En Passant 16-08-16:
DNA becomes DNA: a letter from O. Avery
Have been reading M. Cobb’s excellent account of the search for the genetic code (Life’s Greatest Secret), more a re-telling of the history of DNA ->RNA -> protein, but a very good retelling. The book has a good discussion of the crucial figure of OT Avery (for the youngsters, the person whose work put the finger on DNA as the carrier of heritable characteristics. His account brings out excerpts of a letter from Avery to his brother (also a biologist) which I first learnt about in a light but wonderful account of the history of Genetics by Simon Mawer (Gregor Mendel: Planting the Seeds of Genetics). Here is the end of the letter which has some absolute gems of what science should be and is, and of the humble account of a momentous occasion in the history of Biology by one of its heroes. Some people consider Avery’s work more significant than that of Watson and Crick. It is not difficult to agree. It was the piece of information that inspired Watson and, when you think: it is some result! But will leave you with the words of Avery. After some years of work (some through WWII) focusing in purifying what we now call DNA from strains of Pneumoccocus and testing its transforming power, he felt he had gone as far as he could to make sure the DNA was the transforming principle.
“Sounds like a virus, may be a gene. But with mechanisms I am not now concerned. One step at a time and the first is, what is the chemical nature of the transforming principle? Someone else can work out the rest. Of course, the problem bristles with implications. It touches the biochemistry of the thymus type of nucleic acids which are known to constitute the major part of the chromosomes but have been thought to be alike regardless of origin and species. It touches genetics, enzyme chemistry, cell metabolism and carbohydrate synthesis, etc. today it takes a lot of well documented evidence to convince anyone that the sodium salt of deoxyribose nucleic acid, protein-free, could possibly be endowed with such biologically active and specific properties and this evidence we are now trying to get. It’s lots of fun to blow bubbles-but it’s wiser to prick them yourself before someone else tries to.
So there’s the story Roy-right or wrong it’s been good fun and lots of work. This supplemented by war work and general supervision of other important problems in the Lab has kept me busy, as you can well understand. Talk it over with Goodpasture but don’t shout it around-until we’re quite sure or at least as sure as present method permits. It’s hazardous to go off half cocked-and embarrassing to have to retract later. I’m so tired and sleepy I’m afraid I have not made this very clear. But I want you to know-and sure you will see that I cannot well leave this problem until we’ve got convincing evidence. Then I look forward and hope we may all be together-God and the war permitting-and living out our days in peace”
How times change! In an episode of the making of molecular biology, Sydney Brenner was lying on a beach in California thinking about why the experiments he had been doing were not working. He had gone to California with F. … Continue reading
NB. As I was writing this post, a couple of comments came up on Twitter on whether the machine metaphor was a useful one for biological systems. The discussion did not change the view that is expressed here: a machine is a … Continue reading
following the Science is Global campaign we have had a chance to look back at our history and have realized that the mantra of the campaign is true and that, indeed, our science has always been international, something we have enjoyed and valued. These … Continue reading
Lists, catalogues and classifications have always been the business of the biological sciences. The nature cabinets of the XVII and XVIII centuries, the collections that occupied much of the XIX century and which fuelled the work of Darwin are good … Continue reading
I few months ago I was asked to speak at the Society of Spanish Researchers in the UK (SRUK) annual Symposium in London. SRUK is a grass roots organization which has evolved over the last few years to act as … Continue reading
The issue of publications of science manuscripts is reaching breaking point. Breaking in the sense of tearing down the enthusiasm of young investigators, the patience of seasoned ones and generating a lot of debate at institutional level. A few days … Continue reading
Look what happened in the lab when there are fish embryos, chicken embryos and just ES cells
Just ES cells:
Good luck Christian in Dortmund and good luck to Meritxell in inheriting Christian’s spot in the lab.
The case of the Irish Elk, a parable for the weight of the glamour journals In one of his wonderful and educational essays, SJ Gould discusses the story of the Irish Elk, a spectacular species of elk that became extinct … Continue reading
“On a summer day in the late fifties a delegation from the Soviet Union appeared in Cambridge demanding to see the “Institute of Molecular Biology”. When I took them to our shabby prefabricated hut in front of the University Physics … Continue reading
The work of our colleagues Christian Schröeter and Pau Rué on the integration of FGF signalling and GATA4, 6 activity in a mouse ES cell model of Primitive Endoderm specification has just been published in Development http://dev.biologists.org/content/142/24/4205. The specification of Primitive Endoderm requires and integration of a transcriptional input provided by a transcription factor of the GATA family and FGF signalling. In this work, a combination of live imaging, quantitative analysis and modelling reveals that FGF signalling sets up a threshold for the activity of GATA. The work also uncovers a simple bistable system which can account for the experimental observations and also provides a framework to think about events in the embryo.
The lab also published a video account of how to make gastruloids (http://www.jove.com/video/53252/generation-aggregates-mouse-embryonic-stem-cells-that-show-symmetry ). In the organoid world reproducibility is all and, for this reason, following the publication of our finding about symmetry breaking and axial elongation from ES cells (http://dev.biologists.org/content/141/22/4231.full ), we have now made a detailed account of the protocol. You might also want to have a look at our perspective on the organoid field from the point of view of developmental biology (http://onlinelibrary.wiley.com/doi/10.1002/bies.201500111/abstract ) – maybe not that much self organization. And while on this, watch this space; coming soon a study of the early events in the patterning of the gastruloids.
To see our other publications press here.
There are now videos of both the lecture and the subsequent panel discussion available at www.responsibleresearch.graduatecenter.uni-muenchen.de/presentations/videos/index.php
These are notes for a lecture given by AMA in a workshop about Responsible Research held at LMU in Munich (Germany) on 24 July 2014 (www.responsibleresearch.graduatecenter.uni-muenchen.de/index.html). The lecture is broken into two parts, the first one dealt with biomedical publishing, … Continue reading
We are interested in the structure and function of Living Matter with a special focus on the processes that generate tissues and organs from single cells through interactions between protein and gene regulatory networks. Cells use these networks to create and read programmes of gene expression and use these to interact with each other and differentiate into the multiple cell types that configure the building blocks of an organism. Our research is focused on how the activity of molecular networks is transformed into tissues for organ building. We address this problem through a combination of classical genetics, quantitative cell biology, image analysis and modelling.
We use mouse Embryonic Stem (ES) cells and Drosophila Intestinal Stem Cells (ISC) to ask questions about:
The lab has strong collaborations with Nicole Gorfinkiel (Centro Biologia Molecular, Madrid, Spain), Anne Grapin-Botton (Danish stem cell center: http://danstem.ku.dk/research1/grapin_laboratory/), Ana Katerina Hadjantonakis (Sloan Kettering Institute, New York, USA), Kathryn Lilley (Department of Biochemistry), Jenny Nichols (Cambridge Centre for Stem Cell Research), and Emma Rawlins (Gurdon Institute).
We also have strong collaborations with physicists and engineers which respond to the increasing need to trascend the data that is generated by classical biological approaches. In particular we have close interactions with Jordi Garcia Ojalvo (Universidad Pompeu Fabra: http://dsb.upf.edu/) and Jeremy Gunawardena (Department of Systems Biology)