It’s not just the lives of individuals who eat crap (which is most of the country, frankly, even though they have no idea how toxic what they are eating is).  It’s the happiness and achievement potential of today’s youth.  It’s the emperor with no clothes at the center of the healthcare debate.  And it’s a lynchpin for economic recovery and sustainability.

Watch the premiere, and spread the word…

Related posts:

1. Two Important Links
2. Is Hunger Really a Problem in U.S.?
3. The Problem With Processed Foods

The key scientific findings are:

- For strength training, one set is enough.  The standard regimen at most gyms is to instruct people to do three sets of each exercise. Sets two and three are a waste of time for the average person.  Much better to either save your time or do a greater variety of exercises.  See here.  (For highly trained individuals, you do need to use a multi-set periodized regimen to achieve additional gains.)

- For strength training, once per week is enough. The standard regimen at most gyms is to instruct people to do a complete weightlifting routine three times a week. However, training once per week gets you about 75% of the benefit of training three times per week.  3x the effort for 33% more gain seems like a poor payoff.  See here.  (For highly trained individuals, your workouts may be so intense that once per week is actually optimal.)

- For cardiovascular training, high intensity intervals produce the best results in the least time.  Long distance cardio is beneficial, but you’ll actually improve your performance about as well with intervals in much less time. See here. (For highly trained individuals in long distance disciplines, you must also do distance of course.)

- For cardiovascular training, running has the most cross training benefit. If you want general fitness, running is therefore the best exercise.  See here. (For sports participants, sports specific drills are of course the best conditioning.)

- Stretching is not a very beneficial activity. Contrary to popular belief, it does not reduce the incidence of injuries. The evidence here is really strong.  Moreover, stretching before strength training or sports actually dramatically decrease your maximum power, potentially increasing the potential for an injury. The only thing it does is increase your range of motion, which does not even indirectly prevent injury though it may improve the performance of activities that require more flexibility.  See here.

- To maintain a healthy weight, you need to burn calories.

Thus, here is my recommended program:

- Do 2, 1/2 hour strength training sessions per week, one for upper body and one for lower body.  The issue is that most people can’t maintain intensity for more than 1/2 hour.  So splitting strength training into upper and lower body enables you to intensely train the entire body.

- Do 2, 1/2 hour interval training sessions per week, one of which is running on a track or treadmill.  The pattern here should be 30-60 seconds of maximum output followed by 2-4 minutes of rest.  Repeat 4-7 times.  The key here is that you should be completely wiped at the end.  Increase the interval intensity and time as well as the number of intervals to achieve exhaustion.

- Walk 2 miles every day. If you weigh 150lbs, this will burn the same amount of energy in a year as is contained in 20lbs of fat.  At 225lbs, it’s 30lbs fat equivalent.  I also find this is a great stress reliever when done at the end of the day.  It’s a great time to make calls to friends and family to catch up too.

That’s it.  Not a huge commitment.  But the gains for the average person would be substantial.

Related posts:

1. The Exercise Book that Could Have Been

I get the feeling that Little and McGuff started with a pre-conceived exercise ideology and then went hunting for science that supports it. I would sum up this ideology as: less is more, weight machines are better than free weights, cardio is bad. The actual science on this is strong, non-existent, wrong.

What really rubbed me the wrong way was how they evangelized their specific program . I categorize the objectionable evangelical tactics into three categories: blinding readers with science, selective application of principles, and just plain wrong.

Blinding Readers with Science

BBS contains discussions of physiology (primarily cell biology and endocrinology) that one would find in a mid-level college text. Two problems.  First, the vast majority of readers simply won’t understand it. Second, it’s misleading because it looks at physiological features in isolation.

My guess is the first problem is intentional. The authors want to overwhelm readers so they will believe the book’s conclusions: blinding them with science. My guess is the second problem is inadvertent. The authors sincerely believe they can draw causal conclusions by analyzing narrow subsystems: ignoring complex systems effects.

There’s a lot of discussion of various endocrine circuits and how the fact that a particular pathway exists implies that optimizing the execution of that pathway will lead to the desired macro results. The problem of course is that the endocrine system is actually a complex system of interdependent, nonlinear circuits so it’s difficult to predict the macro results of changes to a pathway or group of pathways.

Selective Application of Principles

Having tried to get readers to accept them as experts, Little and McGuff proceed to selectively apply various principles.  Many uninitiated readers probably buy these arguments as objective applications of scientific results. Nothing could be further from the truth.

The prime example is the principle of specificity: that whatever exercise you perform trains your body to perform that specific activity. The first problem with BBS is that it treats specificity as a binary property, either the exercise is exactly like the target activity or it isn’t. Of course, this can’t possibly be true.  Running on a track at Stanford is similar enough to running on a track at UCLA to hold athletic competitions. Running on a track is similar enough to running on a flat road to allow track runners to run very well roads. Running on a flat is similar enough to running on a hill to allow flat runners to run fairly well in the hills. There is a spectrum of specificity.

Of course, specificity is multidimensional.  There is tempo as well as mechanics. Will a marathon runner or a sprint cyclist win in a 50m foot race?  Good question.  I’d give even odds.  But I’d go with the runner at 400m.  And either one would smoke a sprint swimmer at 50m.

Now, Little and McGuff use the principle of specificity to argue against cardio. Cardio won’t help your practical endurance more than weightlifting because they put the same strain on the cardiovascular system.  If you want endurance for a sport or recreational activity, you should just do that activity. Huh? A lot of activities involve running of some sort so it seems like hitting the track or the treadmill might be a good idea for general fitness.

Of course, they fail to apply the specificity principle to the question of free weights versus weight machines. They argue that free weights are potentially more damaging to the joints and no better at building muscle. But doing a free weight hammer curl is really similar to picking up a gallon of milk and a free weight deadlift is really similar to picking up a box. Much more so than the machines targeted at those body parts. Funny, no mention of that.

Just Plain Wrong

BBS also supports its exercise ideology with assertions that are just plain wrong. The most egregious is that you shouldn’t do cardio because all endurance adaptations occur in the muscles. So if you just lift weights then you’re getting the same benefits as doing cardio that works the same muscles.

Hmm. Stroke volume, blood volume, blood pressure, lung capacity, and pulmonary diffusion are just some of the systemic adaptations that occur from aerobic exercise.

And contrary to the assertions of the authors, cross training does improve performance (presumably due to the systemic effects).  Not as much as additional training in the specific activity, of course. Running seems to be the most beneficial cross training discipline (see here and here).  So again, it seems like a good idea to hit the track or treadmill.

Now, I’m used to exercise books and articles that are full of misinformation. But this book had such potential that it bothered me much more than most.

Related posts:

1. What the Science Actually Says About Exercise

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

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1. The Link Between Food & Healthcare Reform
2. The Most Important TV Show in America

The table below shows the salient aspects of each plan.  To compare apples to apples, I had to estimate the 2010 premiums for the previous plan. I used a 9% increase over 2009, which is what a PricewaterhouseCoopers survey says will be the average for employer sponsored plans. Note that this is less than the 10.8% actual increase my company saw from 2008 to 2009 on this plan.

We see something very interesting here. The annual premium on the new plan is $9,833 less than the estimated annual premium on the old plan. Now, we all get checkups each year.  Also, my wife and son have monthly medications they take for allergies.  Adding in the copays for those yields extra $500 on the old plan, pushing us to $10,333 more guaranteed expenditures on the old plan than the new plan. Obviously, this excess is more than the new plan’s deductible.

So there’s no way I can loose on the new plan.  If we stay healthy, I get to pocket $10,333 minus the cost of routine visits and medications.  If something bad happens and someone has a major medical issue, I save at least $8,333 due to the deductible and coinsurance on the old plan. Probably much more due to co-pays for additional office visits and prescriptions, which are not limited by the out-of-pocket maximum.  I actually ran the scenarios and there’s no way I don’t save at least $5,000 per year.

Moreover, the new plan is much better at insuring against catastrophic loss.  The lifetime maximum is 2.5 times as high.  That’s a real selling point for me. I don’t want the plug pulled on my ventilator because my insurance ran out.

How can this be? Why do we even have PPO plans? You may think the tax deductibility of employer-paid premiums is the reason.  But this doesn’t explain why employees wouldn’t choose an employer-sponsored version of the high deductible plan. Those are paid with the same pre-tax dollars.  (It also doesn’t affect me because I’m technically self-employed and deduct my premiums anyway). It certainly explains why the CEO of Whole Foods is absolutely right to offer his employee’s a high deductible plus HSA plan.  It saves everyone money. The math speaks for itself.

The only explanation that makes sense is that people want to spend more on health care when it doesn’t come out of their own pockets. A combination of moral hazard and mental accounting. On the moral hazard front, they go to the doctor more often than they otherwise would because the marginal cost to them is so low. On the mental accounting front, the automatic monthly deduction from their pay is less painful than personally writing checks to pay doctors. But it’s irrational.

Perhaps some marketing wizards should figure out how to pitch high-deductible plus HSA plans in a way that the average person would find attractive.  How about an infomercial that promises to save you thousands of dollars every year with a proven system and throws in a set of handy dandy steak knives if you act now?

Related posts:

1. Quest for Insurance Part I: The Search
2. Fixing Health Care I: The Uninsured
3. Fixing Health Care III: Hospitals

I started by going to eHealthInsurance and hitting up the big three companies: Aetna, Anthem (BlueShield/BlueCross), and HealthNet. My first disappointment came when I discovered that there is no universal application. You have to type in roughly the same information in substantially different formats for each company. What value exactly is eHealthInsurance adding here?

My second disappointment came when they all rejected the applications for different reasons. There are four people in our family. One of them was rejected by two companies, two of them were rejected by one company, one of them was not rejected at all. The reasons were allergy shots, acne, possible acne, and being underweight. The first two are minor ongoing issues.  Considering we were applying for $10K deductible plans with no office visit or prescription coverage, it’s hard to see what the problem is. The second one was unconfirmed by the first doctor, totally minor, and subsequently excluded by a second doctor. The last one is the only one that should have been of any concerned and a check with that person’s doctor would have eliminated the concern.

My working hypothesis is that these companies don’t actually want to offer individual health coverage. For regulatory or political reasons, they have to appear to offer such coverage. But unless an individual is so low risk as to be obscenely profitable, why go to the effort? It’s so much easier to focus on selling group coverage to employers.  This is a side effect of the tax deductibility of premiums for most companies but not most individuals.

Luckily, there are niche providers that pursue opportunities that are not attractive to the largest players. One of them is Assurant Health. After filling out the online application at their Web site, I received a call from their underwriting department within two days. They wanted to review the medical records for the two family members receiving allergy shots to make sure these were not indicative of larger issues. No problem, we had signed a release and I had no objection to paying a premium based on actual risk.

Now, the story takes a funny turn. Apparently, HIPAA has made doctors so paranoid about penalties for breaching patient privacy, that they don’t want to give out your medical records to anyone. Despite the general release we signed, two medical clinics wanted us to sign special releases. It took a month to actually get these special releases so we could sign them. Even then, one of the clinics also required us to call them on the phone and give them verbal permission as well. Government intervention strikes again! If the government had clearly specified the mechanism for releasing medical records, there wouldn’t have been a problem. Even better, if the government hadn’t distorted the market for insurance toward employer-sponsored coverage, this transaction would be so routine that the free market would have solved the problem

The story has a happy ending.  In Part II, I will analyze the excellent coverage we got from Assurant in the context of my previous recommendations.

Related posts:

1. Quest for Insurance Part II: The Coverage
2. Fixing Health Care II: Doctor’s Visits
3. Fixing Health Care I: The Uninsured

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

Related posts:

1. Cancer as Evolution — 2008 Summary
2. Cancer as Evolution, part 2
3. The Conflict Between Complex Systems and Reductionism

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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