http://www.livescience.com/health/worm-therapy-stimulates-gut-mucus-101201.html

http://www.baltimoresun.com/health/la-heb-worm-healing-20101201,0,2645483.story

http://discussions.latimes.com/20/lanews/la-heb-worm-healing-20101201/10

From Scientific American: http://www.scientificamerican.com/article.cfm?id=helminthic-therapy-mucus

For the Good of the Gut: Can Parasitic Worms Treat Autoimmune Diseases?

Helminths could suppress immune disorders by promoting healthy mucus production in the intestine

By Ferris Jabr December 1, 2010

In 2007, parasite immunologist P’ng Loke sat down for lunch at a University of California, San Francisco, cafeteria with an inquisitive man who had called him earlier that week. Their chosen topic of conversation would deprive many people of an appetite, but the scientist and his guest shared an intellectual hunger for a stomach-churning subject: gut worms—specifically, tiny worm-like parasitic organisms called helminths that live nestled in the gastrointestinal tracts of their hosts.

Loke was fully prepared to answer the man’s questions about the parasites he knew so well, but what he did not realize was that his companion had more than just questions—he had worms burrowed in his intestinal walls, worms he had deliberately swallowed. Together, Loke and the worm-wrangler embarked on a research project, the results of which appear today in the December 2010 issue of Science Translational Medicine.

The 35-year-old man who had lunch with Loke was quite healthy in 2007. But only a few years earlier he was in the throes of an inflammatory bowel disease known as ulcerative colitis. An autoimmune disease, ulcerative colitis inflames the colon and leaves it rife with open sores; patients experience intense abdominal pain, vomiting, diarrhea, rectal bleeding and weight loss. While searching for treatments, the man discovered the work of Joel Weinstock, a gastroenterologist, parasitologist and immunologist at Tufts University who has pioneered research on helminthic therapy—treating autoimmune diseases by deliberately infesting patients with parasitic worms, such as whipworm and hookworm.

The results of Loke’s new case study—the most recent of only five studies that investigate helminthic therapy in people instead of animals—suggest that helminths may ease the symptoms of autoimmune diseases by increasing mucus production.

“It’s a unique study—there’s nothing like it before,” says Weinstock, who was not involved in the new research. “In this case they had a very unique patient—one who was self-infecting with helminths.” Clinical trials on helminthic therapy are particularly difficult to arrange because helminths are live pathogens and have not been officially approved as therapeutic agents by any governmental agency, although the U.S. Food and Drug Administration has granted pig whipworm (Trichuris suis) the status of Investigational New Drug. In contrast to human whipworm (Trichuris trichiura), the porcine variety cannot survive inside the human gut for very long.

“The researchers noticed a specific pattern of behavior, cycling between remission and active disease depending on when the patient infected himself with helminths,” Weinstock adds. “This is not a double-blind study, but the pattern is highly suggestive that the worms helped this patient. The major point of this paper is the potential mechanism—mucus production—which has not been looked at properly before.”

The Might of Mucus

In the new study, Loke—who is now with New York University—analyzed the man’s medical records prior to 2007 and personally tracked the man’s health from 2007 onwards. In 2004 the man swallowed a vial of salty liquid brimming with 500 human whipworm eggs, which he obtained from a parasitologist in Thailand. Three months later, he slurped down another 1,000 eggs. The larvae hatched and matured within his gastrointestinal tract, burying their heads in the intestinal wall. By mid-2005, he was virtually symptom free and required no medical treatment for his colitis, except occasional anti-inflammatory drugs to suppress flare-ups. The nearly complete dismissal of colitis symptoms is especially striking because human whipworm infection can itself cause digestive problems, including diarrhea, abdominal pain, nausea, vomiting and, in extreme cases, rectal prolapse. Severe infections can also cause anemia and stunt the growth of children.

In 2008, the number of whipworm eggs in the man’s stool began to dwindle, dropping from more than 15,000 per gram to fewer than 7,000 per gram. As the eggs disappeared, the symptoms of colitis returned. So the man infected himself with another 2,000 whipworm eggs and, a few months later, his symptoms practically vanished once again. Repeated colonoscopies revealed that wherever worms colonized his colon, the symptoms of colitis were significantly reduced or nonexistent.

During the 2008 relapse, the researchers found that immune cells in tissues with active colitis produced large quantities of an inflammatory signaling molecule named interluekin-17 (IL-17), but very little IL-22, the latter of which has been linked to wound healing and mucus production. When worms recolonized the colon, however, immune cells began manufacturing much more IL-22. Blood profiling and genetic analysis further revealed that tissues in which helminths thrived increased carbohydrate metabolism—a prerequisite for mucus production.

“Ulcerative colitis is often associated with decreased mucus production and the worms seem to somehow restore mucus production, possibly by inducing a population of immune cells that make IL-22,” Loke says. “It’s possible the mucus serves as a defensive barrier between bacteria and the gut that prevents bacteria from causing inflammation and crossing over into other tissues.” Autoimmune diseases generally occur when the immune system overreacts to benign—and even beneficial—organisms living within the body. In the case of colitis, researchers suspect the reaction is directed toward the bacteria in the gut. Loke thinks that the human body may boost mucus production when it detects helminths as a defense against the parasites; for a patient with ulcerative colitis, the extra mucus may also help calm an excessively aggressive immune system.

“We saw an association with remission and immune cells that make IL-22, but we don’t know for sure if these immune cells are actually induced by worms,” Loke says. “You can’t tell with a sample size of one,” which is especially susceptible to the placebo effect. Still, Loke adds, “the results seems quite compelling, especially when you consider the background—all the animal studies and clinical trials that show worms can suppress colitis and other autoimmune disorders.”

Mounting Evidence

In fact, in numerous animal studies, helminth infestation has protected rodents against colitis, asthma, rheumatoid arthritis, food allergies and type 1 diabetes.

Researchers have conducted few human studies, but most have shown promise. In a clinical trial published in 2005 in the journal Gut, Weinstock asked 29 participants with Crohn’s disease (another autoimmune inflammatory bowel condition) to ingest 2,500 pig whipworm eggs every three weeks for six months. Twenty-three patients (79.3 percent) improved significantly, and 21 (72.4 percent) experienced remission. Both the researchers and participants, however, knew exactly what treatment they were receiving, which makes excluding a placebo effect impossible.

In a controlled clinical trial published in 2005 in Gastroenterology, Weinstock and his colleagues gave 52 participants with colitis 2,500 pig whipworm eggs or a placebo every two weeks for three months. Thirteen of the 29 patients (44.8 percent) who received whipworm eggs improved, compared with only four of the 23 participants (17.4 percent) who received the placebo.

Weinstock and his collaborators point to these trials as experimental evidence that fits a global pattern: immune disorders are much rarer in less developed countries where helminthic infestation is widespread than in industrialized countries where much smaller populations host helminths. The “old friends hypothesis” proposes that the human immune system cannot learn to regulate itself without exposure to common pathogens like helminths that have coevolved with people and that modern hygienic practices deprive people of this necessary exposure, possibly explaining the relatively higher and more recent prevalence of immune diseases in industrialized countries like the U.S.

Loke plans to continue researching helminthic therapy in people and in monkeys. “We are talking about doing a small trial of, say, 10 people and basically doing colonoscopies on them before and after giving them pig whipworm,” he says. Loke also mentions that colitis plagues many juvenile monkeys in primate research centers and that he has received a pilot grant to treat diseased monkeys with human whipworm, an as-yet-unpublished experiment that is already returning promising results.

“When I first sat down to lunch with the guy who called me and he started telling me his story, I was really quite skeptical,” Loke recalls. “But now I am completely changing my mind about helminthic therapy.”

I approached the registration and soon became known as the “hookworm woman!”

I met Dr. Sherman, and he informed me that he was going to change the schedule around a bit.  Because Dr. Pritchard wasn’t there to introduce the science and the whole helmitherapy concept, he moved the documentary “Parasites: A User’s Guide” first, followed by my talk afterwards, then a Q and A session.  I was only shaking minorly.

Biomonde sponsored the event, so I got a nice complementary bag.  I went up to the Biomonde crew and introduced myself, saying I had just purchased TSO from his company and had a terrible reaction.  After some confused interchange, he said that his Biomonde is different then the Ovamed Biomonde, and he is only involved in maggot therapy.

I loved being at a conference of leech, maggot, worm, fish, and bee therapists.  I have to say here that I have never met a more interesting group of people in one location.  Almost everyone I approached was kind, intelligent, and was working with a biotherapy that had been used for years, even centuries, but the general theme of the evening was trying to get FDA approval and medical acceptance for these therapies.  There was quite a crew of apitherapists, and I always love beekeepers.  I quickly became attached to what the other apitherapists described as “the man,” an older gentlemen who’s been keeping bees for over 50 years.  I’ll talk more about the bee people later.

Dr. Sherman was a very kind man with much humor, and I am still so appreciative that he allowed me to come and be a speaker at this event. Thursday started with a history of maggot therapy, and the story of Dr. William Baer who was a well-respected medical doctor in the 1930′s who discovered accidentally what healing properties maggots had for wounds.  He went on to cultivate the flies and designed little cages to put over the wounds, and methods to incubate the maggots cleanly so that they didn’t transfer bacteria from their intestinal tracks to the wound.  Fascinating man.

The next talk was on bacteriophage therapy, and this is something I knew nothing about and want to learn more.  Phages are basically viruses that attack bacteria.  They are more common then bacteria in the world, and have been used before antibiotics to attack and destroy bacteria.  When antibiotics were developed, research into phages plummeted in this country, but in Georgia and the Soviet Union, they continued to develop phages that targeted specific bacteria. As the development of antibiotics fell, the list of phages grew.  There are now phages that target bacteria that are antibiotic resistant, and they have unique phages for many bacteria.  There were photos of staph infections before and after (these are the kind of photos that you can’t help but look, but you WANT to turn away.)  They are now experimenting with phages for cystic fibrosis, staph, klebsiella, the list is so long, it makes you wonder why the hell they are not using phages in this country.  There are virtually no side effects, and when the bacterial population is gone, the phages are gone as well.  (This is a horrifyingly simple explanation of bacteriophage therapy, I’ll try to post reputable links when I have time to research it more.)

A periodontist from Georgia showed how they are using phages for periodontal disease.  The before and after pictures were impressive.   I asked Dr Elizabeth Kutter if phages could be used for IBD, since we know that our gut flora is often out of balance, and she said they use phages for infant diarrhea in Georgia, but of course research specifically for IBD is lacking.

This might be a nice compliment to helmitherapy, since the phages do not act like antibiotics; they only target one specific bacteria, and leave the rest behind, and they take bacterial samples beforehand so they can know what bacteria to target, what phages to use.  I’m going to look into it further, since I feel my colonic bacteria are so out of balance, and it’s hard to control it with diet and probiotics alone.  (and worms)

Next we had a little break, then Sharon Shattuck’s documentary.  After the very scientifically heavy presentations, it was a lighthearted change.  The lighting was suboptimal, but the audience reaction *seemed* to be positive.  There was much murmering in the audience when it was said that the worms were considered a drug.  No applause afterwards, just a hush.

Then it was my turn.

Dr. Sherman introduced me as a patient of helmitherapy, and a reminder to the researchers why they were doing what they were.  I went up and gave my talk.  I had good audience reaction; lots of sensitivity over the horrors of Crohn’s.  When I went through my medical options (Humira, methotrexate), there were murmurs.  The before and after CRP and ESR got some reactions, and most of my jokes were laughed at.  I felt it went very well, I delivered it without messing up, I added some off-the cuff humor, and finally wrapped it up with my urgent questions.  I was feeling victorious.

Until the Q & A began.

Dr. Sherman put my slide with my questions back up, (#46) and invited the audience to help answer them.  A doctor stood up immediately and started a long comment that made my heart fall as he went on.  His first point was my blood tests were meaningless.  Without colonoscopy tissue samples, my case was anectodal (which I said in my talk), and stories like mine and the video hurt the science.  He, as a doctor, could not use a therapy that lacked the case studies, or the proper FDA approved studies that proved efficacy.  Even if they knew it worked (he’s a bee venom therapist who’s been trying to work with the FDA for over 25 years).

It was the very thing I feared standing up in front of a group of researchers and doctors, and knowing that I hadn’t done a colonoscopy when times were good…that I was only an anecdotal case.  As he went on, you could sense a change in the audience, and I was feeling like everything I went up there for had failed.

He sat down finally, and another doctor popped up (later found out he was a pain management specialist and he gave an excellent talk on the merits of bee venom therapy for pain), and said that I didn’t have to prove anything, and reminded me that I only needed to take care of myself.  People applauded.

Then one of the phage researchers from Georgia very kindly asked me why I didn’t do the damn colonoscopy, and I answered that at the time I was trying to see how long my worms would last, I didn’t know what the prep would do to the worms, and I traditionally have violent reactions to the prep, resulting in a CD flare-up. He asked if there was proof of the hygiene hypothesis, and I responded that I wished Dr. Pritchard were here, but yes, there was a lot of proof, one study in Africa showed that after deworming, the schoolchildren developed dust mite allergies for the first time.

Then an old, distinguished man with a British accent stood up and said he had worked as a doctor in Nairobi many, many years ago, and they had over 25,000 patients.  During that time, there was not one single case of IBD.  Later, he lived and worked in Rwanda, and they were switching to a Western lifestyle. Over the years, the cases of appendicitis became their #1 operation, whereas before, there had been few to none.  So in his experience, he had seen the hygiene hypothesis firsthand, and I felt like applauding.

One MD asked if the worms caused any havoc, couldn’t one just take an anti-helmithic, making this therapy very safe in that the worms could be killed off in a matter of days?  I answered that yes, just a 2 day course of mebendezole should kill the worms.

Another woman suggested I try contacting the various gastroenterology boards, but I answered that the fellow who worked with Dr. Terdiman at UCSF, when I had my remarkable remission the first 4 months after trying hookworms, tried to write an article for the CCFA, but it was rejected.  But yes, I thought that the various auto-immune associations perhaps could come together and help fund more studies since the worms could work for many autoimmune diseases.  Another person said I was very, very brave to come up in front of this audience and speak, and they were very appreciative of my efforts.

And that was the end of our time, so we broke.

The first man who argued I was hurting the science came up afterwards and presented a long theory about chronic illness, involving stress, the mind, exercise, and disease.  Some good suggestions.

The people who walked up to me after him overwhelmingly thanked me for my talk.  (Of course, I didn’t hear from the ones who disagreed. )  Most were interested in helmitherapy and wanted to learn more.  One MD has 2 MS patients who were interested in trying this, and had written down the MS study that I had shown.  We talked about side effects, about the two severe CD patients I knew who were hospitalized for their reaction to 20 and 25 hookworms.  (Earlier the pain management specialist jokingly told me that he hospitalizes his patients all the time, that even his FDA approved therapies can be dangerous, the worms are like any drug in that respect.)

There were several people who had someone close to them suffering from CD, and wanted to know if they could contact me for support.  Another wanted to contact my husband for support, for advice to the spouse who has to live with a sick loved one.  One CD woman was told she shouldn’t have children because she’s had 5 bowel surgeries, and could she talk to me?  It just reminds me how my stubborness has gotten me far.  (I was told when I was 23 to go on methotrexate and I shouldn’t have children.  I went on SCD instead and had two wonderful girls when I was 25 and 29, and though it’s been really hard, and it’s no fun to have bloody diarrhea when you are nursing an infant, I feel so blessed that I’ve been able to conceive and raise a family with this wretched disease.)

And then I got swarmed by the bee people.

Bee venom therapy does much the same T cell switch as helmitherapy, it turns out.  And many of the apitherapists had used propolis (what the bees use to line their hives to keep out viruses, fungi, bacteria) to great effect for CD.  I heard about patients on 10 medications reduce their medicines to none after using propolis and bee venom therapy.  They felt that my worm experience had been too hard, and they knew what the bees could do.   Fascinating, lively people.  I have heard somewhere that bee keepers live long lives, and hearing the apitherapy lectures on Saturday now suggests why; bee stings, propolis, pollen, all have anti-aging properties, immune modulating modalities, high nutrition, antibiotic, antifungal, antiviral…I’m inspired to use honey for certain wounds, the before and after photos were so impressive.  I have a hive in the backyard, though the bees left months ago, but in the spring, I will be getting several hives and hopefully in another 5-10 years I’ll be joining the bee people in a little bit of knowledge.

Dr. Sherman felt that it was a very important thing I did; not to feel discouraged by the doctor in the Q and A, but that here we planted a seed.  And he reminded me about his work with maggots, (and he’s been at this for over 25 years), how he had to design a special trial that met with the FDA guidelines, but couldn’t be double blind.  (Because, what’s a maggot placebo?)  In other words, we must carry on.

The dinner ended, I thanked him for this opportunity, and we went back to my sister’s house, only to get up early and begin day 2 of the worm weekend.

Friday, my husband and I drove to Tijuana and I got infected with 10 more hookworms, and my darling husband got 25, through wormtherapy.  There is nothing seriously wrong with Karsten, except that he has high cholesterol, and is 30 pounds overweight.  Metabolic syndrome may respond to hookworm therapy.  This also gives all of us experimenting with hookworms  a “normal” baseline, since how many people are doing this who aren’t desperate or suffering from some disease?  You can be assured that we will be doing egg counts on my husband, and I might create a separate “husband’s corner” on this blog, so people can follow his progress.  I think it’s almost more powerful that he would be willing to do this.  One of my husband’s friends thought it was the greatest act of love that he had ever encountered, and we joke about what my poor husband was getting into marrying me….in sickness and in health, in hookworm infection ’til us part.  But I digress.

I got to hang out with Dr. Llamas for a few hours.  I love Dr. Llamas.  He massages you, laughs with you, is totally encouraging.  “You worry too much.  Let me worry for you,” he says, and though I try to follow his advice, I don’t succeed usually, especially as I’ve adopted this role as “worm activist”.  It’s so nice to have a warmhearted doctor to comfort you when needed.

Karsten got his lecture on fish oil, diet, and exercise, how to prepare beans (you want them whole, not mashed and broken up like Karsten’s been doing; the increased fiber helps attach to the cholesterol), and Garin gave Karsten a huge amount of exercise advice. He recommended an app for his new phone that measures caloric intake, how much you expend with walking (it includes stride length).  Karsten’s been walking up hills for an hour each morning since, and is much inspired by his little phone application.  Though it won’t be solely the worms that help, I still think the act of getting infected and having a coach is what he’s needed to make the changes for his health.  We’re inspired.

We drove to TJ and back, got our worms, and finally made it through traffic to return to my sister’s house by 9 PM.  We put our beautiful girls to bed (they had been taken to Universal Studios that day by my mother, so were full of their own happiness), and day 2 was done.

Absolutely no “hookworm high”, darn it.  I feel nothing but an itch.

I woke up the next day early, and reading the program realized that the apitherapy lectures were that morning, so Karsten and I went back to the conference.  I was a little late, but got to hear most of the apitherapist lectures, including the one by Dr. Kim, who had criticized my lack of science.  Listening to what he’s been through over the last 30 years makes me realize where he’s coming from.  He’s a Korean doctor who has a history in acupuncture, who’s been using bee venom therapy for years on acupuncture points.  However, he’s also been doing all of the studies that the FDA requires; the animal studies, proving venom is safe with the most common 25 prescribed drugs in the US, the list is so long what he’s had to go through, and finally the double blind studies are being done.  The merits of bee venom are vast, and he showed many horrific slides of various diseases, from RA to rashes, where the bee venom therapy helped.  The most interesting thing for me was that they use bee venom on acupuncture points; depending on whether you are treating MS or RA or pain, they use different points to bring it to the nerves, the spine, etc.

The older gentlemen who had seen the hygiene hypothesis in action lectured on the history and many uses of apitherapy, including some impressive properties of bee pollen and propolis.  He described how they can minimize pain with the bee venom therapy, by using one bee sack but stinging many locations with it.  If helmitherapy stops working, I think I may move on to the bees…

I decided not to attend the workshops on Sunday, since all the helmitherapy workshop was going to be was another viewing of the film: Parasites: A User’s Guide.  I also had made contact with all of the people that mattered to me, and I was becoming exhausted from my travels, so just wanted to get home.

I thanked Dr. Sherman again, I got phone numbers for the bee people and the phage therapy MD’s, and left.

I would say it was a success.  Seeds were planted, much information was exchanged.  I met so many interesting people.  Like I mentioned in the beginning, this was a very colorful collection of people, all working with living organisms, all having to fight for FDA approval, medical acceptance, all knowing what merits each of their therapies offer, and trying to get their therapies the attention they deserved.

I would have to pick bacteriophage therapy as the most exciting of the group.  These phages treat cholera, staph, cystic fibrosis, the lists of bacterial infections are so long, it makes you wonder why the hell this is not being more researched in this country with all of the c. difficile cases rising, the antibiotic resistant staph infections.

I did not attend the ichthyotherapy workshop (using little fish to eat psoriasis), nor the leech and maggot lectures, nor the dogs who can sniff out cancer and diabetes.  (Fascinating, but it must be hard to be sniffed.)

I think I did a good job of providing a voice to the patient’s side.  I tried to be conservative looking, well spoken, intelligent, cautious.  I think more than anything people appreciated a patient going up before a very prestigious group of researchers, presenting a 30+ minute lecture with slides, and daring to take the criticism from the researchers.  I hope that I represented all of the patients adequately, and helped helmitherapy move forward a bit in people’s attention.  I wish more helmitherapy patients had attended, it’s hard being one of the few who’s active and willing to be interviewed and step out of my comfort zone.  But I think helmintherapy has so much merit, we’re just in the early days.  (But c’mon helminth users out there, stand next to me next time!)

Hopefully my presence helped a bit.  I just wish Dr. Pritchard were there.

They took videos, but I’m uncertain if they will be available publicly, or only to BTER members.  But if the latter, it’s very inexpensive to become a member, and I encourage all of you helmintherapy users to do so.  We need all the legitimacy and help we can get.

I left the conference to an early Thanksgiving with my family, and we celebrated my worm-filled weekend with cranberry sauce and pumpkin pie (crustless, made with honey and coconut milk; I’m back on SCD).

All in all, a fruitful weekend, very full. Thank God I had the health to do all of this.  We’ll see what the new worms bring me.   I think it was a success.

http://openetherpad.org/deborawade-bter-slides

My talk:  (numbers in parentheses are the slides)
(1)My name is Debora Wade and I have had Crohn’s disease for over 20 years.  Since December of 2007 I have been experimenting with helmitherapy.  In other words, (2)I have approximately 15 of these hookworms living in my small intestine as I speak.

(3)Crohn’s disease, is an auto-immune disorder that primarily effects the digestive track.    Right now 1.5 million people in the United States alone suffer from Inflammatory Bowel Disease which includes ulcerative colitis.  It is one of the many autoimmune diseases that is becoming an epidemic.  According to the American Autoimmune Related Diseases Association, Approximately 50 million Americans, 20 percent of the population or one in five people, now suffer from allergies and autoimmune diseases.

As diseases go, Crohn’s Disease is one of the more miserable.  The immune system attacks the digestive wall, causing severe inflammation.  This can result in a host of complications.  Surgery to remove portions of diseased bowel is common.   Symptoms range from minor to severe, these can include pain, bloody diarrhea, fistulas, strictures, abscesses. I have moderately severe ileal-colonic Crohn’s disease. I was diagnosed when I was 16 years old, I’m currently 38.   I’ve already had my descending colon removed and resected.  I’m trying to avoid another surgery, but statistically my chances are grim.

In late 2007, I reached the place that every patient with a chronic, incurable disease fears:  I ran out of good medical options. (4) I had failed the  biologic medication Humira, (or adalimumab).   Humira tripled my inflammation and made my symptoms 3 X worse.  It also can cause a fourfold increase in certain cancers, or life threatening infections, part of the ever present risk to benefit ratio we patients must choose every day.

At this time, I was 137 pounds.  (I’m currently 155 pounds, so I was very underweight.)  I had bloody diarrhea over 10 X a day.  I was anemic,  weak,  house bound, unable to work.  I could tolerate about 5-10 blended foods. I was in severe pain.  I had low grade fever, night sweats, and on no medication, because even steroids had failed to work.

All that was left to try was (5)methotrexate, a chemotherapy drug, or the two drug trials at UCSF, but because I had failed Humira, I needed to wait 90 days to qualify.

So I started to research other options.

(6)I had read about the University of Iowa trials in 2004 with pig whipworm ova, trichuris suis ova or TSO.  Dr. Weinstock had done several small studies showing that TSO was effective and safe for IBD.    So I asked my doctor if he approved of TSO therapy.  He would, and I went to order the ova.

(7)I found the company Ovamed, an online order form.  It cost 300 euros a dose, which is currently about $420 and you have to drink the eggs every 2 weeks.  IF it worked, this therapy, which is not covered by insurance, would cost me over $10,000 a year.  I couldn’t work, we were financially on the edge.  But I thought I’d give it a few months’ try. If it worked, I’d figure out how to pay for it later. (8)  But the FDA had temporarily blocked importation of the organism, citing one case of a patient where a mature worm was found in his colon, so I couldn’t get any TSO.

I started reading about the hygiene hypothesis, which is also called the Old Friends’ Hypothesis, or now the Depleted Microbiome Theory, and found many intriguing studies. (9) Helminths and harmony  (10)Parasitic worms and inflammatory diseases. (11) Inhibition of autoimmune type 1 diabetes. (12) Association between parasitic infection and immune response in MS,    (13)Does the failure to acquire helminthic parasites predispose us to Crohn’s disease?  Articles were pouring in, all hypothesizing that worms were a natural part of our microbiome,  part of the development of the human immune system, and because we had, for the first time in human history, lost our symbiotes, our bodies were responding with inflammatory diseases like never before.

The research was overwhelming, but I couldn’t get any worms. <5 minutes>

(14)I found a dose ranging trial with necator americanus and CD patients in Australia.  I started reading about Dr. Pritchard’s work.  At the U. of Nottingham he had completed a safety trial, an allergy trial, and an asthma trial, and had just begun a (15)Crohn’s disease trial testing the efficacy of 10 Necator Americanus for 3 months, and I asked if I could join.   It turned out I could participate as an American, but I had to visit Nottingham 6 times over  3 months, and as it was a placebo controlled trial, I had 50% chance of getting nothing.  I really wanted to  join that trial, but I was too sick to fly, let alone 6 times from California.  If it weren’t a placebo trial, or I were  guaranteed to get the worms, I would have done it.  But I put aside my opportunity to participate in helminth research, and I kept looking for worms.

(16) I found a private company selling hookworm larvae online.   I contacted the provider, Jasper Lawrence, to get more information.  Strangely, he lived in my hometown, and I thought of all the places in the world, what an odd coincidence that there would be a hookworm provider who lived just a few miles away.    But he only offered the infection in Tijuana, so I’d have to travel across the border to get my  hookworms, and pay an enormous amount of money for them.  But it was less money than 1 year on TSO.

I talked to Jasper Lawrence.  I  asked a lot of questions.  Since  the organism went through the skin and I couldn’t find much evidence of coinfection amongst hookworms,  I figured at the very worst I would get an empty band-aid, but since Jasper lived in my town, I thought I could always knock on his door and demand my money back.

(17)So I went to Mexico.  For the very first time.  I grew up in LA, and I had many opportunities to cross the border, but I’ve had Crohn’s disease since I was 16, so the irony is I never went to Mexico for fear of catching parasites.

I met Jasper Lawrence.  I met Dr. Llamas who he was working with at the time.   I asked for 10 hookworms to mimic the Nottingham trial.   I felt the sensation of the worms going into the skin.  (You feel a sensation of tiny fingers drumming against your skin, then all I can describe it is like tiny worms burrowing into your skin.)  I got my $7,800  band-aid, which to be fair, included 3 infections total.   I drove home.  It was December 17th, 2007 and this was my Christmas present to myself.

As a patient putting parasites into my skin, I am often told that I am very, very brave. People wonder how I could possibly stand to have hookworms enter my body and live in my intestines.

I always answer that the drugs used for my condition require much more courage.  I almost died from neutropenia (which is a reduction of white blood cells) caused by a standard drug used for Crohn’s disease, 6mercaptopurine.   The drug Remicade, or infliximab, is delivered via IV often in your local hospital infusion ward.  Receiving this medication, surrounded by chemotherapy patients, knowing the medicine itself can cause a fourfold increase in lymphoma, is very frightening.   A few hookworms seem like nothing compared to the risks we take with our medical choices everyday.

My arm itched a little, but not badly. (18) I had a single red dot for a rash.  I had read about the intensive itch that hookworms could cause, so this was very anti-climatic.

Day 3 I came down with a 100.3 fever.  My diarrhea increased from about 7 X a night over 15-20 X  a day.  I had no idea if I had just picked up a bug on the way to and from Tijuana, if it was the hookworms.   I had no one to ask advice from.   My doctor was unsupportive of trying hookworms, besides the too little evidence, he reminded me that I had no idea what I was getting in Tijuana.  I had been the one to inform him of their current use in research,  so I simply took lots of Immodium, probiotics, and I waited.

<10 minutes>By week 3, my ankles started to swell.    They soon grew so painful, I could barely walk.  I went to my doctor and he diagnosed them as arthritis and edema.   so I suspected the hookworms, but no one could be sure. I almost took an anti-parasitic medication, because at this point the arthritis spread to all joints.

But my bowel pain also began to recede.   By week 6 things started to improve, by week 9 my ankles were normal and the arthritis had gone.    I started getting an enormous appetite, and it I carefully introduced one food at a time.

By month 4 I had gained 20 pounds, I had added over 30 new foods, I had no bowel pain, and I was going to the bathroom about 3-4 X a day.  My skin was clearer, I had no more rectal bleeding.  People who hadn’t seen me for a while said I looked better then I had ever looked before.

(19)I took a blood test before introduction of the worms and at 16 weeks.  During this time I was on no medication.  Before, my ESR and CRP (two blood markers of inflammation) were 31, normal being less then 20 and 5.4, normal being <0.8.  (20)At month 4, these numbers came down to 7 and 0.9 respectively.  I visited Dr. Terdiman at UCSF, we compared the numbers, he weighed me, palpitated my abdomen,  it was soft. We determined the great hookworm experiment a triumph! (21)   I had at last found something that worked, was natural, I’d gone through the side effects, and I would live happily ever after!

But I made a terrible mistake.  At the time, the trials using 10 hookworms seemed to be chosen with safety in mind, rather than the best number for efficacy, and there was much debate among those of us experimenting with worms, as to the number of organisms necessary to elicit an immunological response.  So I thought I’d increase my population by adding worms in 2′s and 3′s, weekly or biweekly.  I added 25 more worms to the original 10 for a total of 35 worms over a 6 week period and soon after my wonderful blood test, I began to regress.

(22) I found a study that showed that two healthy volunteers with an established hookworm infection, when adding more hookworms, ended up with the same number they started with, documented with pill cameras that they swallowed.  I started wondering if adding worms so frequently had caused my immune system to reject some of the new worms, or perhaps I lost some of the  initial 10 worms, leaving me with not enough to sustain benefit.

I thought I could find a lab to do an egg count for me.  I tried UCSF, then Quest lab, Stanford, UC Davis, no one could help me.  All labs would do a standard O&P, but no one would do an egg count.

Meanwhile, my symptoms were progressively getting worse, I was losing tolerance to the foods I had added, I was losing weight again.  Months were passing, and I didn’t know if I still had hookworms, if so how many, if I was a treatment failure because I lost my worms or because I had added too many too soon.

Finally, in December of 2008  3 O&P’s came back negative, and I figured the hookworms were dead.

But I had had such an initial positive reaction to those 10 hookworms,  I thought before I threw in the towel, I’d try one single dose of 10 more and wait and see what happened.  So I got 10 more hookworms on February 2 of 2009.  This time they caused more of an itch, more of a rash.  I felt an initial elation for the first few days after infection, which many patients describe.  I took a before blood test, and I waited.

I had fleeting joint pain.  No edema.  No fever, and a little diarrhea, some fatigue. (23) By the 4th week, my CRP and ESR had returned to normal. (24) I got hungry.  I started sampling new foods.  I tolerated wheat.  I was in food heaven.

I kept a blog to document my effects. (25)   (26)There’s a Yahoo forum where other patients write about their progress. I heard from many patients with all sorts of autoimmune diseases who were reversing their symptoms with a small number of hookworms.   A patient with Sjogernes syndrome had recovered moisture in his mucus membranes.  Reports of allergies, asthma, MS cessation came in. I personally had a friend with CD dramatically improve.   It was a very exciting time.  (27)  CBS San Francisco contacted me and  I did an interview for them.  Here I am  in my backyard lamenting the lack of research into helmintherapy in the US.  (28)Here’s my gastroentrologist, Dr. Terdiman, who remember hadn’t heard of the use of hookworms in 2007, now supporting the theory, if not the practice of helmintherapy. <15 minutes>

(29)And here’s  Dr. Homer Boushey, Chief of Division of Allergy and Immunology at UCSF saying quote:

” Of course, ideally I’d like to see us figure out what part of the hookworms is responsible for this benefit, so we could develop a therapy we could give without having actually to infect people with a parasite that does, after all, cause problems.”

Let me interject here by saying that although I am glad research into worm products that mimic the effect of the live worm are underway, and are needed, we all must realize that many patients can’t afford to wait the amount of time it will take to develop these drugs.   And we are more then happy to experiment with the live worm in the meantime.

And what problems do hookworms cause? Anemia?  I realize in the third world they can be devestating, especially to developing children.   What are the numbers necessary to cause anemia, and since we can control the hookworm population,  (they do not reproduce in side of the body), isn’t this a side effect we can manage with adequate nutrition or iron supplements?    Whereas our other drug choices cause considerably more side effects, many more dangerous then merely anemia.  I want to remind doctors and researchers of this: the live worm is still far safer to experiment with then most things we have to try.

But back to my story.  It was a very exciting time.  I was able to ride my bike.  I played with my girls. I had energy, I looked healthy.  I reached 165 pounds.

But because I had lost my worms the first year and didn’t know how or why, I was more determined than ever to quantify my worm burden. Because I could find no laboratory to do them for me, (30) I went on the internet and found a tutorial on McMaster egg counting. I figured out all of the equipment I needed.  I borrowed a microscope.  And one morning, I did my first McMaster egg count!

(31) It was fun identifying the hookworm eggs under the microscope.     I started measuring eggs per gram every month, and as I was already taking monthly blood tests to assess my inflammatory levels,  this was the way I tracked my population all last year.

Unfortunately, I never did a colonoscopy at this time, which would have most likely shown the dramatic benefits I experienced from helmitherapy.

The good times lasted about 6 months.  And then the pain in my ileal-cecal region started to rise.  I began to have more reactions to some of the foods I was eating.  My stools were becoming more frequent.    So I decided to add 10 more worms and see what would happen.

10 more hookworms on September 26th, 2009.   The lift, (32)the rash, the temporary digestive worsening and fleeting ankle pain until about week 6, when this cohort matured. The interesting thing for me is my egg count doubled, showing that the new worms didn’t necessarily displace the resident worms, and perhaps I had added to my population.

My inflammation stayed normal for another 6 months, and my egg count started to decline, which brings us to March of 2010.   Jasper Lawrence had been raided by the FDA, and fled the country with his wife and his worms.  None of us could get access to the worms for a while and it started to become clear that outside of the research setting, we really had few legal rights.

There is a lot of confusion right now amongst those of us experimenting with worms, what we are allowed to do at home regarding egg counts or incubation and self infection, since legally the worms are only available in the study setting, and are classified by the FDA as biologics.  For those of us who receive worms either in the wild, or through a private company, are we allowed to incubate the worms and infect ourselves in the US? What rights as patients do we have with these parasitic organisms? (33) A new wiki site has been formed to help the “underground worm community” collate this information.  It’s an interesting problem that occurs when people are using infectious organisms to control their disease.  <20 minutes>

The legal way to get helminths is to participate in one of the current trials.  But there are few helminth studies available.  If you have MS (34), there’s currently a study with 20 patients testing TSO.  (35)There’s  a TSO trial for 18 people with peanut allergies  (36) There is a third TSO trial for 10 adult patients with autism here in the US.  For hookworms,  a celiac trial has been completed in Australia, hopefully that will lead to more studies there, and there will be a (37)MS study in Nottingham, England.

You can order TSO now and get it shipped to your door, at 300 euro a vial.
There are 3 other commercial companies selling worms, (38)AIT, which ships hookworms or human whipworms anywhere outside of the US.  (39) wormtherapy, which requires going to Tijuana to get infected if you live in America, and (40) Immunologica, a company in Spain selling hookworms, but who knows how long these companies will be allowed to stay in business?  And of course, you could always go to the tropics and get the worms yourself.

But back to March, April, May. My inflammation started to rise.   My egg count steadily declined.   I considered switching to TSO since it was currently available, but I was back to the enormous expense.   I finally ended up buying new hookworms through the other commercial company, wormtherapy, with Garin Aglietti and Dr. George Llamas, who I met when I first worked with Jasper Lawrence.   Back to Mexico. June 2010.  This time I tried 15 hookworms.

I had done an MRenterography two days before I went, and at this point, I was down to 50 epg at best, and the sigmoid colon was very inflamed, with a complex fistula going from my sigmoid colon to my right ovary.   But I was hopeful that the new worms would  make things right, and it was the longest I had gone before reinfecting  So I  payed  $2,200, got my hookworms, drove back home.

(41)I got my worst rash yet.  Here it is 24 hours later,(42) 48 hours.

The new worms hit my gut at around 3 weeks, and things got very bad.  I started having abdominal pain, increased diarrhea.  Finally after 2 weeks of this I decided to go on Prednisone, a systemic steroid that dampens the inflammatory cascade.   Finally, at week 9, my egg count shot up to about 500-750 epg, I started feeling better, and I was almost weaned off the Prednisone.

But this is where I made another terrible mistake.   Because I’ve had surgery,  knew about the fistula, and I was hearing excellent reports of colonic improvement with trichuris trichuria,   I thought perhaps if I added the safer TSO to the hookworms, I would have a better effect than just hookworms alone.

So I payed another $4000 and bought 7 vials of 2500 trichuris suis ova.  It wasn’t blocked importation, and the box came to my door.  The box was very interesting.  “A Pearl of Nature for Immune Therapy”.

I drank my first vial (8 weeks) after getting the 15 hookworms.  The liquid tastes slightly salty.
I felt a little queasy for a few days, and my bowel symptoms worsened.  I waited 2 more weeks.  And drank another vial.

This time, I had diarrhea the next few days, a lot of colonic pain, and a low grade fever.  But my daughter had the flu.  So I wasn’t sure what was what.

I tried one more TSO dose 3 weeks later.  The third dose was thoroughly rejected.  I had explosive diarrhea for days, another low grade fever.  My abdominal pain became severe, I  started having night sweats.  I finally went back on Prednisone, this time at a higher dose to control the symptoms.  I checked my egg count after a few weeks, and the hookworms survived the onslought,  but the egg count seems to have fallen a little bit, so I may have lost a few worms to my response.

Why did I react so badly to TSO?  Was the combination of hookworms and pig whipworms? Did I introduce TSO too soon after  the hookworms? Was it too high a dose?  Is there a bacteria in my gut that was activated by the presence of the whipworms?   I don’t know, but that’s the end of the TSO experiment.

(43)That was 6 weeks ago.  I still haven’t fully recovered. It was very hard coming here today and giving this talk,  besides having difficulty in traveling with digestive symptoms, I wish I could have come as a stunning success story, like last year.  I’m now up several times a night to use the bathroom. I have some rectal bleeding, some pain, loose stools.  I lost 10 pounds in 2 weeks after that third TSO dosage.  I am no where near where I was earlier this year, but I’m still hopeful.

Am I a failed helmintherapy patient?  Or have I demonstrated remarkable efficacy for a relatively small amount of worms? Should I stick with hookworms or give up and go back to traditional drug therapy?   Should I do them both combined?    Should I try trichuris trichuria?

I have 3 new drug options now that I didn’t have before.  All biologics.  One in the same class as the last one I failed.  There’s a new drug approved for psoriasis but it’s being used off label for CD, so there are not much data on it.  My last option, Tysabri, or natalizumab has a 1 in 1000 chance of (PLM) a rare infection of the brain that cannot be treated, prevented, or cured and that usually causes death.  And of course, there’s always methotrexate.

I’m crossing the border tomorrow, going to Tijuana to get 10 more hookworms.  If these next hookworms fail to bring me back into remission in the next few months, or if I get considerably worse in the meantime, I will try the next drugs, and hope for the best.

This journey has been a great adventure.   For better or for worse, I am a voice for all the patients out there who want to get worms safely, who want to participate in worm research.

If I can do anything to influence you, I urge you to help us patients connect with you researchers and our doctors, so together we can prove or disprove the hygiene hypothesis quickly.  The research is going much too slowly, we will lose our colons, or  forever be confined to a wheelchair if we wait for all of the proper studies to be carried out, especially if we have to wait for a pharmaceutically derived worm product.  We are willing to be case studies right now, to do before and after testing.  We want to help educate our doctors and experiment with what is so much safer then most of the remedies they have to offer. We have thousands of years of co-evolution with these worms, hosting them is not as dangerous as the diseases we are trying to treat left unabated. We have money to donate to research, but we don’t have the collective organization needed to unite the 1 in 5 Americans currently suffering who may benefit from this therapy .

(44)There was an article online recently  in a journal called the Evolution and Medicine Review.  “Reconstituting the Depleted Microbiome to Prevent Immune Disorders”  and from this article I’ll read  a few paragraphs that I think most eloquently represent the urgency that  patients  feel about the slow pace of research into this remarkable field:

(45)”We as immunologists are now faced with the unsettling realization that the immune system we have spent all of our effort and energy studying over in the past fifty years has turned out to be dramatically different than the system derived by natural selection. We find that “normal” is not helminth-free, and that our co-evolutionary partners must be included if we want to address the “normal” state of things. From a medical perspective, it is difficult to imagine that we will be able to restore the immune system to normal using a pharmaceutical that is directed at one cog in the immune apparatus, when in fact the entire apparatus is entirely out of sync with nature.  Pharmaceuticals do not effectively recapitulate biology derived by hundreds of millions of years of natural selection.
At present, we need to direct intensive research toward biome reconstitution. We need to know which organisms to utilize, and when and how to utilize them… We need to know the effects of biome reconstitution not only on one generation, but on subsequent generations.  In short, we need to know how to reconstitute our biome and keep that biome healthy. It is time for a paradigm shift in the enterprise of biomedical research and subsequently of medicine. Our evolution and our resulting biology require it.”
I should not have to be traveling to Tijuana to get infected with hookworms.  I should not be doing my own egg counts. I should not be worried about my legal rights if I wish to self infect.  I should not be paying thousands of dollars for some larvae.  I should not have to wait years for this research on the depleted Micribiome theory to be proven.  I should not have to wait for a pharmaceutically derived worm product, when the worms themselves are available now.

(46)What can we do to make this easier for all of us?  How can we influence helminthic research?  How can we unite the various autoimmune communitites together? How can we start repleting the microbiome?  How can we educate and convince the medical establishment to support us in our experimentation?    Would more case studies be beneficial?   Is there a way we can help fund the research?    Can we share the information that we’re gathering? Is it possible to create a public database so that those of us experimenting with the worms outside of the research trials could have a place to collate our side effects, our blood tests, our MRI’s, our colonoscopies,  whatever proof we have of the worms effects’.   There are over 200 patients trying this right now, how can we let our data go to waste?  How can we make worms safely available?

There are still so many unanswered questions. I realize we are at the forefront of all of this.  I was once told that I was in uncharted immunological territory.  I realize the limitations that researchers and doctors find themselves in, and we have to work under the guidelines of the FDA, of standard medical practice.  But this is a worm.  And if we are meant to be parasitized with a small number of these worms, we have to figure out a way to make them available before the years if not decades that our standard research and medical system will take to prove their effects.

I am only one patient of helmintherapy.   I’ve experimented far more than the average patient.  I’m the only patient I know of who’s doing egg counts, and I may be doing them wrong.  I’ve used 3 out of 4 of the commercial providers. I regret not participating in the trials, but the stakes were too high. A small amount of hookworms have seemed to give me remarkable results, for about six months’ time. And I admit that CD can be a waxing and waning disease, so since I did not get my tissue or blood analysed immunologically, my case is an anectdotal  at best.  However, I’ve had gains from the hookworms, like being at the heighest weight ever in my entire history of Crohn’s disease, and tolerating foods I could not eat in the past, even when on Remicade or the best drugs that exist for CD, so though I cannot prove to you the benefits I’ve gotten from hookworms, I know my body and I’m all too familiar with my disease, and I’ve experienced what the hookworms can do.  Like all patients with an incurable, life-threatening autoimmune disease, I am desperate for a therapy that is safe, natural, and works, and I feel that I’ve found one that is at least partially effective for reversing my Crohn’s.  I’m still ironing out the species, dosage and other details, but I do still have hope.

I can’t tell you if helmintherapy is going to be successful for me in the longterm, or if I’ll have to abandon it and try the next conventional drugs. I’m only 3 years into this…I’ll get to show you all my rash on Sunday if I have one.  But I will have to wait several months to see if the worms are effective again in bringing my inflammation back to normal, if I’m able to taper off of Prednisone without ill effect, if the hookworms alone will be enough.

(46)So the worm journey continues.  I hope that I have inspired some of you to help make this therapy more available so that other patients do not have to follow in my footsteps.  I hope that there are people in this audience who can bring this therapy greater attention. I hope I’ve provoked a lively discussion on our legal and evolutionairy rights as human beings.  I thank the commercial providers for giving us the chance to try this therapy now. And, I thank the doctors and researchers for moving forward with their studies, for your research is truly life altering.  Thank you all for listening.

The light of evolution points toward reconstitution of the biome as the only reasonable therapy for a wide range of immune-associated disorders, including allergy, autoimmunity and perhaps autism.

By William Parker, Duke University

It is now widely appreciated that humans did not evolve as a single species, but rather that humans and the microbiomes associated with us have co-evolved as a “super-organism”, and that our evolution as a species and the evolution of our associated microbiomes have always been intertwined. This co-evolution has biological consequences that are readily apparent. For example, decades of work with gnotobiotic (microbe-free) animals consistently demonstrate that the painstaking separation of a mammal from its associated microbiome results in an underdeveloped immune system that is a mere shadow of its naturally occurring counterpart.

The vital role of the microbiome in shaping the development of the immune system is, thankfully, becoming widely appreciated and the subject of more intensive inquiry. On the other hand, it is less well appreciated that, like the microbiome, a wide range of our fellow eukaryotes have co-evolved with us and have become intertwined with the development of our immune system. All mammalian species with the exception of humans in post-industrial societies and their domesticated animals co-exist with a wide range of intestinal worms, called helminths. Unfortunately, we are only now beginning to appreciate the consequences of our deceptively painless separation from these animals.

The co-evolution of helminths and the organisms they colonize can be traced back far deeper than the evolution of mammals, to the beginnings of immune systems. From this view, the immune system can be seen as having evolved as an interface with symbiotic organisms more so than as a defense against invading organisms, although defense against invading organisms was almost certainly a part of that interface. The co-evolution of helminths and their host’s immune systems has shaped the biology of both parties. Helminths have evolved to secrete dozens if not hundreds of molecules that exquisitely turn down the host immune system.  Mechanisms by which several of these helminth-derived immunosuppressive “drugs” function have been elucidated, and generally appear to be adapted for specific host species.  It is unreasonable to hope that host immune systems have not, in turn, adapted to the presence of helminths.  The idea that natural selection has left us dependent on the immunosuppressive  drugs produced by our evolutionary partners seems not only likely, but unavoidable.

The “hygiene hypothesis” was first proposed more than 20 years ago, and, having undergone an evolution of its own, is now more appropriately termed “The Lost Friends Theory” or “The Biome Depletion Theory”.  This theory, in its present form, describes the medical impact of separating us from our partners in co-evolution by means of widely appreciated medical care in combination with technology that we now take for granted, including running water and toilets. The Biome Depletion Theory embodies the central idea that epidemics of immune-related diseases associated with post-industrial society are due to a pathologically over-reactive immune response, which in turn is caused by a loss of components of our biome that normally interact with our immune system. These diseases include essentially all allergies and autoimmune disease, as well as appendicitis. The incidence of these diseases is staggering, with as much as 40% of the population suffering from allergies, 8% suffering from autoimmunity of some sort, and 6% undergoing appendectomy following inflammation of the appendix. Although components of the biome other than helminths may be important in this plague of diseases, a wide range of studies in rodents and emerging observations in humans demonstrate consistently that helminths are the component of the biome that is most missed by our immune system in post-industrial culture (Capron et al. 2004; Wilson and Maizels 2004; Fumagalli et al. 2009; Rook 2009).

The Depleted Biome Theory does not suppose that biome depletion is the single cause of allergies and autoimmune disease. Indeed, evidence is incontrovertible that such hyper-immune associated diseases are connected with genetic and epigenetic factors that predispose to disease as well as environmental “triggers” which initiate pathogenesis. The Biome Depletion Theory does, however, state that it is the change in the biome that is responsible for the epidemic nature (i.e. the increased incidence) of the disease. Unfortunately, failure to appreciate this distinction has been a source of confusion. The identification of genetic factors or a “trigger” (often a viral infection or some other environmental stimulus) does not invalidate the applicability of The Biome Depletion Theory to a particular disease. Rather, it is the incidence of a particular disease in post-industrial countries and in developing countries, in conjunction with the presence of an immune component of disease, which is indicative of the involvement of biome depletion in pathogenesis.

The potential complexity of the biological effects of biome depletion is staggering. Not only must the effects of biome depletion on a particular generation be considered, but the epigenetic effects on future generations may be profound. Further, the fact that biome depletion is not an all-or-nothing proposition adds vast complexity to the potential down-stream effects. Even more concerning is the obvious fact that the immune system and our biome did not evolve in isolation. Other organs, including our brain, were evolving at the same time, and are intertwined with our immune system in ways that are only beginning to be understood (Bilbo et al. 2005; Davis 2008). The implications are potentially far reaching. For example, the association of autism with inflammation (Ashwood et al. 2006; Braunschweig et al. 2008; Ashwood et al. 2009; Patterson 2009) and the epidemic nature of this disease in post-industrial societies (Becker 2007) point toward The Biome Depletion Theory. The identification of viral “triggers” which may be involved in autism (Lintas et al. 2010) is consistent with the idea that epidemics of autism (although, almost paradoxically, not autism, per se) are a result of biome depletion.

Although it may be impossibly difficult at the present time to sort out the potential effects of biome depletion, it has thus far proven surprisingly simple to restore the balance of nature for those suffering from biome depletion. Laboratory rodents, of course, were the first to benefit from such restoration, with a number of studies showing that colonization with helminths prevents adverse immune reactions associated with allergy and autoimmune disease (Capron et al. 2004; Wilson and Maizels 2004; Fumagalli et al. 2009; Rook 2009).  Studies in humans demonstrate that colonization with helminths provides an effective cure for many patients with inflammatory bowel disease that had proven untreatable with modern medicine (Summers et al. 2003). Even more exciting are data showing that the progression of multiple sclerosis is halted by helminth colonization (Correale and Farez 2007). Perhaps we should not be surprised.  Co-evolution can easily lead to co-dependency.

Although I take for granted the presence of a toilet in my house, it was only very recently, less than 100 year ago, that the toilet was imported to the United States. My father and all of my grandparents were born in houses with no indoor plumbing, although the concept of no toilet is foreign to me at my age of less than 50 years.  We seem to have forgotten that it was only a very few generations ago, at most, that our ancestors first acquired indoor plumbing and access to modern medicine, which effectively eliminate helminth reproduction. Connecting this recent history of hygiene with the epidemiology of disease, the evolution of our species, and the potential effects of epigenetics through time, it is possible to arrive at a remarkably simple conclusion that can account for a wide range of post-industrial disease: Biome depletion has left us with an overly reactive immune system. William of Ockham, the founder of Occam ’s razor, would approve. The frightening aspect of this conclusion is that we do not yet know if the effects of biome depletion have reached a climax. On the other hand, we can be reassured that biome reconstitution as a means of resolving the problems associated with biome depletion gives every indication of being quite feasible.

The idea of intentionally introducing organisms classified as parasites into the human population might seem, at first glance, repulsive. To some, hayfever seems a worthwhile price to pay for avoiding these co-evolutionary partners. Crohn’s disease and multiple sclerosis are certainly less tolerable, but therapies which usually alleviate the symptoms of these diseases at least to some extent are available. Despite the high costs of many pharmaceuticals, the general consensus may be that some disease can be tolerated as a side effect of being parasite free. This view, however, is undermined by two arguments. First, we do not yet know the extent of disease that must be tolerated in order to avoid our co-evolutionary partners. Certainly autism, if indeed it is associated with biome depletion, seems to cross over a reasonable line. This disease affects our very humanity…our cognition. The bottom line is that we are not at all certain of the price we are currently paying for biome depletion, and we are left in an uneasy “wait-and-see” position, not knowing what immune-associated epidemics are yet to come. Secondly, although helminth infections extract a horrible toll in developing countries, this price need not be paid by any post-industrial society that wishes to enjoy the benefits of colonization with helminths. In developing countries, one or more of the following three scenarios are necessary ingredients for morbidity and mortality associated with parasitic infection:

1. The presence of starving and malnourished populations.
2. The absence of water treatment facilities and sewer systems.
3. The presence of parasites that are not well adapted to the host (e.g. ones that hurt or harm a healthy host).

These three factors are simply not considerations in over-nourished, post-industrial societies. Individuals with pre-existing conditions that would be contraindications for helminth therapy (e.g. anemia or clotting abnormalities) are easily identified. Given a proper selection of helminths for colonization, uncontrolled infections are impossible in the face of modern sewer systems and water treatment facilities. Finally, adverse reactions can be readily reduced to far below acceptable levels by careful biomedical research in advance of widespread therapeutic application. After all, helminths represent a potential therapeutic that is readily reversible and that has been trained by hundreds of millions of years of natural selection not to encumber the host. No pharmaceutical company can boast that record for any drug. We have the luxury of selecting controlled colonization with helminths, not pathologic infection. The natural products are readily available and cost effective, with no need for expensive therapies. The technology and clinical implementation of the treatment should prove no more difficult than immunization during a routine visit to the doctor’s office, with follow-up visits to confirm immunity.

The learned thinking pattern for medical professionals and biomedical researchers is to envision isolation and characterization of the individual components produced by helminths, with the goal of creating new helminth-inspired drugs to treat disease. On the one hand, this approach is consistent with the general practice of modern medicine and the common approach used to find new drugs today. On the other hand, recapitulating the effects of an integral member or members of the biome using a single or even a handful of pharmaceuticals may prove extremely difficult.  Indeed, given the complex and continuous nature of the interactions between host and helminth that have evolved over hundreds of millions of years, the design of therapeutics to entirely and effectively recapitulate this interaction may prove impossible. In support of this idea, our laboratory, using a wild-caught rat versus laboratory rat model, has found that biome depletion potentially throws a wide range of parameters associated with cellular and humoral responses into disarray (Devalapalli et al. 2006; Lesher et al. 2006). Ongoing research in our lab using the same model indicates that biome depletion can affect the overall maturation of the immune system as well as the fundamental nature of both the adaptive and innate immune responses. Traditional paradigms associated with allergy and autoimmune disease (e.g. Th1 versus Th2 versus Th17) simply do not address this effect. We as immunologists are now faced with the unsettling realization that the immune system we have spent all of our effort and energy studying over in the past fifty years has turned out to be dramatically different than the system derived by natural selection. We find that “normal” is not helminth-free, and that our co-evolutionary partners must be included if we want to address the “normal” state of things. From a medical perspective, it is difficult to imagine that we will be able to restore the immune system to normal using a pharmaceutical that is directed at one cog in the immune apparatus, when in fact the entire apparatus is entirely out of sync with nature. Such an approach is tantamount to treating a despondent widow or widower with a topical ointment containing the recombinantly expressed MHC II complex of the absent partner. Pharmaceuticals do not effectively recapitulate biology derived by hundreds of millions of years of natural selection.

A synthesis of evolutionary biology, epidemiology, modern medicine, and immunology strongly suggests that biome reconstitution and maintenance should be a major thrust of the medicine of the future. Old paradigms of pharmaceuticals as a cure for immune-associated disorders are potentially as inferior to biome reconstitution as anti-cholesterol drugs are inferior to a healthy diet and adequate exercise. We cannot escape the biology imposed by our evolution, and the medical science of the future will take that fact fully into account.  At present, we need to direct intensive research toward biome reconstitution. The approach needs to be devised systematically rather than piecemeal. We need to know which organisms to utilize, and when and how to utilize them. We need to know the safety and efficacy of biome reconstitution for various conditions, including which hyper-immune conditions can be cured versus which can be prevented but not cured by biome reconstitution. We need to know the effects of biome reconstitution not only on one generation, but on subsequent generations. We must determine if new technologies are needed to reduce potential side effects of helminth colonization. In short, we need to know how to reconstitute our biome and keep that biome healthy. It is time for a paradigm shift in the enterprise of biomedical research and subsequently of medicine. Our evolution and our resulting biology require it.

References:

Ashwood, P., J. Schauer, I. N. Pessah, and J. V. de Water. 2009. Preliminary evidence of the in vitro effects of BDE-47 on innate immune responses in children with autism spectrum disorders. Journal of Neuroimmunology 208:130-135.

Ashwood, P., S. Wills, and J. Van De Water. 2006. The immune response in autism: a new frontier for autism research. Journal of Leukocyte Biology 80:1-15.

Becker, K. G. 2007. Autism, asthma, inflammation, and the hygiene hypothesis. Medical Hypotheses 69:731-740.

Bilbo, S. D., J. C. Biedenkapp, A. Der-Avakian, L. R. Watkins, J. W. Rudy, and S. F. Maier. 2005. Neonatal infection-induced memory impairment after lipopolysaccharide in adulthood is prevented via caspase-1 inhibition. Journal of Neuroscience 25:8000-8009.

Braunschweig, D., P. Ashwood, P. Krakowiak, I. Hertz-Picciotto, R. Hansen, L. A. Croen, I. N. Pessah, and J. Van de Water. 2008. Autism: Maternally derived antibodies specific for fetal brain proteins. Neurotoxicology (Amsterdam) 29:226-231.

Capron, A., D. Dombrowicz, and M. Capron. 2004. Helminth infections and allergic diseases. Clinical Reviews in Allergy and Immunology 26:25-34.

Correale, J., and M. Farez. 2007. Association between parasite infection and immune responses in multiple sclerosis. Annals of Neurology 61:97-108.

Davis, M. M. 2008. A Prescription for Human Immunology. Immunity 29:835-838.

Devalapalli, A. P., A. Lesher, K. Shieh, J. S. Solow, M. L. Everett, A. S. Edala, P. Whitt, R. R. Long, N. Newton, and W. Parker. 2006. Increased Levels of IgE and Autoreactive, Polyreactive IgG in Wild Rodents: Implications for the Hygiene Hypothesis. Scandanavian Journal of Immunology 64:125-136.

Fumagalli, M., U. Pozzoli, R. Cagliani, G. P. Comi, S. Riva, M. Clerici, N. Bresolin, and M. Sironi. 2009. Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions. J Exp Med 206:1395-1408.

Lesher, A., B. Li, P. Whitt, N. Newton, A. P. Devalapalli, K. Shieh, J. S. Solow, and W. Parker. 2006. Increased IL-4 Production and Attenuated Proliferative and Proinflammatory Responses of Splenocytes from Wild-Caught Rats (Rattus Norvegicus). Immunology and Cell Biology 84:374-382.

Lintas, C., L. Altieri, F. Lombardi, R. Sacco, and A. M. Persico. 2010. Association of autism with polyomavirus infection in postmortem brains. Journal of Neurovirology 16:141-149.

Patterson, P. H. 2009. Immune involvement in schizophrenia and autism: Etiology, pathology and animal models. Behavioural Brain Research 204:313-321.

Rook, G. A. W. 2009. Review series on helminths, immune modulation and the hygiene hypothesis: the broader implications of the hygiene hypothesis. Immunology 126:3-11.

Summers, R. W., D. E. Elliott, K. Qadir, J. F. Urban, Jr., R. Thompson, and J. V. Weinstock. 2003. Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease.[see comment]. American Journal of Gastroenterology 98:2034-2041.

Wilson, M. S., and R. M. Maizels. 2004. Regulation of allergy and autoimmunity in helminth infection. Clinical Reviews in Allergy and Immunology 24:35-50.

William Parker, PhD.

Department of Surgery

Duke University Medical Center

DUMC Box 2605

Durham, NC 27710

Phone: 919-681-3886

E-mail: bparker@duke.edu

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November 11-14 in Los Angeles, the BTeR Foundation (BioTherapeutics, Education & Research Foundation) is hosting an international conference on biotherapy, including helmintherapy:

http://www.bterfoundation.org/icb/icb2010.htm

Dr. Pritchard from University of Nottingham will be giving a talk:  “A Critical Appraisal of Worm Therapy” on the 11th, and on the 14th will be having a workshop on “Practical Helmintherapy”.

http://www.bterfoundation.org/icb/program.htm

I’ve been invited to speak as a patient trying this therapy.

I’d like to present an honest account of my and other people’s experience with helmintherapy.  Mostly, I’d like to establish a liaison between patients and researchers.  What would you, as a potential or current patient of helmintherapy like to tell or ask the researchers?  What has your experience been with your disease and helminths?  What would you like to see in the future with this therapy?  Are you interested in becoming a case study or linking your physicians with other researchers?  How can we best unite the community of researchers and the “underground worm therapy” movement to help legitimize and share our data?

You can comment here, or privately at: http://waitingforthecure.com/I/contact/

Thank you!

November 11-14 at the Hollywood Hilton in Los Angeles, there will be a conference on biotherapy, which is the use of living organisms to treat or diagnose medical illnesses.  On Thursday at 4:00 Dr. Pritchard from the University of Nottingham will be giving a talk on helminth therapy.  On Sunday, there will be a breakout session and workshop at 9:00 AM on the Clinical Use & Administration of Medicinal Helminths.  Those of you interested in learning more about these topics should attend.  Price for the day is $175 or $105 for students,  a workshop only is $235 or $105 students.  All 4 days costs $425 / $190 students.  Members of the BTeR foundation pay less.

I’m planning on attending this.  Hopefully some of our burning questions will be answered.  Maybe those interested in helminth therapy in the Los Angeles area could meet somewhere to talk about it?  A worm date.

http://www.the-scientist.com/blog/display/57492/#ixzz0r7JuTFKP

http://www.manchester.ac.uk/aboutus/news/display/?id=5841

From the articles:

“A new class of organisms may be cutting in on the classic, co-evolutionary, immune system-boosting tango between mammals and the beneficial bacteria that inhabit their guts: parasitic worms.”

Trichuris muris eggs with Escherichia coli Image courtesy of Kelly Hayes, University of Manchester

“Importantly, the work also showed that the presence of worms and bacteria altered the immune responses in a way that is likely to protect ourselves, the bacteria and the worms.

Intestinal roundworm parasites are one of the most common types of infection worldwide, although in humans increased hygiene has reduced infection in many countries. High level infections by these parasites can cause disease, but the natural situation is the presence of relatively low levels of infection. The team’s work suggests that in addition to bacterial microflora, the natural state of affairs of our intestines may well be the presence of larger organisms, the parasitic roundworms, and that complex and subtle interactions between these different types of organism have evolved to provide an efficient and beneficial ecosystem for all concerned.

Professor Roberts says: “The host uses its immune system to regulate the damage caused by the bacteria and the worms. If the pathogens are missing, the immune system may not give the right response.”

Professor Grencis adds: “The gut and its inhabitants should be considered a complex ecosystem, not only involving bacteria but also parasites, not just sitting together but interacting.”

I don’t know how this relates to hookworms or whipworms, but the thought before was that no pathogens could be transmitted from the parasites. This study shows that even when washed in an anti-microbial solution, certain pathogens remained and were capable of being passed on to an infected host.

It mentions mycobacteria avium was isolated from parasites that had fed on an infected host. Considering a theory that Crohn’s is often associated with MAP, one might be a little hesitant in sharing one’s infection with other parties if you have Crohn’s. Since there is little way to get testing for this organism at this time.

How does one assure oneself that the hookworms or whipworms are pathogen free, if an anti-microbrial buffer only washes the outside of the organism? I guess this is why TSO was chosen; pathogen free pigs. I wonder how Nottingham got past this, and how often and for what infections the resevoir donor is tested for?

For those DIY’ers, something to consider. And for those buying the parasites, something to ask about.

Schistosoma mansoni proteins attenuate gastrointestinal motility disturbances during experimental colitis in mice

http://www.wjgnet.com/1007-9327/16/703.asp

Injecting worm proteins  into mice given colitis resulted in decreased gastric motility (less bowel movements) and amelioration of inflammation.  Pretty good stuff.  This means that worm proteins will eventually be the next Prednisone, and the live worm won’t be necessary.  I wonder how often we would have to take them?  Will they be a shot, a pill, or an enema?  Can we get out of the mice model into some human studies before those with IBD lose their colons in waiting?

Abstract

AIM: To investigate the therapeutic effect of Schisto­soma mansoni (S. mansoni) soluble worm proteins on gastrointestinal motility disturbances during experi­mental colitis in mice.

METHODS: Colitis was induced by intrarectal injection of trinitrobenzene sulphate (TNBS) and 6 h later, mice were treated ip with S. mansoni proteins. Experiments were performed 5 d after TNBS injection. Inflammation was quantified using validated inflammation parameters. Gastric emptying and geometric center were measured to assess in vivo gastrointestinal motility. Peristaltic activity of distal colonic segments was studied in vitro using a modified Trendelenburg set-up. Cytokine profiles of T-lymphocytes isolated from the colon were determined by real time reverse transcriptase-polymerase chain reaction.

RESULTS: Intracolonic injection of TNBS caused severe colitis. Treatment with S. mansoni proteins significantly ameliorated colonic inflammation after 5 d. TNBS did not affect gastric emptying but significantly decreased the geometric center and impaired colonic peristaltic activity 5 d after the induction of colitis. Treatment with S. mansoni proteins ameliorated these in vivo and in vitro motility disturbances. In addition, TNBS injection caused a downregulation of effector T cell cytokines after 5 d, whereas a S. mansoni protein effect was no longer observed at this time point.

CONCLUSION: Treatment with S. man­soni proteins attenuated intestinal inflammation and ameliorated motility disturbances during murine experi­mental colitis.

© 2010 Baishideng. All rights reserved.

I got 10 new hookworms in February 2009, then 10 more in late September 2009. My last egg count was 1400 epg. My CRP (measure of inflammation) has been normal since March 2009.  So 20 worms are working for me.  Weight’s been normal since March, I can eat most foods but still get diarrhea from too much fiber.  Now my hormones are causing anxiety/depression, but I’m assuming that’s un-worm related.   I’m almost 38 years old.

I wish we knew the ideal dosing number and dosing schedule.  It seems that those with the best response are getting at least 20-30 hookworms, though I also know of Crohns patients who had to terminate because 20-25 worms were way too much at once.  I wish these studies were faster since we’re just dosing in the dark.

The asthma study:

http://www.ncbi.nlm.nih.gov/pubmed/20030661

Experimental hookworm infection: a randomized placebo-controlled trial in asthma.

Feary JR, Venn AJ, Mortimer K, Brown AP, Hooi D, Falcone FH, Pritchard DI, Britton JR.

Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.