What many people don't understand about the very important concept that controlling body weight is not a matter of will power is that people can still be healthy, or improve their health dramatically, no matter what they weigh. Everyone can make changes in their lives that will improve their health. It is absolutely true that a sedentary lifestyle combined with poor eating habits is clearly linked with disease, such as diabetes and heart disease. The important thing is the process of learning to incorporate healthier habits, while doing away with prejudice or discrimination against fat people. Shaming fat people will not lead to improvement in anyone's health. Instead, it will continue to engender low self-esteem, unhealthy dieting practices that will slow down metabolic rates, and eating disorders. In short, the focus should be on learning to live a healthier lifestyle that doesn't involve beating oneself up on a regular basis, based on one's appearance or a number on a scale. Check out Linda Bacon's website and the website for the Association for Size Diversity and Health.

In the first part of the book, in order to draw parallels with current scientific evidence for the “epidemics of obesity and diabetes,” he puts forth a detailed historical analysis of the decades-long debate on the correlation, or causation, of heart disease with dietary fat intake. The upshot of this work is to point out what happens when a researcher, who becomes prominent for various reasons, can influence health care policy even when the researcher’s scientific data are far from conclusive. In this particular case, Taubes discusses the work of the prominent physiologist Ancel Keys, who was convinced, based on his research that the rise in incidence of heart disease in the developed world from the 1920s through the 1950s was due to increased blood cholesterol levels, which was in turn due to increased total dietary fat intake. Keys was apparently a formidable character who felt very strongly that his data conclusively proved this hypothesis, and was very quick to strongly criticize those who opposed his theories. Throughout this time period, and even into the 1960s, there were many prominent researchers who had serious reservations, based on scientific analysis of his data as well as their own, that Keys’ results were inconclusive. Nevertheless, because Keys was so forceful, Taubes brings various elements to show that the media picked up Keys’ theories, and physicians began to recommend low fat diets to their patients, despite lack of strong scientific evidence for increased dietary cholesterol intake (mainly from animal fats) causing a rise in heart disease.

In such a scenario, the question becomes one of correlation versus causation, i.e., depending on how solid the scientific evidence is for any given observed public health phenomenon, one might be able to say there is a CORRELATION of a dietary trend with observed disease incidence, rather than being able to state, through a solid base of scientific evidence, that a given dietary trend CAUSES disease. This concept is one that the Health at Every Size paradigm considers regarding current dietary habits with the incidence of “obesity” and diabetes. The bottom line is that there is still much scientific work that needs to be done to determine whether lifestyle in the developed world causes, versus merely correlates with, “obesity” and diabetes.

One reason for this phenomenon of correlation overpowering the media is that it provides a solid message to address what appears to be an alarming trend. Understandably, people don’t have the patience to wait for conclusive scientific evidence to be produced when faced with a potentially scary scenario. When scientific evidence that contradicts the popular theory is published, it tends to be ignored, because it doesn’t fit what has become DOGMA, based on the popular correlation. Taubes skillfully points out that when correlations are not thoroughly researched scientifically, and they become socially accepted dogma, real scientific progress just breaks down. Ultimately, I believe, the truth always emerges in the end, and the road of public health history is littered with the corpses of what used to be very popular theories. But while the dogma exists, well meaning but misguided health professionals may in fact do more harm than good, by encouraging unrealistic weight loss goals rather than focus on lifestyle changes.

This past Sunday my husband and I visited the Neuberger Museum of Art at SUNY Purchase. In their permanent collection of Modern Art were some examples of Dada Art. The Dada movement was started by a handful of artists, both American and European, who were deeply affected by the atrocities of World War I. The disintegration of societal norms during the war brought out in the Dada-ists a sort of nihilism and a desire to mock contemporary culture. The presence of the war in Europe drove many artists who were living in Paris to the relative peacefulness of the United States, where the Dada movement blossomed in the 1920s. There they found plenty of fodder for their cynicism in the industrial revolution and the rise of new forms of advertising. After viewing several Dada Art exhibits over the years, I finally realized I was on common ground with them.

At the Neuberger Museum, the piece that caught my eye and imagination was a gelatin silver print by Man Ray of Marcel Duchamp in a female alter ego whom they called Rose Selavy, which in French means “Eros, that’s life!” The original perfume ad was for “Belle Helaine, Eau de Violette”. In Man Ray and Marcel Duchamp’s version of this ad, the face of the woman, displayed prominently on the label of the perfume bottle, was replaced with the face of Rose Selavy, and the text on the bottle was replaced with the words “Belle Haleine, Eau de Voilette” which means “Beautiful Breath, Veil Water.” At first glance, this makes no sense, which is characteristic of Dada art. The description of this photo at the museum described its meaning best:

“This gesture [changing the image and text on the perfume bottle] alludes to the idea that [the reigning image of] feminine beauty [in the 20^th century industrial revolution] is not natural, but rather a social construction – a masquerade perpetuated in the images of women circulated in commercial and mass cultural forms like advertising and the cinema.”

To Man Ray and Marcel Duchamp, feminine beauty lay much more in the spirit of the soul, rather than crass, glossy, manufactured images. Too bad their images and ideas were completely eclipsed by the power and money of advertising – this to the true detriment of our health as a society.

Rob Townley, one of these students, had found himself in his 4^th year of graduate school, having, in his words, “burned all of his bridges” and in limbo without a lab to go to. Clearly he had left the lab he had been working in on less than ideal terms and was hilariously honest about what a troublemaker he was. I understood exactly how he felt, having been in the same position in my own graduate work, only I was in the fifth year of my graduate career at that point (and not nearly as candid or hilarious as Rob about how difficult I was). Rob was lucky that at that relatively late stage in his career he was accepted into another lab, and was doubly lucky to find Dr. Shapiro. In order to get my PhD, I had to stay in the lab I started in because no other mentor (that I wanted to go to) was willing to take me at such a late stage. The “fire in my belly” and a sense, expressed by one of the other graduate students in the film, that I would be “quitting” if I gave up, gave me the resolve to mount an argument convincing enough to my original mentor to keep me on.

Despite the difficulties experienced by Rob and his fellow students, I found myself grinning throughout most of the film, laughing at certain points that were all too familiar. Watching the students burn their fingers retrieving glycerol stocks of desired bacterial strains from the -80° C freezer or liquid nitrogen, growing up countless liters of the bugs in 2 liter flasks on shakers in the warm (37° C) room, vortexing test tubes, making liters of buffer, engineering DNA plasmids (which were transformed into bacteria) and loading and running hundreds of gels by electrophoresis reminded me of the everyday experiences that took up so many years of my life (in college, as a technician, and as a graduate student).

There were also moments in the film when I remembered the sadness and desperation of repeatedly failed experiments. A particularly poignant moment was when Rob spoke of such desperation that he did basically no work in the lab for 3 months – he was just too despondent after so many failures. I did the same thing at one point, although I used that time to write a proposal for a new project that ultimately got me my PhD (and my neck out of the proverbial noose). Many PhD students go through something like this, and as individuals will react in their own way. But the all too real feeling of wanting to quit repeatedly, experienced by most if not all graduate students, was very effectively conveyed.

Another aspect of graduate work in science that was very effectively conveyed in the film was the “luck” factor. No matter how hard, intelligently, diligently and doggedly a researcher works, it can take years before any of his/her work bears any fruit at all, and learning how to conduct independent research at the same time makes it all the more difficult. Dr. Shapiro described the balance mentors have to try to strike in terms of the amount of guidance they provide a student, and I think he must be one of the more successful mentors around. Shapiro happened to be at the screening last night and was invited by the panel moderator to speak to the audience following the conclusion of the film. There was one thing he said which brought me a feeling of intense joy and vindication, which was that prior to participating in and viewing the film, he did not have a real appreciation for how hard it really is for graduate students. I just wanted to shout “thank you, thank you, thank you!”

This life-long love of animals has prompted me to join organizations dedicated to wildlife and nature conservation, such as the Natural Resources Defense Council and the Center for Biological Diversity. I joined their army of email activists, and began to receive many messages from these organizations about the wanton killing of wolves in the Rocky Mountains. As I participated in every email campaign to support the legal efforts of these organizations to protect wolves, I became increasingly curious about the motivation behind the slaughter.

As a dog lover and as someone who has never had a close encounter with a real wolf or wolf pack, I was very offended that the US Fish and Wildlife Service was taking steps, with the blessing of the recent, dearly departed Bush administration, to make it easier for hunters to slaughter wolves. Apparently, wolves are inconvenient to domestic cattle ranchers whose ancestors settled the “wild” west in the 19^th century. The original settlers slaughtered buffalo in order to make room for their domestic herds to graze. The buffalo were the natural prey of wolves, so when they all but disappeared, the wolves naturally turned to preying on domestic livestock and cost the ranchers a bundle. What must have been an inborn fear or hatred of wolves on the part of these pioneering ranchers manifested as the aggressive hunting and killing of these “pests”, to the point where they were practically eliminated from Yellowstone National Park in the early 20^th century. Since that time, the US Fish and Wildlife Service has coordinated the re-introduction of wolves into the Rocky Mountains. The population has been reviving, along with the old animus between the wolves and the ranchers. The thought of another round of wolf slaughter saddened me terribly. Being a city slicker, I look at pictures of wolves and want to see big, huggable dogs, but I’ve probably always known on some level that this is very inaccurate.

On a recent trip to the library, I came across a book entitled Of Wolves and Men by Barry Holstun Lopez. I was hoping it would provide some of the answers I was looking for, and found much more than I expected. I was not surprised to discover that this book was a National Book Award finalist for which Lopez also received the John Burroughs and Christopher medals. A 25^th Anniversary Edition was printed in 2004 by Scribner.

Although Lopez does discuss scientific studies of wolves (performed prior to 1978), he weaves them together beautifully with his own encounters in the Arctic, observations by other naturalists over the past several hundred years, and the historical and cultural insights of the Eskimo people and North American Indians. It was primarily though the intimate relationships he developed with these people that he gained most of his knowledge of wolves.

To most Westerners, wolves are shrouded in myth and mystery, and elicit a vast range of emotions including awe, fear, loathing, and love. Certain Eskimo and Indian tribes, on the other hand, live very close to the land, and tend to model their hunting skills after careful, painstaking observations of the way wolves hunt. As their lives depend on capturing the same prey as wolves do, these people have developed an extraordinarily fine sense of very subtle cues that would completely escape others – something that Lopez experienced first hand. The Eskimo and North American Indian people tend to regard wolves as sacred beings with souls, distinct from domestic dogs, which to them are largely utilitarian.

Wolves exhibit amazingly complex, sometimes unfathomable methods of interaction with their prey and with one another. As Lopez so beautifully explains in his Introduction, “To be rigorous about wolves—you might as well expect rigor of clouds.”

He asked that I post his response verbatim:

Dear Ms. Gordon:

What I learned from my correspondence with Dr. Christakis and a review of some of his vast trove of publications was that what had originally motivated him to study how feelings/perceptions spread through social networks was his work with terminally ill patients, which served as his initiation into clinical medicine. Through his interactions with these patients and their families, he understandably became concerned with the feelings of the family members and how it affected them and their social networks in turn.

I was surprised that as a Sociologist, Dr. Christakis would have been taken aback at the overwhelming attention received by his obesity study. Surely he must have been aware of the hair trigger emotions surrounding obesity in our society. It then occurred to me that perhaps, due to his initiation by fire into what must be one of the most difficult fields a physician can choose (end-of-life care), his attempt to approach the spreading of emotions through social networks through mathematics and statistics took him a step back from what must have been a very potent emotional experience. I felt that there was a certain detachment in thequantitative work involved in these analyses.
When I posited this to him, he explained:

Dr. Christakis is not primarily studying the "obesity epidemic" but rather how social networks work.

After watching this interview and looking over Dr. Christakis' website, I composed this email to him:

Dear Dr. Christakis,

When your paper came out in NEJM in 2007, I was participating in a weight loss program at St. Luke's (NYORC). I remember our group leader, Rich Weil, presenting your findings to us. From what I recall, he seemed to have no opinion on it one way or another, but I don't really remember.

I participated in the group for 2.5 years, and left it this past summer in disgust. I had lost about 12 lbs during the first year, and gained it back over the course of that time. I started and ended at around 225 lbs. I'm a 5'5" 45 year old female. I have repeatedly, over the course of my life, even as a little girl, tried to lose weight. I was maybe 10-20% overweight as a child and young adult, but once I hit my early 30s, I hit 200 lbs. for the first time. After reaching 225 for the first time, I joined Overeaters Anonymous and became "abstinent" (from all refined sugar, flour and wheat), and lost 60 lbs. I maintained my abstinence but still gained back about 10 lbs before falling off the wagon 5 years later and returning to 225. I repeated this same cycle, fell off the wagon again after 5 years, and again went up to 225. It was at this point that I said - ENOUGH.

I have a Ph.D. in Developmental and Molecular Biology from Einstein (2001), so I try to follow the basic science literature on obesity. I'm also very interested in sociology and the impact of scientific communications on society - something which attracted me to your research.

I just viewed, online, the 3 minute interview with you about your paper, and I must admit that your reported findings don't sit well with me at all. I have always battled my weight but felt that I have always been surrounded by (and shamed by) thinner people. I would classify myself as middle class, from a middle class background. My mother was never obese - in fact, there was not one obese person on her side of the family, going back 3 generations. My Dad was overweight and his brother was obese for most of his adult life. I have one sister, 3 years younger than I (we share both parents and are not stepsisters), who has never had a weight problem. Most of my classmates, fellow students and colleagues throughout my life were thin.

I think the social pressure is very much the opposite of obese people influencing those closest to them to be obese - I think its very much the other way around. And this pressure does nothing except force obese people to try everything and anything to maintain completely unsustainable weight loss. Your reported findings vilify obese people, by implying that it is desirable to shun them to maintain ones health. Obese individuals in western society already carry a huge social burden of great shame. I don't appreciate the implications of your findings one bit.

From a brief review of your website, I understand that you make heavy use of mathematical models to support your conclusions. The current state of the economy should be much more than enough to demonstrate to you that the maxim "lies, damn lies, and statistics" has never been so relevant. You're a sociologist - get out of your lab, your ivory tower, and talk to people on the ground, for G-d's sake.

It will be interesting to see if Dr. Christakis responds to my email and what he has to say. If I do get a response, I will report the gist of it.

We are living at a truly monumental moment in history, as we stand on the brink of what will probably be one of the most important presidential elections in all of United States history. The air is absolutely crackling with the anticipation of the election of the first African American President of the United States of America.

If Barack Obama does indeed win the election, as he is expected to do based on numerous national polls, it will energize the majority of the people in this nation with the feeling that the most tenuous and lofty of our dreams can become a reality. Back in 1955, when Rosa Parks performed one of the most famous acts of civil disobedience in United States History, who would have guessed that African Americans, who were slaves in this country just over a century ago, could reach the heights of acceptance and affirmation that we are witnessing at this moment?

For me, this aspect of the election eclipses so many of the issues that will no doubt come into stark relief once the honeymoon is over. John McCain is a great man and a true American hero, but with the economy so bad, any incumbent would hardly stand a chance. Despite McCain’s status, he can not possibly eclipse what Barack Obama stands for. In troubled economic times, Obama offers the sheer energy of dreams come true. The citizens of this country need this feeling, desperately. In this aspect, it resembles the hope that Franklin Delano Roosevelt offered the American people during the depths of the Great Depression.

Undoubtedly, there are Americans who still harbor racial prejudice, and will view the election of Barack Obama as a tragedy. I can only hope that they, or their children, will be able to overcome this prejudice once they see what Barack Obama can do for them and their country.

I am an obese, white, Jewish woman who is a member of not one, nor two, but three maligned social constituencies. I support Barack Obama’s candidacy for many reasons, not just those I mentioned above. If he wins, I will be overwhelmingly elated. There is a poem which first aired on NPR’s All Things Considered on October 28, 2008, that best sums up these feelings:

"Rosa sat so Martin could walk.

Martin walked, so Obama could run.

Obama is running so our children can fly."

These sentiments, which represent the struggle and ultimate triumph of the black community in the United States, truly mirror life’s struggles, and in that sense, speak to all humanity.

In a ground-breaking study entitled “Variants of the Adiponectin (ADIPOQ) and Adiponectin Receptor 1 (ADIPOR1) Genes and Colon Cancer Risk” (JAMA. 2008 Oct 1;300(13):1523-31), Virginia G. Kaklamani et al found a statistically significant correlation of a SNP in the ADIPOQ gene with incidence of colon cancer in a large cohort of subjects with Ashkenazi Jewish ancestry. This work is ground-breaking because it is the first published study to establish a real statistical correlation of a SNP based variant of the adiponectin gene with the incidence of colon cancer, after many circumstantial, indirect observations. Ironically, the SNP in the ADIPOQ gene was negatively correlated with colon cancer risk. In other words, individuals with the SNP containing GG or GC (found in 48% of all study participants) at the variant site were 27% less likely to develop colon cancer than those with the more common CC genotype. It is very important to remember, however, that as the authors caution, these results must be confirmed with further studies.

Adiponectin is an adipokine, or a hormone secreted by adipose tissue, that facilitates insulin sensitivity. Paradoxically, as adipose tissue mass increases, adiponectin levels decrease, and this is correlated with insulin resistance. Insulin resistance is correlated with elevated levels of other proteins, such as C-peptide and insulin-like growth factor binding protein-1 (IGFBP1) that is linked to increased risk of colon cancer. The results of this study suggest that there may be some identifiable genetic and biochemical connections between obesity, diabetes, and colon cancer.

]]> http://www.talkingscience.org/2008/10/here-a-snp-there-a-snp/feed/ 2 http://www.talkingscience.org/2008/09/this-time-its-physiological/ http://www.talkingscience.org/2008/09/this-time-its-physiological/#comments Thu, 25 Sep 2008 21:28:28 +0000 Miriam Gordon http://talkingscience.org/blogs/?p=232 According to the diagnostic test in the ground-breaking book The Highly Sensitive Person by Elaine Aron, Ph.D., I am a "Highly Sensitive Person" (HSP). In her book, Dr. Aron, a pioneering psychologist, cites major studies demonstrating that approximately 15-20% of the human population possess a nervous system that, due to genetically inherited physiological characteristics, cause them to experience greatly heightened sensitivity to stress in any environment they find themselves in. This inherited trait of heightened arousal is demonstrated also in similar proportions (15-20%) in several other mammalian species. In other words, highly sensitive individuals are much more easily aroused by subtle cues in their environment, which many people are less likely to pick up on.

I am currently reading a book based on Dr. Aron’s book entitled Making Work Work for the Highly Sensitive Person, by Barrie Jaeger, Ph.D. Dr. Jaeger explains that, in light of the characteristics explained above, finding the right work situation, which is very difficult for most people, is even more difficult for HSPs. Because of our sensitivity, we are affected emotionally, even to the point of somatizing negative emotions so that we become physically ill, in a situation where we sense that something is not in line with our ideals and values. The chapter that I am reading in Dr. Jaeger’s book now is entitled “Time Out For Healing”. Unfortunately, HSPs are affected so deeply by difficult past work and life situations that we need more time to heal than most people. It is not easy to be this type of person in this ultra-fast paced western society. In response to the prevailing work environment in our society, highly sensitive people will often put up a brave front and try to suppress these feelings.

In light of what I have just told you, and in keeping with the theme of this blog, I am thrilled to report that I have found a great parallelaphor. I have coined this term to describe parallels and/or metaphors between natural phenomena and events that occur in our everyday lives.

Here’s the parallelaphor: I have 2 pet cockatiels that I love dearly. In the wild, these birds are usually lunch for birds of prey, and depend on their flock for security. Having taken care of my birdies through various illnesses for over 5 years, I have learned that their instinct is to hide their illness, which makes taking care of them particularly challenging. In their natural habitat, this behavioral mechanism helps them avoid being ostracized and left behind by the flock, thus leaving them vulnerable to birds of prey. This is often how I feel, and how I’m sure many of my fellow HSPs feel, much of the time.

There is a quote by Henry David Thoreau on the cover of this little notebook I’m currently jotting down my thoughts in: “In wilderness is the preservation of the world.” I haven’t found any sources confirming that the author of Walden Pond was an HSP, but I suspect that he was, because like many HSPs, he found such deep comfort in the solitude of nature.

Just a final note: I happen to love buying fancy little notebooks, as much as I love nature and conservation. The notebook I just mentioned is composed entirely of recycled paper, and is put out by a little company called “ecojot™” (no, I am not getting a commission from them, unfortunately). If these things appeal to you, I would encourage you to take a look at their site.

Find your peace.

We all know that in this life, there is a price to pay for everything. Supposedly, the metformin I’m taking is helping to lower my blood sugar. So either I get diabetes or I get diarrhea, or I attempt to deprive myself to the point where I am physiologically compelled to binge. This “most appropriate” punishment for those who “dare” to be obese applies also to those taking Xenical, or its over the counter version, Alli. If you eat food with excessive fat content while taking these drugs, you will either be sitting on the toilet all day or forced to wear a diaper. So either deprive yourself of the food your brain is screaming at you for, or suffer those consequences. Either way, we are punished for doing what feels natural for us.

Another version of punishment reserved for the fatties amongst us, compliments of the medical establishment, is weight loss surgery. Having your stomach stapled or a lap band put around your stomach internally to restrict the amount of food you can ingest is tantamount to punishing yourself for eating too much. Do you know how violently ill you become if you try to eat more than a few spoonfuls of food after you’ve had this surgery? Bad, bad fattie!! You deserve to be punished for your gluttony and sloth!

The same woman who prescribed the metformin for me gave me a scientific paper to read, by a prominent childhood obesity expert, who questions whether the obesity “epidemic” is based on gluttony and sloth! His take is that children are not at all in control of their nutritional environment, so they are innocent of these cardinal sins. However, what is he saying about the adults? I wonder if the woman who prescribed the metformin for me and gave me this article to read is attempting on a subconscious level to tell me that I am gluttonous and slothful.

If one searches PubMed for articles with the word “obesity” in the title and “gluttony” in the Title or Abstract, 12 papers come up! This proves that there is as much anti-obesity bias amongst the most prominent academic obesity researchers as there is in the general public. Most of these articles attempt to convey that the popular view of fat people as gluttonous and slothful is wrong, and that scientific progress is providing more and more evidence to combat this hideous notion. However, I believe they need to use these words because they are trying very hard to convince themselves of this. After all, from the moment they were born, they were immersed in the same western culture which has held absolute contempt for fat individuals, and it is therefore an intractable part of their consciousness.

There is no need to include incite-ful (no pun intended) words, such as gluttony and sloth, in any publication written to present scientific data in an objective manner. These words are included in scientific publications in order to attract the attention of those (read: everyone in western society, including fat people) who have a strong, unfavorable gut reaction (again, no pun intended) to fat people and obesity.

My initial reaction to Matthew Brown’s blog entry about the work of Dr. Gray’s lab brought to mind the recent imbroglio that got James Watson booted from his post as the Chancellor of Cold Spring Harbor laboratory in response to comments he made about the genetic basis of intelligence in black people (see the recent New York Times article by Cornelia Dean). Anything that biological scientists, particularly those who are prominent and high profile, say about the biological basis of intelligence is incendiary in the extreme because of the inevitable and very unfortunate consequences for many, many people. The real danger in the scientist’s statements lies in the subjective interpretation of these ideas by idiots (for example, the principal of my high school) who have enough power over people’s lives to determine their future. This, in turn, highlights the essential nature of communicating science to laypersons in a way that is accurate, understandable, and sensitive. The more successfully science journalists are able to do this, the less abuse will result, and the more positive impact they can have on society. This is something that I am striving to work for in addressing the science of obesity.

As with all scientific studies, the key to really taking away the true message conveyed by the data is an understanding of the quality and reproducibility of the data and the experimental designs, the limitations on the conclusions that can be drawn based on the experimental methodology used, and how the new data fit into the existing literature. Unfortunately, only trained scientists, or those who have written about science for many years, can handle the information on this level. This ability is narrowed down even further by their respective specialties. It is very easy for someone with ulterior motives to manipulate the results of a scientific study or series of studies to suit his/her own purposes (in one of the most extreme and vile cases, read Hitler and the Eugenics movement). So how to solve this problem? I believe that the ideal combination of science and journalism would include an explanation of the scientific method with the reporting of any scientific study. Somehow, the public needs to be educated, through engaging and easily readable material, that one study does not make anything fact. They must understand that science progresses only through constantly challenging existing theories based on a growing body of high quality experimental evidence, and therefore, they must always leave room for further questioning.

Today, I got a lecture from Judith about my poor pancreas, which really cares that my blood glucose levels are too high, and therefore futilely keeps pumping out insulin to try and reduce it (high blood glucose levels are toxic to the body's cells). Alas, due to insulin resistance, the cells in my body (primarily in my liver, skeletal and cardiac muscle and adipose tissue) that routinely take up glucose in response to insulin are not responding to the insulin because THEY JUST CAN'T TAKE IT ANYMORE. They are saying to the increased levels of insulin that keep trying to bind to the receptors on my body's cells, "get lost, we're sick of you already!" (by decreasing or "downregulating" the number of insulin receptors on their surfaces). They've shut the door in the insulin's face. But my poor pancreas just can't hear what the liver and muscle cells are saying, and can't tell that they've rejected the insulin that it works so hard to make. So it keeps churning out insulin. Eventually, if I continue to ingest too much sugar, the cells in my pancreas that manufacture the insulin (called beta cells) will just get tired and wear out, like a treadmill that has been left on constantly for months. Then my pancreas will never make its own insulin again (I think - I have to look into this), and my blood glucose will shoot up to levels that will eventually kill my organs and me, unless I inject synthetic insulin (as do most people being treated for type 2 diabetes). According to my blood work, my insulin levels have always been in the normal range. However, this is not conclusive evidence that I am not insulin resistant.

My question is, is Judith an alarmist? If one is clinically defined as obese, does it necessarily mean that one is insulin resistant? If I maintain my weight (my BMI is roughly 36, I am not morbidly obese), do regular moderate exercise, watch what I eat and monitor my glucose levels by getting my blood tested every 6 months or so, will I necessarily become diabetic? I eat a lot of healthy foods - lean protein, fruits and vegetables, whole grains, but I also need my chocolate. Is this an attempt to scare me straight? How much is Judith's concern motivated by actual scientific evidence and how much is it motivated by cultural bias against obesity, which all of us carry around with us, just like unwanted extra pounds? Time will tell. I guess the clock is ticking for me.

In the 1995 film "The Basketball Diaries", Leonardo DiCaprio brilliantly portrays Jim Caroll's descent into heroin addiction. When I attempt to explain to people who do not suffer from obesity what complete, sudden withdrawal from refined carbohydrates is like, based on my own experience, I get a mental picture of what DiCaprio's Jim Carroll goes through as he suffers the torture of withdrawal from heroin. Although this is an extreme example, withdrawal resulting from completely eliminating refined carbohydrates or other binge foods from one’s diet is more than a matter of putting up with a migraine, insomnia, or general feelings of malaise, although all of these symptoms may result. Kay Sheppard, the author of "Food Addiction – The Body Knows", explains that the food addict is compelled, as if by knife point, to acquire and devour binge food, and that only complete abstinence from refined flour, sugar and wheat can arrest the addiction. It is Kay Sheppard’s food plan that helped me, twice, to lose 60 lbs. and keep most of it off for 5 years. I was able to do this only with the help of Overeaters Anonymous and the most wonderful sponsor I could ever have hoped for. Unfortunately, she became too ill to continue as my sponsor. I have since fallen off the wagon again, and have regained those 60 lbs. for a third time.

Long considered a joke in contemporary western society, the idea of biologically based addiction to refined carbohydrates and other "addictive" foods is finally gaining a foothold in high quality scientific data. Bartley Hoebel's group at the Princeton University Department of Psychology has published a series of papers detailing their experiments on sugar addiction using an animal model originally established for studying opiate addiction. Nicole M. Avena is the lead author on several studies that provide some of the most compelling evidence yet of the biological mechanisms of addiction to sweets, and their similarity to the biological basis of opiate addiction.

In a recent review article, Nicole Avena, Pedro Rada, and Bartley Hoebel (Avena NM, Rada P, Hoebel BG. Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev. 2008;32(1):20-39. Epub 2007 May 18.) explain why addiction to sugar shares the same basic neurochemical mechanisms that underlie opiate addiction. The first aspect of the theory is based on evolutionary mechanisms that motivated survival in an environment where food was scarce. Feelings of comfort in response to feeding were necessary to insure survival. The same brain mechanisms that are responsible for this feeling of comfort have been shown by many laboratories to underlie opiate addiction. They also cite circumstantial evidence from the testimony of many people that they are compelled to eat sugary foods in a way that is comparable to alcoholics who have overwhelming urges to drink. Also, with approximately 25-30% of United States citizens characterized as overweight or obese, along with the multi-million dollar diet and fitness industry, it is clear that many people put considerable effort into weight loss and yet fail to maintain the loss. Therefore, clearly, it is worth investigating the neurochemical mechanisms that are the basis of this seemingly addictive behavior.

Throughout this review article, terms that define addiction, including bingeing, withdrawal, craving and sensitization, are interwoven with scientific data from experiments with rats which have intermittent access to sugar solutions. When ingested, addictive drugs cause an increase in dopamine levels in an area of the brain called the nucleus accumbens. Hoebel's group has found that same phenomenon in rats. Other changes in the nucleus accumbens, including decreased enkephalin gene expression are also seen both with opioids and sugar. And, as with other opiates and psychostimulants, withdrawal symptoms are observed when the rats are deprived of sugar. Another important series of observations show that as with addictive drugs, after becoming accustomed to having regular intermittent access to sugar each day and then being deprived of the sugar solution, the rats exhibit classic signs of withdrawal, including anxiety, depression, craving, and even "cross-sensitization" to other substances of abuse (substituting another addictive substance in the absence of the drug of choice).

After presenting and analyzing all the available data, Dr. Hoebel’s group concludes that in a rat model which has proven relevance to human addiction, intermittent access to a sugar solution followed by periodic deprivation results in most of the same molecular and behavioral changes associated with rats that become addicted to other drugs of abuse. What this group is proving on a neurochemical and behavioral level would not surprise many of us who have instinctively known "food addiction" for years.

In the spirit of raising awareness of the ethical challenges inherent in today's most advanced medical technologies, the IHEU-Appignani Center for Bioethics and Bioethics International recently sponsored a one-day conference in New York City entitled "New Dilemmas in Medicine". Three panels of distinguished experts, in turn, addressed three pressing issues: Professor Julian Savulescu's theory of "Procreative Beneficence" (Journal of Medical Ethics 2007;33:284-288; doi:10.1136/jme.2006.018184), ethical considerations in pharmaceutical R&D, and "conscientious objection" by medical professionals to performing medical procedures, such as abortions, to patients who want them.

Each of these 3 topics could easily take up their own multiple day conference, and then some. The first thing I found myself having to do, in order to assimilate educated opinions on each subject, is to struggle to overcome my own personal opinions and biases, which was not easy. All of these topics are highly emotionally charged, and bound to be approached therefore in the most subjective manner by each individual who contemplates them. Having said this, I will do my best to impart to you what I got out of each panel discussion, with as much objectivity as possible. This post will address the first of the 3 panels.

Panel #1: To Have the Best Child Possible: The Coming Age of "Procreative Beneficence"?

The idea of "Procreative Beneficence" was jelled into a unified concept by Professor Julian Savulescu of Oxford University (Uehiro Chair in Practical Ethics, and Director of the Oxford Uehiro Centre for Practical Ethics), and basically states that having the choice to screen human fetuses for various genetic characteristics, select embryos with desirable traits and discard those with undesirable traits is a positive thing, or eugenics by choice, if you will. (Click here for a "down to earth" discussion of Professor Savulescu's ideas). The idea is to give parents the chance to improve the quality of their children’s lives by allowing them to be born as attractive and intelligent as possible, without the burden of physical or mental deficiencies, using the latest reproductive technologies.

The first brave panel expert to express her opinion of "procreative beneficence" was Jennifer Kimball, Executive Director of the Culture of Life Foundation, a non-profit policy organization dedicated to education regarding Christian pro-life views on bioethics. Ms. Kimball characterized Savulescu’s theory as procreative "maleficence", in that it devalues the inherent "natural, authentic, and noble" desire of humans not to create human life, but rather to procreate. Married couples who procreate in effect "consent to an initiative that precedes them". They are aware that through their sexual union they have consented to the possibility that their union will result in the birth of a child, who like the parents have innate nobility that the parents naturally respect by taking responsibility for raising the child. In Kimball's opinion, procreative beneficence is a contradiction in terms, i.e. artificial reproductive technologies force a life that was not naturally conceived into being solely to satisfy the will of those who want the child. Kimball points out correctly that artificial reproductive technology is an industry, and that those who use the technology are in effect customers who are shopping for something they want. This is something that, in Kimball's eyes, is tantamount to "autonomous hedonism". Kimball and those who are like-minded see this as negative, and in regard to the commercial aspect of the industry I can see her point. I couldn’t help thinking, as I listened to her, that she is only looking at the negative aspects. What about all of those parents who abuse their naturally conceived children, or who otherwise just don’t want them? How much suffering does that cause, and how could that possibly be more against the inherent nobility of humanity? Unfortunately I didn’t get to ask her this. Also, what could be wrong with parents who desperately want to have their own genetic offspring? In these sorts of cases, the parents may have many reasons to go through with assisted reproductive procedures apart from their natural desire to procreate, although because it is such an emotionally charged issue, it can be impossible to tease out their true motivation(s). It is this fundamental motivation that Kimball and her colleagues are concerned with.

The next panelist was Dr. Arthur Cooper, Professor of Pediatric Surgery, Columbia University College of Physicians and Surgeons, and Director of Pediatric Surgical Services at Harlem Hospital in New York City. Dr. Cooper approaches the topic of procreative beneficence from the perspective of a physician upon whom parents and families depend for treatment of a child born with various physical problems. In his view, there are many considerations, and the role of a physician is to educate his patients about all the options available to them, not to choose for them. Dr. Cooper teaches his residents that surgeons are not G-d, and at best they can aspire to be "G-d’s hands". In effect, Dr. Cooper was saying that there are just no easy answers to the question of procreative beneficence, but that physicians should take part in the debate and become as educated as possible, in order to provide the best possible service to their patients.

Dr. Eva Feder Kittay, Professor of Philosophy at SUNY Stonybrook, in New York, cited various psychological theories regarding the issue of the "choice" aspect of procreative beneficence. Dr. Kittay is mother to 2 daughters, both now adults, and one of whom is disabled. She describes the experience of raising a child with disabilities in the context of an article written by Emily Pearl Kingsley in 1987 called "Welcome to Holland". Ms. Kingsley is a mother of a child with Down's syndrome, and in her article she describes the experience of giving birth to this child as having taken a plane to Italy but instead arriving in Holland. The process of coming to terms with the birth and the raising of this child is akin to accepting that you’ve arrived in Holland and are making the best of it. In time, you realize that you're not in a bad place, but instead in a place with its own unique charms, and you adjust. Dr. Kittay's basic message was that often, what we think we desire turns out to be very different from the reality. We need to realize that even with all the choices that are offered now in reproductive technology, we actually have far less control over the outcome than we think, and that coming to terms with this can facilitate adaptation to the realistic outcome, whatever that may be. The best we can hope for is guidance.

Dr. Barbara Katz Rothman, a Professor of Sociology at CUNY, observed that sociology doesn't really seem to make any impression on bioethics. In studies of social structure, the zip code of the family is the primary predictor of producing happy children. This emphasis on the financial bottom line is far more prevalent in American society than in the Netherlands, for example. Dr. Rothman was once asked by the Dutch government to attend a presentation given by sales reps of a biotech company trying to aggressively market serum testing for markers of various birth defects. The Dutch government made clear that they were not in favor of eugenics and would not base their decision on an economic bottom line. The biotech reps simply could not understand why the Dutch government wouldn’t want to save money by preventing the birth of children with defects that were enormously expensive to treat. When Dr. Rothman interviewed Dutch midwives about testing for birth defects during pregnancy, the midwives felt that the testing would "spoil the pregnancy", or take away the joy of being pregnant by introducing additional worry into the whole process. In other words, there is a "slippery slope of value judgments for increasingly shaky scientific decisions". The family is the context in which quality and reality of life is defined. Such things as "family balancing" by sex selection of fetuses seems extremely immoral in this context. Quality of life is proportional to the level of sanity in the family. The language of procreative beneficence, with its emphasis on too much choice, actually silences the individual by blurring this reality.

The last panel member to address the idea of procreative beneficence was Professor Udo Schuklenk, Professor of Philosophy at Queen's University in Canada. He is also the founding editor of the Developing World Bioethics Journal. Professor Schuklenk agrees with Savulescu up to a point, in that his theory lives in a pro-choice environment. The harsh reality of life is that no matter how much an individual is loved by his/her family, the cold cruel world will still discriminate against those with physical and mental disabilities, and these individuals will have a decreased quality of life. Therefore the choice to abort fetuses with such disabilities is something that should be permitted. However, when it comes to non-disease traits, such as intelligence or homosexuality, the distinction becomes less clear. Intelligence is not a guarantee of a good quality of life; if you look at the lives of many famous authors, artists, and inventors, they were absolutely miserable. Take Van Gogh, for example, or any graduate student, for that matter. A homosexual person will most likely have decreased quality of life, but if certain individuals choose to abort a fetus that is determined to be a future homosexual, life for those who survive will be even more difficult.

In summary, these experts eloquently their expressed their position on the spectrum of moraland ethical issues surrounding the debate on procreative beneficence. The only real fair outcome of this discussion is that the more people know about these issues, preferably before they are expecting a child, the better decision they will be able to make. The more informed the decision, the easier it will be to sort out realistic expectations from the illusion of what life could be like for the family after their child is born.

Seismic testing off of the world's coastlines, conducted to find new sources of oil, creates underwater noise levels similar to that of military SONAR (approximately 230 – 260 decibels) and causes serious harm to aquatic mammals that rely on highly sensitive echolocation. To a whale or dolphin, these sound waves are comparable to what we would hear if an ambulance siren was right up against our ear. These sounds are extremely painful to them, and can cause disorientation, interruption of normal behavior such as feeding or mating, and brain hemorrhaging. You can read much more about the science behind how whales and dolphins are affected by sonar and seismic testing in Greenpeace’s special report.

A recent editorial in the New York Times (“Of Whales and National Security”) outlined the policy considerations posed by these very serious dilemmas, which are now being debated in the nation’s highest court. Greenpeace, the Natural Resources Defense Council (http://www.savebiogems.org), and other environmental and wildlife organizations have all mounted rigorous legal campaigns against unregulated seismic testing, as well as the Navy’s efforts to conduct military drills with mid-range SONAR off our nation’s coastlines (http://www.nrdcactionfund.org/campaigns/oceans/save-marine-life-from-deadly-sonar.html).

In response to the rude awakening I experienced when I opened that email from Greenpeace, I searched the ExxonMobil website for a public relations contact phone number, to no avail. The only way I was able to contact them was by sending an email through an online form (no email addresses were provided, let alone names of contact people). This is what I wrote to them:

“This is a plea. I just saw a very heartening commercial on TV that espoused Exxon's commitment to developing new technologies that will reduce global warming. I then opened an email from Greenpeace showing a dead beached whale, with news of a pod of rare melon-head whales that beached themselves due to seismic testing conducted by Exxon off the coast of Madagascar. I was absolutely devastated by this.

I searched the ExxonMobil website for a public relations contact phone number, to no avail, which is why I'm settling for emailing you. All I ask is that you keep the promise you stated in your commercial, to protect the environment to the best of your ability. I am aware that by addressing issues of climate change, you are faced with your greatest and most difficult challenges ever. However, I know you have the resources to accomplish your goals. Please, spare the suffering of innocent creatures and the impact on our children's future by committing yourselves to the much more difficult task of developing alternative, safe fuel sources, rather than drill for oil at any cost. Thank you so much.”

I never got a reply from them. I can only hope that someone at the company was listening.

Scientists like Harvard Medical School's Bruce Spiegelman would like to figure out a way to help us do just that! Spiegelman, who studies mammalian embryonic fat cell development, is conducting research to understand the adipogenic (i.e. how adipose, or fat cells arise) lineage. One key question that Dr. Spiegelman and his group seek to address is how white and brown fat cell fates are determined.

To answer this question, Dr. Spiegelman's group performed a screen for molecular regulators including transcription factors that may be unique to either brown or white fat cells. The researchers identified a transcriptional co-regulator called PRDM16, which is expressed exclusively in brown fat cells. When the investigators studied the effect of increasing PRDM16 expression in white fat cell precursors in culture, they observed that the overall gene expression profile was distinctly that of brown fat cells. Then, they made transgenic mice that selectively overexpressed PRDM16 in white fat cells, and found that pockets of brown fat cells grew in the white fat cell depots. Similar results are obtained when mice are exposed to low temperatures for extended periods of time, or by prolonged exposure to b-adrenergic stimulation. Together, these results suggest that PRDM16 is an excellent candidate for a master molecular switch that can convert white fat cells into brown fat cells. However, since "suggestion" is not proof, the researchers performed additional experiments to investigate this.

To their surprise, the scientists found that when PRDM16 expression is inhibited in primary brown fat cells in culture, they differentiated not into white fat cells, but into myotubes, or skeletal muscle cells! This result suggested that brown and white fat cells did not come from one common progenitor cell type. Instead, they may in fact be two entirely separate lineages. Additional experiments provided strong evidence for this.

So where do these results leave Bruce Spiegelman and his group? The data showing that white fat cells can become brown fat cells by overexpression of PRDM16 still hold promise for therapy. Spiegelman aspires to make this type of therapy a reality, by employing a transplant model. White fat cells, which are easily obtained by liposuction, can be engineered to express PRDM16, and transplanted back into the original fat cell donor. These experiments are currently being performed in mice.

Important questions remain. For example, how many cells would be needed for the procedure to succeed, and how the body would respond to the engineered cells? Could these engineered "brown" fat cells lead to positive results by reducing obesity and restoring energy balance, or could there be negative effects? Bruce Spiegelman as well as many people suffering from obesity are sincerely hoping for the former.

This entry is based on a talk given by Dr. Spiegelman on Thursday, May 15, 2008 at the New York Academy of Sciences. Dr. Spiegelman was a featured speaker at the NYAS Conference on Integrative Physiology.