There have been some recent write-ups, (Gene therapy helps counter hemophilia B,   ASH:Gene Therapy Puts Merry in ‘Christmas’ Bleeding Disease) about a new gene therapy treatment for a particular rare disease known as Hemophilia B, or Christmas Disease.  The findings were formally published just this past month in the New England Journal of Medicine.  This particular subtype of hemophilia is perhaps best known historically for having disproportionately affected the English aristocracy and notably affecting the son of Czar Nicholas of Russia.  It is caused by an inability to make Factor IV in the blood, one of a number of enzymes involved in the coagulation cascade which allows blood to clot normally.

Archibold Garrod around the 1920s was the first one to start to write of what he termed “inborn errors of metabolism” where some key piece of the metabolic machinery is absent from birth.  We would now also term these inborn errors of metabolism a subset of genetic diseases and a subset that comprises many of the most rare, serious and tragic of genetic diseases; ones which often lead to death in childhood.  Hemophilia B is not an exception as the affected is always as risk of hemorrhaging to death from even minor trauma.

There are two ways at the present time we would look in conventional medicine to try and treat the root cause of these diseases.  The first would be to replace the enzyme that is missing in metabolism.  The most well known example of this is insulin replacement therapy in those with type I and some with type II diabetes, though type II diabetes is really an acquired not inborn metabolic problem.  So at first tremendous expense and effort was made to carefully extract a small amount of insulin from say pig or cow sources.  With the improved understanding of genetics it was subsequently learned how to take a simple bacterium, insert the gene for human insulin into the bacterium and soon have bacteria merrily churning out human insulin.  This is the first, best known and still most widely used of the class of therapies known as transgenic enzyme replacement therapies.  This is the approach used to treat Hemophilia B at the present, inject bacterially derived human factor IX.  While it is a great advance there are limitations and problems with the approach which might take a page or so to adequately discuss.

The other idea would be to see if you could correct the genetic blue print itself in the same way that a bacterial genome was altered.  At first glance this looks like an ideal, straightforward and even simple approach.  On paper this also looks simple in that bacteria will generate large amounts of foreign protein while a small change is all that is needed for human metabolism to normalize.  Human physiology is very forgiving as regards enzyme function.  With a whole organ system like lungs or kidneys there is a lot of leeway one needs to get below 50% functioning and really often down to below 30% functioning before one is in serious trouble.  With enzymes there is even a far greater level of safety.  One has to get down to below 10% functioning before there is a usually a noticeable problem and really down to 5 or 3 % before one has serious, life threatening disease.  With how well things went with bacteria, you just need a small effect to correct the human inborn errors of metabolism.  So in the late 1980s and early 1990s there was tremendous enthusiasm for gene therapy with the thought that genetic diseases might be a thing of the past.  History has shown that it isn’t so simple and we don’t know as much as we thought.  To date there has not yet been a single successful definitive gene therapy, and this most recent study is quite notable in that it may be the first.

While I am tremendously thankful for this wonderful advance in treating a tragic and life threatening disease which causes so much suffering to patients and families, there is still reason to be only cautiously optimistic and even to wonder if such a technology were mastered would it always be put to such necessary uses.  As regards the second point, one might look at what I learned with my recent review of Marie-Monique Robbins excellent and spot on book, “Die, Monsanto Die!!!” er … rather “The World According to Monsanto”.

As an aside I don’t want to get off track on a technical discussion of different gene insertion approaches or gene modification in bacteria versus plants versus humans just to point out it occurred to me that Monsanto is altering the germ cell line of plants, something ethically outrageous and practically speaking, seriously dangerous.  It is not at all the same thing as altering the somatic cell line in a single seriously ill human patient.  This approach technically is also why they are able to have a measure of “success”. If you shoot ten thousand seeds with a gene gun and one survives you are on your way, however, you can’t kill 99.9% of your patients in a gene therapy trial.  Again, as regards gene modification in higher organisms we still really don’t have a clue what is going on.

The approach used in clinical human trials to try and change the genome involves using a virus to carry the new gene as a payload and hope it inserts itself into the genome.  So as regards the second point I made a while back about being cautious with these results, for one this study was only in six patients with a, at this point short term, increase in enzyme function of, if memory serves to 3-11%.  There have been a number of times in the past that it also appeared a gene therapy was successful only to not turn out so.

One was the treatment of a small number of patients with the disease Severe Combined Immunodeficiency of the adenosine deaminase deficiency type, one of the “boy in the bubble” immunodeficiency syndromes.  While the treatment was initially successful, about half, from memory, of the treated patients went on to rapidly develop a specific rare type of serious leukemia.   It was later concluded that the particular virus used to deliver the gene most likely had a propensity to insert itself into a particular area of the DNA that would cause this cancer.

Even more concerning and tragic was the case of 18 year old Jesse Gelsinger.  Mr Gelsinger suffered from a moderate case of a genetic disease known as ornithine decarboxylase deficiency.  This gene therapy study was funded in part by the Office of Orphan Products while I worked there and though I was not directly involved I did encounter data, clinical records, photos and hear the opinion of pathologists and other experts.  In essence all of his major organ systems melted over about three days after receiving the treatment.  As far as I can tell no one knows what the hell happened.  It was classified as a massive systemic immune response. This is also notable because the viral “vector” used to deliver the gene was a modified adenovirus.  So just as viruses will recombine with human DNA they are also quite promiscuous in recombining with each other, hence the attempt to match the influenza vaccine to the strain that has arisen that year.  It is both a theoretical and experimentally documented concern that genetically modified viruses can revert through recombination to the “wild” type strain.  Adenovirus is better known as the most frequent cause of the common cold.  Seeing as the cause of death was not clear, one can not help but speculate what could have possibly happened if Mr Gelsinger had had a cold at the time of his treatment.  While it is science fiction like, again no one obviously enough knew what they were doing, and there is certainly a theoretical concern that you could have ended up with a pathogen that spreads as easily as the common cold and kills in three days from multi-organ system failure.  Damn it, I started out so cheery and optimistic!  Anyways that one shut down all gene research in the country for a few months.  In this new hemophilia study though they are not using an adenoviral vector, they are using an adeno-associated viral vector, whew, no worries eh?

So where does this leave me?  I am delighted that there may, possibly, be a start towards a new way to treat an awful and tragic disease.  If by chance we master such a technique I sure hope we know how best to use it, you know use it to treat others as we would want to be treated ourselves, the Golden Rule isn’t it called?  Now didn’t I hear some physician or maybe “politician” talking about something like that the other day?

Ciao,

Paul

Related Posts

The World According to Monsanto, Marie-Monique Robins

The Astonishing Court Case of Becky McClain

The Armageddon Bug

Potentially Landmark Gene Patent Ruling

Introduction to Genetics: Parts  I , II, and III

What Really is DNA, Parts I and II

All this is by way of preface for a write-up on a recent study on prostate cancer screening.

Yearly Prostate Cancer Screening Does Not Lower Total Number Of Deaths

“Mass prostate cancer screenings do not lower total number of deaths from prostate cancer, researchers from Washington University School of Medicine at St. Louis reported in the Journal of the National Cancer Institute. They added that mass routine screenings do not even reduce numbers of deaths among males in their fifties and sixties, as well as patients with underlying health conditions.

The authors cited a US study involving 76,000 males that revealed that after six years of aggressive, yearly prostate cancer screening, there were more tumor diagnoses, but the number of deaths from prostate cancer did not drop.

The latest results of PLCO (Prostate, Lung, Cancer, Colorectal and Ovarian), which were published on January 6th, showed that the majority of men do not need to be screened every year for prostate cancer.

Lead author, Gerald Andriole, MD, wrote:

“The data confirm that for most men, it is not necessary to be screened annually for prostate cancer. A large majority of the cancers we found are slow-growing tumors that are unlikely to be deadly.”
In the PLCO study, males aged 55 to 74 were randomly selected to receive routine care or a PSA test once a year for six years plus a digital rectal exam for four years. Routine care means the patient only gets a PSA screening test if the doctor recommends one.

Dr. Andriole explained that this report provides updated data on an earlier report published in NEJM (New England Journal of English), 2009, when the team could not find any mortality benefit from routine prostate cancer screening.” Read More

Even back when I was doing database work urologists where trying all sorts of variations on the PSA test to see if things could be improved, for instance PSA density (i.e PSA levels/volume of prostate) or PSA velocity (i.e. rate of change of PSA over time).  Actually, I was fortunate enough at that time to help co-author a study looking at using a neural net based system and a number of variables (PSA, Gleason grade, surgical margins etc) to see if prostate cancer recurrence after surgery could be predicted.  I’ll dig out the paper if anyone is really interested but in a nutshell, while not a huge advance, neural nets are cool and they look to actually work a little better than traditional statistical approaches, on the downside who knows exactly what they are doing or how they are working.

So to sum it up it turns out that despite the Prostate Specific Antigen name, PSA just isn’t a very good test for prostate cancer and even when it accurately finds a cancer there isn’t a great home-run type of intervention.   Really what the evidence and studies are telling us is that as regards survival (a really good end-point) prostate cancer screening is worthless, but far be it from me to put it so bluntly.  With what a slow growing cancer prostate cancer is (which is one of the reasons the traditional kill all fast growing cells approach doesn’t work well) it is probably a great candidate for things like improving anti-oxident levels and the like.  Haven’t looked in the literature to see if there is anything on more natural, orthomolecular approaches and prostate cancer will try and do that some time.  However, seeing as traditional medicine doesn’t have a great offering, the traditional approaches have very serious to awful side effect profiles and one has time with the slow growing cancer to try alternative approaches I can’t imagine why anyone with prostate cancer shouldn’t look into them.

I recall now that one of the residents who rotated through the Center for Prostate Disease Research was one Dr. Finger and so it also occurs to me that a side benefit to this recent study is that the routine yearly finger wave or digital rectal exam of the prostate should now also be a thing of the past.  Yet another bizarre and as it turns out useless practise brought to you by conventional medicine.

Alright, the first and foremost point is, never, ever, ever, take Tylenol(TM) (generic name: acetaminophen or paracetamol) to treat a hangover.  The reasons for this are pretty straight forward.  First on the alcohol side, a common sequelae of chronic alcohol consumption is alcoholic liver disease, which can proceed to cirrhosis of the liver, which can proceed to liver failure and death.  Even with a successful liver transplant one is faced with attempting to forestall immune rejection of the foreign organ and left with a decreased quality of life and expected lifespan.  Alcoholic liver disease is the most common cause of liver failure in western societies.  The CDC estimates some 14,406 deaths per year from alcoholic liver disease, while Johns Hopkin’s puts the figure at around 20,000 deaths per year.

Let’s turn now to Tylenol.  With an estimated 2,000 cases per year, acute liver failure is much less common then chronic liver failure.  However, just as alcohol is the number one cause of chronic liver failure, Tylenol is the number one cause of acute liver failure in Western societies and accounts for nearly half of all acute liver failure diagnoses.  As the authors of a recent study on this commented, “acetaminophen hepatotoxicity far exceeds other causes of acute liver failure in the United States.”  So we have in alcohol and Tylenol the number one causes of chronic and acute liver failure respectively.  “Hey you got chocolate on my peanut butter, you got peanut butter on my chocolate.”  You can begin to see why it is never a good idea to mix these two drugs, it is a recipe for disaster.

Before going further it should be noted that acetaminophen is the most widely used analgesic in the United States.  Why is this drug still on the market, much less sold like tic tacs over the counter?   I don’t have an answer for that.  The U.S. Food and Drug Administration has recently made some weak and half hearted efforts to limit the individual dose size of size of acetaminophen, but despite all the sound and fury over looking into the issue that is all they have done, this is quite clearly an inadequate response.  One could eliminate without any cost the number one cause of acute liver failure in the United States.  This drug should be pulled from the shelves immediately and at best be available as a prescription drug with a black box warning concerning its dangerous hepatotoxicity.  Considering its rather unimpressive anti-inflammatory effects, the availability of similar less toxic alternatives and the thousands of people it has killed already it likely should not even be available with a prescription.  The negligence and turpitude of the FDA in this matter is responsible for the lingering deaths by liver failure of somewhere in the ball park of 500-1,000 people in the United States every year.  I suppose they are too busy trying to limit access to vitamins and harassing walnut growers and Amish farmers.

A study out of England was released just this past November that confirms the danger, known for decades now, of using acetaminophen in conjunction with alcohol.  This research extends previous findings by documenting a synergistic toxicity between alcohol and tylenol.  The researchers found that staggered doses over a period of a few days of even slightly too much acetaminophen could potentially cause liver failure.  Even more concerning, while the total dose was less in the staggered use, than that seen from liver failure caused by a single Tylenol overdose, the mortality was higher from repeatedly taking a little too much Tylenol in conjunction with alcohol.  Often times, these patients had no idea, nor sometimes even their doctors as the blood levels of Tylenol would be only slightly elevated, that they had overdosed on acetaminophen and were facing the prospect of liver failure.  Lastly, as with alcohol, there are known genetic variations in how individuals process acetaminophen.  While they would not be aware of it, some individuals would be far more sensitive to the toxicity of this hepatotoxic drug.

Alright, that’s it, my first Health for the Holidays tip, don’t take Tylenol for a hangover!  You also don’t want to take aspirin, though in that case you are facing a synergistic effect that can lead to a greatly increased risk of a potentially fatal gastrointestinal bleed.  Not a very cheery holiday post, but then again as I said, I’m not really aware of what is common knowledge and what I picked up along the way.  Will try and do the next post on what you actually could do that would be healthy for a holiday hangover.

Paul

‘yet the literature shows that again and again the lesson was lost, buried by every kind of obfuscation that medicine, prejudice, and perhaps parsimony could produce.‘

It made me feel like you were talking about the FDA (grin)’

——-  is undergoing chemo for inoperable cancer……. would it be OK to let them have a copy of this to read and consider please? Then perhaps she could share it with her oncologist.

Blessings and take care,   Clare & Ken in Tasmania

_________________________________________________________________

Hi Paul:

Fabulous article on Vitamin C. Very thought-provoking. … I got a large number of tips/ideas from this article.

Dr. Stephanie Senneff, PhD: Alternative health lecturer and University of MIT Computer Science Professor

_________________________________________________________________

Paul, both of these are amazing accomplishments!  And they are enjoyable to read as well.  …. Thanks for sending me these.  They are great papers

Andrew, Physician, California

_________________________________________________________________

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Ciao,

Dr. Maher

I have said on this site previously that I don’t do politics and I don’t do peoples motivations – at least as much as possible.  I have good reasons for this, for one the science is enough of a topic unto itself.  Secondly, I am not a politician or a psychiatrist.  Thirdly, let’s suppose I spend hours and hours of time and finally conclude two things 1) take 50 mg of A and 250 mg of B to be happy and healthy and 2) So and So is a jerk.  What has 2) really added, especially on the happy and healthy front?

Then again there are times when the “so-and-sos” really impact on health in a way that one can’t so easily avoid.

In such cases, with recent reading I have found new respect for investigative journalists, who do such a great job with the wither dos and why fors.  My first introduction to this was Mr. Chris Bryson’s excellent tome “The Fluoride Deception.”  If you have read this yourself or realize how highly I think of this work, then you can see what a great compliment I give by saying that Marie-Monique Robin’s “The World According to Monsanto” is in the same realm, both as regards the quality of writing and as regards the dramatic importance of what she discusses.

Also like the Fluoride Deception, The World According to Monsanto is deeply and viscerally disturbing, while if anything the potential for harm being discussed is far greater than that even from water fluoridation.  While I have an extensive background looking at the genomics of rare diseases, I suspected the topic of GM foods would be incredibly broad, even overwhelming to get a handle on.  Instead, I came to realize from this book, that due to specific policies, the exact opposite is true.  There is almost nothing at all that has been peer-reviewed published on the topic and that is the result of very specific regulatory decisions taken concerning GM foods.  I will say again, there are hardly a handful of articles in the peer-reviewed literature looking at the health effects of any given GM food, let alone the incredibly complex issue in general.

As noted in the book, this is due to a curious decision by the U.S. Food and Drug Administration (FDA) regulators to declare a-priori, and over the objection of FDA scientists, that GM foods are “substantially equivalent” to non genetically modified foods and thus can be released without any oversight, studies or regulation.  The terrible absurdity of this position (and why there are no studies on the health effects of these new organisms) takes a moment to sink in and requires departure from the book review for a brief moment.

Prior to Oswald Avery’s experiments in the 1940s proteins were thought to be the molecule of genetic inheritance.  Avery showed this wasn’t the case by inoculating mice with a lethal and a non-lethal strain of bacterium.  When mice were inoculated with dead lethal bacterium and live non-lethal bacterium, the non-lethal bacterium somehow became lethal and killed the mice.  Avery showed that the lethal “transforming principal” from the dead bacterium was in fact DNA paving the way for the whole science of genomics.

The key word in all this is “lethal.”  As Watson and Crick showed us, DNA is the blueprint of life.  One can now, through genetic engineering add any given gene to a food.  One could add the gene for botulinum toxin, or Avery’s lethal transforming factor; one could add the sequence for a bacterial pesticide toxin – oh wait, that is what is being done.

The reason, again as brought out in the book, why this is being done goes back to an equally preposterous position and to money.  You see it is the position of the U.S. government, as it also attempts to “harmonize” with other governments around the world, that genes are patentable.  This is “patently” absurd.  Genes are products of nature, one could just as easily patent hydrogen.  Nor does it acknowledge the poorly understood potentials and dangers of dealing with self-replicating organisms, not to mention the ethical problem of patenting the mechanism for inheritance in life.  As Crystal Gayle sang, “Don’t it make my brown eyes blue.”

Still, having no regulation and being able to patent the food supply raises the possibility of both enormous profit and draconian control.  The self-contradiction of being able to “patent” a novel food, which has already been declared as not needing to be regulated by the FDA as it is “substantially equivalent” to the un-modified food hasn’t apparently concerned any of the involved business interests. Well, so there is a real theoretical danger here, but how bad could things really be, who would exploit all this?  Here the author does a great service in detailing the history, behavior and ongoing policies of the Monsanto company.

Monsanto got its start as a chemical company in St. Louis, Missouri.  In part I of the book, “One of the Greatest Polluters in Industrial History”, Ms. Robin details an astonishing number of environmental tragedies that Monsanto either directly caused or has played a large role in.  One of these is the widespread production of polychlorinated biphenyls or PCBs.  These persistent organic pollutants (POPs) have devastated whole towns, led to massive litigation, against Monsanto and as the name implies are difficult to remove from the environment, increasing in concentration as one goes up the food chain.  Indeed, a scientific paper caused some stir, years back, when researchers documented PCB contamination in the food supply within the Arctic circle.  Another, persistent organic pollutant, is the well known, DDT, the subject of Rachael Carson’s book “Silent Spring“ which is credited with helping to launch the environmental movement.  Monsanto has been a major manufacturer of both DDT and another POP, dioxin, and faces lawsuits for the damage they caused.

Monsanto has always maintained close ties with the defense industry, being an important participant in the WW II Manhattan project to develop the atom bomb.  However, where they really made their money in this area was with the production of the defoliant Agent Orange, which they supplied to the military throughout the Vietnam War.  Again this product has led to the deaths, disability and/or congenital deformity of thousands of U.S. citizens and untold thousands of Vietnamese citizens.  In chemical consumer products, Monsanto cut its teeth with the artificial sweetener saccharine and for a time was a major producer of aspartame.

In recent decades Monsanto has transitioned towards agricultural products and this remains its focus today.  Monsanto has championed the use of chemical herbicides and much of its revenue stream is built around its RoundUp(Tm) brand herbicide.  When Monsanto became aware of GM technology they refocused much of their company around it.  So we have Monsanto to thank for recombinant bovine growth hormone in North America, a topic I hope to address on the blog and one which itself could be the subject of a whole book.

Far worse than the recombinant bovine growth hormone debacle has been Monsanto’s entrance into the realm of genetically modified seeds.  As I said at the start of this review I expected this topic would be enormously complex.  The genome is the whole blueprint of life, there must be all sorts of approaches to make foods more nutritious, drought resistant, tailored to certain soils and climates.  Nope, Monsanto produces 90% of the GM foods in the world and they have two primary GM product approaches.  One is a manipulation that makes plants resistant to their RoundUp(Tm) herbicide so they can sell more of it, the second is the insertion of gene for a bacterial pesticide, B. thuringiensis toxin.  So we now have round-up ready corn, soybeans, cotton etc., and likewise Bt corn, soybeans and so forth.  While there is lip service paid to things like vitamin A enhanced rice and the like, the truth of the matter is this manufacturer of Agent Orange views the genetic modification of the world’s food supply as entirely a commercial opportunity to exploit to enhance their market share and claim legal rights over the food supply.

How they were allowed to get away with this is a study in regulatory capture.  Michael Taylor who served as a lawyer for Monsanto went to work for the FDA as the Deputy Commissioner for Policy.  There he guided and signed off on the policy of “substantial equivalence” between GM and non GM foods, meaning no toxicity studies were needed for marketing and even no labeling required of GM foods for consumers.  This is how companies, most notably Monsanto are able to modify the genetic blueprint of a food in any way, be it the addition of a gene for vitamin A, or rattlesnake venom, market the food as though it is unchanged from the natural food, yet use bogus patent law to claim ownership not merely of say a bushel of rice seeds, but of the whole abstract concept of a particular variant of modified rice.  After getting the policy passed Mr. Taylor returned to Monsanto where he served as a vice president.

In part III of The World According to Monsanto the author explains just how ruthlessly and rapidly Monsanto pressed its advantage.  Over whole countries and whole continents in the time frame of a couple decades crops have shifted from no GM, to 80, 90% and more GM.  There are no published safety studies on these modified foods.  The few people who have looked into it, such as highly respected plant expert Dr. Árpád Pusztai have reported very disturbing health findings in mice.  Dr. Pusztai was soon sent unceremoniously packing, fired from his job of 36 years at the Rowett Research Institute for having the misfortune of publicizing valid but politically unpopular findings concerning the safety of GM foods.

While there is not time to go into it in this book review, I would just say that the process of inserting a gene into DNA is not single technology but a whole family of varied approaches, while genetic uptake is both unreliable and sloppy, or imprecise if you prefer.  Even if one used the exact same approach with the exact same gene and plant a second time one would get a different product depending on where the gene gun (the most common technology for commercial plant genetic manipulation) happened to shoot the gene into the host genome on that particular attempt.

Upon reflection I am not certain if “terrifying” isn’t too strong a word to use (see The Armageddon Bug) when contemplating that these untested, self-propagating organisms have been released into the wild and now comprise a significant portion of the world’s food supply.  We are conducting a massive, unmonitored experiment, with unknown consequences upon billions of people.

Ms. Robin describes the lengths to which Monsanto goes to ensure monopolistic, even feudal control over farmers.  In North America a veritable army of private detectives is sent throughout farmland trying to spy if any farmers might be illegally harvesting and storing patented seeds from year to year, and ruthlessly prosecute them if any suspicions arise.  In other countries whole ecosystems are wiped out to be replaced by monocultures of herbicide ridden land.  Farmers are sold on the purported benefits of Monsanto’s GM products, less pesticides and herbicides, better harvests, only to find that after a few short years they are using more pesticide and herbicide have less yield and unhealthy plants in addition.  However, because of the seed patents, the farmers contracts have often trapped them in money losing bondage to Monsanto.  There has been a documented spike in suicides amongst Indian farmers who adopted GM seeds, with one of the most frequently seen forms being death by ingestion of the RoundUp(Tm) herbicide.  In America, non GM farmers have had to band together to pool legal resources, amazingly enough to defend themselves from being charged as thieves when their crop lands are harmed by Monsanto’s patented GM seeds blowing onto their lands.

In summary, Monsanto has been an astonishingly destructive company, they are the primary financial impetus behind the whole global GM food campaign, their policies and influence pose a threat to the health and food supply of much of the world.

This brief review doesn’t begin to do justice to the excellent, detailed investigative work of Marie-Monique Robin, work for which she won the 2009 Rachel Carson award.  It is an astonishing piece of investigative journalism on a vitally important topic that was desperately in need of some light.  I can just say that she has done us all a great service by putting out this disturbing and authoritative book.

The World According to Monsanto has been translated into over a dozen languages and is available at Amazon.  Ms. Robin has also directed a groundbreaking movie covering the same topic.

To read other book reviews on this site visit the Book Reviews section. ___________________________________________________________

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I have been meaning for some time to ramble on about topics I know nothing about and, as I am pressed for time to do a really focused health post at the moment, I thought this was as good a time as any to start.  Hey it works for 90% of journalists, talk show hosts and media personalities so back off, okay just back off!  I am also considering rudeness, overt condescension, belligerence and rampant egotism as a marketing ploy.  People make careers out of this in TV and Radio these days, its all the rage, yea, you heard me nitwits, shheeez.   For some reason I seem to be channeling one of the puppets from Mystery Science Theater 3000, anyways the shows starting. 

So the first thing that got my attention recently was this article about the long awaited Chevy Volt with its batteries bursting into flames.  Isn’t that odd.  Tesla Motors has made a number of cars with lithium ion batteries and hasn’t had a problem.  GM briefly had a battery (not lithium ion) powered car a decade ago and had no problems.  The battery issue hasn’t been a show stopper with hybrids.  The car is named after Allesandro Volta, the inventor of the battery.  Why is the number one U.S. car maker having such a problem with finding a reasonable battery technology.

To cut to the chase GM doesn’t want the Volt to succeed and the “energy problem” has been solved repeatedly in the past, in small and large ways and possibly even in astonishing ways.  I am entirely outside my area of expertise here, however I won’t let that stop me.  And yes, of course the magnificent one is right, I can’t believe I have to put up with so many nitwits questioning my excellence, let alone certitude -you know it kinda grows on you- at least I’m not calling for WW III.  As a somewhat related aside anyone ever notice that if you put a little different spin on it, The New York Times motto of “All the News That’s Fit to Print” sounds suspiciously like, in the words of The Who, “You Only See What We Show You”.

Alright, enough nonsense, on to example one.  I recall following with great interest some years back Brian Appel and his Changing World Technologies.  This company was looking to commercialize a form of thermal depolymerization technology.  Regarding this technology, in a nut shell what has been found, was that oil took millions of years to form because it was waiting for the proper conditions to occur.  If one replicated the necessary temperatures and pressures oil could form in a matter of hours from almost any organic feedstock.  Agricultural waste, old tires, municipal waste it doesn’t matter.  Even hazardous medical waste could be treated this way, destroying any pathogens while yielding oil to boot.  Other valuable elements would also result as side products of the process.  A pilot plant was producing oil from different feed stocks and it was estimated when scaled up would produce oil at below market prices.  A commercial plant was built in Carthage, Missouri to process the waste from a nearby Butterball turkey plant.  Somewhere around this time I saw that ex CIA director James Woolsey had come on board as a corporate advisor for Changing World Technologies.   At the time I recall thinking, “Oh, lucky, lucky you, see what high level political support you have”.

Well once the Carthage plant was up and running there began to be complaints issued against it that it smelled bad.  This led to a number of fines.  Scrubbers were put on the outlet pipes but apparently this didn’t solve the problem, there were more complaints, people in town saying they were ill from the smell, this led to more fines, decreased output, increased cost of production and threats from state authorities that they would shut down the plant.  More changes were made and I recall though I can’t find it now, an article with Mr. Appel in the middle of his plant saying he couldn’t smell anything, while some complaints were coming on days the plant was closed.  Because of the complaints the governor of Missouri ordered the plant closed. To make a long story short, the company eventually went bankrupt, though they have recently re-opened, however the contract with butterball Turkey was rescinded and they are now using used fry oil as a feedstock. Two people in Carthage have also apparently sued the company for their stink.

This is all very odd.  We have municipal sewage treatment plants in every county, I can’t imagine decaying turkey waste from Butterball itself is a treat to be around.  More to the point, both Union Carbide (Bhopal disaster) and British Petroleum (Gulf oil spill) are ongoing concerns.  From memory, I believe Mr. Appel estimated that something like 20- 40% of domestic U.S. oil consumption could be supplied by applying this technology to various waste streams, with the added benefit of helping to keep the environment clean.  While I personally consider CO2 a red herring, it might also be worth mentioning that this approach would be essentially carbon neutral.

As far as I can tell this technology was never invalidated, and at this very early stage was either cost effective or at least very close to economically competitive.  Instead of being developed, after Bhopal, the Gulf Oil Spill, Cherynobyl, Fukishima, etc, etc. the approach is ignored.  The only thing standing between thermal depolymerization and widespread adoption as far as I can find is that it supposedly smells bad.  Oh, lucky, lucky you Mr. Appel, you have a former head of the CIA as a corporate advisor.

I have come across so many positive, often simple, small incremental advances I wouldn’t know where to begin discussing them.  I would just say that I owned twenty years ago a car that got 35-40 mpg and these were available decades earlier.  Isn’t it odd that there is no improvement.  There seems to be a policy cap in the U.S. at about 35-40 mpg with a limited number of 50-55 mpg hybrids.  Things are about ten mpg better in Europe, however, I think without any real innovation at all one could market a 75 mpg car that is inexpensive and consumers would want to purchase.  You might say that sounds overly ambitious, well here are the specs on the 2011 diesel Mercedes Benz  C250 CDI,  201 horsepower, 0->62 in 7.1 seconds, top speed 149 mph, fuel economy, 58.9 miles per gallon.   Yes 59 mpg, somehow I suppose if I was looking for fuel economy and you really pressed me I suppose I could make do with just 125 horses.  Of course this Mercedes isn’t a hybrid, just a diesel, an approach which is inherently more fuel efficient, in fact I’ve never seen a diesel/hybrid, isn’t that odd.  How about a 110 horsepower Volkswagen diesel/hybrid that gets 80 or 90 MPG, nah … that would never sell.   To be honest, I even wrote Volkswagen and asked them to do this and they were kind enough to get back to me and thank me for annoying them.

Enough with the gear head stuff, let’s switch gears again and talk about some more esoteric stuff.  Some time back I did a couple posts making the case that chickens might in fact be alchemists.  The question that this really boils down to, and one I am not really in a position to evaluate, though that won’t stop me, is whether there are in fact, low energy nuclear reactions, better known as cold fusion.  While I’ll likely take some heat for it, I suspect, under very certain and specific conditions, it is valid.  In any event there is an Italian scientist who claims he has a functioning cold fusion system that can generate megawatts of power for pennies on the dollar and produces no radioactivity or pollution.  Ahhh, you probably don’t want to hear about that, and this post is getting sort of long.  Tell you what, I’ll try and finish it up tomorrow and until then leave you with …

Steve Wiest and the sounds of “Cold Fusion” (Amazing what you find on the web)

The Telegraph:  Wonder drug that stole my memory,

When I read many of the comments on this story I also find myself wondering, should a first hand patient report of disease be considered more or less authoritative than a second hand write-up by a physician in the peer-reviewed literature?

Scientific American:  It’s Not Dementia, It’s Your Heart Medication: Cholesterol Drugs and Memory

NewsWithViews.com: FDA, TEXAS MEDICAL BOARD FIGHTS TO KILL CANCER CURE

Interesting article, I’ll give a brief bottom line on this as I see it.  Dr. Burzynski is an MD/PhD who graduated first in his class in medical school in Poland.  The laboratory analysis of the composition of blood and urine is at the heart of modern diagnostic medicine.  Decades ago Dr. Burzynski noticed something that hadn’t been discovered prior to this.  The profile of various small peptide molecules in the blood and urine is different between healthy and cancerous patients.  Further research indicated that this class of small peptides was involved in the epigenetics of cancer, i.e. played a role in the turning on and off of the expression of various genes that were being aberrantly expressed in cancer.  From here he developed a treatment based on “neoplastins” to replace the missing small peptides in cancer patients and restore their gene expression to normal.  That therapy is in phase III trials.  He also by using this new analysis of blood and urine has been able to more clearly define the genetics of any particular cancer, allowing for individualized treatments with often off labels use of conventionally approved drugs.  His approach to cancer treatment has shown great success.  If you visit his website you can see the testimonies of individuals cured of glioma (aggressive brain tumor).  Glioma, under standard care is basically a death sentence.

For his fundamentally advancing the understanding of cancer, opening up a new realm of laboratory diagnosis and showing great clinical success in treating cancer patients, what has been his reward?  Well, the state of Texas spent a decade trying to take away his medical license.  When this was finally definitively defeated  in court, they just recently brought a new complaint against him and are at it once again.  Really makes you wonder if some people genuinely don’t wish to see cancer cured. Anyway interesting article.

NewsWithViews: FDA PROPAGANDA ATTEMPTS TO DESTROY THE DIETARY SUPPLEMENT INDUSTRY

Along these line’s I have noticed that Dr. Ron Paul’s proposed budget slashes funding for the FDA by 40% and for HHS overall by 20%.

RON PAUL’S BUDGET PROPOSAL:  Oh sure it sooounnds great, but who is going to raid the Amish farmers at 4:00 A.M. if the FDA doesn’t do it, Who Ron, Who!

Alright I got rid of my TV, I guess over a year ago now, but while entirely off topic I do recall this was a pretty good political documentary that in my view sums up our current situation pretty well.

Ciao, Paul

“The story of Vitamin C then begins with the disease of scurvy.  Hippocrates first described this often fatal vitamin deficiency disease some 2,500 years ago noting that it was characterized by bleeding gums, hemorrhaging and death.  While not a pretty picture, clinical scurvy is also thankfully, generally rare as vitamin C may be found in both plant and animal sources.  Nonetheless, a diet devoid of fresh fruits, vegetables and meats if eaten for extended periods will lead to disease.  One such environment historically was long ocean going voyages where scurvy sometimes took a horrendous toil.  In 1499 Vasco Da Gama lost some two thirds of his crew to scury, in 1529 Magellan lost 208 of 230 crew, primarily to scurvy.  Legend has it that the use of fresh fruit to reverse scurvy was the result of a voyage of Christopher Columbus. …”

Skeptic’s Health Journal Club Medical Monograph

I have talked a fair amount previously on this site about why I felt salt wasn’t bad for you, see (Is Salt Good for You? Part I, Is Salt Good for You? Part II, Did They Just Say Salt Cures Heart Disease?) .  In the first two articles I noted that, as with water soluble vitamins though even more so the body can easily waste excess sodium in the urine and has strong systems in place to prevent hypernatremia.  I also mentioned that the literature seemed to show people with greater sodium intake living longer and having less disease.  In the third article I mentioned a recent, massive study from Europe that found not only was salt not bad for you but astonishingly in this large study there was an 80% decrease in heart disease amongst those who took in the most salt!  Salt was found to prevent the very disease that we have always been told that salt restriction would prevent. 

I concluded that last article by noting that perhaps the American Heart Association, which continues to champion drastic salt restriction might start looking for a new hobby horse to ride.  In this light I am quite encouraged to see others are buttressing and coming around to my point of view.  An extensive meta-analysis review of the literature on salt was just released by widely read and respected in medical circles Cochrane reviews.   This review published in the American Journal of Hypertension and widely picked up on by the media may be read in full here.

One of the reasons we got in this mess with salt restriction is because of another trend I have railed about on this site, an over reliance on risk factors or surrogate markers for endpoints.  High blood pressure (within reason), is not a disease in and of itself, rather a risk factor for other diseases.  As “debunkers” are so oft to robotically exclaim, “correlation is not causation.”  So is the case here.  While I do believe that high blood pressure is a valid marker for increased risk of heart disease, when ever one has gotten away from looking at the disease itself one runs into the potential for a number of problems.  First off might be, often seen in retrospective studies, the “cart before the horse fallacy” i.e maybe it was the heart disease that caused the high blood pressure not vice versa.  Second maybe a common pathology, say small vessel inflammation has caused both and correcting blood pressure has no effect (again this is not the case as seen in the literature but is presented to illustrate why one is always better off dealing with an actual disease).  Finally and worst of all, the association may be a compensatory response.  For instance someone with severe anemia would be expected to be tachycardic (i.e. have a fast heart beat).  In this case though correcting the tachycardia would not only not be helpful, it would make things much worse.

Alright I think I have beaten that horse to death, I say all this just by means of preface that the Cohrane review restricted itself to only examining a number of laboratory values for levels of various electrolytes and hormones.  They did not formally delve into any clinical endpoints.  My guess, and that is all it is, is that things might have looked worse if they did and that it was a political decision to restrict the scope of the review in this way so as to provide an easy way to save face while changing public health policy.  Even with this restricted scope the findings are almost laughably bad.

First, again not talking about heart disease here, as mentioned in previous write-ups sodium seems protective against that disease, looking at salt’s vaunted effect on blood pressure, yes salt restriction lowers blood pressure.   In people without high blood pressure, after looking at some 167 previous studies, salt restriction caused an average 1% lowering of BP and in those with high blood pressure a whopping 3.5% decrease.  In other words if your blood pressure was 120/80, by restricting salt you could expect to get it down to 119/79.  If your blood pressure was 160/100, it would on average reduce to 154/96.  This is about the most perfect illustration I have ever seen of the distinction between statistical significance and clinical significance.  Yes there is after looking at thousands and thousands of people a clear, statistically significant decrease in blood pressure, it is also so small as to be basically worthless.

The reviewers also note that, as sodium is essential for life, the body has multiple mechanisms in place to attempt to prevent it from being lost in the urine if there is not enough present to easily keep it in its tightly regulated normal physiologic range.  So one point that they bring out that I hadn’t touched on in previous posts is that people who chronically take in too little sodium have elevations in renin, aldosterone, adrenaline, noradrenaline, cholesterol and trigycerides.  While the elevation in cholesterol is the one played up primarily in the press, it can also be noted that a number of these substances would be seen to be involved with 1) attempting to prevent salt loss, (renin and aldosterone) and 2) attempting to preserve blood pressure (adrenaline and noradrenaline).

While it was not the primary theme of their analysis, the reviewers also commented briefly on some clinical endpoints, noting,

“Furthermore, reduced sodium intake seems to harm patients with heart insufficiency and diabetes type 1 and 2. In all three patient groups reduced sodium intake is associated with increased mortality.^3,4,5,6“

Ho hum,  nothing to see there.   They conclude by stating in part,

“Due to the relatively small effects and due to the antagonistic nature of the effects (decrease in BP, increase in hormones and lipids), these results do not support that sodium reduction may have net beneficial effects in a population of Caucasians.“

I would go further and say that interfering with the normal levels of the most prominent extracellular cation, that is to say sodium, looks to be a really reckless way to try and reduce blood pressure.  The evidence tied to clinical end-points at best indicates no effect on heart disease rates, while more likely, restricting sodium is contributing to heart disease and overall mortality in other common diseases.

Of course to get an idea of the conundrum this sort of study poses we can look at an excerpt from a recent news write-up on the article.

“The researchers’ bottom line?

“In my opinion, people should generally not worry about their salt intake,” Graudal told HealthDay.

The findings are published in the Nov. 9 issue of the American Journal of Hypertension.

In July, another review found “no clear benefit” to cutting back salt, saying it did not reduce the likelihood of dying from heart disease or having a heart attack, CBS News reported.

Some experts disputed the new study.

“Over 50 public health organizations can’t be wrong on this one,” Dr. Lawrence Appel, professor of medicine, epidemiology, and international health at Johns Hopkins Medical Institutions in Baltimore, told WebMD.”

Why it’s preposterous I tell you.

So perhaps in about five to ten years time or so after the whole unprofitable and in hindsight nonsensical salt reduction campaign has been swept under the rug it would not surprise me at all to see articles along the lines of “Are You Salt Phobic??? Take the Quiz!“  This would again be to not ever dare mention that medical authorities were morons and dead wrong for decades harming thousands of people along the way, but that once again, an ignorant public is screwing up by being dumb and not following the medical community’s advice.  I would see it reading something like this

“For a long time the medical community debated the merits (and functions) of salt in heart disease.  These complicated and intense discussions often led to some confusing advice for Joe (and Jane) Q Public looking for a simple answer to how much salt should I have in my diet.  The good news, for many years now the majority of authorities have agreed, that with a few exceptions, salt is not so bad for people as once thought and may even have some benefits. 

However, those with a more conspiratorial bent among us, and even some of us who just don’t keep up as much with things as we should aren’t always ready to let it drop so easily.  With urban legends like fluoride being bad for you refusing to die it is understandable that a few people remain “salt phobic” perhaps even thinking, that like the myths on fluoride, the government now doesn’t care about harming them with excess salt in the diet.  Or they simply don’t have the education to get with the times.  So what you need to know is that salt is really not so bad for you.  Get The Facts!  Take the Quiz and learn your Salt IQ.

… Darn, I would have made one heck of a propagandist.  … If someone asks me where the quiz is I will really get frightened

Ciao,

Paul