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08
May
10

the universe: it scales

In a recent post I listed books that really made an impression on me over the past couple of decades. They all had one thing in common: they all addressed parts of the scientific challenge of understanding the world from its most fundamental forces at the infinitely small-scale of sub-subatomic particles all the way up to the vastness of the outer fringe of the universe.

The trick is, regardless of where phenomena fall on the space/time scales, they observe laws and constants that are consistent with one another. Science, as a cardinal principle, rejects the notion that some phenomena work in ways that contradict phenomena on a greater or lesser scale.

That’s not to say that there aren’t some knowledge gaps in that concept. Some ssubatomic particles are still being sought by pushing smashing energies to new thresholds at the recently fired-up Large Hadron Collider (LHC). The goal of the LHC  is: “To smash protons moving at 99.999999% of the speed of light into each other and so recreate conditions a fraction of a second after the big bang.” The most minute fragments of matter and energy that come from these head-on collisions are consistent with the awesome images seen with other science tools like the cosmic gaze of the Hubble Space Telescope.

But the most fascinating thing for me is the very, very special scale of size and energy that has produced — at least here on Earth — the most complex processes of matter and energy we know of. We call it life. Even one cell is a more complex, subtle configuration of matter than any non-living entity. But life’s working processes are consistent with all the rest of natural forces smaller or greater in the universal scale. The universe permits complexity at all levels, but the greatest complexity evidently is reserved for a relatively narrow band of size (from macromolecules to the largest mammals) and of energy (from bacteria living in sub-surface lakes in Antarctica to the ecosystems of “smoker” vents of volcanic gas deep in mid-oceanic ridges).

Another reason this is fascinating is that the 21st century is seeing an intense examination of the size range of the constituents of living organisms. Physicists are making the most exquisitely sensitive measurements ever done of forces within atoms and molecules. Those measures and the incredible instruments that do them are not only providing insight about how the complex molecules of life operate (e.g., protein folding and mechanics) but we are on the verge of practical application in nano-scale devices previously considered the unfettered dreams of science fiction. For the last decade proofs of concept in nanotechnology have been making huge strides. Now attention is turning to the practical production of useful devices for medicine and electronics.

Since the industrial revolution we have mastered the control of vast energy to transform gross matter for what we needed. We’ve marveled at river-changing dams, skyscrapers, equipment that scrapes out hundreds of tons of earth in one pass, and rockets with thousands of tons of thrust. Now it will be our time to marvel at things way below our range of vision but that do things we’ve not experienced before. Mastery of the minute details of life processes will likely have greater transformational effect in the centuries to come than anything that has gone before.

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21
Apr
10

good news from the abyssal plain

I saw something the other day about life on Earth that gave me a lift. Science Now reported that the Census of Marine Life, after a decade of surveying marine organisms all over the world, has documented that 90% of the ocean’s biomass consists of microbes, larvae, and plankton. The total mass of these little critters is equivalent to 240 billion elephants! Elephant-equivalents. The researchers pulled the creatures from the sea itself, from the mud, from the deep-sea vents, and from the bottom of the abyssal plain. (The phrase “abyssal plain” gives me the chills!)

Using new generation sequences researchers identified 18 million DNA sequences. Mich Sogan, a Woods Hole scientist, says “there could be as many as a billion bacteria and archaea, another group of single-cell organisms like bacteria.” A couple of interesting findings are: 1) the microbial diversity increased the deeper they looked in the water column, 2) but sometimes a microbe’s environment  is simply one other organism.

A bonus interest for me is to learn that the richest marine organism environment is the plateau off the Pacific Northwest Coast where 25,000 to 35,000 different microorganisms live in each litre of sea water. I’m writing this post from Beaverton, Oregon, where my wife and I are planning to move next month. So I can just drive to the coast and wade in the rich microbial soup.

All this lifts me because I relish the thought that here on Earth, whether or not we humans commit to being responsible stewards to the one life-perfect planet we know of, the richness of life code on the planet is ineradicable. Human affairs often discourage me, but life is indomitable. The Earth has occupied a sweet-spot for life for billions of years and will continue to for many more.

12
Apr
10

books that changed my life

My wife and I are moving out of state next month, so we’re unloading stuff we don’t want to transport. I’ve had to look at my book collection and cull the ones I can live without. In the process I realized there’s a small set of books that have framed my way of looking at the world and kindled passions that will continue the rest of my life. They’re the books that have old yellow stickies sprouting from between the pages, yellow highlights and scribbles in the margins. I donated about 60 books to the local library, but these I’ll keep to the end.

Eric Jantsch, The Self-Organizing Universe: Scientific and human implications of the emerging paradigm of evolution, 1979.

Actually, I found this book after reading James Gleick’s, Chaos. Chaos was an unusual best-seller in ~1987 I guess because we all experience “chaos” (in the colloquial sense) in our lives, and people evidently were looking for some insight. A lot of readers never finished the book because it explored the physics and mathematics of chaos, not necessarily the common term. Nevertheless, Chaos made the term “butterfly effect” part of our vernacular. It was a good introduction to chaos theory, but by the end of the book I was wondering: “With chaos being so pervasive in nature, how is it we see order and organization?” Jantsch’s book tackled that conundrum.

Basically, Jantsch presented a framework for how the world organizes via hierarchical systems from the fundamental dynamics of the micro (atomic forces, molecules and basic physical properties) through simple living entities, complex organisms, ecosystems, and social systems. It is a set of concepts that are a theory of organization from basic dynamics up through the most complex things we know, living systems and our own societies. Here’s how Jantsch defines systems:

The notion of system itself is not longer tied to a specific spatial or spatio-temporal structure nor to a changing configuration of particular components, nor to  sets of internal or external relations. Rather, a system now appears as a set of coherent, evolving interactive processes which temporarily manifest in globally stable structures that have nothing to do with the equilibrium and solidity of technological structures.

The mind-blowing idea that came through in this work is that there are processes that, when fed by external energy flows, can become so stable that we think of them as things. Especially in living systems, a lot of things are really just processes that persist as long as the right conditions exist and only that long. They’re called “process structures.” It looks like an oxymoron, but you can perceive some persistent processes as structures. When you get that, it tends to alter your notions of permanence and change. Some complex systems such as living organisms persist during what we call life, but when the sustaining conditions end the processes collapse and it’s all over.

Humberto Maturana and Francisco Varela, The Tree of Knowledge: The biological roots of human understanding, 1987.

The authors of this book set out to show that cognition is not simply our eyeballs and brain somehow internalizing what’s “out there” but is absolutely contingent on our biological structure and processes. Moreover, cognition is a result of our experience and interaction with other people through language. Their notions are pretty trippy. The book’s cover art is a Salvador Dali painting. But the key for me is that they build their argument for how “knowledge” works from the ground up, starting with processes of self-organization at the molecular level. From there they describe how living things come about through a process of  “learning” clear up through humans with our shared knowledge and shared cognition.

Maturana and Varela’s key idea here is autopoiesis, self-organizing systems similar to Jantsch’s ideas.

Our proposition is that living beings are characterized in that, literally, they are continually self-producing. We indicate this process when call the organization that defines them an autopoietic organization. […] The most striking feature of an autopoietic system is that it pulls itself up by its own bootstraps and becomes distinct from its environment through its own dynamics, in such a way that both things are inseparable.

Werner Loewenstein, The Touchstone of Life: Molecular information, cell communication, and the foundations of  life, 1999.

Backing up all the way, Loewenstein goes about explaining the organization that enables the complexity of living things by starting with entropy and information theory. You can’t get more basic than the laws of thermodynamics!

Neither Jantsch’s or Maturana and Varela’s books deal in detail with how information in chemistry figure into their notions of self-organization, but it’s there. Loewenstein makes the idea of information the theme of his book and caries it through from the idea of macromolecules clear up through cells, intracellular information exchanges, inter-cellular communication, and special information structures like neurons. But what I took away from this treatise is that the molecular structures at the cellular level are information devices as surely as the laptop I’m using to write this post. We’re so used to thinking of information in terms of human language and symbols that it seems strange to think that the conformations of proteins, DNA chains, “messenger” RNA and the intricate interactions among them are just as informational. But the robust and growing science of bioinformatics is based on just such ideas.

Dennis Bray, Wetware: A computer in every cell, 2009.

Actually, I’m just finishing this one. It’s a very interesting look at the internal informational working of cells that give these basic units of living things a capability of awareness and appropriate responsiveness that deserves more attention and respect. Cells aren’t just bricks in the wall; they’re participants in some astute biology. Wetware brings together in the cell Loewenstein’s molecular informational processes and Maturana and Varela’s philosophical views of life processes as forms of cognition and learning.

What runs through all these books is the idea that the universe’s fundamental properties and rules allow the emergence of processes of great complexity; complexity sufficient to reach the level of life and at least one organism — us — with the capacity for self-awareness and splendidly subtle thought. That’s a truly amazing range of possibilities based on some very foundational laws. How this is possible is a chain of events that we can only partially explain at this point. The rest of the story requires details we’re only getting a glimpse of right now. It’s certainly a set of riddles that will keep me fascinated the rest of my days.

27
Mar
10

do patients need doctor navigators to use the internet?

In the March 25 New England Journal of Medicine Drs. Pamela Hartzband and Jerome Groopman of published an opinion piece titled “Untangling the Web — Patients, Doctors, and the Internet” in which they expressed a lot of concerns about how the internet is putting patients in touch with a lot of questionable information about disease and about how it is changing the doctor-patient relationship in an adverse way.

Since, overall, my views are about 180 degrees in the opposite direction, I’d like to quote some of their remarks and comment on them. (I recommend reading the full article so the context isn’t neglected.)

Information traditionally flowed from doctor to patient; the physician described the genesis and course of a disease and the options available for treating it. Often, pamphlets were provided to reinforce the doctor’s explanation and advice. The patient might then receive additional input from family and friends, usually in the form of anecdotes about people who faced similar clinical situations.

I can only say from my experience that the first sentence about information flowing from doctor to patient is pretty ideal. When I started working at the community level for a large national cancer organization in the ’70s there were doctors who not only didn’t explain the disease well but there were some who chose, on the basis of their judgement about the emotional frailty of the patient, not to tell some patients they had cancer. They’d tell a spouse or adult child perhaps. Fortunately, things have improved and, hopefully, the “don’t tell” practice has been replaced by informed consent. Still, I think for many situations the amount of information going to patients is limited by the short time allocated to face-to-face interaction with doctors. I am a Kaiser Permanente client. They have implemented email to doctors, online lab results, and an online information resource. The docs don’t give full explanations unless you press them on it.

Other patients whose diseases have no ready cure are drawn to chat rooms and Web sites that may make unsubstantiated claims — assertions that macrobiotic diets cure aggressive lymphoma, that AIDS can be treated with hyperbaric oxygen, that milk thistle remedies chronic hepatitis, and myriad other fallacious claims. Falsehoods are easily and rapidly propagated on the Internet: once you land on a site that asserts a false rumor as truth, hyperlinks direct you to further sites that reinforce the falsehood. Material is perceived as factual merely because it is on a computer screen. We sometimes find ourselves in the uncomfortable position of trying to dissuade desperate and vulnerable patients from believing false testimonials. Doctors may be perceived as closed-minded, dismissive, or ignorant of “novel therapies” when they challenge such Internet rumors.

Firstly, there is absolutely nothing new about charlatans and doctors who have been peddling snake oil and gimmick cures for generations. Again, when I went to work in cancer control my organization had a major effort to combat “quackery.” Many, many cancer patients were getting all kinds of bad advice and misinformation from naturalistic health magazines and other sources. (For a thorough tour of the quackery hall of infamy, see Dr. Steven Barnett’s site Quackwatch.) People by the thousands were going to clinics in Mexico for cancer treatments no responsible doctor would perform. This was rampant decades before the internet. There was an epic, nationwide legislative battle over Laetrile, the marketing name for amygdalin from apricot pits. Despite the best efforts of medical and public health organizations, especially in California, Laetrile production was legalized in 27 states . The arguments about “freedom of choice” from the ’70s seem to have echoed down the decades and have turned up again in the rhetoric against health reform, especially in the condemnation of  comparative effectiveness determination.

Secondly, even highly authoritative institutions have to change their tune once in a while. When I joined cancer public health in the ’70s the medical community almost universally rejected the idea that food and nutrition had anything to do with the prevention of cancer. People who talked about a relation between nutrition and cancer were sneered at and called the “fruits and nuts” crowd. Thirty-five years later as I approached retirement I had to chuckle inwardly many times about the current enthusiasm for the view that diet and nutrition are key to the prevention of much cancer. These days ya gotta eat your greens and grains!

Thirdly, doctors themselves are not always reliable sources of informaiton. That’s why we have second and sometimes third opinions. Drs. Hartzband and Groopman cite anecdotes about people who believe unsubstantiated information from the internet and suffer anxiety or waste doctors’ time. But I think most of us who have been around a few decades have our own fist full of stories from our own experiences or those of friends and acquaintances where doctors have failed to diagnose something or misdiagnosed situations, where lab tests have been wrong or complex treatments have been bolixed up in a hospital. I think the public knows all too well from well-publicized reports about medical errors by the Insyitutes of Medicine that the medical system itself is far from fault free. With regard to health it’s a risky world, even in the bosom of the medical establishment.

The article concludes:

As physicians, we are struggling to figure out how best to use this technology in the interests of our patients and ourselves. Although the Internet is reshaping the content of the conversation between doctor and patient, we believe the core relationship should not change. A relative recently asked us, “What can you possibly learn from your doctor that is not available on the Internet?” We suspect we’ll hear such radical sentiments increasingly in the future. Knowledge is said to be power, and some of the past imbalance of power between patient and doctor may be equalized. But information and knowledge do not equal wisdom, and it is too easy for nonexperts to take at face value statements made confidently by voices of authority. Physicians are in the best position to weigh information and advise patients, drawing on their understanding of available evidence as well as their training and experience. If anything, the wealth of information on the Internet will make such expertise and experience more essential. The doctor, in our view, will never be optional.

Uh, count me among the radicals. Let me say that the doctors are not totally negative about the internet, but their overall conclusion is that every patient should vet all their information through their physician. It sounds like they’re saying — like other professionsals who’ve had their domain disrupted by the internet — we’d all be better off if the internet went away and we could return to the status quo ante.

I’m just here to assert that that’s just not going to happen. The genie has been out of the jug for years and it’s not going back in. The Pew Internet and American Life Project has been documenting for years now the growing reliance of the public on the internet in health matters. Doctors just don’t seem to get it that there are needs that they’re just not satisfying. The use of digital media for health information and support is only going to increase, and rapidly.

My position is not that doctors are somehow unnecessary. However, I do believe that ordinary citizens are capable of knowing much more and doing much more about their own personal health and digital systems are an evolving platform for that. And after the so-called “health reform” slugfest we’ve been through I’m even more convinced that we all need to be more autonomous. We can’t continue to depend on a cabal of politicians, doctors, hospitals, insurance and pharmaceutical companies for our health. It’s just too important.

My suggestion to physicians is, instead of promoting a somewhat idealized notion of the doctor-patient relationship unsullied by the internet, why not work with citizens, professionals, and organizations to make the internet a better platform for the public and for doctors and patients to work together around their health issues? There are many support measures that can be undertaken. If docotors are worried about accurate information then why not build a comprehensive, evidence-based, easily accessible, user-friendly information resource? Medpedia, a project started by a consortium of medical and public health schools, is an interesting and constructive exercise along this line. Only thing is, the site is not public-friendly and so far the effort appears not to have attracted much involvement from anyone but professionals.

The concern about people not being able to critically evaluate health information is certainly legitimate. In fact, evaluating ALL internet information is an issue. But where is the support system for helping people learn how to do that? Why don’t doctors and organizations get busy spelling out some guidelines for evaluation and get them disseminated through many channels? That would be constructive and doable.

There already is a kind of parallel world of information and tools starting to envelope the health sector. (Tip: If you think the internet is something, check out the apps in the iPhone App Store supposedly intended for medical professionals but perfectly downloadable by anybody.) It’s like the way the blog-o-sphere enveloped journalism. After a lot of pining for their old, defunct newspapers, more far-thinking journalists have learned how to work with digital media and to reclaim their futures. Something similar is happening in medicine and, hopefully, perceptive medical professionals will learn how to work with it rather than try to will it away.

17
Mar
10

playing by the rules

Last week I read something disappointing. An article (that I didn’t bookmark) said that in some survey Americans don’t see climate change as as much of concern as a year or two ago. That amazes me. I know it was a horrendous winter on the East Coast, and some hanky-panky dug up about some scientists involved in climate research exposed the all-too-human backside of science; but how can people with bigger stakes in the future than I have become complacent about something with such far-reaching consequences?

I’m 64 so I won’t personally experience the full consequences of climate change; I’ll have  been recycled by the worms well before the whole thing plays out. I don’t have any children, but I do have a couple of young-adult grandchildren by way of marriage who I care about. They call me “Uncle Dave.” But I don’t see how people with responsibility for tomorrow’s children can get blase about what’s going to happen 30 to 100 years from now. As I pointed out in one of my first posts to this blog, the children being born today have a 50/50 chance of living to 100. When I see a tyke being wheeled down the sidewalk in one of those strollers that looks like a spaceship escape pod I feel a pang of sadness to think that he or she might have to live in a badly degraded world with perhaps unprecedented human turmoil.

Then I read an opinion piece from the LA Times that expressed my perception of the situation very well. In a column titled “The Earth has its own set of rules,” B.E. Mahall and F.H. Bormann said the following:

The Earth has its own set of rules, solidly grounded in laws of physics and chemistry and emergent principles of geology and biology. Unlike our economic model, these are not artificial constructs. They are real, and they govern. Earthquakes, tsunamis, volcanic eruptions, hurricanes, tornadoes, 100-year floods, massive wildfires and disease epidemics are dramatic examples of parts of nature, neither all service nor all harm, creating and destroying, and governed by rules that are indifferent to humans. Our anthropocentric economic model for interacting with the world ignores and is proving to be incompatible with Earth’s rules, and is therefore on a direct collision course with them.

To achieve a more accurate model of our relation to nature, we need to see ourselves as part of nature, governed by nature (not economics), beholden to nature for ecosystem services and subject to nature’s disturbances.

Precisely! The Earth is a platform that has occupied a sweet-spot around the sun for several billion years that has permitted the most complex things in the universe we know of to evolve. Humans are at the apex of this process having evolved a capacity to comprehend the workings of Earth’s rules, to have some degree of insight and foresight about what might happen down the road, and a capacity to make choices and decisions that affect the whole. But, overall, a lot of people seem content to continue with business as uaual and just wait to see how it all ends up.

Earth is a unique place for a prolonged, open-ended experiment with life. The outcome is not determined. The universe is neither for us or against us: it’s indifferent to our welfare. It’s up to us to actively make it work out well…or not.

16
Mar
10

Article: Remember the Tamagotchi?

In Wired News last week Thomas Goetz wrote an article about how — in the rapidly emerging world of sensors and self-monitoring — we may become something like the Tamagotchis kids wore a decade or so ago. The Tamagotchi (in case you’ve forgotten) was a little character on a watch face that you had to pay attention to during the day or it got sick and even died from neglect.

The new thing is to use the medical sensors that are being developed to get real-time information from your body and use it to give you a reading on how you’re doing. This could be constructive information for a variety of health situations. I referred in my post last week on things that need to be done for a new health paradigm as an avatar system. It could live on your smartphone, pick up sensor information from your body, compare it with your on-phone health profile, and tell you how you’re keeping up with health goals like exercise. It could feed you — or nag you — with appropriate health information. I agree with Goetz that a game interface may be the most interesting way to interface with some health informaiton.

This evening I’m attending the VLAB meeting at Stanford called “The Internet of Things: Sensors Everywhere.” I hope to get a better fix on where body sensor tech is and what we can expect in the near future.

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11
Mar
10

The family genes

I’ve written several posts about how there’s been a lot of criticism this year of the meager results of gene sequencing in finding therapies for diseases. The genetic keys to diseases have proven elusive to the point there has been discouragement in the field. But there’s perhaps a more positive note in today’s NY Times about two studies being published in journals on Friday. For the last decade the operating assumption of genetics and disease is that common diseases like cancer come from common mutations in genes. But a lot of tests on the connection between genetic mutations commonly seen and common diseases was not strong. Instead the conclusion has been emerging that diseases are really linked to rare mutations. So all those news headlines you’ve seen over the last 10 years of so that declare “gene for depression found” were wrong. It’s not that simple.

For three diseases — Charcot-Marie-Tooth disease, Miller syndrome and ciliary dyskinesia — it turns out that the genetic inheritance comes from more obscure genetic changes by way of Mendelian family inheritance. The studies sequenced the whole genomes of not only the children with expressions of the disease but the parents as well. So they got what you might call the whole-family genome. Identifying diseases that manifest differently depending on the mix of genes coming from mom and dad means that the genomes of the whole troop might be needed.

Fortunately the cost of doing a whole genome is dropping, fast. Complete Genomics of Mountain View, Calif., did the genomes in one of the studies at $25,000 each. That’s a whole lot better than the $3 billion for the first genome ten years ago. They’re promising the $10,000 genome to be followed by the $5,000 genome. Remember, the holy grail is $1,000.

I said in my previous post about the 21st century medical model that our personal health record will need to contain our whole genome. This suggests that linking the genomes of the rest of the family will make the assessments of lifetime disease risk a lot better.

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