The Doctor Weighs In

By Dov Michaeli MD, Ph.D

Sometimes, When I read something extraordinarily egregious or stupid I catch myself shaking my head in disbelief. I even mutter to myself a few choice expletives. Here are 2 items from the New York Times appearing on 2 consecutive days.

“ The New Jersey Public Health Council is expected to vote tomorrow on a rule that would require flu vaccines for any child entering day care or preschool. If it is approved, New Jersey would become the first state in the country to impose that mandate.

“The flu vaccine is one of four that the council will consider. There is a vaccine that would be given to children entering day care or preschool to protect against pneumonia and two others that would be given to those entering sixth grade: one to guard against meningococcal disease, a fast-killing strain of meningitis, and the other an additional booster of a three-part shot already administered at a younger age against tetatanus pertussis and diphtheria.”

I thought “Hooray”, finally states are recognizing that vaccination is the most cost effective therapeutic modality we have. Sometimes, the only modality we have. A short trip to other industrialized nations around the world would reveal that we are woefully behind on this issue; all children are vaccinated annually, and barring allergy to eggs--no exceptions. The mortality rate in children who contract the flu is astounding. The decision to propose the additional vaccines, especially the one for the flu, was based on recommendations by the federal Centers for Disease Control and Prevention and the FDA. Each year, 108 of every 100,000 children 5 or younger are hospitalized with complications from the flu, and about 100 die, according to the C.D.C.

Would you expect anything but praise for the public health authorities of New Jersey ? In fact, I would have asked what took them so long. But the article goes on to tell us that

“At a public hearing in January, about 30 people complained about the proposed vaccines, citing possible side effects and insufficient evidence that they help prevent disease. On Friday, a group opposing the new vaccines held a news conference at the State House in Trenton . And people will have a chance to speak at tomorrow’s meeting, at the health department building in Trenton . ’

And then, today’s item from Maine :

PORTLAND, Me., Dec. 7 — “Hundreds of students at the University of Southern Maine have been barred from its campuses here and in nearby Gorham over mumps vaccination. Skip to next paragraph

The Maine Center for Disease Control and Prevention recently issued an emergency order that full-time or resident students at the campuses — 5,996 people — must have had a second vaccination for mumps. The order came after two cases of the virus were confirmed at the university; other cases are suspected.

“I shouldn’t be here right now,” said Caleb Field, a junior who has not had two shots but was studying at the university’s student center Friday afternoon. “I’m waiting until they drag me down there. I don’t like shots. If I don’t have to get it, I’m not going to get it.”

Caleb Field, whatever your major is, they should flunk you for poor judgment. If you get it, it’s really your problem alone. But what if you spread it around? What if a person who comes in contact with you is for some reason immunosuppressed? You may very well cause her death.

Twelve mumps cases have been confirmed in Maine since September, the largest outbreak in Maine in 25 years. Last year, more than 1,000 cases of mumps were reported in an outbreak in eight Midwestern states. Most of those affected were college students.

Vox populi

What does the voice of people say on the subject? A recent study published in JAMA and cited in WebMD is instructive.

In February, University of Toronto researchers screened 153 vaccine videos posted on YouTube. The videos included clips for and against immunization, and some of the videos showed anxious parents or crying babies.

About half of the videos didn't explicitly support immunization: 48% were positive about immunization, 32% were negative, and 20% were ambiguous about vaccines. Negative videos tended to get higher ratings from YouTube users.

Vaccines and autism

The scare mongering by various religious sects about vaccines has a history as long as vaccines themselves. But it has got its present momentum in the 1990’s, when a pediatrician at the Royal Free Hospital in London published a paper purporting to show that children who were vaccinated with the MMR vaccine (mumps, measles, rubella) had an inordinately higher rate of autism. He attributed this “epidemic” growth to the presence of thimerosal, a mercury-based preservative. The scientific methodology used by the investigator was woefully deficient. Every respectable pediatric professor in the UK expressed outrage that such poor science should be published.

But the damage was done. Within weeks autism support groups latched onto the new information. More fuel was poured into the fire by a variety of religious groups and just plain kooks opposed to vaccination, or to “establishment medicine” in general. And believe or not, even libertarians of the political right weighed in with the bizzare argument that vaccination is not a function of the state, and children should not be “coerced” as a matter of principle.

Litigious America

In 2004, the prestigious Institute of Medicine concluded that neither the preservative, known as thimerosal, nor the measles-mumps-rubella vaccine was associated with autism and that various hypotheses about how they could trigger autism lacked supporting evidence. Even after thimerosal was phased out of pediatric vaccines, autism rates did not fall. This opinion was based on reviews of literally hundreds of studies—not one of them offering even a scintilla of suspicion that autism is in any way related to vaccination.

So what is an advocate to do? Sue, of course. This is from a New York Times editorial, June 4, 2007 .

“A federal vaccine court in Washington is confronting the contentious and highly emotional issue of whether early childhood vaccinations might have caused autism in thousands of children. Virtually every major scientific study and organization that has weighed in on the issue has seen no link. But many parents of afflicted children remain unconvinced. Their lawyers will try to prove that some 4,800 children were harmed by the mass vaccination campaigns that protect the nation’s youngsters from potentially devastating childhood illnesses . “

One of the obvious, and most common, fallacies in cases like this is a matter of simple statistics. Assume that childhood autism in all its manifestations has a prevalence of 75 /10,000. If we examined a cohort of 100,000 children who received MMR vaccination, you could predict that 750 of them would also have some form of childhood autism. This is just a coincidence, however unfortunate: children are diagnosed as autistic at a young age, and they also get vaccinated at a young age. But there is no cause and effect relationship here.

The lawyers’ argument? Mercury suppressed the plaintiff’s immune response. There is not a shred of scientific evidence for this claim, but that never stopped anybody from going to court. In fact, even the plaintiffs’ lead attorney acknowledged that mass immunization programs are “a great public benefit” that have prevented tens of thousands of deaths and serious injuries. Go figure.

The case of the leaky breast implants

Remember the uproar caused by the claim that women whose silicon breast implant sprung a leak developed all kinds of bizarre symptoms that were lumped together as ‘autoimmune’? Well, scientists got to work immediately when these claims were made, and found absolutely nothing—silicon had no effect on the immune response, and when examined carefully, most of the individual claims were found to be without merit. But by then it was too late. High powered class action lawyers (some of them are today under Federal indictment for fraud) extracted a huge settlement from the manufacturers of the implant, and even from the manufacturers of the silicon. The outcome? Companies went out of business leaving thousands of people jobless.

More seriously, Dow Chemicals, the manufacturer of silicon, refused to supply the material to pharmaceutical device companies. One such device was artificial heart valve. How many patients with heart valve defects, or with bacterial endocarditis, had to go without an implant? How many lost their lives? Who speaks for them?

Dov Michaeli MD, Ph.D is in the biotech industry

By Dov Michaeli MD, Ph.D

On November 11 I read an Op Ed article in the New York Times titled “This is Your Brain on Politics”. Being interested in neurobiology, and an addict of all things political, I homed in like a laser beam: is this the holy grail of neuroscience? Are we capable of deciphering our innermost thoughts (in this case, political thoughts) using brain imaging techniques?

The article was written by three neuroscientists: Marco Iacoboni, Joshua Freedman and Jonas Kaplan of the University of California, Los Angeles, Semel Institute for Neuroscience; a communications professor, Kathleen Hall Jamieson of the Annenberg Public Policy Center at the University of Pennsylvania; and Tom Freedman, Bill Knapp and Kathryn Fitzgerald of FKF Applied Research.

The experiment

The authors used functional magnetic resonance imaging (fMRI) to scan the subjects' brains while they viewed images of political candidates. This imaging technique can be used to measure changes in oxygenated blood and hence to infer changes in metabolic activity in different parts of the brain. Some parts of the brain reliably alter their activity under certain conditions, and scientists have used this fact, along with information drawn from other techniques in both humans and animals, to document which brain area is associated with which cognitive function. For example, greater activity in the insula is often reported when people experience disgust, whereas more activity in the amygdala is reported when people are anxious.

While in the scanner, the subjects viewed political pictures through a pair of special goggles; first a series of still photos of each candidate was presented in random order, then video excerpts from speeches. Then they were shown the set of still photos again. On the before and after questionnaires, subjects were asked to rate the candidates on the kind of 0-10 thermometer scale frequently used in polling, ranging from “very unfavorable” to “very favorable.”

The results

Here are some excerpts from the findings:

1. Voters sense both peril and promise in party brands. When we showed subjects the words “Democrat,” “Republican” and “independent,” they exhibited high levels of activity in the part of the brain called the amygdala, indicating anxiety. The two areas in the brain associated with anxiety and disgust — the amygdala and the insula — were especially active when men viewed “Republican.” But all three labels also elicited some activity in the brain area associated with reward, the ventral striatum, as well as other regions related to desire and feeling connected. There was only one exception: men showed little response, positive or negative, when viewing “independent.”

2. Emotions about Hillary Clinton are mixed. Voters who rated Mrs. Clinton unfavorably on their questionnaire appeared not entirely comfortable with their assessment. When viewing images of her, these voters exhibited significant activity in the anterior cingulate cortex, an emotional center of the brain that is aroused when a person feels compelled to act in two different ways but must choose one. It looked as if they were battling unacknowledged impulses to like Mrs. Clinton.

Subjects who rated her more favorably, in contrast, showed very little activity in this brain area when they viewed pictures of her.

This phenomenon, not found for any other candidate, suggests that Mrs. Clinton may be able to gather support from some swing voters who oppose her if she manages to soften their negative responses to her. But she may be vulnerable to attacks that seek to reinforce those negative associations.

7. John Edwards has promise — and a problem. When looking at pictures of Mr. Edwards, subjects who had rated him low on the thermometer scale showed activity in the insula, an area associated with disgust and other negative feelings. This suggests that swing voters’ negative emotions toward Mr. Edwards can be quite powerful .

Oh, Yeah?

Take John Edward’s “problem”, for example. Is the fact that the insula showed higher activity dooms his campaign? increased activity in any brain area is rarely exclusive to any one function. That insula activity did not necessarily mean the subjects were disgusted. Insula activity has also been associated with drug craving, the taste of chocolate, pain and the quality of orgasm (!). Not necessarily such bad news after all.

This is not “junk Science”; it is purely junk

The authors wouldn’t dare publish such an article anywhere else but on an Op-Ed page; a peer-reviewed journal would send a rejection notice by return mail.

Here is a response of Brandon Keim in Wired science magazine:

“As science, it was a joke. As political theory, it was shallow. As an op-ed, it should have been thrown out at first glance. Uninformed opinion is tolerable in an editorial, but not when it purports to be validated by bad science .”

And the response of 14 heavy-weight neuroscientists:

“The results reported in the article were apparently not peer-reviewed, nor was sufficient detail provided to evaluate the conclusions.

As cognitive neuroscientists, we are very excited about the potential use of brain imaging techniques to better understand the psychology of political decisions. But we are distressed by the publication of research in the press that has not undergone peer review, and that uses flawed reasoning to draw unfounded conclusions about topics as important as the presidential election .”

Why shame on the NYT?

After all, you might think, why not open a window of expression to all scientific observations, valid or not? We do publish rubbish like “intelligence design”, or “creationist theory” side by side with “evolutionary theory”. As chief Justice Brandeis famously said: sunshine is the best disinfectant. But as Nature magazine stated: “What is troubling about the NYT is that the results described in the op-ed are apparently the claims of a commercial product posing as a scientific study. This is only partially transparent. Three of the authors list their affiliation with FKF Applied Research, a company based in Washington DC that is notorious for using similar brain-scan analysis to conclude which TV adverts (pardon the Britishism) aired during a major sporting event were most effective. In its own words, the company is a "business intelligence firm selling fMRI brain scan-based research to Fortune 500 companies".

More troubling for a mainstream newspaper that prides itself on its balanced reporting is the absence of declarations from three other authors. Rightly listed as affiliated to a neuroscience institute at the University of California, Los Angeles, one is also a co-founder of FKF Applied Research and all three, according to a previous publication, have benefited from funding from the company.”

Any harm done?

Yes, and yes. First, harm was done to the reputation of Science as a self-monitoring and self-correcting mechanism, whose only fealty is to the Truth. It gives credibility to political hacks in Congress and other branches of the government who claim that global warming is a figment of statistical models conjured up by “UN scientists”, that Evolution is “only a theory” propagated by atheist-scientists, that the medical harm of tobacco smoking is not supported by credible evidence, and so on and so on. In a day when the assault on science has not reached such a magnitude since the days of the medieval church—we don’t need to provide more weapons for their armamentarium.

And second: The “Twinkies Defense”, used in supervisor Dan White’s defense of his murder of S.F. mayor John Moscone and supervisor Harvey Milk, was a harbinger of things to come. This junk science was presented to the court by a psychologist-“scientist”. Brain imaging “evidence” is now being presented in court by hired gun-“neuroscientists”. Genetic information is being twisted beyond recognition in the service of racists and other malevolent rabble.

This is why an article such as this one is not just an innocent romp through neuroscience and politics, maybe even with a faint sense of humor. It is harmful, and shame on the NYT for publishing it.

Dov Michaeli MD, Ph.D is in the biotech industry

By Dov Michaeli MD, Ph.D

The question of what makes us "human" has occupied philosophers since  Aristotle. And the well worn, but profound statement of 17th century French philosopher Descartes "I think, therefore I am" or in Latin "cogito ergo sum" (he actually wrote it if French: "Je pense, donc je suis"), has formed the basis for modern Western philosophy to this day. Today, thinking is one of the basic traits attributed to being human. And one of the of the pillars of thinking is language and speech, the ability to express our thoughts. From here, it is only a logical skip and hop to the assumption that Homo sapiens' uniqueness resides in its aqcuisition of the capacity for speech. In fact, molecular biologists discovered that a gene responsible for speech, FOXP2, has undergone mutations in two areas. And it is these mutations that endowed us with the capacity for speech while the chimpanzee, which does not  have these mutation, has no capacity for complex speech and by extension, for expressing ideas.

This finding is really mind boggling. Just stop and think about it for a minute: a couple of completely random mutations in a specific gene have such profound effects so as to transform a non-thinking species into a thinking species - one which,  in time, would grow to dominate not only the world, but also the genetic processes that brought about the critical mutations in the first place. It is nothing short of of amazing. No wonder some people would see the hand of an "intelligent designer" in accomplishing this simple, yet elegant, feat.

But wait, things are not that simple

The New York Times reports on October 19 2007:

Neanderthals, an archaic human species that dominated Europe until the arrival of modern humans some 45,000 years ago, possessed a critical gene known to underlie speech, according to DNA evidence retrieved from two individuals excavated from El Sidron, a cave in northern Spain.  The new evidence stems from analysis of a gene, called FOXP2, which is associated with language. The human version of the gene differs at two critical points from the chimpanzee version, suggesting that these two changes have something to do with the fact that people can speak and chimps cannot.

The genes of Neanderthals seemed to have passed into oblivion when they vanished from their last refuges in Spain and Portugal some 30,000 years ago, almost certainly driven to extinction by modern humans. But recent work by Svante Paabo, a biologist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, has made it clear that some Neanderthal DNA can be extracted from fossils.

Dr. Paabo, Dr. Johannes Krause and Spanish colleagues who excavated the new bones say they have now extracted the Neanderthal version of the relevant part of the FOXP2 gene. It is the same as the human version, they report in today's issue of Current Biology.

What's the big deal?

We used to think of our cousins, the Neanderthals, as primitive, cultureless cave dwellers, who became extinct because they were just too dumb to compete with us, the intelligent creatures chosen to inherit the earth.

Bit by bit evidence is emerging that they were not primitive at all, compared with contemporary Homo sapiens. They made tools, just like us. They even made jewelry, similar to ours. What that implies is not only artistic capacity, but also the capacity to think abstractly; jewelry is fundumentally a symbolic expression of feelings, of desire to attract the opposite sex, and of social status. So not only were our "poor cousins" quite sophisticated, they must have had some kind of social hierarchy--just like us.

Now, we know that they could communicate using language. FOXP2 is critical for the capacity to speak, but it would be an oversimplification to assume that that it is the only gene involved in speech. Nevertheless, what we know today is that speech did not make us unique, and that we were not exclusively endowed with intelligence, with abstract thinking, or with a sense of community and society.

FOXP2: what does it do? 

When we talk about the endowment of the capacity for language, don't you think about some complex neurological circuits in the brain, somehow miraculously transformed into the the substrate on which grammar and syntax grow?  I always felt that there is something really abstract, almost magical about the acquistion of the capacity to express ourselves through speech.

Puff, the magic dragon

Like all other magical things, when we learn the mechanics of the "trick", the awe is replaced with a feeling of let down; is that all there was to it? I thought about it today, as my wife and I toured the Johnson Space Center in Houston, saw Mission Control in its true dimensions (much smaller  and drab than we saw on "Appolo 13" or on TV), and the Astronaut Training Center. The latter was especially deflating. I always had a sense of wonder about those competent, knowledgable, daring, cool guys who seemingly could do anything under the most extreme circumstances. They were bigger than life, they were super human. Until we saw the mundane mechanics of their training. It was nothing more sophisticated than mastering certain skills in handling all kinds of hardware, not much more complicated than operating a crane, or learning to drive. Of course, some of the operations are complex, some require extreme eye-hand coordination-but basically, given the ten-year training period, any school teacher could do it. Astonishingly, you don't even have to be a pilot.

What does all this have to do with FOXP2?

Unlike the magical powers I was ready to attribute to this gene, it probably is  involved in control of rapid motor movement , and the mutations that allowed us to speak simply enabled us to utter words, which require extremely rapid and delicately controlled  muscle action.When a chimp sees something breathtaking he may sit, watching in awe, silently (or maybe a grunt or two). We, on the other hand, may wax poetic about it. But the somewhat disappointing difference is not abstract or magical at all, but purely mechanical--we have the mechanical capacity to give immediate expression to our thoughts. And so did our Neanderthal cousins.

What about dolphins, and whales? We still don't know, but I am sure that their FOXP2 gene is being looked at.

Are there other species that have the mutations in FOXP2? Yes. Echolocating bats have it, and it makes sense: the bat has to rapidly respond to a continuous stream of sensations (sonar pulses), and respond appropriately. Bats that are not echolocating do not have these enabling mutations.

Confused? Don't feel bad about it-- so is everbody else. The story of language is still unfolding. What we are witnessing is the uncovering of the mysterious magic of language, and when the details come to light, inevitably some of the mystery and its magical quality will dissipate.

Dov Michaeli MD, Ph.D is in the Biotech industry  

By Pat Salber, MD

There is a haunting photo by Joao Silva on the front page of the NY Times (10/10/07). A young boy is looking inside a bullet-ridden white Oldsmobile. The front window is shattered and the driver’s side door is dripping bright red blood.

We are not told whether the boy knew or is related to the victims – two women -- one a 59 year old mother of three grown daughters; the other woman was her 30 year old passenger.  We can be fairly certain from expression on this youngster’s face, that this is a life-changing event for him. He will not be the same after this witnessing this horrific scene as he was before.

My speculation about this boy's future is supported by an article in the current issue of BMC Public Health. The authors, Asma Al-Jawadi and Shatha Abdul-Rhma, assessed 3079 children from families who attended primary health care institutions in Mosul, Iraq and found mental disorders in more than one third of the children. Let me repeat that, more than one third of children were found to have mental disorders.

Here are the details of the study. Mothers who came to the primary health centers in Mosul for vaccination of one of her children were included in a systematic sampling randomization. All children of these mothers (ages 1-15 years old) were considered in the interview and examinations. 3079 children were assessed. 1152 were diagnosied with a childhood mental disorder for a point prevalence of 37.4%. The ratio of males to females was 1.22:1.

The top ten diagnoses among the examined children were as follows:

• post-traumatic stress disorder (PTSD) ( 10.5%)
• enuresis (bed-wetting) (6%)
• separation anxiety disorder (4.3%)
• specific phobia (3.3%)
• stuttering &school refusal each had a point prevalence of 3.2%
• learning & conduct disorders have the same figure (2.5%)
• stereotypic movement (2.3%)
• feeding disorder of infancy or early childhood (2.0%).

Overall, the highest prevalence of mental disorders was found among children 10-15 year old (49.2%). While the lowest prevalence was in 1-5 year olds (29.1%). Boys were more afflicted than girls (40.2% & 33.2%) respectively.

Now that you have read this, please go back and look again at the face of the little boy in the photo. What is his future? PTSD?...probably. Acting out?...likely. Will he have problems concentrating at school?...yeah, that too. Without therapy – a scenario unlikely in war-torn Iraq- will this young boy be able learn a profession or trade and eventually make non-war-related contributions to his community and his country? Or will he be forever altered, unable to function “normally” in a “normal” society?

These are not just potential social or political problems, rather, they are important health care challenges that have had little, if any, discussion that I have seen in the national or international media. Yet, once this war is over and Iraq enters its post-war period, mental health disorders in the population - both adults and children -- will be a serious health care issue that will have to be addressed if Iraqi’s are able to build a healthy society.

Doubt the seriousness? If so, I suggest you go back and take one more look at that little boy’s eyes.

By Dov Michaeli MD, Ph.D

Neurobiological research has discovered that our brain is an arena for fierce competition: primitive reactions such as fear and aggression competing with cooperation and altruism, risk-seeking competing with risk aversion, male testosterone competing with your inner female—all competing for attention. Whose attention? – your brain’s prefrontal cortex, the executive that gets all the inputs, weighs them one against the other and then makes a decision which one should prevail—and the outcome of this process is your behavior.

Adolescent behavior

Research on the neurobiology of children’s and adolescents’ behavior revealed that the prefrontal cortex is still immature and performs its executive functions in an incomplete, and sometimes in an haphazard way. Sometimes the loud volume of a risk-seeking voice would drown out the more cautious whisper, and the poorly functioning prefrontal cortex, still lacking Solomonic wisdom, does not exert its judgment; the result is ‘adolescent behavior’.

Is it solely a function of the prefrontal cortex?

If all judgment resided in this cortex, one would expect that once all the neurons are programmed, correctly connected, and fully functioning all adults would behave in a, well, adult way. But consider these statistical finding about the behavior of adults age 35-54, published in a New York Times op-ed by Mike Males:

• 18,249 deaths from overdoses of illicit drugs in 2004, up 550 percent per capita since 1975, according to data from the National Center for Health Statistics.
• 46,925 fatal accidents and suicides in 2004, leaving today’s middle-agers 30 percent more at risk for such deaths than people aged 15 to 19, according to the national center.
• More than four million arrests in 2005, including one million for violent crimes, 500,000 for drugs and 650,000 for drinking-related offenses, according to the F.B.I. All told, this represented a 200 percent leap per capita in major index felonies since 1975.
• 630,000 middle-agers in prison in 2005, up 600 percent since 1977, according to the Bureau of Justice Statistics.
• 21 million binge drinkers (those downing five or more drinks on one occasion in the previous month), double the number among teenagers and college students combined, according to the government’s National Household Survey on Drug Use and Health.
• 370,000 people treated in hospital emergency rooms for abusing illegal drugs in 2005, with overdose rates for heroin, cocaine, pharmaceuticals and drugs mixed with alcohol far higher than among teenagers.
• More than half of all new H.I.V./AIDS diagnoses in 2005 were given to middle-aged Americans, up from less than one-third a decade ago, according to the Centers for Disease Control

In Conclusion

To ascribe all behavior, good or bad, to the structure and function of the brain is not only simplistic and incorrect biologically, it is socially dangerous; “The devil made me do it” as an excuse for sociopathic behavior is simply not compatible with a functioning civil society. Unfortunately, defense attorneys are already recruiting expert witnesses who make this deterministic argument in court.

 Males concludes his article thus: “ In reality, human brains are highly adaptive. Both teenagers and adults display a wide variety of attitudes and behaviors derived from individual conditions and choices, not harsh biological determinism. There’s no “typical teenager” any more than there’s a “typical” 45-year-old.

Commentators slandering teenagers, scientists misrepresenting shaky claims about the brain as hard facts, 47-year-olds displaying far riskier behaviors than 17-year-olds, politicians refusing to face growing middle-aged crises ... if grown-ups really have superior brains, why don’t we act as if we do?”

To which I can only add: amen!

Dov Michaeli MD Ph.D is in the biotech industry, and frquently has his doubts about his own prefrontal cortex.

 

 

 

 

 

 

 

 

By Dov Michaeli MD, Ph.D

In my previous posting I reviewed a paper published in the New England Journal of Medicine which showed that obesity can spread among friends and family just like any infectious disease. But unlike infectious diseases, physical proximity did not count for much: obesity did not spread among neighbors. It did spread among family members, regardless of geographical location. The strongest influence on the spread of obesity was friendship, in particular mutual friendship. This was a totally unexpected finding.

The paper had some unavoidable flaws. For instance, in assessing the effect of friendship, the investigators had data on an average of 0.7 “contacts” (or friends) per case. This hardly gives a complete picture of the social network of the average person. So, at this stage I am skeptical but hope I am wrong. I hope that additional studies will corroborate the basic finding of the relationship between social contacts and disease. Why?

Our current understanding of disease

We have been educated to look for physical explanations to biological/medical phenomena. As physicians we were taught to look for the “disease genes” ( for instance Huntington’s disease, sometimes called Guthrie’s disease after the famous folk singer Woodie Guthrie who died of this disease), or the metabolic dysfunction ( diabetes type 2), or environmental influences ( lead poisoning, pollution-induced respiratory diseases), or combination of those ( cancer as a consequence of genetic predisposition and environmental mutation-causing substances). We viewed with suspicion the ancient art of ‘alternative medicine,’ in my view justifiably so. When subjected to rigorous scientific examination, most if not all of those folk remedies turned out to be just, well, folktales.

But ‘hard science’ Medicine is also wanting, and the example at hand is the spread of obesity. Several genes that predispose to obesity have been identified, but they account for only a minority of cases of the ‘disease’. What accounts for the rest? We all answer reflexively: lifestyle. But that’s too glib. Why do some people have to fight mightily to avoid obesity, while others barely move off the couch with nary an ounce of weight gain? Again, metabolic differences sometimes exist, but many times they are at least not readily apparent.

Enter social networks

The surprising finding that friendships are powerful factors in the spread of obesity, if corroborated, would go a long way toward explaining the puzzle of the ‘obesity epidemic’. And not only obesity: many other diseases are now becoming susceptible to this analysis. Why is it that we are having an ‘autism epidemic’? Why is it that certain school districts have an inordinately higher prevalence of autism? No suspected physical agent, including the much abused vaccination of children, stood the test of rigorous examination. Increased awareness? Erroneous or loose diagnoses? They don’t account for the rise.

The possibilities are even more amazing. If you examine the genes of obesity and diabetes type 2, you’d find that these two diseases share at least three genes. Which raises the possibility that there exist networks of diseases, all interlinked. This may explain, at least in part, why a certain drug given for disease A would affect disease B, or cause side effects unforeseen by our knowledge of the drug’s mechanism. A wonderful example is the drug imatinib (or Gleevec), designed to work specifically on a mutation of the enzyme tyrosine kinase (called Bcr-Abl) that causes CML or Chronic Myelogenous Leukemia. Lo and behold, despite its great specificity it turned out to inhibit another tyrosine kinase called c-kit, that is responsible for rare a stomach cancer called stromal tumor. What’s the connection? The drug action uncovered an unsuspected close link between the two enzymes; both evolved from a common ancestor gene, and the two cousin proteins resemble each other like twins. But wait, there is more... even more unexpectedly, it was discovered that the drug activates a certain immune cell (IKDC) that is active in killing infectious organisms and tumor cells. The mechanism for that is largely unknown. This is only one example, but it hints at as yet- undiscovered complex networks of diseases.

Question: all these examples deal with molecular networks, which makes it intuitively easy to visualize interactions between molecules and the effect of these interactions rippling through the networks. But how would something spread through social networks? The answer: through memes.

Memes, and spread of ideas (and diseases)

What is a meme? The definition I like the best is from the Wikipedia:

meme , (IPA: /mi:m/ ) as defined within memetic theory, comprises a unit of cultural information, cultural evolution or diffusion that propagates from one mind to another analogously to the way in which a gene propagates from one organism to another as a unit of genetic information and of biological evolution. Multiple memes may propagate as cooperative groups called memeplexes (meme complexes).

Biologist and evolutionary theorist Richard Dawkins coined the term meme in 1976. in his book “ The Selfish Gene”. He gave as examples tunes, catch-phrases, beliefs, clothing fashions, ways of making pots, and the technology of building arches.

Amazing; units of cultural evolution spread like genes or viruses, which like genes, are packets of DNA or RNA, and obeying Darwinian laws. No wonder we use such phrases as “an infectious idea” or “the virus of extremism”. Or here is David Brooks of the New York Times on the subject of naming newborns:

“Naming fashion doesn’t just move a little. It swings back and forth. People who haven’t spent a nanosecond thinking about the letter K get swept up in a social contagion and suddenly they’ve got a Keisha and a Kody. They may think they’re making an individual statement, but in fact their choices are shaped by the networks around them. “

Well, networks networks everywhere… from the molecular level, to the cellular level, to whole organisms, to social units, to nations, to the whole human race. I remember reading in the early 70s the essays of Lewis Thomas, “Notes of a biology Watcher”, published periodically in the New England Journal of Medicine. It was poetry in science, and science in poetry. This is from his introduction to the collection of his essays, “The Lives of a Cell”:

“Viewed from the distance of the moon, the astonishing thing about the earth, catching the breath, is that it is alive”. And later: “It has the organized, self-contained look of a live creature, full of information, marvelously skilled in handling the sun”.

In today’s less poetic terminology we could call this earth-creature 'an infinitely interconnected complex networks'.

The battle of the memes

Memes, like genes, spread among people, only they do it a lot faster. The idea of agriculture, invented in Anatolia (today’s Turkey ) about 10,000 years ago, spread all the way to the Iberian Peninsula within 2000 years. This is lightening speed, considering that a new mutation would need hundreds of thousands of years to establish itself in a given population. Or take the meme of the industrial revolution: within 100 years industry spread throughout the ‘industrial world’ of today. Or the computer, or the iPhone, or… what’s the next meme to spread like a virus throughout the world?

But not all memes are created equal. Like genes, they have to be accepted by the individual’s mind, and if need be demolish competing memes. An example: the idea (or meme) of monotheism, displacing polytheism that had reigned supreme for thousands of years. What was needed for it to triumph was the cultural readiness to be accepted. The early Christians were mocked, tortured and fed to the lions. But with time they became tolerated, tacitly accepted, and finally, following an approval from an authority figure ( Emperor Constantine , 312 A.D.), the whole Roman Empire converted. Mind you, the people did not have to be coerced—they were ready, the meme of Christianity had already infected them.

What does all that have to do with obesity?

Just like many other memes, the beginning of the obesity meme may have been hard. The sight of an obese person clashed with the body image of most people. An obese woman in shorts? Unheard of! With time, with more and more obese people in shorts and swim suits it ceased to be novel; in fact, it became sort of accepted. And the road from acceptance of obesity to the powerful influence of an obese friend on his close friends to become obese is quite short, and plausible.

Why doesn’t it work in the other direction, you might ask? Why doesn’t the thin person influence his or her obese friends? I think the answer lies in the biology. Our metabolism is geared toward storage of energy as fat. To go the other way is energetically (in the metabolic sense) and psychologically an uphill battle. So in the battle of the memes, obesity wins because biology is on its side.

Are we doomed to everlasting obesity?

A perfect example of how to win the battle of competing memes is the reversal of the smoking epidemic. Education and peer pressure rendered our mind ‘unready’ to accept smoking despite its addictive properties. Intensive education, coupled with unrelenting peer pressure and regulation can form a countervailing force to resist the path of least resistance offered by the biology.

Will it work? There are encouraging signs . There is a website, http://www.peertrainer.com/, that brings together people who are trying to lose weight, and even more difficult--to maintain it. The whole premise is for the members of this network to publish daily their diet, their elation at success and the heartbreak of failure. The other members of the network are supportive, cheering on, encouraging, and when appropriate--dispense some tough love. Judging from the enthusiastic testimonials and almost fanatical belief in the network's help--it works. Yes, these are still testimonials, but to paraphrase senator Everett Dirksen, a testimonial here, a testimonial there, and pretty soon you are talking  real sample.

Epilogue

So here we are , at the end of our journey through biological networks, linked to social networks, and then completing the circle in the biological network again. I fervently hope that it will turn out to be true. Wouldn’t it be wonderful if the World-Wide Web assumed a new meaning, that of a brand new vision of life on earth? All interconnected, all intimately dependent on all. 

Dov Michaeli MD, Ph.D. is in the Biotech industry and has an abiding interest in all things biological.

By Dov Michaeli MD, Ph.D

A few days ago the media were abuzz with the news that a tooth may have solved a mummy mystery (The New York Times, June 27, 2007 ). As a great fan of anything ancient and mysterious I ignored the really important news of Paris Hilton getting out of the slammer and delved into the article with great anticipation.

Who was Hatshepsut?

The 18^th dynasty of pharaohs started at the beginning of the 15^th century B.C. (that’s about 3500 years ago!), after about 200 years in which Egypt was in cultural, economic and military decline and was ruled by nomadic tribes, the Hyksos, that had come down from what is today Turkey. Ahmose I liberated Egypt , and established the arguably most powerful dynasty in ancient Egypt ’s history. Hatshepsut was his granddaughter.  She married her half brother Tuthmose II. He promptly died, and she became regent to his son from another marriage, Tuthmose III, who was too young to rule.

Now it’s getting more interesting. After seven years as a regent, Hatshepsut takes the extraordinary step of proclaiming herself a pharaoh (or a king, as in male king). Mind you, there had never been a female pharaoh before her; in a feat of diplomacy and cunning she managed to overturn over 2500 years of Egyptian tradition. And she proceeded to initiate a 15 year reign of extraordinary flowering of Egyptian art, architecture, and economic progress. Remarkably, this was accomplished without resorting to war and plunder, as was the rule in those days. And her reign came to a mysteriously abrupt end. I think we now know what happened.

You wouldn’t have guessed…

Using modern techniques, Egyptian archeologists examined a female mummy that had been discovered early last century. She was dubbed “the obese lady”, and was considered unimportant. They subjected a box that had the name Hatshepsut inscribed on it to a CT scan, and lo and behold they found there a tooth that seemed to belong to the obese mummy, as well as her embalmed liver. CT of the body confirmed that she was obese, diabetic, and had bad teeth. She died at age 50, probably of cancer; the reports vary between liver cancer and bone cancer.

Queen HatshepsutWhy would nobody guess such an ignominious demise? Because her statues depict a woman exuding beauty and power, with a gaze that will transfix you and a body that beats that Paris Hilton. Go see it in the Metropolitan museum when you are in New York .

There is still hope

I was crestfallen. To me she was more beautiful than Nefertiti (king Tut’s wife), and wiser than the ever-scheming Cleopatra. How could she fool me so and be fat, diabetic and worst, with poor teeth?

But all is not lost. With all due respect to the Egyptian dentist who determined that ‘if the tooth fits’, it must be hers. I would like to see independent confirmation based on forensic dentistry, including DNA analysis. And how did they make the diagnosis of diabetes? Show me the data! The claim that the fat lady belonged to the 18^th dynasty sounds convincing: mitochondrial DNA analysis showed connection to the matriarch of the dynasty. Still, can we please have some samples sent to bona fide molecular biology lab?

Diabetes: an ancient disease

We ‘pride’ ourselves for inventing Diabetes type II, because we massively overeat and are disgustingly inactive. but did we? I am reminded of my childhood neighborhood rabbi, who expressed his pride in the Jewish ancient culture by saying that “when they (meaning the Goyim) were still climbing trees, we Jews already had diabetes”. Point well taken.

But rabbi, wherever you are today, I just got the bad news: before there were any Jews at all, the Egyptians already suffered from diabetes, high blood pressure, and cancer. I hope this new Egyptian claim to fame does not inflame nationalistic passions and trigger a new war in the Middle East .

 

Here is the first post of new TDWI writer, Brian Klepper, PhD -- a different kind of doctor, true, but one who knows the health care industry inside and out.  Dr. Klepper is the Founding Director of the Center for Practical Health Reform, a broad-based non-partisan effort to re-establish stability and sustainability to American health care.  He is also an independent health care analyst.

 

Here you go:  The cognitive dissonance of conflicted care

A few days ago the New York Times ran yet another article exploring the deep financial conflicts in oncology drug prescribing. This one described two facts.

First, even though Medicare has limited the profits of oncologists who prescribe drugs, Medicare’s total cancer care expenditures keep rising because oncologists have found new treatments and procedures to bill for.

Second, the rules guiding Medicare reimbursement for cancer and drug rebates are complex, compromising the financial abilities of some oncologists – particularly those in smaller practices – to administer drugs to their patients. As a result, those patients often must receive the drugs in more costly and possibly less-friendly hospital settings.

Over the last year, the Times has been on this topic like white on rice. Last month it ran an article on conflicts in anemia drugs, which demonstrated just how much money was available to doctors who prescribe them. A just-fired practice administrator of a six-oncologist group in the Pacific Northwest presented the Times with papers from Amgen. They showed that, over the past year, physicians in that practice had written $9 million in prescriptions for the two anemia drugs Aranesp and Epogen. Amgen returned the favor with $2.7 million in "rebates." These numbers work out to $1.5 million/physician in prescriptions, with returns of $450,000 (30%) per physician and profits of $300,000 (20%). The Times also ran a chart showing that dosing levels in the US, where rebates that encourage more prescriptions are standard practice, are as much as three times higher than in other countries where the rebates aren’t permitted. (Whether outcomes are better here is not clear.) These drugs were only two of many that oncologists prescribe, and there are rebates associated with many of those others as well. Of course, oncologists also make money, though far less, for actually being doctors.

I distributed the anemia drug rebate article to my network, which includes a number of cancer professionals. One response, from a nationally known oncologist, said, “If I don’t have the rebates, my income will go down!”

I first became interested in oncology drug practices about a year ago when the Times reported on a study that had been published in Health Affairs showing that oncologists prescribing behaviors were influenced away from best practice and toward the incentives provided by their rebate arrangements. The study had been conducted by highly credible health services researchers using a large sample of Medicare claims data from 1995-1998.

While the study’s findings were interesting, they were hardly news. After all, financial conflicts permeate every area of health care. Far more interesting was the righteously indignant response from the Community Oncology Alliance, a professional group that represents private practice oncologists. In the opening sentence of a remarkable email distribution to its membership, Steve Coplan, the administrator of the West Clinic in Memphis, called the report “incredibly outrageous and unsubstantiated” and “an unbelievable rehash.” Sentence two referred to “incomprehensible statements by government bureaucrats, so-called oncology advocates, well-paid consultants, non-practicing physicians, payers and specialty pharmacies.” In other words, only community oncologists can understand or question the deep complexities inherent in the practice of cancer care. Everyone else is infused with malevolent intent.

Many oncologists will tell you that rebates cover the costs of drug administration and are necessary because 1) Medicare doesn’t pay for office administration and 2) Office administration costs far less than it would in a hospital setting. In effect, the drug companies convinced Congress to let them pay for these services, though the compensation is far more than Medicare would ever pay. This gave them significant influence over the practice patterns of the nation’s community oncologists.

Medicare could correct this situation by outlawing drug rebates to oncologists (and other physicians), while paying doctors a reasonable rate to administer the drug. Medicare and commercial plans could offset the additional cost by reducing reimbursement to the drug companies by about 20 percent, or the amount of the doctors’ rebates.

The recent exposure in the Times, the Wall Street Journal and other major papers has shone a bright light on the uncleanliness of these practices, and many oncologists have complained to me that they’re feeling picked on. I’m sure the drug companies aren’t crazy about it either. The typical oncologist now makes about twice as much from drug rebates as from practice. Of course, they’re not happy at the prospect of losing any of that income. We can be certain there’s a great deal of maneuvering going on behind the scenes by pharma and the oncology lobby as Medicare reassesses its approach.

It’s a fascinating problem. Oncologists (correctly) see themselves as righteous practitioners, caring for very sick and sometimes terminal patients and families in the most distressed periods of their lives. It appears very difficult for them to confront the fact that the way the money works maybe isn’t so healthy. They argue that they’re simply following the incentives that have been set up for them, without acknowledging that their complicity compromises patient care, their own position, and the stability of the larger health system.

I have an article in the journal Community Oncology this month that calls on oncologists to look squarely at this problem, understand the damage it's doing to their credibility and reputation, and work with the various payers to remedy it. The rebuttal article, by the prominent and dedicated Linda Bosserman MD, raises all kinds of peripheral questions involved in drug rebates that were, to me, obfuscatory and beside the point. And there lies the rub. Ultimately, she argues for the same things I do – for changes to the reimbursement mechanisms that keep clinical decision-making detached from financial consideration. But it is difficult for her to directly confront the financial conflict inherent in the current system.

As Dr. Michaeli has argued in this blog before, a new transparency is uncovering excesses in every health care sector. People outside the industry are shocked by what they see as egregious behaviors, and hopefully their recognition will eventually have a cleansing impact on how health care is supplied, delivered and financed in this country.

We know that half or more of health care cost is wasted, inappropriate or unnecessary, largely the result of the behaviors discussed here. Until financially conflicted health care is addressed in oncology and elsewhere, we don’t have the remotest chance of re-establishing stability and sustainability to American health care.