Translational medicine. The concept was invoked frequently last week at the Days of Molecular Medicine Conference (DMM). It’s an approach to medicine in which researchers are urged to take the data they have collected in the laboratory and find a way to apply it directly to patients. The term also suggests that researchers and doctors must work together, and that collaboration among researchers in different fields is essential if medicine is to advance.

The Marshall Protocol epitomizes translational medicine, which is why, in my opinion, our poster presentations at the Conference were, for the most part, viewed with great interest and optimism.

The researchers who filled the lecture and poster halls at DMM had travelled to Sweden from the most prestigious universities in the world. It didn’t take long to realize that many of them have spent their entire careers looking for faulty genes that might be able to cause mental illnesses such as autism or obsessive-compulsive disorder.

The problem with such research is that the genetic mutations found in people with mental illness can easily be attributed to the fact that, once inside the body, the Th1 pathogens mutate our DNA. Thus, as a person acquires a significant bacterial load, mutations become more common and can even be passed from generation to generation. This alternate hypothesis for genetic mutations in people with various mental illnesses has been largely ignored by mainstream medicine, a fact confirmed by the talks at DMM. Many researchers spoke of only 5 -10% correlations in the genetic mutations found among patients with a particular mental disease such as autism. As I sat through lectures that discussed such correlations, the reality that only pathogens can cause such a diverse array of mutations became increasingly clear.

One might think that researchers looking for a purely genetic cause of disease would have become discouraged by this point. After all, as one of the researchers who gave a talk admitted, back in 1990 geneticists were sure they would identify direct correlations between specific genes and specific diseases by 2000, allowing them to cure most forms of illness. But the researchers at DMM seemed determined not to see this as a sign of failure. Instead, they put forth a new philosophy – namely the idea that genetic research has failed to generate any successful treatments because it has proved to be much more complex than expected. So, based on this notion of complexity, the geneticists at the Conference have yet again pushed back the date at which they expect to find a way to treat mental illness using gene therapies. Those of us familiar with the MP realize the date will be pushed back endlessly until pathogens are finally recognized as the agents causing the complex mutations observed by so many researchers.

After a talk on the genetics of obsessive-compulsive disorder, I threw my arm up in the air. By that point, I had realized that I would be given one of the few opportunities to ask the researcher a question, only if I did some serious arm flailing. “Have you considered pathogens?” I asked. “Have you considered the fact that perhaps the reason you are finding such random genetic mutations among your study subjects is because the mutations are simply the result of active changes to the DNA created by bacteria?” Dr. Matthew State of Yale University, who had given the talk, was thoughtful in his response. He agreed that certain environmental factors could be contributing to cognitive disease, and that pathogens are among these factors. The audience seemed interested in his response. Perhaps, like me, they were wondering just how complex genetic research will have to get before they are given any concrete explanations from geneticists about how to treat so many severe cognitive diseases.

Much of the research presented at the Conference focused on mice, and how we could poke, prod, and medicate them towards becoming alternately quicker learners and more chipper. And what would a neuroscience conference be without mice running mazes? We were not let down, as many researchers at the Conference had created novel ways to test the cognitive abilities of their furry subjects. In fact, one researcher whose talk hadn’t focused on mice squeezed in some data on rodents at the end of his speech, joking that he wouldn’t be believed unless he verified his data on mice. Again, I found it difficult to see how the implications of such studies on rodents could be applied to human beings, particularly since I’m well aware of the fact that the rodent VDR and immune system is vastly different than that of humans.

All of the speakers gave concise, deliberate presentations, and I have a lot of respect for the sophisticated techniques they have mastered in order to conduct their research. It’s just that the DMM’s aim is to stress translational medicine. At a Conference that is supposed to demonstrate how basic research can drive clinical care, none of the data presented by geneticists can be used to actually help even one person with any type of mental illness.

While the lectures inside the grand auditorium at the Institute focused largely on genetics, three posters lingered in the poster hall that implicated pathogens, rather than genes, as the cause of chronic disease. These posters were, of course, the posters created by Dr. Marshall, Meg Mangin, and myself.

Dr. Marshall lucked out in the sense that his poster slot was #53 – meaning that, because of the way the posters were positioned, his poster was the first one every person saw as they entered the poster hall. Just around the corner from his poster were Meg and her poster. This provided an excellent atmosphere in which people could learn about the MP. First, researchers would wander over to Dr. Marshall’s poster where they would get an in-depth explanation of the molecular science behind the treatment. Then, they would turn the corner and Meg would explain the practical side of the science – the way it has been used to create a medical treatment in which patients are monitored over an open study site.

It didn’t take long for people who spoke with Dr. Marshall and Meg to realize that Autoimmunity Research Foundation was the only group at the conference truly exemplifying translational medicine. For this reason, his work attracted many visitors. It didn’t hurt that Dr. Marshall had two small video players velcroed to his poster that ran videos of L-form bacteria inside the blood of a patient with CFS. The blood, which is absolutely overtaken by long biofilm tubules with bacteria inside, was a rather large wake-up call to those researchers who incorrectly consider the blood to be sterile.

In fact, Dr. Marshall was an endless source of electronic gadgets at the Conference. Out of a meticulously packed suitcase came small video cameras, recording devices, computer cables, and essentially any other device that successfully allowed Paul Albert of Weill Cornell Medical College – who came down to help with the technical aspects of the conference – to videotape large segments of the Conference. If Paul was missing a device, be it a cord or tripod, all he had to do was ask, and Dr. Marshall inevitably had it on him. It’s clear that focusing on molecular biology has not prevented Dr. Marshall from keeping up with the latest electronic trends.

My poster was on board space #89, which was on the far side of the auditorium. I was glad that my poster was separated from Dr. Marshall’s and Meg’s posters because people who wandered down the left side of the auditorium would hear me speak first and my poster seemed to spark enough interest so that they would continue on down the line to Dr. Marshall’s.

But the hypotheses put forth on my poster interested people in their own right. For starters, I was pleasantly surprised that everyone whom I spoke with seemed to realize that Chronic Fatigue Syndrome is an extremely debilitating disease with a very serious mental component. Nancy Pederson, the associate dean at Karolinska Institute, made a point of coming over to my poster because she is actually studying Chronic Fatigue Syndrome in identical twins. She admitted that her group is not finding any significant genetic trends among their study subjects. So her team is considering pathogens, namely viruses. We proceeded to discuss how the viruses observed in some of her study subjects might just be co-infections, co-infections that are able to take advantage of the immunosuppression generated by bacterial blockage of the VDR. She seemed interested. In her case, and in the case of others, I found people constantly picking up my handouts, my brochures about Autoimmunity Research Foundation, and my business card for Bacteriality.

I discussed several topics that related to my poster, but women in particular seemed extremely interested in understanding why women often feel better during pregnancy, then relapse after giving birth. The reason being that during pregnancy the active vitamin D metabolite 1,25-D rises to extremely high levels, interfering with the activity of the nuclear receptors that control many families of antimicrobial peptides. Because the peptides are produced at a much lower rate during pregnancy, women experience much less bacterial die-off and subsequent relief during that time. However, because women with Th1 disease are immunocompromised during pregnancy, the Th1 pathogens they harbor spread easily, causing them to feel worse after giving birth when 1,25-D drops back into a lower range.

A lot of people admitted that what I was putting forth “just really made so much sense!” After hearing so many complex explanations about the genetics of mental diseases, I guess Dr. Marshall’s hypotheses seemed exceptionally logical. I spent a long time discussing the scientific topics on my poster with Dr. Yujiang Shi from Harvard. After he had absorbed the details of the Marshall pathogenesis, he literally turned to me and stated confidently, “You know, Dr. Marshall is going to win the Nobel Prize.” I said, “Yes, I know!”

The concept of the poster hall is a good one because food is served at the back of the hall, meaning that anyone who wants to eat has to walk by all the posters in the process. Then, they can take their plate of food and wander around looking for posters that catch their eye. I didn’t have time to eat. Before I could even reach for a plate of food, someone had come over to my poster and wanted an explanation. Dr. Karl Deisseroth from Stanford (who later presented an amazing talk about new technology his team has developed to track the action of neurons in the brain) again commented that he was very open to the idea that chronic inflammatory diseases might have a bacterial cause. I spoke to several doctors who seemed eager to try the MP on their patients, particularly doctors who worked with children with behavioral disorders. Most seemed amazed that we were actually putting forth a potential treatment backed by so much scientific data.

Every so often I would glance down the hall and see Dr. Marshall’s yellow shirt and red tie gleaming under his jacket. He seemed to be talking non-stop as well. On the first day, I actually lost my voice for a while because of the fact that I talked so much.

Because of its location, my poster was quite close to the poster of the researcher next to me. He was a researcher from Northwestern University who sadly was presenting data that might allow for the development of yet another immunosuppressive drug. I have to say that people walked right by his poster and over to my poster instead. At one point, a good natured older man appeared behind me and tapped my shoulder. He said, “Your poster is getting so much attention, it’s too bad that you’re standing between me and my money.” I realized that he had funded the research for the immunosuppressive drug and that the crowd looking at my poster was largely blocking the poster about the medication. I tried to move over to the side, but at that exact moment one of the deans of the Karolinska Institute barged right in front of the other scientist’s poster to ask about mine. The older gentleman sighed and walked away. Any feelings of sympathy were short-lived as I was happy to see that people were more interested in the MP than immunosuppressive drugs.

A researcher a few posters away had travelled to the conference from the Longevity Institute in Japan. He was working with VDR knockout mice. He was so excited about Dr. Marshall’s work that he spent more time by my poster than his own. At one point he even asked me if I would be willing to put my name on one of his papers. I told him that if I thought the paper was accurate, I would be happy to do so. I’ll see how that works out.

Some of the other talks at the Conference, those that didn’t focus completely on genetics, were actually quite interesting. A speech that focused on estrogen sparked Dr. Marshall’s interest. He was also extremely interested in a talk by Dr. Adriano Aguzzi from the University Hospital of Zurich about prions. Prions are small infectious agents made purely of protein that are believed to propagate by refolding abnormally into altered structures that accumulate in infected tissue, causing cell death and tissue damage. I’ll be writing more about prions in another article.

After the poster sessions and presentation ended on Friday, we had just enough time to return to the hotel, rest for about five minutes, and then get ready for a welcome reception at the Town Hall. The words “Town Hall” don’t spur thoughts of glorious architecture in my mind, but I soon realized that the Stockholm Town Hall is an exception. When we entered the gates, we found ourselves just steps away from the water with slim arches bending gracefully over our heads.

Upon entering the reception hall we were offered glasses of wine. The head of the Karolinska Institute gave an inspiring welcome speech, to which we all responded “Skål!”, which is an all-purpose Swedish toast. At that point I started to realize, “Hey, I’m really here. This is the place where the top minds in medicine get together to advance the understanding of medicine.” A little chill ran down my spine as I gazed out the window at the beautiful buildings across the water that were illuminated in the setting sun.

Next, we made our way along a table replete with a smorgasbord of food which unfortunately consisted of a large variety of delicious looking salmon and other fish. Luckily, there was a large platter of Swedish meatballs that saved me from starvation.

Soon, we were ushered on a tour of the entire Town Hall. Having failed to read anything about the Stockholm Town Hall, I was amazed to walk into a room in which the walls were literally made of gold and a massive image of the maternal figure symbolizing Stockholm gleamed on the opposite wall. After that, we entered the “Blue Hall,” the space in which the Nobel Prize banquet takes place on December 10th every year. We then proceeded to enter an ornate room where the Stockholm city council meets. Finally, we ended up standing at the bottom of a tremendous stone tower that is one of the city’s landmarks.

It was tough to leave and go back to the hotel, but I needed to sleep so that I could present my poster with zeal the following day. After another day of long and successful talks and presenting our posters, we were bused to the Museum of Modern Art. First, we were given a tour of the Museum’s Andy Warhol exhibit, which was very well done and included many multimedia effects in an attempt to create an atmosphere that mimicked Warhol’s lifestyle. Dr. Karl Deisseroth from Stanford alerted me to a video which showed a transvestite slowly eating a banana. We had a good laugh over how eccentric Warhol was. Since Warhol’s art clearly reflects the fact that he suffered from anxiety, depression, and other mental afflictions, I could almost see each scientist there trying to come up with their own explanation for his cognitive issues. My biases are more than a little obvious– I think Warhol was just suffering from a tremendous number of Th1 pathogens.

Dinner was served right on the waterfront with a view of the old Swedish city across the water. Towards the end of the meal, Dr. Kenneth Chen of Massachusetts General Hospital and Harvard Medical School, one of the conference organizers, stood up to give a toast. After his own short speech, he selected other important members of the audience to stand up and give a few words about the Conference. I was half-listening, half-eating my delicious piece of steak, when I heard him ask Dr. Marshall to give a short speech. Dr. Marshall has attended the DMM Conference for the last three years and is thus something of a veteran. Dr. Marshall spoke about the importance of translational medicine, which, of course, is the focus of his work. As his words blended with the clinking of wine glasses and the lights of the beautiful buildings across the river, I felt an immense sense of pride in Dr. Marshall. I admire his relentless drive to push forward his scientific discoveries, and to consistently attend conferences even when some researchers dismiss his work. Now, here he was, being given the same recognition as any other scientist at the event.

During those rare moments of down time, I chatted with Meg, her husband Tom, and Dr. Marshall’s wife, Liz. I’ve known Meg for three years over the internet so it was great to finally meet her in person. She’s spunky, fun, and full of interesting stories. Her husband Tom took full advantage of being in Sweden. Instead of attending the Conference, he spent most of the time at an Irish pub where he made friends with several Swedish natives, one suspiciously named Jim Beam. In fact, both Meg and Tom love Irish pubs. Meg even has her own special toast, part of which Paul caught on video. We discussed how, to a great extent, there are two different Megs. There is professional Meg who must be very careful about adhering to FDA regulations on the study site, and then there’s fun, laid-back Meg who loves to travel and has eight adorable grandchildren. Tom told me about the fact that Meg answers questions on the MP Board from the moment she wakes up until the moment she goes to sleep. He does all the shopping and cooking. Even when they go out to eat, Meg takes her laptop along so that she can post on the study site during the time when they are waiting for the food to arrive.

The Conference was partially sponsored by Cell Press, a group that runs a number of medical journals. The staff from Cell Press didn’t seem very interested in the MP. For one thing, I think they simply weren’t prepared to hear an explanation for chronic disease that was so different from those explanations offered by the lion’s share of articles their journals feature these days. As Dr. Marshall has commented, the editors of medical journals are petrified of publishing something that may turn out to be wrong, and perhaps the MP seemed almost too good to be true.

Interestingly, the representatives from several drug companies were very interested in my poster. A man from AstraZenica asked me a lot of questions. I told him that if his company wants a heads up, they should start creating drugs that prevent the formation of L-form bacteria. He laughed, but it may not be that long before he realizes that I was completely serious. At the museum dinner, I sat across the table from several drug chemists who told me they were disappointed that none of the speeches had really given them any clues about how to create more effective drugs for mental disease.

Their comments reenforced my belief that, at the moment, the timing is ripe for acceptance of the MP. Drug companies have little to work with in order to create palliative drugs for mental illness or illness in general. Genetic researchers claim they need a few more decades before their work will be able to help patients. Meanwhile, doctors are getting restless. They are tired of telling patients, “I can’t explain your illness and I can’t help you get better.” These doctors are increasingly attracted to the MP, or at least they were at Karolinska. Presenting information about the MP in person made a big difference. It makes me wish that I could sit down with every doctor and give them a 15 minute talk on the MP.

The day after the Conference should have been a day of rest, but I had made a commitment to give a speech about the MP to a group of Swedish patients and doctors who were interested in the treatment. Aside from having a few difficulties when it came to balancing the microphone and my script in the same hand, it went well. Everyone seemed open-minded. One lady in particular, in the front row, kept nodding her head as I moved from concept to concept, as if all of a sudden her disease was starting to make sense. At the end of the presentation most patients seemed eager to do the MP. However, the Swedish government prevents them from doing any treatment that is not deemed “standard.” My message to the group – go to Norway, a country nearby that allows doctors to do the MP without a problem. I hope they follow my advice despite the obvious hardship such advice entails. I’ll be creating a video version of my speech that should be up on this site soon.

On Sunday, after the conference had finished, all of us took the bright red #47 bus down to the Stockholm Square. By that point, I had realized that everything in Sweden runs smoothly. The buses come exactly on time. There is no traffic, the streets are so clean that sometimes the buildings look as if they are part of a movie set. In Sweden, an elevator is called a “hiss”, a term which makes me smile. It took me a while to learn that in Sweden hiss doors do not open automatically, rather they must be pushed open by the people inside. Particularly during the first days of the trip, I would forget this fact and wait inside the elevator for the door to open, much to the amusement of the Swedish people around me.

The Square was lined with other architectural masterpieces. Again, we could gaze out over the water and watch boats dock into the harbor. I had been looking forward to seeing the Square. After all, it’s the place where almost 20 years ago Dr. Marshall realized that sunlight plays a role in exacerbating chronic disease. He had been told that people in Sweden barely ever get enough vitamin D, but while waiting for a walking tour of the Square, sun streamed down on his face, and he felt physically ill. It was at that point that he started to question whether the current dogma on vitamin D and latitude makes sense.

Paul Albert encouraged Dr. Marshall to re-enact his eureka moment, which he did while standing in nearly the exact same location he had decades before. As I watched him joke around with Liz in an effort to recreate the moment, I was struck by how far he has come in the 20 years since that walking tour. I was struck at how far all of us on the MP have come, in terms of being part of a movement that will change so many paradigms in the medical world. I also marveled about the implications of the Marshall pathogenesis and how the best is yet to come.

Below is a link to a video created by Paul that chronicles some of what I have described above:

Here is a link to a second video clip which contains “outtakes” that did not make it into the main video: