“Eighth day of Creation” for developmental biology?

“Eighth day of Creation” for developmental biology?

I’ve just posted a list of science books that I recommend for all molecular, cellular and developmental biologists. In this list I included the classic book “The Eighth Day of Creation: Makes of the Revolution in Biology” by Horace Freeland Judson.

The “Eighth Day” has become a classic for several reasons. First, the subject matter: the discovery of the double-helix structure of DNA and the subsequent work in molecular biology rank as some of the important breakthroughs in 20th century science. Second, the personalities: an incredible group of unique, quirky, but ultimately brilliant scientists. Finally, and perhaps most importantly, the writer, Horace Freeland Judson: Judson portrayed the science and scientists with great style and insight.

What could or would a modern “Eighth Day” look like? Certainly, there is plenty to write on the theme of the original book – molecular biology. But what about an “Eighth Day” for modern developmental biology? This is something I started to think about following a twitter conversation with @avinashtn. To my knowledge no such book exists. However, I think there is a fascinating story to tell – perhaps too much to tell (flies, fish, worms, screens, molecular genetics, and more) – and plenty of interesting characters and personalities. But who would write it? Who is the Judson of our time?

Books that educate, stimulate and inspire.

Scientific research is portrayed as an objective pursuit – we experiment, we observe, we draw logical conclusions, and we write ‘matter-of-fact’ scientific papers. But behind every scientific discovery is a largely neglected ‘human’ story – a narrative that is shaped by different emotions and forces: joy, frustration, rejection, validation, egotism, confidence, worry, friendship, competition, intuition, luck, success, failure. For better or worse, it is these forces that influence how discoveries are made and how science is communicated.

I enjoy reading books that uncover this narrative and that reveal the passion, politics and personalities behind scientific research. I’ve come up with a list of books that I recommend. Many delve into the stories behind research discoveries. Others are great resources for understanding, communicating and teaching science. I hope you enjoy these books and feel free to suggest others – I’m always looking for a good read.

The list is in no particular order, but the first four are books that I particularly like.

(Note: Part 2 of this list is here)

The Eighth Day of Creation: Makers of the Revolution in Biology (Horace Freeland Judson). The book is the authoritative account of the people and personalities that shaped the early years of molecular biology, from the work leading up to the discovery of the structure of DNA to studies in ‘60s and early ‘70s on the control of gene expression. This is a fantastic book and a must-read for every molecular, cellular and developmental biologist.

On Writing Well (William Zinsser) Writing well isn’t easy – in fact it is often very hard. But in this book, Zinsser writes with great wit and warmth about the struggle to put down on paper what we really mean to say. He does a wonderful job of highlighting the bad habits that creep into our writing – excess words, unnecessary clutter, and unclear sentences. It’s an incredibly enjoyable and valuable read. I bore students to death talking about how good this book, and I always re-read it before writing any new papers or grants.  Every lab should have a copy of this book.

The Statue Within (Francois Jacob). A poignant memoir from Jacob, the 1965 Nobel Prize winner.  The book contains amazing accounts of his wartime experience in Northern Africa and his time at Institute Pasteur where he made his pioneering discoveries on transcriptional control in E Coli (along with Jacques Monod).

Oh the places you’ll go (Dr Seuss). There are many good books that discuss the challenges of being a young scientist (student, postdoc, new PI) and of establishing a career. But none can match than this book…seriously. Read it in moments of despair and it will provide inspiration….that’s 98 and ¾ percent guaranteed.

The following are other good memoirs and biographies:

The Emperor of All Maladies: A Biography of Cancer (Siddhartha Mukherjee), An amazing book that does a beautiful job of describing the history of cancer medicine, therapy and research – a comprehensive book written with great style.

Egg and Ego, an almost true story of life in the biology lab (Jonathan Slack). The title says it all – Jonathan Slack does a wonderful job telling the reader about the “real” life in a biological research lab – the bizarre way in which scientists compete for publication in “prestige’ journals, the ego of lab heads striving to be the ‘best’, the warped way in which competition to work in the most ‘fashionable’ research areas drives the scientific agenda.  This is a brilliant book.

Avoid Boring People and The double helix (both James Watson). Much has been written about the Double Helix, but “Avoid Boring People” is also a great read. Both books provide a revealing insight to the personality of Jim Watson – an incredibly smart guy who was also a bit of an ass.

Francis Crick – hunter of life’s secrets (Robert Olby), and What Mad Pursuit (Francis Crick) – The other half of the Watson/Crick duo. What Mad Pursuit is an autobiography and a more measured account of the discovery of the structure of DNA. Richard Olby’s biography provides a wonderful insight into Crick’s remarkable scientific life.

I also recommend looking at the Crick papers in the archives of the National Library of Medicine. These archives contain (almost?) all of Crick correspondences throughout his research life. These letters provide a fascinating first-hand picture of Crick as the “Godfather” during the ground-breaking days of molecular biology- sharing his ideas and thoughts with his peers, advising others about their research, and sometimes admonishing colleagues for their less then collegial approach to science (see the letters between Crick and Alex Rich concerning Rich’s sneakiness when publishing the structure of tRNAs).

Max Perutz and the secret of life (Georgina Ferry) and I wish I’d made you angry earlier (Max Perutz). Georgina Ferry’s excellent biography captures the quirky but brilliant Max Perutz, who won the Nobel Prize for elucidating the structure of haemoglobin. Perutz was also a very thoughtful scientist and effective leader (I’d wish I’d made you angry earlier is a series of essays from Perutz). He was the head of the Laboratory of Molecular Biology in Cambridge during the ‘60s and ‘70s – a period in which the LMB was making groundbreaking discoveries in molecular biology (and in the process, garnering many Nobel Prizes). Money quote from Perutz that should be in bold in every university administrative office:

Creativity in science, as in the arts, cannot be organised. It arises spontaneously from individual talent. Well-run laboratories can foster it, but hierarchical organisation, inflexible, bureaucratic rules and mountains of futile paperwork can kill it”.

RNA – life’s indispensible molecule (James Darnell) – A detailed and enjoyable account of RNA research, from early studies that identified the existence of mRNA, rRNA and tRNAs to recent work on miRNAs. Darnell does an excellent job of highlighting the key studies and researchers, and providing important historical context to models of gene expression that we sometimes take for granted.

The Art of Politics and Science (Harold Varmus).  In this brilliant memoir, Varmus describes his path from English Literature PhD student to head of NIH and Memorial Sloan-Kettering Cancer Center. In particular, the book provides a fascinating insight into how Varmus managed the switch from running a lab to running the NIH – similar approach, larger scale.

The beginners Guide to winning the Nobel Prize (Peter Doherty), and How to Win the Nobel Prize (Michael Bishop) I’ve read both these enjoyable books but I’m still waiting for my Nobel Prize.

Ahead of the Curve (Shane Crotty) An entertaining account of the scientific life of David Baltimore. It does a good job of covering the Imanishi-Kari case – one of the high profile cases of alleged scientific fraud.

Lords of the Fly (Robert Kohler) – an enjoyable account of the early days of Drosophila research covering the discoveries and research of Thomas Hunt Morgan and his scientific “offspring”.

Reconceiving the gene: Seymour Benzer’s adventures in phage genetics (Frederic Holmes) and Time, Love and Memory (Jonathan Weiner). Two entertaining books about Seymour Benzer, one of the great biologists of the 20th Century. Holmes’ book provides a detailed account of Benzer’s early work on phage genetics and in particular his incredibly clever approach to map genes. Weiner’s excellent book provides a superb account of Benzer’s later work (and the work of his scientific ‘offspring’) using Drosophila to study the genetic basis of behaviour.

Phage and the origins of molecular biology (Edited by John Cairns, Günter Stent and James Watson) andOrigins of Molecular Biology: A Tribute to Jacques Monod (edited by Agnes Ullmann) – two collections of essays and reminiscences about Max Delbruck and Jacques Monod, Nobel winning biologists during the ground-breaking days of molecular biology. These revealing and often candid essays uncover the personalities of both scientists – intellectually brilliant, but also forceful, dominating and sometimes ruthless (see essay on Monod by Martin Pollock).

We can sleep later: Alfred D Hershey and the Origins of Molecular Biology (Edited By Franklin Stahl). Another collection of essays, this time about Nobel prizewinner and phage geneticist Alfred Hershey. He was more reserved that Delbruck and Monod but no less brilliant and influential during the early days of molecular biology. He inspired the concept of “Hershey heaven” – having an experimental approach that always works and performing it over and over again. He was also a very thoughtful scientist and a great writer. The title “We can sleep later” comes from the last line of a letter that Hershey wrote to contributors of a book on Phage that he was editing, urging them to work harder to get their manuscripts submitted to him.

A slot machine, a broken test tube (Salvador Luria).  A revealing, but sometimes dry, autobiography of Luria, who along with Delbruck and Hershey, was awarded a Nobel prize for work on phage and bacterial genetics.

Decades of scientific research have provided exquisite details about all manner of complex biological phenomena. But sometimes the hardest job is to step back from the intricate details and clearly convey the ‘big-picture’ logic by which biological systems – from the smallest molecular machines to entire organisms – are assembled and function.  The following books do a fantastic job of this:

A Genetic Switch  (Mark Ptashne) and Genes and Signals (Mark Ptashne and Alexander Gann) Two wonderful books that describe the logic behind gene transcription, from simple genetic switches in phage to developmental control of gene expression in animals.

The Making of a Fly (Peter Lawrence). Lawrence writes with style and clarity about the genetic mechanisms by which a single cell (the fertilized egg) develops into a multicellular animal (the adult fly).  This classic book is a little old (1992) but the scientific logic that underlies the developmental processes described in the book still largely hold true.  Buy it from Amazon, if you have a spare $23 million!

Wetware: A computer in every living cell (Dennis Bray) and Life’s Ratchet: How molecular machines extract order from chaos (Peter Hoffmann) – two great books that outline the ‘molecular machinery’ within cells. Although the books are mainly for a more lay audience, they make excellent reading for all molecular and cellular biologists especially graduate students.

Finally some more great books on communicating  

Field Notes on Science and Nature (edited by Michael Canfield) – a series of fascinating essays from a range of biologists on how they on document and record their scientific findings.

Visual Strategies: A practical guide to graphics for scientists and engineers (Angela de Pace and Felice Frankel) and Slide:ology: The art and science of creating great presentations (Nancy Duarte) – two great resources on how to draw scientific figures, how to clearly present data and how to make visually appealing slides and presentations.

 Several short sentences about writing (Verlyn Klinkenborg) Inspiring words about writing.

This week’s lab journal club: CRISPR/Cas9 mutagenesis in Drosophila

This week we finally got around to talking about the recent CRISPR/Cas9 papers in Drosophila. We mostly focused on Bassett et al, but also discussed Gratz et al.

Like other Drosophila researchers we’ve talked to, we are excited by these techniques and we can’t wait to try them out in the lab (Our new postdoc, Byoungchun Lee will be doing a lot of the work here) – CRISPR/Cas9-mediated mutagenesis will very likely develop into a “must-have” genetic technique for model organism labs.

Questions/comments we had: We mostly talked about how we would use this technique for our lab, with our favorite genes. In the Bassett et al paper the efficiency and frequency of mutagenesis for y and w looked good (although there was a high level of lethality – even in the non-injected controls ?!). But will this high efficiency hold true for all genes? Will genomic/chromatin context matter? (some of our favorite genes are in heterochromatic regions) Also, what’s the most efficient fly injecting/crossing scheme to generate stable mutant stocks (especially if the mutation efficiency ends up being quite low for some genes)? Finally, we’re interested to see how well the combination of CRISPR/Cas9 with donor oligos can be used to engineer specific alterations in our favourite genes. Gratz et al did a great job of using the approach to introduce attP sites into yellow, and presumably a similar approach can be used to introduce specific nucleotide substitutions into our favourite genes (e.g. to generate serine-to-alanine mutations at known phosphorylation sites).

Overall, two great papers. Exciting times ahead for fly genetics!

This weeks Lab Journal Club..Mlx-Mondo transcriptional regulation and sugar tolerance in larvae

This week in JC we discussed a recent paper on high sugar tolerance in larvae from the Hietakangas lab:

Mondo/ChREBP-Mlx-regulated transcriptional network is essential for dietary sugar tolerance in Drosophila. Havula E, Teesalu M, Hyötyläinen T, Seppälä H, Hasygar K, Auvinen P, Orešič M, Sandmann T, Hietakangas V. PLoS Genet. 2013 Apr;9(4):e1003438.

The paper describes how the Mlx-Mondo transcriptional complex is required for larvae to tolerate a high sugar diet –  Mlx mutants can develop to pupae on normal food, but show reduced larval growth and fail to pupate on a high sugar diet. The paper goes on to describe alterations in carbohydrate and lipid metabolism that may account for the high sugar sensitivity in mlx mutants. In particular, two targets of Mondo-Mlx – the transcription factor cabut and the detoxifying enzyme Aldehyde dehydrogenase type III  – are required for high sugar tolerance.

Overall, we liked this paper. We think a lot about how dietary protein can influence larval growth via insulin/TOR signaling. But clearly alterations in dietary sugar, and probably changes in the ratio of sugar: protein, can have important effects on larval physiology and growth.

Questions we had: How do larvae sense and respond to high sugar? via changes in insulin signaling? (see Pasco and Leopold, 2012). Does Mondo-Mlx transcriptional activity respond to changes in diet and/or insulin signaling? (increased expression? increased DNA localization?). Do Mondo-Mlx mutants show altered responses to dietary amino acids and do alterations in the relative balance of dietary sugar: protein influence larval growth?