Friday, June 22, 2012

How About A Fecal Transplant?

Yes, you read correctly.  A fecal transplant.  "Fecal" as in "poop."  "Transplant" as in "from one person to another."

This new medical procedure makes the idea of using leeches, maggots, and flesh-nibbling fish seem appetizingly appealing by comparison.  I recently learned about it from a couple of New York Times science articles by Carl Zimmer and Gina Kolata, and it was so interesting I did some followup investigating of my own. The transplant is one promising development in the treatment of all kinds of health problems that has emerged from the field of medical ecology, a branch of microbiology which studies the complex interactions between health and a person's microbiota (or microbiome), the collection of 100 trillion microbes that live on and in each human body.

The two to five pounds of complex microbial communities that inhabit our bodies are apparently essential to not just our health but to our very existence.  Without them we would be unable to digest food, synthesize certain vitamins, and fight off many infectious diseases.  While it is certainly true that quite a few bacteria are harmful to us, many more are beneficial to the point that we can't live without them.  Our microbiome is as essential to us as our heart or our brain.

A microbiome is a true ecosystem in the sense that it involves a complex balance among the many different species of bacteria, viruses and fungi that comprise it.  In fact, one difficulty in studying these organisms has been that they are so adapted to living surrounded by other microbes and are so dependent on their host body that many can't be isolated and grown in the lab, and even if they do survive outside of the body they often behave differently than in their natural environment. However, a recent five-year federally funded research program has begun to give a clearer picture of our microbial communities and their impact on our health by using DNA analysis that doesn't require laboratory cultures. Called the Human Microbiome Project, the study involves 200 scientists at 80 institutions who have sequenced the genetic material of bacteria taken from nearly 250 healthy people, an immense effort that has led to some surprising findings.

For one thing, the researchers discovered more strains than they had ever imagined — as many as a thousand bacterial strains on each person. And each person’s collection of microbes was different from the next person’s, a kind of microbial fingerprint that uniquely identifies each individual.  Also surprising was that there were genetic signatures of disease-causing bacteria and viruses lurking in the microbiome of every one of these healthy individuals.  Instead of making people ill, or even infectious, the disease-causing microbes were simply living peacefully among their neighbors, held in check by the complex interactions of the microbiome community.

Another finding is that a person's microbiome changes throughout life in response to environmental and biological influences.  This process begins at birth, when certain key bacteria are transferred from mother to child during delivery and afterward during nursing. In pregnancy the relative concentrations of certain bacteria change in a women's birth canal in response to hormonal shifts.  One species of bacteria that is normally rare but becomes dominant is lactobacillus johnsonii. It is usually found in the gut, where it produces enzymes that digest milk. It’s an odd species to find proliferating in the vagina, to say the least. Dr. Aagaard-Tillery, one of the scientists who made this discovery, speculates that during delivery a baby will be coated by lactobacillus johnsonii and ingest some of it, an inoculation that prepares the infant to digest breast milk. The milk, it turns out, contains some 600 species of beneficial bacteria and also certain sugars that the baby can't digest but which nourish the bacteria. It seems the mother is not only feeding the child but also the child's bacteria and thereby promoting the development of the child's microbiome.

Our cultural attitude toward microbes is decidedly negative and non-selective:  "The only good microbe is a dead microbe."  However, the more we learn about the microbiome the clearer it becomes that this is not really justified and may be very harmful to us in the end.  For example, the use of broad-spectrum antibiotics to treat infections, while effective in the short run, wipes out not only the bad bacteria but also many of the the ones that are necessary to restore and maintain health.  We have generally assumed that the microbiome would return to normal on its own, but scientists are now realizing that assumption isn't justified -- it would be like assuming that lettuce and tomatoes would spontaneously return after spraying the whole garden with herbicide to kill the weeds.  In fact, there appear to be certain strains of harmful bacteria that thrive in disrupted or diminished microbiomes following broad-spectrum antibiotic treatments, like the antibiotic-resistant Clostridium difficile.  Re-establishing a healthy microbiome is very difficult in these circumstances.

Enter the fecal transplant.

According to Lita Proctor, program director for the Human Microbiome Project, "Half of your stool is not leftover food. It is microbial biomass.”  Assuming the donor is healthy, this means stool contains the complex collection of microbes needed to restart a depleted microbiome in another person.  And it seems to work.  Initial studies using fecal suppositories to treat Clostridium difficile infections have been very promising, and larger clinical trials are underway.  Fecal transplants are also being studied as a way to treat obesity by transplanting fecal samples from lean donors to obese patients. Researchers at the Academic Medical Center in Amsterdam are running a clinical trial to see if fecal transplants can help treat obesity. They have recruited 45 obese men; some are getting transplants from their own stool, while others get transplants from lean donors. The scientists are finding that the transplants from lean donors are changing how the obese subjects metabolize sugar.

Efforts are also underway to isolate the bacteria from the poop, to remove the "ick" factor, as researcher Dr. Alexander Khoruts puts it.  He would eventually like to develop probiotic pills that contain just a few key species required to build the intestinal ecosystem  -- Poop Pills, so to speak.

I certainly learned a lot from researching this topic, and the information has changed my outlook about who and what I am. For one thing, I realize how wrong my belief is that I am separate and independent from my environment.  "I" am composed of trillions of other organisms without which I could not exist.  They are as much "me" as any other part of my body.  As Dr. Barnett Kramer of the National Cancer Institute has said,  "humans in some sense are made mostly of microbes. From the standpoint of our microbiome, we may just serve as packaging.”

Certainly a humbling thought.





Friday, June 8, 2012

Disney Dreams

Walt Disney opened his California theme park in 1955 with these words: "To all who come to this happy place, welcome."

"This happy place" quickly morphed into the slogan of the park that persists to this day -- "The Happiest Place on Earth."  The recognizability of the phase as referring to Disneyland and now to other Disney parks certainly attests to its success as a marketing logo, but also to the fact that several generations of visitors have agreed with the sentiment it expresses.

Although Walt clearly wanted to make people happy, there was quite a bit more to it than that.  At the 1955 opening ceremony he went on to say,
 "Disneyland is your land. Here age relives fond memories of the past...and here youth may savor the challenge and promise of the future. Disneyland is dedicated to the ideals, the dreams and the hard facts that have created America...with the hope that it will be a source of joy and inspiration to all the world."
His own dream was embodied in his plans for Disney World in Florida,  a project that went way beyond anything he had accomplished at Disneyland.  As I mentioned in my last blog, Disney World was opened in 1971 but sadly Disney died of lung cancer before it was completed. The official motto of WDW became "Where Dreams Come True," perhaps a reference not only to the dreams of visitors but also to Walt's own. At the grand opening Walt's brother Roy alluded to this:
"Walt Disney World is a tribute to the philosophy and life of Walter Elias Disney ... and to the talents, the dedication, and the loyalty of the entire Disney organization that made Walt Disney's dream come true. May Walt Disney World bring joy and inspiration and new knowledge to all who come to this happy place ... a Magic Kingdom where the young at heart of all ages can laugh and play and learn ... together."
And Julie Andrews, host of the televised ceremonies, made the connection very clear, referring to the park as "...a joyful land built by an inspired dreamer for other dreamers and dreams still to come."

It is hard to find fault with these sentiments.  They seem particularly uplifting in this time of economic, political, and social malaise.  After the deaths of Walt and Roy, it fell to the corporate structure they created to carry on the ideals they had espoused in these dedication speeches. For the most part I think the Disney brothers would approve of the changes in the parks and the numerous other new projects and developments that have taken place in their name over the years.

The many times I have visited the parks (almost always WDW) I have enjoyed myself thoroughly.  However, my last stay at WDW produced some nagging qualms that I have been struggling to deal with.  In my last blog I explored one of them, the presence of thousands of school-age children before the end of the school year who did not seem to be there to "...savor the challenge and promise of the future" nor to appreciate "new knowledge."  But they were certainly managing to "...laugh and play"  (well, when they weren't on their cell phones).

Another qualm has to do with the message that seems to underlie the current use of the slogans mentioned above.  It was about five years since I was at WDW, and I'm not sure whether it is me who has changed or whether it is the way the taglines are being used, but during my most recent visit I began to detect a shallowness to the constant emphasis on dreams, wishes, memories and magic -- a shallowness that certainly doesn't do justice to Walt and Roy.  The message, delivered in performances and attractions that were invariably entertaining and thoroughly effective at evoking warm and fuzzy visceral emotional responses, seemed to be that your dreams will always come true if you just wish with all your heart.  Just wish it and it will happen, no matter what you want.

This idea appeared in many venues and was especially evident in the spectacularly well-produced nightly fireworks show called, appropriately enough, Wishes. The show begins with some great fireworks and a few words from the Blue Fairy, who proclaims that when a star is born it has the power to grant a wish.  A song follows ending with the well-known refrain "When you wish upon a star, makes no difference who you are, anything your heart desires will come...to...you."  Jiminy Cricket then directly addresses those who might be skeptical:  "I'll bet a lot of you folks don’t believe that, about a wish coming true, do ya? We'll I didn’t either. Course, I’m just a cricket, but lemme tell you what made me change my mind. You see, the most fantastic, magical things can happen, and it all starts with a wish!"  The evidence is then presented in the form of the wishes-come-true of Tinkerbell, Cinderella, Snow White, Ariel, Peter Pan, Pinocchio, and Aladdin.  Jiminy concludes "You see, its just like I told ya. Wishes can come true, if you believe in them with all your heart."

Well, ok.  But I wonder if a more beneficial lesson might not be drawn from Disney's own life.  His dreams didn't come true just because he wished them to but rather because he worked hard, took great risks, and sacrificed much to overcome many difficulties and obstacles.  He was frequently on the brink of financial disaster;  his creative ideas and plans were often met with skepticism and derision;  a number of his projects were failures, or were abandoned before they were started.  Despite these challenges he persevered when many of us would have given up.  Wishing and dreaming were necessary to his success, but hardly sufficient. 

In my view that's the true legacy of Disney.