This is by far the most constructive article on healthcare, because it clearly identifies the fundamental issue in healthcare – our internal conflict.  Here are the excerpts, but read the whole thing and forward it on.  I dare anyone to challenge this of course; that’s the whole point of discourse:

“Those following the long march to health-care reform know that one of the few things beyond argument is that the old approach is unsustainable and threatens to bankrupt the country. Perhaps a little belt tightening and bargain hunting of this sort might make our health-care dollars stretch farther”

“To help maximize the overall benefits in health care under a utilitarian framework and conditions of constrained resources, health economists use an analytic tool called cost-effectiveness analysis (CEA) that quantifies the added expenditure necessary to obtain a unit of health benefit (typically measured in quality-adjusted life years or QALYs, pronounced “kwallies”). The most common application of CEA is to examine the value of medical innovations compared to the standard of care routinely available, since new technologies are an important cause of the increase in health-care costs.

If the “unit cost” for a QALY of benefit (that is, the cost-effectiveness ratio) is less than some threshold (conventionally $50,000 or $100,000 per QALY), then adoption of the innovation is deemed “incrementally cost-effective,” since the benefit obtained compares favorably to that obtainable at similar cost using accepted medical technologies (such as dialysis, which has a cost-effectiveness ratio variously estimated at between $50,000 and $80,000 per QALY). Above the ratio, they are deemed not to be cost-effective. That is, the (relatively small) incremental benefits of the intervention do not justify the (relatively large) incremental costs.

“

“Of special interest is “Bernie’s kink” at the origin, which reveals how medical markets actually behave.  People prove to be unwilling to surrender quality using the same formula they would use to accept increased cost.”

“Of course, if all innovation in health care fell into this northeast quadrant, innovation could only increase the costs of care. That is, even so-called cost- effective health-care innovations would always cost more money than the alternatives they replaced. This is often a point of confusion, sometimes purposeful, as when our political leaders claim that “preventative medicine” is highly cost-effective and would therefore save money. In fact, while most recommended preventative services are cost-effective (meaning the value of their benefits in terms of QALYs gained justifies the costs in terms of dollars spent), only very rarely are preventative services actually cost-saving, even when all the “downstream” avoided medical expenses are folded into the analysis. Indeed, new “cost-effective” innovations are one of the principal reasons that health-care costs continue to soar.”

“the selling price (often referred to as willingness to accept, or WTA) and the buying price (willing to pay, WTP) of a QALY should be similar, and the societal threshold for accepting or rejecting a technology should be symmetric and pass through the origin of the cost-effectiveness plane as a straight line. However, as David Hume anticipated, a reproducible observation is that consumers’ willingness to accept monetary compensation to forgo something they have is typically greater, and often much greater, than their stated willingness to pay for the same benefit. Several explanations exist, including the so-called “endowment effect,” the psychological principle that people value items that they already have simply because they already have them.

A 2002 review of 20 studies by the late Bernie O’Brien and his colleagues at McMaster University found that the ratio of individuals’ WTA to WTP was always greater than 1 and ranged from 1.9 to 6.4 for two scenarios specifically related to health care. They suggested that rather than a symmetric accept-reject threshold on the cost-effectiveness plane, societal thresholds should reflect the WTA-WTP gap seen in individual preferences, which would be captured by a downward “kink” (subsequently known as “Bernie’s kink”) in the threshold as it passed through the origin, indicating that a QALY’s selling price in the southwest would always be higher than a QALY’s buying price in the northeast.

Thus, there may be an inherent cognitive bias against relinquishing the gains of health-care interventions that have already been accepted, and the cost savings from decrementally cost-effective innovation may need to be substantially greater than conventionally used thresholds suggest.“

“Indeed, fewer than 2 percent of all comparisons were classified in the cost- and quality-decreasing “southwest quadrant”, and only 9 (involving 8 innovations) were found to be decrementally cost-effective (0.4 percent of the total)—that is, they saved at least $100,000 for each QALY relinquished.”

 “That decrementally cost-effective innovations are so rarely described in the health-care literature suggests that medicine is distinct from most other markets, in which cost-decreasing, quality-reducing products are continuously being introduced—think IKEA, Walmart and the Tata car. Several reasons may explain this “medical exceptionalism.” First, there is fundamentally a lack of incentives both for physicians to control costs, especially under a fee-for-service regime, and for patients to demand less expensive treatment when insurance shields them from the direct costs of care. Second, medical “bargains” frequently come with health risks, and trading health for money strikes some as vulgar, regardless of ratio. The inherent ethical unease that decrementally cost-effective innovations can elicit poses a serious public relations and marketing challenge.”

 “But regardless of the mix, expanding coverage to the uninsured, caring for our aging baby boomers, and accommodating new, effective technologies—while still feeding, clothing, housing, and educating ourselves, and catching an occasional movie—will require our system of distribution of health services to be more cost- sensitive, and will almost certainly mean the adoption of some decrementally cost-effective strategies for saving money. For example, Canadian-style delays for expensive diagnostic or surgical procedures certainly pose real, albeit small, medical risks, and would fall into this southwest category. Getting insured Americans to accept such new risks may be difficult, but slightly quality-reducing (that is, risk-increasing) cost-saving strategies have already been widely adopted within the American system, even if not studied or widely acknowledged. The gradual increase in the “hassle factor” in accessing medical care is one covert way that the industry has found to limit the distribution of services. More overt examples of rationing already adopted include aggressively shortening hospital stays and limiting formulary options (which sometimes require patients to change from a medicine they have been tolerating well to another in the same class). Despite the fact that doctors regularly (although sometimes disingenuously) deploy patter informing patients that the hospital is a dangerous place to stay and that the formulary medication is “just as good” as the one they’ve been taking, these strategies are certainly associated with small but real risks. Even a preadolescent quickly learns the true meaning of “just as good”; perhaps a more mature citizenry can also come to appreciate some of the upside of having “just as good” alternatives.”

Related posts:

1. If Rafe Were In Charge: Major Medical Edition
2. The Climate or the Uninsured?
3. Fixing Health Care I: The Uninsured

But I have to be prepared to be more confused — and question more assumptions than I intended to — because chances are my new random placement on the landscape is initially lower than the local maximum I was on prior.  This part is scary.  People around me don’t understand what I’m saying initially because I necessarily need new words, new language, to describe the new landscape.

And rather than start totally afresh with a new lexicon, I notice it’s more productive (personally and in communication) to overload old terms and let them slowly blend into their new meanings.  We all resist the strain, especially those who did not sign up for the jump through hyperspace.  They use the hill-climbing techniques that incrementally achieve higher ground (logical deduction, reductionism) in order to deny that we are in new territory at all and “prove” every new claim as false.  But unless we eliminate most or all of our old assumptions and embrace the new ones, these techniques will always yield inconsistency.

Thus, it seems like a good idea to resist the urge to bring to in the heavy logical artillery until it’s clear we are on the upslope.  In practice what this means is adding more novelty — but not as much as last time.  This is the Boltzmann technique of simulated annealing: start with a high degree of heat/randomness and turn it down slowly, all the while pounding away with the tools of logic and reduction.

What I mean by Science 2.0 is an intentional (and methodological) injection of novelty into the scientific method.  This is the beginning of a series of posts on the hows and whys of such activity.  I hope you will join in constructively and creatively.

Related posts:

1. Non-Dualism
2. Why Falsifiability is Insufficient for Scientific Reasoning
3. Two Books On Cognitive Science You Should Read

Lee Smolin claims that AP is bad and favors a Cosmological Natural Selection view instead (on grounds of falsifiability).  I believe this is a false dichotomy and that they are really one and the same.  Here’s why:

1. Normally natural selection requires some form of “replication” or it’s not actually natural selection.   But replication is not needed if you start with an infinity of heterogeneous universes.  In other words replication is simulated via the anthropic lens over the life-supporting subset of all possible universes.
2. Replication is a red herring anyway since it presupposes time (or at least well-ordered events).
3. I conjecture that the distribution of universes is unimportant, as long as all possible universes are represented in the multiverse (i.e. the distribution can be random).

It’s worth noting that this is a purely a metaphysical/logical argument and says nothing about specific physics or cosmologies.  One of the things that makes it hard to see why this is true from reading the Smolin/Susskind debate is that they bounce between the logical argument and various proposed, unimportant details (like whether black holes are the replication mechanism in question or not).

More importantly though, we hear scientists call one another “unscientific” whenever they propose an hypothesis that is unfalsifiable.  Here’s why I think that’s problematic:

• Ever since Popper, science has been obsessed with falsifiability, which is really about assuring consistency.
• Godel proved that there are true statements that cannot be proved.
• More specifically he unpacked “truth” into completeness + consistency and showed that we can’t have both simultaneously.
• Due to extant complexity (let alone potential infinity) completeness is out the window.
• If science is only concerned with consistency, then it’s a pointless endeavor; I can sit here all day and generate tautologies that are neither interesting nor useful.
• If science is about truth, then there needs to be a way of expanding the set of discovered tautologies along the completeness dimension as well.
• There are at least three formal logical systems which do that without sacrificing consistency: deduction, induction and abduction.
• Only deduction is formally falsifiable.
• But science relies on induction and many other forms of evidence too (statistical reasoning, clinical trials, simulation, storytelling, etc); this is the “democracy” Smolin himself referrs to in his TED talk.
• The structure of the Anthropic Principle is abduction.  So is the structure of Occam’s Razor.  And depending on who you believe Bayesian inference is either induction or abduction.
• Conjecture: Newton’s Calculus is a formalism based on abduction.
• Conjecture: strong emergence (aka novel emergence) is fundamentally abduction.  This may be why science has such a hard time with it.
• Conjecture: natural selection is fundamentally emergence/abduction.  This may be why Creationists have such a hard time with it.

There is no one true definition of what constitutes “Science.”  We hear reference to the so-called Scientific Method.  Ultimately, the holy Scientific Method is whatever scientists as a whole do; no more and no less.  To say otherwise is ad hominem.  Now I’m not claiming that ad hominem argument shouldn’t be counted as scientific evidence, but anyone who bows before Popper would.  The irony there is that ad hominem is a form of Bayesian inference.  And if you’re keeping score, that means that anyone who claims that you are being unscientific if you don’t forsake all unfalsifiable idols, is themselves committing the sin of inconsistency.  Which by their own logic means they are unscientific too.

To which I respectfully submit, their pants are on fire, hanging from a telephone wire.  And that’s a scientific fact.

Related posts:

1. The Process
2. Science 2.0
3. Non-Dualism

Now lets assume there is some process for picking out universes from the multiverse.  Since there’s no time in the multiverse, the process has no beginning and no end.  It’s like a computer program, but it’s infinitely complex.  Let’s call it The Process.

If The Process is infinitely complex and has no beginning and no end, what can we know about it?  We know that it picks some universes but not others, which effectively creates an “in group” (all those that are picked) and an “out group” (all those that are not).  Of course, both sets are infinite and still have no structure.  But note that all the universes in one group or the other now stand in relation to one another.  That is, they share the property of “in-ness” or “out-ness”, and between the two groups there’s the relationship of “different”.

The Process further divides these sub-multiverses in unknown ways, and this sorting creates other relationships between universes.  You can visualize a network of universes with the connections representing these relationships.  The network is infinite, and if you consider any subset of the network, it’s also infinite.  But these subnetworks are no longer arbitrary, they are networks themselves and networks have structure.  And since a subnetwork by definition shares the same connection relationships as the original network it is a “sub” of, the subnetwork is structurally similar to the network itself.  That is, the network is self-similar, which in mathematical terms means it’s fractal.  Of course this fractal we are talking about is infinite, and so wherever you start, it’s turtles all the way down, and all the way up.

Notice that the process of identifying subnetworks does something interesting, it creates an asymmetry that wasn’t distinguishable before.  For any network N, if you choose a subnetwork, n, then N “contains” n but not vice versa.  This containment relationship can viewed as a network where the connections are arrows, meaning they have directionality, N –> n.  You may have noticed that we just went from talking about a network of universes to a network of networks (of universes), but that’s okay.  Remember the multiverse is infinitely infinite, and we’re just chatting about some arbitrary aspects of it.  There’s lots of other aspects we could talk about instead, but it’s starting to get interesting here, so let’s continue….

Somewhere in the fractal multiverse network of networks described by The Process there is a subnetwork (actually an infinite number of them) where the structure is like this: each universe is connected to by only one other universe but connects to an infinite number.  Let’s call this structure, Time, and note that there are an infinity of subnetworks of the network which have this Time structure.  Unless stated otherwise, I’ll be talking from now on about networks with Time structure.

Remember though, the multiverse itself has no structure; The Process overlays structure on top of it and thereby allows us to know about things like Time.

Now let’s start using the words network, system, particle, entity, agent and universe interchangeably, so we can say things like “time network”, “temporal system”, “particles over time”, and “A causes B” to refer to roughly the same thing.  I realize that by overloading these terms I’m jacking into (and hopefully hijacking) your intuition about what these words mean, but that’s my intent.  Hopefully you’ll continue playing along by my rules and try not to project what you already know onto this alternative cosmology.

When we use the words network, system, particle, entity and agent, you might wonder whether we are talking about a universe or a multiverse.  The answer is Yes.   Remember, the multiverse is infinitely infinite and self-similar, so in some sense we can say it contains itself.  We have a hard time with infinity so this concept is mind-boggling, but if you follow the logic, hopefully you’ll accept this paradox as true.  So lets just use the word universe from now on and forget about multiverses.  And to not get confused, let’s refer to what we used to think of as the Universe as the known universe instead.  The known universe is where you live (or more precisely where you think you live) along with everyone and everything you know about or can imagine.

The known universe is expanding the more you learn about it.  The known universe is temporal.  And as we know from Einstein, it must therefore also be spatial — remember it’s not space and time but rather the spacetime continuum.  The known universe consists of particles (i.e. matter) and therefore — also thanks to Einstein — it consists of energy.  Time, space, matter and energy here may or may not be totally in sync with our intuitions of them, but just suppose they are the same thing and that our intuition is slightly biased by our particular experiences in life and could use adjustment.

We haven’t really talked explicitly about laws of nature, fundamental constants, invariant equations or even mathematics.  And I kinda jumped the gun when bringing Einstein into the equation (so to speak).  But it’s really hard to follow a line of thought without some sort of logical paradigm, some structure of thought.  In the end it doesn’t really matter what I’m saying, what you’re hearing, or whether any of this is “true”.  I’m just telling you a story, and hopefully it’s amusing enough for you to finish reading.

Originally we talked about The Process, which is infinitely complex and which describes all sorts of possible realities.  The known universe is one of those possibilities, one in which we see structure and patterns, order and complexity all around us.  Somewhere “out there” there may be portions of the multiverse (whoops, I said I wasn’t going to use that term anymore, sorry) where it’s still appears, unstructured and thus unknowable.  But let’s come back to the known universe and the “knowable” universe.

Because of the fact that we are here in the known universe thinking and talking about it, and not in some unknown or unknowable part, the non-random patterns that we see may look to us like universal laws (E=mc^2, the second law of thermodynamics, etc.)  Well, we know that even these laws are not truly universal, they apply to only certain scopes.   For example, “relativistic but not classical or quantum realms”, or “closed systems but not open systems.”  String theorists are looking for universal laws, but so far none have been found.  But let’s just grant them that they will eventually find some (or one).  How would we be able to distinguish between a true Law and just a pattern that is very very persistent over all known scopes?

How about we stop using the word “law” and instead replace it with the word “principle” to suggest that it may really just be a pattern that we see in the known universe.  And as the known universe expands via our increase in knowledge/understanding/awareness, we might find exceptions to the pattern.  After all, that’s what’s happened to every “law” ever considered in the history of science so far, and why should that pattern stop?  (Sorry, my paradox detector just went off, let me reset it….)

Coming back to principles, there’s one that emerged from the last few paragraphs, did you notice it?  Cosmologists call it the Anthropic Principle, which is the notion that the universe appears ordered in the particular way that it does with these nifty laws and constants because of the very cosmic coincidence that we are here observing it!  In other words, we live (and can only live) in the known universe, by definition.  And we wouldn’t be “here” and able to “notice” anything if we were in some unknowable part.  That’s a pretty trippy concept, but one that many physicists take very seriously.  It’s the same kind of argument as for why we haven’t been contacted by aliens yet: there’s a decent chance we are the most advanced intelligence out there and we’ll have to wait for others to catch up so we can communicate.  It’s also the reason that your keys are always in the last place you look.

Remember the Anthropic Principle because it’s really useful.  It has the same logical structure as Darwinian evolution and other “emergent” phenomena.  Is this Generalized Anthropic Principal (GAP) a universal/fundamental one?  Who knows.  Probably not.  We anthropic agents are so self-absorbed.

Another principle that emerges from our cosmology is Coherence.  Because of The Process, birds of a feather flock together.  Actually, The Process defines which birds are of which feather, so this is a tautology, though it’s fun to think of it as “like attracts like”.  But we know that really it’s just co-incidence: the birds exist at the same Time.  Using the analogy of birds, we can ask whether these coincident birds are different birds or the same bird.  But it’s a silly question because the answer is Yes.  Think of quantum coherence, if you like.

Now let’s say we are talking about particles and not birds, and instead of Coherence we’ll say Gravity.  Isn’t it the same thing?  We talk about stars and planets and other astral bodies as if they were coherent entities, but If there were no gravity, would those entities exist?  Or let’s talk about the Cooperation of the cells in your body; without it, would you exist?  We’ve all heard about the “law of attraction” from The Secret, isn’t it the same thing?  You imagine the future you want, and that acts as a beacon guiding you in every decision you make, every micro-decision, every unconscious action until at some point you find yourself living in the future you imagined.  Coherence, cooperation, attraction, unity.  Same thing.

Here’s a secret: there is no Process.  Or if you prefer, The Process is completely random.  Yet that doesn’t change anything I’ve said above.  Think of it this way: in an infinite series of random numbers, all patterns appear eventually, right?  So “somewhere” in the infinite randomness, The Process “produces” the structure I’ve been talking about.  Or maybe the fact that we’re anthropically talking about it produces the structure.  We are The Process.  Or more generally, we humans are part of The Process.  The Process is the universe.

Related posts:

1. Why Falsifiability is Insufficient for Scientific Reasoning
2. Notes from TED
3. Synthesis of Complexity Theory

Now we find out that some of the more sensational claims about potential consequences contained in the IPCC AR4 report are not actually backed up by peer-reviewed research. Instead, they come from assertions made by advocacy groups such as the WWF and Greenpeace. Then there’s the dependence on anecdotal newspaper and magazine reports.  Oh, and an amusing reference to a boot cleaning manual from an Antarctic tour operator.

It all started with the infamous, “Himalayan glaciers will be gone by 2035,” claim, which was substantiated solely by a WWF report. Not cool because IPCC rules state they should only reference peer-reviewed research from respectable journals.

Things get worse.  Bear with me here.  The story is a bit involved, but it reveals how feckless the guys at the top of the AGW food chain can be. India’s environmental minister tried to call BS by referring to, you know, actual measurements of glacial retreat.  But the chairman of the IPCC called this “voodo science.” Of course, the scientist who lead the development of that section of IPCC AR4, eventually admitted that the claim about glaciers disappearing by 2035 was not supported by peer-reviewed research. And it turns out that the chairman of the IPCC was actually informed about the problem months earlier.

Now for the cherry on top of this crap sundae. The chairman of the IPCC runs an institute that received a ton of money based on… wait for it… the claim that Himalayan glaciers would be gone by 2035.

I realize that people want to defer to the leading scientists in an area.  It’s perfectly rational. In fact it was what I did before I started looking into AGW myself.  But there should be some evidence that will cause you to update this position. I think we’ve reached that point.

Related posts:

1. Will The Real AGW Skeptic Please Stand Up?
2. Why You Should Be A Skeptic
3. Peer-Review vs. Info Prizes and Markets

Target & Kill Approaches

Biris and Zharov are making some exciting progress in using nanotubes to tag and then track cancer cells inside the body as they move around.  They propose to kill the cancer cells by heating up the nanotubes using lasers, while others are using nanomagnets and still others siRNA. Glazier is in agreement with the target and kill approach and outines a number of such methods in his book, Cure, in which he also argues forcefully for the importance of taking somatic evolution seriously in our approaches to treating cancer.

One potential problem with target and kill, as Glazier points out, is that if you don’t get all cancer cells, you run a high risk of recurrence.  Which belies an even bigger problem: how do you detect which cells are cancerous and which are not?  Glazier calls for behavioral pattern recognition, i.e. looking for cells that are proliferating and also exhibiting invasive behavior at the same time.  But it remains to be seen whether such pattern recognition is possible in practice.  A possible way to keep tabs on cell behavior is to do continuous in situ monitoring or ultrasonic nanotech.

Enhance Immune Response

The immune system is really good at identifying and killing cells behaving badly (although the majority of the time the immune system’s targets are foreign invaders like viruses).  But what if we could boost the immune system so that it was better able to deal with cancer cells?  Essentially create a vaccine for cancer.

The difficulty with immunotherapies for cancer has always been that it’s not in the “charter” of the immune system to fight the body’s own cells; when it does we can get what are know as autoimmune diseases.

Reiter, et al are working on a clever hack of the a class of immune cells called tumor-infiltrating lymphocytes (TILs) wherin they extract TILs from a tumor, enhance their tumor-fighting potential and reinject the enhanced TILs back into the tumor.

The achilles heel of immune enhancement will always be comprehensiveness.  That is, if you don’t get everything, cancer can eventually evolves resistence by becoming too hard for the immune system to detect or by learning how to fight off the immune response.  And if you get overly aggressive, you risk harming the patient in other ways.  And cancer has proven to be extremely tricky in outwitting the immune system.

Genetic Modification Approaches

Modifying genes, either by enhancing tumor suppressors or reducing tumor promotors, has been a popular appoach in recent years.  Often the approach has been to focus on individually important genes or to try to find exhaustive sets of genes which, when modified appropriatly, stop cancer progression.

One problem is that genetic information is not organized into atomic functions or even sets of functions, but rather in complex, multi-scale functional networks with built-in redundancy.  In such networks, you can modify, add or delete many nodes and links without changing the overall network behavior significantly.  Still, recent advances do show promise, as with microRNA replacement.

Another confounding factor is genetic modification is that the genetic code seems to be organized a bit like a toolbox of mix-and-match parts that get shuffled around by evolution.   Thus if a trait or function is adaptive, it might emerge by more than one evolutionary path using different arrangements of genetic code and entirely different mechanisms (this is known as convergent evolution).  Theoretically the malignant behaviors that characterize cancer — unregulated proliferation and invasiveness — could re-evolve, just as happens in organismal evolution; after all, to the cancer cells malignant behaviors are are adaptive, it’s just us mulitcellular beings that view the behavior as bad.  What I mean by this is the following; vision has been achieved a number of different ways by organismal evolution with the genetic toolbox, so what’s to stop somatic evolution from achieving proliferation and invasiveness in different ways than is normally seen in human physiology?

Viewing the problem from a slightly different angle still, consider the following.  Cancer itself works by making massive numbers of changes to individual cells’ genetic networks.  This source of heterogeneity is what provides the grist for the evolutionary mill.  The vast majority of these mutations don’t work out and the cells die off or — more problematically — the mutations remain dormant in successive generations of the cell line.  But every once in a while you end up with a rearrangement of the network that is viable and which creates cells who don’t “play nice” with their neighbors (i.e. cancer).  Thus, if you have created a therapy targeted to a particular gene, there’s a good chance it won’t work anymore because the gene now sits in a different functional context; the original function you were targeting may now be served via different mechanisms.

A more harmonious variant of genetic modification is to replace entire cells with stem cells and allow them to differentiate into the appropriate cell type, effectively cleansing the genome.  This type of work is being done but is very preliminary and the stems cells themselves are prone to becoming cancerous, presumably due to their pluripotency and robust replicative potential.  Still, this line of inquiry seems promising to me, because it honors the body’s own developmental programming to replace badly acting cells with good ones, instead of just, say, killing bad cells and leaving a physical (and behavioral/ecological) void for surrounding cancer cells to exploit.  While currently solid tissue cell replacement requires surgery, down the road we can expect a veritable Cambrian explosion of nanobots that will be able to precisely navigate to targeted areas and do the work of cell replacement and genetic modification.

Prophylactic / Preventative Approaches

Aubrey de Grey works on the radical extension of the human lifespan and believes that there’s no theoretical limit to how long we can live if we hack our biological inheritance appropriately (BTW, many others agree, including Ray Kurzweil).  Organ replacement and regrowing failed body parts is a forgone conclusion (it’s happening already), and de Grey says that the only disease that presents a problem long-term is cancer, due to the relentlessness and “cleverness” of somatic evolution.  De Grey proposes therefore that the only real approach is one of indefinite prophylaxis, i.e. take specific steps to intervene on a regular basis so that somatic evolution stays in check and we don’t get the unregulated proliferation and invasiveness that is cancer.  His WILT approach argues we achieve this by regulating the length of telomeres which are critical to the proliferation process.

Carlo Maley says that the WILT approach should work, but the technology is a far way off and it’s hard work to go this route.  Maley believes that we may be closer on the prophylactic front with by boosting cancer-suppression genes, as in the super p53 approach.

Several months ago I started asking cancer researchers the following question: if we were somehow magically able to replace the DNA in every cell in your body with a clean copy at regular intervals, would that prevent cancer entirely?  While most who answered thought that in theory this would work, some startling research recently has me wondering whether it would.  The discovery of non-genetic forms of persistent heterogeneity (Brock, et al, Spencer et al, and Sigal et al), combined with the logic of somatic evolution and the genetic toolbox, leads me to be fearful that unregulated proliferation and invasiveness might re-emerge without genetic (or genomic) heterogeneity.  Even if non-genetic heterogeneity is not broad enough to provide an “escape hatch” from full DNA replacement, it might be broad enough to thwart a WILT or super p53 approach.

Other preventative approaches focus on detecting pre-cancerous cells — ones that are most likely to turn malignant at some point — and removing them either surgically or with more advanced technology like radio waves.

Hijacking Microorganisms

Then there’s the approach of co-opting existing viruses and bacteria (also here, here,and here) since these microorganisms have exquisitely evolved to be effective at targeting and dismantling individual cells and cell types in multicellular organisms like humans.  There are several issues with this approach though.  First is that in order to “repurpose” these critters to do our therapeutic bidding, we have to simultaneously help them outsmart our immune system while making sure they don’t harm normal cells; not such an easy task.  Second, there is a danger in messing with viruses and bacteria in that these are populations with the potential to evolve (despite whatever measures are taken to avoid this) and as such could get out of control.  Third, there are always unintended and unpredictable consequences when injecting a body with foreign substances, especially ones that are alive….

Fighting Evolution with Evolution

There are a number of ways to approach fighting cancer “with” evolution, one of which was mentioned already (the TIL approach).  Another is to use evolution as a mad tinkerer/designer to create sophisticated biological agents that empirically do the job well.

Maley and Pepper are looking at changing the microenvironment to shape somatic evolution so that there is less selective pressure for cells to compete with one another.  David Basanta and his colleagues at the Moffitt Research Center modeling various aspects of evolution in the hopes to be able to one day shape it’s direction.

David Rasnick suggests that if we are to really take somatic evolution seriously we need to recognize that normal human cells are vastly more robust than cancer cells and that most cancer cells die off with the smallest perturbation to their environment.  The problem is that they mutate and adapt very quickly.  Rasnick’s “perturbation theory” says we should look to induce stresses into the body that normal cells are equipped well to deal with and on a relative basis, cancer cells are not.  While one could think of chemo and radiation in this regard there are two problems: (1) they can damage DNA making the heterogeneity worse; (2) normal cells are not equipped to deal with these perturbations either.  Examples of perturbations normal cells are equipped to deal with include radical changes in various lifestyle dimensions (extreme exercise, extreme diet changes) or inducing natural stress reactions.  Rasnick notes that many cases of “spontaneous remission” occurred after prolonged periods of extremely high fever.  One thing that’s for sure, as technology advances we will have more and more ways to cleverly perturb cells.

Doing Less

In our “Just Do It” society we often forget that sometimes less is more:

• Surgery Not Necessary For Most Late-Stage Colorectal Cancers
• Chemo spurs some cancer cells
• To Survive Cancer, Live With It

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But there is a gnawing concern among some doctors and researchers that certain prescription generic drugs may not work as well as their brand-name counterparts.

I personally believe that many practitioners have been aware of this issue for decades. But, you can only obscure the truth for so long.

The problem is not pervasive, but it’s something consumers should be aware of — especially now that more insurers insist that patients take generic medications when they are available.

Generic drugs are for the most part great. But they are not all created equal. The real issues here are about awareness, understanding, knowledge, and truth.

Some specialists, particularly cardiologists and neurologists, are concerned about generic formulations of drugs in which a slight variation could have a serious effect on a patient’s health. The American Academy of Neurology has a position paper that says, in part, “The A.A.N. opposes generic substitution of anticonvulsant drugs for the treatment of epilepsy without the attending physician’s approval.”

Small differences matter. Why this is confined to a 2006 paper regarding epilepsy, I do not know.

But insurers tend to argue otherwise. On Thursday, ExpressScripts, which handles drug insurance for big employers, put out a news release announcing results of a study it sponsored that found no difference in hospitalizations or emergency-room visits for people on brand-name epilepsy drugs compared with those taking generics.

No surprise here. A company with a huge monetary interest in providing generic drugs has come up with a study to support their stance.

The Food and Drug Administration, meanwhile, says it stands behind generic medications and its methods for approving them.

The American Medical Association concurs. A spokeswoman for the group told me in an e-mail message, “the A.M.A. position is that as a whole generic drugs do work as well as name-brand drugs.”

Naturally, after years of advancing the opinion that all drugs are created equal, the FDA and AMA are not about to change.

According to F.D.A. rules, the new generic version must “have the same active ingredient, strength and dosage form” as the brand name or reference product.

Sounds pretty good. So what does it really mean?

Generally, the only test that a maker of a generic medication must perform to receive F.D.A. approval is one that establishes the “bioequivalence” of the product. This test is done on healthy volunteers and compares the blood levels of the reference drug to the generic one. According to Mr. Buehler of the F.D.A., to be considered bioequivalent, the generic drug must reach a blood serum level that is 80 to 125 percent of what the reference product achieves. But Mr. Buehler said that in reality the spread was not nearly that large. He noted that the F.D.A. conducted a large study and found that the average difference in absorption into the body between a generic and brand name drug was only 3.5 percent.

Interesting. So 80% = 100% = 125% I think I get it. Make something similar and you are good to go. I don’t believe the 3.5% from the study is representative or necessarily relevant. There is still a problem. The differences may be smaller than we thought but the message is still the same, we need better standards.

Some specialists, though, worry that the allowable range for bioequivalence is too wide, especially for patients who are taking medication to control problems like arrhythmias or seizures.

I’m no specialist, but I have a problem with 80%=125% What about you? And it’s not just for arrythmias and seizures. Many psychotropic and hormonal medications exhibit dangerous variability in their bioequivalence as well. Want to increase your hormone levels by 50% I didn’t think so. Even a 5-10% difference can be significant when we consider non-linearity in complex systems.

Stephanie Ford, 29, who spoke on condition that she not be otherwise identified, had been taking Lamictal to control her bipolar disorder. When a generic version came out two years ago, her insurer switched her to it.

Ms. Ford found that the generic drug, lamotrigine, worked just as well as the name brand and cost her just $10 a month instead of the $45 copayment she had been spending on the brand name. (For a person without insurance, Lamictal can cost about $300 a month, depending on the dosage.)

But when her insurer then urged her to order her medication by mail, she received another generic version of Lamictal and her symptoms returned.

“After about a week,” she wrote in an e-mail message, “I noticed a difference in my emotional state (and nothing changed in my life) and by a week and a half, I had digressed to the state I had been before being on medication.”

Ms. Ford has found a local pharmacy that carries the original generic. She now buys the medication directly from that store. Because her insurer charges her a $5 penalty for not using mail order, her copayment is now $15.

She says her condition has once again stabilized.

I believe there are countless variations on the story above. I think doctors need to come forward, share their experiences, and pressure the FDA for more rigid measures of “bioequivalence.” Individuals need to be careful and self-aware when switching medications, even when the medications are supposedly the same.

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If you grew up like me you were brought up in a culture based on a dualist metaphysics, one that asserts that there is an objective reality outside of ourselves (whatever “we” are) and that we know about it indirectly through our senses and conscious reasoning.  This is the basis of the Western traditions of science, liberal arts and symbolic systems (such as mathematics and human language).  Essentially anything that can be studied is part of this metaphysics.  Gödel showed us that this metaphysics will never lead to complete knowing, though everyone agrees we can continually refine our knowledge and thereby at least asymptotically approach enlightenment.

Descartes proved to us that each of us individually do indeed exist, and he tried to argue further that the universe as we perceive it — however imperfectly — does indeed exist too.  But before you drink too deeply from the Cartesian well, keep in mind that his argument for an external reality depended on the existence of a benevolent God, one that would not deceive us with such an elaborate ruse as to make the world seem so real when it wasn’t.  His whole argument after cogito ergo sum is logically flawed.

There are other metaphysics that assert reality is entirely subjective, that there is no reality outside of ourselves.  This of course begs the question of who “we” are such that reality can exist or not outside of us.  But to even ask this question is to miss the point.  Knowledge is direct, we “experience” it; and if we have no expectation, no attachment, no judgement, then we can truly understand.  Anytime we engage in the act of thinking, we break from our direct, immediate, complete knowledge of who we are and knowledge of everything there is to know.  This of course is the metaphysics of Zen Buddhism, Taoism and other Eastern traditions.

I am in danger of losing anyone reading this if I don’t immediately disavow this second way of knowing in favor of the first.  There are many who consider themselves intelligent — whose very self-image is based on intelligence — who will be saying to themselves right now that experience without thought is all well and good as a tool for getting to insight.  But ultimately insight (and knowledge and knowing) requires thought.  And in particular it requires thought that is self-consistent, which is to say rational and logical.  The worst things in the world to such a person are logical inconsistency and paradox.  There are fundamental laws at work, not just about the universe but also about knowing.  These believers will invoke the trinity of Occam, Bayes and Popper, but they forsake the word of Gödel: you can choose consistency, or you can choose completeness, but you can’t have both.

For those of us who have already cast ourselves out of the garden of completeness, all I can say is that it is never too late to reconsider how seriously we take all this cogitation.  I mean after all, what’s the harm in exploration as long as we always have our very capable minds to help us navigate?  With this in mind, I have begun to reconsider certain assumptions.  And for those of you who recall my very first post, the willingness to do so was the only rule that I imposed on myself and insisted of those who wish to engage.

Because we all have different experiences in life, we each have a different internal “language” with which we receive truth and gain understanding.  Those of us who come from the Western tradition — which is to say anyone who thinks of themselves as a thinker — we are in need of more practice in letting go of the map and experiencing the terrain directly.

Have you ever noticed that when someone speaks deep truth (no matter what “language” they are speaking) you get a sense of deep resonance that is beyond words and conscious thought?  I certainly do.  And another thing I notice about these experiences is that they only happen when I stop engaging my analytical mind to critique or compare what the person is saying to what I already “know”.

If we cling to faulty assumptions in the face of truth we feel discord of some form (anger, embarrassment, indignity, righteousness, etc).  But I view this as really another form of recognition of the truth before us.  It’s a sort of allergic reaction to the invading memes that would damage our internal edifices, the faulty assumptions that protect our egos and our ideas of who we are.  To embrace the truth often means a level of change we are not yet willing to undertake, and which we may never be willing to undertake.  In the face of such high stakes, we rationalize away the truth in order to preserve internal consistency and harmony.

As an experiment to illustrate this point, consider your immediate gut reactions to the following statements one at a time:

1. “There are ways of knowing that are beyond science, beyond analytical thought, and they are crucial for you to engage in if you wish to get past your limited understanding of the universe.”
2. “Think about that one thing you know with all your being to be true.  Got it?  Well, it’s not true. You believe in a falsehood, a convenient fiction that you use to deny the veracity of your deepest fears.”

Is it possible to not have a negative reaction to at least one of these two statements?  Most people would say no.  If you are comfortable with both statements, congratulations, you have broken free of the shackles of narrow-mindedness that bind most of the world.

If you are like me, you have no trouble at all with Statement 2, but feel at some level that Statement 1 is new-age horseshit, at best an opiate for the masses but at worst a very dangerous conceit.  So let’s take a deep breath and use this as an opportunity to explore what’s causing the negative emotion so that we can challenge those assumptions and thereby learn.

My reaction to Statement 1 is based on the denial of the value of my personal identity as a thoughtful, analytical, intelligent person, one that doesn’t do things that are irrational.  If Statement 1 is true, then my life is less valuable than I had presumed, perhaps even valueless.  Man that would suck.  If I take Statement 1 to be true then I will be forced to change who I am in order to once again feel as valuable.  I might even be forced to participate in a seance and other freaky and totally pointless activities.  Not gonna happen, I don’t have that kind of time to waste.  I could be making the world a better place or at least pursuing my own happiness.

Sounds a bit silly when I type it out.  After all, what’s the point in making the world a better place if we’re all dead anyway (on average a true statement if you are a stats geek).  And as for happiness, I know most of the literature, and I have to admit, as happy as I am there are some proven paths to happiness that I have yet to fully explore and they fit squarely in the experiential, non-analytical sectors of life.  So what could be the harm in turning off the analytical mind a bit more and experiencing without judging?  At worst maybe I’ll be a bit happier, and at best maybe I will become more effective at making the world a better place. But is this direct experience actually valid from an ontological perspective?

Even within the Western analytic tradition there are themes of experiential knowing.  Psychologists now speak (very analytically of course) about the state of Flow.  In Flow, we are so thoroughly engaged in the task at hand and so perfectly in sync that our experience of time changes dramatically.  We are able to achieve extraordinary performance, effortlessly and without thinking.  Gladwell popularized this concept in Blink, claiming that the vast parallel processing power of the human brain and nervous system for useful cognition is largely untapped (or masked) when we focus on conscious reasoning.  To tap into the full potential of the mind, we need to apply techniques to short-circuit our conscious thought processes.

Every professional athlete, musician and performance artist is familiar with Flow/Blink, and you’ve no doubt experienced it many times yourself.  For me, it’s usually been when engaged in a sport where there is little time to think (like ping-pong, volleyball or snowboarding).  In the mental realm, I have been able achieve leaps in performance and rely heavily on on my “blinking” ability — whether it be playing poker, brainstorming, writing, or just interacting in a positive way with those around me — by orchestrating a Flow state.

I’m still learning what best puts me into Flow, but it seems to be some combination of prolonged intense concentration, mild sleep deprivation and small amounts of psychoactive substances like caffeine, modafinil, marijuana, or alcohol (though I must say that too much substance, or combining it, always kills the flow for me).  Recently I’ve found that adding in physical movement or music also help trigger Flow.  On this last front, while most people would say “what took you so long,” it’s worth pointing out that every person is unique in terms of what works for them.  For instance, what most people refer to as meditation (i.e. eyes closed, absolute stillness of body and mind) doesn’t do much for me.  My mind somehow responds better to hyper stimulation than tranquility.

Early in life, learning is mostly the process of of creating new structure out of noise.  As our adult minds form, this structure creation that was once crucial in our learning process becomes a beast of burden and we lose our mental plasticity.  To counteract this imbalance we must consciously re-integrate those activities that we had no trouble jumping into as a child.  The challenge is not to let our egos and silly notions of personal identity get in the way of our beginner mind.  Ken Robinson makes this point as well as anyone I’ve encountered, and I invite you to sit back and enjoy for the next 20 minutes with your own beginner mind:

Click here to view the embedded video.

As for me, I’m off to my favorite yoga studio to participate in kirtan and tap into some good communal vibes.  Maybe I’ll even hit the Buddha along the way.

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Second, the email correspondence is pretty damning. It won’t affect my position much because I was already fairly sure these types of shenanigans were going on. But if you put your faith in the “consensus”, you should consider updating your position. There are numerous instances of three types of egregious behavior from senior scientists:

• Coordinated efforts to portray all results as supporting the conclusion that anthropogenic global warming (AGW) is a serious threat. Such efforts included the spinning of results, application of statistical “tricks”, and selective use of data.
• Coordinated efforts to suppress professional dissent. Such efforts included going after editors of journals that published articles supporting a skeptical view and lobbying university administrations to pressure researches who didn’t toe the line.
• Coordinated efforts to evade Freedom of Information Act requests and destroy data that might support the skeptical position if disclosed.

By themselves, these actions should be alarming because they obfuscate the real answer to the question of how serious a threat AGW presents .

But the real take home point is the tone of many emails. These are leading scientists in the field. Yet they clearly hold bitter contempt for colleagues who don’t agree with them. This isn’t business.  This is personal.  To paraphrase, Robin Hanson, climate science isn’t about the science of climate. It’s about social status. The AGW proponents see themselves as an “in group” and AGW skeptics as an “out group”. They are more concerned about destroying the out group than actually figuring out what’s going on with the climate.

Given this attitude, it’s hard to have any confidence that we’ll get a rational, scientific answer any time in the near future.

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The opening line of the article is “CT scans of Egyptian mummies… show evidence of… hardening of the arteries, which is normally thought of as a disease caused by modern lifestyles….”  One of the researching cardiologist draws this conclusion: “Perhaps atherosclerosis is part of being human.”

The LA Times reporter covering the story (Thomas Maugh) rightly points out at the end, “The high-status Egyptians ate a diet high in meat from cattle, ducks and geese, all fatty.”  Which of course entirely negates the hypothesis of heart disease being part of the natural human condition.

It’s clear why the researchers — both cardiologists — would want ancient evidence to support the notion that heart disease is normal.  But the fact is that the preponderance of evidence around the world in epidemiology as well as cardiology indicates that diet and lifestyle are largely responsible.  Don’t trust me, just start digging around for yourself, it’s not hard to find the data.

Okay, so researchers are trying to get their work into the mainstream, what’s new?  Any thinking person can see through their faulty logic, right?  Not according to all the research on behavioral psychology.  That’s why I’m mostly disappointed in the reporting as opposed to the research.

Maugh and the LA Times bit so hard on this succulent morsel of pseudo-science that the net result is false information which is damaging to public health.  Had Maugh flipped his article upside down and lead with his commentary at the bottom, he would have come much closer to serving the public good with the dark leafy vegetables of truth.

hat tip: @DannyHorowitz

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