March 4, 2004

ON THE OTHER HAND, THEY GOT LOTS OF GRANT MONEY (via Mike Daley):

Another God That Failed (Tom Bethell, 3/4/2004, The American Spectator)

HUMAN DNA IS A GREAT STRING of four nucleotides, three billion letters long.
Some of these sequences -- the "coding regions" -- are called genes. They control the construction of proteins in the body. But far greater stretches of the same DNA are "non coding regions," and for many years they were called "junk." That was the word scientists used. Junk DNA had no function and could be ignored. These enormous sequences, amounting to 98.5 percent of the whole genome, were dismissed as the accumulated rubbish and detritus left behind by the constant trial and error of evolution.

Now the white-coats are beginning to suspect that they made a mistake. Wayt Gibbs reported in November's Scientific American that "journals and conferences have been buzzing with new evidence," contradicting the old idea that genes "are the sole mainspring of heredity and the complete blueprint of life." Included in this "unseen genome" is the 98.5 percent that had been
"written off as irrelevant." Some scientists now suspect that the key to understanding what makes one person different from the next is, precisely, "hidden within our 'junk' DNA."

Sooner or later this will make its way to the front pages, and we will realize that the genome project was based on a misconception. Some scientists are already arguing that the gene must be rethought and may have to be abandoned in favor of something more fluid. [...]

THE GENE MANIA OF THE LAST generation has had serious consequences. Above all it has led to what is surely the most serious error of modern medical science -- the unproductive 25-year pursuit of the theory that mutations or "spelling errors" in the genome turn normal cells into cancer cells. (Wayt Gibbs also discusses this matter -- more tactfully and politely than I have
here -- in an earlier [July] issue of Scientific American.)

I believe the underlying problem is that government funding, which increasingly dominates medical research, demands that a "political" consensus be substituted for the exploration of rival theories by the normal trial and error of scientific method. Government agencies won't fund rival
theories.

A year ago, the writer Michael Crichton gave a lecture at Caltech in which he explored the harmful transition from science to consensus. His argument was fascinating. The search for extraterrestrial intelligence somehow morphed into nuclear winter, and from there, from "second hand smoke to
global warming." Science and policy have become inextricably mixed, he said. We have seen this most strikingly with AIDS -- turned now into a grossly politicized rationale for the expansion of foreign aid. We have seen it with cancer -- over 100 "oncogenes" have been catalogued, not one of which has been shown to cause cancer. And we have only begun to see it with the Human Genome Project.


Human Genome Project: Help or Hindrance? (Matthew Albright, May 2001, Genewatch)
[T]wo related indicators ––the multiple unexplored functions of the DNA sequences that constitute “the gene” and the definition of the gene itself–– may demand that the United States Patent and Trademark Office examine more closely the “utility” requirement when reviewing gene patents (Ed. Note: see Warren Kaplan’s companion article). In other words, it is hard to award a patent to an inventor who appears to have very little idea of what their invention is or how it functions.

Already, some predict that the number of lawsuits between companies that own patents on specific genes and those that try to conduct further research or explore new uses for those genes will be on the increase. 40,000 genes are not a lot to work with and the patent system does not facilitate sharing of research materials. The outcome of these lawsuits may yet find that general patents on specific genes are too broad and unsupportable in courts of law.

More likely, however, even broader monopolies may be given to those who have already patented genes or will do so soon. The human genome project has made clear that corporations that have already claimed genes as their own have, in fact, laid claim to a higher percentage of the entire human genome than they at first realized. Looking at the four leading private companies who patent genes, about 750 human genes have been patented by them so far and applications for about 20,000 more are pending. In the case that the pending patents are all awarded (which is unlikely, as many will prove to be redundant), those four private companies could own half of the human genome.

Furthermore, as Craig Venter has already indicated, the new fish to catch with patents may be the proteins. The reductionism that we have seen with the now antiquated idea of a single-function gene may simply be reconcentrated on the proteins. Proteomics, the analysis of complete complements of proteins, will take over where genomics has proven inadequate: giving simplistic genetic determinants for human health and behavior.

In order for the biotech industry to survive at all ––at the very least it has yet to break even financially–– the reductionist and determinist ideals must be maintained in their marketing. Easily definable, single-function units of biological material are necessary for making any real money. It is hard to market genes and proteins if molecular biology is continually described as a hornets’ nest of undecipherable relationships.

In the end, the results of sequencing the human genome may not affect gene patenting one way or another. Gene patenting will continue to depend on the lawyers, the biotech industry’s public relations, and the economic powers that be, who will all put their own spin on research data. Scientific results – no matter how humbling -- can never be politically neutral.


Defying Genomania: a review of It Ain't Necessarily So: The Dream of the Human Genome and Other Illusions. Richard Lewontin and The Triple Helix: Gene, Organism and Environment. Richard Lewontin (Robert Dorit, American Scientist)
[A]s Lewontin's books make clear, with the success of the Human Genome Project, the era of naive reductionism—the very perspective that promoted an almost exclusive emphasis on genome sequencing over the past decade—may take its final bow.

For the past three decades, molecular biology has been a phenomenally productive branch of the natural sciences. Successes have come in part from a commitment to the notion that complex organisms can best be understood by examining their parts. The advent of DNA sequencing promised to reduce life to its simplest components, the units of inherited information. Decoding the sequence of DNA (soon rechristened "the master molecule") seemed to promise the resolution of the most recalcitrant problems in biology. Yet as soon as significant amounts of sequence began to accumulate, it became obvious that things were not as simple as we might have hoped. My molecular biologist colleagues have voiced their frustration and bewilderment at discovering just how unintuitive, disorganized and plain inefficient genomes have turned out to be (an outcome less surprising to evolutionary biologists). Nonetheless, despite this messiness, molecular biologists have kept the faith—at least in public—by arguing that the sequence was incomplete, with key bits missing, or was the wrong kind of sequence. Those excuses no longer hold.

The completion of the Human Genome Project means we will soon have to confront the fact that, fascinating and useful as the complete genome of a complex eukaryote is, sheer information will not resolve the central questions in human biology. Personally, I find it comforting to think that our mission as biologists goes beyond the tedious accumulation of sequence (sequencing being one of the more numbing activities in our profession). After all, it confirms that the difficult problems in our field are conceptual—more data are always welcome, but not in lieu of thought.

For some time now, Lewontin has been warning that the pieces of the human puzzle will not all simply fall into place when the sequencing is done. The Triple Helix and It Ain't Necessarily So take clear and direct aim at the way much of biology is now being done. Lewontin's claim is radical and convincingly argued: The world is complicated, and the current way we approach that world is in subtle ways defective. These essays make clear that the problem has never been insufficient data, but rather insufficient understanding of that data, and specifically of the relationship between parts and whole in living systems.

Much has been written about the tension in biology between holistic and atomistic perspectives. Unfortunately, critiques of reductionism have often suffered from a certain romantic longing for a more mysterious, less explainable world. Lewontin will have none of it. From the outset, these books make clear that a commitment to material explanation is not negotiable, nor is it automatically a vote for the reductionist approach. Lewontin makes a riveting case for the interactionist perspective, based on the notion that living systems arise at the intersection of multiple weak forces. That postulate carries with it profound ontological implications: No single force, factor or source of data is likely to explain fully the world as we see it. Equally important, if the interaction of many weak forces dominates outcomes in living systems, we cannot learn much by isolating a single factor and studying it intensively, since in so doing we obscure the very interactions that we wish to understand. Lewontin's version of the uncertainty principle is that the emphasis of reductionist biology on parts, on holding everything constant while we tweak a single variable, destroys precisely what we need to examine.


Gotta love Mr. Lewontin's faith that the problem lies in the naivety, not the reductionism.

Posted by Orrin Judd at March 4, 2004 7:55 AM
Comments

HAH! I knew it, I knew it, I KNEW IT! I wrote a short fan story about three years ago in which I postulated that the "junk" DNA was really encoded instructions that were decrypted on the fly to guide the pregnancy process from zygote to near birth: There was just too much happening in 9 months was my argument. At the same time, although I disclaimed any proof that "junk" or "Vestigial" DNA was used to build babies, I DID express doubts, based on prevously failed arguments advancing "vestigial" organs as proof of evolution, that the labelling of the DNA as "junk" was premature!

Thank you!

Posted by: Ptah at March 4, 2004 8:11 AM

While I won't argue with the latter two articles or OJ's response to the last, I have to note that the American Spectator piece, as American Spectator pieces are wont to be, is moronic. How is it, exactly, that the genome project--which involved not only the sequencing of the genes themselves, but of all of that presumed "junk" as well--was misconceived, when the data that came from it will be crucial in evaluating the contribution of all of that "junk?" How can anyone claim that the theory that mutations can lead to cancer is unproductive, when we know of several inherited genetic mutations that do in fact predispose to cancer (and often very specific ones, at that), and we have at hand an extremely useful model for colon cancer that involves nothing less than a cascade of mutations?

The "consensus" forced by government funding is a real issue, although not as debilitating as Crichton would have it; similarly, there are problems with the genome project as well, most notably the fact that the human genome is a moving target. But the Spectator article gives the impression that more is at stake than is the case, and it suffers from a political agenda ("white coats?") that imposes a willful ignorance. On the scale of despicableness on which any Spectator article must be ranked, this one isn't so high, but it's sad nonetheless.

Posted by: M. Bulger at March 4, 2004 9:33 AM

I think most scientists working in the field already know the genome sequence is not going to be the instant key to solving all the questions regarding biology.

But having it does make experiments and research on any number of smaller, more focused questions much easier. It's going to be a very helpful tool in years to come.

The article itself seems like something cooked up by a writer with a grudge against evolution and abysmally little knowledge about science. For some reason he spins off into a weird tangent into how cystic fibrosis is yet to be cured. The failure to design an effective gene therapy vector is another problem altogether entirely separate from the utility of sequencing.

And he must have been on crazy pills with his oncogene remak.


Posted by: M Ali Choudhury at March 4, 2004 9:33 AM

M:

What good has knowing any of that done?

Posted by: oj at March 4, 2004 11:33 AM

OJ: Knowledge of genetic predispositions to cancer facilitates earlier detection--if you know you're predisposed to cancer of the retina, you're more likely to have the doctor make a thorough check every year, whereas most people wouldn't need (or ask for) such attention to a given part of their anatomy. Knowledge of the sequence of mutations that lead to particular cancers has provided a more rational basis for choosing drug targets, and a number of new treatments have emerged from this approach. Should you eventually develop a tumor yourself someday, you will doubtless learn all about them. No magic-bullet cancer "cure," perhaps, but 5-10 years of life where it didn't exist before.

You could argue about whether or not this was worth the billions in government money invested in the research that led to it. You really can't say that it was unproductive money, though, unless you're just not bothering yourself with facts.

Posted by: M. Bulger at March 4, 2004 12:46 PM

M:

And we didn't know who was predisposed before just by doing family histories?

And when I have that tumor we aren't going to attack it with the same methods we have been?

Posted by: oj at March 4, 2004 1:05 PM

I think I can answer for M. No and no.

It would really help if people who want to critique biology would first find out what it is biologists do think.

Most evolutionary biology is not reductionist, and it would not be too hard to find strong antireductionist statements in various special fields.

Futhermore, I cannot remember any research scientist ever saying that the goal of decoding the human genome was to have a list of the genes. They all referred to it as a fundamental tool, rather like the biannual list of subatomic particles issued by Lawrence Livermore Laboratories. Nobody memorizes the masses of the particles just to know their masses. You look up the masses to plug into interesting questions.

Genome, same way.

Besides, for nearly the last 40 years, if you examine, for example, inaugural addresses to biological societies, you will find a consensus that the current great project of biology is to decipher what is sometimes called the riddle of development. What Ptah wrote about (and an intriguing hypothesis it is, too).

It isn't the 1860s any more, except at the ICR.

Posted by: Harry Eagar at March 4, 2004 2:07 PM

"And we didn't know who was predisposed before just by doing family histories?"

You didn't know with as much certainty. And not everyone is privy to their family history. Beyond this, if the Spectator imbecile is right and the theory that mutations can lead to cancer is unproductive, then why would family histories be useful at all?

"And when I have that tumor we aren't going to attack it with the same methods we have been?"

In part, you will. But there are more tools in the arsenal now, and many of them work better and with fewer complications than the older ones.

Posted by: M. Bulger at March 4, 2004 2:27 PM

So we've got some increase in certainty and some technical innovation? Wow!

Posted by: oj at March 4, 2004 2:34 PM

Yeah, those extra years of life, and the added quality of it, are just so trivial.

Posted by: M. Bulger at March 4, 2004 2:47 PM

An interesting read is "How the Leopard Changed its Spots."

It is a critique of Darwinism, in that the current synthesis, and biology in general, takes too simplistic a view of how the phenotype and genotype are related.

But never mind that. Even a journey of a thousand miles starts with the first step, without which the destination can never be reached.

Posted by: Jeff Guinn at March 4, 2004 6:42 PM

Tell it to Burke & Wills

Posted by: oj at March 4, 2004 6:44 PM

My eye doctor uses laser surgery on me, and according to him, 15 years ago, he'd have just had to let me go blind.

But he says that within a short time -- maybe just 3 years -- laser surgery (which is expensive and kind of dangerous) will be obsolete, I'd just have to take a pill.

I don't have retina cancer, but Orrin's idea that medicine has gone far enough is just silly.

Posted by: Harry Eagar at March 4, 2004 8:39 PM

That's technology, not science.

Posted by: oj at March 4, 2004 8:43 PM

It's not only science, it's darwinian science. Depends on a knowledge of molecular biology that in turn depends on evolution being the correct description of how physiologies develop.

Posted by: Harry Eagar at March 5, 2004 12:00 AM

How can technology be separated from science ?

Posted by: Michael Herdegen at March 5, 2004 4:51 AM

Harry:

It's surgery done with light instead of a blade.

Michael:

We don't need to understand things in order to do them, as with Harry's eye or cancer surgery. We still treat things exactly the way we did a hundred years ago--find the thing causing the problem and forcibly remove it. We still, for the most part, just treat symptoms, not causes. And that only requires technology.

Posted by: oj at March 5, 2004 7:06 AM

Jeff:

"Even a journey of a thousand miles starts with the first step, without which the destination can never be reached."

How positively teleological of you.

Posted by: Peter B at March 5, 2004 8:05 AM

heh.

Every teleological journey starts with a bold first step.

Every non-teleological journey happened to blindly stumble this way.

Posted by: Brit at March 5, 2004 9:59 AM

But they all know where they're going--to right here.

Posted by: oj at March 5, 2004 10:11 AM

Aye, of course they know where they're going...

One stromatolite to another:

"keep reproducing son, and in 3.5 billion years your great-great-times-googolplex-grandson can build a Starbucks in this very spot..."

Posted by: Brit at March 5, 2004 10:44 AM

Strombolites don't believe in Darwinism, Darwinists do and all it had to do was offer an explanation of how we got here.

Posted by: oj at March 5, 2004 10:52 AM

Laser surgery is, indeed, just surgery. But the pill that will replace the surgery -- it's almost here -- is being developed out of darwinian science.

My eye doctor, who is something of a ham, puts it this way (imagine theatrical gestures): In a few years, the young doctors will be saying, "You cut them? How barbaric!"

Posted by: Harry Eagar at March 5, 2004 11:36 AM

My wife had laser surgery--very much a cast-aside-your-crutches kind of miracle. From 20-600 to 20-20 in little enough time to return change on a half-hour.

Except it wasn't a miracle. Lasers and optics and computers are all very much the products of science.

Peter:

I think you are beginning to see the difference between teleological and non-teleological.

Scientists typically start with a goal in mind.

Posted by: Jeff Guinn at March 5, 2004 7:54 PM

When we were kids we used to burnb ants with a magnifying glass, all we've done is build off of that. It's simple technical innovation, not any added understanding of ourselves or the world.

Posted by: oj at March 5, 2004 9:10 PM

You speak of technical innovation as being simple.

I'll bet if you had actually done some, you wouldn't think it simple at all.

Posted by: Jeff Guinn at March 6, 2004 8:55 AM

As the co-inventor (along with the Other Brother) of the snurf board (now called snowboarding), I can indeed say that technical innovation is child's play.

Posted by: oj at March 6, 2004 9:14 AM
« NO LONGER STARTLING: | Main | BRING IT ON: »