News Release

NIH answers PARA's call for action on Paratuberculosis and Crohn's disease!

World's foremost research minds target Crohn's disease.

In the Summer of 1998, The Paratuberculosis Awareness and Research Association issued a plea to the United States Government to investigate the relationship between the cattle pathogen, Mycobacterium avium subspecies paratuberculosis(MAP), and the devastating human condition known as Crohn's disease. In December 1998, The U.S. National Institutes of Health answered that plea, and organized what will likely be recorded as a watershed in the research of Crohn's disease.

The National Institute of Allergy and Infectious Diseases(NIAID), in collaboration with the National Institute of Diabetes, Digestive and Kidney Diseases(NIDDK), issued an invitation to some of world's foremost scientific and medical researchers. The invitation was to attend a meeting whose subject was the relationship between MAP and Crohn's disease. PARA was also invited to the meeting, as were many agencies of the U.S. Government. Among the organizations represented were

• National Institute of Allergy and Infectious Diseases (NIAID)
  
  
• National Institute of Diabetes, Digestive and Kidney Diseases. (NIDDK)
  
  
• International Association for Paratuberculosis (IAP)
  
  
• Paratuberculosis Awareness and Research Association(PARA)
  
  
• United States House of Congress
  
  
• United States Department of Agriculture(USDA)
  
  
• United States Food and Drug Administration(FDA)
  
  
• United States Army Medical Corps
  
  
• United States Centers for Disease Control(CDC)
  
  
• The Institute of Genomic Research(TIGR)
  
  
• The Crohn's and Colitis Foundation of America(CCFA)
  
  

PARA's reaction

Ms. Karen Meyer, Founder and Executive Director of PARA, said "All in PARA wish to express our deepest gratitude to the National Institute of Allergy and Infectious Diseases for tackling this complex issue, which has a direct effect on the lives of millions of people both in this country and around the world. That an agency with a worldwide reputation for research excellence such as the National Institutes of Health would invest so much energy to deal with MAP and its relationship to Crohn's disease is a clear vindication of the position that PARA has held since its foundation:- That the questions about MAP and Crohn's disease must be both asked and answered, as a matter of great urgency."

Echoing these sentiments, Ms. Cheryl Miller, Assistant Executive Director of PARA added "Now that the National Institutes of Health have acted, it is time for other Government agencies to stop sitting on the fence. In particular, it is long past time for those agencies responsible for Food Safety to act decisively. They must conduct and fund research that guarantees to the consumer that both they and their families are not being infected with this dangerous bacterium through the cattle derived products on sale on our grocery store shelves."

Mr. Stephen Merkel, a member of PARA's Board of Directors, added "It is important to remember that the NIH meeting is but the first step on a long and arduous path. There is much work ahead of us yet. There are 1.5 million sufferers of Crohn's disease in this world, and there will be nearly 2.5 million by the year 2005. But the NIH meeting is an important milestone and it gives me great hope for the future. I am immensely grateful to all involved with the organization of this meeting."

Mr. Alan Kennedy, a co-founder of PARA and himself a sufferer of Crohn's disease, simply said "I'm overjoyed to finally see this day."

The First Supper?

The weekend of the NIH meeting was the first occasion when all board members of PARA met together in person. It was a time for much celebration, and for a coming together of minds as never before. But it was also an opportunity for much work, since the barriers of physical distance and telecommunication had been removed.

PARA was also delighted to host a meal on Sunday evening, when all researchers whose prime focus of research is MAP and Crohn's disease were invited to attend. PARA members present were Karen Meyer, Cheryl Miller, Steve Merkel and Alan Kennedy. Medical researchers who joined us were Prof. John Hermon-Taylor, Dr. Rod Chiodini, Dr. Michael Collins, Dr. William Chamberlin, Dr. Tim Bull and Dr. Fouade El-Zaatari. Dr. Saleh Naser did not arrive in Washington until that night.

All PARA travel, accomodation, dining and other expenses for the NIH meeting were met personally by the PARA board.

The Meeting

The NIH meeting took place in Bethesda, Maryland, on 14^th December 1998. The title of the meeting was "Crohn's disease - Is there a Microbial Etiology? Recommendations for a Research Agenda".

Dr. George Curlin, Director of the Division of Microbiology and Infectious Diseases, NIAID, and co-sponsor of the meeting, welcomed all present. He also thanked Dr. Frank Hamilton, Director of the NIDDK, for his co-sponsorship of the meeting.

Dr. Dennis Lang then invited Dr. Rodrick J. Chiodini, co-founder of the International Association for Paratuberculosis, to take active part in the meeting. Dr. Chiodini is a world acknowledged authority on MAP, and was the first researcher to isolate M. paratuberculosis from humans with Crohn's disease.

The meeting was opened by the chairman, Dr. Patrick J. Brennan, who remarked on the unique nature of the meeting, and the diversity of the groups gathered around the meeting table. Dr. Brennan requested each attendee to identify themselves and give a brief description of their connection to the subject, for record-keeping purposes.

Timetable of Speakers

The first speaker was Dr. Bayless, of the Crohn's and Colitis Foundation of America. The title of Dr. Bayless talk was "Crohn's disease as a clinicopathological entity", an explanatory lecture which was necessary since there were some present who were unaware of the nature of Crohn's disease. Dr. Bayless also took the opportunity to inform us why MAP could not be the cause of Crohn's disease, and in the process perpetuated some commonplace misunderstandings of mycobacterial disease. For example, Dr. Bayless told us that if MAP was the cause of Crohn's disease, then patients with Crohn's disease should get worse when treated with steroids, and not better. In fact, animals infected with paratuberculosis do not get worse when treated with immunosuppressive drugs, but the immunosuppression also permits uncontrolled replication of the bacterium, potentially leading to more severe clinical symptoms when immunosuppressive therapy stops. The reason why paratuberculous animals are not treated with immunosuppressives is simply because the use such of such drugs is prohibited in food animals. This example illustrates clearly the wide knowledge gap that must be bridged between gastroenterological and microbial disease researchers.

The next speaker was Dr. Michael T. Collins, President of the International Association of Paratuberculosis. Dr. Collins gave a thoroughly compelling talk which captivated all present. The subject of Dr. Collins' talk was "Johne's disease and its similarities to Crohn's". Dr. Collins gave a wide overview of the different forms of animal paratuberculosis, with particular reference to the similarity between Crohn's disease and ovine (sheep) paratuberculosis. He also gave us a thorough overview of the epidemiology of Johne's disease in food animals. Many attendees later professed to PARA, in private, that they were both nauseated and abhorred to find that animals with severe clinical paratuberculosis were channeled into the human food chain to make hamburgers. Lastly, Dr. Collins reminded us that since MAP had to date been isolated from four different species of primates that it was unwise to assume that it was incapable of causing disease in humans. Dr. Collins also reported some preliminary results from his research into the presence of MAP in the intestines of people with Crohn's disease.

Dr. Collins then responded to questions.

Professor John Hermon-Taylor, Chairman of the Department of Surgery, St. Georges Hospital Medical School, London, gave us a detailed review of the enormous scope of his research. Among the topics he discussed were

• Genetics. Prof. Hermon-Taylor and his team have discovered the only two genetic "insertion sequences" known to be unique to MAP. Both hold some promise as targets for development of a vaccine.
  
  
• Clinical Medicine. Prof. Hermon-Taylor has pioneered groundbreaking new treatment regimes for Crohn's disease.
  
  
• Food Safety. Prof. Hermon-Taylor and Dr. Rodrick J. Chiodini, were the first to propose and research the presence of MAP in the food chain.
  
  

Dr. Herb van Kruiningen gave a competent talk on the case for MAP not being the cause of Crohn's disease, but seemed to make little impact on the proceedings.

Brief Recess

After a short break, speaking resumed with Dr. Norman Pace, of the Pace Laboratory at University of California at Berkeley. Dr. Pace gave us a thorough understanding of the means and motivation of his methods of Microbial Ecology Analysis. Using the example of his work with Prostate Cancer, Dr. Pace reminded us that microbial diseases are seldom a simple matter of one phenotype of a bacterium causing one single disease condition. More frequently, a "cluster" of closely genetically related phenotypes can cause disease "syndromes", the symptoms of which depend on both the bacteria and the hosts immune reaction to them.

Dr. Relman gave a talk entitled "From Sequence to Causation", which explained how genetic information about an organism can be applied to elucidating the disease causing mechanisms of that organism. From a practical point of view, Dr. Relman explained to us how advances in genetic technology ("DNA microchips") can be used to greatly accelerate the discovery process.

Dr. Fleischmann of The Institute of Genomic Research gave a comprehensive talk on the rapidly-advancing technology involved in sequencing genomes, and how he is currently applying that technology to Mycobacterium avium. MAP is a subspecies of M. avium, and the two share approximately 95% of their genes. M. avium is the most frequent cause of life-threatening infection in people whose immune systems are compromised by Acquired Immune Deficiency Sydrome.

After Lunch

Dr. Sartor, of the Crohn's and Colitis Foundation of America, gave us a detailed analysis of the role of the normal flora in the exacerbation of the disease process in Inflammatory Bowel Disease, with particular reference to his work on simulating colitis by genetically deleting the immune systems of mice and then infecting them with everyday bacteria.

Dr. El-Zaatari, of Baylor College of Medicine, Houston, TX, talked about his work on the immune reaction of Crohn's disease patients to mycobacterial antigens. He also showed us some results recently published by a researcher with whom he has collaborated in the past, Dr. Saleh Naser, University of Central Florida. Although he didn't give a talk, Dr. Naser made some valuable contributions to the meeting.

Dr. Schauer talked on his CCFA-funded work on simulating colitis by genetically deleting the immune systems of mice, and infecting them with various species of Helicobacter, including H. hepaticus. A related bacterium is H. pylori, the bacterium which is now known to be the cause of a majority of cases of Ulcers, and which can be eradicated with a simple 2 to 4 week course of antibiotics.

Discussion

Discussion between lectures varied widely, with the more notable points being

• The Immediate problem. Karen Meyer, Executive Director of PARA, reminded all attendees that the subject under discussion was of direct and immense importance to the 1.5 million men, women and children in the world who suffer from Crohn's disease, and who are in need of urgent help.
  
  
• Shortage of Funding. Dr. Chiodini explained to those unfamiliar with the research field that although there was much inconclusive research published, the reason for this was the chronic and desperate lack of research funding. All research had been conducted "on a shoestring budget". For this reason, Dr. Collins described Mycobacterium avium subspecies paratuberculosis as the "orphan mycobacterium".
  
  
• Syndrome. All those present who had direct clinical experience agreed that Crohn's disease is likely to be more than one disease, which complicates research. A further complication was the continued confusion with Ulcerative Colitis and other Inflammatory Bowel Diseases.
  
  
• Focus. Prof. Hermon-Taylor reminded us that it was important to stay focussed on patient care. For example, if Helicobacter infection was responsible for some cases of Crohn's disease, then Crohn's patients should respond quickly to treatment with a simple course of antibiotics.
  
  
• Caution. Dr. Sartor stressed that it was important to exercise caution when interpreting data about bacterial infections in the intestines, because the alimentary canal is a complex ecosystem full of dangerous organisms, i.e. a "sewer".
  
  
• Risk. Alan Kennedy pointed out that while it was obvious that there was some risk that MAP posed a threat to human health, there seemed to be no discussion of how to quantify that risk.
  
  
• Somebody Else's Problem. Two of the representatives from the United States Department of Agriculture bantered across the room about how MAP was definitely not the responsibility of their offices. Both expressed a degree of frustration that there seemed to be no office where "the buck stopped".
  
  

Closed Meeting

While all of the attendees of the open meeting left the room, the principal organizers of the meeting held a closed session, with the express purpose of discussing the priorities for research. Their recommendations will be published at a later date.

In conclusion

PARA would like to thank the following for their involvement in the sponsorship and hosting of this meeting.

• Dr. George Curlin
  
  
• Dr. Dennis Lang
  
  
• Dr. Frank Hamilton
  
  

For further information contact

Paratuberculosis Awareness and Research Association, Inc.

1. To raise awareness of the zoonotic (disease-causing) potential of the bacterium, MAP, in the national community of sufferers of Crohn's disease, in medical, veterinary and food science research communities, in governmental agencies and in the public in general
2. To urge governmental agencies to directly address control and eventual eradication of MAP from the human environment, particularly from foods of animal origin
3. To urge governmental and medical research agencies to make funding available for research which will determine the role played by MAP in causing Crohn's disease