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JFS: Immune therapy started with Dr. William Coley at the end of the 19th century and the beginning of the 20th century. However, the 20th century has been the century of the pharmacology approach in medicine. Teams and researchers like yourself are now working in the 21st century on immune therapy, and have rescued this fundamental approach to the future of medicine. Bearing all this in mind, how do you forecast the future of medicine in the years to come?



MR: It is interesting that you mention the work of Dr. Coley, the father of immunotherapy, since such an approach is being rediscovered in these very days. In a publication in PubMed, aptly titled "Back to the Future," the author writes: "Cancer patients infected with various bacteria were reported, for at least two centuries, to have spontaneous remission. W.B. Coley, of what is now the Memorial Sloan-Kettering Cancer Center, pioneered bacterial therapy of cancer in the clinic with considerable success beginning in the late nineteenth century. After Coley died in 1936, bacterial therapy of cancer essentially ended. Currently there is much excitement in developing bacterial therapy for treating cancer using either obligate or facultative anaerobic bacteria." (Methods Mol Biol. 2015;1317:239–260). It should be noticed that Dr. Coley had spectacular results in very advanced cancer cases, results that we cannot even dream of with our most advanced therapeutic strategies. The problem with Dr. Coley's approach, however, was the lack of standardization and, because of this, the difficulty of reproducing the results that he consistently obtained on a large scale. Quite obviously, our knowledge of the mechanisms of cancer is now much more refined, at the molecular level, and we also know the role of the microbiome in health and disease; therefore, many researchers think that the time is ripe to rediscover Dr. Coley's observations and interpret them in light of today's knowledge, with the hope of finding a reliable way to treat patients otherwise labeled incurable. Such an approach is becoming "mainstream," up to the point that the journal Science recently wrote: "A new class of cancer treatments that unleash the power of the immune system on tumour may depend on some unlikely allies (the microbes)" (2015 Nov 6;350[6261]:614–615). In my opinion, these words do justice to the work of Dr. Coley, since they clearly state that the microbes "unleash the power of the immune system" that in turn represents "a new class of cancer treatments." It has to be said that researchers are exploring rather innovative ways to exploit the abilities of microbes to fight cancer, and they are finding allies that are even more "unlikely": the viruses! In a paper titled "Combined Bacterial and Viral Treatment: a Novel Anticancer Strategy," the author argues: "An idea for a new combination therapy will be described herein. It is a proposition to combine viral and bacterial anticancer therapies and make them fight cancer in concert" (Cent Eur J Immunol. 2015;40[3]:366–372). It may come as a surprise to learn that a virus that could potentially be exploited to fight cancer is no one less than … HIV! As I write, together with John W. Anderson, in the Encyclopedia of Cancer, " … there exists a HIV accessory protein termed viral protein R (Vpr) that plays a key role in virus replication and also induces cell cycle arrest and apoptosis in various cell types including T cells, neuronal cells, and tumor cells." Thus, as odd as it may seem, a protein produced by HIV could be exploited as a beneficial antitumor agent in cancers. … In recent years, several investigators have studied the potential use of Vpr as an antitumor therapeutic. … "The antitumor properties of certain HIV proteins might even have been responsible for establishing a symbiotic relationship in humans. … " (Encyclopedia of Cancer. doi:10.1007/978-3-642-27841-9_562-4). These observations are consistent with a rather odd report from Columbia University describing how women carrying HIV, or at least its antibodies, appear to have a better 5-year survival rate (80%) when compared with the general population (70%) (J Surg Oncol. 2005 Jan 1;89[1]:23–27). All these results and the deriving considerations lead me to speculate that we may be on the verge of a revolution in cancer therapy and ready to rediscover and appreciate the long-neglected work of Dr. Coley.



JFS: Could this approach, at least in Western countries, counterbalance and refocus the dominance of pharmacological approach in modern medicine by giving more freedom to doctors in order to be able to use all the tools at their disposal?



MR: I truly think that rock-solid scientific evidence is accumulating and supporting those approaches once labeled "alternative." The microbial therapies of cancer are just an example of such a rapidly evolving field. Regrettably, laws and regulations follow much more slowly, and it may take years before such approaches are officially recognized by regulatory bodies. However, the use of Internet by patients is rapidly changing the scenario within which therapists are called to operate. In fact, it often happens that patients are more updated and prepared than therapists, and it is not infrequent to notice that patients go to their doctors asking for approaches that have solid scientific evidence although they may not yet be approved by regulatory bodies. Patients are often prepared to travel long distances to have therapies performed when these are not available in their countries. Internet, low-cost flights, and globalization are changing also the way that patients perceive their quest for health, and the world of medicine has to adapt if it wishes to survive. The same reasoning applies to doctors as well. It is now commonplace to find European or American doctors in wealthy countries in Asia or the Middle East, free to practice innovative therapeutic approaches with great benefits for those patients who can afford the expenses. If Western medicine does not adapt itself, this phenomenon will only increase, and, sadly, only the wealthy will be able to benefit from the latest discoveries in medical science.



JFS: The lack of development of molecules such as GcMAF or heparin could be interpreted as "laziness" by the pharmaceutical industry. The production of such immune components has shown amazing results, being much less harmful that conventional treatments, and less toxic when those treatments need to be administered. Why? Is there a conflict of interest or simply a lack of interest from allopathic medicine and Big Pharma?



MR: Having worked in the pharmaceutical industry in the US and in Europe, I can say that, just like any other industry, the pharmaceutical industry is not driven by ideology but by profit. Therefore, so-called Big Pharma is not for or against alternative or complementary medicine; it simply follows the paths that lead to profit, and as of today the research and development of allopathic drugs has proved very effective in this respect. The responsibility for such a situation also lies in part in the alternative-practitioner community, which sometimes has a sort of ideological approach to medicine and health-related issues and is against the industrial approach a priori. It is also true that many natural remedies show little appeal to the pharmaceutical industry because it is difficult to patent them and therefore profit. However, I have the perception that things are changing and I am observing a phenomenon that I have already witnessed in the 1980s. Back then, Big Pharma was not interested in the emerging field of molecular biology and biotechnologies; it was focused on the old-fashioned approach of skilled chemists' synthesizing thousands of putatively helpful molecules in their labs. The community of molecular biologists, however, was composed mainly of hippie-type biologists, rather than chemists in their white coats, and they focused on the biological processes that lead to the onset of diseases, with the goal of exploiting such a knowledge to develop naturally based molecules aimed at restoring cells' physiology. Those scientists begun founding their microscopic companies, sometimes in little more than their garages, with the goal of producing one single antibody or one single biologically derived molecule. Thirty years later, such companies evolved into the gigantic biotech industries that we know today and lead the market in the research and development of remedies based on the knowledge of how cells function. I hope that such a transition will occur also for what is now defined as alternative or complementary medicine, and I see many signs that this is already occurring.



JFS: The final chapters of Your Third Brain raise a fascinating field ultrasonography and ultrasound. To what extent could this "remote control" science revolutionize the field of immune therapy?



MR: At variance with common perception, ultrasounds are not generated exclusively by machines such as those that are used in diagnostic ultrasonography, a branch of radiology that I mastered in the past. Ultrasounds are commonly generated in nature and are perceived by animals, as anyone who has a god knows very well. According to some theories, ultrasounds have shaped the universe as we know it, and they may have contributed to shaping the DNA that codes for life on this earth. Therefore, it is not surprising that there are genes in our DNA that are turned on by ultrasounds, and, by a leap of imagination, we could visualize someday having a remote control that lets us turn on or off genes, just as we zip between television channels from our sofas. And such a day may be closer than we think. Since 2013, we have published papers demonstrating that ultrasounds alter mental states and may be useful in the treatment of a number of diseases. Quite recently, we published two papers demonstrating how ultrasounds improve neuronal connectivity and how such an effect may be applied to neurological conditions such as autism (Conf Proc IEEE Eng Med Biol Soc. 2015 Aug;2015:8131–8234; Biomed Signal Process Contr. 22[2015]:44–53). These results of ours are consistent with previous observation by Hameroff and colleagues, who described how ultrasound could be used to address untreatable pain (Brain Stimul. 2013 May;6[3]:409–415), and more recent reports describing the potential use of ultrasounds in a series of neurological diseases (Nat Rev Neurol. 2016 Mar;12[3]:161–174). As far as of cancer immunotherapy is concerned, there are not very many studies demonstrating such an effect of ultrasound, probably because most researchers, including ourselves, were mostly interested in its effects on the brain. However, in some preliminary experiments that have not yet been published, we noticed that ultrasound at certain frequencies can kill cancer cells, leaving the healthy cells unharmed. This selectivity can be explained by taking into account the fact that cancer cells have a metabolism quite different from that of normal cells, and therefore the effects of the ultrasound seem to be detrimental to them. Interestingly, healthy cells not only do not suffer any damage as a consequence of ultrasound treatment, but they also seem to be stimulated in their functional activity. In other words, at least in vitro, ultrasounds seem to have a sort of "magic touch" on cells; they kill the cancer cells while benefiting the healthy cells at the same time. Although the precise mechanism of action still has to be determined, such effects are currently being exploited in the field of cancer immunotherapy. For example, in 2014, our Japanese colleagues and competitors in the field of GcMAF research published a paper demonstrating how the combination of GMAF injections and ultrasound therapy (designated sonodynamic therapy) was very effective in breast cancer treatment (Anticancer Res. 2014 Aug;34[8]:4577–4581). In the past few days, working together with one of the most respected medical doctors in the field of integrative medicine, we noticed that a careful application of ultrasound after specific immunotherapy significantly amplified the effects of the immunotherapy itself. Since ultrasound is inherently safe and harmless, as demonstrated by some 50 years of diagnostic ultrasonography, I think that such an approach will become commonplace in a very short period of time.



JFS: What last message could you give to our readers?



MR: I wish to give the same message that I used to give my patients not long ago: every day we are witnessing a new boost in scientific discoveries that, at variance with the past, now can immediately be applied to the individual case. Therefore, diseases that yesterday were deemed incurable today can be successfully fought. We are learning so many things about the immune system, the microbiome, the relationship between our human and nonhuman brains, that yesterday's knowledge already is obsolete. Cancer, autism, and neurological or cardiovascular diseases can now be approached with a variety of options that offer realistic hopes to cases previously designated incurable. We live in a most exciting time, and it seems that there are no boundaries to what we may achieve in health and medicine if we are open to the progress of knowledge. Jacques Fernández de Santos is an independent journalist based in Spain who has covered different countries, analyzing their economies, politics, and social issues. He has covered missions in countries such as Ukraine, Brazil, Jordan, Bulgaria, Kurdistan-Iraq, and Turkey. His last mission was in Morocco in 2015 (www.marco-hub.fr). He also occasionally undertakes scientific interviews with researchers such as Dr. Marco Ruggiero. Page 1, 2, 3, 4