The class I currently teach in generative medicine uses a content system called Blackboard. Blackboard allows me to upload material and pose questions to a forum-like discussion area. One of my students, upon reading the assignment in the textbook made the following comments:
You talk about the division between classical science and naturopathic science, which you equate, respectively, with reductionism and emergence (p. 30). Do they necessarily have to oppose one another and can they not coexist. And does not naturopathic medicine incorporate some degree of reductionism and classical science some degree of emergence?
I guess this goes back to the old question of: can't we all just get along but, further, isn't it sort of imperative that we not categorize conventional versus naturopathic medicine in such black and white terms? Or maybe it is a more useful distinction than I'm discerning?
If, indeed, scientific reductionism is dead (p. 20) and the biomedical community is unaware, how do you best suggest we, as NDs (or future NDs), start to make inroads into that community to convince them that the idea of emergence/holism/a generative approach is worth substantively incorporating into the larger paradigm of "modern" medicine?
I would argue that there is a global groundswell of desire among consumers of healthcare for this generative approach, but it might be up to us as practitioners of naturopathic medicine to bring it mainstream. But the path to that end is not clear. At the end of the day, not only do we have to all get along, but we need to understand what the other is saying.
To which I replied:
If we define 'dead' as having lived a life with purpose, and perhaps even being so lucky as to exhaust that purpose, then reductionism is quite dead in the sense of being 'not alive'. [Which leads to the question: if an idea has no purpose, hence no life, does it even get to die?]
There will always be a reason to think in reductionist terms when the facts do indeed fit the scenario. IMHO there will always be opportunities for non-complex thinking (and indeed one should seize them whenever one can).
My position is that, as a profession, we are perhaps running the risk of being overly seduced by the simplicity of fitting our oeuvre to the existing allopathic framework. In essence we will be moving into a neighborhood in which the prior occupants have already sucked out the life and are themselves moving on to new areas.
Moreover in doing so we may well be creating a nascent culture of new dogmatists, apparatchiks who insist on only dealing with issues on these terms. If that was not bad enough, this then runs the risk of creating its own response element, its own duality, such that a second subculture results that does the exact opposite, accepting facts a priori.
So, what about this generative medicine idea? As you so astutely point out, the goal is to blend both the complex-systems approach with the mechanistic-reductionist approach, point being that we, as naturopaths, should have a pretty good feel for where the work needs to be done and how to go about doing it. Perhaps this duality is itself a power law: we may be using an 80% reductionist formula to discern 20% of our total causalities. Certainly systems-complexity-network (SCN) medicine comprises only a small fraction of current biomedical information analysis. Generative Medicine, as I see it, should resolve that duality.
No matter what, the informational chasm does indeed lay which complexity, as well as any future potential for understanding and treating the life process itself.
Like they say, if you really want to learn something, teach it.
The year 1956 stands out in my mind for a variety of reasons, the most important being (at least for me) that it was the year I was born. It also marked the year of the only ‘perfect game’ even thrown in a baseball World Series. Music fans might remember that it was the year that Elvis Presley entered the United States music charts for the first time, with 'Heartbreak Hotel.'
1956 was also the year a scientist named Roger Williams published a book called Biochemical Individuality, which attempted to relate inherited individual distinctions to nutritional requirements. Although Williams was no small figure in medicine (at the University of Austin he had discovered pantothenic acid, one of the critical B vitamins, and had published skews of articles detailing some of the most basic biochemical discoveries) Biochemical Individuality attracted little, if any attention from the medical community, probably due to the fact, as Jeffrey Bland speculates in his book Genetic Nutritioneering, Williams expressed many of his ideas in biochemical terms, which doctors of the time were far less comfortable with compared with today.
How prescient is the following phrase:
“The existence in every human being of a vast array of attributes which are potentially measurable (whether by present methods or not), and often uncorrelated mathematically, makes quite tenable the hypothesis that practically every human being is a deviate in some respects.”
It’s a strange choice of words, but the word deviate in this context signifies a turning away from the normal or a variance of some sort. Of course, we tend to think of the word more as a term for individuals who deviate from some sort of social norm; but norms are norms.
Williams was certainly deviating from conventional medical wisdom. Nobody at the time was looking at peculiar and individual aspects of nutrition that might be predicted genetically. More importantly, in 1956 there wasn’t anywhere near the enormous genetic industry and technology that exists today; it had only been three years before that James Watson and Francis Crick deduced the basic structure of DNA, (Deoxyribonucleic acid) –the double helix-- that contains the genetic instructions specifying the biological development of all cellular forms of life.
Thus when Williams talked of “attributes that are potentially measurable (by present methods or not)” he is taking an amazingly huge step into the future.
So Williams’ phrase “often uncorrelated mathematically” should probably be reinterpreted to mean “we can’t see the connections because of our current puny computational abilities.” Nowadays we link supercomputers together into vast neural networks and process data at a speed and accuracy that just boggles the mind. It was just this type of muscular computing that allowed scientists like Craig Venter and his firm Celera Genomics to help crack the human genome in record time. Today, the combination of gene sequencing and supercomputers is a day to day event in hundreds of laboratories worldwide, and is a prime part of a vast new field called bioinformatics.
In 1956, nutrition science was still in its infancy, concerned mostly with deficiency types of diseases such as pellagra and anemia, and making sure that we all ate “balanced meals.” There was no link between diet and cholesterol or between cholesterol and hardening of the arteries and medical journals often featured cigarette ads on their back pages. Ulcers were often treated by telling the patient to drink copious amounts of milk, the so-called “sippy-diet.” In other words, nutritional thinking at the time was predominantly disease-based, which is odd, since almost everything we do with food has absolutely nothing to do with disease. This resulted in what my friend and colleague Jonathan Wright used to call "The Association Diets.'
This is not to say that pieces of the puzzle weren’t evident, or that intelligent people were not already beginning to ask the right questions. It’s just that the questions could only be based on what was thought to be known, and what was known was not very much.
I can remember taking a computer class in high school (already well into the 1960’s) where we were taught to diligently inscribe a series punch cards with a 'number 2' pencil, which were then collated and fed to a machine the size of a large refrigerator, which then hacked and coughed for a while, finally yielding a half page printout of a list of fifty prime numbers.
Unless, of course, you had the misfortune to have penciled in the wrong box, in which case you just started all over again; a frustrating experience, which lead to one of my young colleagues, in a rage of frustration, placing one of the cards on the floor and proceeding to stomp on it repeatedly with his shoed foot, sending it on to the card reader --and probably producing the first computer virus-- a trick many of us would repeat when similarly frustrated. Your home computer can do these functions in micro-seconds, and the software to do it is considered so basic that it is usually packaged for free with the operating system.
More 'damned data' (Charles Fort's words, not mine): studies from the scientific literature which could pass for some of the more outlandish statements in The GenoType Diet:
The phenotype of an individual is the result of complex interactions between genotype, epigenome and current, past and ancestral environment, leading to lifelong remodelling of our epigenomes. Various replication-dependent and -independent epigenetic mechanisms are involved in developmental programming, lifelong stochastic and environmental deteriorations, circadian deteriorations, and transgenerational effects. Several types of sequences can be targets of a host of environmental factors and can be associated with specific epigenetic signatures and patterns of gene expression. Depending on the nature and intensity of the insult, the critical spatiotemporal windows and developmental or lifelong processes involved, these epigenetic alterations can lead to permanent changes in tissue and organ structure and function, or to reversible changes using appropriate epigenetic tools. Given several encouraging trials, prevention and therapy of age- and lifestyle-related diseases by individualised tailoring of optimal epigenetic diets or drugs are conceivable. However, these interventions will require intense efforts to unravel the complexity of these epigenetic, genetic and environment interactions and to evaluate their potential reversibility with minimal side effects.
Nutri-epigenomics: lifelong remodelling of our epigenomes by nutritional and metabolic factors and beyond. Clin Chem Lab Med. 2007;45(3):321-7
Epigenomics or epigenetics refers to the modification of DNA that can influence the phenotype through changing gene expression without altering the nucleotide sequence of the DNA. Two examples are methylation of DNA and acetylation of the histone DNA-binding proteins. Dietary components - both nutrients and nonnutrients - can influence these epigenetic events, altering genetic expression and potentially modifying disease risk. Some of these epigenetic changes appear to be heritable. Understanding the role that diet and nutrition play in modifying genetic expression is complex given the range of food choices, the diversity of nutrient intakes, the individual differences in genetic backgrounds and intestinal physiological environments where food is metabolized, as well as the impact on and acceptance of new technologies by consumers.
Epigenomics and nutrition. Forum Nutr. 2007;60:31-41.
Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables, such as broccoli and broccoli sprouts. This anticarcinogen was first identified as a potent inducer of Phase 2 detoxification enzymes, but evidence is mounting that SFN also acts through epigenetic mechanisms. SFN has been shown to inhibit histone deacetylase (HDAC) activity in human colon and prostate cancer lines, with an increase in global and local histone acetylation status, such as on the promoter regions of P21 and bax genes. SFN also inhibited the growth of prostate cancer xenografts and spontaneous intestinal polyps in mouse models, with evidence for altered histone acetylation and HDAC activities in vivo. In human subjects, a single ingestion of 68 g broccoli sprouts inhibited HDAC activity in circulating peripheral blood mononuclear cells 3-6 h after consumption, with concomitant induction of histone H3 and H4 acetylation. These findings provide evidence that one mechanism of cancer chemoprevention by SFN is via epigenetic changes associated with inhibition of HDAC activity. Other dietary agents such as butyrate, biotin, lipoic acid, garlic organosulfur compounds, and metabolites of vitamin E have structural features compatible with HDAC inhibition. The ability of dietary compounds to de-repress epigenetically silenced genes in cancer cells, and to activate these genes in normal cells, has important implications for cancer prevention and therapy. In a broader context, there is growing interest in dietary HDAC inhibitors and their impact on epigenetic mechanisms affecting other chronic conditions, such as cardiovascular disease, neurodegeneration and aging.
Dietary histone deacetylase inhibitors: from cells to mice to man. Semin Cancer Biol. 2007 Oct;17(5):363-9. Epub 2007 May 5
The purpose of this paper was to selectively review the literature on the role of epigenetics in mental illnesses. Aberrant epigenetic regulation has been clearly implicated in the aetiology of some human illnesses. In recent years a growing body of evidence has highlighted the possibility that epigenetics may also play a key role in the origins and expression of mental disorders. Epigenetic phenomena may help explain some of the complexity of mental illnesses and provide a basis for discovering novel pharmacological targets to treat these disorders.
Role of epigenetics in mental disorders. Aust N Z J Psychiatry. 2008 Feb;42(2):97-107.
A complex combination of adult health-related disorders can originate from developmental events that occur in utero. The periconceptional period may also be programmable. We report on the effects of restricting the supply of specific B vitamins (i.e., B(12) and folate) and methionine, within normal physiological ranges, from the periconceptional diet of mature female sheep. We hypothesized this would lead to epigenetic modifications to DNA methylation in the preovulatory oocyte and/or preimplantation embryo, with long-term health implications for offspring. DNA methylation is a key epigenetic contributor to maintenance of gene silencing that relies on a dietary supply of methyl groups. We observed no effects on pregnancy establishment or birth weight, but this modest early dietary intervention led to adult offspring that were both heavier and fatter, elicited altered immune responses to antigenic challenge, were insulin-resistant, and had elevated blood pressure-effects that were most obvious in males. The altered methylation status of 4% of 1,400 CpG islands examined by restriction landmark genome scanning in the fetal liver revealed compelling evidence of a widespread epigenetic mechanism associated with this nutritionally programmed effect. Intriguingly, more than half of the affected loci were specific to males. The data provide the first evidence that clinically relevant reductions in specific dietary inputs to the methionine/folate cycles during the periconceptional period can lead to widespread epigenetic alterations to DNA methylation in offspring, and modify adult health-related phenotypes.
DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19351-6. Epub 2007 Nov
Major efforts have been directed towards the identification of genetic mutations, their use as biomarkers, and the understanding of their consequences on human health and well-being. There is an emerging interest, however, in the possibility that environmentally-induced changes at levels other than the genetic information could have long-lasting consequences as well. This review summarises our current knowledge of how the environment, nutrition, and ageing affect the way mammalian genes are organised and transcribed, without changes in the underlying DNA sequence. Admittedly, the link between environment and epigenetics remains largely to be explored. However, recent studies indicate that environmental factors and diet can perturb the way genes are controlled by DNA methylation and covalent histone modifications. Unexpectedly, and not unlike genetic mutations, aberrant epigenetic alterations and their phenotypic effects can sometimes be passed on to the next generation.
Environmental and nutritional effects on the epigenetic regulation of genes. Mutat Res. 2006 Aug 30;600(1-2):46-57. Epub 2006 Jul 18
Welcome to The Weekly Transfusion, 1.4 for the week of April 6, 2009.
Editorial: Medical journal statistics for autodidacts
You can become a better consumer of health information if you take the time to read the research source material (i.e the scientific publication in which the original claim was made). Of course if the study is technical you can see quite a bit of jargon that you may or may not understand. However many medical terms are widely understood and where you bump up against the odd phrase or name that you don't comprehend, there are usually places on the Internet where you can find simple, easy to understand explanations. Wikipedia is actually pretty good for this type of look-up, as long as the subject at hand is not controversial.
However, methodology and monikers aside, most scientific studies distill down to a simple testable premise which is easily understand by almost anyone. Did the medicine work? Was the association between this gene and that disease valid? Past asking the question, what is needed next is to look at and gauge the value of the answer. Surprisingly, even though this is usually some sort of statistical type of answer (and most laypeople are not well versed in statistics) once you know what to look for, you'd be amazed just how easy it is to evaluate most studies.
Most research studies feature a subsection entitled Results or Conclusions. It is here that the results are most often given. There are many way of calculating statistical significance, but the premise is quite simple: What is the chance that the thing we just observed/ hypothesized was random versus the odds of it being due to the relationship we are studying. This is known as probability and in statistics is usually called the P value. To find out just how significant the results of any study are, just look for the P value. The smaller this number is, the less likely the results occurred by chance. Put another way, the lower the P value the more likely you'll want to view the results as significant or important.
The great Ronald Fisher viewed P values as measures of the evidence against a hypotheses, sort of like how a prosecutor presents a case based on exceeding the jury's sense of 'reasonable doubt.'
Now for the secret (OK, not so secret) key to taking control of the medical facts in your life: The standard level of significance used to justify a claim of a statistically significant effect is when P is equal to or less than 0.05; in essence, a one-in-twenty chance that the result had nothing to do with your hypothesis.
For better or worse, the term 'statistically significant' has become synonymous with P<=0.05.
So when looking at any published results, always look for the P value and if it is greater than five cents on the dollar (0.05) you'd probably want to ignore that results (unless the premise of the article was that the researchers failed to show a relationship, which is of course just another type of observation; however, these types of studies usually don't make it out of the researcher's file cabinet) or take a look at the methodology behind the study (scientists are human; studies can be poorly designed and the conclusions derived may not have been the best test of the hypothesis).
So, P<0.05 means the results are significant, but just barely. Good enough to convict, but also likely to send a few innocent people to jail as well, since there are still strong indications that the hypothesis fails to account for the whole of the facts. Personally I like to see P values of at most 0.01-0.02 before I get excited about anything I'm reading. However I do make exceptions for studies with small numbers of participants, or if the we're dealing with an herb or vitamin where the effects studies may be slight or slow to surface.
Oftentimes you'll see P values with lots of zeros. That means they've found a more statistically reliable result. For example, the P value in the following article is P<0.001. This actually means that there 1 in a 1000 chance of the result being a random occurrence and a 999 in 1000 chance that the result was related to the premise of the study.
Just remember, look for at least a P<0.05. That means the results were statistically significant. Beyond that the more zeros you see in the P value, the better. Try your new-found statistical powers on the articles below. Look for the P values in the studies. What do they signify?
Now that you can evaluate scientific material at its source, you'll be less likely to fall for the 'man bites dog' con-jobs that are all too commonly reported in the news or as what passes for scientific discussion these days.
Resting heart rate as a low tech predictor of heart problems in women
In a large, diverse group of postmenopausal women, resting heart rate was an independent predictor of coronary events, with higher heart rate associated with greater risk. The relation between resting heart rate and risk of coronary events was stronger in younger postmenopausal women than in older ones. Resting heart rate did not independently predict stroke.
In general, age, body mass index, and saturated fat consumption were higher and cardiovascular risk factors such as hypertension, diabetes, smoking, hypercholesterolaemia, and depressive symptoms more prevalent in women with higher resting heart rate, as was self reported nervousness. Physical activity and alcohol use were inversely related to heart rate (both P<0.001), and heart rate was lower in women who used postmenopausal hormone therapy than in those who did not (P<0.001).
One can't argue that this is about as low tech a predictor of future health problems as one is likely to find. It has already been shown that resting heart rate predicts coronary events in men. For women however, the relation between heart rate and coronary events or stroke has been uncertain. The study broke the participants into groups including a 'high heart rate group' whose heart rate was greater that 76 beats per minute and 'low heart rate group' whose heart rate was greater than 61 beats per minute. The association with 'coronary events' (aka heart attacks and death). This association appears stronger in women aged 50-64 than in those aged 65 or older
Being overweight makes you age faster
Obesity and weight gain in adulthood are associated with an increased risk of several cancers. Telomeres play a critical role in maintaining genomic integrity and may be involved in carcinogenesis. Using data from 647 women ages 35 to 74 years in the United States and Puerto Rico (2003-2004), we examined the association between current and past anthropometric characteristics and telomere length in blood. These findings support the hypothesis that obesity may accelerate aging, and highlight the importance of maintaining a desirable weight in adulthood.
A telomere is a region of repetitive DNA at the end of chromosomes, which protects the end of the chromosome from destruction. When DNA needs to be read (to replicate itself, or generate RNA so as to begin coding proteins) a problem arises in that the enzymes that duplicate the chromosome and its DNA cannot continue their duplication all the way to the end of the chromosome. They need a blank area to 'park' much like the cassette tapes of days past had white 'leader tape' at their front and the back so that the tape head did not start in the song itself. Unlike cassette tape, every time DNA reproduces, a bit of the white leader tape, the 'telomere' at the end, is frittered off and has to be replaced. Telomeres and replenished by an enzyme, the telomerase reverse transcriptase. Telomeres protect a cell's chromosomes from fusing with each other or rearranging - abnormalities which can lead to cancer - and so cells are normally destroyed when their telomeres are consumed. In the women studies for this article, those having a higher body mass index (BMI) in their 30s were associated with shorter telomere length in their 40s (P < 0.01).
I suspect some of this association is epigenetic, and points again to the fact that the GT5 Warrior epigenotype may well need to get their weight profile optimized early in life and be increasingly calorie conscious as they age.
Vitamin D, adult-onset diabetes and metabolic syndrome
Vitamin D is a potent immunomodulator that also enhances the production and secretion of several hormones, including insulin. Vitamin D deficiency has been associated with increased risk of type 1 diabetes. Glycemic control and insulin resistance are improved when vitamin D deficiency is corrected and calcium supplementation is adequate.
More and more information is surfacing about vitamin D (actually more of a hormone than a vitamin) and insulin resistance. Studies consistently show that vitamin D levels in both North America and the Pacific are typically lower than optimal. In the USA , most vitamin D intake from foods is provided by fortification. Canada and New Zealand have fewer fortified choices, and intakes are correspondingly lower. The mechanism of action of vitamin D in adult onset (type 2) diabetes is thought to be to its role in the control of plasma calcium levels, which help regulate insulin synthesis, but may also be the result of vitamin D stimulating the insulin secreting (beta) cells of the pancreas directly. If you have a history of metabolic syndrome or adult onset diabetes in close family members you may want to consider adding vitamin D to your supplement regimen. However, make sure that you do it in partnership with a nutrition professional.
One from the vaults: Mom's blood type can influence child's risk of Strep (1978)
In a prospective study of maternal genital colonization with streptococci at the time of delivery, epidemiological data, including blood type (ABO group), were recorded for the 1,062 patients studied. Blood type B was found in a statistically significant (P <.005) higher proportion of patients colonized with streptococci (28%) compared with the total population (16.4%)
Evidence suggests that probiotic supplementation does change the vagina flora of women. Since it appears that the route of transmission of Streptococcus is from the birth canal, physicians should recommend probiotic supplementation for pregnant women beginning 3-4 weeks prior to expected date of delivery as a way to prevent streptococcus infection in neonates. This should be especially emphasized if the mother is either blood group B or AB.
This study again illustrates the fact that some of the best ABO correlation studies are outside the purview to today's physicians, most of whom would tell you that any research from 1978 is better suited to a history class than to any thing taught in medical school.
Since Mother's Day is fast approaching, also remember that recurring otitis media (ear infections) is strongly associated with the child's mother being blood type A. In fact the correlation here is quite startling. Children of mothers who are blood type A are twenty seven times more likely to get a second ear infection within one year of contracting the first. To give you an idea of just how strong this association is, look at the chart below to compare the RR (relative risks) of a few other disease/ lifestyle links.
Update: IfHI 2009
Just a quick word to the wise about the IfHI Conference, Norwalk Connecticut, June 5-7. We had run out of available rooms at the Dolce Center Campus. However 10 additional rooms have just been made available. Unlike previous conferences, where attendees could book almost to the day of the event, IfHI 2009 looks like it will be completely booked by the middle of May, a full month before the event. If you are planning on attending, either for certification or just personal enrichment, please make your reservations ASAP, especially if you want to stay overnight on campus.
Until next week.
As is typical of this time of year, it’s been a very active time for your humble physician-author-blogger.
January started off with a whirlwind visit out to Arizona for a daylong presentation to the Arizona Naturopathic Medical Association. This was followed by a two week intensive period of website redesign, overhauling the website of The D’Adamo Clinic in addition to the navigation system for North American Pharmacal. The Clinic website is a simple white design that I like very much and it conveys what being inside the Clinic feels like to me. I’m not normally a fan of all-white walls, but in the Clinic it works.
One problem you come across again and again when you program for the Internet is cross-browser support. I’ve learned the hard way that a web page that works and looks good in Firefox for the Mac may not necessarily look or work the same way in Internet Explorer for Windows. Many, many times it’s been a last minute check on an outdated browser running Windows 95 that kiboshed a terrific idea.
Putting the final touches on the SWAMI software. I’ve decided to port it to two platforms. One will be the traditional SWAMI GenoType for professionals, the other will be a SWAMI Xpress that will be available online. Introduction of the SWAMIGenoType will be linked to the IfHI 2009 Conference, where Tom Greenfield, Natalie Colicci and I will have the time to take the attendees through the interface, filters and matrices. If you are a physician or IFHI certified educator planning to use SWAMI GenoType in your practice, you’ll need to attend IfHI 2009 to get the full training.
SWAMI Xpress will contain all the base programs of his more muscular brother, but is being designed for general-purpose use. SWAMI GenoType has advanced filters and controls that allow a physician to exert complete control over the client diet and is geared to practitioners who want to have a more micrometric control over things. Introduction of SWAMI Xpress will be as part of NAP’s “Do It For A Month” program.
On the lecture horizon, I’ve got a webinar with the Massachusetts College of Pharmacy on March 31 and an upcoming Grand Rounds presentation at the University of Bridgeport College of Naturopathic Medicine on February 11. After that things calm down until the IfHI 2009 Conference June 5. IfHI should be challenging. I’ve scheduled myself for something like 9 hours of lecture time, and if you could believe it I’m stressing out about not having enough time to do justice to the material. Figured out how to control my slide show from an iPhone, which is very cool. I should be able to pace around the room and use the iPhone to cue the next slide.
After completing a few movies/animations I’ll be pretty much done preparing material for the conference, leaving plenty of time to perfect the software and get the 1971 VW Camper ready.
Got lucky yesterday. Found a site that had the entire LP of the 1974 classic The Portsmouth Sinfonia Plays The Popular Classics available as a download. I certainly don’t support intellectual property theft but this album has never made it to CD and I think the original record label is now extinct. The Portsmouth Sinfonia is the ultimate ode to amateurism: Take a bunch of English art school students --who either cannot play a musical instrument or are willing to play one they are unfamiliar with-- and put them into an orchestra. The only rules being that you had to come to rehearsal and you could not purposely play the wrong notes.
What resulted were renditions of the popular classics (Peer Gynt Suite, The Blue Danube Waltz, The William Tell Overture, etc) in which the inexperience and lack of talent produces a series of acoustic near-misses that collect into this cloud-like approximation of what the proper pitch and notes should sound like. Popular classics were selected on purpose since everyone in the orchestra would know the music and could at least aspire to what the piece should resemble--or at the very minimum whether they should be sounding higher or lower pitched notes.
Here is their rendition of Blue Danube Waltz, Op. 314 (Johann Strauss)
Beethoven was supposedly fond of listening to amateur productions of his work, and I’ve often thought that this would be among the most perfect of medical education paradigms.