Ray Kurzweil’s people sent me a copy of his book The Singularity is Near quite a while ago when it first came out. I kept meaning to write about it, but several things kept interfering. One of the things was the book itself.

I’m of two minds about Kurzweil and the worldview he represents. As many will know, he’s about as much of a technological optimist as it’s possible to be, and I have a lot of that outlook myself. But I wonder – does it extend to my own field of research? More generally, and more disturbingly, am I only optimistic about the areas whose details I don’t know very well?

These questions came up again when I read a recent op-ed by Kurzweil in the Philadelphia Inquirer. It’s a good summary of his thinking, and it includes this paragraph:

“The new paradigm is to understand and reprogram our biology. The completion of the human genome (our genetic code) project three years ago is now allowing us to do that. This process is also exponential: The amount of genetic data we are able to sequence (decode) has doubled every 10 months, while the price for decoding each gene base-pair drops by half in the same time frame (from $10 per base pair in 1990 to less than a penny today). For example, it took us 15 years to sequence HIV, yet we sequenced the SARS virus in only 31 days, and can now sequence a virus in just a few days.”

That, to me, is a mixture of accurate information, reasonable optimism . . .and unreasonable assertions. Yes, we’re sequencing things faster than ever before, and part of that increase comes through computational advances, which are a ferocious driver of everything they concern. But it’s a very long leap from that to saying that such sequencing is allowing us to “reprogram our biology”. Reading the DNA letters quickly does not, unfortunately, grant us an equally speedy understanding of what they mean. And we shouldn’t forget that sequences are only a part of biological understanding, a realization that the genomics boom of the late 1990s drove home very forcefully and expensively.

Then we come to this:

“Being able to decode the human genome allows us to develop detailed models of how major diseases, such as heart disease and cancer, progress, and gives us the tools to reprogram those processes away from disease. For example, a technique called RNA interference allows us to turn unhealthy genes off. New forms of gene therapy are also allowing us to add healthy new genes. And we can turn on and off enzymes, the workhorses of biology. Pfizer Inc.’s cholesterol-lowering drug Torcetrapib, for example, turns off one specific enzyme that allows atherosclerosis, the cause of almost all heart attacks, to progress. Phase II FDA trials showed it was effective in preventing heart disease, so Pfizer is spending a record $1 billion on the phase III trials. And that’s just one example of thousands of this “rational drug design” approach now under way.”

Oh, dear. Let’s take these in order. First, being able to decode the human genome does not allow us to develop detailed models of how major diseases progress. It allows us to begin to think about doing that, and to be, for the most part, mistaken again and again. Many diseases have a genetic component, or two, or a thousand, but we don’t understand them yet, nor their incredibly tangled relationships with development and environment. You’d think we’d know the genetic components of diabetes or schizophrenia, but we don’t, and it’s not for lack of trying. And as for the diseases for which the genetic component is less important, the sequencing of the human genome has been a non-event.

And yes, there is a highly interesting technique called RNA interference which can turn “unhealthy genes” off. It works quite well (although not invariably) in a glass tube or a plastic dish. A plastic dish, that is, in which you have carefully cultered cells in which you have carefully determined the presence of the gene of interest. And for many interesting conditions, you first need to find your gene, for which see above. Moving out of the cell culture labs, it should be noted that RNAi has significant hurdles to overcome before it can do anything in human beings at all, and may (like its forerunner, antisense DNA) still be destroying venture capital twenty years from now. Readers of this site once voted it the currently hyped technology most likely to prove embarrassing.

As for new forms of gene therapy allowing us to add healthy new genes, well, that’s another hope that I’d like to see fulfilled. But there have been a number of disturbing and fatal complications along the way, from which the whole gene therapy field is still trying to recover. For Kurzweil to leave that sentence in the present tense, in the sense of this-is-happening-right-now, is putting it rather hopefully.

And yes, we can turn off enzymes. Some of them. This has nothing to do with gene sequencing or RNA interference, though, or any other particularly new technologies – enzymes as drug targets go back decades, and enzyme inhibitors as drugs go back centuries. Of course, you need to find your enzyme and make sure that it’s relevant to the disease, and find a compound that inhibits it without inhibiting fourteen dozen other things, but that’s how I earn my living.

And yes, Pfizer hopes to make all kinds of money off torcetrapib, but I’m not aware that they used a “rational drug design” strategy. In the industry, we tend to use that term, when we can use it with straight faces, to mean drug design that’s strongly influenced by X-ray crystal structures and computational modeling, but I don’t think that this was the case for torcetrapib. Kurzweil seems to be using the phrase to mean “drugs targeted against a specific protein”, but that’s been the dominant industry mode since the days of bell-bottoms. And if there are thousands of programs comparable in size torcetrapib, they must be taking place on other planets, because there’s not enough drug development money here on Earth for them.

Finally, the end of the paragraph. Where does all this lead? Later in Kurzweil’s article, he says:

“So what does the future hold? By 2019, we will largely overcome the major diseases that kill 95 percent of us in the developed world, and we will be dramatically slowing and reversing the dozen or so processes that underlie aging.”

And here, I think, is where I can clearly differentiate my thinking from his. As opposed to a pessimist’s viewpoint, I agree that we can overcome the major diseases. I really do expect to put cancer, heart disease, the major infections, and the degenerative disorders in their place. But do I expect to do it by 20-flipping-19? No. I do not. I should not like to be forced to put a date on when I think we’ll have taken care of the diseases that are responsible for 95% of the mortality in the industrialized world. But I am willing to bet against it happening by 2019, and I will seriously entertain offers from anyone willing to take the other side of that bet.

Why am I so gloomily confident? For us to have largely overcome those conditions by 2019, odds are excellent that these new therapies will have to have been discovered no later than 2014 or so, just to have a chance of being sure that they work. That gives us seven years. It isn’t going to happen.

So I’m back to wondering: am I a technological optimist at all? I must be, because I still think that science is the way out of many of our problems. But am I only optimistic about things of which I’m ignorant? That’s probably part of my problem, yes, painful though it is to admit. Am I willing to be as optimistic as Ray Kurzweil? Not at all. . .

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