Research Articles

Proteogenomics Interview 9/2/2012


When Dr. James Ryan and I announced the completed patent application and provisional patent for Proteogenomics LLC last month, I was a bit unprepared for the response. Instead of people saying something like, “This is a nice idea; let’s see how it works out,” what we received was a series of excited inquiries. This series of comments was just the earliest indication that users of this website are indeed way ahead of the crowd in the mold world. 


Maybe a recent interview I did for the Surviving Mold website would help answer some questions and stimulate (I hope!) some more.


Q.  How long have you been working on this project?

A.  We started drawing PAXgene tubes in 2007.  The saved blood has been stored in a cold freezer, one that is not frost free.  The clinical condition but not the patient names are included in a roster that now has more that 3000 entries.  Those patients who did not permit their blood to be saved for future research are not included.


Q.  What is PAXgene tube?

A. This tube is designed to treat whole blood with an ingredient that preserves the messenger RNA and micro RNA of white blood cells.  Once mixed, the tube will preserve the evidence of differential gene activation that occurs in illnesses.


Q.  What is differential gene activation? What significance do genes have in illness?

A. In the end, what our bodies do and how the body does what it does is determined by our genetic make-up.  Our DNA contains the coded messages of over 22,000 genes which can be activated, meaning the genetic message is being transcribed; or suppressed, meaning the message is kept quiet. Given that inflammation is a response to stimulus (attack), we would expect that (1) there will be a genetic basis of such response and (2) there might be differences in responses based on the characteristics of the invading antigen.  While the innate immune response system relies on pre-formed mediators, like cytokines and complement, release of these mediators results in the formation of new players that all are released in a coordinated fashion to (i) identify the offending antigen, (ii) create the series of events (called antigen presentation) that lead to antibody formation and then (iii) to stop the inflammatory response once the antigen is successfully removed.  The formation of these new players can only occur by virtue of gene activation.  Diseases of persistent inflammatory response are the result of problems with genes either doing unwanted things at unwanted times or not doing what the body needs to stay healthy. Failure of antigen presentation is an important concept here and this failure is believed to be the mechanism of association of certain gene types (HLA DR) with increased relative risk for given illnesses. This idea of aberrant antigen presentation is well represented in peer reviewed literature.


Q.  So let me make sure I understand.  I’m going to skip over antigen presentation for now. The body can fine tune its response to antigen attack by differential genetic activity? And if the genetic mechanisms aren’t working right, then normal physiology will be disrupted? That would mean that there would be a reason to look at abnormal labs and genes at the same time.   

A. Sure.  You are really on point with this question. We know a lot about gene activation and suppression in some diseases.  You might have heard of the genetic basis of cystic fibrosis, Charcot Marie Tooth disease, sickle cell anemia and Huntington’s chorea, for example.  The list of known genetic illnesses is actually quite long.  But looking at the much broader picture involved in acute and then chronic inflammation means that we are looking at many agents that could cause particular differences in illness presentation.  We would expect, for example, that lupus and rheumatoid arthritis would have a number of “bad” genes that are similarly activated and some “good” genes that are suppressed. But the illnesses look different, despite having many similarities, so we would expect the overall pattern of gene activation and suppression to be different for the two illnesses.


Q. Hold on.  It just occurred to me that what you are talking about is the possibility that each disease could have a unique pattern of genetic activity, a fingerprint if you will permit use of that word, which you could identify by looking at 22,000 genes.

A.  Precisely.  You hit that one right on.


Q.  Oh my.  Now I have a lot more questions!

A.  So do we!


Q.  So what is the patent for?

A.  We have asked for permission to say that we have a unique process that begins with history, physical, lab evaluation (called proteomics), adding differential diagnosis along the way that includes differential gene activity (called genomics).  The reason that the genomics is important is that simple recording of symptoms does not account for individual differences in what they feel and certainly won’t separate similar illnesses from each other. As we have seen in mold and Lyme (and illnesses from dinoflagellates and cyanobacteria, among other biotoxin illnesses), for example, is that the symptoms are identical.  Even worse for the clinician, labs can be eerily similar too, as usually the chronic inflammatory illness ends up presenting with the final common pathway of lab findings, as shown by the Biotoxin Pathway.  What the genomic information does is add the final assessment of diverse gene activation and suppression that separates one illness from another.


Q.  I think I get it.  As Dr. Robert Barnes has said, you start with a steering wheel, some tires and an engine that might be similar to other car manufacturers, but how you put everything together has enough differences that the final result is a car that doesn’t look the same as another, even though it has tires, and a steering wheel that might be the same. But more importantly the diverse series of elements that go into making a car are not the car itself. The patent is on the car: it involves the process of putting all the pieces together and the finished product.

A.  Right again.  Keep in mind that the process of making cars must be coordinated too, so that you aren’t painting the hood before the rear tires are put on.  Maybe that isn’t a great example, but the idea is that inflammatory responses, like making a car, should involve a one step at time in a series of events. There might be several things going on simultaneously in different parts of the body, like you would see in an assembly line, but the healthy inflammatory response gets to the end of the assembly line looking the same every time.  We don’t yet feel that you can simply look at genomics without using the entire process that begins with time-honored approaches to diagnosis.  Having said that, we feel the day is coming and isn’t too far off though for mold illness, as our data sets are robust for those patients.  Also, the proteogenomics of (1) untreated Lyme; (2) Lyme after a few weeks of antibiotics; and (3) Lyme after the inflammatory process is corrected is here now too.


Q. This is getting a bit deep.  So you are telling me that you think that sometime in the future, you will have enough information to say Lyme is there or not, or mold is there or not, with just one PAXgene tube?

A.  Yes, that day is here for mold and almost for Lyme; though because of all the controversy about Lyme we are still working on fine tuning the genomic assay.


Q.  Oh, so mold isn’t controversial?

A. Not really.  For anyone who has accumulated data bases on a cohort of successfully treated patients, there is no question that the illness is a systemic, chronic inflammatory response syndrome.  It is clearly shown as a result of the combination of genetic factors like the HLA DR immune response genes, inflammation from cytokines, inflammation from complement, inflammation from TGF beta-1 and IL-17, coagulation defects and the whole group of factors involved in loss of regulation of inflammation.  Treatment protocols have been peer reviewed and published for adults and children; then used by physicians all over the world. The problem with mold being called controversial is that in litigation, there are lawyers and their medical consultants who have never treated their first mold patient who simply make up things about the illness and allowed to say those things as facts in court. Shameful, really. Telling untrue stories under oath in exchange for legal and financial advantage ought to be called fraud.  Throw in perjury too.


Q.  Ok, I hear you about courts and expert testimony.  But let’s make sure I understand what the patent means.  You have identified a fingerprint that shows unique genomics for a variety of illnesses.  And you can use those unique sets of genomic findings to diagnose an illness.  So what about treatment?  Isn’t that what we all want is successful treatment? I mean if a gene is doing bad things, can’t you just turn it off?

A.  You weren’t kidding about a lot of questions.  But the simple answer is indeed so.  Remember I use an involved sequential protocol to treat the chronic inflammatory response syndrome. We are not done until the last step that needs to be taken is then taken. We say that the illness isn’t treated until final symptoms equal controls, final proteomics equal controls and final genomics equal controls.  The problem is that differential gene activity isn’t treated overnight with an antibiotic like the treatments that might help strep throat. We now know that many factors contribute to gene activation.  Maybe an analogy to a freight train might help.  Imagine 10,000 tons of steel roaring down towards Union Station.  You won’t stop that train right away by just pulling on the brake.  For some, the illness is like 10,000 tons of inflammation.  Treating these illnesses means learning patience! The point is that some genes aren’t turned on and off easily.


Q.  If inflammatory illnesses involve differential gene activation/suppression, and I really do get it now, how does genomics help us understand treatment?

A. That question is so important.  We know that many factors contribute to genomic findings.  For example, in years gone by I knew that if the biofilm-forming coag neg staphs, those multiply-antibiotic resistant, commensal bacteria that colonize the back of the nose, aren’t removed, the patient won’t get better.  We now know some of the genomic reasons why that observation is correct. We know that TGF beta-1 and C4a have genomic effects and that treatment with VIP appears to be phenomenally successful in correction of genomic factors as well.  Those data need some more work before we share our findings with the public. Be patient with us here. We have also looked to see if some treatments out there don’t provide genomic benefit (like methylation and glutathione, for example). I am not going to talk much about failed therapies, except that we all should learn from failure.


Q.  Anything else before I go?

A.  Well, there is a lot of detail that we didn’t go over that is important too. You need to know that the PAXgene tubes can be sent in by physicians to us for analysis.  We encourage physicians to contact this website ( if they want more information about genomic testing. We do need to polish the invention before we can simply open up these tests to the general public, but that work should be done in a few months.


Q. I am hearing your excitement now.  Will this invention be life-changing?

A. It already is.  The applications are countless.  For example, we are seeing in early data a genomic finding that might just be the unique fingerprint for chronic pain patients; another for those with demyelination; and those with hyper-flexibility too.  If patients are interested in learning more, for now, have their physicians contact the website. In the near future, there will be website just for the proteogenomics.  That site is It is now under construction.  I will let you know when it is up.