Essential Guide to Reading Biomedical Papers E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 549

Veröffentlichungsjahr: 2012

Beschreibung

Essential Guide to Reading Biomedical Papers: Recognising and Interpreting Best Practice is an indispensable companion to the biomedical literature. This concise, easy-to-follow text gives an insight into core techniques and practices in biomedical research and how, when and why a technique should be used and presented in the literature. Readers are alerted to common failures and misinterpretations that may evade peer review and are equipped with the judgment necessary to be properly critical of the findings claimed by research articles. This unique book will be an invaluable resource for students, technicians and researchers in all areas of biomedicine. * Allows the reader to develop the necessary skills to properly evaluate research articles * Coverage of over 30 commonly-used techniques in the biomedical sciences * Global approach and application, with contributions from leading experts in diverse fields

Leseprobe

Contents

Cover

Title Page

Copyright

List of Contributors

Foreword

Preface

Aims of Each Primer

Acknowledgements

Introduction

Section A: Basic principles

Chapter 1: Philosophy of Science

1.1 What is Science?

Further Reading

Chapter 2: Ingredients of Experimental Design

2.1 Is the Study Experimental?

2.2 Is the Study Properly Replicated?

2.3 How are the Experimental Units Allocated to Treatments?

2.4 Are Controls Present and Appropriate?

2.5 How Appropriate are Manipulations and Measures as Tests of the Hypothesis?

2.6 Final Words

Further Reading

Chapter 3: Statistics: A Journey that Needs a Guide

3.1 Is the Design Suitable?

3.2 How are the Data Presented: Is their Nature Evident?

3.3 Proving an Effect: do the Authors Make Proper use of their Statistical Analysis?

3.4 Is the Experiment Designed Properly?

3.5 How Many Groups are Being Compared?

3.6 Does the Study Relate to Rare Events?

3.7 What are the Data, and How are they Distributed?

Further Reading

Answers to the Question Posed in Section 3.3 Above

Section B: Cell and Molecular

Chapter 4: Organ Bath Pharmacology

4.1 Basic ‘how-to-do’ and ‘why-do’ Section

4.2 The Apparatus

4.3 Required Controls and Limitations

4.4 Experimental Design

4.5 Common Problems and Pitfalls in Execution or Interpretation

Further Reading and Resources

Chapter 5: Small Vessel Myography

5.1 Basic ‘how-to-do’ and ‘why-do’ Section

5.2 Required Controls

5.3 Common Problems and Errors in the Literature

5.4 Complimentary and/or Adjunct Techniques

Further Reading and Resources

Chapter 6: Mammalian Cell Cultures: The Example of Airway Epithelial Cell Cultures for Cystic Fibrosis Research

6.1 Basic ‘how-to-do’ and ‘why-do’ Section

6.2 Required Controls and Common Problems and Pitfalls in Execution or Interpretation of in vitro Experiments

Further Reading and Resources

Literature Cited

Chapter 7: Electron Microscopy (TEM and SEM)

7.1 Basic ‘how-to-do’ and ‘why-do’ Section

7.2 Common Problems or Errors in Literature

7.3 Complementary and/or Adjunct Techniques

Further Reading and Resources (Biological EM only)

Chapter 8: Fluorescence Microscopy

8.1 Basic ‘how-to-do’ and ‘why-do’ Section

8.2 Required Controls

8.3 Common Problems and Pitfalls in Execution or Interpretation

Further reading and resources

Chapter 9: Intracellular ‘Sharp’ Microelectrode Recording

9.1 Basic ‘how-to-do’ and ‘why-do’ Section

9.2 Required Controls

9.3 Problems and Pitfalls in Interpretation and Execution

9.4 Complementary and/or Adjunct Techniques:

Further Reading and Resources

Chapter 10: Single electrode voltage-clamp (SEVC)

10.1 Basic ‘how-to-do’ and ‘why-do’ Section

10.2 Pitfalls

10.3 Alternative Techniques

10.4 Comparison between Sharp Microelectrode versus Patch Electrode Recordings

10.5 Issues in the Literature

10.6 Complementary and/or Adjunct Techniques

Further Reading and Resources

Chapter 11: Patch Clamp Recording

11.1 Basic ‘how-to-do’ and ‘why-do’ Section

11.2 Patch Recording Configurations

11.3 Required Controls

11.4 Pitfalls in Execution or Interpretation

11.5 Complementary and/or Adjunct Techniques

Further Reading and Resources

Chapter 12: Production of Antibodies

12.1 Basic ‘how-to-do’ and ‘why-do’ Section

12.2 Primary Antibodies

12.3 Secondary Antibodies

12.4 Choice of Antigens for Antibody Preparation; Their Advantages and Limitations

12.5 Purification of Antibodies

12.6 Required Controls

12.7 Common Problems and Pitfalls in Execution or Interpretation

12.8 Complementary Techniques

Cited Work, Further Reading and Resources

Chapter 13: Immunocytochemistry and Immunohistochemistry

13.1 Basic ‘how-to-do’ and ‘why-do’ Section

13.2 Basic Procedures

13.3 General Considerations

13.4 Required Controls

13.5 Common Problems and Pitfalls in Execution or Interpretation

13.6 Complementary Techniques

Cited Work, Further Reading and Resources

Chapter 14: Immunoprecipitation (IP)

14.1 Basic ‘how-to-do’ and ‘why-do’ Section

14.2 Required Controls

14.3 Common Problems and Pitfalls in Execution or Interpretation

14.4 Complementary and/or Adjunct Techniques

Further Reading and Resources

Chapter 15: Immunoblotting (Western)

15.1 Basic ‘how-to-do’ and ‘why-do’ Section

15.2 Required Controls

15.3 Common Problems and Pitfalls in Execution or Interpretation

15.4 Complementary Techniques

Further Reading and Resources

Chapter 16: Applications of Green Fluorescent Protein (GFP)

16.1 Basic ‘how-to-do’ and ‘why-do’ Section

16.2 Required Controls

16.3 Common Problems and Pitfalls in Execution or Interpretation

16.4 Complementary Techniques

Further Reading and Resources

Chapter 17: Fluorescent Measurement of Ion Activity in Cells

17.1 Basic ‘how-to-do’ and ‘why-do’ Section

17.2 Methodology for Measuring ion Concentrations

17.3 Required Controls and Problems or Errors in Literature

17.4 Molecular Techniques

17.5 Complementary and/or Adjunct Techniques

Further Reading and Resources

Chapter 18: Detection of Exocytosis – Real Time

18.1 Basic ‘how-to-do’ and ‘why-do’ Section

18.2 Common Pitfalls in Execution or Interpretation and Required Controls

18.3 Complementary and/or Adjunct Techniques

Further Reading and Resources

Chapter 19: Viral Vector Transgenesis

19.1 Basic ‘how-to-do’ and ‘why-do’ Section

19.2 Common Pitfalls in Execution or Interpretation & Required Controls

19.3 Complementary and/or Adjunct Techniques

Further Reading and Resources

Chapter 20: Polymerase Chain Reaction (PCR) and Reverse Transcription (RT)-PCR

20.1 Basic ‘how-to-do’ and ‘why-do’ Section

20.2 Required Controls

20.3 Common Problems and Pitfalls

20.4 Complementary Techniques

Further Reading and References

Chapter 21: In Situ Hybridisation (ISH)

21.1 Basic ‘how-to-do’ and ‘why-do’ Section

21.2 Required Controls

21.3 Common Problems and Pitfalls in Execution or Interpretation

21.4 Complementary and/or Adjunct Techniques

Further Reading and Resources

Chapter 22: Methods of Interference (Antisense, siRNAs and Dominant Negative Mutations)

22.1 Basic ‘how-to-do’ and ‘why-do’ Section

22.2 Types of Interference

22.3 Required Controls and Problems or Errors in Literature

22.4 Common Problems and Pitfalls in Execution or Interpretation

22.5 Complementary and/or Adjunct Techniques

Further Reading and Resources

Chapter 23: Transcriptome Analysis: Microarrays

23.1 Basic ‘how-to-do’ and ‘why-do’ Section

23.2 Required Controls

23.3 Common Problems or Errors in Literature

23.4 Complementary and/or Adjunct Techniques

Further Reading, Resources and References

Chapter 24: Experimental Proteomics

24.1 Basic ‘how-to-do’ and ‘why-do’ Section

24.2 Important Considerations

24.3 Required Controls

24.4 Common Problem or Errors in Literature and Pitfalls in Execution or Interpretation

24.5 Complementary Techniques

Acknowledgements

Further Reading and Resources

Section C: In vivo / Integrative

Chapter 25: Behavioural Methodology

25.1 Basic ‘how-to-do’ and ‘why-do’ Section

25.2 Animal Models and Behavioural Testing

25.3 Required Controls (and issues of experimental design)

25.4 Pitfalls in Execution or Interpretation

Further Reading and Resources

Chapter 26: Genetically Modified Mouse Models

26.1 Basic ‘how-to-do’ and ‘why-do’ Section

26.2 Required Controls, Common Errors and Pitfalls

26.3 Complementary and/or Adjunct Techniques

Further Reading and Resources

Chapter 27: Wireless Recording of Cardiovascular Signals

27.1 Basic ‘how-to-do’ and ‘why-do’ Section

27.2 Required Controls

27.3 Common Problems/Pitfalls in Execution or Interpretation

27.4 Complementary and/or Adjunct Techniques

Further Reading, References and Resources

Chapter 28: Electrical Stimulation Methods

28.1 Basic ‘how-to-do’ and ‘why-do’ Section

28.2 Required Controls

28.3 Common Problems and Pitfalls in the Interpretation and Execution

28.4 Complementary and/or Adjunct Techniques

Further Reading and Resources

Chapter 29: Extracellular Recording

29.1 Basic ‘how-to-do’ and ‘why-do’ Section

29.2 Required Controls

29.3 Common Problems and Pitfalls in the Interpretation and Execution

29.4 Complementary and/or Adjunct Techniques

Further Reading and Resources

Chapter 30: Antidromic Identification

30.1 Basic ‘how-to-do’ and ‘why-do’ Section

30.2 Required Controls

30.3 Common Problems and Pitfalls in the Interpretation and Execution

30.4 Complementary and/or Adjunct Techniques

Further Reading and Resources

Chapter 31: Event-Triggered Averaging, Including Spike-Triggered Averaging

31.1 Basic ‘how-to-do’ and ‘why-do’ Section

31.2 Pitfalls in Execution or Interpretation

31.3 Complementary and/or Adjunct Techniques

Further Reading and Resources

Chapter 32: Axonal Transport Tracing of CNS Pathways

32.1 Basic ‘how-to-do’ and ‘why-do’ Section

32.2 Required Controls

32.3 Common Problems and Pitfalls in Execution or Interpretation

32.4 Complementary and/or Adjunct Techniques

Further Reading and Resources

Chapter 33: Cardiovascular Methods: General Considerations for Human Studies

33.1 Basic ‘how-to-do’ and ‘why-do’ Section

33.2 Required Controls

33.3 Common Problems or Errors in Literature and Pitfalls in Execution or Interpretation

33.4 Complementary and/or adjunct techniques

Further Reading and Resources

Chapter 34: Measuring Cardiac Output in Humans

34.1 Basic ‘how-to-do’ and ‘why-do’ Section

34.2 Measurement of Cardiac Output by Dilution (Category A Methods)

34.3 Non-Invasive Cardiac Output (Category B Methods)

34.4 Complementary and/or Adjunct Techniques:

Further Reading and Resources

Chapter 35: Measuring Peripheral Blood Flow in Humans

35.1 Basic ‘how-to-do’ and ‘why-do’ Section

35.2 Venous Occlusion Plethysmography

35.3 Ultrasound-Based Methods of Blood Flow

35.4 Complementary and/or Adjunct Techniques

Further Reading and Resources

Index

Companion Website

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Library of Congress Cataloging-in-Publication Data

Essential Guide to Reading Biomedical Papers:

Recognising and Interpreting Best Practice / editor, Phil Langton.

p. ; cm.

Includes bibliographical references and index.

ISBN 978-1-119-95996-0 (cloth) – ISBN 978-1-119-95997-7 (pbk.)

I. Langton, Phil.

[DNLM: 1. Biomedical Research–methods. 2. Biological Science Disciplines–education. 3. Research Design. W 20.5]

610.72'4–dc23

2012028144

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

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.

Cover Design: Dan Jubb

List of Contributors

Prof Richard Apps, Physiology & Pharmacology, University of Bristol, UK

Dr Nina Balthasar, Physiology & Pharmacology, University of Bristol, UK

Dr Neil Bannister, Physiology & Pharmacology, University of Bristol, UK

Prof David Bates, Physiology & Pharmacology, University of Bristol, UK

Dr Harold A. Coleman, Physiology, Monash University, Australia

Dr Nick Colegrave, School of Biological Sciences, University of Edinburgh, UK

Dr John Crabtree, Physiology & Pharmacology, University of Bristol, UK

Dr Lucy F. Donaldson, Physiology & Pharmacology, University of Bristol, UK

Dr Gordon Drummond, Anaesthesia and Pain Medicine, Royal Infirmary, Edinburgh, UK

Dr Allison Fulford, Centre for Comparative and Clinical Anatomy, University of Bristol, UK

Dr Ingeborg Hers, Physiology & Pharmacology, University of Bristol, UK

Dr Charles Hindmarch, Clinical Sciences, University of Bristol, UK

Dr Mark Jepson, Physiology & Pharmacology, University of Bristol, UK

Prof Michael J. Joyner, Anesthesia Research, Mayo Clinic, Minnesota, USA

Dr Tomoko Kamishima, Cellular and Molecular Physiology, University of Liverpool, UK

Dr Helen Kennedy, Physiology & Pharmacology, University of Bristol, UK

Prof James Ladyman, Philosophy, University of Bristol, UK

Dr Phil Langton, Physiology & Pharmacology, University of Bristol, UK

Dr Thierry Le Bihan, School of Biological Sciences, University of Edinburgh, UK

Dr Fiona D. Mcbryde, Physiology & Pharmacology, University of Bristol, UK

Prof Elek Molnár, Physiology & Pharmacology, University of Bristol, UK

Dr Samatha F. Moore, Physiology & Pharmacology, University of Bristol, UK

Prof Helena C. Parkington, Physiology, Monash University, Australia

Prof Julian FR Paton, Physiology & Pharmacology, University of Bristol, UK

Dr John M. Quayle, Physiology & Pharmacology, University of Liverpool, UK

Dr Scott H. Randell, Cell and Molecular Physiology, University of North Carolina at Chapel Hill, USA

Dr Emma Robinson, Physiology & Pharmacology, University of Bristol, UK

Dr Joshua S. Savage, Physiology & Pharmacology, University of Bristol, UK

Dr Anja Teschemacher, Physiology & Pharmacology, University of Bristol, UK

Dr Paul Verkade, Wolfson Bioimaging Facility, Physiology & Pharmacology and Biochemistry, University of Bristol, UK

Dr Jon Wakerley, Centre for Comparative and Clinical Anatomy, University of Bristol, UK

Dr Erica A. Wehrwein, Physiology, Mayo Clinic, Minnesota, USA

Foreword

Biological research is an experimental science in which the testing of hypotheses through experiments generates knowledge and ultimately, understanding. However, while the construction of a hypothesis is open to the imagination, the experiments that produce the data to be analysed in the light of the hypothesis are only useful if they are reliable, accurate, reproducible, and come from carefully designed and controlled experiments. In the acquisition of data, therefore, there is no room for the imagination and even less for wishful thinking – the vice that reads the data to fit the hypothesis and not the other way around. Therefore, although it is true that a hypothesis guides the gathering of information, the primacy of the data is obvious since without them all hypotheses remain in the “to be done” drawer.

Biological research nowadays can be approached using a variety of techniques, the majority of which have been developed in the last 50–60 years. The power of these new techniques is such that biologists often forget two fundamental things, (1) that the usefulness of the technique does not lie so much in its intrinsic power but in the way it is applied to a biological question and (2) that all techniques have been designed for a specific purpose and therefore have limitations. There is not a single technique that can inform us about the whole of a biological problem and therefore it is advisable, wherever possible, to use more than one complementary technique.

These are the reasons why the present book by Langton and colleagues is so important. It is not merely about techniques; it puts techniques into context – their potential, their limitations and possible pitfalls. This is accompanied by useful primers on the philosophy of science, on experimental design and on statistics. As such, this volume will undoubtedly be of great interest and value, not only to the novice scientist but also to the experienced investigator and mentor.

I highly recommend this book to all practitioners of biological research.

Professor Sir Salvador Moncada

FMedSci, FRS

27th July, 2012

Preface

Imagine you are interested in buying a used car. Are you likely to be entirely trusting of the person selling the vehicle? Will you accept everything they tell you without question and without evidence? I suspect not. I suspect that you will have a healthy scepticism. The seller wants your money and it is your responsibility to ensure that you are satisfied with the trade – hence the phrase ‘caveat emptor’, which means ‘let the buyer beware’.

I would argue that you should regard journal articles with the same healthy scepticism, but I imagine your reaction to this is either disbelief or a mixture of confusion and panic. If you are sceptical, good! I need to provide evidence for my argument. If you are confused, let me explain.

How is a journal article like a used car? It is easier to consider how the seller equates to the author(s) of a journal article. The seller wishes to get the best price and is unlikely to point out defects and flaws; certainly not with the same enthusiasm as they have for the plus points. The authors of a journal article are also selling something – their interpretation of their experiments, including their underlying assumptions. It is hugely important that the authors win the reader's confidence; that they convince you that their work is showing true facts (see Primer 1 for an expansion of this idea). Science is big business and careers depend on how widely and how securely the views of the authors are endorsed by the scientific community. In some ways, it is possible to regard journal articles as advertisements for a particular doctrine.

Some of you will have picked up a counter-argument in the shape of the peer-review process. Good for you, you are reading with scepticism. Surely the peer-review process means the reader can have confidence that an article in a peer-reviewed journal is accurate and true – at least at the time it was published? Sadly, this would not be a safe assumption. Though it is arguably the best system we have to ensure the quality and validity of what is published, peer-review is very far from perfect and even the most prestigious journals make mistakes.

Science makes use of an approach that has become known as the Scientific Method (see Primers 1 and 2). It was developed into something we can recognize today in a process that can be traced back nearly 400 years to a succession of great thinkers and great philosophers. In 1601, Francis Bacon (1561–1626) wrote:

‘Read not to contradict and confute; nor to believe and take for granted; nor to find talk and discourse; but to weigh and consider.’

From Bacon's essay of Studies (published in full in 1Madden, 2007).

It is too easy to read and simply accept as facts those things that are offered as such. It is highly likely that excellence in your written work, which relies upon your interpretation of the academic literature, will be judged on your ability be demonstrate that you are ‘critical of what you read’.

Unless you have knowledge of the experimental techniques used in a study, however, you will find it difficult to discriminate between studies that are well designed and/or controlled and those that are not, and you will find it hard to be critical. Therefore, in essence, each primer in this book is intended to provide you with the means to be critical about studies described in journal articles.

Aims of each primer

It is important that you are aware of the aims of these primers. Each one is designed to:

provide orientation and guidance to readers who have no experience of the technique;

suggest reasons/motives for electing to use a specific technique;

provide details of a method only where detailed knowledge is required;

provide limits on what can ‘reasonably’ be claimed of data – specificity, selectivity, etc.;

describe control experiments that should be included in a journal article;

explain why particular controls are performed;

list other techniques that are commonly used in conjunction;

list common misconceptions about a technique or the data produced by a technique;

list some caveats about interpretation of data [where appropriate].

However, they are not:

intended to be encyclopaedic manuals or reviews;

‘how to’ guides;

sufficient in themselves as resources (hence the further reading);

likely to be useful to persons experienced with the technique.

I want to end this preface with another quotation from Francis Bacon:

“If a man will begin with certainties, he shall end in doubts; but if he will be content to begin with doubts, he shall end in certainties.”

From Bacon's 2The Advancement of Learning (1605) book 1, primer 5, section 8

What I take from this quotation is that it is not healthy for scientists to believe too fiercely in what appears today to be true. We must be prepared to question anything; there should be no 3dogma in science, because our current understanding reflects a continuum beginning with the tentative ‘more probable than not’ and moving to greater and greater probability of being accurate or true – but never reaching certainty. Ultimately, nothing is ever proved.

Phil Langton

Notes

1. Madden, P. (Ed., 2007). Quotidiana (http://essays.quotidiana.org/bacon/studies/). Accessed 22 Apr 2012.

2. Available from: www.lifesmith.com/Berkeley%20Teaching/The%20Oxford%20Dictionary%20Of%20Quotations.pdf; accessed 22nd April, 2012.

3.Dogma – ‘a principle or set of principles laid down by an authority as incontrovertibly true’. Source: Oxford Dictionaries.

Acknowledgements

This book can trace its origins back to about 10 years, to learning and teaching resources for undergraduate students studying anatomy, neuroscience or physiological science at the University of Bristol and this explains in large part why Bristol academics are involved with the majority of the primers you will find listed. The aim for the book is simple, as it was for the original resource; to communicate some of the practical wisdom that can only come with years of experience and scholarship in laboratory research. It does not pretend to make the reader an expert or to train the reader to use these research techniques but it does provide insight into the assumptions and issues that can lie beneath the surface of seemingly transparent and persuasive research reports. In editing the book, I have been surprised on a daily basis by the scope and significance of the aspects highlighted by my colleagues. Indeed, I have learned so much that I would now view with extreme scepticism the claim that one can read contemporary research reports without, as minimum, the sort of insight that this book aims to provide.

The original resource would not have been possible without the enthusiastic support of my colleagues in the University of Bristol and it is to them that I am most deeply grateful. I wish also to thank the team at Wiley-Blackwell who saw the potential for a book and the independent reviewers who reacted so positively to the preliminary outline and example primers. The first edition required a significant expansion from the original resource and had involved a large number of people from Universities in the United Kingdom, Australia and North America to whom I am enormously and sincerely grateful.

I wish to express my gratitude to the University of Bristol for its encouragement of excellence in learning and teaching as well as excellence in research. For some time the prevailing wind within UK HE has benefitted a focus on research above all else and yet Bristol has striven consistently to promote the interests of its students and the education they receive. This book reflects the ethos of enquiry and excellence that is so typical of the University of Bristol.

I need to acknowledge the support (and patience) of my partner, Rosie, without whom this project would have failed. Finally, I gratefully acknowledge my parents who taught me to respect the potential in dedication and hard work and the value of integrity; attributes that no research scientist should ignore. Lastly to Alice, Polly and Jess who just wanted to see their names in print.

Dr Phil Langton

August, 2012

Introduction

Phil Langton

This introduction explains the structure of most of this publication (Primers 4 to 35). The first three primers escape this structure, as their aim is different. These first three primers cover:

1. The philosophy of science

2. Experimental design

3. Statistics

These are topics of fundamental importance in science. Reading these first will allow maximum benefit from the other primers and indeed from every journal article you read in future. Switch on your scepticism!

As Claude Bernard said in his 1textbook, “L'expérimentateur doit douter, fuir les idées fixes et garder toujours sa liberté d'esprit”, which means “the investigator should doubt, avoid preconceptions, and always keep an open mind”

Primers 4 to 35 will have the following structure:

Basic ‘how-to-do’ and ‘why-do’ section

This section will cover what the technique is used for. For some techniques, the answer is far from obvious. If there are facets of the technique that require insight into how the experiments are done, then they will be included in this section. It will be basic – just enough to make sections on required controls and pitfalls in execution or interpretation intelligible and to help you tackle articles in the reference section.

Required controls

If your eyes have at tendency to glaze over at the mere mention of ‘experimental controls’, then give yourself a slap and read on. Without well-judged experimental design and comprehensive controls, the results of an experiment are next to useless. There will endless possible interpretations – so much so that the experiment will not advance our understanding. Each primer will list the controls that should be present, and particularly those that require special attention, because these are frequently absent or poorly designed in published articles. If appropriate, the section will indicate what failure of a particular control might indicate. For example, failure of the negative control in a PCR experiment suggests contamination of the RNA by genomic DNA – mRNA implies ongoing transcription, but the presence of genomic DNA says nothing about transcription.

Common problems or errors in literature

The errors pointed out should be findable by undergraduate students who have little or no practical experience of the technique. This does not mean there are not others – just that you will not be able to recognise them without first-hand experience, i.e. without using the technique to perform experiments.

Pitfalls in execution or interpretation

If you think that the peer-review process prevents the publication of studies that contain significant errors then, again, give yourself a slap – you're being naïve! Consider this example: a study uses immunocytochemistry (Primer 13) to provide evidence that a protein is expressed in sections of tissue or in isolated/cultured cells; it then goes on to do immunoblotting (Primer 15) to back up the immunocytochemistry (demonstrating that the protein bound by the antibody has the correct apparent mass), but uses different primary antibodies for the immunocytochemistry and immunoblots. Yes, it does happen! If the significance of this logical error is lost on you, then you need to read Primers 12 to 15.

Complementary and/or adjunct techniques

This will list techniques that are often used together.

Further reading and resources

Some of the articles will be those cited in the text, while others will be suggestions for further reading. You need to keep in mind that these techniques require years of careful scholarship and training to master. The primers have been written by researchers who have developed true expertise with each technique but each primer is very short and of limited scope – hence the term, ‘2primer’.

Notes

1. ‘Introduction à l'étude de la médecine expérimentale’, 1865.

2.Primer: a book (or text) that covers the basic elements of a subject. Source: OED.

Section A

Basic Principles

Chapter 1

Philosophy of Science

James Ladyman

Philosophy, University of Bristol, UK

1.1 What is Science?

Dictionary definitions speak of a systematic body of knowledge, and the word ‘science’ comes from the Latin word for knowledge. However, not any old collection of facts – even one that is organized – constitutes a science. For example, an alphabetical list of all the words that are used in this book and all the others published on the same day would make no contribution to scientific knowledge. Something else is needed, and there are two obvious supplements to what has been said so far: