It seems remarkable now to think that the first draft of the human genome was announced by US President Bill Clinton and UK Prime Minister Tony Blair. That these too popular politicians – in 2000 Clinton was coming to the end of his term in office but his approval ratings were at a level that his successors can only envy and Blair was still riding high in the polls at that point – wanted to associate themselves with the project is a testament to the skill of those who communicated its aims and achievements.
What will happen at the end of structural genomics? I doubt very much that President Barack Obama or potential Prime Minister David Cameron will even notice, though a interesting opinion piece by Aled Edwards, the head of the Structural Genomics Consortium, writing in Structure envisaged a press conference in 2030 announcing that the problems of climate change and the lack of drinkable water have been conquered thanks largely to the efforts of the US structural genomics group, the Protein Structure Initiative.
Edwards’ optimism for a glorious ending isn’t widely shared. But why was the Human Genome Project so popular and structural genomics much less so? There are several reasons, and the use of metaphor to explain genome sequencing was one of them.
I asked my family (all non-biologists) why the Human Genome Project was important. “That’s easy,” they said, “it’s about us. It about what makes us who we are.” They didn’t say ‘blueprint’ – the metaphor used by Clinton when he announced the first draft – but full marks to the Human Genome Project on communicating their work.
OK then, so what is structural genomics all about? “Er, structures of genomes?” they suggest. What type of structures? “Genome ones”. No, you haven’t got it.
I need a metaphor. I need an explanation that’s going to work for the man in the pub.
Gregory Petsko tried the Rosetta Stone. This stone has three inscriptions, one in hieroglyphs, one in demotic and one in greek and it was the key to solving the puzzle of hieroglyphics. Each inscription was useful, but all three were needed to explain what it meant. In the same way, sequencing of the human genome produced lots of valuable information, but it will only be when we put it together with all the other pieces, such as structural genomics, that it will make sense.
A less flattering metaphor came from Thomas Steitz who compared structural genomics to butterfly collecting. While the collection can tell you something about the size and shape of butterflies, it can’t tell you how they fly.
A metaphor that is beginning to surface from within the field is about the ‘dark matter of protein space’. What this means is that now we have solved lots and lots of protein structures we see that certain shapes or ‘folds’ are common but for some reason all the theoretically possible folds aren’t used. As we’re only looking at structures from organisms on Earth (as if that wasn’t enough!) we can’t exclude the possibility that these fold exist elsewhere, and so in an analogy with physics, Willie Taylor, a scientist at NIMR, said, “The universe is very big and, like dark matter, the bulk [of folds] might exist elsewhere.”
This is not going to go down well at The Black Swan.
How do I see the structural genomics researchers? I think they are like the explorers in the Age of Discovery. They spent the first five years building their boats and undertaking a few short journeys to make sure their vessels were seaworthy. And then they set sail for far-off lands. These explorers cannot visit every land, every sea and every mountain. It isn’t important; the important thing is to produce the outline, the map of the world.
No doubt people in the fifteenth and sixteenth centuries thought these journeys utterly pointless. But these discoveries kick-started the modern era, having huge economic impact through trading routes and it was the start of science as we know it.
I think the structural genomics people are in the process of mapping Australia and New Zealand right now.