HMP: Reductionist verses Holistic Thinking in Medicine

Dear Friends,

The announcement by the National Institute of Health (NIH) that the NIH Human Microbiome Project (HMP) provides “opportunities to improve human health through monitoring or manipulation of the human microbiome” is a major step forward, merging the holistic approach for building health with mainstream medicine. The HMP requires mainstream
researchers to face the reality that the healthy functioning of the human body is not governed by human cells alone, but is dependent upon a healthy amalgamation of human cells and bacterial cells, collectively expressing proteins, that together orchestrate the proper functioning of the human organism.

Modern, mainstream medical science has been dominated by reductionist thinking, which maintains that an understanding of the parts explains the functioning of the whole. This mode of thought has resulted in many of our medical advances today, but also has fostered the notion that Homo sapiens are separate from their environment. There is another way to look at life, the system’s approach—a holist model that views a human life as intimately connected to all that surrounds it. Reductionist thinking has allowed us to drill down deeply into things and system thinking allows us to connect the dots. Are we now witnessing the convergence of these two paradigms of thought?

The HMP is a five-year project that will be funded at a level of $150 million over that period. It is envisioned that, by the conclusion of the HMP, the project will have created the needed resources (data, technology, computational tools and preliminary analyses of the ethical, legal and social implications of the research) and will have documented enough examples of the microbiome’s importance to human health that support of microbiome research will become a priority in the human disease portfolio of many of the NIH institutes and Centers and of many other funding agencies. If the importance of considering the impact that changes in the normal microbiome can have on health and disease can be demonstrated, it will have the potential to transform medicine. (Authors: NIH HMP Working Group)

Thus far, in regards to the Human Microbiome Project, we have talked about the Jumpstart Phase. Initiated in 2007 with the selection of four large-scale sequencing centers supported by NIH— the Baylor College of Medicine, The Broad Institute, The J. Craig Venter Institute and the Washington University of Medicine—to complete the sequencing of 1000 organisms which will function as the Reference Genome, and to accomplish the metagenomic analysis of six microbiome sites of 250 normal individuals—the skin, the nasophyarynx, the oral cavity, the gastrointestinal tract, the genitouruinary tract and the blood. As of July 2009, roughly 375 bacteria are in draft sequencing pipelines or have been completed and deposited in GenBank, and ¾ of the 250 volunteers (approximately equal numbers of men and women) have been recruited and sampled with planning for collection of a second sampling within the year.

The Second Phase which began in the Spring of 2009, while the Jumpstart Phase continues towards completion, is the awarding of 150 millions dollars in grants to 15 research institutions across the country for Demonstration Projects.

The Demonstration Projects aim to tackle the most important question of the HMP: whether changes in the microbiome can be related to human health and disease. Because of the short time frame of the HMP, the primary goal of these projects is to establish a correlation between microbiome changes and health/disease rather than demonstrate causation. If a project can successfully demonstrate correlation early in the timeline, work to begin to establish causation may be undertaken.

The Fifteen investigator-initiated projects have been funded for an initial one-year pilot phase, during which each investigator will have the opportunity to demonstrate the feasibility of his/her project. At the end of the pilot phase, the subset of the projects that demonstrate the most promise, as judged by peer review, will be scaled up and continued for three additional years.

Here are some of the Demonstration Projects that HMP is supporting:

1. GI Disorders: James Versalovic, PI. (Baylor College of Medicine) “The Human Microbiome in Pediatric Abdominal Pain and Intestinal Inflammation.” This proposal will explore the nature of the human intestinal microbiome in healthy children and children with gastrointestinal disorders. The overall goal is to obtain a robust knowledge-base of the intestinal microbiome in a set of GI disorders that represent a broad spectrum of important disease phenotypes in pediatric gastroenterology. In addition to the detailed clinical assessment of healthy children and children with irritable bowel syndrome, constipation, and inflammatory bowel disease, multiple strategies will be deployed to navigate and understand the nature of the intestinal microbiome in childhood.

2. GI Disorders: Frederic Bushman, PI (University of Pennsylvania) “Diet, Genetic Factors and the Gut Microbiomes in Crohn’s Disease.” We propose to investigate the hypothesis that consistent changes in the human gut microbiome are associated with Crohn’s Disease. The bacteria present in the intestinal tract, probably play a role in the pathogenesis of Crohn’s Disease, but the mechanism remains unclear. In this study, we propose to determine the composition of the gut microbiome associated with Crohn’ Disease while controlling factors known to alter the gut microbiome, such as host genetics and diet. Ultimately, the discoveries from this project may allow physicians to manipulate microbes in the intestine in order to promote health and cure or prevent disease.

3. GI Tract: Claire Fraser-Liggett and Alan Shuldiner, (University Maryland Baltimore) PIs. “The Thrifty Microbiome: The Role of the Gut microbiome in Obesity in the Amish.” Obesity is a major health problem in the US. This project directly addresses the causes of obesity by testing the “Thrifty Microbiome Hypothesis,” which poses that gut microbiome plays a key role in human energy homeostasis. Previous studies have indicated that a difference in the gut microbiome can be found in obese and lean adults.

4. Skin: Martin Blaser, PI. (NYU School of Medicine) “Evaluation of the Cutaneous Microbiome in Psoriasis.” Psoriasis, a chronic disease involving the immune system, affecting more than 7.5 million people in the US. The goal of this study is to examine how changes in the normal cutaneous microbiome may contribute to the disease. The skin microbiome of 75 donors with and without psoriasis will be examined at several taxonomic levels. Additionally, the research will seek to examine whether the immunosuppressive agents used to treat psoriasis alter the microbiome.

5. Vagina: Jacques Ravel and Larry Forney, PIs. (University of Maryland Baltimore) “The Microbial Ecology of Bacterial Vaginosis: A high-Resolution Longitudinal Metagenomic Analysis.” BV is a common condition that is very difficult to control. This project will test the hypothesis that vaginal microbiome dynamics and activities are indicators of risk to BV. 200 women will be examined.

6. Cancer of the GI tract: Zhiheng Pei, PI. “Foregut Microbiome in Development of Esophageal Adenocarcinoma.” Esophageal adenocarcinoma (EA), the type of cancer linked to heartburn due to gastroesophageal reflux diseases (GERD), is the fastest rising malignancy in the US. Initial research by the PI’s laboratory has shown that patients carrying particular types of microbiome are more likely to have the early stages of EA than those that do not.

This past week I had the pleasure of interviewing Delphine Saulnier PhD, a member researcher in Dr. James Versalovic’s team at Baylor. Dr. Saulnier shared some very important insights with me resulting from her research that I am excited to share with you in future newsletters.

Trying to keep these emails in bite-sized portions for you.

Sincerely yours,

Seann Bardell

BioImmersion.com

Clinical Note:

Therapeutic Foods provide a new platform in medicine that is 1000s of years old. I love this little phrase because it encapsulates the Therapeutic Foods concept. I’ll explain: Here is the old part—Let food be your medicine. Lets medicine be your food (Hippocrates- 400BC) — and here’s the new—utilizing modern science to analyse, carefully select and produce real organic whole foods that function as medicine.

We look to nature, history and science with the biosphere providing us our food, history informing us of cuisines that heal and science providing the tools necessary to produce the quality attained in the Therapeutic Foods Line.

The Last Quiz Answer: The wild turkey was Benjamin Franklin’s choice for the United States’s national bird. The noble fowl was a favored food of Native Americans. Yet by the early 20th century, wild turkeys no longer roamed over much of their traditional range. They had been wiped out by hunting and the disappearance of their favored woodland habitat. Wild turkey reintroduction programs began in the 1940s, and the birds were relocated to areas where populations had been decimated but woodlands were recovering. Such efforts worked so well that wild turkeys now live in areas where they may not have occurred when Europeans first reached the Americas. Today, flocks are also found in Hawaii, Europe, and New Zealand.

It is useless to force the rhythms of life. The art of living is about learning how to give time to each and every thing. (Carlo Petrini, founder of Slow Food.) Founded in 1986 in Italy, Slow Food became an international non-profit organization in 1989 and is currently made up of nearly 1000 chapters whose vast network of 80,000 members is the greatest strength of the movement. Anyone can become a member. We are enslaved by speed and have all succumbed to the same insidious virus: Fast Life, which disrupts our habits, pervades the privacy of our homes and forces us to eat Fast Foods. Take the time to check this amazing movement out—click on this link to the Slow Food Compendum. It provides the foundation to right our world.