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RSC_ECDDD_Prelims.qxd 2/27/2006 3:18 PM Page i

Exploiting Chemical Diversity for Drug Discovery

RSC_ECDDD_Prelims.qxd 2/27/2006 3:18 PM Page ii

RSC BIOMOLECULAR SCIENCES

EDITORIAL BOARD

Professor Stephen Neidle (Chairman), The School of Pharmacy, University of London, UK

Dr Simon F Campbell FRS
Dr Marius Clore, National Institutes of Health, USA
Professor David M J Lilley FRS, University of Dundee, UK

This Series is devoted to coverage of the interface between the chemical and biological sci-
ences, especially structural biology, chemical biology, bio- and chemo-informatics, drug
discovery and development, chemical enzymology and biophysical chemistry.

Ideal as reference and state-of-the-art guides at the graduate and post-graduate level.

TITLES IN THE SERIES:

Biophysical and Structural Aspects of Bioenergetics

Edited by Mårten Wikström, University of Helsinki

Structure-Based Drug Discovery: An Overview

Edited by Roderick E. Hubbard, University of York, UK and Vernalis (R&D) Ltd,
Cambridge, UK

Visit our website on www.rsc.org/biomolecularsciences

For further information please contact:

Sales and Customer Services
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Telephone +44 (0)1223 432360, Fax +44 (0)1223 426017, Email sales@rsc.org
RSC_ECDDD_Prelims.qxd 2/27/2006 3:18 PM Page iii

Exploiting Chemical Diversity

for Drug Discovery

Edited by

Paul A. Bartlett
Department of Chemistry, University of California, Berkeley

Michael Entzeroth
S*Bio Pte Ltd, Singapore
RSC_ECDDD_Prelims.qxd 2/27/2006 3:18 PM Page iv

ISBN-10: 0-85404-842-1
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RSC_ECDDD_Preface.qxd 2/4/2006 1:09 PM Page v

Preface
The methods of drug discovery in the pharmaceutical industry have changed dra-
matically in the last two decades. By the late 1980s, a strong belief had emerged that
drug development is purely a numbers game, with anticipated drop-out rates at each
stage of the process such that only one compound out of 10,000 synthesized would
survive to make it to the market. Technologies to accelerate both synthesis and
screening were developed and adopted by virtually every pharmaceutical and
biotech research division. The race for-ever higher numbers had started and the
implementation of high-throughput technologies resulted in quantum changes in
both chemistry and in vitro biology that transformed the search for new drugs.
However, a counterwind began blowing in the late 1990s, when the number of
New Drug Applications (NDAs) at the regulatory authorities dropped to its all time
low, and it became evident that more compounds screened were not going to trans-
late directly into more drugs discovered. High-throughput synthesis and screening
has to be informed by knowledge of what has worked and not worked in the past, in
short, medicinal chemical intuition. Paradigms such as Christopher Lipinski’s
“Rule-of-Five,”1 resulting from an empirical analysis of the physical properties of
successful drugs, represents a milestone in the codification of this intuition. Data
mining strategies, assessments of diversity and “drugability,” and the design of high-
content biological screens have thus become indispensable in complementing high
throughput chemistry and screening technologies. The melding of a number of dis-
ciplines into the field now known as chemical biology has created the foundation and
driving principle for modern drug discovery. This volume encompasses the changes
that have occurred in both chemistry and screening as applied to drug discovery. In
addition, we have distinguished the conceptual from the operational advances in
each area, although we recognize that, like a good tango duo, neither would progress
without the other.
Perhaps nowhere is the interplay of conceptual and operational advances more
apparent than in the organic chemistry of drug discovery, where high-throughput
concepts and automation have had a truly transforming effect. Stimulated by the
automation of peptide synthesis on solid support, the concepts now embodied in
combinatorial chemistry have completely changed the way in which compound col-
lections are assembled and structure–activity relationships (SARs) are explored.
Reactions are accelerated by microwave and other non-traditional techniques, reac-
tion workups are streamlined with solid-phase reagents, and parallel or mix-and-split
formats enable chemists to make hundreds of analogues in the time they used to syn-
thesize one or two. These changes have not only altered the operational aspects of
organic synthesis, but also given rise to entirely new strategies in synthetic plan-
ning.2 The design of a chemical library will depend on whether it is destined for a
RSC_ECDDD_Preface.qxd 2/4/2006 1:09 PM Page vi

vi Preface
discovery screen against a novel target, in which case diversity is key, or whether it
will explore the SAR around a particular chemotype for a specific target. Will the
library be based on a novel scaffold, or derived from a peptide or natural product?
Should it be prepared by automated, parallel techniques, or can a biosynthetic path-
way be pressed into service? Often there is no right answer to these questions, and
debate is likely to continue for a long time on the key issue of “diversity:” how is it
measured, how is it designed, and, ultimately, what does it mean in the context of a
chemical collection?
High-throughput screening (HTS) has always played an important role in the lead-
identification phase of drug discovery, so the impact from recent technological
advances is more operational than conceptual. Nevertheless, HTS, and now ultra-
HTS, has dramatically accelerated the discovery of initial hits from compound col-
lections by increasing both the quantity and quality of information obtained.
Increases in capacity have been driven by increases in the size of compound
libraries, and modern screening technologies have greatly improved the analysis of
the interaction of small molecules with novel pharmacological targets.
Assay methods are increasingly moving away from the use of radioisotopic labels.
Modern fluorescent technologies now play an important role and are widely
employed for the evaluation of more complex target systems, such as peptide–protein
or protein–protein interactions. Reporter-gene assays have been developed to analyze
functional responses to the activation of cellular signaling systems, such as membrane
receptors, receptor tyrosine kinases, and ion channels. Using these techniques,
inhibitors, allosteric, and transcriptional modulators, in addition to direct agonists,
can be identified from chemical libraries. Moreover, both fluorescence- and reporter
gene-based screening systems provide sufficiently high sensitivity that interactions of
high-affinity ligands with targets present in low abundance can be probed.
At the other extreme, there is also interest in identifying low-affinity ligands for
pharmacological targets. In fragment-based screening, the goal is to identify phar-
macologically active partial structures. If different fragments for adjacent binding
sites on the target are found, they can be linked to form ligands with higher affinity.
As the small probe molecules normally bind with low affinity, this approach requires
specific tools to detect and characterize their interaction with the biological target.
NMR-based techniques have emerged as the most powerful of the methods used to
detect low-affinity ligands in biological systems.
In addition to dynamic range and throughput, compound consumption remains one
of the major issues in HTS. Miniaturization as well as high-density array formats have
not only greatly improved the throughput of HTS campaigns, but also significantly
reduced the amount of chemical material needed to determine ligand affinity. The vol-
ume of an individual assay well nowadays is in the low microliter range, down con-
siderably from the milliliter volumes still used in the early 1980s, yet the quality of
biological data obtained remains very high. Increases in daily screening throughput
from automation and miniaturization have in turn required expanded capabilities in
compound library storage and material handling. Technology continues to advance,
with developments in nanotechnology and microfluidics opening new perspectives in
reducing both time and sample amount. Chemical microarrays and bead-based appli-
cations may further enhance performance, although these formats have not yet been
RSC_ECDDD_Preface.qxd 2/4/2006 1:09 PM Page vii

Preface vii
broadly introduced in pharma-screening laboratories because new detection capabil-
ities are required. However, as we look to the future, it is clear that these formats will
find their place in the initial hit identification process as the techniques advance.
The newer screening techniques are able to analyze many different types of lig-
and–target interactions and have provided research teams with a huge number of hits
from HTS campaigns and, in turn, leads for the optimization phase of drug discov-
ery. However, the output of preclinical and clinical candidates has failed to keep
pace. Inadequate pharmacokinetic properties or adverse toxicological effects have
been identified as the predominant reasons why drug candidates fail during devel-
opment.3,4 The pharmaceutical industry has responded by paying increased attention
in the early phases of library design and lead identification to important “drug-like”
attributes, such as metabolic stability, physicochemical properties, and membrane
permeability. In fact, early awareness and corrective action to avoid potential liabil-
ities has resulted in a modest decrease in the number of compounds that fail because
of adverse pharmacokinetic properties.5 With the expansions of the knowledge base,
in silico predictive methods have become available to assess very large compound
datasets, helping scientists to classify and rank compound collections or library
designs according to their predicted properties or compliance with established rules.
The potential for compounds to interact with cytochrome P450 enzymes6 or to
exhibit favorable absorption characteristics7 are only two of the many examples of
these predictive methods. Such machine-learning techniques are likely to play an
increasingly important role in pharmaceutical screening and optimization processes
in the future.
The concept of understanding more about a compound’s biological behavior ear-
lier in the process underlies the new concept of “high-content screening” (HCS).
Indeed, it is in this area that the greatest conceptual advances in screening can be
anticipated. The HCS approach has led to the development of a new generation of
dedicated instruments that enable intracellular signaling pathways and cascades to
be elucidated and analyzed. In large-scale, multiplexed, cell-based assays, the large
amount of information that is generated can be captured and processed for this pur-
pose. HCS combines specific components of assay and reagent design with robust
instrumentation for automated fixed-end-point and live-cell kinetic analysis to gen-
erate information-rich data from multiple cellular targets.8 By using multiple fluo-
rescent reporter systems, combined with high-resolution imaging and
high-throughput image processing, scientists can observe multiple intracellular
events on a cellular level. HCS enables a functional analysis of how potential drug
candidates modulate a particular pathway or target in living cells and has evolved
into an integrated solution for accelerated drug discovery.
Over the past decade, drug discovery has undergone a dramatic evolution. It is
clear that no discipline stands alone, that no breakthrough technology is “the solu-
tion,” indeed, that integration of techniques and knowledge at the earliest stage is
essential. The title of this volume emphasizes diversity, and we think the content of
the following chapters reflects this concept in many ways. The closer integration of
chemistry, biology, and technology that is transforming drug discovery has stimu-
lated advances in numerous areas at the interfaces of these disciplines. While the
individual chapters take on separate aspects of this on-going transformation, each
RSC_ECDDD_Preface.qxd 2/4/2006 1:09 PM Page viii

viii Preface
chapter itself reflects an integration of different disciplines, techniques, or view-
points. While the specific descriptions in the chapters that follow can only be snap-
shots of this evolving field, the concepts of cross-disciplinary integration,
incorporation of medicinal chemical knowledge from the outset, and high-capacity
information acquisition and analysis will always be relevant. It is our fervent hope
that this volume will not only give readers a sense of the state of the art of drug dis-
covery, but also stimulate the next generation of scientists to think how they could
advance the field themselves.

References
1. C.A. Lipinski, J. Pharmacol. Toxicol., 2000, 44, 235.
2. M.R. Spaller, M.T. Burger, M. Fardis and P.A. Bartlett, Curr. Opin. Chem. Biol.,
1997, 1, 47–53.
3. R.A. Prentis, Br. J. Clin. Pharmacol., 1988, 25, 387.
4. T. Kennedy, Drug Discov. Today, 1997, 2, 436.
5. I. Kola, Nat. Rev. Drug Discov., 2004, 3, 711.
6. R. Arimoto, J. Biomol. Screen., 2005, 10, 197.
7. W.J. Egan, K.M. Merz Jr. and J.J. Baldwin, J. Med. Chem., 2000, 43,
3867–3877.
8. K.A. Giuliano, Assay Drug Dev. Technol., 2003, 1, 565.
RSC_ECDDD_Ackno.qxd 2/6/2006 12:26 PM Page ix

Acknowledgements
The number of different molecules we could make – conceivably – exceeds the num-
ber of particles in the universe. How do we exploit this diversity – practically – for
drug discovery? The cover image, combining a hypothetical diversity plot with rep-
resentative molecules from screening libraries and a 384-well HTS plate, portrays
the breadth of topics addressed in this volume. We thank Alan C. Gibbs for creating
this montage and Robert Gendler (www.robgendlerastropics.com) for giving per-
mission to use his image of the Great Galaxy in Andromeda as the background.
RSC_ECDDD_Ackno.qxd 2/6/2006 12:26 PM Page x
RSC_ECDDD_TOC.qxd 2/7/2006 9:59 AM Page xi

Contents

Section 1 Operational Developments in Chemistry

Chapter 1 The Use of Polymer-Assisted Solution-Phase
Synthesis and Automation for the
High-Throughput Preparation of
Biologically Active Compounds 3
Steven V. Ley, Mark Ladlow and
Emma Vickerstaffe
1 Introduction 3
2 PASP Synthesis Approaches to Biologically Active
Compounds 7
2.1 Applications to the Synthesis of
Commercial Drug Molecules 7
2.2 Applications of PASP to the Synthesis of
Biologically Active Natural Products 10
2.3 PASP Synthesis in the Library Production of
Biologically Active Small Molecules 12
3 Automated PASP Synthesis of Biologically Active
Molecules 19
3.1 Stepwise Automation of PASP
Synthesis in Batch Mode 19
3.2 Fully Automated PASP Synthesis of
Drug-Like Molecules in Batch Mode 21
3.3 Flow Chemistry and Automation in the
Synthesis of Drug-Like Molecules 23
4 Conclusion 28
References 28

Chapter 2 Accelerated Chemistry: Microwave,

Sonochemical, and Fluorous Phase Techniques 33
Kristofer Olofsson, Peter Nilsson and
Mats Larhed
1 Introduction 33
RSC_ECDDD_TOC.qxd 2/7/2006 9:59 AM Page xii

xii Contents
2 Microwave Enhanced Chemistry 34
2.1 General 34
2.2 Applications in Medicinal Chemistry 35
2.3 Applications in Solid-Phase Chemistry 37
3 Sonochemistry as a Means to Accelerate Synthesis 37
3.1 General 37
3.2 Organometallic Sonochemistry 38
3.3 Heterocyclic and Pericyclic Chemistry 38
3.4 Applications in Medicinal Chemistry 39
4 Fluorous Phase Techniques 40
4.1 General 40
4.2 Reagents, Linkers, and Scavengers 42
4.3 Fluorous Protecting Groups 44
4.4 Fluorous Mixture Synthesis 44
4.5 Peptides and Oligosaccharides 45
4.6 Fluorous Applications in High-Throughput
Chemistry 46
4.7 Microwave-Enhanced Fluorous Chemistry 46
5 Conclusion 48
Acknowledgements 48
References 48

Section 2 Conceptual Advances in Synthesis:

“Prospecting” – Design of Discovery
Libraries and the Search for Hits
Chapter 3 Biosynthesis of “Unnatural” Natural Products 57
Yi Tang and Chaitan Khosla
1 Introduction 57
1.1 Polyketide Assembly 58
1.2 Three Major Classes of Polyketide Synthases 60
1.3 Methods for Engineered Biosynthesis 60
2 Type I Polyketide Synthases 61
2.1 Modular Architecture 61
2.2 The Erythromycin Synthase 63
2.3 Engineered Biosynthesis of Multimodular
PKS Products 64
2.3.1 Domain Engineering 64
2.3.2 Module Engineering 66
2.3.3 Primer Unit Engineering and
Precursor-Directed Biosynthesis 68
2.4 Multimodular PKSs that Exhibit Special Features 70
2.5 Fungal Type I PKSs 70
RSC_ECDDD_TOC.qxd 2/7/2006 9:59 AM Page xiii

Contents xiii
3 Type II Polyketide Synthases 72
3.1 Dissociated Architecture 72
3.2 Combinatorial Biosynthesis of
Type II Polyketides 75
3.2.1 Chain-Length Variations 76
3.2.2 Mix and Match of Tailoring Enzymes 76
3.2.3 Primer Unit Modifications 78
3.2.4 Reshuffling of Downstream
Tailoring Enzymes 80
4 Type III Polyketide Synthase 81
4.1 Type III PKS Consists of a Homodimeric
Ketosynthase 81
4.2 Engineered Biosynthesis of Type III Polyketides 84
5 Conclusions 85
Acknowledgments 86
References 86

Chapter 4 Combinatorial Synthetic Design:

The Balance of Novelty and Familiarity 91
A. Ganesan
1 Biological Macromolecules – Strength in Numbers 91
1.1 Congruence between Biological and
Chemical Space 93
1.2 The Libraries are Exhaustive within the
Defined Boundaries 93
1.3 Highly Optimized Synthesis Procedures
were Available 94
2 Oligomer Synthesis – Improving on Mother Nature 94
3 Random, Discovery, or Prospecting Libraries –
the Quest for the Universal Scaffold 96
4 Privileged Scaffolds – Look Where the
Light is Brightest 96
5 The Decoration or Synthesis of Novel Scaffolds –
Aid for the Underprivileged 97
6 Target Class Libraries – Diversity with a Purpose 100
7 Peptide and Nucleotide Libraries Redux 101
8 Lead Discovery or Drug Discovery – Size
does Matter 102
9 Natural Product Scaffolds for Combinatorial
Chemistry – Why Reinvent the Wheel? 103
10 From Natural Products to Natural Product-Like
Libraries – Hubris or Progress? 104
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xiv Contents
11 Lead Discovery and Combinatorial Chemistry –
What have We Learned? 105
11.1 The Drug-Discovery Process cannot be
Simplified to a Single Blueprint 106
11.2 Combinatorial Chemistry is an Extremely
Powerful Technology 106
11.3 Combinatorial Chemistry is at its Best in
Lead Optimization 107
11.4 Combinatorial Chemistry is about Making
the Compounds that Fit Your Needs,
not How They are Made 107
References 107

Chapter 5 Compound Collections: Acquisition,

Annotation, and Access 112
Reg Richardson
1 Introduction 112
2 Commercial Offerings 113
3 Companies Providing Non-Proprietary,
Non-Parallel Synthesised Libraries
(Shared-Pool/‘Collected Collections’) 115
4 Companies Providing In-House Designed,
Parallel Synthesised Libraries 117
5 Compound Selection and Database Filtering 119
6 Sub-structure Similarity/Dissimilarity 119
7 Pharmacophore Analysis 120
8 Annotation 124
9 Lipinski Rule-of-Five (LRoF) 126
10 Topological Polar Surface Area (tPSA) and
Blood–Brain-Barrier Permeability (Log BB) 126
11 Solubility 128
12 Examples of the Use of Chemical Annotation and
Pharmacophore-Based Lead-Hopping 129
13 Compound Acquisition 132
Acknowledgments 134
References 134

Chapter 6 Chemical Diversity: Definition and

Quantification 137
Alan C. Gibbs and Dimitris K. Agrafiotis
1 Introduction 137
RSC_ECDDD_TOC.qxd 2/7/2006 9:59 AM Page xv

Contents xv
2 Diversity Metrics 138
2.1 Distance-Based Metrics 138
2.2 Cell-Base Diversity Metrics 140
2.3 Variance-Based Diversity Metrics 142
3 Molecular Description 143
3.1 Two-Dimensional Descriptors 143
3.2 Three-Dimensional Descriptors 145
3.3 Physicochemical and Electronic Descriptors 146
3.4 Descriptor Selection 146
4 Dimensionality Reduction 147
4.1 Principle Component Analysis 148
4.2 Singular-Value Decomposition 148
4.3 Factor Analysis (FA) 149
4.4 MultiDimensional Scaling 149
4.5 Stochastic Proximity Embedding 150
5 Subset Selection and Classification 151
5.1 Clustering 152
5.2 Partitioning Methods 153
5.3 Experimental Design 154
5.4 Reagent-Based Versus Product-Based Design 155
5.5 Random Versus Rational Design 155
6 Conclusion 156
Abbreviations 156
References 156

Section 3 Conceptual Advances in Synthesis:

“Mining” – Turning a Hit into a Lead
Chapter 7 Focused Libraries: The Evolution in Strategy
from Large-Diversity Libraries to the
Focused Library Approach 163
Ruben Tommasi and Ivan Cornella
1 Introduction 163
2 A Synergistic, Multidisciplinary Approach to
Library Conception 164
2.1 Improvements in Synthetic Methods 164
2.2 Impact of In Silico Tools for Library Design 165
2.3 Influence of Biology in Library Design 166
3 Library Design Concepts 167
3.1 Impact of Diversity on Library Design 167
3.2 Diversity-Oriented Synthesis in Prospecting
Library Design 168
3.3 Target-Oriented Library Design 168
3.4 Focus on Drug-Like Libraries 170
Exploring the Variety of Random
Documents with Different Content
EMMANUEL ALTHAM

21
 Emmanuel Altham (1600-1635/1636)
Emmanuel Altham was born a gentleman, though his family had its
connections with commerce and the legal profession rather than the
titled aristocracy. His two older brothers successively held the
family’s country seat at Mark Hall, Latton, about twenty miles north
of London. As a younger son, Altham inherited little of his parents’
wealth and so, over objections by his relatives, sought excitement
and his fortune in the expanding world of English overseas trade.
Altham began as an investor in the Company of Adventurers for New
Plymouth, served for a time as agent of the Company, and became
an admirer of the colonists and New England with such ardor that he
could more easily envision the colony’s future success than see the
hardships which the planters were enduring when he first arrived.
He went to the New World with a sense of honor, moreover, rather
than the qualities of a hard-driving trader. Perhaps he was not a
typical Adventurer: his devotion to the cause of colonization and
taste for the heroic side of commerce rather than the ledger went
beyond the ordinary, and helped keep English backing for the Pilgrim
plantation alive when profit did not.

Altham crossed the Atlantic to Plymouth the first time in the summer
of 1623. He went as “Captain” of the Little James (James Bridge,
master), the pinnace of about 44 tons which the Company was
sending to the plantation for use in fishing and fur-trading
expeditions. In 1623, the expert in charge of sailing a ship was her
“master,” and if there was a captain, he had command over the
military and mercantile affairs of the voyage. Since his ship carried
authorization to operate as a privateer, Altham had the decision
about taking prizes as well as the transaction of business. 22
After a year in New England waters, described in the first three of
Altham’s letters printed here, he recrossed the ocean with the ship.
She was seized for the satisfaction of debts to two of the Company’s
members, Thomas Fletcher and Thomas Goffe, who sent her (but
not under Altham) on a second voyage in 1625.

Altham’s fourth letter from New England describes the occasion of

his second expedition, on his own. Evidently his hopes for a future
with the colony faded, for he returned to England some time before
July 1626 and soon afterwards began to look for employment as a
soldier with the East India Company.

Through the influence of his brother, Sir Edward, he was sent to the
Company’s fort at Surat and spent over two years in exploits around
the Indian Ocean. The East India Company’s business was a mixture
of trade and raid—competing with the Portuguese for control of port
cities in India and the trade to which they gave access. The climax
of these years, for Altham, was an expedition to Madagascar and
Mozambique to intercept the fleet of caracks from Portugal.

After a visit to England in 1630, Altham returned to India a more

important man: Factor and Captain of the fort at Armagon (now
abandoned, at a place about sixty miles north of Madras), the
Company’s main post on the east side of India. He served the firm
well, rebuilt the fortifications, and finally began to accumulate
wealth. He expected to return to England permanently and live in
style—had even begun to order paintings and fancy bedding, but
died at Armagon in January, 1635/1636.

The originals of the letters of Emmanuel Altham to Sir Edward

Altham belonged to Dr. Otto Fisher, of Detroit, who before his death
generously consented to their first publication here. The letter of
Altham to James Sherley has been published in Massachusetts
Historical Society, Proceedings, XLIV, 182-189, from a transcript of
the original in the English Public Records Office (Admiralty Court
Misc., bundle 1142), with editorial comment and notes by J. F.
Jameson.

23
 Emmanuel Altham to Sir Edward
Altham
September, 1623

Most loving and kind brother,

My promise doth put me in remembrance, with the first opportunity

[63]
of a messenger, to write unto you. And if I were not by promise,
yet that special nearness that is between us obliges me to the same,
for as I have always to this time found your constant affections
towards me, so have I, and shall continually, acknowledge the same.

And now, loving brother, since I have undertaken a voyage not

altogether pleasing to some of my friends—and because of my
forwardness in the same, I may be taxed with many censures—
therefore, as it doth more nearly concern me, I will here lay down
not what my ear hath heard, but what I have with my eyes seen to
be true.

After our departure from the Cowes in the Isle of Wight, we

recovered our desired passage three months and one day after,
being the 5th of August, with many bitter a storm. And I have
learned by this voyage that God hath made the seas more for use
than pleasure, but I praise the Lord for his goodness that I never
had my health better. And likewise by the blessings of God, I have
and hope to learn that at sea which will prove for my extraordinary
advantage. But everyone hath a time, although some sooner than
others.
After our arrival in New England, we found all our plantation in good
health, and neither man, woman or child sick. And here, likewise, we
[64]
found the other ship set forth by the Company, who came 24
from Portsmouth six days after us, and arrived here at New
England ten days before, with all her people well—as we with our
[65]
people did the like. And yet one good wife Jennings was brought
abed of a son aboard our ship and was very well. And then, we had
an old woman in our ship about four score years of age, which was
in good health—and this I speak not as needful to write of, but to
show that God did give us our health when we looked not for it, and
to those, likewise, that had not been well a year before on the
shore.

And now to come more nearer to that I intend to write of, and first
[66]
of the situation of the place—I mean the plantation at Patuxet. It
is well situated upon a high hill close unto the seaside, and very
commodious for shipping to come unto them. In this plantation is
about twenty houses, four or five of which are very fair and
pleasant, and the rest (as time will serve) shall be made better. And
this town is in such manner that it makes a great street between the
houses, and at the upper end of the town there is a strong fort, both
by nature and art, with six pieces of reasonable good artillery
mounted thereon; in which fort is continual watch, so that no Indian
can come near thereabouts but he is presently seen. This town is
paled round about with pale of eight foot long, or thereabouts, and
in the pale are three great gates. Furthermore, here is belonging to
the town six goats, about fifty hogs and pigs, also divers hens. And
lastly, the town is furnished with a company of honest men, that do,
in what lies in them, to get profit to the adventurers.

And now to speak more at large of the country and what profit 25
is to be raised here; and first, to speak of the fishing that is in
this country. Indeed it is beyond belief, but I can assure you thus
much: that if a man be well provided with all things necessary for to
make a fishing voyage, he may easily make his voyage two for one.
[67]
But lest this should seem incredible to some, I will give you an
instance of the same. Before we got hither to Patuxet, we had many
fogs at sea, insomuch that we were driven to lie at hull and to take
down all our sails—and so went to fishing. In one hour we got 100
great cod, and if we would have but stayed after the fog broke up,
we might quickly [have] loaded our ship—and, I am persuaded, had
we been prepared with all things necessary for a fishing voyage, we
might have loaded our ship in a week. I think we got 1000 in all.
And indeed, when we had nothing else to do, my people took delight
to catch them, although we threw them away again, as I think we
did 300. One fish we got, I think, weighed 100 pound: it was as big
a cod as ever was seen. We got many turbots, likewise, and one
turbot we got gave all our ship a meal and to spare. And to speak
what voyages of fishing hath been found and made this year, here
hath been at Monhegan, Damerill’s Cove, Anquam, Pemaquid,
[68]
Sagadahoc, and the Isles of Shoals —all principal places for fishing
—about 400 sail. And every one of them, by their confession, say
that they have made good voyages, and now most of them are gone
into Spain, to sell their fish where they have ready gold for it. And
now to speak what sorts of other fish are here to be had. Here are
great store of sturgeon—I mean abundance; likewise great of
salmon, bass, trout, eels—and lobsters such infinite that when we
have them the very multitude of them cloys us. There are likewise
great store of other fish which I cannot remember, as clams and
oysters.

And now to speak somewhat of our store of beaver’s skins 26

that are round about us both to the norward and southward.
And now at this present, we are going to the southward into
Hudson’s River, where the Dutchmen have all their skins of the
savages. We hope there to get good store of beaver’s, otter’s and
martin’s skins, as also fox skins and raccoon skins—all which will
yield money good store in England. And towards Christmas we are
to return to our plantation again. And then, before the fishermen
come in February to the norward, we mean to go trade for all the
skins that are to be had thereabout, and then to take the best stage
for fishing in the country, and so to fish in the beginning of the year;
[69]
and then about May, 1624, to go trading for furs again. And then
it may be so, that we will come home about Christmas come
twelvemonth, but look not for me before I come. Divers occasions of
employments may fall out so that I may be hindered—and indeed, I
shall not desire to come for England unless I bring good store of
profit with me, which I make no doubt of, by God’s help.

Thirdly, I will speak somewhat of the timber in the country, which

will raise great profit to the Adventurers. We have here as good
timber as ever I saw—of many sorts. We have here cedar, beech,
pine, oak, and divers other sorts, of which we have here sent a
sample of about two or three hundred pounds worth, and with it a
good many beaver’s skins and furs of divers sorts.

Fourthly, we will say somewhat of the sarsaparilla and sassafras—as

[70]
also, alkermes berries —all which are worth good store of 27
money in England, and of which, when I come myself, God
willing, I will bring a pattern to London. For when I was at London,
sarsaparilla was of two shillings a pound, at the least, and we have
here enough to load a ship.

Fifthly, to speak of the profit that may arise by salt—and I make no

doubt we shall make much salt before I come for England. And if we
could but have salt to sell to the fishing ships that come hither
yearly, I think we might compare our plantation to the Spaniards’
Indies. And we have good hopes of making salt about a mile from
[71]
our plantation, and it shall be put in execution ’ere long.

Sixthly and lastly, here are many other things in this country to raise
profit, as for example, at the place whereto we are now bound with
[72]
our ship to the southward—the place is called Capawack —there is
 [73]
a mountain of bole armeniac and divers other metals. No English
hath been there, but only one Captain Dermer whom was killed by
[74]
the savages there; for the savages in this place are very strong
and are men of very able bodies. But notwithstanding, we mean to
put it upon trial and to go well armed among them. We hope there
to get store of skins.

And now, having spoken what is but the truth concerning the 28
profit that may with small labor be got for the Company of
Adventurers, I will now, as briefly as I can, show you what good will
redound to those that live here. And first, of the fish in the country,
which, as I said before, is of all sorts in infinite number; and two, for
the fowl that are in the country. Here are eagles of many sorts,
pigeons, innumerable turkeys, geese, swans, duck, teel, partridge
divers sorts, and many others fowl, [so] that one man at six shoots
hath killed 400. And then to speak of the healthfulness of the air. It
lieth in 42 degrees of northerly latitude. We have here the wind
come off the land all the day time, and in the night off the sea,
which is wondrous wholesome. Some few have had agues at the
first coming over, but not sick above a week—and myself was ill for
three or four days, but I thank these good friends of mine at the
plantation, I am recovered pretty well, thanks be to God. Thirdly,
those that live here need never want wood, for here is great store.
Four (fourthly), here is as good ground as ever I heard of, whenas
[75]
the ground yield five or six hundred for one—nay, some 1400!
And this year they have great store of corn—as goodly corn as ever I
saw—of which I have sent you six ears. And if God will, when I come
myself, you nor my worshipful friend, Sir John Leventhorpe, shall not
want so much beaver’s skins as will make each of you a hat. But to
our purpose, I say that none of these commodities can be got
without a little pains, and the most pains and cost is to be stowed at
the beginning; for men must provide for the worst, that they may
have provision for themselves a twelvemonth if these things fail—
and then the[y] must take pains to build them houses and the like.
And because I have spoken somewhat large of the country—and
indeed I have good cause, because if I were well provided with all
things necessary, as servants and the like, I could live here
contentedly with great pleasure—but I shall better think and
determine of such matters when more important business doth not
call me aside.

And now I will speak somewhat of the savages in the country 29

about—I mean the native Indians. The nearest that any dwell
unto [Plymouth] is fourteen miles, and their town is called Manomet.
Only without our pales dwells one Hobomok, his wives and his
household (above ten persons), who is our friend and interpreter,
and one whom we have found faithful and trusty. He I carry away
with me to the southward. And now, likewise, in this bay wherein we
live, in former time hath lived about 2000 Indians. Here is not one
living now, nor not one living which belonged to this plantation
before we came, so that the ground on which we are planted
[76]
belongs to nobody.

And now to speak of the king of the country, who is a great emperor
[77]
among his people. Upon the occasion of the Governor’s marriage,
since I came, Massasoit was sent for to the wedding, where came
with him his wife, the queen, although he hath five wives. With him
came four other kings and about six score men with their bows and
arrows—where, when they came to our town, we saluted them with
the shooting off of many muskets and training our men. And so all
the bows and arrows was brought into the Governor’s house, and he
brought the Governor three or four bucks and a turkey. And so we
had very good pastime in seeing them dance, which is in such
manner, with such a noise that you would wonder. And at that time
when we gave Massasoit his hat, coat, band and feather, I craved a
boy of him for you, but he would not part with him; but I will bring
you one hereafter.
And now to say somewhat of the great cheer we had at the
Governor’s marriage. We had about twelve pasty venisons, besides
others, pieces of roasted venison and other such good cheer in such
quantity that I could wish you some of our share. For here we 30
[78]
have the best grapes that ever you say —and the biggest,
and divers sorts of plums and nuts which our business will not suffer
us to look for.

And now to speak somewhat of Massasoit’s stature. He is as proper

a man as ever was seen in this country, and very courageous. He is
very subtle for a savage, and he goes like the rest of his men, all
naked but only a black wolf skin he wears upon his shoulder. And
about the breadth of a span he wears beads about his middle. And
these beads they make themselves, which they account as gold
above silver before the beads we bring out of England.

Lastly, to speak a little in what peace and friendship we are with the
savages, which peace we have had with Massasoit ever since our
coming. And he never expressed his love more to us than of late; for
in the Massachusetts there was a colony—I may rather say a
company of idle persons, for they had no civil government among
themselves, much less were they able to govern and rule Indians by
them. And this plantation was begun about one year and one half
[79]
since by one Mr. Weston, who came this year to see his
plantation. But by many notorious deeds among themselves, and
also having in their necessity stolen corn from the Indians, the
Indians began to condemn them and would have killed all the
English, but they feared that when the English of Patuxet did hear
what they had done, then they would set upon the squaw sachem in
the Massachusetts and so kill all the Indians in the 31
Massachusetts. Whereupon they determined another
resolution: to cut the English at Patuxet, whom they stand in fear of
now, and the English at Massachusetts both at one time. But in the
mean time, the great Massasoit sent to Patuxet for some physic,
because he was fallen very sick, and so, by God’s help, he was
cured. And upon his recovery, he made known the plot of the
Indians of Massachusetts against us, and told us that if we would
not go fight with them, he would. So at the return of our surgeon
from Massasoit, came a messenger from Mr. Weston’s plantation at
Massachusetts, telling us that there was a plot against us by the
Indians of Massachusetts. Whereupon the Governor, Mr. William
Bradford (well worthy the place), sent Captain Standish with some
six or seven others to the Massachusetts to bring away the head of
him that made the broil. And so, by God’s goodness, he killed our
chief enemy and five or six others without any hurt to our part, and
[80]
brought away the head of the chiefest of them. And [it] is set on
[81]
the top of our fort, and instead of an ancient, we have a piece of
linen cloth dyed in the same Indian’s blood, which was hung out
upon the fort when Massasoit was here. And now the Indians are
most of them fled from us, but they now seek to us to make peace.
But we are informed by Hobomok that eight shallops of Indians, well
provided, are coming this way. They say themselves that they come
to fight with other Indians that have killed a friend of theirs, 32
but if they come at us to offer any violence, I doubt they will
never carry their shallops back again—it may be, not with their lives.
And these Indians, we hear, have muskets and fowling pieces, with
powder and shot, which they have bought of the Frenchmen in
Canada and of the Englishmen at the Isle of Monhegan; but that
trade is already stopped by the King’s proclamations concerning the
same trade.

And now, loving brother, I have little else to write of unto you—but
only one thing I thank you kindly for, and that was for the last letter
you sent me in England, wherein you desire [me] to hold fast to the
truth and likewise to be diligent in my place. Of both which make no
doubt—no! be persuaded that I will rather die a thousand deaths
than once to shame God or my country. And now, seeing that I am
entered into this place, doubt not but that I will always increase in
knowledge. And indeed, when I undertook this voyage at first, I
always held the art of navigation to be most hard and difficult, but
now, through some practice and reading, I have attained to that I
hope never to forget. And I hope by that time I see old England to
be able to conduct a ship myself, safe into any harbor in New
England. But God disposeth of all things. And truly, I never lived
better to my content nor among those who can more respect me as
[82]
the Company in old England and here likewise do, who think
nothing too good for me. I praise God, I have my health ’till now
that I wrote this letter—but I mended apace.

And now, loving brother, I must make an end, although I think no

pains sufficient to express my love unto you. I doubt not but you will
show yourself a friend to me in taking care for that little stock I
have. I am desirous it should increase—and in your hands, if you
think it profitable to you. I know you will deal the more providently
for me, because of divers reasons well known to yourself. I 33
pray let that same £100 be taken of my Mr. Hawes or his heirs
when it is due (and that will be about March, 1624), and if you and
[83]
my brother Hawtry think good, take it into your own hands. I
have wrote to my brother Hawtry to buy me the books of English
voyages, which will do me great good. I pray look that they be
bought me, and send by this messenger that is come from New
England and hath lived there three years. And he comes away about
December from London, that he may come with the fishermen, to be
here in February. I pray let those books be of the same voyages that
[84]
is lately put forth by Mr. Purchas, minister about Ludgate.

Thus much I have thought good to let you understand concerning

the estate of myself and New England, and now I will take my leave
of you, desiring the God of hosts to guide you and yours in your
going out and coming, so that all your labors may prosper under
your hands, and that your life in this world of misery may be such a
life that may prepare you to a better in the world to come.
And thus, my kindest love and best affections being remembered to
you, desiring you to accept of this mite (being compared to my
mind). Likewise, as I am bound to respect, so let my love be
remembered to my sister your wife, and to my worthy friend, Sir
John Leventhorpe, and to his good lady, and all the rest of that
noble house, as to my Lady Fowle and Sir John Fowle, my brother
[85]
Thomas, and my sister Mary. And I pray merrily tell her it will be
no tarrying for me because I know not when I shall come into
England. But I pray likewise tell [her] that I could here give her
much land if she will come and live among this wild scene of 34
Indians. I hope this will make her smile. And now, I pray let
my love be remembered to my aunt Wolley, hoping that she will
have me in her mind, although not in her eye; I mean I hope she
[86]
will remember me at her death, which must be one day. Pray
remember me likewise to Mr. Denn and his wife and old goodwife
Stracy, and to my worthy Adventurer Henry Stracy, who, if he claims
his money, let him have it, I pray you, for I see it will come in with
profit. Pray likewise remember my love to Mr. Bland and William
Watson, and pray tell them thus much: that because a ship could
not be got when I had cattle in my hands, and likewise because I
could get nobody to join with me, I put that money into the common
stock; and it shall be answered in that, which, if they be not
contented, I will repay again. The like, I pray, do to goodman Wells.
Remember me to him and tell him I find great need of his cousin,
[87]
the potter. I pray, sir, let them read this letter—either the same or
a copy of the same—and so, likewise, I pray let my noble friend, Sir
John Leventhorpe; although I have wrote to him, yet I refer him to
particulars in your letters.

And so I take my leave of you; but I pray remember me to my father

Adee and mother Adee, and to all the rest of my friends to whom I
am by any way tied—as to Seth Haggar and Edward Skoles, whose
so long continuance and good service in your house have caused me
to speak well of them.
And thus I end, desiring the Lord to direct you in all your ways,
words and actions, and to guide you by his Holy Spirit and so to
enable you, that in what you have been wanting to glorify his name
in this world among men, your heart may be more and more
touched with the reverence of so great a God, and to labor more
and more to glorify him here, that so you may be glorified by 35
him in the world to come, where one day, if I see you not in
this world, I make no doubt but to meet you, which God, for Christ
Jesus’ sake grant unto us. And so I bid you, Farewell! Farewell in the
Lord; and the God of heaven, earth, seas and all things be with you
and protect you in your going forth and coming in. And so, being
guided and directed by God’s holy angels, you may not be ashamed
to show yourself before God and the Lord Christ at that great day of
account when all things shall be made known. And so, even from my
heart and soul, I take my leave of you and the rest of my other
friends who are mentioned in my other letters. Vale!

I shall be glad to hear from you. In the beginning of December, pray

[88]
send your letters to Mr. Sherley’s in Crooked Lane. Divers matters
I could write, but only this let me tell you: that I would entreat you
to stir up a few friends to venture four or five hundred pounds with
me when I come myself. For I then intend to make a voyage to fish,
which I make no doubt but I can get two of one in eight months.
This thing I thought good to impart to you, and do entreat you to
provide such a course against I come home, if you can.

Forth, this is a most ordinary voyage undertaken.

Thus I rest,

your most loving brother,

EMMANUEL ALTHAM.

I have sent my sister Altham six ears of Indian corn and beans to
sow in her garden. Also, I have sent you a tobacco pipe which I had
of the Indians.

36
 Emmanuel Altham to Sir Edward
Altham
March, 1623/1624.

Loving and kind brother,

My love being remembered to you and the rest of my loving friends,

these few words being caused by the fitness of a messenger, they
are to let you understand that I am in good health and so have been
a long time, as I hope also of you.

I have been upon a voyage to the southward of New England, where

we have discovered many brave places where never any Christians
were before. And this part of the country—I mean to the southward
of New England—is far better land and more commodious places for
[89]
situation than are in any part of this country besides. For there is
not only good ground in abundance, with excellent good timber, but
here are great store of furs which now the Dutchmen get because
our Company of New England have not sent by us so good trucking
stuff as they should have, and so have disappointed themselves
much. Insomuch that whereas we thought for to have got with our
pinnace three or four hundred pounds worth of skins, we have now
got small store, to my exceeding great grief.

But this is not all they have hindered themselves of, for in their
plantation is the better half women and children, and divers of the
rest are very unwilling, so that only the burden of the plantation lieth
on the shoulders of some few who are both honest, wise and
 [90]
careful. And if it were not for them few, the plantation 37
would fall, and come to nothing—yea, long before this time;
and it is so much the more likely because that now by a sudden fire
one half of the plantation was burnt down by fire, upon the 5th of
November last, wherein was burnt and spoiled the goods of all such
that came this last time into New England and are now by reason of
[91]
this loss forced to come again for England.

But, although it hath pleased God to lay his heavy hand on these
poor people and plantation, yet the fault is neither in some of the
planters here nor in the unfruitfulness of the country. For I assure
thus much: that a better country was never seen nor heard of, for
here are a multitude of God’s blessings; but they are not to be
enjoyed by idle people that think to have all things at wishing for.
But if men will take pains at first, they may live afterwards bravely.
Indeed, in this country is no clothes to be had, nor divers other
things which a man may make a good shift without. Yea, here is all
things to be had to a contented mind; and it is not for men to live
here that think of their former prosperity and company— 38
friends and kinsfolk, but it is good for such that resolve to
forget and leave all these things for a time, and do labor as they
think to live by it hereafter.

Neither can I speak but well of the profits that are to be raised here
by fishing—indeed, it is such that you would admire. But the best
actions whatsoever, being badly undertaken, come to little or no
effect. So this plantation, being undertaken by men unexperienced
in plantations, is like to feel the smart of it. And also, how is it
possible that those men that never saw fishing in their lives should
raise profit by fishing? And if they had known it never so well, yet if
they had not [been] able of body, they could not perform any
matter; for how shall women and children do men’s labors? The
reason, in conclusion: this I say to you, that unless some other
means be taken, which to do is impossible, no means of profit can
be raised to the Adventurers for their money again.
If any man thinks to adventure money to have land, this I tell thee:
that if they will give me a very small matter, I will make sure to them
10,000 acres of as good land as any in England. And this I am sure
of. But although at this time I do fully declare to you the estate of
this plantation, yet I pray conceal it ’till others have reported the
like. And although these matters may seem strange to you, in regard
of the ample relations that have been made in the praise of this
plantation, yet take it no otherwise than thus: that it hath been the
Company’s fault in England, who have sent over so many helpless
people that the Governor here (who is a wise gentleman) will not
entertain some of them. And secondly, their fault hath been that the
planters here have not had good trucking stuff to please the Indians.
Indeed, no question, if we had commodity, we might have skins
great store. And now I hope this is apparent to you, that the fault is
not in the country, which is so good that if my ability would reach, I
would settle some plantation—and yet, I hope I would not over-
reach myself with hopes—but until that time I do resolve, if I 39
can conveniently, to come hither a-fishing yearly, if God bless
me homewards. And I do not doubt but to do the like that other
men do, for other ships that come the last year (and this year) have
got more fish than their ships could carry; and so carry it for Spain
and sell it for great rates. But of this hereafter, if God bless me now
home.

Indeed, the Lord hath preserved me miraculously. For, coming to

anchor by a great many sands, when it was little wind, it proved at
last great store of wind and a great storm, insomuch that our
anchors came home and almost laid us upon the sands. And the
storm increasing, we were fain to cut our mainmast overboard, and
had much ado to save our lives in our ship. But thanks be to God,
we were saved and our ship, and are at this time in a good harbor at
[92]
Patuxet, blessed be God! And here in this harbor we are to stay
this winter, for this country is subject to wonderful storms in the
winter time; and here it is very cold weather. Yet we have very poor
[93]
fare here all this winter, being cold water and beef, sometimes,
because we have but little of it; and now and then we have good
store of fowl. But for all these crosses and disheartenings, I was
never better nor better contented in my life, which I thank God for,
for I know it cannot be mended with wishes and wailings.

Thus much have I declared unto you concerning our plantation,

entreating you to keep it close from the Company and not to think
the worse of this country, in which nature hath almost emptied
herself to replenish it. And although our beginning is bad, yet I hope
that the fishing voyage I am now bound out upon will bring
somewhat to the Adventurers, and also enable my own judgment to
undertake the like for myself, if God prosper me now. Indeed, if the
making of salt here did not require a greater charge of money 40
from the Company, it would do well; but this I say: that if salt
be made here to reap store of profit, it requires a greater charge
than hath been laid out already, which I think the Company will not
disburse without seeing more hopes of profit.

Thus entreating you not to expect me before I come, for when it will
be I know not—indeed, I do not desire to come before I have made
what profit I can to the Adventurers; which, if it may not be, I have
done my utmost and I hope they will accept of it. In the mean time,
my love and well wishes being remembered to you, to my sister and
to all your children, especially to my three cousins, James, John and
[94]
Leventhorpe. I pray likewise remember my service to my most
worthy and kind friend, Sir John Leventhorpe and his Lady, to both
whose services I acknowledge myself bound many ways. Likewise,
pray remember me to Sir John Fowle and his Lady, and to my
brother Thomas, and also to my sister Mary, and to all the rest of
that worthy stock. Also, pray have my love remembered to Mr. Denn
and his wife, and also to Henry Stracy, goodman Watson, and Mr.
[95]
Bland and Thomas Wells. And pray tell them that if they mislike
their adventure I have put into the Company for them, I will return
them their monies again; but I pray do you agree with them as you
will. I pray, good sir, be as a loving brother to me (which I doubt not
of) in increasing my little stock which, if God take me away, may be
the better for yours. But whether I live or die, you shall never be the
worse for it. Thus, loving, loving brother, have I wrote in haste,
entreating you to hold me excused if I have done anything that
might not seem worthy of your love. Thus taking my leave of you, of
the rest of my good friends, I bid you farewell, entreating the Lord
to be with you and to guide you in your ways; that so, you having
dealt honestly and conscionably here, serving the Lord in truth and
uprightness of heart, you may for the same be rewarded in 41
the kingdom of heaven, where all tears and sorrows shall pass
away; which God, for Christ’s sake, grant unto us. Even so, Farewell,
loving brother; and, if it be God’s will, to send us once again to
meet.

Your ever-loving and kind brother, till death,

EMMANUEL ALTHAM.

[96]
I pray remember my love to Edward Skoles and Seth Haggar. And
I pray let Edward Skoles know I would have wrote to him, but my
leisure would not give me leave.

42
Emmanuel Altham to James Sherley
May, 1624.

Most worthy friends,

Your loving letters I have both received much about one time (being
about the middle of April, 1624), wherein I conceive both your great
love and care over me, which for my part shall never be rewarded
with ingratitude. It pleased God that your ship called the Charity
arrived at Plymouth in New England about five weeks after her
departure from the English coast, but the certain day I know not,
because I was at that time sixty leagues from thence at Pemaquid a-
fishing. But after she had delivered her passengers and goods, she
went immediately to Cape Ann, where, in all likelihoods, they are like
to make a good voyage, if God withhold it not. For in all possibility,
the settled course which yourself and the Company have taken will
bring in much profit—for indeed, it is the only means above all other.
Yet notwithstanding, the trade of furs may help, but that is not so
sure a thing, by reason of divers (as I may call them) interlopers.
[97]
So soon as Mr. Peirce his coming into the land came to my ears, I
was forced much against my mind, both by the importunity of Mr.
Bridge and insolences of all our company, to make a voyage from
Pemaquid to Plymouth; which, had I not undertaken, although with
much hazard of my person, all our company had and would have
dispersed themselves. And if either myself or the master would
detain them, they openly threatened a more speedy revenge: either
to kill us or to blow our ship up. But these things are past, and the
party dead who spake it, and I fear that God who knoweth all 43
hearts, prevented him by death from acting those villainous projects
[98]
which, by his words in his life, he professed to do. The occasions
of this was two: first, in regard provisions went very hard with us,
and the next was a foolish and needless fear they had of their
wages. To prevent all this and farther mischief, I went to Plymouth
about the beginning of April; where, by the way, I was forced with
contrary winds and foul weather to stay somewhat longer than I
wished. But at my coming to Cape Ann, I there found Mr. Winslow
[99]
and master Peirce, for which I was very joyful. And so, having
received of them divers commendations and letters from yourself
and my other friends, I went with all possible speed to Plymouth to
know the Governor’s resolution. For thus it was, that provisions we
had but very few before Christmas, but were fain to have some
[100]
pease out of Plymouth store. And so, because we were going to
fish among our countrymen, we thought to get divers things by
reason of Mr. Bridge his acquaintance, but these our hopes were
much frustrated. For, coming to the fishermen, we could have no
provision without present pay, which I was destitute of,
notwithstanding I offered to become bond for anything I took up.
But they not regarding neither the Company’s nor my word did
rather solicit our men to come work with them, for their victuals, and
to leave the ship, than to show any love or friendship to us in
helping us. Therefore, rather than our company should go away and
our voyage be overthrown, we were constrained to use a 44
[101]
present, though unwilling means to get some provision (as
bread and pease) which before we were destitute of. So, having
dispatched my business at Plymouth and received my order from the
Governor, Mr. Bradford, and his Assistants, which was that look what
fish we had caught in our pinnace should presently be brought to
Cape Ann and to deliver it to Mr. Peirce, and afterwards to aid and
help Mr. Peirce in his voyage, in what we could, both with our men
and boats. To all which, as I am in duty bound, so I consented unto
it, and with all convenient speed went away to our ship, Mr. Winslow
being with me.

And by this time, which was about the last of April, I thought Mr.
Bridge had killed about 10,000 fish, for more I think our salt would
not have saved; but by the backwardness of our people, and strange
mishap, these hopes were quite altered. For, coming within one day’s
journey of our ship, this untimely news came to me that our pinnace
was cast away and Mr. Bridge and two of our men drowned, being
John Vow and Peter Morrett. All which news did not a little trouble
me, knowing what great cost and charge you have been at for us,
and also knowing that upon the good and prosperity of the ship and
voyage depended part of my reputation and profit. But this
unwelcome news did, in conceit, deprive of both. But coming home
to our ship, I there found this news true thus far: that Mr. Bridge,
our master, was drowned and the two men, and the ship in a very
strange manner spoiled. For thus it fortuned that upon the 10th of
April, 1624, happened a great storm, and some of our cables that
we were moored withal gave way and slip off on the place they were
made fast to ashore. And so, the wind and sea being very high,
[102]
drave our ship ashore upon rocks where she beat. In the
meantime, being night, the master and company arose, and 45
every man shifted for themselves to save life; but the master
going into his cabin to fetch his whistle, could not get into any boat
about the ship, the sea brake so over the ship. And so by that
means, before a boat could come, the ship overset and drowned him
and the other two. And the rest, that were got into our shallops that
hung about the ship, had much ado to recover the shore—your
cousin, for one. For the ship oversetting, pitch her mainyard into one
boat where were six or seven of our men, and so sunk her. For those
that could then swim got to the shore with much hurt; the rest that
could not swim were drowned. And so, before the next morning, our
ship was quite under water sunk, and nothing to be seen save only
the tops of her masts sometimes, for the sea did rake her to and fro
upon the rocks. All which disasters did not a little trouble me, for our
ship was not only spoiled, our men drowned, but we that were
saved lost the most part of what we had in the ship. Myself,
especially, lost my books and some clothes, and most of what I had.
But my comfort is that God will restore me something one day again,
for afflictions are but trials of his love. We lost three shallops, and
[103]
our ship’s boat and another shallop we borrowed which we

After my coming to our ship and seeing how all things stood, and
that although the ship were much spoiled and bruised—insomuch
that some of our neighbors very dishonestly enticed our men to
leave the ship and to seek out for their victuals, showing them that
the ship was unrecoverable and using many arguments of disuasion
to them, God knoweth, who were willing to entertain anything
against us before, but now laying hold on of this opportunity
[104] [105]
rejoicing or I here departed. But at my coming home, I got
them all together and sought far and near for help to recover 46
our ship, if it were possible, which to do seemed difficult. But
[106]
by the help of one Mr. Cooke of Bastable and divers of his
friends and my acquaintance, weighed her out of the water, and so
by the help of many hands we got the ship into a place nearby,
convenient to see what possibility there was of saving the ship. So,
having viewed her, there was broken of her starboard side six or
seven plank and some timbers, which we mended with help; and on
her larboard side, half her plank, timbers and knees were broken in
such sort that then she was thought impossible to hold together, by
reason of the hurt she had received outward and the shaking of the
beams and timbers inwardly. But blessed be God, by the help and
means that I have got of carpenters, she is now made up as strong
[107]
and sufficient for the sea as ever she was. And if not one of our
company come in her, yet by the help of God, we being fitted with a
sufficient man master, I will come in her.

And do not doubt but, through God’s mercies, to do well in her,

although for this time we shall not make so good a voyage as is
expected. For whereas we thought to have got ten or twelve
thousand fish, we had scarce one thousand, and some of that was
lost, and all our salt. For the ship being beat ashore, brake down our
stages, and there we lost both the salt and fish that was in it. And all
the rest of the salt, powder, provision, and many other things 47
(which, if God spare my life, I will give account of) were lost.
The rest of the things that we saved shall safely and truly be
delivered by me to you, with an account of all our men’s carriages
and behaviors, that so you may reward some and reprove others.

And now, loving sir, since that I have troubled you with writing thus
far, pardon me if I be too tedious; for it makes me continually be the
more larger to you in writing, because I know both you and many
other good men have laid out much money upon Plymouth
plantation, and especially as for the goods upon this ship. So do I
conceive and know your eyes are upon us in a more especial
manner. And for that this voyage hath not begun nor ended so well
as either you or I could wish, yet I pray pardon me for a while in the
same, until I shall come to speak with you and the rest of the
Company. For until then, I will neither commend my care and
diligence, nor discommend the want of either of them, for full soon
may a man err. But as my labor and care was never wanting
heretofore, so, until I shall make a full accomplishment of this
troublesome voyage and then to deliver all things into your own
hand, I will continue the same. And as at this time I have no man to
assist me that I can trust (the master being gone), so will I strain to
the uttermost of my knowledge to bring everything to the same
order it was, and then to come for England, if our Governor
pleaseth. And he hath sent me word that he will provide me a
[108]
sufficient man for master, notwithstanding Richard Gardiner hath
earnestly requested it, claiming it as his due by place, but some say
not by sufficiency. I will say no more concerning him because I know
you shall understand it by others; only thus much I must needs say:
that so far as he could, he was willing to help us with the ship. And
now he takes it somewhat unkindly that, seeing the Company have
sent our ship’s company assurance for their wages, that he is not
intimated therein. So much for that, which is to be left to your 48
and the Company’s wisdom.

And once again let me be pardoned if I seem to be overbold. I

understand by your letter to Mr. Bridge that you are somewhat
discontented with me for not taking a Frenchman which we met
withal; but to the contrary, wonderfully commend and extol Mr.
Bridge for his courage and forwardness in the same, notwithstanding
my backwardness. To answer which, I will do in few words. It so
happened that about 400 leagues off the Lands End of England, we
[109]
met with a small Frenchman. As I take it, he was of Rochelle. In
the morning we had sight one of another and he stood right with us
and we with him. Coming near us, he spied us to be an Englishman,
so he stood away from us and by a sudden puff of wind brake his
mainmast. For we being desirous to hear news and also to see if he
had any skins aboard or if he had been a-trading on the coast of
New England, we stood after him and hailed him what he was and
whence for. He told us he was of Rochelle and that he had but 7000
[110]
of cor-fish aboard of him and that he was come from the Bank
of Newfoundland a-fishing; and also that his ship was leaky, so he
made the more haste home before he had made his voyage. But we
mistrusting him, sent our boat aboard him to see if he had skins, but
in conclusion we saw he was very poor and had not been ashore on
no place; and so gave us some fish which at that time we stood in
great need of as also of wood (of which he had none because he
had not been on land nowhere). All these things being considered, I
hope you will not blame me, for I would do in your behalf in 49
that kind rather more than less than my commission would
bear me out in. But this ship was 500 leagues from any part of New
England when we met her and if I should have done it, I had
brought a great trouble both upon you and myself. For I will assure
[111]
you and all the Company that if you will but get a letter of mart
and a safe protection from His Majesty of England for taking of
Frenchmen on Newfoundland Bank, you might easily with this
pinnace take and leave what ships you list. For we had sight of
twenty sail of Frenchmen at one time, and I believe never a one had
any ordnance. But to end, pray pardon me if I have done amiss, but
what I did, I have done (in my opinion and in the opinion of all the
companies at Plymouth) for your peace and my own safety. For the
Governor hath seen my commission and saith, himself, I could not
have answered it. Therefore, pray blame me not for my good will
and care, for I should be very loth to lose a friend for nothing and
upon no occasion, especially when friends are hard to get. And as at
this time, although I might complain of my time all spent because it
hath been a troublesome time to me, yet I am quite of another
mind; for as I was called by God to this place, so, through his
blessing, I will discharge it honestly, whether I lose or get by it.
[112]
But out of all question, the course that you have settled now will
bring in profit enough, for they make salt at Plymouth, and have
good store of boats, all which is means to bring in profit. And I make
no question now but that New Plymouth will quickly return your
money again. For the most part they are honest and careful men.
However, they have had many crosses; yet now they will flourish,
God blessing them, which God grant.
[113]
I do understand that Thomas Dawson, the surgeon, hath been
very large on his tongue concerning myself, or that I should be
displaced by Mr. Bradford, and many other contumelious 50
speeches, as also he informed you about the Frenchman. For
all which, I pray, sir, if you see him, certify him that I will make him
answer it in England; and although it cost £100, I will make him see
the jail for it. And there he shall lie, if God bless me homeward. If it
please God to deal otherwise with me, I pray God give him more
grace, but I hope you do not believe him. But I would wish you
rather suspect him, for he is the veriest villain that I ever knew, as
hath been testified by his carriage both to Plymouth company, your
own self and Company, and also to me. And truly, I fear that I shall
justly lay that to his charge which if it be prosecuted will go near to
hang him.

At this time I do expect news from our Governor, Mr. Bradford, and
[114]
as I think, he will determine that we shall bring home Mr. Peirce
[115]
his cor-fish and train. But I think it will fall out otherwise, for I
have at this present received a letter from one of my acquaintance
that is owner of a ship in this country, and he proffers me for to hire
our ship and to take our men out and to put them into his own ship,
[116]
which goeth for the Straits. And so by this means I hope to get a
good freight and to save wages and provisions for some of my own
company. And this answer I have returned him: that I demand £140
for our ship, and to come for England presently; so that then we
shall be defrayed of all charge and have our ship brought home for
nothing. And indeed, we must be forced to come for England very
soon, because we have no provisions nor have any means to get
any. But of all these things I write in what I think, for I have (and
ever will do) refer all these matters concerning your ship to the
Governor and his Assistants’ directions; and if good suffer me, 51
they shall be followed.

I pray, sir, let the 40s. I gave Mr. Mastige a bill for be paid at first
sight, for he did me a great kindness in it; for otherwise I could not
have got some bread which I did.

Thus my love being remembered to yourself and wife, with thanks

for your token I received by Mr. Winslow, being three gallons of “hot
water.” Pray remember my love [to] Mr. Terrill Bacco, Mr. Stubs and
his wife, your brother Robert, and Mr. John Sherley and his wife, to
Mr. Brewer, Mr. Collier, Dr. Ran, Mr. Marshall, Mr. Thorrell, and to Mr.
Pocop (my good friend), and especially to Robert Cushman, and all
these the rest of my loving friends of the Company and out of the
[117]
Company.
And I pray, sir, if you please, let the Company see my letter. For look,
what I have wrote to you in particular, so much would I have wrote
to them in general, but time did wonderfully prevent me, in such
manner that I am put to straits every way.

I pray remember me kindly to my two brothers and my sister, and

the rest of my loving friends; and pray let them know I could not
have time to write to them. Only I pray tell them I am well, and that
I hope one day to see them again, but the time is uncertain. Yet I
fear we shall come sooner than I desire, since our great expectation
is so hindered by misfortune. But I do not doubt of the profit that
may be raised the next year, for now you have laid as good a
ground-plot as ever was—and better than before, for without this
[118]
course of fishing, you cannot have your monies again. Thus,
praying to God daily for them and you and for all well-willers to this
foreign plantation, I ever rest

yours and others’, to my power,

EMMANUEL ALTHAM.

I pray tell Mrs. Bridge I will save her husband’s things for her, 52
so much as we saved, it being almost all lost.

The haste of this messenger makes me forget divers things which I

should have wrote to you of; but I hope all things will be for the
best, seeing it can be no better. For be not discouraged at this bad
news, but hope the next year for better, which I do promise, if you
hold on the course begun.

Vale!

[Addressed:] To the worthy and my most respected loving, kind

friend, Mr. James Sherley, Treasurer for New Plymouth Adventurers,
dwelling on London Bridge, at the Golden Horseshoe.
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