I wake with a not insubstantial hangover. Colin’s tiny shower offers little solace for my aching head, but slowly I return to normality and head into Manhattan to meet Rachel Holtzman, my US publisher at Penguin Avery for lunch. This is the first time I’ve met Rachel in person, although we’ve had many phone conversations since she bought the American rights for the book (demonstrating her obvious good taste and intelligence).
There’s an easy, but steely calm to Rachel. If she were an animal she’d be a swan, a powerful grace that I suspect, if necessary, could quite quickly become formidable, but rarely has a need to. “I don’t have trouble with many authors,” she says, “but some do turn out to be stealth assholes.” I laugh. I’m looking forward to working with her. She just seems, well, solid.
I’m full of excitement about the book and talk hurriedly and a little disconnectedly about everything I’ve been discovering (there is so much in my head it’s still a little jumbled up). It’s pouring out of me in a less than coherent fashion, not helped I’m sure by the bath of red wine and beer I subjected my neurons to the previous evening. On the basis of this I suspect Rachel may be thinking ‘If he talks like this, then God alone knows how much editing his writing will need.’
One thing that does concern me is the proposed publication date for the book, a whole 18 months after I’m due to deliver my manuscript. I’m worried this may compromise its grasp of the zeitgeist. For instance, there’s a very high possibility that synthetic life will have been created by the time the book hits the stores, yet my manuscript will read as if it hasn’t happened. Sub-orbital tourists will likely be in space by the time you can buy a book that describes them as a near-future possibility. Advances in machine learning (already moving faster than I had expected) may have delivered headlines in the time between the delivery of my manuscript and publication that will make my work seem, well, behind the curve (hardly good for a book about the future). I’m struck by how fast everything I am investigating is moving, and how slow book publishing seems in comparison.
Ideally I’d like the book out before Christmas 2010 but both Penguin and Profile (my publishers outside the US) are talking of mid-late 2011. It seems impossibly far away, but there are a number of good reasons for the delay. There is the process of working with my editors to hone the manuscript – an experience I’m rather looking forward too (I tend to work better with a sounding board). There is the need to consider marketing strategies, design book covers, and schedule promotional activities. The various TV, radio shows, book fairs etc that will form part of my promotional duties need to be approached and slots booked well in advance. In the end, the speed of publication is largely dependent on the quality of my initial manuscript. The closer it is to the mark, the easier it is for Rachel and Mark (Ellingham, my publisher at Profile) to expedite its route to market.
All that said, I’m feeling that the book will be a lot more about ethics, attitudes and moral frameworks than I had previously thought. These themes are perennial, and if I weave them well into the text, it should remain ‘current’ whatever the publication date. Indeed, Juan Enriquez’s As the Future Catches You is largely out of date, in terms of the statistics and studies he quotes, but the intellectual and moral issues he asks us to consider have a ongoing resonance. Perhaps I’m worrying too much…
I spend the early part of the afternoon walking down the west side of Manhattan spending time in Rockefeller Park and watching yachts sail up the Hudson. On one I see an advert for ‘America’s only gay sailing tea dance’ – surely one of the few businesses where a single supplier can saturate the market. Seriously, how many gay sailing tea dances can one economy support? Wandering into the island I hit a sea of humanity, a wall of intent. Everyone has something to do in New York, somewhere to go, someone to see, something to be getting on with. I too have an appointment, with neuroscientist René Hen.
René is the head of Colin’s neuroscience lab at Columbia University Hospital where his team research Stem Cell Biology and the ‘Neurobiology of Learning and Memory’. He’s also incredibly French. Immediately you know you’re in the presence of someone with a wildly playful spirit. It goes beyond the kind of comic book Gaelic exuberance you might imagine (although he has this in abundance). It’s a look in his eyes. They’re bright from deep within as if little pinpricks of pure inspiration are burning somewhere behind the retina. He smiles easily, laughs easier. He wears his brains like a great musician wears his instrument, not as a badge of honour, or a mark of their profession – but as something they just have a great deal of fun with.
René Hen - impossibly French
I ask René how he got into neuroscience. He laughs. “Um… it was my experience with magic mushrooms a long time ago. The idea a tiny amount of this discrete compound could have such a powerful behavioural effect was interesting. You take half of a mushroom and you get effects that are pretty profound and last for hours…”
“In fact they’ll turn you into a neuroscientist,” I say.
“Yes! But beyond that I thought that a lot of the mystery had gone out of biology and immunology. Then, and now, the biggest mysteries lie in the brain. That was the other attraction.”
The problem with neuroscience, to put it bluntly, is it’s bloody complicated. One of the reasons ‘the biggest mysteries lie in the brain’ is that it is an inordinately complex piece of kit. There are, for instance, 400 miles of blood vessels and100 billion nerve cells in that jellylike mass of fat and protein sat inside your head (that’s approximately the same as the number of stars in the galaxy). Trying to understand the interplay of all that cognitive wetware is a mammoth task. Isolating and studying specific in-brain systems or processes is hard to do, akin to trying to concentrate on a single shade of blue throughout a picture of the entire ocean.
For many years neuroscience made use of those unfortunate enough to have suffered a brain injury or ‘lesion’ as a way to try and understand how the whole system worked, the method of deduction roughly being, ‘well it seems if you take that chunk of the brain out then the patient loses the ability understand basic social etiquette’ (this is actually a direct quote from a physician looking at a brain scan of Boris Johnson). The brain is not divided into neat departments. As René says, “you can lesion many parts of the brain and get similar behavioural deficits, say in memory or mood. Or, you can lesion one part of the brain and get a particular behavioural outcome, but there could be 50 reasons for it.” Similarly, even though the genetic mutations that are related to diseases like Alzheimer’s, Parkinson’s or Huntington’s are long identified we still don’t understand how these mutations eventually lead to behaviour we see in patients. There’s just too many variables to consider in the way the brain develops and compensates for us to have a model of how these diseases develop. “If you have a mutation early on, you have the whole cascade of developmental compensations, re-wiring afterwards, and at the end there is no way to trace it back to the mutation,” says René. At least not yet.
Trying to ask specific questions about brain chemistry and physiology is a bit like asking my mum about whether she enjoyed her dinner. “Well, I had fish, which reminds me that there was a great deal on fish at Sainsburies this Saturday, which I found out from talking to Beryl, you remember Beryl? we met her on holiday in Greece and it turned out she lived just down the road in Dunchurch, where by the way the statue in the square was hit by a car, it was in the paper, front page, did you know your brother’s bought a new car…?” (My mum does an amazing thing. She will eventually tell you if she enjoyed her dinner and in the process of getting there will tie up any loose ends she’s left hanging during her tangential asides. It all comes together like the video of an explosion being played in reverse.)
Because the physiology of the brain is not unlike my mum’s method of answering a questions (everything is related to everything else) isolating useful lines of enquiry is quite hard. You need to get rid of a lot of ‘noise’. This is why when I visit Colin’s bit of the lab (which I have to say needs a damn good tidy up!) he is peering at individual rat neurons under his microscope. Neuroscience is now a largely ‘bottom up’ profession. When neuroscientists therefore find a system that seems to behave in a predictable way within the brain they get excited. Neurogenesis – the ability of the brain to generate new neurons is one such system.
That our brains generate new brain cells still comes as a surprise to a lot of people, even though it’s been 20 years since neurogenesis was discovered occurring in the hippocampus (a part of the brain associated with long term memory and spatial awareness). “The dogma was that no new neurons are added in the mature brain,” says René..
(Another popular myth is that alcohol kills brains cells. Roberta Pentney, professor of anatomy and cell biology at the University at Buffalo concluded it doesn’t, but it does hamper the ability of your brain cells to communicate – although the effects are not permanent. René, I notice has a fine selection of beers and spirits sat on his desk).
“For some reason we still don’t understand anti-depressants stimulate the production of young neurons – neurogenesis – in the hippocampus,” says René. “So here we have a form of brain plasticity that’s very easy to manipulate, it’s a cell type that’s very unique, you only find it in the hippocampus and maybe one other area. So it’s a window into a brain function. In a sense nature gave us a tool here.”
“Almost a little laboratory in the brain?” I ask
“Exactly.”
You can stimulate neurogenesis yourself. Exercise, learn something new. ‘Enrichment’ says René is good for your brain. “It’s probably a good idea to have more of these neurons,” he says. “We actually don’t know for sure how much more is good though”.
The discovery and understanding of neurogenesis offers hope to those battling neurodegenerative disorders. If we can learn to switch on the process, coaxing stem cells in the brain to become neurons then we may be able to reverse the damage done to memory by Alzheimer’s, or to repair brain damage caused by more direct means (say a head injury or listening to James Blunt).
Warning. May contain Andrew Lloyd Webber.
“There are stem cells all over the brain,” says Rene. “So even though there are only two niches where neurogenesis is taking place in normal conditions you could wake them up in other parts of the brain. We know that they are elsewhere because if you lesion other parts of the brain, you can get neurogenesis there. So clearly the stem cells are there or are recruited from outside. Theoretically you could treat any neurodegenerative disease. Or a spinal cord injury. Or a cortical injury. That’s something that’s still science fiction but I would not be surprised if we can achieve that.”
“That’s an incredibly exciting proposition?”
“Yes, it is very exciting. The interest in this area is enormous.”
My time with René is up, but I’ve been invigorated by talking to him. He’s like a cross between Winnie the Pooh, Jean Reno and Albert Einstein. That’s a compliment.
Colin takes me to the pub with another neuroscientist, Clay, who I am reliably informed is ‘beyond clever’. We drink Guinness and talk about girls.
