Watch a Grizzly Bear get an MRI

Well wishes for Lucy a 3-year-old grizzly from the Montana Grizzly Encounter who received an MRI today #GoCougs
— WSUVETMED (@WSUvetmed) January 17, 2014

The story.

We the Genes!

We the Genes of the United Cells, in order to form a more perfect Union, establish equilibrium, insure homeostasis, provide for the common immunity, promote the general Welfare, and secure Liberty to ourselves and our Posterity, do ordain and establish this Constitution for the United Status of Life. 

In the coming month the United States Supreme Court will likely rule on whether a private company can hold a patent on a human gene.  The company in this case (Myriad  Genetics) has spent a substantial amount of money and time figuring out that mutations in the BRCA1 and BRCA2 genes are associated with an increased risk of developing early-onset breast and ovarian cancer.  Because of this investment the company feels entitled to hold a monopoly on testing and reporting this information to patients who ask their doctor to be screened.  Recall Angelina Jolie's double-mastectomy headlines in recent weeks.

The company feels it has the right to be the only one to read a particular page in a book handed down to a woman by her mother and father.  This book of genes is called the genome. The human genome like the genomes of all other living things has been copied, proof-read, edited, re-drafted and copied again and again countless times over earth's rich and chaotic history. The current edition of your genome is without question a product of nature.

PCR happens.

Using a routine process in basic scientific research called the polymerase chain reaction (PCR) the company can isolate the BRCA1 and BRCA2 genes.  Once the genes are isolated from a blood sample they can be read by any of the well established methods for DNA sequencing.  Neither the method for isolating the genes, nor the method for sequencing the genes are at issue in this case. The patents associated with these decades-old processes have long since run out.  No, The object in question in this case are the BRAC1 and BRCA2 genes themselves. 

Can a company own exclusive rights to read your genes?

I say no. We ought to have the right to pursue any path we like to uncover the information we were each born with. Whether that path be through Myriad genetics, the Harvard-based personal genome project, or sending your blood samples to whoever has access to a PCR machine. Trust me, they are pretty darn common. We should have access to the secrets inside our own cells.

I think there is a fundamental misunderstanding among the justices in this case. The misunderstanding is that in cases of genetic testing the "product" is not necessarily any physical thing but rather naturally occurring INFORMATION.

A technical work-around attorneys representing Myriad Genetics are trying to use is that coding, composite, complimentary DNA (cDNA) is not present in nature and can be patented because it is only produced by scientists. cDNA conveys the sequence information of messenger RNA produced by nature. Though the cDNA itself can be construed as product of human tinkering, the information cDNA holds is not. The information therein is an impression of nature, like a plaster-cast of a wolf-print in the mud, or the ink-blot of a small mouthed bass.  The key piece of information the attorneys for Myriad Genetics leave out is that the cDNA is not used directly but only to gather information from nature.

The patient dos not need or care to have the amplified DNA prepared from their blood sample, the patient wants to know some information so they can make an informed decision about how best to proceed with preventive health measures like a mastectomy or hysterectomy.  Genetic information is a product of nature and is therefore off-limits according to a century of court precedent.

What incentives will researchers have to make discoveries?

While listening to the Oral Arguments in the case between the Association for Molecular Pathology v. Myriad Genetics I am struck at what little credit is given to the motivation propelling scientific discovery.  It seemed to me that the Justices kept asking questions with a particular concern for maintaining a clear market incentive for big genetic discoveries.

It was almost as if the justices were under the impression that market forces are the main drivers of scientific discovery.  This may be a matter of opinion but I do not think Charles Darwin, Jonas Salk, or Carl Woese were in it for the money.

The tone of the Justices' questions regarding market-incentives and scientific discovery reminded me of a conversation on the recent Freakonomics podcast in which the hosts Stephen Dubner and Steve Levitt have the following exchange.

DUBNER: Since fighting cancer is big business, what’s the incentive to find a cure?  

LEVITT: So I would say the incentive for a cancer cure is not really a market incentive, it’s a being a hero kind of incentive. That there are so many doctors out there, researchers, medical researchers who if they could be the one who was forever remembered as the one who prevented cancer, who got rid of cancer, they would do anything to do that. So I think there are really strong incentives out there. And they aren’t exactly market incentives, although I think that person would be quite rich anyway...

I think the "being a hero kind of incentive" is the kind of incentive that pushes the world into a progressively safer more peaceful context. A context where human life-span lengthens and justice systems move away from a punitive to a rehabilitative mode. It is my opinion that knowing as much as we can about our bodies and specifically our genes will allow us to attain an unprecedented state of self-awareness, health and social responsibility.

A Big Problem in Science Publishing

In the following video a prominent medical doctor, author, and anti-anti vaccine activist named Ben Goldacre rails against a big problem in the way scientific data is published. His point is that only exciting and dramatic results get published. Because of this reality all those boring negative results that show no difference between experimental and control groups do not get published.

Take a simple experiment... a bunch of different scientists ask - does drug X work at curing a particular disease? So they get people to volunteer. They give half the people drug X and the other half a sugar pill (placebo). Now say there are 10 different studies set up just like this but only 5 show any difference in the group that took drug X. The studies that show that drug X "works" will get published while those that do not show the drug to have any effect will not get published. Why is this a problem? because the deciders at your bedside (aka doctors) will only see the papers with positive results, while never knowing that there were a bunch of unpublished studies that show drug X to be ineffective. This is a disservice to patients and doctors alike and does not help anyone.

The onus is on publishers to publish everything no matter how un-sexy the result. There is no reason in the internet-age that all results can not be archived in a universally searchable data-base. Doctors and patients need the whole picture when they make decisions, not just the bright shiny bits editors choose for them!

Witches, tree-rings, and LSD

In the moonlight mothers and fathers watched the shriveled toes of a poor beggar swing from the gallows. They placed their faith in God that the death of this "witch" might take away the torment, fits, and visions that plagued their children. That somehow through supernatural forces the sensations of ants crawling underneath their skin, delusions of bursting into flames, and frenzied shrieks of terror in the night would cease. As the the seasons brought new harvests the number of swinging bodies dwindled. But bouts of bewitchment would visit the same valleys for centuries.

This was a typical scene in the medieval villages that lined the Rhône and Rhine rivers. Here, and in other curiously coincidental micro-climates all over Europe something dark and treacherous lurked in the farm fields.

During the cold, wet harvest seasons a deep purple fungus Claviceps purpurea reared its ugly sclerotium amongst the ears of rye. Looking much like the rooster's spur the killer was given the french name - erogot. When rye was milled the flour could contain up to 30% ergot by dry weight. And so it goes that the biochemistry of bewitchment had its origins under the millstones of fifteenth century Europe. 

During this age the peasantry ate an enormous proportion of the darker cheaper rye; upwards of three pounds a day. As the chemicals made by the ergot made their way into the blood and brains of those apparently seized by demons, the unaffected were left to assume they had been bewitched. The linguistic fossil preserved in the very word - seizure - describes the uncontrolled fits the affected displayed. A condition known at the time as "St Anthony's fire"  (aka Ignis Sacer) did not become known as ergotism until 1853 when the clinical connection to the fungus was finally made.

Mycotoxins are poisons produced by fungi and mold. The variety of mycotoxins contained in ergot-infested rye cause two distinct varieties of ergotism - gangrenous or convulsive ergotism. Ergotamine, a powerful vaso-constrictor, prevents blood flow to the extremities and is the main culprit in gangrenous ergotism.  Whereas ergine and lysergic acid hydroxyethylamide cause convulsive ergotism. These lysergic acid compounds found in the ergot fungus have similar effects on the human brain as the psychoactive drug - LSD.  Both LSD and the ergot alkaloids induce hallucinations by a similar and yet poorly understood mechanism.  Structurally similar to serotonin these compounds bind serotonin receptors in the brain. It is not known how this induces hallucinations but it is thought that agonist activity to serotonin releases higher concentrations of the neurotransmitter glutamate in the brain's cortex exciting neurons in random ways.  This would explain the varied psychological effects reported by individuals under the influence of this class of drugs.

By their activity these compounds were known long before their chemical makeup was uncovered. Ergotamine had been used for nearly two centuries in midwifery to stop hemorrhaging after birth and also to induce abortion. In the first half of the 20th century the other ergot alkaloids were probed for alternative medical uses such as blood pressure and migraine treatments.  A young chemist named Albert Hofmann working for Sandoz pharmacueitcal company in Basel, Switzerland literally stumbled across LSD while performing organic synthesis of ergot alkaloids.  His wild bicycle ride is a story of scientific lore worthy of its own post.

But here we are focused on the science behind medieval bewitching. The connection between ergotism and witch trials was first proposed by Linda Caporael in 1976 where she hypothesized in the Journal Science that Ergot could have been the real world cause of the supposedly supernatural events that transpired in the village of Salem, Massachusetts in 1692.  
 

In her paper Caporael outlines the evidence for ergotism being the scourge that set off the string of hangings accompanying the infamous witch trials in Salem.  She points out that the symptoms of ergotism; spasms, the sensation of ants crawling under skin, and the feeling of being disemboweled - were all recorded by the court clerk when taking the testimony of the affected teenage accusers.  Indeed the very fact that the accusers were female and in their teens also implicates ergotism as these are the most susceptible individuals in any community where there is an outbreak.  Lastly, she turns to the geographic distribution of the bewitchment. Here she reconstructs a map of Salem village where she hypothesizes that a contamination of grain grown on the eastern bank of the Wolleston river could have been the only source of ergot and still affected all the families involved.
  

Caporael's work inspired historian Mary Matossian to conduct further investigations into the possible connection between witch trials and ergotism outbreaks throughout the middle ages up until the 19th century.  In her book Poisons of the Past Matossian lays out an incredibly convincing argument that outbreaks of ergotism indeed correlate to increased incidence of witch trials throughout the medieval period.  She explains how tree ring thickness measurements compiled for every year from 1269 - 1977 C.E. can be compared to an annual index of number of witch trials with statistical correlation in southwestern Germany and the Swiss alps. 

 

Years in which the growing season was cool and wet correspond to thicker tree rings and therefore seasons in which the amount of fungus growing amongst the rye was high.  These long wet seasons directly preceded autumns with more witch trials. Like the medieval trials the Salem affair was also preceded by two years of unusually cold spring weather.

I was and still am utterly fascinated by the potential connection between a nefarious fungus and the waves of witch trials throughout the middle ages. So fascinated that I have continued seeking further evidence for this biochemical culprit in primary sources.  As I have said, the mid-wives of medieval Europe knew how to use ergot to treat hemorrhaging after birth, but did they know they could use this fungus to induce abortion? Surely they must have, and this would only have placed them higher on the list of public enemies by church rulers. Interesting observation, but how can I use this bit of information to test the claim that the presence of ergot in the diet of medieval peoples lead to witch trials?

There was a guide-book to hunting witches written in Germany in 1486 and approved by the papcay - the Malleus Maleficarum. Translated to English from Latin this means "the hammer of the witches."

The main purpose of the Malleus was to attempt to systematically refute arguments claiming that witchcraft does not exist, discredit those who expressed skepticism about its reality, to claim that witches were more often women than men, and to educate magistrates on the procedures that could find them out and convict them.

Might I use this primary text to hunt for clues connecting ergot to geographic regions affected by witchcraft?   Ergot can induce abortion in humans, right? Well, ergot in rye can also induce abortion in cattle. With this fact in mind I went to the text of the Malleus which is available through Google Books and project Gutenberg. When I searched in the book for the word "cattle" I found several references and even a whole chapter on how witches injure cattle in various ways. To my astonishment, there was even mention of bewitched cattle spontaneously aborting their calves! To the witch-hunters and inquisitors of the middle ages this phenomenon was a sign of witchcraft but the reality was most likely a rotten rye crop!

Thanks for reading! I hope you liked this story. If you did please share it! I would like to make this part of a storytelling series I am planning on you tube. Stay tuned here in the coming weeks for more biochemistry of Halloween content! You can subscribe to Tom Paine's Ghost at the link in the upper-right sidebar. If you like what you read here please make a donation of any size so I can continue to do what I love :)  Donate button also in the sidebar.

I would like to thank Nick Clark for our many discussions and collaboration on this topic and George Hudler for his kind advice and additional references.


Caporael, L. (1976). Ergotism: the satan loosed in Salem? Science, 192 (4234), 21-26 DOI: 10.1126/science.769159  

Schweingruber, Fritz H., BrÄker, Otto U. & SchÄr, Ernst (1979). Dendroclimatic studies on conifers from central Europe and Great Britain Boreas, 8, 427-452  

Fate or Feedback: is the microbiome driving our behavior?

Once upon a time there was an unsuspecting ant on the rainforest floor somewhere in Thailand. Marching along single-file between his brothers he was minding his own business, when he suddenly cocked his head and sniffed a moldy kind of smell. Thinking nothing of it, he kept on walking but soon found himself compelled to get out of line and began wandering off into the forest alone. He felt disoriented, confused, not knowing what was happening to him. 

Our tiny friend then found himself at the base of a towering leafy plant. Looking up at the massive translucent leaves he began to climb. Higher and higher he climbed up the central trunk, passing branch after branch, all the while loosing any idea of where he was or what he was doing. Once he reached a height where the air was thick with humidity he stopped climbing and began to walk out onto a leaf. Over the edge of the leaf he could see the long homeward-bound procession of his brothers far below. But before he could make another move he felt an overwhelming urge to bite down on the central vein of the leaf where he found himself perched. As he bit down he felt all the energy in his tiny body flow to the muscles in his head and mandibles and he bit harder than he had ever bit before. His life flashed before his eyes and in an instant he was dead, frozen. 

What has happened to our little ant friend?

Just a few days after the ant's demise a long grey tube began to grow from inside his head, eventually puncturing the top of his ant-skull it continued to grow into a large mushroom. As soon as the fruiting body had fully unfurled tiny spores were released from the cap and sprinkled like snow, slowly down over a fresh line of brother ants where the entire sordid tale began anew.

This is a true story. As you can see, this fungus has hijacked the ant's body turning it into a zombie of sorts, bending the ant's behavior to work exclusively for the benefit of the fungus.This is not the only example of this kind of fucked up relationship in nature. There is nematode worm that lives part of it's life cycle inside the guts of birds. When the birds poop in the jungle, ants eat the poo and with it the nematode larva. Inside the ant's stomach the nematode enters the next phase of its life cycle causing the ant's abdomen to swell and turn bright red. The round red ants look like ripe local berries to hungry birds and the cycle starts again.  Crazy!

Humans are still plagued by extreme parasites as well. The killer gut bacteria Clostridium difficile (widely known as C. diff) causes 14,000 deaths in the US annually according to the Centers for Disease Control. The extreme diarrhea symptomatic of C.diff.  can cause patients to loose a third of their body weight or more. As C.diff usually proliferates in the wake of long antibiotic regimes it is often resistant to antibiotics.  At the same time C. diff. ferociously out-competes the diversity of benign bacteria (part of the microbiome) that regularly inhabit the ecosystem inside the human gut. 

Fear not! A radically simple and effective treatment has emerged for this problem. Fecal transplants! That's right, people get so desperate when they have lost 80+ lbs and are too weak to walk they will try anything. But this shit actually works! Doctors get a "donor" to poop into a container, then they mix it up into a slurry with some water, and deliver the slurry to the colon with a colonoscopy-style tube, or... the doctors can also deposit the donor's poop slurry through a nose-tube into the stomach. I almost just barfed typing that out.  Usually the fecal "donor" is a spouse or a parent, and four out of five patients who receive this poop infusion are cured on the first go!

It is hard to think of near-fatal diarrhea as a behavior but, strictly speaking, it is. The point I want to make by bringing up C.diff infection is that a human behavior - extreme diarrehea - can be changed by a fecal transplant. A transfer of the microbial garden from one field to another can literally change the culture.

So far I have examined extreme examples of behavior modification by parasites. They are extreme in the sense that the victims pay with their lives, but what if there were a whole lot more of these relationships than we ever thought? Relationships in which the host's behavior only had to be manipulated slightly to help the parasite. What if much of human behavior is largely dictated by the the non-human denizens of our bodies? One out of ten cells making up  a person's body are actually of the species Homo sapiens. The rest? Fungus, bacteria, mites, protozoa and a whole ecosystem of diverse fauna. The question is, how democratic is the human body in decision making? Do the peptides secreted by your gut bacteria help decide what to eat, who to mate with, when to fight and when to run?

Enter Toxoplasma gondii, a protozoa that has just such subtle effects on human behavior. In an article published in the European Journal of Personality researchers report that human beings inoculated with these tiny creatures are more outgoing socially, have a higher rate of car crashes, and become less and less conscientious the longer they carry the parasite (especially men).  The shocking part of this study was the number of people who host this little bug - 22.4% of the US population over the age of 12! T. gondii is generally thought to be benign unless present in pregnant women or infants where it can cause damage to developing tissue.  The protozoa is so small during the stage of its life cycle when it lives inside humans it actually penetrates the cells, living in heart and brain tissues. As it replicates it can form benign cysts in the heart and brain... yuck!  The prevalence of T. gondii is underscored by it's signature behavioral modification - extroversion.  By rendering its host more outgoing it increases the likelihood it will spread to additional hosts. Diabolical! Are there any benefits to knowing this? could someone with chronic shyness inoculate themselves with this bug and make themselves more sociable? Might we extract the biochemical mechanism this bug uses and just make an extroversion drug instead? Who knows! Time will tell.  

To me, it is interesting to ponder how deep this connection between medical ecology and human behavior will play out. Are we, like the ant at the beginning of this story, bouncing like a pin-ball between the needs and desires of tiny creatures that call our bodies home?

By writing out these thoughts I want to get my readers thinking about behavior and the unseen factors that influence it. You know that person at work who really gets on your nerves with the constant close-talking? Maybe it's not their fault. May they're acting on a whim of one of their microbial free-riders. Maybe this is true for a lot of human traits. Will we identify more human behaviors that operate under direct feedback by bacteria? fungus? protozoa? cats? dogs? Can we "fix" people by modifying their microbial clouds? Should we? How will super-cheap gene sequencing affect social dynamics?

I do not have the answers to these questions. Maybe you do. Is this a worthy line of scientific inquiry? Share your thoughts below or find me on twitter @thorsonofodin.

Written by Kristopher Hite

1.) Andersen SB, Gerritsma S, Yusah KM, Mayntz D, Hywel-Jones NL, Billen J, Boomsma JJ, & Hughes DP (2009). The life of a dead ant: the expression of an adaptive extended phenotype. The American naturalist, 174 (3), 424-33 PMID: 19627240  

2.) Khoruts A, Dicksved J, Jansson JK, & Sadowsky MJ (2010). Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. Journal of clinical gastroenterology, 44 (5), 354-60 PMID: 20048681  

3.) Jitka Lindová1,, Lenka Příplatová,, & Jaroslav Flegr (2012). Higher Extraversion and Lower Conscientiousness in Humans Infected with Toxoplasma European Journal of Personality, 26 (3), 285-291 DOI: 10.1002/per.838

Rebecca Watson on Homeopathy and the FDA

Rebecca Watson has been at the center of a lot of heated debates lately over at Pharyngula as well as the recent subject of a famous you-tuber named Thunderf00t. This dust-up stems from her suggestion that something ought be done about sexual harassment at various free-thinking conferences like The Amazing Meeting (TAM) and so on.  All this controversy coupled to me finally listening to the skeptics guide to the universe podcast on a regular basis, brought me to Rebecca Watson's Blog - Skepchick. On the sidebar I found this wonderful video (above). Though it is old by web standards (posted 8 months ago) I want to share it today to give anyone with even a passive interest in the whole current controversy a view of Rebecca Watson unfettered by the kerfuffle. I stand in solidarity with her as I think she is a force to be reckoned with in the world skeptical thinkers. I have dealt with a constant barrage of alternative medicine hocus pocus thrown at me my entire life. Read about my experience with this here. From my perspective I appreciate her concise description of of the shortcomings of homeopathy and also the suggestions of how to participate in raising awareness about this perennial scam.

Jack Andraka - Health Care Superman

As the United States Supreme Court upheld the Affordable Care Act today we can hope health care will become more cost effective. The following videos make me think improvements in efficiency and performance have a head start. Jack Andraka, a high school freshman has implemented a carbon nano-tube paper to develop an unprecedented method for early cancer detection. This method will likely bring the cost of cancer screening down dramatically. Worthy of highest praise he has been awarded a $75,000 prize from the Intel Corporation at an international science fair held May 2012.

In the first video Jack explains the mechanism of his invention.  In the second video you see his acceptance of the first place award.  It is epic and has gone viral. I hope I help it spread.

The Paradox Behind the PRKCA Gene

A guest-post by Phillip Moore

The PRKCA gene is a paradox of sorts in that it has been identified by European researchers to improve memory, but also to increase the risk of post-traumatic stress disorder (PTSD). The magazine Nature just recently released a fascinating article that highlights the curse of possessing a good memory in certain traumatic situations. Let's examine the important details of this study conducted by Dominique de Quervain of the University of Basil in Switzerland and then explore future work that must be done to better understand the PRKCA gene.

Brief Details of 3-Part Study

Dominique de Quervain and his colleagues recruited 700 healthy young European volunteers in order to obtain their DNA samples to analyze the sequence of their PRKCA gene. This gene is just one of many known to impact our emotional memories. The researchers displayed emotionally disturbing images to the participants and then soon after asked them to write brief descriptions of the images. The participants either carried two copies of the A allele or two copies of the G allele, both of which are variants within the PRKCA gene. Those participants who carried two copies of the A allele remembered the most details about the traumatic images, while participants who carried two copies of the G allele remembered the least.

The researchers then recruited 394 other participants to perform the same task while undergoing brain imaging. The study also confirmed that variations in the PRKCA gene impact emotional memory. The brain imagine scans revealed that the A allele was affiliated with enhanced activity in the lateral and medial prefrontal cortex, both of which are regions involved in the encoding of memories.

Finally, the researchers explored the distribution of the A allele among the 347 survivors of the 1994 Rwandan genocide who fled the civil war. This results of this study were consistent with the other two studies in that survivors who possessed two copies of the A allele were almost twice as likely to suffer from PTSD.

Moving Forward

The PRKCA gene is just one of many known to influence our emotional memories. It is important to examine the role that other genes play in shaping our memories. Massive genomic studies will likely reveal a multitude of other gene variants associated with the greater risk of developing PTSD. Also, more research must be done to understand exactly why the A allele leads to differences in brain activity during the process of memory encoding.

The research conducted by Dominique de Quervain and his colleagues really demonstrates that a good memory can be both a blessing and a curse.

Phillip Moore is an online instructor and coordinator for The College City. As a molecular biologist, Phillip was very interested in this European based study and wants to conduct his own research on the PRKCA gene.

Drano for your heart?

There is a growing number of people around the world who believe they have found an alternative treatment for clogged arteries. The idea is to use a kind of molecular Drano and slowly remove the plaques that line the artery walls. It is called chelation therapy.

Is there any evidence that shows this treatment is good or bad?

Almost...

The National Institutes of Health (NIH) has completed data collection on a large-scale double-blind clinical trial to assess the efficacy of chelation therapy to treat coronary artery disease (CAD). This study is called the Trial to Assess Chelation Therapy or TACT. Though the trial itself has had its own trials and tribulations the study is now complete and the results are being mulled-over by the primary researchers at the Mount Sinai School of Medicine with the intention of publishing results within this calendar year - 2012.

UPDATE: Publication of results now postponed until February 2013!

Why am I interested in this? Doesn't this study pang of "alternative medicine" aka - quackery? 

I await the results with extreme anticipation because of my father. 

My decision to go into science and complete a PhD in biochemistry was made in direct response to my father and his seemingly unreasonable evangelism of chelation therapy as treatment for clogged coronary arteries. My father is a firm believer that chelation therapy saved his life. I think he perhaps got lucky somewhere amid the myriad "alternative" treatments he underwent with no scientific way to assess whether the chelation therapy helped or harmed him. The reality is that until this point there has not been a sufficient study to make a scientifically sound assessment of this treatment.   

While I was in high school in the late 1990s my father (now 80 years old) had heart problems - namely congestive heart failure and arrhythmia. He was a lawyer-turned-vitamin salesman and had it in his head that he did not want to end up dead like many of his contemporaries. I watched as many of his life-long buddies had open-heart surgery only to die weeks or months later from pneumonia, MRSA or other illnesses brought on by their chest cavities having been cracked open. 

After having a spiral CAT-scan of his heart at age 65 my father was told he had up to 80% blockage in some of his coronary arteries. His cardiologist suggested bypass surgery but my father did not want his chest opened up. He had heard through friends in Erie, PA that he could try an alternative treatment with no surgery. He signed up and against the advice of his cardiologist began to receive weekly doses of intravenous EDTA and tetracycline in order to remove the plaque from his arteries. He repeated this every week for many months. After the initial intravenous treatment he switched to a maintenance program of monthly EDTA suppository that he has been on ever since. 

The idea that EDTA or ethylene diamine tetraacidic acid injected in a person's blood could wrestle away calcium deposits (aka apatite) from the walls of hardened arteries seemed to-good-to-be true to me. This was until I went to the dentist's office in graduate school.  I had and still have a orthodontic retainer behind my lower front teeth (I am now 29 years old).  Every 6 months I have to have the accumulated plaque removed from the back of my lower front teeth which builds up due to higher concentration of dead and dying bacteria there due to the retainer.  While I was in graduate school visiting the school dentist the dental hygienist told me that keeping plaque cleared from a person's gums helps fight heart disease by keeping plaque in their coronary arteries low. I was flabbergasted. Here I had a direct link between  bacterial plaque and coronary artery disease.  I could understand that calcium deposits on the tooth enamel were similar to calcium deposits in hardened arteries.  I saw that injecting high concentrations of EDTA would impose Le Chatelier's principle on the calcium ions present in a clogged coronary arteries and thus reduce the size of the atherosclerotic deposits. Despite this theoretical comprehension I was and still am highly skeptical of EDTA chelation therapy. I see my father's success with the treatment as anecdotal. Perhaps he was not as likely to have a heart attack as his vital statistics would have him believe.  My skepticism remains.

Beyond the chelation therapy, my father has for as long as I can remember advocated "preventive medicine" like vitamins and various concoctions sold by his former company - Rexall Showcase International (Now called Unicity).  My father  had unfortunately fell into a pyramid scheme run by a bunch of crooks in the early 90s. I could see right through this bullshit when I was 12 years old! A company named "Sundown" acquired the brand-name "Rexall" in 1985 and used it to lure in "sales associates." Think AMWAY for vitamins. Rexall Drugstores had a shining reputation with old-timers like my father who remembered the good-old-days when Rexall Drugstores were synonymous with root-beer floats and grandpa's heart-burn remedies. Sundown bought the company and used the brand-name (with no connection to the remaining chain of Rexall drugstores) to sell vitamins and weight loss products in big package deals to "sales associates" who could then sell the product to whomever they could convince. I recall the most touted of the panacea powders my father peddled was called BiosLife 2. A disgusting chalky version of what we know as "Emergen-C." But, as Rexall Showcase International's stock tanked, my father's enthusiasm for the brand waned.

In addition to Rexall my father has also evangelized the writing of Julian Whitaker MD. Dr Whitaker as Dad so fondly calls him, writes a weekly newsletter lauding the new advances in "alternative medicine" and telling all subscribers exactly where they can purchase all the new supplements - FROM HIM. 

As much as all this bothered me as an adolescent what really bothered me was that I could not have a rational conversation with my father - a very reasonable man. I love my father and I could not understand how he was so sucked in to to all this crap. I have a hypothesis that he so desperately wanted to be healthy and live a long time so he could be with us into old-age, that he would believe anything. I can't say that he was wrong as he has survived several bouts of congestive heart failure and a mini-stroke. But the fact that he was so manipulated by executives at Sundown/Rexall Showcase International fills me with an uncontrollable animosity towards these snake-oil salesmen. 

I am admittedly skeptical of most of my father's self-prescribed therapies. But as for TACT I have my mind open as "THERE WILL BE DATA!" The pricipal investegator in this study is Gervasio A Lamas, M.D. of Mount Sinai School of Medicine. I have heard that the results will be published and made publicly available around June 2012. Please join me in the assessment of said data! Finally I can have a rational discussion with my father grounded in data on a subject quite literally near and dear to his heart. 

Lamas, G., Goertz, C., Boineau, R., Mark, D., Rozema, T., Nahin, R., Drisko, J., & Lee, K. (2012). Design of the Trial to Assess Chelation Therapy (TACT) American Heart Journal, 163 (1), 7-12 DOI: 10.1016/j.ahj.2011.10.002

Ernst, E. (2000). Chelation therapy for coronary heart disease: An overview of all clinical investigations American Heart Journal, 140 (1), 139-141 DOI: 10.1067/mhj.2000.107548

Orchestra Under the Hood

PROTEIN EXPRESSIONS - Study N 3 from Scientific Visualization Unit on Vimeo.

A Brush with Madness

I'm giving myself ten minutes to do this. To write whatever storms into my mind then hit post.

I think the archaic revival might run into some barriers. Like starvation, no communication, and other electrical difficulties if it embraces the Abbey-esque Luddite philosophy entirely.

As much as I want to get onto that other boat I think I will just slip between the hulls and end up swimming by myself among the sea-monsters, bullets whizzing past my head with bubbles trailing behind in dark water.

What will this same attempt look like when I'm able to just think the text into existence without the trouble of commanding my fingers. We're almost there.

Have I done this before?

What were some of the ideas I was having earlier today? I was going to write a post entitled "a brush with madness" and I even logged into research blogging several times with the intention of creating HTML tags for the citations I found via pubmed search about psychotic manifestations in patients with the blood related disease - porphyria.

You see, I had a most jarring experience a few days before Halloween this year. It's ironic I went to the "Rally to Restore Sanity" the weekend after this experience.  I speak of a secondary encounter with real madness at a free public lecture fellow graduate student Nick Clark and I presented at the Park Hill library in Denver on October 26th, 2010. Our talk took place downstairs in the community room at the library. It felt like the community room at Saint Peter and Paul Church in Jamestown New York; the one where my parents met in choir - threadbare carpet and the dank smell of stale coffee. It was in the basement and it felt like a basement. We were presenting our lecture "The Biochemistry of Halloween" as a fun science-out-reach type event. After a successful presentation last year we were asked for an encore lecture by the CSU alumni association. Nick and I showed up about an hour and a half early to make sure we had a functional projector and helped set up seats. When we finished setting up a young woman with curly black hair entered the otherwise empty room and excitedly asked us

"Are you the guys talking about VAMPIRES?"

"Indeed we are, but the talk does not start for another 45 minutes." I replied

"Oh that's OK I'll just wait here." She said and sat giddily waiting it the front row.

We had decent turn out for an event in the basement of a public library held at 5:30 on a weekday. About 35 people showed up to hear about the "Biochemistry of Halloween" and there was really positive audience participation and several intelligent questions. All ages were represented.

(We recorded some of it here)

At the end of the lecture the excited patron was the first to run up to Nick and I . She quickly asked for all our references linking dementia and porphyria. We took her e-mail address and said no problem. The woman then went on to explain that she was particularly interested in the topic as her ex-boyfriend was afflicted with porhyria. She knew the specific form - coproporphyria. Nick and I both immediately felt bad and responded by saying that we did not want to offend anyone by implying that patients with porphyria were actually vampires. Her reaction to this was most shocking. She said she was fascinated by the idea that historical cases of porphyria might explain the origin of vampire myths because her ex-boyfriend was in fact presently in jail because he went "nuts" and tried to cut her head off with a knife!

Well, that just hit me like a ton of bricks! Here we are trying to be super politically correct by not offending anyone connected with any of these diseases we were talking about and here was a real world case where a patient with porphyria was acting deranged. This rose a significant ethical dilemma in my mind. Current treatment of porphyria is diet control and injections of properly formed heme - analogous to diabetes patients receiving insulin as treatment - replacing the body's missing thing. But in the case of porphyria it is not just replacement of the problem chemical that needs to be addressed. The mal-formed chemicals stay in the blood stream and cause problems in the brain of the patient; hallucinations, dementia, and severe anxiety to name a few. To entirely alleviate the affects of the disease those "bad" molecules need to be removed as well. This is probably not an option as it would require the patient to be on constant dialysis.

The question then arises. If a patient experiences mental disturbances including psychopathic behavior because of a disease is that patient responsible for his/her actions? Can a patient plead insanity in this instance? What extent should the public help this individual manage their psychological problems to protect its members? I had heard of this type of scenario in ethical thought experiments before but this was the first time a case like this was staring me in the face. She said that she thought her ex was crazy and hoped he rotted in prison. But how much of his bad behavior was of his own free will and how much was due to biochemistry? Could his attempted murder have been prevented if medicine was able to safely remove the detrimental chemicals from his blood? This is much different that a badly behaving drug addict - in that case an individual is choosing to put the delusion -inducing chemicals in their blood while in the case of porphyria the patient has no choice. What if the patient was simultaneously abusing drugs?  To what degree is that self-medication attributed to the disease? Are patients in this situation doomed to the fate of this guy? How does society deal with this situation?

In looking for answers to some of the clinical aspects of these questions I stumbled on a surprising medical speculation.  Some scholars have attributed the bouts of madness experienced by the great impressionist painter Vincent Van Gogh to acute intermittent porphyria!  His self mutilation, delirium, agitation, paranoia and sporatic timing of his attacks may all be explained by him having this disease. Exacerbated by poor diet and subsnace abuse - especially absinthe - may have pushed him over the edge.  Though he had produced some of the world's most stimulating paintings on July 29th, 1890 in a northwestern suburb of Paris Vincent took his own life by shooting himself in the chest. 

This medical scenario begs the question.  If Van Gogh were to be born today with the advent of contemporary medicine and diagnosis would his paintings scream with such beauty?

 

Sedel F, Baumann N, Turpin JC, Lyon-Caen O, Saudubray JM, & Cohen D (2007). Psychiatric manifestations revealing inborn errors of metabolism in adolescents and adults. Journal of inherited metabolic disease, 30 (5), 631-41 PMID: 17694356  

Rose FC (2006). Van Gogh's madness. International review of neurobiology, 74, 253-69 PMID: 16730519  

Altintoprak AE, Ersel M, & Bayrakci A (2009). An unusual suicide attempt: a case with psychosis during an acute porphyric attack. European journal of emergency medicine : official journal of the European Society for Emergency Medicine, 16 (2), 106-8 PMID: 19262206  

Mandoki MW, & Sumner GS (1994). Psychiatric manifestations of hereditary coproporphyria in a child. The Journal of nervous and mental disease, 182 (2), 117-8 PMID: 8308532

Cheating Death - Colbert on Fire!

Oprah is a prominent gate-keeper and her constant promotion of quackery opens up the topic of responsibility when using free speech from certain platforms. I surely can not, with good conscience, stand by while Oprah spearheads the charge to flay the hypothetical Hypatias of our time.

How do you think these matters of free speech vs. phony speech should be handled? Perhaps a network sponsored special running for several weeks consisting of a panel debate on each claim inviting experts from academia and clinics in for each issue - vaccines, the secret, Dr. Phil etc etc.

Some would argue that this would be a bad idea because it gives equal footing to those making fraudulent health claims. But I say the truth should be able to defeat any imitations using the "disinfectant of sunlight" as justice Louis Brandeis might have put it.

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