Maps: resolution and insight in biology

 

(thoughts after reading Simon Garfield “On the map: why the world looks the way it does” Gothan books 2012 )

Much of Biology is about maps . Maps of genomes, of cells, of genetic interactions, protein interactions, of the brain, networks. Maps are essential because they orient us, guide us, help us find relationships between objects of the same kind which are otherwise invisible, and  reveal how global pictures emerge from components. But how accurate are our maps? How good are our current biological maps as representations of the reality they try to capture?

I often worry about these issues and in one of these musings, recently, I learnt the story of R.L. Stevenson’s Treasure Island map. Apparently the story emerged from a map that he drew, as the detail in the map grew, he saw a story emerging and one fed back onto the other until Treasure Island was finished.  He then sent the book to the publisher in London but the map, as a central illustration, went in a different post. The text made it to the publisher but not the map. Stevenson found himself in the position of having to redraw the map but as he could not remember every detail, he had to draw it from the story he had written. He was not happy. Not only because he had to read the story to get details, but because he knew the map the book was suggesting was nothing like the original map –and had another person drawn a map from the same story, the island would look different (look up Treasure island map (adding Stevenson if you want to narrow the search) in Google images).

Hearing this story made me think about our endeavours to figure out how a cell works, the use we make of maps in this exercise and the source of those maps. The map that Stevenson used to write the book was a real map. When he saw the map, he saw the story, he understood what was happening and how it happened and used it to run the adventure. But once the map was lost, the story is orphan because the story is not the map. The story uses the map as a background for the adventures, for the readers for the publishers. But it ain’t the map. Had he been interested in mapping the map, he would have used a different narrative. What he produced from the text is only an inaccurate and probably misleading representation of a reality. He only realized this once he lost the map. There is much for us, biologists, in this story.

Mapping genomes is a first hand exercise, there is a straightforward relationship between the plot (the sequence) and the map (the large scale genome). What it represents, a sequence of A, T, G and Cs is exactly what is supposed to represent. Protein structure is not very different and, for that reason, pretty good –though molecular interactions are a different matter. The problem arises when we go one level up and try to get maps about cells, their structure and how this generates function. And things get worst as we go up and try to represent how these molecular interactions at the cellular level generate tissues and organs. What we get from out toilings, largely through genetics, is a narrative which, in the format that we have at the moment, we express as Figure 7 or 8 or 9, of a paper. And we leave it there to act as a seed for another figure 7, 8 or 9 of another paper or the basis of the review. The problem is that, if we are serious, what we have to picture is the island that Stevenson wrote from the book and not the real one, the one that led him to the book. How do we solve this?

We know that the maps that we draw are not accurate and this spurs us to try better maps, and by ‘better’ we mean more resolution, more detail …and thus we forget that the beauty of maps does not lie (only) in their detail but (more importantly) in the insights they generate, in their ability to show us the shape of things, the relationship between different elements. More resolution will not give us that. As my colleague Ben Simons often reminds me, in the end one can have a 1:1 map but this, as Lewis Carroll tells us: such map ” has never been spread out, yet, the farmers objected: they said it would cover the whole country, and shut out the sunlight!” and of course, they cannot harvest anything. Their solution is ingenious: “ So we now use the country itself, as its own map, and I assure you it does nearly as well” (Sylvie and Bruno Concluded by Lewis Carroll, 1893) . Whereas a 1:1 map (as long as we choose the right dimensions) of the map and the mapped, might suit genomes it does not provide us any information that we did not have already. This approach is clearly not working for the cell, let alone the inaccuracies on which it is often based. This is not surprising as we are creating the narrative and the map at the same time and, really, with few exceptions we never test if it works. Figures 7, 8 or 9 are just gimmicks to get our papers published, regurgitations of the data and not something that we can (or want) to test.

Engineers and architects also use maps but these are different. They do not try to represent anything that preexist but are blueprints for existence. The object, the building, does not predates the map. If an engineer or an architect would make fanciful designs (like many that appear in computer games or sci-fi movies) they might not be able to exist. A design needs to work. In fact, our knowledge of DNA and some basic properties of proteins does allow us today to make such designs for some of simple tasks. This is the burgeoning field of ‘synthetic biology’ and it works. But this is not what we need to do when we try to work out the functional essence of the cell. In Biology and beyond DNA, we have hardly had a chance to test our maps.

We need to think about our approaches. We need to think about the questions that we want or need to answer and then work accordingly. Use the right scale for our maps, but also and more importantly, what it is that we want to map. The detail that is required for a map of Madrid is not useful when trying to map the coastline of Spain. The contours that tell us so  much about mountains and ridges are of no interest when we find our way when riding the underground. I do not have an answer yet, but wanted to call our attention to the fact that we might be misguided in our approaches. Anybody who has looked at a cell with an open mind will feel like RL Stevenson with the map he drew from the book: it is not the original one. The original one is more interesting.

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