The power of delusion -- genetic causality

What was reported as a dramatic event came this week, if we are to believe, in the official recognition of the fact that human genes co-operate as complex systems, not as some sort of "one gene, one function" machine tools.

Here's the heart of the New York Times article today (7/2/07) by Denis Caruso, identified
as follows: "Denise Caruso is executive director of the Hybrid Vigor Institute, which studies collaborative problem-solving. E-mail: dcaruso@nytimes.com."
A Challenge to Gene Theory, a tougher Look at Biotech

The $73.5 billion global biotech business may soon have to grapple with a discovery that calls into question the scientific principles on which it was founded.

Last month, a consortium of scientists published findings that challenge the traditional view of how genes function. The exhaustive four-year effort was organized by the United States National Human Genome Research Institute and carried out by 35 groups from 80 organizations around the world. To their surprise, researchers found that the human genome might not be a “tidy collection of independent genes” after all, with each sequence of DNA linked to a single function, such as a predisposition to diabetes or heart disease.

Instead, genes appear to operate in a complex network, and interact and overlap with one another and with other components in ways not yet fully understood. According to the institute, these findings will challenge scientists “to rethink some long-held views about what genes are and what they do.”

[T]he report is likely to have repercussions far beyond the laboratory. The presumption that genes operate independently has been institutionalized since 1976, when the first biotech company was founded. In fact, it is the economic and regulatory foundation on which the entire biotechnology industry is built.

But when it comes to innovations in food and medicine, belief can be dangerous.

Overprescribing antibiotics for virtually every ailment has given rise to “superbugs” that are now virtually unkillable.

The principle that gave rise to the biotech industry promised benefits that were equally compelling. Known as the Central Dogma of molecular biology, it stated that each gene in living organisms, from humans to bacteria, carries the information needed to construct one protein.

The scientists who invented recombinant DNA in 1973 built their innovation on this mechanistic, “one gene, one protein” principle.

Because donor genes could be associated with specific functions, with discrete properties and clear boundaries, scientists then believed that a gene from any organism could fit neatly and predictably into a larger design — one that products and companies could be built around, and that could be protected by intellectual-property laws.

In the United States, the Patent and Trademark Office allows genes to be patented on the basis of this uniform effect or function.

In the context of the consortium’s findings, this definition now raises some fundamental questions about the defensibility of those patents.

“We’re learning that many diseases are caused not by the action of single genes, but by the interplay among multiple genes,” Ms. Caulfield said.

Even more important than patent laws are safety issues raised by the consortium’s findings. ...

“Because gene patents and the genetic engineering process itself are both defined in terms of genes acting independently,” he said, “regulators may be unaware of the potential impacts arising from these network effects.”

With no such reporting requirements, companies and regulators alike will continue to “blind themselves to network effects,” he said.

Now, the field of "Systems Dynamics", celebrating its 50th anniversary this week, is devoted to studying how to describe, analyze, and design complex systems made up of many components interacting in "non-linear" ways -- which is to say, interacting so that any given "function" is carried out by many different components acting in concert.

This property, which I've been calling a "scale-invariant" design principle, can be found at all levels of life, or any computer system, from cellular components to genetic "circuits" to humans in a sports team or office, to scientists themselves doing research, to the role individual corporations have in the ecology of the economy.

The big question in my mind isn't really that genes interact and cooperate in getting their chores done -- it's that our best researchers took 31 years to figure this out, working together, in the face of what is sure to be seen, in hindsight, of overwhelming evidence that it is true.

This gets me back to yesterday's post on "The Power of Yarn", and the single sentence that captured the essence of that for me in the Yarn Harlot's story " There are some truths. Things that just are the way they are, and no amount of desperate human optimism will change them."

One of these truths is that living things operate in complex ecologies, not designed to make life easy to analyze. Another such truth is that "feedback is important" and that, again quoting the yarn harlot,

See how 10 is bigger than 9? See how there is no way that 10 can be made smaller than 9?

I've been asserting almost daily that the "scientific method" has a major weakness, as practiced, in that it focuses our attention on separable parts and analysis based on the General Linear Model, that assumes critically that causality is not circular - that is, that there are no feedback loops. Unfortunately for those who wish for such simplicity, Life is dense with such feedback loops, if not actually defined by such loops.

It is an astonishing fact of life, which the Times article reveals, that the desire for life to be simpler is so powerful that it can cause 10,000 "trained" scientists, with PhD's, to take 30 years to finally collectively observe what others outside their mutual-blindness-field already knew.

As I've said, textbooks such as "Feedback Control of Dynamic Systems" are in their 5th editions in Control System Engineering, but biologists, and much of public health's biomedical research community, discount that literature to the point of invisibility and effectively treat it with contempt. To them, this literature does not exist. When seen, it "comes as news to them", and is promptly forgotten, because it conflicts with the shared myth of their culture, and cultural myths always win out over boring contrary evidence.

Science, as an enterprise, as practiced by real people in the real world, is not immune or exempt from such behavior. I really must tip my hat to the late Dorothy Nelkin, who gave a graduate seminar back in the 70's or so at Cornell in "The Sociology of Science", for awakening me to this fact, which, as a physicist by training, was "news to me."

Similarly, Science, as an enterprise, and Medical Science as well, should not be astonished, but often are, that people outside their internally-blinding-fields have less regard for the collective ability to discern truth than the scientists inside the myth-field would expect. In fact, it sometimes appears from outside that the "scientific method", as practiced, produces a type of "idiot-savant" who can see with tremendous power along such a narrow trajectory that they have almost complete peripheral blindness. Their history of crashed theories and trail of mistaken certainties are painfully evident to outsiders, but almost invisible from within.

If confronted with the trail of past casualties of the "scientific method" we get a response that "see, it works!" when , as with biology, in only 30 years they get around to being forced to see something that makes their life more inconvenient and part of their training irrelevant or impotent. Comfortable delusion wins out, especially if shared with everyone nearby and only challenged by distant outsiders who are clearly ignorant fools.

So, yet, it is true, that some biologists have started to realize that in some cases Life involves complex systems and feedback. Perhaps in another 30-50 years, this will be dealt with, and, golly, they might realized that feedback crosses the vertical hierarchy and "local" events may in fact be determined by "distal" factors or even social factors. But I won't hold my breath, because, (a) I can't hold it that long, and (b) this fact would be so inconvenient, and such a problem, that it will find some way to be rejected yet again for another 30 years.

Yesterday, somehow prompted by doing the Time's Sunday Crossword puzzle, I came across a history of how the US Military stubbornly refused to see that airplanes could possibly damage ships at sea - a fact that flew in the face of existing "doctrine." Just as Semmelweiss was ostracized and removed for his myth-challenging assertion that it was doctors' dirty hands that were causing women to die in labor or surgery, so Billy Mitchell was court-martialed for convincing the military that their official doctrine had clay feet.

It is a little puzzling that very good researchers, who wouldn't think of peeking at the identifiers of samples in doing a double-blind experiment to defend against bias, can operate in a world with such huge, collective bias against certain ideas and be oblivious to it and resistant to the meta-idea that such bias exists and that they, caught up in that non-level playing field, have a huge effective bias affecting their results that they are unaware of and not properly countering.

If they knew it was there, yes, the would adjust for it. I love scientists. Part of my heritage is science. They're good researchers, but they're simply not familiar with the power of context to focus and blind and bias their very own selves to facts that are trying to leap off the page. Stephen Jay Gould documented much of the power of this effect so well in The Mismeasure of Man, but most scientists haven't read that, or think it doesn't apply to them because "they're very careful."

This is the heart of all the work in high-reliability systems as well-- how to overcome collectively formed mental models and myths and paradigms that have taken hold and are now blinding everyone to facts they should be seeing, but aren't.

Well, maybe at last, with computer modeling and the power of interactive animations, researchers may realize at last that bias comes in many sizes, and the larger models are almost as hard to see from those embedded within them as gravity waves.

It's not just scientists that are prone to this, but many of the rest of us have a little more humility or experience and realize our judgement is not 100% reliable. Scientists when they have checked off the boxes within their own tiny trajectory that has now become their entire world seem, collectively, to lack such humility - sort of an iatrogenic side-effect of the PhD process and of hanging around a very non-diverse crowd that shares the same viewpoint.

These silos of tertiary specialization are the source of much friction, particularly if it is not recognized that the distortion of the perspective of the silo is causing the blindness.

More on this in some later post. It's too important to breeze by, and core to the frustrating battle between religion and science over large-scale social processes.

This is the challenge all organizations, all cultures, all s-loops face -- how to achieve dynamic stability, to be resistant to type-1 errors of being too gullible and believing flashes in the pan, but of being still capable of avoiding type-2 errors - of being to stubbornly fixed on a particular data value, or mental model, or paradigm, or goal-set, or identity that it cannot accept any feedback at all and there is no reasonable way to get updates up to the top where they do any good.

This is perhaps the single largest core cybernetic challenge for a survival-enhancing model.


Wade

Should the FDA regulate tobacco?

According to the New York Times today, "Report Seeks FDA regulation of Tobacco",

A report from the Institute of Medicine, part of the National Academy of Sciences, urged Congress and the president to give the Food and Drug administration the authority to regulate tobacco.

Use of tobacco is recognized in Public Health as the second largest cause of premature death in the world today. The World Health Organization estimates that half of the smokers will be eventually killed by that habit, with the death toll 5 million people per year now, and rising.

So, this is a surprising thing. The USA launches a whole occupation army and spent over a trillion dollars because 3000 people were killed. But the same country sits by and watches the tobacco industry kill 5 million people a year, every year, and that's no big deal.

We really need to pause and make sense of these observed facts, and what they can teach us about ourselves.

There is a very long history of attempts to regulate tobacco, which has a specific exemption put in place by our very own Congress, specifically to prevent such regulation. Any consideration of that kind of regulation also has to look at the dismal results when the US tried to regulate the sale of alcohol during "prohibition" with a constitutional amendment.

The Times story continues:

The report said cigarettes contained carcinogens and other dangerous toxins and would be banned if federal laws did not exempt tobacco. A bill before Congress would give the F.D.A. regulatory authority, but the agency’s commissioner, Dr. Andrew C. von Eschenbach, expressed skepticism, saying that if nicotine levels were reduced, smokers would change their habits to maintain current levels. The report also called for higher tobacco taxes and a national ban on indoor smoking.

The Johns Hopkins Institute for Tobacco Control estimates that 1 billion people will die prematurely, in the 21st century, from use of tobacco. According to that site, "The Institute for Global Tobacco Control works to prevent death and disease from tobacco use through research, education and policy development."

Apparently, "research, education, and policy development" have not been very successful and solving this problem.

In fact, while non-smoking areas are now commonplace in places wealthy Americans hang out, the companies have only moved operations abroad and expanded them tremendously. The death toll is expected by WHO to double in by 2020, to 10,000,000 people - a year, each year.

I would like to suggest that "research, education, and policy development", while helpful locally, will never solve this problem.

There are two reasons I think that, related to the whole theme of this weblog.

First, our ability to reason about such things is poor. The fixation on numbers in much of Science, and explicit belief by many that only numeric results are meaningful, has short-circuited our ability, as a society, to reason correctly about things that cannot be measured with numbers. Even for things that can be measured with numbers, the fixation on linear statistical models has short-circuited our exploration of feedback models.

In the perverse way of complex systems, our biggest problem is now of our own making. Like the blades of a helicopter, we must travel in our own wake. The very success of the mechanical view of the universe, of Science and technology, and of linear statistical models have made it almost impossible to now move forward from there. These techniques have, effectively, become religions, defended with blind religious zeal against perceived enemies at the gates.

So, when we are confronted with a problem which shimmers and changes with the size and scale of the observer, we are effectively paralyzed. Do tobacco companies kill people? On the scale of populations, the cause and effect is clear and unambiguous, and satisfies all the requirements of causality, except one we'll get to. Raised marketing efforts by tobacco companies precede and have a dose-response relation to the number of people smoking and the number of people dying. Etc. The problem is that if we shift lenses, on the scale of individual humans, this relationship is no longer "causal." Individuals have free will. Any particular individual may or may not respond to marketing efforts by the tobacco industry. The solidity dissolves.

It's not that there is no solidity to the causal argument - it's that the solidity depends on scale, which is a concept that is not yet recognized as pervasive and important.

I go on about this at great length in some other posts. ( Search "scale" or "causal" in the search window above to find them. ) See "Ten most important lessons from physics" for a discussion of how even water pipes have this property. From a human scale, there are entities called pipes, and water towers, and faucets and there are measurable factors like pressure and volume and flow-rates. These seem very solid. But if you drill down to the molecular level, this solidity dissolves. Molecules don't think, or act, or respond to any of that. Those words are meaningless to molecules. Molecules just respond to their local environment, and their neighboring molecules. A given molecule may linger at the pipe wall forever, it doesn't matter.

A few more such examples are given in my post: Amazing devices to impress your friends.
These include hollow tubes that cause air to separate into boiling hot air and air so cold it creates frost, pumps that pump water uphill with no power source and essentially no moving parts, hollow spaces that convert battery power to microwaves in one step with no moving parts, etc. These are all commercial, off-the-shelf devices, not my imagination gone wild.
They also all have the property of being globally causal and locally non-causal. Like the photo of Marilyn Monroe or Einstein, depending on how far back you stand from your monitor, they are both at once and fall into a space we are not taught about in school.

The second reason that "research, education, and policy development" have not been very successful and solving this problem of tobacco-related deaths is that this is a spiritual problem, and it will never yield to technology.

As T. S. Eliot noted, in Choruses from The Rock (1934):

They constantly try to escape
From the darkness outside and within
By dreaming of systems so perfect that no one will need to be good.
But the man that is shall shadow
The man that pretends to be.

Or, more precisely, the society that is shall shadow the society that pretends to be. Any individual effort to change the situation with respect to tobacco use will fail on two fronts.
First, the industry will fight back, and that is a cross-scale fight that pits corporations against individuals and guess who will win. Second, human weakness will fight back against our best intentions for our own behavior, and we will give in, as we did with alcohol. The latter is what the FDA Commissioner was referring to, in that regulations limiting tobacco per cigarette would only increase the number of cigarettes smoked until the same physiological hit was obtained, making the industry even richer.

In the contest between an individual and a multi-billion dollar corporate marketing campaign, it is not likely the individual will win.

There are exceptions. For instance, the population of Latter Day Saints (Mormons) in Utah has a well-documented life expectancy ten years longer than the average for the US, and one reason is that they prohibit smoking and drinking.

Look what is going on here. It is not the individuals that are fighting off the temptation to smoke or drink, but the larger scale entity, the, gasp, organized religion, that has succeeded where
"research, education, and policy development" have all failed.

One of the youth in our community asked one day "Why do we need organized religion? Why can't we all just worship God on our own?" The answer is visible in Utah -- larger scale entities can do things that smaller scale entities cannot possibly ever, ever, ever do on their own.

This is not a "cognitive" thing. Yielding to temptation and losing ability to deliver on one's own intentions is a function of being disconnected from a larger entity that helps shape and define and support you, and provides you what structural engineers call "active strength." The simple fact is that human beings are heavily influenced by peer pressure, whether they like it or not, or believe it or not, or have IQ's of 200 or 20.

It's not so much a question of which entity to belong to. Pick one that looks good. What matters is belonging to something larger that supports the values you desire your "self" to have.

Life is too complex to go it alone. We've seen to that. The one church that does not work, and will never work, is "rugged individualism." Whether you believe in God or not, or evolution or not, the math is the same - no individual will ever be as strong as a strong group. In the end, strong groups will win. Multi-celluarism always wins out, in the end - it's just a better solution. The fact that you're reading this shows that multi-cellular architecture can work, because that's exactly the operating principle your body uses to orchestrate a trillion cells and get one body. We're swimming in examples of this working.

Wrapping up the social thought - tobacco deaths continue because we accept them. If we, as a society, collectively, decided we didn't want our companies killing 5 million people a year, we could stop that cold. Such an action requires moral conviction and group solidarity of a type that will not come from "research, education, and policy development".

Such an action requires a change of heart.

Change everyone's heart, and the "problem" will dissolve. Suddenly, "we" will be at the same scale as "the problem", and the "problem" will simply evaporate.

So, I'd suggest that focus as the most likely to succeed. It demands that we come to grips with larger questions of society, morality, religion, science, and our own nature. It's not a simple thing to do, but, from the reasoning above, it looks to me like the easiest thing to do that has a chance of working, based on fundamental principles of what's going on here and the evidence at hand of what works and what doesn't.

Religion, like gasoline, is volatile. It releases tremendous energy in people, for good or bad. It can be misused, and it can kill. It can also power our lives with non-polluting ability to cope.

We don't need to throw out religion. We need to understand, when it works, why it works. There is no shorter path to the solution to the problems we've now made for ourselves, and no path that doesn't involve these questions.