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by William Parker
of a threadworm, a parasitic nematode of the small intestines of numerous animals. Photo by Steve Geschmeissner
Science
Photo Library But our war against intestinal worms has damaged our immune systems and mental health...
One in every six seems to be a few too many, I would think.
When asking why we get sick, we take the first step in understanding the origins of disease.
If we find the answer to
that question, we become empowered to prevent disease.
In line with this attitude, our biomedical research focuses on elucidating detailed mechanisms aimed at developing the next drug, but not on why we need a new drug in the first place.
Modern medicine asks what and how:
But we should be asking why - this is the first critical step toward prevention.
If we don't know why something happens, we can't hope to stop it. We might or might not be able to pull drowning people out of the river, but we really should ask how these people got in the river in the first place.
Where are the sinking
boats that left these people stranded in the water?
Our Western diet is certainly a factor. And our stressful lifestyle. But we and others are coming to a fascinating conclusion: intestinal worms are almost certainly involved. But it's not the presence of the worms that is hurting us.
To the contrary, the almost complete loss of intestinal worms in modern society is, surprisingly, a very significant problem.
Intestinal worms, called 'helminths', have caused untold human suffering, killing the weak and disabling the strong. Labeled uniformly as disease-causing parasites by biologists, they have inspired fear and hate, leading to major campaigns aimed at their eradication.
The Rockefeller Foundation, for example, was originally formed to eliminate hookworm from the southern US. Their genocidal campaign was very successful, and similar campaigns are now underway in developing countries.
This fearsome menace has been virtually eradicated in the US and in western Europe, and we hope to accomplish the same in developing countries.
Good riddance...
Indeed, my research and the research of many others tell us that helminths are necessary for our health.
A barrage of scientific evidence points toward helminths as being important regulators of immune function. Because of this, our genocidal campaign against intestinal worms apparently has a very nasty backlash that nobody saw coming. But science moves very slowly.
All helminths are still
labeled as parasites in textbooks, despite the fact that we now know
this to be incorrect.
Given that the field of immunology was founded to combat infectious disease, a view that embraced bacteria as the ever-present enemy made sense. But following this accepted dogma, my research team got bogged down in inexplicable observations.
The results in the lab didn't make sense.
Then one day 20 years ago, standing in front of the fume hood in my lab that is still there today, something clicked in my brain, and everything fell into place.
The organization of bacteria for gut health was immediately obvious, and numerous puzzling observations we had long struggled to grasp fell quickly into perfect order like brawling soldiers suddenly hearing the voice of a fearsome drill sergeant.
The immune system was actually supporting rather than fighting off most of the bacteria in our body!
This paradigm-shifting
idea had far-reaching implications for the field of immunity. For
example, the function of the vermiform (worm-like) appendix, that
troublesome little structure in our gut, could now be seen clearly
as a type of safe house for beneficial bacteria.
But repeated rejections by scientific journals and funding agencies along with sarcastic critiques from anonymous reviewers were the norm for the lab during those early years.
Fortunately, the paradigm shift made perfect sense to scientists working on the microbial ecology of the gut, and support from that field eventually overcame bias in the field of immunology.
We'll never know how long
the paradigm shift in immunology would have taken if it weren't for
the microbial ecologists researching
the microbiome.
Unfortunately, this new battle has more at stake, with tens of millions suffering from diseases that appear to be related to our loss of helminths. But there is hope.
Once again, biologists
with expertise in the organization of ecosystems are on our side.
Preston reported that
other individuals 'amongst a large series of patients' continued to
suffer from allergy. Then, six years later, a young British
scientist, John Turton,
found that intentionally
inoculating himself with hookworms eliminated his seasonal
allergies.
At the same time, Maizels
also compiled an impressive list of studies using laboratory mice,
showing that helminths attenuate a multiple sclerosis (MS)-like
syndrome, a Type 1 diabetes-like condition, inflammatory bowel
disease, gastric ulcers and allergic reactions, including allergic
reactions to peanuts.
Then, in 2007, shortly after Joel Weinstock's work came to light, the neurologists Jorge Correale and Mauricio Farez at the Institute for Neurological Research in Buenos Aires published results (Association between Parasite Infection and Immune Responses in Multiple Sclerosis) looking at the effects of intestinal worms in humans with MS.
At that time, the disease
was essentially untreatable and deadly, and, as Maizels had pointed
out, work in laboratory animals had suggested that intestinal worms
might help.
has something to do with the high rates
of mental-health
disorders in children...
They had hundreds of patients with MS, and decided to see if any who accidentally got an intestinal worm might get relief from their disease. Eventually, Correale found a dozen patients who had accidentally contracted an intestinal worm.
During the study period, there were three clinical relapses of MS in the infected group compared with 56 relapses in the uninfected group, showing that, in general, the presence of worms offers protection against the symptoms of MS.
Correale followed his patients for more than 10 years, and found that, as long as patients kept their worms, their autoimmune disease did not progress. But if they lost their worms, their disease returned.
Importantly, it did not
seem to matter which intestinal worm the patients had. Some patients
had flatworms, while others had roundworms, two very different types
of worms, both apparently having the same benefits.
But we did find one puzzler:
Ultimately, we began back-translating the results we were finding in people to see if we could recapitulate the effect in laboratory animals.
In collaboration with Staci Bilbo, a renowned neuroscientist at Duke University in North Carolina, we gave benign (harmless) helminths to female rats before the rats became pregnant. Surprising to some but anticipated by us, we found (Got Worms? - Perinatal exposure to Helminths prevents persistent Immune Sensitization and Cognitive Dysfunction induced by Early-life Infection) that the brains of baby rats (pups) are protected from inflammation if their mother has an intestinal worm.
Thus, it seems likely that a complete loss of intestinal worms has something to do with the high rates of mental-health disorders in our children.
Of course, most studies
tapping these finds are aimed at using something the helminths make,
the molecules produced by the worms, to design a new
anti-inflammatory drug. The thought of actually using a helminth as
a cure doesn't seem to be under consideration, perhaps because we
are locked into the view that only a drug can help us.
In fact, trying
to recapitulate a complex
biological relationship using a single molecule in a pill might be a
lost cause. In contrast, the naturally occurring worm will
apparently work just fine.
In a school I'm very familiar with, the hallmark problem with nutrition as defined by the Centers for Disease Control and Prevention is that many children do not have breakfast.
Our government 'solves' this problem by providing free breakfasts in the public schools. The children have a choice of waffles or cinnamon rolls made from highly processed grains and topped with high-fructose corn syrup, or a colorful round-shaped cereal, again made of highly processed grains and added sugar.
In this particular school, my colleague observed that about 70 per cent of the children attending a required health class recognize unhealthy food when they see it. But they generally don't worry about it very much because they feel that their diet could be worse than it is. In other words, they know that what they are eating is not good, but they don't worry because they could find even unhealthier food if they really tried.
I doubt that their lack
of concern is valid. And I wonder why we don't seem to be trying to
fix the problem.
The transfer of fecal material from a healthy donor to an unhealthy one was shown, as long ago as 1958, to cure Clostridium difficile colitis.
This recurrent C diff
colitis is initiated by the destruction of the friendly microbes in
the gut by prescription-antibiotic use. Without the friendly
microbes to protect the system, the naturally occurring C diff
bacteria overgrows and essentially converts the human gut into a
toxic, inflamed wasteland that cannot digest food.
But, sadly, recurrent C diff colitis has continued to take the lives of thousands of Americans each year. Estimates vary, but in terms of American casualties, the death toll was equivalent to repeating the entire Vietnam War every three to five years.
Now emerging as a first-line therapy, but still not universally in place, the poop transplant will probably soon become the standard of care. The question is,
The answer is that the
life-saving solution just didn't get out to the doctors who were
treating the dying patients.
whether anybody can successfully patent
a worm that
occurs in nature...
First, they involve naturally occurring organisms that are difficult to patent. With no patent, or 'intellectual property', the financial incentive for developing the associated therapy vanishes. The prospect of striking it rich with a new drug under these conditions is nonexistent.
One might think that the incentive to heal people and save lives would be sufficient, but the fact is that the current drug pipeline costs more than $100 million. That cost leaves the drug business in the hands of large corporations, and large corporations, regardless of the propaganda they serve in their advertisements, are not interested in making people healthy.
If it doesn't make money, large corporations are not interested.
Worse, if the new therapy would undermine millions or maybe even billions of dollars in profit from pharmaceutical sales, corporations are obliged to shy away.
It is not their business to put themselves out of business. In the assessment I published with several colleagues, we boiled down the problem to one factor: our government assumes that anything that will treat disease will make enough money to drive the drug past the current cost barriers.
This is not true for
'orphan drugs' that
treat rare diseases and conditions,
and it is certainly not true of naturally occurring organisms that
are
difficult to patent.
Erb has a good point.
How can any company stay in business if it invests more than $100 million and then can't protect its investment? It remains to be seen whether anybody can successfully patent a worm that occurs in nature, and that possibly hundreds or even thousands of people are already buying from a local supplier and using without approval from regulatory agencies.
Rather than wait and hope for a miracle, our view is that the problem needs to be acknowledged, and that the policy needs to change.
Rather than being classified as a drug, helminths need to be classified as something new:
A second thing that helminths and poop transplants share in common is that they don't require any of the panoply of modern molecular, genetic tools to sort out what's going on.
What was lost has been found, and now the biological system is restored. It's easy to comprehend, akin to a vitamin, with no PhD required to grasp the picture. This might seem to be an advantage.
Indeed, I believe that it should be an advantage.
But, oddly enough, it doesn't work that way in reality. The reason is that most research on inflammatory disease focuses on the mechanisms and genetics underlying those diseases, and any work not digging deep into mechanistic underpinnings is simply considered to be unscientific.
If engineers were in charge of biomedical research, this would not be a problem. I suspect that we might have other problems imposed by engineers (I have a family full of them), but straightforward solutions that make sense would move forward rapidly if engineers were in charge.
That's not true in the current science-driven environment.
Anything that doesn't
involve a few molecular-signaling pathways and up to four
unrecognizable acronyms just isn't science these days. Fifty
unrecognizable acronyms might be overkill, but at least a few are
required to get federal funding.
I remember the day an experiment confirmed my hypothesis on why we have an appendix attached to our caecum.
We knew that, if our hypothesis was correct, intact films of bacteria, called biofilms, should be present in high quantities in a healthy human appendix. It took two years to run that experiment, but I remember the moment when the predicted bacteria showed up on the imaging screen.
I found the only other human I could at that time of night, and showed the bewildered fellow the exciting result! I remember a few missed calls as well, and I still have ideas that I would love to test one day. I love science, but science can wait.
First we need to implement commonsense therapies to alleviate suffering to the extent possible, and then it would be interesting to dissect out many of the fine points of how those therapies work using modern scientific approaches.
Those reductionist
details could possibly help us refine the therapies. And it would be
fun for scientists such as me to dig up the details. But to wait
indefinitely on science when the therapy is available and ready for
testing is much worse than unreasonable. It is inhumane...
But what if worms offer a cure for many of our modern inflammatory conditions?
We don't expect them to be a magic bullet, but in combination with a healthy lifestyle, increasing evidence suggests that the reintroduction of worms will effectively prevent or even treat many of our modern inflammatory diseases.
What if allergy, autoimmunity, digestive disorders and neuropsychiatric disorders were a thing of the past? Our research dollars could be spent on fun things, such as space exploration, particle physics or even the biology of the life on this planet.
Understandably, we do not spend our research dollars studying scurvy or rickets. We have a cure for those conditions (vitamin C and D supplementation, respectively), and there is no point in studying a disease that is easily prevented.
But just maybe we are in fact spending most of our energy studying readily preventable diseases.
That's akin to studying a fish out of water. That fish is going to be sick, and the sickness will be complicated. But if the goal is to make the fish well, we should stop studying the sickness and put the fish back in the tank.
For better or worse, the
water tank for humans contained a few intestinal worms.
those successful experiments with helminths if nobody is going to translate them
to the clinic?
Most of the work we do in science is geared toward understanding exactly what components of our body are affected by disease and precisely how those components are affected. That's important if we want to develop the next generation of drugs.
But I believe we deserve more...
With the vast resources we have dedicated to our health, our society could be very close to disease-free. If we don't start asking why, however, the trend toward sickness and dependence on medicine will only continue to spiral out of control.
As that happens, the struggle for access to costly but limited medical resources will intensify, and that struggle will continue to blind us to the central question:
The toxic food served to our children by our government is an obvious indication that something is horribly wrong with public-health policy in the US.
The lack of acceptance of proven and commonsense therapies such as faecal transplants is yet another.
Failure to fund work aimed at the reintroduction of intestinal worms to alleviate inflammatory disease, despite compelling evidence from the laboratory, is another indication still.
I'm often asked if some nefarious pharmaceutical corporation might be flying the plane of public health in this country.
I don't think so. I have come to understand that this plane is on autopilot, and is built of certain assumptions that look reasonable at first glance. Sadly, those assumptions are false, and the infrastructure of that plane is fatally flawed.
We need to withdraw our
faith and our focus away from creating an ever-increasing litany of
drugs for treating an increasingly sick population, and design a new
plane that asks why we get sick - and aggressively address the
answers to that question.
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