A Nobel Laureate’s views on creating Meaning from Data

Image © MRC Laboratory of Molecular Biology, Cambridge, UK

Praise for the Praiseworthy

Today the recipients of the 2017 Nobel Prize for Chemistry were announced [1]. I was delighted to learn that one of the three new Laureates was Richard Henderson, former Director of the UK Medical Research Council’s Laboratory of Molecular Biology in Cambridge; an institute universally known as the LMB. Richard becomes the fifteenth Nobel Prize winner who worked at the LMB. The fourteenth was Venkatraman Ramakrishnan in 2009. Venki was joint Head of Structural Studies at the LMB, prior to becoming President of the Royal Society [2].

MRC Laboratory of Molecular Biology

I have mentioned the LMB in these pages before [3]. In my earlier article, which focussed on Data Visualisation in science, I also provided a potted history of X-ray crystallography, which included the following paragraph:

Today, X-ray crystallography is one of many tools available to the structural biologist with other approaches including Nuclear Magnetic Resonance Spectroscopy, Electron Microscopy and a range of biophysical techniques.

I have highlighted the term Electron Microscopy above and it was for his immense contributions to the field of Cryo-electron Microscopy (Cryo-EM) that Richard was awarded his Nobel Prize; more on this shortly.

First of all some disclosure. The LMB is also my wife’s alma mater, she received her PhD for work she did there between 2010 and 2014. Richard was one of two people who examined her as she defended her thesis [4]. As Venki initially interviewed her for the role, the bookends of my wife’s time at the LMB were formed by two Nobel laureates; an notable symmetry.

2017 Nobel Prize

The press release about Richard’s Nobel Prize includes the following text:

The Nobel Prize in Chemistry 2017 is awarded to Jacques Dubochet, Joachim Frank and Richard Henderson for the development of cryo-electron microscopy, which both simplifies and improves the imaging of biomolecules. This method has moved biochemistry into a new era.


Electron microscopes were long believed to only be suitable for imaging dead matter, because the powerful electron beam destroys biological material. But in 1990, Richard Henderson succeeded in using an electron microscope to generate a three-dimensional image of a protein at atomic resolution. This breakthrough proved the technology’s potential.

Electron microscopes [5] work by passing a beam of electrons through a thin film of the substance being studied. The electrons interact with the constituents of the sample and go on to form an image which captures information about these interactions (nowadays mostly on an electronic detector of some sort). Because the wavelength of electrons [6] is so much shorter than light [7], much finer detail can be obtained using electron microscopy than with light microscopy. Indeed electron microscopes can be used to “see” structures at the atomic scale. Of course it is not quite as simple as printing out the image snapped by you SmartPhone. The data obtained from electron microscopy needs to be interpreted by software; again we will come back to this point later.

Cryo-EM refers to how the sample being examined is treated prior to (and during) microscopy. Here a water-suspended sample of the substance is frozen (to put it mildly) in liquid ethane to temperatures around -183 °C and maintained at that temperature during the scanning procedure. The idea here is to protect the sample from the damaging effects of the cathode rays [8] it is subjected to during microscopy.
A Matter of Interpretation

On occasion, I write articles which are entirely scientific or mathematical in nature, but more frequently I bring observations from these fields back into my own domain, that of data, information and insight. This piece will follow the more typical course. To do this, I will rely upon a perspective that Richard Henderson wrote for the Proceedings of the National Academy of Science back in 2013 [9].

Here we come back to the interpretation of Cryo-EM data in order to form an image. In the article, Richard refers to:

[Some researchers] who simply record images, follow an established (or sometimes a novel or inventive [10]) protocol for 3D map calculation, and then boldly interpret and publish their map without any further checks or attempts to validate the result. Ten years ago, when the field was in its infancy, referees would simply have to accept the research results reported in manuscripts at face value. The researchers had recorded images, carried out iterative computer processing, and obtained a map that converged, but had no way of knowing whether it had converged to the true structure or some complete artifact. There were no validation tests, only an instinct about whether a particular map described in the publication looked right or wrong.

The title of Richard’s piece includes the phrase “Einstein from noise”. This refers to an article published in the Journal of Structural Biology in 2009 [11]. Here the authors provided pure white noise (i.e. a random set of black and white points) as the input to an Algorithm which is intended to produce EM maps and – after thousands of iterations – ended up with the following iconic mage:

Reprinted from the Journal of Structural Biology, Vol. 166. © Elsevier. Used under licence 4201981508561. Copyright Clearance Center.

Richard lists occurrences of meaning being erroneously drawn from EM data from his own experience of reviewing draft journal articles and cautions scientists to hold themselves to the highest standards in this area, laying out meticulous guidelines for how the creation of EM images should be approached, checked and rechecked.

The obvious correlation here is to areas of Data Science such as Machine Learning. Here again algorithms are applied iteratively to data sets with the objective of discerning meaning. Here too conscious or unconscious bias on behalf of the people involved can lead to the business equivalent of Einstein ex machina. It is instructive to see the level of rigour which a Nobel Laureate views as appropriate in an area such as the algorithmic processing of data. Constantly questioning your results and validating that what emerges makes sense and is defensible is just one part of what can lead to gaining a Nobel Prize [12]. The opposite approach will invariably lead to disappointment in either academia or in business.

Having introduced a strong cautionary note, I’d like to end this article with a much more positive tone by extending my warm congratulations to Richard both for his well-deserved achievement, but more importantly for his unwavering commitment to rolling back the bounds of human knowledge.
If you are interested in learning more about Cryo-Electron Microscopy, the following LMB video, which features Richard Henderson and colleagues, may be of interest:


The Nobel Prize in Chemistry 2017.
Both Richard and Venki remain Group Leaders at the LMB and are actively involved in new scientific research.
Data Visualisation – A Scientific Treatment.
Her thesis was passed without correction – an uncommon occurrence – and her contribution to the field was described as significant in the formal documentation.
More precisely this description applies to Transmission Electron Microscopes, which are the type of kit used in Cryo-EM.
The wave-particle duality that readers may be familiar with when speaking about light waves / photons also applies to all sub-atomic particles. Electrons have both a wave and a particle nature and so, in particular, have wavelengths.
This is still the case even if ultraviolet or more energetic light is used instead of visible light.
Cathode rays are of course just beams of electrons.
Henderson, R. (2013). Avoiding the pitfalls of single particle cryo-electron microscopy: Einstein from noise. PNAS This opens a PDF.
This is an example of Richard being very, very polite.
Shatsky, M., Hall, R.J., Brenner, S.E., Glaeser, R.M. (2009). A method for the alignment of heterogeneous macromolecules from electron microscopy. JSB This article is behind a paywall.
There are a couple of other things you need to do as well I believe.


From: peterjamesthomas.com, home of The Data and Analytics Dictionary


No-fooling: A new blog-tagging meme – by Curt Monash

Software Memories - a Curt Monash blog

By way of [very necessary] explanation, this post is a response to an idea started on the blog of Curt Monash (@CurtMonash), doyen of software industry analysts. You can read the full article here. This is intended as an early April Fools celebration.

A summary:

[…] the Rules of the No-Fooling Meme are:

Rule 1: Post on your blog 1 or more surprisingly true things about you,* plus their explanations. I’m starting off with 10, but it’s OK to be a lot less wordy than I’m being. I suggest the following format:

  • A noteworthy capsule sentence. (Example: “I was not of mortal woman born.”)
  • A perfectly reasonable explanation. (Example: “I was untimely ripped from my mother’s womb. In modern parlance, she had a C-section.”)

Rule 2: Link back to this post. That explains what you’re doing.
Rule 3: Drop a link to your post into the comment thread. That will let people who check here know that you’ve contributed too.
Rule 4: Ping 1 or more other people encouraging them to join in the meme with posts of their own.

*If you want to relax the “about you” part, that’s fine too.

I won’t be as dramatic as Curt, nor will I drop any names (they have been changed to protect the guilty). I also think that my list is closer to a “things you didn’t know about me” than Curt’s original intention, but hopefully it is in the spirit of his original post. I have relaxed the “about me” part for one fact as well, but claim extenuating circumstances.

My “no-fooling” facts are, in (broadly) reverse chronological order:

  1. I have recently corrected a Physics paper in Science – and please bear in mind that I was a Mathematician not a Physicist; I’m not linking to the paper as the error was Science’s fault not the scientists’ and the lead author was very nice about it.
  2. My partner is shortly going to be working with one of last year’s Nobel Laureates at one of the world’s premier research institues – I’m proud, so sue me!
  3. My partner, my eldest son and I have all attended (or are attending) the same University – though separated by over 20 years.
  4. The same University awarded me 120% in my MSc. Number Theory exam – the irony of this appeals to me to this day; I was taught Number Theory by a Fields Medalist; by way of contrast, I got a gamma minus in second year Applied Mathematics.
  5. Not only did I used to own a fan-site for a computer game character, I co-administered a universal bulletin board (yes I am that old) dedicated to the same character – even more amazingly, there were female members!
  6. As far as I can tell, my code is still part of the core of software that is used rather widely in the UK and elsewhere – though I suspect that a high percentage of it has succumbed to evolutionary pressures.
  7. I have recorded an eagle playing golf – despite not being very good at it and not playing at all now.
  8. I have played cricket against the national teams of both Zimbabwe (in less traumatic times) and the Netherlands – Under 15s and Under 19s respectively; I have also played both with and against an England cricketer and against a West Indies cricketer (who also got me out), but I said that I wasn’t going to name drop.
  9. [Unlike Curt] I only competed in one chess tournament – I came fourth, but only after being threatened with expulsion over an argument to do with whether I had let go of a bishop for a nanosecond; I think I was 11 at the time.
  10. At least allegedly, one of my antecedents was one of the last hangmen in England – I’m not sure how you would go about substantiating this fact as they were meant to be sworn to secrecy; equally I’m not sure that I would want to substantiate it.
  11. And a bonus fact (which could also be seen as oneupmanship vis à vis Curt):

  12. One of the articles that I wrote for the UK climbing press has had substantially more unique views than any of my business-related articles on here (save for the home page itself) – sad, but true, if you don’t believe me, the proof is here.


Other Monash-related posts on this site: