Can't we work on getting a real study funded to figure out the real causes, differences in diseases, treatments and cures? Where is the help to be found? Who can write up the request among you? Design proper controls?
Sorry for the delayed response. Frankly, I have hesitated but now I feel it would be necessary to share what I experienced during the more than a decade pursuit in IBD, so we may have a more clear vision of the situation and problems in current IBD research and where could be the likely simple solution for IBD.
Regarding funding, as mentioned in the paper discussed here (
Qin X. Etiology of inflammatory bowel disease: a unified hypothesis. World J Gastroenterol. 2012 Apr 21;18(15):1708-22) I have tried many times to apply grants from different agencies such as NIH, Crohn's and Colitis Foundation of America (CCFA), Broad Foundation, and Rainin Foundation, etc. However, all the submitted applications were triaged, meaning the applications were so bad that they were even not worthy to be brought up for a formal discussion at the study sections, or the Letter of Interest was turned down, meaning the idea is so bad that there is no need to submit a formal application. Right now the annual funding in IBD research by National Institute of Health (NIH) of the United States alone is about 120 million (
Here is the link). It is not a lot, but still can do a lot of things. As discussed in multiple of my early posts (see posts
on 08-19-2012,
on 01-12-2013,
on 03-29-2013,
on 03-31-2013, and
on 08-24-2013), I feel the big problem is not the resource but rather the attitude. As discussed in my early
post on 08-19-2012, I found the possible link between saccharin and IBD in 2001, about the same time of finding the first IBD gene, NOD2/Card15, also called IBD1, associated with Crohn’s disease. During the last decade, people conducted genome wide analysis of 75,000 patients and controls with the cost of hundreds or even thousands of US dollars at early times for each and thus hundreds of millions for the whole study. However, nobody have interest to spend a little effort to check out if dietary chemicals like saccharin could be indeed a risk factor for IBD as I demonstrated in the paper published in 2002, by just collecting the urine or feces from some patients and controls and conducting an analysis with the well-established methods that are sensitive enough for an accurate assay for these chemicals even in the contaminated rivers and lakes (here is a recent paper from Canada:
Spoelstra J, Schiff SL, Brown SJ. Artificial sweeteners in a large Canadian river reflect human consumption in the watershed. PLoS One. 2013 Dec 11;8(12):e82706). As the result, although we still do not know how NOD2 related to IBD, we found about 200 more risk genes (
Jostins L, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012 Nov 1;491(7422):119-24). It generated a lot hypotheses and theories, but they can hardly explain anything happened in the real world. NOD2, the gene with the strongest association with Crohn’s disease, not only failed to show an association with CD in Asian, but also failed to show a correlation with the incidence of CD in the western countries that encompass three continents: Europe (France, Germany, UK, Italy, Belgium, Finland), Northern America (US and Canada) and Australia (
Hugot JP, et al. Prevalence of CARD15/NOD2 mutations in Caucasian healthy people. Am J Gastroenterol. 2007 Jun;102(6):1259-67). This would have simply reflected the fact that the dramatic increase of IBD since last century is caused by factors in the environment rather than the gene. Nobody can catch the moon appeared in the water, because the moon is not there, but it still can generate a lot of hypothesis such as the water is too deep, the rope is not long enough, etc. Similarly, as discussed in my early
post on 01-12-2013, despite of the low explaining ability, these genetic studies were presented as great achievements and explained as extra complexity of IBD that can only be deciphered by finding out the much more risk genes and the interactions among these genes, the gut microbiota with genes being 100 times of human genome, and many other epigenetic and other factors. In contrast, I believe the hypothesis I proposed a decade ago without any funding provided much better explanation and prediction for what happened in the real world, as demonstrated by the multiple papers I wrote. In my opinion, a simple breakthrough more likely lays in finding out the principal causative factors in the environment and thus the root mechanism of IBD. Probably, several hundreds of thousands may make even bigger progress than the hundreds of millions or even billions spent in the last decades. But we need finding the people who would like to do so.
Regarding the help, when I found the possible link between saccharin and IBD, I thought I may get some help from government or international agencies in charge of food safety, and foundations or professionals related to IBD research, but it turned out that none of these seemed really helped. Following is a list of some of my efforts:
- National Institute of Health (NIH) of US: I contacted in December 2001 the Director of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) responsive for studies in diseases of digestive system like IBD. The director responded through a person at the Office of Communications and Public Liaison, suggested me to apply grants from NIH or Crohn's and Colitis Foundation of America (CCFA). At that time, I had no way to do so, as I was ousted from my job since July 2001 largely due to my pursuit in the possible role of digestive proteases in diseases like IBD, then the immigration agency messed up my record and I had to stay at home for more than one year waiting for the correction and new process of hiring. After I went back to research and became a faculty I indeed tried very hard to apply some grants from NIH and CCFA, but all these applications were triaged as stated above.
- Food and Drug Administration (FDA) of US: I contacted in December 2001 the Director of the FDA’s Center for Food Safety and Applied Nutrition (CFSAN), but failed to get any response.
- Crohn's and Colitis Foundation of America (CCFA): I contacted in December 2001 the Chair of CCFA's National Scientific Advisory Committee and I was suggested to apply grant. I did try multiple times, but all triaged. During the last decade, I have also contact quite a number of the annually rotating Chairs of CCFA's National Scientific Advisory Committee suggesting a discussion on the evidence I gathered regarding the possible link between dietary chemicals and IBD, but I got no positive response.
- Center of Disease Control (CDC) of US: In February 2008, I learnt from CDC web site that some scientists/epidemiologists there were conducting an epidemiological study on IBD. I contacted the people there. The medical officer of CDC participated in this study told me that they were working as collaborating scientists with CCFA. Then she introduced me to the top officer in CCFA in charge of research and this officer then introduced me to a well-known IBD researcher. The professor told me he would like discuss with me after reading the material I sent him, but I failed getting any response.
- Joint Food and Agriculture Organization(FAO)/World Health Organization (WHO) Expert Committee on Food Additives (JECFA): I contacted in December 2001 the Secretary of JECFA and I was told in the response that they do not have sufficient resources to undertake work in this area.
- The European Union: I contacted in January 2002 the office of Scientific Committee for Food of European Union, but failed to get any response.
- Health Canada: I contacted in January 2002 the top officer in Canadian Food Inspection Agency. I got a response by the end of April telling me that my email was forwarded to Chemical Health Hazard Assessment Division in Health Canada. Then I got the opinion that saccharin was unlikely an important causative factor as Canada restricted its use after finding its carcinogenicity in animals in 1977. I felt this opinion reasonable and started to believe that even there is a link between artificial sweeteners and IBD, the link may not be strong. However, this notion changed after I found a paper in 2011 that sucralose inhibited gut bacteria and further leant that this new artificial sweetener was first approved by Canada in 1991. I immediately realized that sucralose may have played an important role in the high incidence of IBD observed in Canada in recent years. More evidences I collected seemed to support this notion. I wrote a paper on this that was published in Canadian Journal of Gastroenterology (
Qin X. What made Canada become a country with the highest incidence of inflammatory bowel disease: could sucralose be the culprit? Can J Gastroenterol. 2011 Sep;25(9):511). Meanwhile, I contacted Health Canada again and tried to reach those I communicated about a decade ago, but failed to get any response.
- Food Standard Agency of UK: I contacted in March 2002 people in the Chemical Safety and Toxicology Branch of Food Standard Agency. They told me that they would be most interested to see new published data in my possession that casted doubt over the safety of saccharin. I sent them a draft of the manuscript that was eventually published in Medical Hypotheses (
Qin XF. Impaired inactivation of digestive proteases by deconjugated bilirubin: the possible mechanism for inflammatory bowel disease. Med Hypotheses. 2002 Aug;59(2):159-63), but I never got any further response.
- IBD professional: As mentioned in
my previous post on 01-30-2014, shortly after I found the possible link between saccharin and IBD, I contacted and would like to get an opinion from Dr. Joseph B. Kirsner, Professor at University of Chicago Medical Center and one of the most renowned IBD researcher in the world, but failed to get any response. During the 2003 Digestive Disease Week (DDW) conference, I also handed a copy of my paper published In Medical Hypotheses in 2002 as mentioned above to Dr. Stephen B. Hanauer, also a professor at University of Chicago Medical Center and one of the most renowned IBD researcher, and the multiple year co-Chairman for the yearly Advances in Inflammatory Bowel Diseases, Crohn’s & Colitis Foundation’s Clinical & Research Conference, asking for his opinion, but failed to get a response. As stated in
my early post on 01-12-2013, I also started a discussion at several IBD-related LinkedIn groups including the European Crohn's and Colitis Organisation (ECCO), CCFA (Crohn's & Colitis Foundation of America), IBD - Crohn's disease & Ulcerative Colitis – CCF, and IBD Research Foundation, entitled “We should put a little bit more effort to find out the cause of inflammatory bowel disease”, in hoping to generate some in-depth discussion on the cause and etiology of IBD among the IBD professionals, but none of the IBD professionals responded. I had also submitted an abstract to the 2012 Advances in Inflammatory Bowel Diseases: Crohn's and Colitis Foundation's Clinical and Research Conference and the 8th European Crohn's and Colitis Organisation Congress of Inflammatory Bowel Diseases 2013, in hoping to have the chance exchanging information, evidences and views with IBD professions regarding the etiology of IBD, but the abstract was rejected by both of the conferences. As stated in
my early post on 03-17-2013, shortly after the publication of this paper discussed here, I have emailed a copy of this paper to each member of
the Epidemiology and Natural History Task Force of the International Organization of Inflammatory Bowel Disease (IOIBD) advocating them checking out this possibility. Apparently it failed to raise any attention, which is reflected by the fact that this group later published a paper regarding the environmental risk factors in IBD (
Ng SC, et al. Geographical variability and environmental risk factors in inflammatory bowel disease. Gut. 2013 Apr;62(4):630-49) without mentioning the existence of such a hypothesis. I submitted a manuscript as a letter to the editor entitled “Dietary chemicals like saccharin and sucralose should not be omitted by epidemiologists as the possible important causative factors for inflammatory bowel disease”, but was rejected (see
the post on 03-17-2013 for the rejected paper).
From my experience, and time and again demonstrated in human history, the only thing that can ultimately help to differentiate truth versus false is time, despite that the behavior of human may greatly affect how long it will take to achieve this. It took nearly 2000 years from someone proposed the earth turning around the sun to people really accepted it, and It took nearly a century from someone proposed the spiral-shaped bacteria may have played a role in the pathogenesis of gastric diseases to the finding of H. Pylori as the primary cause of peptic ulcer. We still do not know how long it will take for a final solution of IBD. However, as stated in
my previous post on 08-24-2013, “I and the mainstream presented two totally different scenarios: I feel I, as a spare time IBD researcher and without any funding on IBD, may have virtually solved the mystery of IBD more than a decade ago, while the mainstream presented an extremely complex IBD that may need billions, if not trillions, and decades, if not centuries, to decipher it”. Which one is right? Some very easy tests can tell. As described above, I have tried so hard in the last decade to get this test down, either by myself through a grant or others capable of doing so. However, none would like to provide the tiny bit of resource or spent a little bit efforts. With time passing by, more and more evidences suggest my concern on the possible link between dietary chemicals and IBD is likely real rather than lunatic illusion, as demonstrated by the multiple recent epidemiological findings in IBD that I have commented on (
here included some of these papers I wrote). As an individual, I often feel so helpless in front of the mainstream. The mainstream is so powerful. They can get and spend billions and asking for trillions under the glories claim to seek a solution of the disease, but put any evidence of the possible easy solution into the abyss of shadow and make the suggestion for this easy solution as heresy and ridiculous. Luckily, time and nature is even more powerful and always teach us, little by little, what is true, although time and again we just take too long to comprehend it. Looking back into what happened during the last decade, now I feel more confident to say there seems simple cause and easy solution for IBD. However, to reach this goal, we may need not only the efforts of the whole society but also, more importantly, the right approach that leads towards to but not away from the solution.
