Human Genome Zzzzz... (Idle Words)#

04.15.2003

The Human Genome is complete!

Big whup.

"It's a bit like moving from a first-attempt demo music tape to a classic CD", says the New Scientist. A hell of a metaphor. I wonder if they'll be releasing the genome on vinyl, for purists who don't think the CD version captures all the nuance of the original?

The same article contains my all-time favorite quote:

"What we've got now is what we'll have for all eternity," says Francis Collins, director of the US National Human Genome Research Institute.

Eternity, Francis? Mind if I take a peek at that diploma you got hanging there?

Funny quotes aside, all this talk about the genome is a bunch of hooey. Yes, the sequencing is very important to doing basic research in biology, and having the error-corrected sequence is a major accomplishment. But the level of hype is out of all proportion to the scientific reality, which is that the sequencing effort is just bookkeeping. We have no idea how the stuff actually works.

Of course, you know it's all empty talk as soon as they start claiming to cure cancer:

The Human Genome Project, which has researchers worldwide mapping the genes of the human body, will likely change how medicine is practiced in the future. By understanding which genes control diseases such as cancer, Alzheimers and hypertension, physicians might someday be able to prevent diseases or reduce their effects by properly assessing and responding to genetic medical risks in advance. #

Which should remind you of statements like this:

The results of John Glenn's historic 1998 space shuttle mission are providing new insights into how drugs produced in the microgravity of space can combat such earthly medical woes as cancerous tumors or help alleviate the ravages of bone cancer, researchers say..." #.

This leads me to postulate Ceglowski's Law of Oncological Hype: The importance of a scientific accomplishment is inversely proportional to its claim to cure cancer. (Caveat: the above does not apply to discoveries that actually cure cancer.)

The truth is that the genome is a big slimy mystery. People are taught about Mendel in high school, genes controlling for specific traits, even though it turns out that the vast majority of physical traits and hereditary diseases are not coded for by a single gene. Of course, there is an important subclass of disorders that are determined by specific genes - sometimes by specific point mutations - and these see real and immediate benefit from the genome project. But it seems to me that people use those exceptions as a smokescreen to avoid talking about the hard reality. Instead of residing in the DNA sequence, much of the information in the system seems to be spread out in the cell, contained the elaborate machinery needed to read the genome, process it, and turn it into proteins. What's worse, a lot of this seems to take the form of non-linear, emergent interactions that are a beast to analyze.

Of the top of my head, I can think of six areas where we don't understand anything:

Development - How do cells in the embryo know how to specialize? Why will a frog arm grow back, but not my own arm?
Expression - what governs whether a certain gene is turned on or off? There is almost certainly complex emergent behavior here, and many interacting feedback loops. But how does it work?
Transcription - what determines how a gene is transcribed into RNA? Pieces get left out, added in, rearranged, modified, swapped out. What governs this behavior?
Translation - many proteins go through heavy post-processing after the basic amino acid sequence has been assembled. How does this work?
Folding - given an amino acid sequence, how can you predict what the shape of the protein will be? Can you work back from a desired shape to a sequence that will create it?
Cross-species transfer - genes have been known to migrate from organism to organism, and across species boundaries. WTF?

And that's coming from a biological dilletante. A real biologist could add many more bullet points. And I'm willing to bet there are whole levels of complexity that we don't even know exist yet.

Why isn't there more emphasis put on our lack of understanding, when we're just reached the very first rung of the ladder? My own conspiracy theory is that it is not in the interest of biotech companies making billions from genetic engineering to stress that fact. Nor is it in the interest of the NIH and the research community to endanger their own funding by giving the public a reality check. We want our cancer cure!

The very phrase "genetic engineering" suggests a level of expertise we don't have. When you build a bridge, do you assemble random girders and keep only those bridges that don't collapse? Do girders from your bridge routinely migrate to other structures? That kind of behavior is par for the course in applied biology.

Plant genetics research, to give one example, consists of shooting DNA-coated pellets into living plants from a shotgun, planting some cuttings, and seeing what grows. Some of the plants 'take' to the target gene, and those you keep. Most of them grow in various deformed ways (why? beats us!) and those you throw away. If it still looks promising after a few generations, and the plant is not snapping its jaws and clamoring for a blood meal, you patent it and sell it to farmers. And you lobby the government to let you put it on store shelves.

Defenders of biotech claim that their procedures are no different than what farmers have been doing through centuries of breeding, just more 'scientific'. But of course, breeding uses the mechanisms of biology, while genetic manipulation circumvents them. It's like poking at the raw memory of a computer, rather than going through the operating system. If you don't know exactly what you're doing, you can't guarantee there won't be a disastrous final result.

Right now, government regulators assume genetically modified foods are not harmful unless proven otherwise. Obviously, if researchers were constantly making a big stink about their level of ignorance in genetics, the government might reconsider this cozy burden of proof. And it would mean huge losses for companies like AMD, Monsanto, and the ag universities that depend on them. So instead, we get glowing press releases about "decoding the book of life", any day now.

Ha! This from the people who can't even genetically engineer a decent tomato.