Molecular Tinkering

Ben Martynoga

Description

Reveals some of the thrilling developments that have transformed biology since the 1960s. Highlights the challenges ahead for biologists but suggests what they can learn from the past.Energetic, jargon-free writing that will appeal to a broad audience.During the 1960s Edinburgh became a hotbed for a forward-thinking group of biologists. This is the story of these innovators who saw that life's big mysteries were best tackled by studying its molecular foundations. It introduces the eccentric thinkers, ingenious tinkerers and tenacious experimenters who broke down the cultural barriers between traditional scientific disciplines. They produced a series of transformative ideas and tools that wholly reoriented biology.Edinburgh scientists invented genetic engineering. They laid the foundations for DNA fingerprinting and the human genome project. They also cloned Dolly the sheep, purified the first gene and kick-started the now-influential fields of epigenetics and systems biology. Yet Edinburgh's leading role in most of these world-changing stories have not been told before. Ben Martynoga intertwines science, biography and anecdote to describe the roots and lasting significance of key biological concepts. He describes the crucial micro-details, the blind alleys, botched experiments, and chance encounters to give a rare insight into the way science really progresses.Now, in the 21st century, biology is increasingly a 'big science' endeavour. A deeper understanding of biology could deliver not only new drugs and diagnostics, but also improved ways to feed, clothe and fuel us. But the world still awaits the long-promised fruits of biology's molecular revolution. The successes of Edinburgh's unsung molecular pioneers remind us why it is crucial to carve out space for small-scale, curiosity-led research.

Sujets

• Sciences et techniques
• Molecular biology
• History of science

Informations

• Publié par: Troubador Publishing Ltd
• Date de parution: 28 septembre 2018
• Nombre de lectures: 0
• EAN13: 9781789011791
• Langue: English
• Poids de l'ouvrage: 5 Mo

Extrait

Molecular Tinkering
The Edinburgh scientists who changed the face of modern biology
Ben Martynoga
Copyright © 2018 Ben Martynoga

The moral right of the author has been asserted.


Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the Copyright, Designs and Patents Act 1988, this publication may only be reproduced, stored or transmitted, in any form or by any means, with the prior permission in writing of the publishers, or in the case of reprographic reproduction in accordance with the terms of licences issued by the Copyright Licensing Agency. Enquiries concerning reproduction outside those terms should be sent to the publishers.

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ISBN 978 1789011 791

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Contents
Foreword
Preface

1. What is Molecular Biology?
2. Molecular Biology Comes to Edinburgh
3. Trapping and Bottling the Gene
4. Seeing the Woods but Not the Trees
5. The Magic of the Southern Blot
6. Snipping, Stitching and Patching DNA
7. The Volatile Geology of the Epigenetic Landscape
8. To Understand the Whole, you Must Look at the Whole
9. The Mutants Invade
10. Drowning in Data but Thirsty for Knowledge

Afterword The Dong with a Luminous Nose
Acknowledgements
About the Author
About the Cover Illustration

Endnotes
Foreword
Professor Sir Adrian Bird
The discovery of the structure of DNA in 1953 was biology’s pivotal moment. Transmission of information between generations – life’s most distinctive property – was until that time a deep and seemingly impenetrable mystery. But, merely by inspecting the beautiful symmetry of the double helical molecule, Watson and Crick were able to predict – correctly – how inheritance must work. The molecular biology revolution was triggered by physicists’ hope that living things might reveal new natural laws. In fact, life turned out not to depend upon novel physical principles, but the single-minded reductionism of physical scientists led to the discovery of the structure of DNA and all that followed from that crucial step forward.
At first, many university biologists were ill-equipped to exploit the new field of molecular biology. It required them to ignore the traditional cultural barriers between disciplines (botany, zoology, chemistry, etc.), so that dialogue could flourish. Professorial fiefdoms, to which universities are often prone, get in the way of free exchange of ideas and opinions and had to be disregarded. Added to this, there was a need to cultivate a healthy disrespect for received wisdom – questioning and challenging conventional ways of looking at biological phenomena. Finally, it was essential to have a steady influx of talented scientists with the imagination and inquisitiveness required to take advantage of such a favourable environment. Through a combination of luck and excellent judgement, Edinburgh University fulfilled these requirements. Yet despite its remarkable achievements in developing key ideas and technologies over several subsequent decades, Edinburgh’s role in building the molecular view of biology is relatively unsung. Ben Martynoga’s book rectifies this omission, illuminating the many happy coincidences, prophetic decisions and the discoveries that contributed to its success.
Where is molecular biology heading now? The publication of the human genome sequence in 2001 was a scientific landmark that appeared at first sight to herald molecular biology’s final phase. With the complete list of human genes to hand, the stage was surely set for a leap forward in knowledge that would solve many of the outstanding mysteries of life. At last, the uncertainties caused by not knowing the components of living systems would be swept away and biological research would become rational and predictable, akin to the exact sciences of physics and chemistry. Medicine would be a prime beneficiary, as the anticipated flood of potential drug targets would lead to a pharmaceutical bonanza. Now we can see that many of these predictions were premature. We are indeed living in a golden age of biological research and knowledge is advancing at unprecedented rates on many fronts, but early optimism was misplaced in one important respect: timescale. Solutions to some of biology’s greatest problems (e.g. how the brain works) are still on the future agenda and the flow of genome-inspired drugs from the pharmaceutical industry is only just beginning. It turns out that even with all protein players described and catalogued, the sheer complexity of biological systems requires considerable time and ingenuity to fathom. The genome project was not the beginning of the end for biology, but the end of the beginning. So, there is much yet to understand, and, who knows, if it plays its cards properly the halcyon days of Edinburgh biology could be far from over.

Edinburgh. January, 2017
Preface
Edinburgh’s First Molecular Tinkerers
“Any living cell carries with it the experience of a billion years of experimentation by its ancestors.”
Max Delbrück 1
Professor Sir Edwin Southern stoops as he enters the low doorway of the bothy and I duck in behind him. It’s a steel-skied winter’s day at the chilly start of 2014 and I’m here to interview one of biology’s most respected innovators for the Financial Times. A little over thirty years ago this early nineteenth-century shepherd’s cottage in the Scottish Borders was knee-deep in chicken manure. Ed rolled up his sleeves, dug it out and proceeded to renovate the place, turning it into the stove-warmed haven that it is today.
I knew Ed as the architect of two famous scientific tools, the microarray and his eponymous Southern blot. Each of these inventions precipitated a step-change in the pace of research into genes, cells and disease. I knew very little, though, of the backstory that led to these transformative technologies and Ed’s quiet rise to eminence.
As Ed talks about the eighteen formative years that he spent in Edinburgh 2 , between 1967 and 1985, his warm, but habitually serious, bearded face lights up with enthusiasm. He describes an unplanned coalescence of creative scientific minds at Edinburgh University’s King’s Buildings science campus. The gravitational pull came from Edinburgh’s new found prowess in the young field of molecular biology. What emerged was a steady stream of discoveries that, in Ed’s telling, launched molecular approaches to biology on a trajectory towards their present-day dominance.
For Ed, Edinburgh was the only place in Britain that could rival Cambridge, the proven scientific powerhouse that had nurtured Francis Crick, James Watson and several other founders of molecular biology.
The strange thing about the stories Ed recounts about Edinburgh is that nearly all of them are new to me. I have over a decade’s experience of doing molecular biology. I completed my PhD in Edinburgh itself, in 2006. Yet no-one there seemed very interested in their university’s illustrious forebears.
That first conversation in the bothy pricked my curiosity. Clearly many of the protocols, hypotheses and contraptions that I took for granted in the lab traced back to Edinburgh. Even so, the standard histories of molecular biology give Edinburgh passing mention, if that. I resolved to find out more.
Happily, Ed agreed that there were important stories to dig out and share. He invited me to apply to the Kirkhouse Trust, one of the science charities he founded with proceeds from his microarray invention, to support me in this endeavour.
At the time I was ambivalent about my own future in the lab. I passionately believed, and still do, in the power of scrutinising life’s molecular foundations. This approach lets scientists chip away at the profound mystery of how life works and why it flourishes with such rich diversity here on Earth. Moreover, molecular biology continues to deliver a constant spray of powerful insights that improve the lot of human and non-human inhabitants of our planet.
Many of the intellectual and practical aspects of lab research thrilled me. But, as a habitual generalist, I sometimes felt hemmed into a narrow corner of expertise. At the same time, I had nagging doubts about the way biology is organised, funded and executed today. Might there be better ways we can do it? Are there useful nuggets we can glean from past successes?
So, starting at the end of 2014, alongside carving out a niche as freelance science writer and raising a young family, I immersed myself in a previous scientific era. I have been reading archaic (fifty years is a long time in modern biology!) scientific manuscripts, delving through archived correspondence and, most importantly, seeking out conversations. Some of Edinburgh’s first wave of molecular biologists are no longer around. Yet many of those who are, retired or approaching the apex of their careers, have generously shared their stories and reminiscences. I have also tracked down some of their scientific progeny, including several stars of today’s research scene.
This book is built on the conversations I have had. I have done my best to step into the shoes of a mid-twentieth-century molecular biologist in Edinburgh, and to stitch together a personal impression of the crucial events and their reverberations.
Some of the scenes that my interviewees described were familiar from my own time at the bench