Monday, November 28, 2011

Question of HIV's pathogenesis an interview with Marco Ruggiero MD, PhD Full Professor of Molecular Biology Clinical Radiologist University of Firenze, Italy

An interview with Marco Ruggiero  MD, PhD  Full Professor of Molecular Biology Clinical Radiologist  University of Firenze, Italy by the

Q: In April of 1984, (I don't know how old you were then) when Dr. Robert Gallo stood before the world at the famous NCI press conference and said his lab had isolated a pathogenic retrovirus that was the "probable" (Heckler) cause of AIDS, what did you think then? *

A: In April 1984 I was getting ready to move as post-doctoral fellow to Burroughs Wellcome Co., Research Triangle Park, NC. I had learned about this “new epidemic” in 1982-83, when I was serving as sub-lieutenant medical officer in the elite corps “Carabinieri”.

marco-ruggiero-carabinieri.gifIn fact I had been trained in non-conventional warfare (nuclear, biological and chemical) and there was interest in learning whether this “new epidemic” could have been of interest for the military both from the point of view of prevention or as a biological weapon. When we learned of Gallo’s claim, we had no opinion at that time and we just recorded his statements. Curiously enough, at Burroughs Wellcome I worked on protease inhibitors, although with objectives other that preventing retroviral replication, and, together with my supervisor, Dr. Eduardo Lapetina, we wrote a paper on protease inhibitors that was appreciated by Nobel Laureate Sir John Vane who communicated it to the National Academy of Sciences of the U.S.; the paper was published in PNAS in 1986 (Proc. Natl. Acad. Sci. USA 83: 3456-3459, l986). In the corridor next to our laboratory, other researchers were working on AZT and similar compounds, and we frequently had meetings discussing the progresses of our research.

Q: Were you trained to think that a) ‘retroviruses’ existed as a new class of viruses, that b) "they" were benign, that c) they were benign but THIS ONE was pathogenic?

A: During the years of the university as medical student (1974-1980), we received little training about retroviruses that, until that time, were considered little less than microbiological curiosities. I began to learn a little bit more about them when, after the military, I moved to the laboratory of molecular biology of the University of Firenze, directed at that time by Professor Vincenzo Chiarugi, heir of the famed Dr. Vincenzo Chiarugi, one of the founders of modern psychiatry. Vincenzo was interested in retroviruses because of viral oncogenes and thus we began studying these viruses, with particular reference to Harvey’s sarcoma virus* harbouring the ras oncogene.
*Harvey murine sarcoma virus: A replication-defective mouse sarcoma virus first described by J.J. Harvey in 1964.
One of the first oncogenes to be defined in cancer research is the ras oncogene. Mutations in the Ras family of proto-oncogenes (comprising H-Ras, N-Ras and K-Ras) are very common, being found in 20% to 30% of all human tumours. Ras was originally identified in the Harvey sarcoma virus genome, and researchers were surprised that not only was this gene present in the human genome but that, when ligated to a stimulating control element, could induce cancers in cell line cultures.

At that time we were all convinced that retroviruses caused tumours and other diseases in animals, but not in humans. At that time we were also very sceptical about HTLV-1 and 2, because these putative human oncogenic viruses did not fit in the retroviral oncogene theory that we embraced at that time. Because of this, we could not understand how, from the molecular point of view (we all were, and I still am, primarily molecular biologists), such a small retrovirus could cause so many damages. In particular, we could not identify the retroviral genes responsible for such dramatic cell damages.
Q: Do you think HIV exists as a unique and exogenous retrovirus?
A: Yes I do. However, as a scientist I rely upon data. If there are data demonstrating that the nucleotide sequence attributed to HIV is homologous to sequences present in the diploid human genome, then I shall have no difficulty in defining HIV as a human endogenous retrovirus. The entire human diploid sequence (at least the sequence of one individual) is freely accessible here: NEW INDIVIDUAL HUMAN DIPLOID GENOME. It will not be difficult for anyone who doubts of the existence of HIV to compare HIV and human sequences in order to find homologies. Such homologies have not been found so far, to my knowledge. However, there is an emerging and fascinating field: the human microbiome project (HMP) (See Also: J. Craig Venter Institute). Maybe HIV could be part of it. If we think about the implications of the HMP, then the very question about the existence of HIV or of myself has to be re-formulated. In fact, so far, I define myself as the organism coded for by my individual sequence ATGGTTAATT … and so on for about 3 billion base pairs. But, from the HMP point of view, I should now define myself as an ensemble of organisms: one of these organisms is the one coded for by ATGGTTAATT. Then there are ten times more cells of other organisms about which we know almost nothing: the entity that calls himself Marco Ruggiero in reality is not ONE organism, but an ensemble of who knows how many. The very question of individual existence is now challenged.
Q: If yes, do you think it is transmitted sexually?
A: With the caveats described above, yes, I do. However, the HMP teaches us that innumerable other micro-organisms will probably be transmitted sexually. For sexual transmission of AIDS (not HIV), please see the data on teenage sex quoted below.
Q: Do you think it "does" anything, cellularly?
A: Yes, as any other micro-organism interacting with our cells. Any retrovirus, harmless or not, by the simple fact of integrating its genome in the human genome, modifies the human genome, adding some information. Because of this, 8% of the human genome is made of retrovirus-like elements/sequences (just to give you an idea, gene sequences coding for proteins, i.e. those sequences that we refer to any time that we speak about the human genome, account only for about 1.5% of the human genome. We could say that we have more retroviral sequences than coding genes, even though such a statement is not completely correct from the molecular point of view). The main question is: does it cause cell death/damage in such a way that a disease arises? In fact, even cell death is not per se pathogenic. As a matter of fact, cell death by apoptosis is a physiological mechanism that protects us from mutations, cancer and a number of other diseases including microbial diseases. Although the evidence for an association between “signs of HIV infection” and AIDS is overwhelming, a cause and effect relationship has been very difficult to prove and such demonstrations are not convincing. I believe that there is no need to remember that the belief, correlation proves causation, is a logical fallacy by which two events that occur together are claimed to have a cause-and-effect relationship. The fallacy is also known as cum hoc ergo propter hoc (Latin for “with this, therefore because of this”) and false cause.
Q: Do you think testing HIV positive means one has been ‘infected?’

A: Any test, by definition, cannot be 100% accurate. Specificity and sensitivity often are inversely related; therefore un-specific diagnoses of HIV-positivity are likely to occur as with any other test. In general, however, once such problems have been resolved, I would say that in the presence of confirmed antibodies and detection of the so-called viral load (although often over-estimated), I would say that an encounter with the virus has occurred. However, this could simply indicate an association between two things that are not necessarily correlated with a cause and effect relationship. If we adhere to the statements of Prof. Montagnier, as I do, then the persistence of signs of HIV infection could simply be an indicator of immune system malfunction. In this interpretation, immune system malfunction is the cause and chronic HIV infection (along with other opportunistic infection) one of the effects, probably not the worst one. In other words, HIV infection could be the symptom of an existing immunodeficiency.

Q: Do you think that "getting rid of" (Montagnier) HIV is the holy grail of restoring immune function in AIDS patients?

A: If we succeed in eliminating the virus by stimulating the immune system without targeting the virus itself, this would demonstrate without any shadow of doubt what I mentioned above. This has been achieved, published in 2009 and never confuted (J Med Virol 81:16-26, 2009). We are now conducting experiments to demonstrate how does this work at the molecular level and some of our data have been published in December 2010 (Cancer Immunol Immunother). There are ongoing clinical trials with GcMAF on HIV-positive and AIDS patients in order to replicate the trials described in J Med Virol. Some of our clinical trials and case reports with GcMAF in HIV+ and AIDS patients will be presented this year at some congress and we shall try to publish them. This approach, however, is not “dissident.” At the XVIII Intl AIDS Conference in Vienna in July 2010, there were communications describing how quitting antiretroviral therapy and shifting to immunotherapy improved quality of life. In one of these communication, the Authors propose an immunotherapy slightly different than the one described in J Med Virol, but using an identical approach. From the Conference of Vienna:


Q: Describe the evolution of your thinking about HIV and AIDS, since you entered the field, and also, how these ideas evolved in Italy.

A: From 1984 until 1987, I did not care much about HIV and AIDS. While in the Military, we had determined that this was not a biological weapon and that it was restricted to risk groups (IV drug abusers and a very small percentage of active male homosexuals); by the way, the same scenario is true as of today, and we published it in the Italian Journal of Anatomy and Histology, vol. 114, 97-108, 2009. Please notice that the Italian Journal of Anatomy and Embryology is the official journal of one of the most prestigious Italian and international scientific societies, the Italian Society of Anatomy and Histology, founded in 1929. The journal is peer reviewed and listed in major indexing systems including . The journal has no commercial purpose and does not host advertisements. All papers are written in English. All information about the journal can be found here: Italian Journal of Anatomy and Embryology.

In 1987, I was working on intracellular signal transduction, i.e. the study of those signals that control cell proliferation, differentiation and death. I had acquired a certain expertise at Burroughs Wellcome and because of this, I was called to join the Laboratory of Cellular and Molecular Biology of the National Cancer Institute at the NIH in Bethesda. The laboratory was then directed by Dr. Stuart A. Aaronson and we were all working on oncogenes with great success. We were located at the first floor of the building, whereas Dr. Robert Gallo had his laboratory at the sixth floor. Several Italian fellows were working with Dr. Gallo and we often met at parties. In October 1987, just as I arrived at the NIH, Prof. Peter Duesberg was visiting our laboratory and we happened to share the office for some time. Needless to say, I remained fascinated by his logic and I began to be interested again in the aetiology and pathogenesis of AIDS. In a memorable lecture, where people had to stand because the main hall was too crowded, Prof. Duesberg convinced me of the correctness of his hypothesis and ever since I have been striving at finding a truly scientific way to demonstrate it. 24 years later, we think that we have found it. You remember that at time Prof. Duesberg was stating that he was not afraid to inject himself HIV provided that it did not come from Gallo’s lab. Therefore, at his farewell party the youngsters prepared a big syringe filled with pink medium, haemostatic lace, alcohol and cotton balls and we teased Peter to go ahead and test his hypothesis. We now know that such an experiment would have been useless and destined to fail. In our paper (Italian Journal of Anatomy and Histology, vol. 114, 97-108, 2009) we report that occupational exposure to HIV is uncommon, and the overall risk of seroconversion after contact with HIV positive blood is extremely low (seroconversion rate, 0–0.42%). It is calculated that, on average 99.7% of health care workers, who are exposed to HIV, will not be infected (Ippolito et al., 1993; Marcus, 1988). In general, most health care professionals found to be HIV-positive have a history of behavioural (male homosexual contact or intravenous drug use) or transfusion exposure (Chamberland et al., 1995). These published statements are for those who propose that dissidents should inject themselves with HIV if they truly believe that it is harmless; well, it has been already done thousands of times with freshly collected HIV-infected blood and it does not work!

Q: Why is it NOT as you say problematic to a career, in Italy, to posit that HIV is not the cause of AIDS? What was it that made the climate safer in Italy than in, say, the United States? You have said you are shocked by the violence perpetrated against HIV dissenters in the U.S. and other countries. Can you elaborate on this a little bit?

A: I guess that there is more than one single answer to the first question. First of all there is the historic precedent of the lack of freedom during the Fascist era. During that era, university professor could not teach freely and their lectures were controlled by the authorities. Because of this, our republican constitution guarantees, in addition to the obvious freedom of speech, a very specific freedom of teaching at the university level. No authority in Italy, including our Prime Minister, should he be interested in the topic, can forbid a university professor to freely teach any kind of theory in his field. And it happens that viruses are among the topics covered by the teaching of molecular biology, as defined and established by the Ministry of the University. As long as I teach a topic that is considered within the definition of my field of expertise, in my case molecular biology, my freedom is total and unquestioned. Of course, during the course of molecular biology I cannot teach, let’s say, a novel interpretation of history or religion. As a matter of fact, quite recently a distinguished Italian professor of microbiology, now retired, close associate of Drs. Gallo and Moore, probably upon instigation of the latter, wrote an accusatory letter to the Chief (Rettore) of my University, denouncing my teaching of “unscientific” theories (HIV is not the cause of AIDS). The Rettore (I do not know how translate this term, maybe Provost, in other words the highest authority of the University), wrote him back a three line letter (that he CC’d me) reminding him, as he should have known, that our constitution guarantees freedom of speech and freedom of teaching. And that was it. Period, end of report. Quite different than the accusations, trials and so on that Prof. Duesberg had to endure last year for an identical occurrence.

Here I refer to the differences between U.S. and Italy. In particular I refer to the management of the accusations that led to the investigation on Peter Duesberg by the University of Berkeley in the spring of 2010. Those accusations led to an investigation and to a sort of a trial on Duesberg. Identical accusations led to nothing more than a few line letter here in Firenze. In fact, having failed with Berkeley that decided, after long hearings and discussions, meeting of experts, lawyers and so on, that Peter had not done anything wrong, they tried with me. These are the details: Professor Michele La Placa, retired Professor of Microbiology, strong supporter of Drs. Gallo and Moore (refer to links below), wrote a letter to the Chief (Rettore) of the University of Firenze, denouncing my approach to HIV and AIDS. I did not read the letter that Prof. La Placa wrote to the Rettore, but I received (as cc) the letter that the Rettore wrote him. It reads (verbatim translation).

Dear Professor La Placa,

I acknowledge receipt of your letter of October 16, 2010 (registered with n. 20.10.2010). As far as the substance of your letter is concerned, I cannot but state that, as you should know, freedom of teaching is in our corpus of laws and it is related with the amplest sphere of freedom of expression and communication of thought guaranteed by our Constitution. Such a freedom, by the way, concerns all dimension of free cultural expression of the profession of teaching that is realized within the laws and rules concerning the matter.

Sincerely yours,
Prof. Alberto Tesi,
Rettore dell’Università di Firenze.

It could be that in the U.S., not having experienced a dictatorial regime, you are not equipped to protect your freedom of speech that includes freedom of teaching. Here, freedom of teaching is sacred and unquestioned.

Another difference with the U.S. could lay in the fact that AIDS is a very marginal health problem in Italy and no one really cares; therefore, disputes about its causes are considered little more than extravagancies. In our beautiful region of Tuscany there have been fewer than 10 deaths per year of diagnosis in 2008 and 2009 in a population of almost 4 million residents. Teenagers happily practice promiscuous and unsafe sex (43.5% of teenagers had had actual sexual intercourse and 37.9% (males) and 26.4% (females) teenagers reported more than 3 partners. Among female teenagers reporting more than 3 partners, 45% reported using condoms), but AIDS is almost non existing among them. Heterosexuals do not use ARVs (only 17.8% of them had been treated with antiretroviral drugs prior to the diagnosis of AIDS) and as a result virtually nobody dies.

Then, there is a subtler consideration: Anti-Americanism and anti-imperialism are rampant among intellectuals all over Europe. With the advent of the Euro, the bankruptcy of once omnipotent U.S. corporations like GM and Chrysler (saved by Italian FIAT, by the way), the U.S. model of development and way of life ceased to lure Europeans. Any “American” thing is considered an expression of a failed and declining imperialism. Therefore, anyone who defies U.S.-based theories and/or interpretations, is almost automatically granted sympathy in Europe. This holds true for AIDS too. It suffices to say “that American scientist attacks me because my theory undermines his lust for money in association with the never enough vituperated Big Pharma” that any scientist or intellectual will take side on my part. Even though generalizations are wrong, here there is the perception that anything done or said by Americans is done for profit regardless of any respect for human life or values. Among highly despised corporations there are, of course, commercial publishers such as Elsevier.

Our censored article in Medical Hypotheses and all the articles and quotations about it that followed inScience and Nature, made us kind of celebrities here. We were admired for our courage to defy the overwhelming power of the corporations. Even more; we (authors) all proudly list our withdrawn Medical Hypothesis article in our CVs and it is highly valued, for example, when one of us is asking for a promotion (it is not my case because as ordinary professor I am at the vertex of the hierarchical pyramid). Last October Dr. Stefania Pacini (the corresponding author of the Medical Hypothesis paper and, incidentally, my wife) was appointed professor by a commission of Italian professors who evaluated her publications, including Med Hypo.

Another peculiar point concerns the city where I live, Firenze, the city where Galileo lived and worked, not too far from where I am sitting now. In the city of Galileo, the mere mention of the words “censorship in science” is considered blasphemy of the worst type. According to all our colleagues, whether dissidents or orthodox, the act of Elsevier of forcibly withdrawing our paper is considered the worst offence against science; we have been perceived (although vastly undeserving) as moral heirs of Galileo, persecuted because of our scientific hypotheses. As a matter of fact, when the Med Hypo article was published, the press office of the University put it in the home page of the University web site as a most distinguished accomplishment of Florentine researchers.


Similarly, the article by Prof. Bauer and myself was published by the Firenze University Press, i.e. the official publisher of the Florentine University (Above).

Just to let you know, the other day I was at a meeting with other full (ordinary) professors of the University discussing the problems of university teaching in prison (I am the Faculty’s delegate for this project); well, distinguished colleagues of human sciences stated that the authoritarian control over individual freedom was much worse in the American organization of labour (in factories or fast-food chains) that in our prisons. This is what they teach to their students. Whether is this true or not, this is the reality in our Universities. In other words, anything coming from or associated with (U.S.) corporations (such as Big Pharma or commercial publishers), here is automatically considered enemy and to fight them is considered honourable.

These considerations could also answer the second question of yours. The violence against the so- called AIDS rethinkers or dissidents, is simply unconceivable here. Whenever some European learns about it, it is considered a further proof that the so called American way of living as portrayed by Hollywood movies is a delusion and that the harsh reality of American workers, including scientists and philosophers, is much worse now in the U.S. than in Europe. The degree of freedom that we enjoy here is unprecedented. We could elaborate that prohibitionism never solved any problem, most often exacerbated it. We learned this lesson the hard way and now there is total freedom of speech and teaching. Freedom of speech and teaching about HIV and AIDS is here associated with the virtual non-existence of deaths attributed to AIDS; take your conclusions.


[* Dr. Harvey Bialy, then editor of Nature Bio/Technology is on record as having said: “A pathogenic retrovirus? That’s just more Bob Gallo bull—t. That’ll never fly.]

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