1974 – Teaching in Papua New Guinea, Trevor Marshall experiences tropical sun - an experience which would prove crucial twelve years later.
1978-1982 – Marshall works towards his PhD thesis. His work includes the design of portable, battery operated programmable pumps for the delivery of pulsatile GnRH and LHRH for treating cryptorchidism as well as both male and female infertility.1) 2) The use of pulsed doses of therapeutic drugs has a key place in the Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis. years later.
1981 – While a Visiting Scientist in the Dept. of Surgery at Toronto's Hospital for Sick Children, Marshall sees IBM's presentation of a few nano-seconds of life of a humulin molecule (synthetic human insulin). The presentation is one of the first in silicoExperiment technique performed on computer or via computer emulation. models.
1984 - Marshall's PhD thesis “Modelling and simulation in diabetes care” reveals the interest in mathematical modeling of human disease which would guide his research two decades later.
1986 – Standing in a city square in Stockholm, nearly the most northerly capital in the World, Marshall's body reacts badly to sunshine. He realizes that his sensitivity goes beyond anything medicine had envisioned, and that vitamin D must in some way be associated with chronic disease.
1999 - Marshall begins therapy for pulmonary hypertension with a class of drugs known as Angiotensin Receptor Blockers (ARBs), specifically the class of Angiotensin II receptor antagonists called the sartans. Drawing on his knowledge of pharmacology from his thesis research, Marshall realizes that the customary 24 hour dosing cycle for ARBs is sub-optimal, and calculates the 8-hour cycle which persisted until 2006.
1999 – Marshall learns that other patients with sarcoidosis who were administered Angiotensin Receptor Blockers (ARBs) often developed a neurological reaction. Marshall starts a sabbatical in early 2001 in order to further investigate this reaction.
2001 - Marshall submits paper explaining that sarcoidosis could have a bacterial pathogenesis. Three revisions of the paper are rejected by the journal Sarcoidosis, Vasculitis and Diffuse Lung Diseases as having no potential interest for its readers.
2001 March - The first early adopter, Elaine Emmi, begins the use of an ARBA drug which is an angiotensin receptor blocker. One of the ARBs is olmesartan (Benicar). Not all ARBs activate the Vitamin D Receptor. to treat her sarcoidosis.
2001 December - Nilsson et al. publish article in Journal of infectious disease showing that deceased sarcoidosis patients contain the genetic material from Rickettsia helvetica in the cytoplasm of cells within sarcoid granuloma.3) Marshall commences using pulsed, sub-inhibitory, doses of antibiotics in an attempt to reverse his sarcoidosis.
2002 March – Marshall registers Sarcinfo.com, a forum-based website where patients sick with sarcoidosis begin to discuss a novel antibacterial therapy for the disease.
2002 May – Marshall changes to using the ARB olmesartan medoxomil (Benicar).
2002 August – Trevor Marshall and Frances (Liz) Marshall publish NetPrint, “Valsartan Dosing Regime Modulates Psychotic Events in Two Sarcoidosis Patients.” The case report shares early observations that valsartan (Diovan) induced hallucinations and psychedelic dreams. Convinced that they have developed a pathogenic description of sarcoidosis, they write the Netprint “Remission in Sarcoidosis”
2002 September – “Remission in Sarcoidosis” is published (in summary) at Mercola.com. Later that month, early adopter (and colleague) Belinda Fenter commences pulsed minocycline.
2002 December – Early adopter (and colleague) Meg Mangin commences pulsed tetracycline.
2003 January – A meeting with Dr. Alan Cantwell brought to light papers by Lida Mattman.4) 5) 6) Seperately, images from Emil Wirostko's group7) 8) 9) finally confirmed that a cytoplasmic microbiotaThe bacterial community which causes chronic diseases - one which almost certainly includes multiple species and bacterial forms. of intraphagocytic, L-form bacteriaDifficult-to-culture bacteria that lack a cell wall and are not detectable by traditional culturing processes. Sometimes referred to as cell wall deficient bacteria. must drive the biochemical changes observed in sarcoidosis.
2003 January – Mangin changes to minocycline and commences concurrent olmesartanMedication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. Also known by the trade name Benicar. . Fenter also commences using olmesartan. They are joined by Ms. Dale Thurlow, and Marshall's Protocol has taken root. Later that month Trevor Marshall and Frances (Liz) Marshall publish “New Treatments Emerge as Sarcoidosis Yields Up its Secrets” on Clinmed, after it is savaged by two pulmonologist peer-reviewers for “BMC Pulmonary Medicine”
2004 April – Autoimmunity Research Foundation is founded.
2004 June – Trevor Marshall and Frances (Liz) Marshall publish “Sarcoidosis succumbs to antibiotics: implications for autoimmune disease.”10) This time it is accepted and published online in the peer-reviewed journal Autoimmunity Reviews, later to appear in the Print Edition. The paper explains how cell wall deficient bacteria are responsible for sarcoidosis and may in fact be responsible for all chronic diseases. It also describes a Jarisch-Herxheimer reaction resulting from endotoxin release as the microbes are killed.
2004 July – Marshall speaks at 4th International Congress on Autoimmunity in Budapest.
2004 July – Marshall registers MarshallProtocol.com, a website where patients sick with a range of chronic diseases discuss an antibacterial therapy since named the “Marshall Protocol.” – Aussie Barb joins MarshallProtocol.com and begins to perform an invaluable behind-the-scenes role on the study site.
2004 December - The Journal of the Interregional Clinical-Diagnostic Center, Kazan, Russia, (ISSN: 1726-6149) publishes, in Russian translation, Marshall's paper “Antibacterial Therapy Induces Remission in Sarcoidosis” in its special issue on Sarcoidosis.
2005 March – ARF's 'Recovering from Chronic Disease' conference held in Chicago. Notable speakers include Lida Mattman PhD and Dr. Andrew Wright.
2005 June - Marshall publishes the English text of the Russian paper “Antibacterial Therapy Induces Remission in Sarcoidosis”
2005 July – Marshall files for patent with US Patent and Trademark Office (eventually published in February 2006) which explains a method of killing the stealthy intracellular bacteria which cause many Th1 and “autoimmuneA condition or disease thought to arise from an overactive immune response of the body against substances and tissues normally present in the body” diseases. A second patent which specifies a broader range of chronic diseases is filed in December 2006.
2006 January – Trevor Marshall, Robert Lee, and Frances (Liz) Marshall publish paper in Theoretical Biology & Medical Modelling explaining how angiotensin receptor blockers directly modulate the immune system via the VDRThe Vitamin D Receptor. A nuclear receptor located throughout the body that plays a key role in the innate immune response., PPAR and CCR2b nuclear receptorsIntracellular receptor proteins that bind to hydrophobic signal molecules (such as steroid and thyroid hormones) or intracellular metabolites and are thus activated to bind to specific DNA sequences which affect transcription..11)
2006 March – As part of Visiting Professor Lecture Series, which is organized by the FDA's Center for Drug Evaluation and Research, Marshall presents on “Molecular genomics offers new insight into the exact mechanism of action of common drugs: ARBs, statins and corticosteroids.”
2006 March – Autoimmunity Research Foundation wins orphan drug status for the antibiotic minocycline, the first Marshall Protocol medication designated with the status.
2006 July – Marshall presents poster at Days of Molecular Medicine, the first of three such annual presentations, which would alternate between Karolinska (Sweden) and Harvard.
2006 October – Marshall presents at American Academy of Environmental Medicine on “A new approach to treating intraphagocytic CWD bacterial pathogens in sarcoidosis, CFS, Lyme and other inflammatory diseases.”
2007 July – Marshall presents abstract at Metagenomics 2007, “Bacterial Capnine Blocks Transcription of Human Antimicrobial Peptides.” The presentation provides proof of concept for the hypothesis that disease-causing bacteria can produce ligands which disable the Vitamin D ReceptorA nuclear receptor located throughout the body that plays a key role in the innate immune response..
2008 February – Marshall publishes in Bioessays, “Vitamin D discovery outpaces FDA decision making.”12) The paper explains how lifelong supplementation of the food chain with vitamin D might well be contributing to the current epidemics of obesity and chronic disease. It also puts forward the first working model of vitamin D metabolism.
2008 September – Marshall chairs session on vitamin D at International Congress on Autoimmunity in Porto, Portugal. Invited speakers for the session include Autoimmunity Research Foundation's Capt. Tom Perez MPH and Marshall. Also speaking are MP physician Dr. Greg Blaney and MP colleague Dr. Amy Proal.
2008 December – Marshall gives keynote address at Conference of the Gene in China.
2009 – A total of five peer-reviewed papers are published by members of the ARF Research Team.
2010 to date - Marshall and his Colleagues travel all over the world to speak at medical conferences and form collaborations aimed at helping Medicine deal more effectively with chronic disease.