to an
inadequate adjustment to the glucose metabolism required during pregnancy (10).
If gestational diabetes in pregnant females is not detected or is not properly
treated, childbirth complications such as hydramnios, fetal anomalies, and preterm
births can occur (11).
The most important factor for patients who have developed diabetes is
glycemic control. There are many forms of insulin for use in insulin therapy for
diabetics to maintain glycemic control. Some of the developments in insulin
therapy to further diabetes treatment and maintain better glycemic control are
summarized below.

Insulin and Insulin Therapies for Diabetics

Insulin is a hormone protein that is synthesized in the b cells of the pancreas.
Insulin is initially produced as a large preprohormone (*11.5 kDa) and later
cleaved into proinsulin (*9 kDa). Proinsulin splits into two pieces, one of which
is common insulin. Insulin (*5.8 kDa) is composed of 51 amino acids and has a
hydrodynamic radius of 20  A (12). The structure of insulin (Fig. 1) consists of an
A-chain with 21 amino acids and a B-chain with 30 amino acids connected by
two disulfide bonds.
Insulin is used to assist in the conversion of glucose to energy and con-
sequently to control blood glucose levels within the body. The mechanism of
insulin release in response to high blood glucose levels begins in the pancreas.
Overview of Biodrug Delivery Systems 3

FIGURE 1 Basic structure of insulin. Insulin contains a total of 51 amino acids composed of
two separate chains connected by disulfide linkages. The A-chain contains 21 amino acids, while
the B-chain contains 30 amino acids. The molecular weight of insulin is approximately 5728 Da.

After food intake or variable glucose change, glucose enters the b cells in the
pancreas via the glucose transporter GLUT2. The glucose in the b cells causes
ATP molecules to be formed, which can cause the potassium channels to close.
Closing of the potassium channels depolarizes the cell, which leads to the intake
of calcium through calcium channels. An increased concentration of calcium
within the cell allows previously stored insulin to be released from the b cell.
After insulin has been released it will reach the bloodstream via the liver.
Freely circulating insulin will interact with several types of cells, the majority of
which are fat and muscle cells. Insulin then binds with the insulin receptors on the
cell surface. Upon insulin binding, the receptor undergoes a rapid conformational
change, resulting in the activation of the tyrosine kinase domain (13). Activation of
this domain is referred to as receptor autophosphorylation. After phosphorylation
of the b-subunits, the insulin receptor activates key enzymes that undergo a
complex series of signaling using several signaling pathways, which ultimately
increase the cell permeability to glucose (14). The increased permeability in the
affected cells allow for increased glucose uptake, providing needed energy for the
normal function of the cells. Overall, improper insulin levels affect the body’s
ability to regulate blood glucose level, which can lead to serious complications (15).
Insulin therapy is essential to maintaining an average quality of life for
millions of insulin-dependent diabetics. Generally, diabetics undergo several
injections a day to maintain their blood glucose levels. Because of this painful
inconvenience, which is required, of all diabetics to maintain a high quality of life,
alternative routes of administration of therapeutic insulin need to be investigated.

Osteoporosis
Protein therapy is used to treat a variety of other illnesses as well. Specifically,
calcitonin is used in the treatment of osteoporosis as well as Paget disease,
hypercalcemia, and bone metastases (16). Osteoporosis is a disease in which
bone structure deteriorates and there is a resultant low bone mass. Osteoporosis
affects 10 million Americans, and it is especially common in postmenopausal
Caucasian women (17).
Osteoporosis is marked by a biological imbalance of osteoclast activity,
which removes bone tissue, and osteoblast activity, which helps to reform bone
Other documents randomly have
different content
as you still may see, and it threatened to burn the dry roof and the
old walls, and the children too. So I caught it up and bore it away,
and the children sleep in safety while I shine gloriously here."
"And so," concluded Guy, "a good deed will shine, and glow, ages
after evil and cruel ones are forgotten."
"That is a pretty story," said Aggie, contentedly, "and I am going to
bed now to dream all night of the good fly, and her fadeless lamp.
Good-night, dear Guy, don't forget that pretty story, for you must tell
it again to-morrow."
 CHAPTER IV.
But on the morrow neither the story of the fire-flies or any other was
told, for late in the afternoon they arrived at Fort Leavenworth,
which is situated on the western border of Missouri, and was then
the last white settlement that travelers saw for many hundreds of
miles.
All felt very sad the next morning when the train proceeded on its
way. Many of them thought they were leaving civilization and its
blessings forever behind, and as they looked toward the vast prairie
of the West they remembered with a shudder how many had found
a grave beneath its tall grass. But there was no delaying or turning
back then, and so they slowly continued their way, pausing but once
to give a farewell cheer for the flag that floated from the fort, and to
look at their rifles and say, "We are ready for whatever may come!"
To Guy it seemed impossible that any one could long remain sad in
the beautiful country they were entering upon. As far as the eye
could reach lay a vast expanse of prairie, upon which the sunbeams
lay like golden halo, making the long, rich grass of one uniform tint
of pale green. Then a gentle breeze would come and ruffle the
surface of this vast sea of vegetation, and immediately a hundred
shades, varying from the deepest green to the lightest gold, would
dance up and down each separate blade, producing the most
wonderful chaos of colors. A great variety of the most lovely and
delicate flowers, too, nestled beneath the grass, and sent forth
sweet odors to refresh the traveler as he passed. Guy gathered them
by handsful and gave them to Aggie, who wove them into long
wreaths which she hung around the wagon, when she declared it
looked like a fairy bower.
At midday they stopped to rest. The mules and oxen were turned
out to graze on the luxuriant grass, and a small party of the men
rode a short distance from camp in search of game. Guy would have
greatly liked to accompany them, but as Mr. Harwood did not tell
him to do so, he remained contentedly behind, assisting his mother
to take care of the baby, and anxiously wondering when she would
become strong and well, for she still looked as pale and weak as
when they left W——.
He was speaking to his mother of this and hearing very thankfully
her assurance that she felt better, if she did not look so, when Gus
and George came up to him, and rapidly told him that their father
had gone to the hunt and had left his powder flask behind and that
their mother said he was to take it to them.
"But he is on horseback," said Guy, "and I should never be able to
walk fast enough to overtake him. I'll go and speak to Mrs. Harwood
about it."
"Indeed you won't!" exclaimed George, "she says you are not to
bother her, but to go at once. You will be sure to meet papa,
because he said they would not go farther than that little belt of
cotton-wood trees which you see over there."
"Why, he did not go that way at all," cried Guy in astonishment. "He
left the camp on the other side."
"Well, I know that," returned George, "but they were going toward
that belt of trees, anyway. Didn't papa tell mamma so, Mrs. Loring?"
"Hallo! where has she gone to?"
"She went into the wagon before you began to speak to me," said
Guy, not very well pleased with the cunning look in George's face.
"Oh, did she? All right! Here, take the flask and hurry along, or
mamma will give it to you for lagging so. I wish I could go with you
and see the hunt."
Guy was so fearful that he would do so whether he had permission
or not, that he hurried away without farther thought, and was soon
quite alone on the great prairie. I think he would not have gone so
fast had he heard George's exultant laugh as he turned to Gus with
the remark, "Isn't it jolly he's gone, but if you tell that I sent him
away, I'll break your bones."
Gus had a very high regard for his bones,—perhaps rather more
than for the truth,—for he promised very readily to say nothing of
what had passed, and indeed thought it an excellent joke, and
laughed heartily.
Meanwhile Guy walked on in the direction George had pointed out to
him, wondering as he forced his way through the tall grass, how Mr.
Harwood could consider it enough of importance to send him with it.
He walked a long distance without finding any traces of Mr. Harwood
and his party, and looking back saw that the wagons appeared as
mere specks above the grass. For a moment he felt inclined to turn
back, but he remembered that his mother had told him always to
finish anything he undertook to accomplish, and so stepped briskly
forward quite determined to find Mr. Harwood if it was at all possible
to do so.
It was a long time before he looked back again for he did not like to
be tempted to return, and when he did so he was startled to find
that the wagons had entirely disappeared. In great affright he
looked north, east, west and south, but all in vain.
At first he ran wildly about, uttering broken ejaculations of alarm,
then he sat down and burst into tears, it was so dreadful to be on
that vast prairie alone. He soon grew calm for his tears relieved his
overcharged heart. He arose and looked carefully around, and for
the first time noticed that the trees which had seemed but a short
distance from the camp, looked as far off as ever.
"It is plain," said he to himself, "that those trees are at a great
distance. Of course, Mr. Harwood could calculate their distance
though I could not, and would certainly never have ventured so far
to hunt. George must have been mistaken."
Then he wondered that the flask he had so long carried in his hand
had not oppressed him by its weight. With many misgivings he
opened it, and found that he had been most basely, cruelly
deceived. The flask was empty.
I think it is not surprising that Guy was very angry, and made some
very foolish vows as to how he would "serve George out" if he ever
gained the camp again. Ah! yes, if he ever gained it! But the
question was how he was to do so, for the long prairie grass quite
covered the tracks he had made and he was uncertain from what
point he had come, and there was nothing in that great solitude to
indicate it.
Oh, how Guy wished that the tall grass, which he had thought so
beautiful, was level with the earth, "Then I should be able to see the
wagons," he thought, "but they have now moved on into some slight
hollow, and I may never see them more."
Oh! how bitterly he reproached himself for his foolish trustfulness in
George Harwood, and again for ever having persuaded his mother to
undertake such a perilous journey. For even then he thought more of
his mother's sorrow than his own danger, saying again and again: "I
shall be lost, and my mother's heart will break. Oh, my dear, dear
mother?"
"Well, well!" he exclaimed aloud, after spending a few moments in
such sad reflections, "it is no use for me to stand here. There is one
thing certain, I can meet nothing worse than death on this prairie if I
go back, and if I stay here it will certainly come to me, so I will try
to make for the wagons, and if I fail I shall know it is not for the
want of energy."
So he forced his way again through the rank grass, this time with his
back to the belt of trees, though he knew that they were growing by
the side of water, for which he was eagerly wishing, for the sun was
very hot, and as he had taken nothing since morning he was fast
becoming faint with hunger and thirst.
At last the air grew cooler and a slight breeze sprang up, but
although it refreshed Guy's weary body, it brought nothing but
anguish to his mind, for he knew that the sun was setting.
In despair he lifted his voice and halloed wildly, crying for help from
God and man, but no answer came, while still the sky grew a deeper
blue, the sun a more glorious scarlet, till at last when it had gained
its utmost magnificence, it suddenly dropped beneath the prairie,
the green grass grew darker and darker, and at last lay like a black
pall around poor Guy, as he stood alone in the awful solitude.
 CHAPTER V.
For a time poor Guy sat upon the ground helpless, and hopeless,
listening intently to the rustling movements of the numerous small
animals, that wandered about seeking food; fearing to move, lest he
should encounter a prairie wolf, or some other ferocious beast, and
equally afraid to remain still, lest they should scent him there.
There was but one thing he could do, he felt then, and that was to
put his trust in God, and entreat His guidance and protection. So, in
the agony of his terror, he prostrated himself upon the ground, and
offered up his petitions. The very act of praying comforted him, and
when he lifted up his eyes, he was rejoiced to see a few bright stars
shining in the sky.
"I think the moon will rise in about an hour," thought Guy, looking
eagerly around, with a faint hope that she might even then be
peering above the horizon; and truly, like a far off flame of fire, she
seemed to hang above the prairie grass.
With great joy Guy waited for her to rise higher, and throw her
glorious light across the wild, but she appeared almost motionless;
and in much amazement at the singular phenomenon, he
involuntarily walked rapidly toward the cause of his surprise, looking
intently at it still. Suddenly he paused, and burst into a fit of
laughter, exclaiming rapturously; "It is no moon; it is a camp fire!
There! I can count one, two, three, of them, They are the fires of
our own camp. Hurrah!"
In his excitement, he ran eagerly forward, shouting and laughing,
but was suddenly tripped by the thick grass and thrown headlong.
As he was quite severely hurt, he walked on much more soberly, but
still at a brisk pace, towards the steadily brightening fires.
The moon he had so anxiously looked for, gave no indication of her
presence in the heavens, and so Guy's progress was much retarded
for the want of light, for the stars were often overwhelmed by great
banks of clouds, and gave but a feeble ray at best.
"It is becoming very cold," thought Guy as he shivered in the rising
wind, "I fear there is going to be a storm; Oh, what will become of
me if it finds me here!"
Suddenly he paused, thinking for a moment that he heard shouting
at a distance, but he listened for a long time, and heard no more,
and continued his walk slowly and wearily, quite unable to repress
his fast falling tears. He was so very tired, so hungry, and so cold, it
was with the utmost difficulty he could force his way through the
coarse grass. Very often too he was startled by some prowling
animal, and thought with horror of all the tales he had read of boys
being torn to pieces by wild beasts. He especially remembered one
he had read in an old primer, of little Harry who was eaten by lions
for saying "I won't" to his mother. He was thankful to know, that
there were no lions on the prairies, and that he had never said "I
won't," to his mother, but he very much feared he had said things
just as bad, and that prairie wolves, or even a stray bear, might be
lying in wait to devour him for it.
Just as he had reached this stage of his reflections, he fancied he
heard some animal in pursuit of him. Without pausing even for an
instant to listen, he set off at full speed toward the still glowing fires,
till his precipitate flight was arrested by some obstacle, over which
he fell, reaching the ground with a shock that almost stunned him.
As soon as he recovered his senses, he attempted to rise, but to his
dismay, found that he could not stand. A sudden twinge of pain in
his right ankle prostrated him, as quickly as if he had been shot.
He thought at first that his leg was broken, but after a careful
examination, came to the conclusion that his ankle was sprained, but
even a broken leg would not have been a greater misfortune then,
for he was unable to walk, and was suffering the most excruciating
pain.
I think no one can imagine what poor Guy suffered, for the rest of
that long night. There he lay helpless, in sight of the camp fires, but
quite unable to reach them or to give any indications of his
whereabouts to his friends. There he lay dying with pain, and
hunger, and cold, yet suffering more in mind, than from all of these
bodily evils, because he knew that his mother must know of his
absence from the camp, and was wildly bemoaning the loss of her
only child.
The long wished-for moon at length arose, hours after Guy had
expected her, but too soon he thought when she made her
appearance, for the camp fires grew dim beneath her rays, and he
had to strain his aching eyes to see them at all. But he had not long
to bemoan her presence, and to say, that she hid the light of home
from him, for she soon plunged into a great bank of clouds; a fearful
blast of wind swept by, and Guy was drenched with rain.
Oh, it was terrible, that passing storm! Short as it was, it appeared
to Guy to last for hours, long after it had passed over him, he heard
it wildly sweeping on, but as it grew fainter, and fainter, the
calmness that came upon the night overpowered him, and he fell
into a troubled sleep. It seemed but a short time before he again
awoke, yet the grey dawn was struggling in the east, and the little
birds were hopping from blade to blade of the wet grass twittering
cheerily as if to thank God for the refreshing rain.
Poor Guy saw all this as if in a dream. He fancied he had been
transformed into an icicle, and that some one had built a fire at his
head, and was slowly melting him. He had no idea where he was,
and talked constantly to his mother, whom he fancied was beside
him, entreating her to put out the fire that was consuming him.
Suddenly he heard his name called, and realizing his position, and
springing to his feet, in spite of his wounded limb, halloed loudly,
waving his white handkerchief and signaling frantically to a
horseman that appeared in the distance. For a few dreadful
moments he was unheard, and unseen, then a shout of joy,
answered his screams, and the horseman galloped rapidly toward
him, and in a few minutes the poor boy lay fainting, but saved, in
the arms of James Graham!
 CHAPTER VI.
Guy knew no more for many hours. When he regained his senses,
he found himself in Mrs. Harwood's wagon lying upon one of the
divans. His mother was bending anxiously over him, and burst into a
flood of joyful tears when she saw that he recognized her. Nothing
could exceed Guy's joy at seeing her again though with traces of
deep anxiety upon her face. Indeed, so delighted was he at his
escape from death, that he was inclined to regard every one with
favor! Even George Harwood, who a few days after his return to the
camp, came to him, according to his father's instructions, to confess
his unkindness and to ask pardon for the pain he had caused him.
"I just thought I would send you off on a fool's errand," said he, "but
I never thought you would go so far, and frighten us nearly to death,
and most kill yourself. I was so scared when you didn't come back I
didn't know what to do. Father missed you, but thought you were
somewhere about the wagons, and I dared not tell him you were
not; but Gus turned coward during the afternoon, and told that I
had sent you away—and then didn't I catch it?" and George
grimaced most dolefully, pointing to poor Guy's sprained ankle, and
declaring that the pain of that was nothing to what he had had in his
back for days past.
Mrs. Loring came in then, and sent him away, as Guy had been ill
with fever ever since his night's exposure, and could bear but little
excitement. It was nearly two weeks before he could rise, and they
had even then to carry him from place to place, because he could
not bear his weight upon his wounded limb. It fretted him sorely
when they camped at night, to see how hard she must have worked
while he lay ill; yet he could but perceive that she looked better and
stronger than she had done since his father's death, and joyfully felt
that the excitement and toil of a journey across the plains would
restore his mother to health, whatever might be the effect upon him.
How kind they all were to him during the time he was slowly
regaining his health and strength. Aggie sat by him constantly, in her
childish way telling him of the wonders she daily saw, or coaxing him
to tell her some pretty tale. Mrs. Harwood always smiled upon him
when she passed, and Amy and Carrie Graham often asked him to
their wagon, and lent him books, or talked to him of the home they
had left, and that which they hoped to find.
All the men missed Guy so much, he had always been so useful and
good-natured. Mr. Harwood daily said, that there should be a jubilee
in camp when Guy got well again. But he recovered so gradually that
he took his old place in the train by almost imperceptible degrees,
and was at the end of a month as active as ever.
They were then on the borders of the Rio Platte, or Nebraska River,
in the country of the Pawnee Indians. They were about to leave
behind them the vast, luxuriant prairie, and enter upon what may
more properly be called the plains. Guy was not sorry to see the
thick grass become thinner and thinner, for he remembered that
amid its clustering blades he had nearly lost his life, and therefore
looked with much complacency upon the broad, shallow river, along
which their course lay; the sandy loam beneath their feet, and the
sand hills that arose like great billows of earth, rolling in regular
succession over the level surface. George and Gus thought the
country most dreary and wretched, and would scarcely believe Guy,
when he told them of a desert called Sahara, that had not even a
blade of grass upon it, save an occasional oasis, many miles apart,
and which were often sought for, by the weary traveler, as he had
himself sought the camp, during his terrible night on the prairie.
"It can't be worse than this," they eagerly contended, "I don't
believe even Indians live here."
But they were soon convinced to the contrary, for a few days
afterwards Guy startled them by the exclamation "see the Indians!
There are the Indians coming!"
George very boldly told them to "come on," but Gus went close to
Guy, and declared that such mere specks as they saw in the distance
couldn't be Indians; yet was suddenly most anxious to know
whether they were cannibals, and if so, whether he looked a
tempting morsel or not.
Guy could not help laughing at his questions, although he himself
felt quite uneasy at the approach of the wild hunters of the prairies,
which were seen rapidly drawing near to them. The men in the train
formed a closer circle about the wagons, and hastily inspected their
rifles, while Mr. Harwood gave them instructions how to proceed in
case of an attack.
That, however, he did not greatly apprehend, as they soon perceived
the Indians were but a small party of middle-aged, or old men, and
squaws, and it is seldom such a party attempts to molest any
number of travelers.
However, Mr. Harwood thought it best to keep them at a safe
distance, and when they approached within a hundred yards of the
train, suddenly commanded them to halt by raising his right hand
with the palm in front, and waving it backward and forward several
times. They, upon this, stopped their horses, and consulted together
a few moments, then fell into a posture indicative of rest. Then, Mr.
Harwood raised his hand again and moved it slowly from right to
left. This they understood to mean "who are you?" One of the oldest
of them immediately replied by placing a hand on each side of the
forehead, with two fingers pointing to the front, to represent the
narrow, sharp ears of a wolf.
"They are Pawnees," said Mr. Harwood. "Ah! there is the chief
making signs that they wish to talk with us."
A long conversation by means of signs, in the use of which the
prairie Indians are very expert, was then carried on between Mr.
Harwood and the old chief. Remembering his promise to Aggie, to
protect her from the Indians, Guy went to Mrs. Harwood's wagon to
assure her there was no danger, and that he would remain near, and
then took a stand behind the wagon where he could see and hear all
that passed.
He was soon joined by George and Gus, for Guy was always so calm
and collected that they felt quite safe near him, though he was no
stronger or older than themselves.
They all watched the Indians with much interest, and were surprised
to see that instead of being giants, as accounts of their cruel and
wonderful deeds had led them to expect, they were of medium
height. In place of the horrible face, and the flaming eyes they had
pictured, they saw the countenances of these Indians were
intelligent, and although of course of a bright copper hue, were in
some instances quite handsome. The hair of the men was very long,
and streamed like black pennants, upon the wind. Their arms,
shoulders, and breasts were quite naked, and their dress consisted
only of deer skin, with a cloth wound around the lower part of the
body. One or two were covered with buffalo robes, of which every
warrior carries one, in which he wraps himself when cold.
Guy thought that the men as they sat proudly upon their beautiful
horses, holding in their hands long bows made of the tough wood of
the osage orange, which is as supple as elastic, looked very noble
and fine. Their bows were about eight feet long and were wound
around with the sinews of deer, and strung with a cord of the same.
The arrows were about twenty inches long, of flexible wood, with a
triangular point of iron at one end, and two feathers intersecting
each other at right angles, at the opposite extremity.
This description Guy quoted to his companions, from a book he had
once read, and they saw at once how perfectly true it was. While
they were astonished at the appearance of the men, they were
much diverted at that of the women. They were very short and ugly;
each had her hair cut short, and they were dressed the same as the
men with the addition of a skirt of dressed deer skin. Their faces
were tattooed in the most uncouth devices, and altogether they
appeared quite hideous, as they sat upon their horses, in the same
position as the men, regarding with much interest the movements of
their chief who had been made to understand that he might come
alone to the train.
At first, he seemed doubtful about the propriety of such an act, but
his wish for gain soon overcame his caution, and he rode up to Mr.
Harwood, making many signs and protestations of friendship, which
were returned most graciously. After a long series of compliments
had passed between them, the old chief gave Mr. Harwood to
understand that his people were hungry and needed sugar, corn,
and many other things. Mr. Harwood replied by saying there were
many deer upon the prairie, which they could kill, that they
themselves had but little provision but would give them some beads,
and bright paints, in token of the good feeling of the whites toward
them.
At that the old man was delighted, for the Indians are very fond of
beads and all kinds of ornaments, and of paints, with which they
daub their faces and arms in the most grotesque manner, upon any
grand occasion. But the old chief disdained to exhibit any
satisfaction, and smoked the pipe, that had been offered him, in the
most indifferent manner while the presents were being procured
from the wagons.
When the old man had entered the camp, George and Gus thought
it prudent to retreat to their mother's wagon, from whence, they
could look out and see all that was going on. Aggie, on the contrary
was so anxious to have a nearer view of the Indians, when she
found them so much less terrible than she had imagined, that she
begged her mother to allow her to stand with Guy outside the
wagon, and after some little hesitation, Mrs. Harwood permitted her
to do so.
When Guy lifted the little girl from the wagon, the savage gave a
grunt of surprise, and gazed for a long time upon her with such
evident admiration that Guy was greatly afraid he would take a fancy
to carry her off. But Aggie, herself entertained no such fears, and
after looking at the old man curiously for some little time,
approached him slowly and examined his strange dress, the circular
shield covered with buffalo hide that was strapped on his left arm,
and the formidable war-club that lay at his side. It was made of a
stone, about two pounds in weight, round which a withe of elastic
wood was bound, being held in its place by a groove which had been
formerly cut in the stone. The two ends of the withe formed a
handle about fourteen inches long, and were bound together with
strips of buffalo hide, which rendered it strong and firm, totally
preventing it from either splitting down, or breaking when used, as
no doubt it often was, with great force, upon the heads of
unfortunate enemies.
The old chief allowed Aggie to examine all those things with the
greatest good nature, and when she touched his quiver of arrows,
and asked him to give her one, he grunted assent; so she took the
prettiest one, and after admiring it for some time, nodded and
smiled, and walked toward Guy with the prize in her hand. But
immediately the Indian darted to his feet, frowning with anger, and
sprang toward the frightened child. Mr. Harwood and most of the
men believed for the moment that he was indeed about to attempt
to carry her off, and with loud voices bade him stand back, and
levelled their rifles upon him, to enforce obedience. The old man
raised his hand, and immediately the whole force on the prairie
commenced galloping toward them.
"Aggie give him his arrow!" cried Guy at this juncture, "he
misunderstood you; he thinks you have stolen his arrows! Give it to
him."
She did so, the old man released her, and she fled to the wagon like
a frightened deer. With a few expressive gestures Guy explained to
the Indian the mistake that had been made, and at the same time it
became evident to Mr. Harwood and his party. The chief signaled to
his party to retire, and in less time than it has taken to describe it,
peace was restored; whereas but for Guy's presence of mind a
terrible battle might have followed Aggie's innocent freak.
But, notwithstanding that peace had been restored, they were all
glad when the chief took up his presents and went back to his
motley followers, and even more so, when they put their horses to
their utmost speed, and returned to their lodges; where no doubt
they gave to their tribe an astounding account of the adventure of
their chief in the camp of the white man.
 CHAPTER VII.
For some time after the encounter with the Indians, which happily
ended so peacefully, the train moved on without meeting with any
adventures. George and Gus thought the days passed very drearily,
and longed for some excitement, but Guy was altogether too busy to
feel dull. Mrs. Harwood's baby was quite sick, and as Mrs. Loring's
time was fully taken up in attending to him, Guy had double work to
do.
You would be surprised if I should tell you half that he did. Of all the
fires he built; the oxen he fed; the water he carried, and even the
breakfasts and suppers he helped to cook. And he did it all in the
best manner of which he was capable too. Although the first biscuits
he made were heavy, the next were light as down, for he inquired
into the cause of his failure and rectified it, and by doing that in
every case he soon learned to do perfectly all that he undertook.
Most children would have thought the life of constant toil which Guy
led very wretched indeed; but he did not, for he had daily the
gratification of perceiving that the great object of their journey
across the plains was being gradually accomplished; his mother's
health was slowly becoming strengthened, by every step they took
toward the snowy mountains, beyond which lay the fruitful valleys in
which they hoped to find a home.
But, as the days passed by, they greatly feared that one of their
number would never reach there; the baby boy grew worse. The
cooling breezes that brought health to his weakly sister, seemed
fraught with death for the lately blooming boy. Guy was greatly
saddened by the sufferings of the child, and by the grief of its
parents, and shuddered when he saw the bones of animals which lay
by thousands bleaching upon the desert, and once was filled with
horror on coming across a human skull, which the prairie wolves had
dragged from some shallow grave, and separated far from its
kindred bones. The idea that the body of the poor little baby should
meet such a fate, filled him with sorrow, and although it had always
seemed to him a natural and peaceful thing that the temple of clay
should rest under its native dust, after the flight of the soul, he
thought that the Indian mode of sepulture, of which they saw
examples every day, by far the best.
Very often they saw a curious object in the distance, and two of the
party, riding forward to examine it, would report an Indian place of
burial. Guy had himself gone forward once and found, to his
surprise, two forked poles, some six or eight feet high, supporting
something wrapped in a blanket. This something was a dead Indian,
who in this strange position, with his weapons in his hands, was
waiting his summons to the "happy hunting grounds."
On his return to the train, Guy hastened to find Aggie, to tell her of
what he had seen. She was listening very attentively, when George
ran up, exclaiming: "Look at the rats! there are thousands of rats on
the plains!"
Aggie looked in the direction indicated by her brother, and crying:
"Oh, the dreadful rats," was about to run away, when Guy stopped
her, telling her, laughingly, that they were the wonderful little prairie
dogs, of which they had heard so much.
Truly enough when she gained courage to look at the little animals,
she saw that although they at first sight resembled rats, on closer
inspection they appeared even more like squirrels. The children were
greatly entertained by watching their quick, active movements, as
they darted about through the low grass. A very busy community
they appeared to be, and with plenty to gossip about. To Aggie's
delight Guy pretended to translate their quick, chirruping barks into
our own language. Some he said were telling how a monster
rattlesnake had come to visit them without any invitation, and that
the only food he would eat, was the youngest and fattest of their
families; and that their constant intruders, the owls, had the same
carnivorous tastes, besides which they rendered themselves
particularly disagreeable, by standing in the doors and staring at
every dog that went by, and even preventing the entrance of
visitors, to the great distress of all the belles and beaux in town.
All this may have been very true, for the excited little creatures
talked so continuously that I am sure they must have had some
grievance, and the children thought it must be the owls that stood
solemnly at the entrance of many of the burrows. They did not see
the rattlesnakes, so even Aggie somewhat doubted the tales of their
ferocity, which Guy said the little prairie dogs related.
But although these little creatures were such chatterers, they
appeared very industrious, for many hillocks of sand indicated where
their homes were burrowed. Each little hole was occupied by a pair
of dogs, one of which was often seen perched on the apex like a
sentinel. But like many other sentinels, they appeared on the watch
for danger, not to combat, but to avoid it, for they darted like a flash
into their holes whenever a lean, prowling wolf stalked near them, or
even a prairie hen flew by.
"I wish you would tell us a story about prairie dogs," said Aggie to
Guy, that evening when they were gathered around the camp-fire.
"I am afraid it is impossible for me to do that," he replied, "for very
little seems to be known about them. Naturalists have never paid
much attention to them, curious as they are."
"But the Indians must know something about them," said Gus.
"Yes, I suppose so," returned Guy, "for before the white man came
to annoy them, they had nothing to do but to watch animals and
learn their habits, that they might know which were fit for food, and
which was the easiest way of killing them. Ah, yes, now that I have
been thinking about it, I do remember a story that the Indians tell
about the prairie dogs!"
"Oh tell it!" cried Aggie, eagerly; Gus seconded the request, and
even George drew nearer, for Guy had a great reputation as story
teller in the camp.
"It is rather a long tale," said he, "but the Indians say, a true one. It
happened years and years ago when each animal understood the
language of all others, and men conversed with them as readily as
with themselves.
"In those days each tribe had its sorcerers, or wise men, who
pretended to cure not only all diseases but to control the destinies of
men. They were accordingly held in great veneration by their simple-
minded dupes, as are their few descendants, which even at this day
practice in a lesser degree the arts of their forefathers.
"Well, it happened that when these men were more powerful among
the tribes than the chiefs themselves, that they combined together
to wrest from the hands of these the commands that they held, in
order that they might hold the people both in bodily and mental
subjection. There had for a long time existed a tradition among
them, that when a daughter of a chief—an only child,—should love a
brave of an unfriendly tribe, they would have power to change her
into a flower or animal, and unless the brave should find the means
within ten moons, or months, to break the enchantment, she would
die, and with her every chieftain and his family. Accordingly these
wicked sorcerers found constant pretexts for involving the tribes in
war, especially if they supposed that the only daughter of a chieftain
loved a brave of another tribe; but for many years all their arts were
in vain, for the Indians were so passionate and revengeful that
immediately an affront was given or received, violent hatred
vanquished love, and the chiefs and their families were saved.
"The sorcerers were almost in despair of ever obtaining the entire
authority they craved, when it came to pass that two rival tribes met
upon the plains, and as was usual in such cases, a battle was
fought. The Ohoolee tribe were victorious, and killed many of the
Gheelees and also took many of them prisoners. Among the latter,
was the only daughter of the chief Sartahnah, the beautiful
Mahdrusa.
"Great was the consternation of her tribe, for this maiden was held
more precious by them than a hundred braves. She was more
graceful than the fairest flower that grew upon the prairie; her hair
was longer than the grass by the riverside and blacker than the
night; her eyes were like those of the young fawn, and her voice
was sweeter than a breeze laden with the song of birds. There was
not a chieftain or brave of the Gheelee's but would have laid down
his life for her, and great was the grief and shame that befell them
when she was taken captive by the Ohoolees.
"From that day there was continual war waged between the two
tribes. The Ohoolees acted on the defensive, the Gheelees on the
offensive. Never a week passed but that a party of braves went forth
to attempt the rescue of the beautiful Mahdrusa from the lodges of
the enemy. The chief, her father, to increase if possible the zeal of
the braves promised her hand to him who should deliver her. There
was great rejoicing when this was made known, for all loved
Mahdrusa, though she cared for none. Her rescue was attempted
with a thousand times more eagerness than before, and one day
Anoctah, the bravest of all the Gheelees, led her in triumph to her
father's wigwam and demanded his reward.
"Mahdrusa heard him with dismay, and clasping her father's knees,
sank down before him, and entreated him to give Anoctah some
other treasure.
"The old chief told her that was impossible, and Mahdrusa wept so
loudly that the whole tribe gathered about the lodge and asked what
had befallen the beautiful daughter of Sartahnah. But she would say
nothing, yet wept continually, so that the sorcerers said the spirit of
the rivers was within her, and that they alone, could deliver her from
it.
"Now these men had reasoned together over her strange malady,
and said, 'She mourns so much over her betrothal to Anoctah
because she loves a brave of an unfriendly tribe. Let us then take
her from her father, and place her in the great medicine lodge where
we can work our enchantments upon her, and make ourselves rulers
of all the tribes.'
"So in the night they took her from her father's wigwam into the
great medicine lodge, which was hung about with the herbs they
used in their incantations, and had in the centre a great heap of
stones, within which was a fire burning.
"Beside these stones, which were kept constantly hot, they made
Mahdrusa sit down, and while she still wept, her tears fell upon the
stones, and a great vapor arose, which the sorcerers condensed
upon clay vessels into drops of water as pure as crystal, and with
them and the herbs that hung around, made a decoction so
powerful that when they had forced Mahdrusa to drink it, she lost all
power and reason, and her spirit lay passive in the hands of her
tormentors.
"'We will take it from her body,' said they, 'and place it where no
brave will ever discover it.
"'Let it fly to the centre of the wild rose,' said one. But the others
demurred, saying her lover would certainly seek it there.
"'Better hide it under the thick skin of the buffalo,' said another.
"'No!' they answered, 'the brave that Mahdrusa loves must be a
fearless hunter, therefore his arrow would bring her forth.'
"In short, they talked of every flower and beast on the prairie, but
found in all some fault, until the most cunning of all mentioned the
prairie dogs. 'No one would look for her in their miserable holes,'
said he, 'and they are such chatterers that the magpies, themselves,
would not have patience to listen to them.'
"So it was agreed that her spirit should dwell as a prairie dog, and
before long out sprang one from a reeking cauldron of herbs, and
they took it to the holes of the prairie dogs and left it there, placing
beside it a terrible serpent, that all others might be afraid to
approach it, and an owl at the door, as a sentinel that would stand
looking patiently for an enemy both night and day, and never
breathe to the gossips around her the tale of the princess that was
prisoned within.
"And that was how the rattlesnake and owl became sharers in the
homes of the prairie dogs, and it was with these awful companions
that the spirit of Mahdrusa spent many weary days. Meanwhile her
body lay in the medicine lodge of her people, and the sorcerers said
that her soul had ascended to the stars, where, in ten moons, she
would be purified from her sin and return to her body, or that it
would die, and moulder away.
"This news soon spread over the prairies, but the brave that
Mahdrusa loved would not believe it. He knew the wicked desires of
the sorcerers, and believed that she was a flower on the prairie, and
that he was appointed to rescue her.
"So he went forth and cut down every flower that he found, and he
toiled so ceaselessly that before two moons had passed not a
blossom remained, and still he found not his beautiful Mahdrusa.
Then he made a strong bow, and arrows that could not miss the
mark, and he slew the beasts of the prairie by hundreds, yet he
could not find his love. And so nine moons passed by, and Mahdrusa
was still in her horrible captivity, and the brave that sought her was
bowed down as if by years, with the weight of his sorrow, and his
body was so steeped in the blood of the animals he had slain that he
was redder than clay, and his descendants continue so to this very
time. All the beasts of the prairie had he slain in his terrible anger,
and all the people had fled to the mountains for food, thither he
thought he would follow them, and he sat down upon a ridge of
sand, to strengthen his bow, and sharpen his arrows, when, lo! quite
unmindful of him, a thousand little creatures he had fancied too
insignificant to notice, sprang forth from their holes, and gathered in
groups for their daily gossip.
"They angered him so greatly by their chatter that he placed an
arrow on his bow to fire amongst them, when his hand was stayed
by hearing a curious tale that a gay young dog was telling.
"'She lives next to my mother's lodge,' said he, 'and the poor thing
never appears either to eat or drink. I took her a delicate slice of
cactus myself, but I dropped it in a terrible fright, for a great serpent
darted towards me, and an owl sprang forward and devoured my
youngest brother before he had time to utter a squeak.'
"The brave rejoiced when he heard these words, and springing up,
went in search of the captive prairie dog. Many weary days he
sought in vain. He asked of her whereabouts from every insect he
met, but none could give him any information, and the prairie dogs,
under the spell of the sorcerers, were silent—on that topic, at least.
"There was but a day left in which he could act. Almost in despair,
he wandered about the prairie dog town, vainly looking for his love.
"At last he remembered that a queer old woman whom he had met,
while hunting one day, had told him that she was his guardian fairy,
and had given him two little pieces of stone which he was to strike
together if ever he was in great trouble, and she would appear and
help him.
"He had taken but little notice of the old woman at the time,
supposing her to be a conjurer or evil worker, and he had dropped
the little stones into his pouch, where they had long lain forgotten.
Without daring to hope that they would be of any use, he took them
out, and struck them together. A tiny spark of fire fell from them
upon some dry grass at his feet, a flame sprang up, and lo! out of it
stepped the old woman he sought.
"'So you have called me at last!' said she, 'what is it that I shall do?'
"'Lead me, kind fairy, to the hiding place of the beautiful Mahdrusa,'
he replied
"So she went before him to a part of the prairie that, in all his
wanderings, he had not visited. But, strangely enough, before his
feet the grass turned into briars, through which he only with the
greatest difficulty could force his way. Every timid hare became a
wolf, each gentle fawn a raging buffalo, but the brave went on
undaunted, brandishing his war-club, and keeping his formidable
foes at bay. Never for a moment did he allow fear to gain possession
of him for he knew if he did he should be lost. It was only faith and
courage that could carry him safely through that enchanted ground.
"'Stop!' cried the fairy, when he had passed unscathed through a
thousand dangers. 'Mahdrusa is before you!'
"But before he could look for her, the owl flew like a fierce hawk in
his face, and pecked at his eyes, and the rattlesnake sprang upon
him burying its deadly fangs into his arm. The brave almost lost his
courage then, but he heard Mahdrusa, though in the voice of a
prairie dog, entreating him to save her. He caught the serpent in his
hands, and seizing its jaws, tore it asunder, and wrapped its writhing
body around his wound, while at the same moment the fairy called
up a terrible wind that blew the owl far away, and to the arms of the
young warrior, the little prairie dog that held the soul of Mahdrusa.
"So was half the task of the lover accomplished; yet all his toil would
be in vain if he could not before the moon set that night place her
soul in the body it had before tenanted. But he was many leagues
from the lodge in which it lay, and he knew that by his own power
he could not hope to reach it in time, so he called upon the good
fairy again, and she turned a rabbit into a fleet courser that bore the
lover and the enchanted maiden, over the prairie with the swiftness
of wind.
"The moon was but a few inches, it appeared, above the horizon,
when they reached the lodge. By command of the sorcerers all the
people had returned from the mountains to see whether the spirit of
Mahdrusa would come from the stars, or her body, which all this
time had lain as if in a deep sleep, take upon itself the signs of
death. All were gathered in the great lodge. The cauldron of herbs
from which the enchanted prairie dog had emerged was boiling over
the fire, and around it the sorcerers were standing. Before them lay
the body of the beautiful Mahdrusa, and beside it stood her father
and Anoctah.
"Into the lodge, into the midst of all the people, the young brave
sprang! The warriors of the Gheelees raised their war clubs when
they saw one of the hated Ohoolees, but the young brave cried,
'strike me not, for I bear the soul of Mahdrusa!"
"Then they all fell back and Anoctah said, 'Restore it to her body,
and she shall be thine, if she loves thee better than me.'
"But the sorcerers sprang upon him, and tried to tear the little prairie
dog from his bosom, but the fairy cried:—
"'Hold her with thy right hand into the cauldron and she shall be
saved!'
"So he broke away from the sorcerers and plunged the enchanted
one into the boiling cauldron, unheeding the agony he suffered or
the cries of the little animal he held, and in a moment the moon
plunged beneath the horizon; Mahdrusa arose from her long sleep;
the sorcerers fell into the boiling cauldron and were consumed; and
all the people shouted for joy, and with one accord cried that the
Ohoolees should from henceforth be their brothers, and the young
brave who had rescued Mahdrusa, their chieftain, when her father
was called to the happy hunting grounds.
"The next day the marriage of the young brave and Mahdrusa was
celebrated with great splendor. And, behold, after the ceremony was
over, a beautiful young maiden stood in the place where the old
woman had been.
"'I too was enchanted by those wicked sorcerers, and condemned to
wear the form of an old woman until I should make two young
hearts perfectly happy. I have completed my task to-day.'
"Then Anoctah who had been very sorrowful, looked up, and seeing
the beautiful maiden, forgot his love for Mahdrusa, and entreated
the stranger to be his wife.
"She loved him well and consented, and thus made a third heart
joyful as those of the young Ohoolee brave and his beautiful
Mahdrusa."
"And they lived happily together all their lives," quoted Aggie, from
the fairy tales she had heard, "Why, Guy, that was a long story," she
added yawning, "and it has made me so sleepy I shall go to bed.
Good-night!"
"Good-night," returned Guy, not very well pleased that she should be
so sleepy, and fearing that his story must have been very stupid as
well as long. Perhaps it was because of this, that he sat down by the
fire again when she was gone instead of going to bed as he usually
did, and it was from sitting there that he got into trouble on the
following day, and to tell you what his trouble was shall be the duty
of the next chapter.
 CHAPTER VIII.
"I say," said George, slapping Guy on the shoulder, the moment after
his father bade them "good-night" and went to his wagon, telling
them to go to theirs, "I say, I have got the best thing to tell you, and
we'll have the greatest fun, if you don't turn sneak and try to get out
of it."
"I'm not likely to turn sneak!" retorted Guy very indignant that he
should be thought capable of such a thing. "What are we to have
such fun at? I don't think you will find that I shall shirk it."
Now, Guy never would have said that without knowing what
George's fun was to be, had he not been vexed at Aggie's cool
reception of his story, and at some other things that had happened
through the day. He was in a very restless, dissatisfied temper, and,
as many other boys do under those circumstances, he felt like doing
any wild thing that was suggested to him, without inquiring whether
it was right or wrong.
George saw that, and, greatly delighted, said: "I told Gus I didn't
believe you would back out, and we will have such a jolly time! You
know there are numbers of antelopes on the plains here, and I
heard James Graham say this morning, that there would be sure to
be a great many of them go down to that little creek to drink just as
soon as the moon rose."
"Well," said Guy, wondering greatly what the herd of antelopes had
to do with their fun.
"Well," returned George, "I have been reading a book that tells all
about hunting them. That was what I was doing when pa thought
me so studious to-day, and I found out how to hunt them at night,
and it's just as easy as can be. You have only to creep up to them
silently, and you can shoot them down by dozens."
"Like partridges?" commented Guy, in a tone of doubt.
"You needn't laugh at what I say," returned George. "You can ask
Gus if it isn't so, and if you don't believe him, I'll show you the
book."
"Oh! I believe it all, of course!" said Guy, hastily; "but I don't see
what difference it makes to us, for we have nothing to hunt
antelopes with."
"There are plenty of guns in the wagon," said George, in a low voice,
"and I don't see why we shouldn't use them."
Guy was greatly startled at this speech, for Mr. Harwood had told all
the boys never to touch one of the guns. He reminded George of
that, but he only laughed, and began a glowing account of the
glorious time they would have in creeping toward the creek, in the
moonlight, and shooting down the antelopes as they bent their
heads to drink.
Guy's imagination was highly excited by George's words, and from
being the most unwilling, he became the most anxious that the
midnight hunt should be attempted, quite forgetting Mr. Harwood's
commands in thinking of the triumph they might have in the
morning, in exhibiting two or three dead antelopes.
He readily assented to George's proposition, that they should then
proceed to the wagon, and choose their guns. No inducements or
threats, even to the breaking of his bones, would induce Gus to
touch one.
"Then," said George, "you shall carry this small hatchet, and a knife,
so that we shall be able to cut the horns and tails off the antelopes
that we can't bring home with us. I don't suppose we shall be able
to carry more than one apiece."
After securing their guns, they left the camp very cautiously, each
one going a different way, and all meeting at a point about a quarter
of a mile from the camp, on the banks of the little stream, where
they expected the antelopes would come to drink.
They stayed there in silence for some time, for Guy, remembering
his former experience on the prairie, was afraid to venture for even a
moment out of sight of the camp-fires. But at last they all became so
impatient at remaining so still and seeing nothing, that they
ventured, very cautiously, a little farther up the stream. Guy took the
lead, and very often would stop, and motion to his companions to do
likewise, whenever he fancied he heard any noise.
Thus two very tiresome hours passed away, and Gus was very
crossly protesting against staying any longer, when Guy motioned
him very eagerly to be still, and with great triumph pointed to a
number of animals that, one by one, very slowly and cautiously,
were going down to the water to drink.
They were very slender and graceful, about the size of a small deer,
and covered with coarse, wiry hair, and bearing upon their small,
well-formed heads a pair of branching horns.
They descended to the water, without exhibiting any signs of
suspicion or fear, for the boys, quite by accident, had got to the
leeward of them—that is, where the wind would not pass from them
to the antelopes, and give to the keen animals notice of their
presence.
"Now," whispered Guy, excitedly, "wait until you see them stoop
their heads to drink, and then fire at them! Now—ready!"
Both boys raised their guns and fired. There was a terrible
concussion. Both were thrown flat upon their backs, with the idea
that their heads, or at least their noses, were shot off, and away
stampeded the antelopes, as fast as their slender legs would carry
them.
Gus began to howl and cry most wildly, believing that his brother
and Guy were both killed. They, however, soon convinced him that
they were both alive, by rising, each declaring his nose was broken,
and pointing to the flowing blood as proof of it.
George was terribly enraged, chiefly at the gun, which he declared
had "kicked" him. Guy, on his part, was very much vexed with
George, for having brought him on such a profitless adventure; but
though he was suffering very much from his rashness, the whole
thing appeared to him so ridiculous, that he laughed long and
heartily.
"I believe you would laugh if you were dying," grumbled George, as
they stood together by the side of the creek, washing their face.
"Pretty figures we shall make to-morrow, sha'n't we? And pa will
give it to you to-morrow, too, for taking the guns."
"You told me to do it!" retorted Guy, sullenly, but quite alarmed at
the thought of Mr. Harwood's impending wrath, as well as angry at
himself for having done anything to incur it.
George answered him very rudely, and then followed a quarrel
between the two, which was at last brought to an abrupt termination
by a terrible scream from Gus. They looked toward him, and saw,
with horror, an immense panther, but a short distance off, making
ready for a spring.
The boys were transfixed with horror, as they saw his glaring eyes
fixed upon them.
They saw him crouch like an immense cat, preparing to spring upon
its prey. They saw a sudden flash of fire before their eyes, heard the
report of a gun, and, with as much fear as joy, beheld the terrible
monster spring high into the air, and fall to the ground, tearing up
the ground with its claws, and foaming at the mouth, in agony.
Another shot ended its struggles and its life together.
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