Charles N. Gutierrez
232 Spring St.
Jonesborough, TN 37659
April 28, 2009
The Honorable Harry Mitchell (AZ) Chairman
Subcommittee on Oversights and Investigations
1410 Longworth House Office Building
Washington, DC 20515
Regarding: Persian Gulf Illness
Research Advisory Committee – Gulf War Veterans Illness
November, 2008 Report
Dear Representative Harry Mitchell,
My name is Charles N. Gutierrez. I retired March 31, 2007 as a Microbiology Supervisor from the James H. Quillen Veterans Administration Medical Center at Mountain Home, Tennessee. I held this position from July 1982 until my retirement. My total government service was 31 years. I also served as a microbiology instructor at the James H. Quillen School of Medicine from 1979 to 1982. I hold a masters degree in Microbiology and a combined Microbiology / Medical Technology BS degree.
The purpose of my letter is to the subcommittee is to first make the subcommittee aware of what I believe, based on clinical work with Persian Gulf Veterans (PGVs), is a gross oversight by the Research Advisory Committee on Gulf War Veterans Illness (RAC-GWVI) on their Scientific Findings and Recommendations in the November 2008 “Report on Gulf War Illness and the Health of Gulf War Veterans.” I have printed and read the total 454 pages of the report in the last few months.
The second reason for this letter is to unburden, again under duress, the anxiety, and sleepless nights experienced over the mishandling of work I performed on PGVs at Mountain Home VAMC. The latest blow was the destruction of hundreds of formalin preserved Gulf War Veteran’s specimens I entrusted to the management of the hospital before I left. I strongly felt and communicated to hospital management that unique physical observations in these specimens were critical to Gulf War Illness (GWI) and further work on these specimens should be performed. After a few days of total depression on hearing this, it became clear. The VA has no interest in finding the cause of GWI. The same fact I previously realized during years of clinical testing of PGVs. Another point that became evident was that these specimens were useless. Who was going to work on them? No one. Would the RAC-GWVI be interested and get involved? No. Their mandate is to review publications. Recommendations I anonymously made years earlier in 2002 (due to fear of VA retaliation) were totally ignored by the RAC-GWVI (see attachment A). Recommendations were not even proposed, much less mentioned. I find this to be my fault. I was not aggressive enough to use outside channels such as the press.
This is difficult to communicate in brief because of the volume of papers, boxes of notes, pictures and admonishment memos I have saved related to work with PGVs at the James H. Quillen VAMC, Mountain Home,Tennessee. One attempt to initiate a re-awareness of these findings ended abruptly by my being physically sick after reading the discrediting memos and punishing actions taken against me by the VA. I will try to provide, as briefly as possible, a chronology of this work and try to make the scientific data understandable.
First, let me quote two statements I found profoundly helpful in initiating this letter. The first is a statement by Rep. Corrine Brown (D-FL), a member of the US House of Representatives Committee on Veterans Affairs. She asked on her web page: “What about what we don’t know?” The second is a statement in the RAC-GWVI 2008 report on page 230:
“The absence of consistent diagnostic indicators from routine clinical testing methods suggested to some that Gulf War Veterans Illness was not a medical problem with identifiable biological abnormalities. An alternative interpretation was that the biological abnormalities that underlie veterans’ symptomatic illness were unfamiliar, and could not be detected by clinical tests routinely used to diagnose more familiar conditions.”
This is a profound statement. This, to me, was the crux of this unbelievable dilemma based on all my comprehensive experience with this matter.
There were consistent diagnostic indicators, mistakenly identified or not identified, present but ignored, on Persian Gulf Veterans. These were my findings, and if I did not strongly believe of their importance, I would not have subjected myself to the VA’s threats of termination, suspension, and repression while employed, and the pain of assembling this letter. I have never asked to be proved right. To be proven wrong would have been a great relief.
Events proceeded as follows:
In the late 1980’s we started using a work intensive stain called the Modified Trichrome Stain (Weber Stain) to screen AIDS patients for microsporidia, a parasite found in stools of severely immunodeficient patients that causes them to experience severe diarrhea. We used a Methylene Blue wet prep with phase contrast microscopy to screen patients for microsporidia and cryptosporidia, both refractive parasites with different size measurements. If size was consistent with microsporidia, a Weber Modified Trichrome Blue stain was performed. The parasite stains red, all other bacteria and parasites do not stain red, but stain blue.
A rotating pathology resident working in my lab did a case study on positive stools from AIDS patients. One patient reviewed was a PGV who did not have AIDS. This was a 27-year-old male who had numerous refractive forms in the stool and a history of chronic diarrhea. The resident had failed to note if the patient was immunodeficient. I had previously found another positive patient who I had not recognized as being an AIDS patient. Further inquiry showed this patient to be a PGV with a three-year history of diarrhea. Recent news reports were stating how PGVs were suffering from chronic diarrhea. There were no VA alerts calling for diarrhea testing on PGVs that had been communicated to us.
2. An article appeared in the local newspaper about a married couple starting a support group for sick Persian Gulf Veterans. Out of curiosity, I was interested in their symptoms, especially the diarrhea, and attended the first and subsequent meetings. I volunteered to serve as a scientific advisor to help them interpret medical terms and to keep them current of any papers published pertaining to their condition. There I learned first hand of the multiple symptoms they were experiencing.
3. I inquired at our VA of who was attending to PGVs and was directed to Dr. Alfred Bennett, who I then went to see. During our discussion I convinced him that all veterans, such as the PGVs who served overseas, should have a routine O and P (ova and parasite) exam performed. Vietnam Veterans came back with asymptomatic parasite infections from service in Vietnam and should have routinely been screened for parasites if they presented to the VA on their initial visit. At the time we were seeing numerous cases of larval parasites (Strongyloides stecoralis) in WWII veterans who were being put on steroids. Dr. Bennett served as a colonel in the local 912th MASH unit in Kuwait and was the commander of many of the sick veterans who knew him personally. Thus, because of their diarrhea, we began O and P testing, under his orders, on all PGVs.
4. Mary Hillesland, a VA social worker, was assigned to work with the PGVs in the hospital, and at their monthly meetings, a position she held until her retirement.
5. In the summer of 1994, we began testing stools for ova and parasites on all PGVs. We were also in close communication with Dr. Bennett concerning other symptoms and tests that might be helpful. Interviews were conducted with all patients, especially to get a handle on the many diarrhea cases being seen. At this time we started a listing of all symptoms being seen in these patients. Routine tests were ordered as needed, an example would be a urine culture ordered by Dr. Bennett if we found complaints of a urinary nature.
6. At this time a microbiologist with a Masters degree approached me and requested to perform volunteer work in the lab. At the time she was unemployed, her kids were grown, and she wanted to get back into the lab. This provided for an opportunity to help with the Persian Gulf veteran’s work on which I was having a hard time keeping up with. Working through Voluntary Services, she started work in the lab. To this project she contributed 40 hours a week for full year and only “called in sick” one day. She helped doing interviews, staining, measurements, and photography and literature searches. This was all done under my supervision. She was a great asset in this endeavor.
7. It was during this period that we noted a consistent finding in the stool of PGVs. Through the use of a Methylene Blue Wet Prep and phase contrast microscopy we observed .5 to 1.0 micron refractive like spore structures consistent in size and staining properties with Enterocytozoon bieneusi. These same structures were found in the rash of one patient, in the sinus, and conjunctiva of another PGV. (See attachment B for pictures).
Since the organism’s morphology met the criteria for a presumptive diagnosis of microsporidia , because of it’s size, the positive stain, and since confirmation by electron microscopic was not available, the following comments were inserted in the results section of the PGVs electronic chart for the stool O and P exam:
“Positive for presumptive Microsporidium sp. type spores based on morphology and staining characteristics. Confirmation by transmission electron microscopy not available. Specimen negative for other ova and parasites. Specimen being preserved for future studies.”
8. To get confirmative proof for Microsporidium, we had to show structures visible only by electron microscopy. This was a huge undertaking, but with the help of one of my old professors at the college of medicine, we were able to examine several specimens. Repeated attempts were unsuccessful. This discrepancy, and the fact that this organism was only found in immunodeficient patients, such as AIDS, or cancer patients, was puzzling. Another finding of our staining showed the organisms to be acid fast. There was no literature on any Microsporidium species being acid fast.
9. From June 1994 to September 1995, we sought help from other individuals and institutions. I took my data to a workshop in Spartanburg, South Carolina given by a CDC microbiologist. After the workshop I showed him my data. He advised me to call CDC. On my return, numerous phone calls turned into a game of phone tag. The only work on PGVs was an epidemiology survey. To Walter Reed I sent droppers of Methylene Blue with preserved samples and directions as to what we were seeing - there was no return communications as I recall. Samples were sent to an international diarrhea expert who said he would look at the samples and promised PCR (molecular DNA) could be performed by a scientist at NIH. After long waits (months), no work was performed. The NIH scientist, we were told after finally making contact, thought these were yeast, and no work was performed. This was absurd. This came from a molecular biologist and not a trained clinical microbiologist. Dr. Didier at the Tulane Louisiana Primate Center, a Microsporidium expert, confirmed our suspicions that these structures resembled Microsporidium, but most likely were not, because of weak staining by the immunofluorescent antibody tests using polyclonal and monoclonal antibodies she had developed in her lab. Even though these tests were negative, she was a ray of sunshine and the person who showed genuine interest. Something rare. Without going into exhaustive details, in attachments C are letters sent in our attempt to get help. These were later used to discredit my work without even as much as a meeting to discuss their contents.
10. Unable to make a definitive identification, and at a dead end, and in an attempt to get help, after other efforts had failed, it was decided that we should present this preliminary information, along with pictures, to President Clinton’s Advisory Committee. This meeting was to be held on September 18, 1995 in Charlotte, North Carolina (minutes of the meeting are on the committee’s web site). We did not want to generate any undue press. We just wanted to present our findings in written form so the committee, in the hope of generating further research, could use the information. I requested a five-minute slot for the presentation, and five minutes would be given to questions.
I requested permission to make this presentation from my lab director, and he asked that we write a memo to the VA director for permission. Dr.Youngberg, a lab pathologist, who I often consulted on this problem, and I wrote the request by memo and presented it to the director. Note that the memo submitted does not mention the term Microsporidia, due to the lack of confirmation data. The Medical Center director denied my request to speak (see memorandum in attachment D).
I called Washington and asked to cancel my schedule slot. They requested why, and I explained the situation. They then asked that I fax them the memo, which I did. A few days later, my lab director asked me for all logbooks, journals, phone logs and all data pertaining to my work performed in the lab. Less than a week later I was ordered to stop and desist from any further work on PGVs with threats of disciplinary action and suspension (see September 21, 1995 memo in attachments E).
I knew this had to do with the director’s memo that was faxed to Washington, but then I thought there would be phone calls or letters of inquiry and the trouble I was going through, would be worth it, seeing that I could then explain our findings. Apparently everything was intercepted and never was a letter or phone call received by me. Years later I was told this was a “political committee”. Being in a very strong conservative Republican district with a sweetheart relationship between the governor, the director, and Congressman James H. Quillen, there seem to be an intense dislike of Clinton, and nothing was to be given to anything with his name on it. This, personally, I felt, as another case of science being mediated by politics. Again Persian Gulf veterans would continue to suffer because of politics.
11. At the monthly meeting of the Northeast Tennessee Persian Gulf Veterans support group, I told the members that I could no longer perform the work I was doing. Since all work was done by physician order, we would probably no longer have this support. Without my knowledge, PGVs wrote letters to Jessie Brown, VA Secretary, Rep. James H. Quillen, and Senator Fred Thompson protesting this action. Some of the veterans showed me the written responses they received. All cited a memo from the Medical Center director to Fran Murray ACMD for the Office of Public Health and Environmental Hazards (103) VACO Washington, DC. Susan H. Mather M.D., Assistant Chief Medical Director for Public Health and Environmental Hazards, answered letters to Jessie Brown (See letters in attachments F).
The facts are:
The exchange of letters from PGVs to the above officials took place from September 25, 1995 to December 1995. I received the October 5 copy of the memorandum sent to ACMD Office of Public Health and Environmental Hazards on November 15, 1995. I made a request to respond officially to this memorandum, but was denied this basic privilege by the Chief of Pathology and Laboratory Medicine at VAMC, Mountain Home.
As a private citizen I started a draft response to doctors Fran Murray, Susan Mather, and Jessie Brown. With my state of mind and the complication of explaining my data and my possibly forcing further retaliations, I found it excruciating, and was mentally unable to finish this task (See attachment G, unfinished hand written draft response).
12. April 1996. Unable to continue working on this matter, a microbiology student (Donna Joyce), was sent to me from the Microbiology Department at East Tennessee State University, for me to offer her any suggestions on a project for her thesis. We had staining issues, such as acid fastness, that we needed to resolve for Microsporidia. She obtained four Microsporidia species from Dr. Didier at the Tulane Primate Center and performed multiple stains on these. Also as a side project not included in her thesis, she performed multiple staining tests on multiple anaerobe spores isolated by another microbiologist (not VA) to test. These were compared to the Enterocytozoon bieneusi and other microsporidium species being used in her thesis. The key result was that Vittaforma cornea was acid fast, but not Enterocytozoon bieneusi, which we thought would be acid fast, as this was the organism we suspected in PGVs. This was a discrepancy we could not explain. (Published thesis available at ETSU Library)
13. Note: sometime in 1995(?) I received a formalin-preserved stool from a PGV suffering from classical symptoms to see if what we were seeing in East Tennessee was the same in Albuquerque, New Mexico where this veteran was from. The stool specimen from 1,200 miles away, showed numerous refractive spore like structures present, exactly what we were seeing in east Tennessee PGVs.
14. In January 1997, I was notified by Mary Hillesland, our social worker, that a very sick PGV who was in our intensive care unit with pneumonia. Apparently he had passed out and wrecked his truck. A sputum for culture and sensitivity (C and S) was ordered by his ICU physician. I told her I would look at it very carefully. For days the sputum never showed up, but was collected prior to his discharge. I missed the specimen and did not have a chance to evaluate it. Later, in March 1997, Mary sent him to my office. He said he was still not well. I checked his appointment schedule and he was scheduled to see the pulmonary doctor. I told him to keep the appointment and to see me later. After his appointment he said the pulmonary resident said he had chronic obstructive pulmonary disease (COPD) and was given bronchial inhalers. This, for a 34-year-old male, seems to me out of the ordinary. He said he was also scheduled to see his primary care doctor the next day. My opinion only, I felt this primary doctor had an antagonistic attitude towards PGVs. Since I did not get to examine the specimen, I asked that he bring me a first morning sputum so that I could do a rapid screening to make sure nothing significant was missed. I performed a routine Gram stain and saw nothing exceptional except an abnormal amount of macrophage cells. When I performed a Methylene Blue direct wet prep and observed it under phase contrast, I observed numerous refractive forms, which I suspected to be Microsporidia engulfed inside the macrophage cells. I was alarmed at what I saw! A follow up Modified Trichrome stain showed them to be red staining organisms similar to what we had been seeing previously.
Very concerned, and fearing possible consequences, I called his primary care doctor to make her aware of this. She came up and I showed her the slide. Angrily, she said she did not know what this was and asked who ordered this smear. I offered to repeat the smear on her orders. She stormed out and issued a complaint to my director.
He later showed up at my office and stated that I had been warned and I did a test without a doctor’s order and I was told I would suffer the consequences (attachment H). At a later date when again threatened with disciplinary action I was told “we do things by the book,” at which time I reminded him that frequent lab testing was being done by lab personnel on themselves, their spouses and families. None of who were veterans. I have done tests on the hospital director with no doctor’s orders, also for doctors who order tests on other doctors who are not veterans (one at a cost of $264). Cost on this PGV was fifty cents at the most. I screwed up, not having a physician-clinician relationship as with Dr. Bennett, who was now out of the picture, would cost me dearly. My concern for the PGV, based on what I saw on his smear, had blown caution to the win. There was no winning.
In short I was given a week suspension without pay (March 31-April 4). I did not file an appeal or a grievance since I felt this was symbolic of our VA’s gross ineptitude in the treatment of PGVs. I served the week suspension (see attachment H).
In early March 1997, the Department of Veterinary Science and Microbiology, University of Arizona, Tucson, published a new paper on microsporidia (Journal of Clinical Microbiology, March 1997). This paper stated “this is a new tool for identifying spores in bodily fluids and biopsy samples and is an efficient diagnostic test” (see cover page of paper in attachments I). A new monoclonal antibody, 386, was developed for this test. This was a chance to test our isolates and eliminate three of four species but not the species we suspected (Enterocytozoon bienieuse). It should be negative. Also I had extra slides of the PGV with the suspected pneumonia. I called John D. Palting at their lab, and he said they would be happy to test our isolates at no cost since they were anxious to test their monoclonal antibody on clinical samples. Already awaiting my suspension, and dejected, I decided this would be my final effort and I would abandon all Persian Gulf dealings after this.
I sent slides of stools that contain numerous spore like forms of the organism we had found, and as a last thought, included a couple of slides of the PGV’s pneumonia case. A few days later I received a call from their lab. I believe I talked to a graduate student. All samples tested negative, as we suspected they would. They were curious about the pneumonia slides from the PGV. I provided them with the case history and they said they wanted to do more tests. I received a call back. They suspected the PGV’s slide was Brucella! Extending the counter stain of the routine Gram stain will show the organism, whereas in the routine stain it could be missed or be very lightly stained. To tell the truth I was stunned.
All other supervisors had long been assigned web access, but I was not for some reason. Finally, after repeated requests, I was given web access. Before this I did manual searches in books and journals. The web search results for Brucella (brucella, brucellosis, Brucella melitensis, and chronic brucellosis) were eye opening for the following reasons:
Were we fooled? Could what we suspected to be Microsporidium actually be Brucella? We were never totally confident of Microsporidium since the organism is mostly found in immunodeficient patients such as AIDS or cancer patients and we felt that PGVs were immunocompetent but no studies were available to show this at that time. The organism in question met the criteria for presumptive identification of Enterocytozoon bienusi because of its size, and mostly because it being positive using the Modified Trichrome test (red) which is the same used to report Microsporidium in the clinical lab. At this period of testing we had worked hard to be competent in the diagnosis of Microsporidium in AIDS patients. This stain, until years later, was very time consuming and was not performed by most clinical labs at the time. Even in the beginning, the only smears provided for control testing by commercial companies were misleading until we made them aware of this problem.
Already given a letter of Notice of Suspension (see attachment H) and no credible doctor to work with, I needed to reopen the Persian Gulf veteran’s case which had got me the five day suspension, which I had to serve in a couple of weeks. I decided to approach the Chief of Pulmonary Medicine, to explain the situation, and hopefully the PGV’s case could be reopened and be evaluated for chronic brucellosis. I did not put in for a research grant. This was excruciating for me to attempt, having done this in the past and having come out feeling humiliated by the chief of some department. These were not even Persian Gulf related cases. I called Dr. Ryland Byrd, the Chief of Pulmonary Medicine, whom I’d never met, and set up an appointment to meet with him. Though I was dreading the meeting, he turned out to be very cordial, very interested, and a doctor with an open and inquisitive mind. After I explained all the details of my dilemma, he said he would review the PGV’s file with the pulmonary fellow who had seen the patient. I made him aware that with his orders I would work up a pulmonary specimen for Brucellosis. I also convinced the infectious disease doctor to order blood cultures for Brucella, after explaining the situation. He did this reluctantly, knowing the controversy with PGVs, and any association with such. Also he was having green card problems, but after I stated that the pulmonary chief was involved, he ordered blood cultures on the veteran.
To do clinical testing on Brucella you cannot do routine standardized testing. Specimen cultures that are routinely terminated at 48 hours need to be held for 21 days or longer. The same for blood cultures, instead of 5 days they should be held 30 days. Preferred specimens are bone marrow and blood cultures. This is why it is imperative that the doctor communicates to the microbiologist if a case of Brucellosis is suspected otherwise the smears and culture work up will most likely be negative and useless. This is a very crucial point! The fact that PGV’s clinicians across the country had no inkling that Brucella may be suspect, they only order routine culture testing.
There is a serious danger in working with Brucella organisms grown in the laboratory, especially Brucella meliensis, which is highly infectious. Even though we worked with millions of particles of Hepatitis C and HIV organisms daily, plus occasionally tuberculosis organisms, special precautions are needed to avoid aerosol formation. Knowing this, I performed all work on the culture after work hours in an empty lab, and under a class two biological hood.
A standard clinical microbiology lab such as used in the VA, cannot fully identify Brucella species unless set up to do so. Special dye testing plates (never used in my career) and special serological reagents are needed. Automated identification systems in use in VA microbiology labs will almost always give you a misidentification on a Brucella isolate. A reference lab is always needed. A presumptive diagnosis can be made based on staining characteristics, growth patterns on media, available biological tests, and a patient’s history. For example, whether the patient was in an endemic area, his symptoms, risk factors such as consuming dairy products such as goat cheese, being around sheep, goats, camels and their droppings, and other environmental factors such as bacteria laden dust, dead animals, and contaminated water.
A sputum culture, ordered by Dr. Byrd, was obtained from the veteran. After 48 hours no suspicious growth was found. After extended incubation, a few suspect isolated colonies were noted. Staining characteristics of these colonies using the routine Gram stain showed very light red staining organisms, resembling grains of sand instead of the deep staining rods and cocci of the control stain. Extended counter staining with carbofuchin as the Tucson laboratory probably did, Made these organisms more visible. 30 of 31 tests performed were characteristic of Brucella. The one test that was uncharacteristic can be variable according to which paper you read. Based on the stain showing macrophages engorged by organisms, and the above testing, and the veteran’s risk factors, a presumptive diagnosis of brucellosis can be made.
This was reported on the veteran’s electronic chart as presumptive Brucellosis based on this testing. The patient was treated by Dr. Byrd for Brucella and apparently responded to treatment. Dr. Byrd also stated that this was very likely a case of chronic brucellosis. He asked that I refer other pulmonary cases that I may come across to him. This was a request too late in the making. I had no access to any doctor who had hands on interest in Persian Gulf syndrome. After the departure of Dr. Bennett, no more specimens were submitted and testing came to a complete halt and totally dried up. If specimens were submitted, we did not know if they were PGVs or not, and they only got the routine work up. Even the successful testing I just described was used in an attempt to further discipline me and possibly terminate my employment. Word had gotten to my pathologist, who most times I felt was divorced from even routine work performed in my lab, that I was illegally working with Brucella. My lab supply orders were screened to see what Brucella related supplies I might have ordered. The pathology chief came to my office, and in a “I got you” demeanor ordered me to produce a written report of any Brucella work I was involved in. I printed all the PGV’s patient reports and turned these in to him. Again I felt I was being harassed and my feelings were that there would be no letup until I could be nailed to the wall. A pregnant employee who was possibly worried about exposure may have precipitated this. This is why I did all work at night and under strict safety conditions. This employee, I always felt, resented my out-of-the-box work and inquisitiveness. The greatest danger is working with what you don’t know, as to working with what you know may be present. These are the risks you take as a clinical microbiology technician and as an employee or supervisor you are responsible for monitoring, using, and applying the strictest safety procedures.
As the microbiologist for the James H. Quillen Veterans Administration medical Center, my responsibility was for all disease testing in the hospital. I did not go out blindly seeking a cause for Persian Gulf syndrome. If a person is sick, and I find the cause through specimen testing, I report that finding. If I find something I cannot identify, I do not put in for a peer review study to identify the organism but persue it. This is easy when you can grow it out. If you run up against a wall you send it to the state lab, and if they cannot identify it, they send it to CDC. I’ve already provided evidence of seeking help. Our aim was to get a solid clue as to the identity of this structure, and proceed from there, and maybe convince others to do a peer review study. Research laboratories have these capabilities. We were not proficient enough, or had enough expertise, to do Polymerase Chain Reaction (PCR) on extracted DNA, which I felt was disparately needed. This was the point we were at when we tried to approach someone to consider doing this work. The management in my lab did not offer help to kick this up higher, or seek help using their authority, which I felt, should have been done. It was the fear of being embarrassed if you are wrong. When someone finds a solid clue that there is something unique that is being found in PGVs and not in the hospital population, what do you do? You discredit the investigator? Say he is wrong, when you really hadn’t studied or been interested in his data? So he is wrong, but still there is something that hasn’t been explained. Shouldn’t that be followed up? Shouldn’t this be of concern when veterans are suffering? I’ve asked my pathologist to write on a paper what this was we were seeing. He said he did not know what it was. But shouldn’t it be his job to find out? If they don’t care, it isn’t their job.
I started my five-day suspension, March 31 to April 4, 1997. Not doing so, I felt, would be a betrayal of my principles. If this was a bluff it was not going to work. I felt deeply that my career and hard struggle to become a microbiologist, and with 10 years remaining to retirement, was in severe jeopardy. Through 1997 I continued to advise the graduate student who was working on some issues we had with Microsporidia staining. One finding later proved significant in support of Brucella and not microsporidium.
In March 1995, an article from Spain appeared in the Journal of Clinical Microbiology entitled “Specific Detection of Brucella DNA by PCR”. I found this between May and October 1997. I was excited upon seeing this paper. If PCR testing for Brucella DNA could be done on PGV’s samples this would answer the question of whether Brucella was the agent responsible for this affliction. Dr. Siddiqui, a researcher, and associate professor at the James H. Quillen College of Medicine, was in my office discussing a paper we were submitting for publication. Somehow, I got into a discussion on PGVs. I mentioned my hypothesis that Brucella may be involved with the Persian Gulf syndrome, and how this paper from Spain would answer that question if I could only get permission to send samples to Spain for testing (knowing it was out of the question). He asked to see the paper, and I showed him the Journal article. I was surprised when he said this could be done in his lab since the primer sequences were published in the paper, and these could be synthesized and purchased. It was totally doable and a “true research” project that could be based on our hypothesis derived from our preliminary information. He said I would have to discuss this with Dr. Berk, who I knew well and worked with at the VA before he joined the College of Medicine as chairman of the Department of Internal Medicine. An appointment was set up, and I hauled all of my data and pictures to his office. After two hours of discussion, he agreed that this was a very credible research project, but there would be one problem. He felt that the director of the VAMC, the same who rejected my request to speak to President Clinton’s Advisory Committee, would not approve it. Right away I felt the reason was maybe bad blood between the two. A reason I understood why but stating it would only be speculation. Again I was foiled by internal politics and personality disputes. The hope of this project going through was tabled that afternoon. Here was a College of Medicine department, on the VA grounds, unable to conduct research that affects veterans with pressing problems. Not long afterwards, Dr. Berk moved to head the medical school at the University of Texas, Amarillo, a position he was denied at the James H.Quillen College of Medicine.
An example of the lack of concern for PGVs was the teleconferences to educate physicians about Persian Gulf syndrome. I always made it a point to attend, and they also helped with my continuing education credits. Most of the time it was only myself in an empty room. Where were the physicians that were caring for these patients? One time only a physician and psychiatrist did attend only to make snide remarks and laugh about a PGV weeping in the film. This behavior; I felt, demonstrated their complete insensitivity to PGVs’ problems. I knew the physician’s name and purposely walked over to the sign-up sheet to find the psychiatrist’s name and look him in the eye without saying a word. This I felt was the typical attitude at our institution. It seemed our psychiatry department always got press in our local newspaper (peer reviewed?) citing PTSD. As one Persian Gulf veteran said to me “They say I have PTSD. The only PTSD I have is dealing with the VA”.
In June 1998 I was again involved in a minor incident, not directly related to Persian Gulf work, that was magnified to again discipline me as a consequence of my previous problem. I had a target on my head and was open game for any minor infraction. After this incident, I had to divorce myself from further hope of getting any help or trying to progress further in my efforts. The Persian Gulf support group, and myself, tired of not getting any answers, focused on how to file disability claims. Katy Renfro, an expert in all aspects of the filing process, helped many PGVs file their claims. She did not work for the VA. Her husband was disabled, and by fighting for his rights, she learned the ropes and was able to help others. When one totally incapacitated PGV was denied his claim, he was told to get a copy of all his medical work from the VA and take them to the Social Security office. In no time he was receiving SSI benefits based on these papers.
Feeling beaten, I focused my attention on the hepatitis C problem at our hospital, mostly among Vietnam veterans. The program was disorganized and wasting up to $2,500 a month on unneeded and duplicate testing. Working with a key person in my lab, we coordinated and streamlined patient testing, result reporting, data collection, and treatment.
Again, through close work and open discussions with a caring Gastroenterology Chief we were able to accomplish a lot. This was stimulating compared with my Persian Gulf experience. In the meantime I was following all Brucella papers being published.
I felt it important to inform someone about the possibility of Brucella melitensis being involved in the Persian Gulf Theater. A letter signed by members of the Northeast Tennessee support group and a two page paper I prepared, recommending studies needed on Brucella, was sent to Bernard Rosker at the Office of the Special Assistant for Gulf War Veterans (OSAGWI). I do not have the date but believe it was around 2001 - 2002. Nothing came of this. (Same as attachment A).
On March 3-5, 2002, at my own expense, I attended the national Gulf War Resources Center Committee meeting at the Holiday Inn Airport in Atlanta, GA. Again I was trying to create an awareness of brucellosis in the Persian Gulf War theater. I was not there as a VA employee, but as a private citizen. I knew I might be in trouble if I did identify myself as a VA employee and said anything publicly. I asked chairman James Binns and Lea Steele of the Research Advisory Committee, who were present, if I could meet in private with them to relay this information. It was agreed and we met in my hotel room where I explained the situation and gave them the two page paper of problems I felt needed to be addressed (see attachment A). They were very receptive and I really fell for once someone would see this through. In hindsight, this was another waste of my time and money. I never saw or read any follow-up on these suggestions. My experience with the Research Advisory Committee on Persian Gulf Illness, despite its burden and massive undertaking, has shown me they are clueless as far as infectious diseases are concerned and in this area I am deeply disappointed. In other areas they deserve a large amount of due credit for the excellent work they have done. The irony of this meeting was that Leo McKay, the Deputy Secretary of Veterans Affairs at the time, attended it. He was also a speaker. Here I am in the audience, muzzled by the VA, but here is another person from the VA totally free to speak. I felt that I had valuable information that could open awareness, discussion and debate, but was being suppressed by “another” VA with a fear of looking bad. I wondered if Leo McKay’s speech was peer-reviewed? One good thing, and I greatly respected him for this, is that he apologize to the PGVs on the VA’s previous insensitivity to their problems. Apparently this stayed in the room. Persian Gulf veterans at Mountain Home VAMC never got the word, and they truly merited this apology.
The following are quotes from published papers and textbooks concerning the difficulties of making a diagnosis of brucellosis:
How would brucellosis fits in context with other research?
1. RAC-GWVI infectious Disease Decision Reversal
On page 9 of the November 2008 RAC-GWVI report it states: “taken together, there is little clear evidence, implicating infectious diseases as prominent causes of Gulf War illness”. This should be disputed since the studies of brucellosis are threadbare to say the least. Page 189 (under: Other Infections in Theater) has one paragraph, and states there is “potential concern” and that “the extent to which veterans were tested for this infection in theater is not clear from available reports”. Yet, in the 2006 annual report to Congress it states that “there is no rationale to continue inclusion of infectious disease as an area of research that will provide answers to the causes or cure for these symptoms”. Also, the report states that “funded projects for infectious disease will be considered to be closed as of FY 2006”.
In my opinion this was a gross mistake. Because no one has published a study, then it doesn’t exist, so it is dropped? The door should be left open for Brucella as an infectious agent and a possible contributor to PGVs illnesses. This until proven otherwise.
2. A Brucellosis Study Panel
An independent panel consisting of the following should be appointed and dedicated only to the study of brucellosis and its possible relation to PGVs illnesses. It should have a mandate to solicit research to answer needed questions. Member should preferably be involved with or connected to Brucella studies. Members would include:
1. A molecular biologist familiar with Brucella DNA PCR testing
2. A serologist familiar with the multiple Brucella tests available here and especially in endemic countries.
3. A microbiologist and veterinarian active in Brucella research.
4. An open-minded Infectious Disease doctor.
5. A foreign doctor from an endemic countries, i.e. Kuwait, who works with brucellosis patients, to serve as a consultant.
NOTE: The American Society of Microbiology (ASM) could possibly help in recommending members.
3. A Historical Study
Again, how did the Brucella outbreak in Kuwait in 1988 correlate with the vaccination of 12,000 dairy cows and 350,000 sexually mature sheep and goats in 1992 after the influx of American troops into Kuwait and Iraq? Were American personnel involved in this vaccination program after the war and if yes, why? (See abstracts in attachments L). (Quantitative Journal of medicine 1988, 249:39-54)
4. Brucella Serology
The whole extent of serology testing for brucellosis; who, how many, what methods and what time frame needs to be answered. Test methods used may be compromised and negative results obtained may have been used to rule out brucellosis, especially in the chronic stage of GWI.
Persian Gulf veterans still sick should be offered empiric treatment by the VA for chronic brucellosis, if in fact they meet the criteria of symptoms, having been in an endemic area, had high risk exposures, such as environmental dust, association with animals, dead animals, barns, and consumed dairy products containing goat cheese, or other local products. Treatment by private physicians should be an option if denied by the VA. All treatments should follow World Health Organization (WHO) guidelines. Note: Do PGVs have more time to wait for another needed drug study? Empiric treatment should be an option for the Persian Gulf War veteran.
6. Another Drug Study
A drug study using doxycycline in combination with either rifampin, gentamicin, and streptomycin, or trimethoprim sulfate (TMP/SMX) plus gentamicin should be conducted. Another combination could be a fluoroquinolone plus rifampin. (The same guidelines used in the doxycyline study can be used).
7. DNA PCR testing and research is needed.
A dedicated lab should be used to perform PCR testing on new or historical clinical samples if available. A clinical sample repository for research would be helpful. This would have been most helpful in the past.
8. Chromotroph 2R (10X) Modified trichrome stain
Staining characteristics of Brucella melitensis with Chromotroph 2R should be evaluated. This was the stain used for Microsporidia.
9. VA Physician Awareness
The military history as taken by the Persian Gulf veteran’s physician (if taken at all) needs to record possible exposure and risk factors to brucellosis if indicated. All VA physicians in contact with PGVs should be aware and educated of the sequalae of possible Brucella exposure in PGVs who served in endemic areas. Persian Gulf veterans should be made aware that they may have possibly been exposed to this pathogen.
In the stools and other specimens tested, I strongly feel that we have located a biological marker unique to Persian Gulf veterans. Hundreds of hours of hands on microscopic work on hundreds of specimens and countless hours of literature review, many going down the wrong path, have contributed to the statements in this letter. Of the above statement I feel certain. The identity of this marker has not been proven beyond a reasonable doubt, but these observations led to the implication of brucellosis as this marker, most likely Brucella melitensis. Based on these observations, a long first step, further testing of this hypothesis is warranted and needed. This is what we are asking for, your consideration, through the proper channels, that this be investigated further. Another omission, I feel would be a another uncalled for mistake. Reiterating again the statement at the beginning of this letter from the RAC-GWVI 2008 report “...Abnormalities that underlie veteran’s systematic illness were unfamiliar and could not be detected by clinical tests routinely used to diagnose more familiar conditions.” This work may be a testimony to the statement.
On page 22 of the same report, it also states that “completing this mission, that is finding answers in treatment for ill Gulf War veterans, requires dedicated effort, cooperation between government officials, scientists, clinicians, and veterans.” Sadly, in my experience, working in the VA system, this was a tall order, with some time insurmountable obstacles thrown in your path, especially by government officials with an unwillingness for true communication and open discussion. I found out you can be an outstanding model employee as long as you were not working on Persian Gulf veteran’s. illness.
This letter, I need to emphasize, is mine only, but I would like to acknowledge those who’s unrewarded efforts were involved in this work. Dr. Alfred Bennett, former VA physician, Dr. George Youngberg VAMC pathologists and true mentor, Mary (Hillesland) Graves, social worker, now retired, employees in my lab, and a vital contributor who chooses to remain anonymous. Outside the VA, there were Katy Renfro, and Barbara Hollifield (deceased), two tireless workers for Persian Gulf veterans. Also an acknowledgment goes to those sadly deceased and living Persian Gulf veterans from Northeast Tennessee who supported and stood by my efforts in bad times, to seek the truth. This was my attempt, hurtful as it was.
Charles N. Gutierrez