Thursday, June 16, 2011

DUSTY MILLER REDUX

Second Email Exchange Between 
Dusty Miller and CFS Central

CFS Central:  You wrote: "Regarding the data in Lombardi et al., I was initially convinced by their extensive analysis, in particular, their ability to grow virus from patient materials. Indeed, we entered the CFS/XMRV field largely on the basis of these data. However, published and unpublished data now indicate that all of these methods were flawed.”
 
As far as I'm aware, no published or unpublished data indicates that the methods of Lombardi et al. were flawed. To what studies are you referring? 

Dr. Dusty Miller:  In the recent Science Express paper by Knox, ..., and Levy, the authors used three techniques to detect XMRV and related retroviruses in humans with CFS, and found none.  These techniques included nested PCR, an assay for infectious virus, and assays for neutralizing antibodies and other inhibitory factors in blood.  Importantly, many of the CFS subjects they studied came from Dr. Peterson's practice in Incline Village, and represent some of the same patients that Lombardi et al. studied.  Therefore, this is a close replication of the Lombardi et al. study.  The Knox study is in addition to many other negative studies cited in this paper (refs. 7-12).  

Lastly, the XMRV viral sequences deposited by Lombardi et al. in GenBank all are very closely related the VP62 XMRV sequence (see the supplemental material in Knox et al.), and the VP62 plasmid from Robert Silverman was apparently present in the labs of Lombardi et al., strongly indicating contamination of the Lombardi et al. PCR assays by VP62 plasmid DNA.  Putting all of this together leads me to conclude that the methods of Lombardi et al. must have been flawed.

CFS Central:  You also wrote: "Regarding the constant accusation that no one has carefully replicated Lombardi's methods, this is not true as far as most scientists are concerned. Initial reports attempting to replicate the study did have flaws, but many later studies are convincing.”

The problem with these later studies as I see it is that not one of the so-called replication studies was a bona fide replication. The patient cohorts and/or methods used were not identical. I learned in 9th grade science that being identical in cohort and methods are necessary for a true replication—otherwise you’re introducing variables that may account for the different findings. In your view, could the different methods/cohorts account for the differences in the findings? Why or why not?
 
Miller:  Please see my response above.  It is difficult to perform an exact replication study, which would involve going to the Mikovits lab and watching whoever did the previous study repeat it with the same patient samples.  Besides which, you may have also learned in 9th grade science that scientific results must be generalizable, that is, competent scientists must be able to repeat the experiments under somewhat different conditions and obtain similar results.  If the claimed result can only be obtained by performing the experiment in one spot in the Mikovits lab, perhaps while singing a particular song, then the results are not generalizable and should be looked on with suspicion. 

Tuesday, June 14, 2011

DUSTY MILLER'S
XMRV STUDY

Dr. Dusty Miller gave this statement to CFS Central about his XMRV study:

"Our paper is in press in the Journal of Virology, and should be available online through the Journal website on Wednesday this week.  We performed our study independently of the Paprotka et al. (including Coffin) study recently published in Science, but the results do overlap.  Essentially, we found an endogenous retrovirus (mERV-XL) in NIH/3T3 cells, a commonly used mouse cell line, that is virtually identical to what Paprotka et al. are calling PreXMRV-2.  You can find both sequences on the NCBI website.  One of the points we make is that all of the PCR primers used to detect the XMRV gag region can amplify a sequence identical to XMRV from NIH/3T3 cells, which are present in many labs.

"Unfortunately, we did not find an intact copy or the right half of XMRV in any of the mouse cell lines or tissue that we analyzed, but clearly we did not look hard enough.  Paprotka et al. firmly established the origin of XMRV from nude mice.  We were pursuing the same hypothesis, but could not get early samples of the cell lines and tissues from which the XMRV-carrying 22Rv1 cells were derived."

Monday, June 13, 2011

The Geniuses and the
Other Guys

 Burzynski's Cure and Coley's Lost Cure

The extraordinary documentary on Dr. Stanislow Burzynski has been making the rounds the past few days. Born in Poland, Burzynski now practices medicine in Houston, Texas, where he pioneered cancer therapy with antineoplastons, nontoxic peptides in the human body that prevent cancers. Burzynski discovered that cancer patients were deficient in antineoplastons and has been successfully treating patients with them for two decades.  His nontoxic treatment is far more successful that most current toxic chemotherapies and radiation, particularly for patients with brain cancer who haven’t had prior chemo and radiation.

Burzynski versus the government
While Burzynski has recorded phenomenal success treating patients, the FDA has tried to shut him down repeatedly.  The agency has taken him to court several times and tried—unsuccessfully —to haul him off to jail, while the National Cancer Institute initiated antineoplaston drug trials using too-low dosages to discredit Burzynski’s discovery, and the government managed to secure patents for antineoplastons, which Burzynski had already secured years earlier. 

My mother's cancer
Back in 1995, my mother was suffering from colon cancer.  My father, a physician, contacted Burzynski, who said that his treatment didn’t work for colon cancer—at least at that time.  So my mother endured the standard chemo—the aptly named 5FU—and died in 1998.

After she died, I started researching chemo drugs like 5FU and realized how useless most standard chemotherapy was for most tumors (the exceptions are testicular cancer, leukemia, lymphoma and Wilms’ tumor).  Boy, was I pissed; I realized how duped I had been. (My father knew 5FU wouldn't cure my mother, but what else was there?)  Reading cancer studies—not just the abstracts—I learned that most chemo and radiation shrink tumors but don't extend life, and when the tumors grow back, they’re often far more virulent.  That certainly was the case with my mother’s cancer.

William Coley
In my research, I came across the pioneering cancer research in the late 1800s of Dr. William Coley, a brilliant, handsome New York doctor at Memorial Hospital, which is now called Memorial Sloan Kettering.  His cancer research began in 1890, when Elizabeth Dashiell, a delicate young woman of 17, was diagnosed with bone cancer in her right hand. William Coley, a graduate of Harvard Medical School, was her 28-year-old surgeon.  Since her diagnosis had come early in the course of the disease, amputation of her afflicted arm below the elbow was swift.  Yet she died a few months later. 

Distraught over her death, Coley began poring over old patient records—for what, he wasn’t sure.  As Coley read the dusty charts, he saw that most cancer therapies failed; most of the patients died.  But curiously, one patient who was severely afflicted with sarcoma, a cancer of the connective tissue, did recuperate.  Hospitalized and near death in the fall of 1884, he experienced two outbreaks of a severe skin infection called erysipelas.  Caused by a strep bacterium, the infections resulted in high fevers and roused his sleepy immune system.  The bumpy, plum-sized tumor below his left ear began to shrink and the patient rallied, recovering completely.  When the tenacious Coley tracked the man down, he was well with no cancer recurrence some seven years later.

Uncharted territory
Because Coley’s discovery transpired more than a century ago when the immune system was uncharted territory, the scientist didn’t understand how the patient’s strep infection could bring about a cancer remission.  Nevertheless, the prescient physician thought perhaps he had stumbled across something important—a novel way to treat cancer—and began a series of experiments, injecting first live strep bacterium and later killed strep, as it was safer, into patients with sarcomas.  The first patient he treated recovered completely, many more followed, and the young surgeon soon published his first paper.  

But because scientists didn’t understand how the toxins worked, the treatment was never fully embraced. When Coley’s boss at Memorial, Dr. James Ewing—a snappish widower who liked his chicken rare, his lamb overcooked, and his clothes dated and baggy— decided to champion a new cancer treatment—radiation—the fix was in.  Radiation soon eclipsed Coley's toxins, Coley and Ewing became fierce rivals, and Coley's discovery was relegated to a footnote in cancer research.  In 1965, in what now seems an incredible lapse of judgment, the American Cancer Society consigned Coley’s vaccine to the list of “unproven” cancer drugs, where it joined the crooked ranks of coffee enemas and laetrile.  In fact, his toxins were a more effective cancer treatment than most current chemotherapy and radiation.

Book proposal
After reading about this extraordinary man, a century ahead of his time, I decided to write a book about him, with the working title The Genius and the Other Guy. My agent loved the book proposal but not the title, which he changed to The Lost Cure.  But the publishing houses didn’t go for it in any event.  “Who cares about a failed cancer treatment?” was the common refrain.
Ah!  If only the sheep didn’t dictate what books were sold, what drugs were approved and what scientific discoveries were embraced, we’d all be so much better off, wouldn’t we?

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Public service announcement:  People interested in being treated with the experimental ME/CFS drug Ampligen in the San Francisco Bay area and can afford the circa $2,500 a month that the drug and infusions will cost, please contact: samp511@comcast.net

ANIMAL FARM

The culture medium for the vaccines that many of us have received over the years includes cells from animals. It’s possible that these cells have harbored animal viruses or retroviruses, which subsequently piggybacked their way, via the vaccines, into humans.  Here are some of those vaccines:
Polio vaccine:  Monkey kidney tissue
Polio vaccine:  Mouse brain
Japanese encephalitis vaccine: Mouse brain
Rabies vaccine:  Rhesus fetal lung tissue
Rotovirus vaccine: Monkey kidney tissue
Vaccinia (smallpox) vaccine: Monkey kidney cell
Yellow fever vaccine; flu vaccine; rabies vaccine:  chicken embryo