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Andrew Maniotis, Ph.D. Program Director in the Cell and Developmental Biology of Cancer Departments of Pathology, and Bioengineering, University of Illinois at Chicago, Chicago, IL 60607
Sept 4, 2007
To Robert GAllo
Dear Bob,
To advance the idea that "the Human Retrovirus," HTLV-1 causes leukemia in Humans at a rate of 0.06% or as Gallo told me on the phone 4%, or as some textbooks say, 5% constitutes causality, is like saying:
"I have 20,000 birds. 10,000 of these birds moult once a year. The other 10,000 moult 3 times a year. Now, 5 of the 10,000 birds that moult once a year died by hitting their head into utility poles.
However, 15 of the 10,000 birds that moult 3 times a year died by hitting their head into utility poles. Therefore, among these 15 birds, their moulting 3 times a year CAUSED them to hit utility poles and die. Moulting 3 times annually
--> hitting utility poles --> death."
Of course, this is purely hypothetical, because I'm not aware of any controlled studies on HTLV-I and ATL that demonstrate causality.
Andy Maniotis
Sept 3 2007, to: Robert Gallo
Dear Bob,
I've been away being filmed again on medical-scientific ethics in an hour-long interview to be dispersed amongst mainly the medical community. Sorry for the delay in responding.
During the interview with a scientist host who interviewed me, I mentioned about 1/3 way through the show, the concept that there are different layers of medical/scientific ethics. As you know all too well, it's not only about people people deliberately fudging data. I reviewed many of the issues involved in IRB's, testing of special groups, protected populations, prisoners, psychological testing, conflicts of interests, special needs of assent versus consent with child subjects, etc.
Then I shifted focus to a different layer of medical/scientific "ethos," where factual info that is not knowable often until years after protocols are placed into action can violate and should reverse what is thought about a disease or procedure. This is not necessarily a breach in ethics: it is called "advancement in medical science" (E.G. people don't treat yellow fever with mercury to the point their tongues turn black or exsanguinate them as did Benjamin Rush in Phily in 1773). This segment involved a treatment of epistemology and different concepts of causality. Such trials as the Fischl 1987 trial are good examples in light of what was found later at Concorde and Hamilton's Veterans Affairs AZT studies and of course many others who used high dose AZT, or which made healthy people sicker as shown by the VA study of Hamilton. I talked equally at length about the scientific impossibility of conducting a truly controlled clinical trial, and emphasized that medicine is perpetually on a learning curve, and collectively, failures and mass harm during such mass human experiments eventually lead to reform and more rational approaches, and even though the investigators directing the research most often are directing things for the welfare of patients, although it doesn't seem to frequently turn out that way. Medicine isn't science. AIDS science has arrived I believe, with reports like:
HAART-HIV TREATMENT RESPONSE AND PROGNOSIS IN EUROPE AND NORTH AMERICA IN THE FIRST DECADE OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY: A COLLABORATIVE ANALYSIS:
Methods: We analyzed data from 22217 treatment-naïve HIV-1-infected adults who had started HAART and were followed in one of 12 cohort studies. The probablility of reaching 500 or less HIV-1 RNA copies per mL by 6 months, and the change in CD4 cell counts, were analyzed for patients starting HAART in 1995-96, 1997, 1998, 1999, 2000, 2001, and 2002-03. The primary endpoints were the hazard ratios for AIDS and for death from all causes in the first year of HAART, which were estimated using Cox regression.
Interpretation: Virological response after starting HAART improved over calander years, but such improvement has not translated into a decrease in mortality.[The Antiretroviral Therapy (ART) cohort Collaboration-www.thelancet.com Vol 368, 451-58, August 5, 2006],
or even like your collaborator, Max Essex's group reported recently on nevirapine:
“Well over 875,000 women and infants have received a single dose of nevirapine. A single dose of nevirapine is the cornerstone of the regimen recommended by the World Health Organization (WHO) to prevent mother-to-child transmission among women without access to antiretroviral treatment and among those not meeting treatment criteria.
However, nevirapine resistance is detected (with the use of standard genotyping techniques) in 20 to 69% of women and 33 to 87% of infants after exposure to a single, peripartum dose of nevirapine. Among 60 women starting antiretroviral treatment within 6 months after receiving placebo or a single dose of nevirapine, no women in the placebo group and 41.7% in the nevirapine group had virologic failure (P<0.001). Women who had received a single dose of nevirapine had significantly higher rates of virologic failure on subsequent nevirapine-based antiretroviral treatment than did women who had received placebo. This apparently deleterious effect of a single dose of nevirapine was concentrated in women who initiated antiretroviral treatment within 6 months after receiving a single dose of nevirapine. We did not find that a previous single dose of nevirapine compromised the efficacy of subsequent nevirapine-based antiretroviral treatment in women who started antiretroviral treatment 6 months or more after delivery. Among the 30 HIV-infected infants, a single dose of nevirapine (one each to mother and infant) as compared with placebo was associated with significantly higher rates of virologic failure and smaller CD4+percentage increases in response to subsequent nevirapine-based antiretroviral treatment”
[Lockman S. et al., Response to Antiretroviral Therapy after a Single, Peripartum Dose of Nevirapine. The New England Journal of Medicine 356 january 11, 2007].
I believe Essex's interpretation wrong, but that's not at issue at this time, nor did I discuss this on film.
Finally, I believe that you'd be proud of me, that during a segment of the filming, I essentially repeated the issues that emerged with an over-zealous Dingell commission I've learned about from you recently. I discussed the Sharma case (where the typo errors in his grant involving the two proteins were reversed because of a typo, and also, the issue of Papovic and the ND (not determined) versus (not done) issue, and how this launched a ridiculous investigation that obscured the far more important underlying scientific issues, and how this in turn launched the events that damaged your credibility and how legal investigations, charges of misconduct, and changing the rules of scientific review to allow uninformed legal criminal considerations instead of having scientific discussions prevail, should be abolished (the issues involving Suk and his stem cells in Korea are other good examples of this as I'm sure you have become aware of regarding the issue of parthanogenesis he supposedly actually blindly stumbled upon with his stem cells-in other words he didn't really understand his own findings until after he was vilified, and the findings turn out to be simply the first evidence for human parthanogenetic development that have ever come to light).
In essence, and in good faith during the filming, I have pro-actively tried to correct the historical misperceptions involving your 5 years of investigation, and done so I hope articulately (I haven't seen it yet, but when it is out I will send it to you), with a motive in the back of my mind to try to convince you and others I am not trying to attack you or your conduct in any way shape or form. I really never was, but I assumed the Crewdson and Dingell stuff was the last word, which obviously, it wasn't.
I hope this shows you in real terms that I am sincere about correcting the historical mistakes.
Regarding the call tomorrow, I don't know the nature of it-you say it is 'serious" but you haven't responded to my last email(s) regarding the correction of the HTLV-1 stuff (number 4 on the list). I had agreed to incorporate the Kostaratos descriptions and not rely on the Adams descriptions, although they are essentially identical regarding this early period of your discovering HTLV-1 and 2 and how you believe it causes both cancer and neurological syndromes in (4%) of the victims who test positive.
You indicated in a previous email, that 4 of the 5 points have been settled and something as to the effect that you couldn't have stated them any better yourself.
So if you'd like to call tomorrow, or for me to call you, I'm completely at your disposal anytime. However, I'd love to tape it to protect both of us, and, taping would be helpful to me and my book so I can refer to exactly what you think, especially if you would like to discuss science, so that I won't get anything wrong again, and so I can prove it is from the horse's mouth to my "denialist" "flat-earthers," which was a term you did suggest appropriate during an interview you gave to Hockenberry in 1993 I believe it was. I'd need some time to tell my wife to set up her equipment, however, if you wanted to do this.
Note: I wouldn't of course ask you anything over the phone
(scientifically) that I wouldn't tell you about beforehand to allow you to think about any response before you answer. In other words, there are only a few difficult points that I could easily convey to you in a few minutes before we taped anything, and you have my word that I wouldn't spring any surprises on you, nor, as you were worried about before, I wouldn't tape anything, not a word, without your specific permission. I'd still like that visit someday to your office on my nickel. And besides, I still owe you a nickel about the endothelial cells.
Otherwise, if this is unsatisfactory for you, could we simply continue to communicate with email for the next several days, since I am absolutely strapped with the beginning of schoolm, teaching, and research and grants at the moment and have numerous student interruptions during both the morning and early afternoon?
Much obliged,
Andy Maniotis
Dear David and Anthony (and others),
I can retract historical info that is wrong (that he stole the virus from Montagnier, or impeded Montagnier's publication when he shepherded it through-although it was Robin Weiss's re-review of the work that got it in, that the press review with Heckler was before the peer review (Gallo's work had to have been in review because it came out a month after the press conference and it typically takes 3-12 months to get papers out in journals like science, etc.), but I can't change the way I feel that HTLV-and 2 were frauds.
Here's why.
If you believe Duesberg's stats it is 0.6% of an HTLV-1 testing positive population that will contract leukemia if they test HTLV-1 positive, or if you believe Gallo (see below) you get 4% leaving 96 HTLV-posives who don't get it. It is a fraud as a cancer researcher, or even a person that can tie their shoe, to see that this is not causality. But its in every medical and molecular biological textbook and we have to teach this shit!
Drop a pen 9,994 times and it floats upward 6 of those times-then I can say that gravity causes pens to float up (sometimes)? Or perhaps my machines didn't work so good 6 of those times? It's embarrassing! Or if you believe Gallo, 6 people of of 94 who test HTLV-1 positive will get leukemia. Therefore, I have discovered that Human retroviruses cause leukemia if 6 who test positive get leukemia but not the 94 who also test positive? I see 100 rain storms. 96 times I see birds flying but 4 times I don't and see birds sitting on branches instead, during the rain. I can now say that birds sitting on branches cause rainstorms? Sheesh!
Andy
---------------------------- -----------------------
Subject: Re: Maniotis Letter to Gallo, 4th version.
From: "Robert Gallo"
Date: Fri, August 31, 2007 3:33 pm
To: "Maniotis, Andrew J."
Andy,
In response to your long last letter I need to make a few clarifications.
1) Regarding Barre-Sinoussi: I do not want to sat I trained her, only that she was in my lab. for a few months to study lymphocyte culturing.
2)Regarding Robin Weiss: Certainly, I (we) never trained him. I needed him to help in tissue culture virus experiments in the mid-1970s, and he wished to come and did. Again, this was probably only for a few months.
3) I deeply resent your reference to me as calling you and others" Holocaust denialists". I do not believe I have ever used that phrase on anyone. You clearly have mixed me up with someone else, if indeed there is any truth in this at all. Really Andy, I do not know where you get your information, but if I were you I'd make a few adjustments.
4)Finally, you end with your concerns that we are not communicating as well, and you predict we may return to an adversarial relationship with censorship.... and only serve to block progress. In this regard I have a serious matter to discuss with you. In many respects more serious than anything before or anything we have ever discussed. It is important and urgent that we speak. In that I will be with some visiting friends this Labor Day weekend-let's try to talk on Tuesday. Please confirm.
Thank you. Bob
________________________________________
Maniotis, Andrew J. wrote:
Bob,
I have taken out a new website and posted on it. But I don't like the post I made regarding HTLV-1 and my apology for the way I stated this history. After reading Kontaratos's description of the early years of HTLV-1 again, and feeling that his material and not only Adam's material is a more appropriate description of that time period because at least there is a picture shown in his book with your quotes, and a better explanation of your resolve to prove the existence of a human cancer-causing retrovirus, that I should quote his work and not only Adam's description, which I will do as soon as possible.
Of course this is the hardest material for me to navigate, because I am so in tune with this science. But navigate through it I will.
However, you are wrong about:
"What is the point except to try to minimize our contributions?"
My statements or anything I wrote about HTLV-1,II are not about the
Japanese, or who discovered what first. Our conversations and emails and my reading of the materials you sent have convinced me (and others I might add), that there was no "misconduct" either between you and Montagnier or with respect to your research efforts and those of the Japanese. In fact you convinced me that you have been consistent and successful in your efforts, perhaps more than most of us, to proliferate your findings, and methods throughout the world in that you have consistently shown a willingness to send out materials, even though others haven't reciprocated as you indicated regarding the Japanese (and methods and train people like Barre-Sinoussi and Weiss in your own lab).
But these aren't the issues (at least from my perspective). The issue is the nature of the molecular signatures you and others have been tying to retroviruses and their effects (on cancer patients on AIDS patients and on:
"spastic paraparesis patients and now retermed HTLV-1 associated
myelopathy" patients."
I have many ideas about these things. I sent you two papers last spring regarding new approaches to testing for the pathogenicity of viruses by looking at chromatin, and our work on reversing cancers, without any reply from you, for example. I was reaching out, even to you who I know won't take the time to try to understand the science that I have developed that really began when I was in Folkman's group, and which I whole-heartedly believe, is the real issue(s) behind trying to reverse cancers.
Just so you know and to clarify my position, I was in error regarding the assumption that Crewdson, and others (even your supporters) were correct in their perceptions of your work and collaborations, which as far as I am concerned, and as as far as I've told the other "Holocaust denialists," as you like to call us (which is not very nice from a Greek immigrant's son's point of view who hid the Jews from the Nazi's and allowed the Russians time to prepare their defenses for 11 months while the Nazi's terrorized Greece-but not the Mani because we were too fierce), that I know and to the other "Holocaust denier's amazement," and also to the amazement of
other people who know you and like you like Mary Hendrix and Judah
Folkman, that you have done nothing but pursue your hypotheses, be they wrong or right, with admirable openness, and resolve as any one of us should.
As a senior scientist, I owed you open apologies for suggesting that your motives have been otherwise, which after this last posting on this new website, I believe will be sufficient (after I add Kontaratos's descriptions). You have no worries about the lose ends floating about the internet with respect to things I have said, written, or suggested: I will not be associated with any wrong information regarding the important historical events surrounding any hypotheses regarding cancer, and all of these things, no matter where they are have been, will be or have been changed to reflect what I said in the previous paragraph.
I wish we could continue to discuss these things as openly as we did a
week ago. I wish you'd see me as an asset to a modification of the
"HIV=AIDS" paradigm, but I know this probably will never happen, and
things will return to an adversarial and bitter exchange, with
characteristic silence, censorship, and other unfortunate behaviors that only serve to stall or block progress.
Regards, Papa Gallo,
Andy
____________________________________________________
On Thu, August 30, 2007 9:40 am, Robert Gallo wrote:
Andy,
This is becoming too time consuming. My schedule is filled , whereas you are doing a book. The problem here is simple to correct: you made
comments related to two bona fide discoveries. HTLV-1 and 2 have been
given (by me) to numerous labs all over the world. I do not know nor do you nor Adams (whoever he is) that the Japanese were about to make the same discovery. If true so what? What is the point except to try to minimize our contributions? The fact is we published 5 papers in peer reviewed journals in 1980-1981 before the first paper from Japan
appeared in late 1981, and yes, we presented data at international
meetings in 1979 ,e.g., Cold Spring Harbor meeting.
As to Duesberg's odd or at least misleading statistic of a 0.06%
incidence: according to Japanese and epid. studies of others, about 4%
of HTLV-1 infected people get this very specific CD4 T cell leukemia,
known as ATL or Adult T Cell Leukemia, occurring in young to middle
aged adults over a 70 year life span, and slightly more get the fatal
neurological disease, first known as tropical spastic paraparesis and
now retermed HTLV-1 associated myelopathy. This was first recognized as an HTLV-1 caused disease in Lyon, France by Gessain and deThe.
As to Adams quotes of me regarding any and all Duesberg phenomena.
including discoveries,I cannot vouch for accuracy. Surely I never said
Duesberg and Vogt "discovered" oncogenes in 1970 because a) I don't
recall date, and 2) the discoveries involved many groups contributing at many different fronts.
Finally, I do not understand your lumping Kontaratos with Adams.
Kontaratos had access to all files, interviewed me dozens of times,
and interviewed numerous co-workers and collaborators of mine before
even beginning to write. I do not recall even meeting Adams. If I did I sure do not recall. I do see that he is an HIV denialist which makes any and all of his views on me more than a little suspect. If you want my primary quotes go to my book, written in 89-90 and published in 91. It is all there and then some.
Andy, I am now really fed up with this. Make the correction and apology simply and fairly..
Thanks, Bob
______________________________________
Maniotis, Andrew J. wrote:
Bob,
RE: "Gallo's discoveries of HTLV-1 and 2 were frauds undertaken to get
funding for a cash strapped virus cancer program at NIH"."
I'm glad the other points are now rectified. For this forth point you'd like me to correct, I have had to do some reading and confering with my colleagues about this period, and about retroviruses. I think my unfortunate statement should be easy to correct. But before I post it, would you varify that the info in the attached document is correct as you remember it. There are some quotes of yours that I don't want to get wrong.
Thanks,
Andy
______________________________
On Mon, August 27, 2007 3:57 pm, Robert Gallo wrote:
Andy,
O.K., I'll wait to see the "final". Then I will send you a note to post.
Bob
_________________________________
Maniotis, Andrew J. wrote:
Bob,
You're right, it wasn't intentional-I was just stating what you said.
But yes, I'll correct it also.
andy
________________________________________
On Mon, August 27, 2007 1:28 pm, Robert Gallo wrote:
Andy,
Thank you for these clarifications. They are nearly precisely what I
would have asked for. However, in point #4, the current wording
corrects the misinformation about the virus cancer program, but seems
to leave standing the misinformation that my discoveries of HTLV-1 and
HTLV-2 were "frauds". I suspect that you simply overlooked that part
as you were correcting the other information. Nevertheless, this is
obviously the most important and serious part of #4, and I would
appreciate you also correcting that information..
Bob
_________________________
Maniotis, Andrew J. wrote:
Bob,
Here's the final revision you asked for. I hope it is now
satisfactory. I will post it upon receiving your approval.
andy
______________________________________
To:
Robert C. Gallo, MD
August 25, 2007
Director and Professor
Institute of Human Virology
University of Maryland
School of Medicine
725 W. Lombard Street
Suite S307
In order to clarify my previous letter, my statements were conveyed
on this public science forum to acknowledge that you had sent me various documents, and a new book you have drawn my attention to, "Dissecting a Discovery," by Nikolas Kontaratos. According to these documents and the book, and my own belief that what you have told me personally makes sense for various reasons, there is little doubt in my mind that, contrary to what the many damaging reports and investigations have portrayed in the media, in books, in various journals, and in other publicly-available records, there could have been no misconduct in the Gallo-Montagnier collaboration.
Regarding your collaborative relationship(s) with the Montagnier lab,
and specifically, the complex specific details about techniques and the molecular signatures both groups associated with 48 AIDS patients and an ARC patient, the following specific statements are questionable in their account of the facts, since they have been contradicted now by these other sources I have listed and which you sent to me. I strongly believe, and I hope that my willingness to make these corrections demonstrates, that an accurate history of this period amidst the confusion of financial, social, and political issues of that time is absolutely critical in order better
assess scientific issues. These inaccuracies include:
1) "The Dingell Commission and others concluded Gallo committed
fraud."
Mr. Dingell himself disavowed the report against Gallo. Also the
HSS's Office of Research Integrity ruling concluded there was no
misconduct.
2) That "Gallo hijacked the virus from Montagnier." This would be
impossible because you shepherded Barre-Sinoussi's 1983 paper.
3) That "Gallo suppressed Montagnier's work". The opposite was true
and Luc Montagnier would confirm this if anyone asked him. This would
also be unlikely since the 1983 paper was shepherded through.
4) That "Gallo's discoveries of HTLV-1 and 2 were frauds undertaken
to get funding for a cash strapped virus cancer program at NIH". The truth is that Gallo did not work in the virus cancer program, and the program was never strapped for funds.
5) That "Gallo's work was not peer reviewed before being published".
The truth is that the work was reviewed, but did not appear before HSS
Secretary Heckler's press conference, but did appear a month later.
As I stated before, I will endeavor to correct these perceptions and
statements not only because I regret passing along this information,
but because it is the right thing to do in order to get to the truth
regarding the molecular signature of the isolates.
Sincerely,
Andrew Maniotis, Ph.D.
Program Director in the Cell and Developmental Biology of Cancer
Departments of Pathology, and Bioengineering,
University of Illinois at Chicago, Chicago, IL 60607
To: Robert C. Gallo, MD August 22, 2007
Director and Professor
Institute of Human Virology
University of Maryland
School of Medicine
725 W. Lombard Street
Suite S307
There is still incorrect information that should be clarified and corrected regarding the statement that "Gallo's discoveries of HTLV-1 and 2 were frauds undertaken to get funding for a cash strapped virus cancer program at NIH," which are independent of the fact that Gallo did not work in the virus cancer program, and the program was never strapped for funds.
The accounts of the AIDS reappraiser, Jad Adams (1) and Gallo’s skillful and complementary biographer, Nikolas Kontaratos (2) are very similar, and present some of the same quotes from Gallo himself regarding the establishment of the discovery of the first Human retroviruses. Therefore, I have here included some of this history as described by Adams because it is easily accessible to all and can be obtained at the URL I have included in the references, and would like you to see if this information regarding this critical period is accurate:
“Reverse transcriptase was discovered only in 1970 by Howard Temin and David Baltimore, who received the Nobel Prize for this work in 1975.”
“Oncogenes were discovered in 1970 by Peter Duesberg and Peter Vogt. They had long been believed to exist, but believing and proving are different things. Duesberg and Vogt defined in molecular and genetic terms the first ‘transforming’ gene which caused a tumour.”
“Could these steps be proof of the gathering momentum towards ascribing causes to the cancers, leading to cures for them?”
“The cancer research programme now received its greatest stimulus. On 22 January 1971, in his State of the Union address, President Richard Nixon declared war on cancer. He said: ‘I will ask for an appropriation of an extra one hundred million dollars to launch an intensive campaign to find a cure for cancer and I will ask later for whatever additional funds can be effectively used. The time has come in America where the same kind of concentrated effort that split the atom and took man to the moon should be turned to conquering this dread disease.’”
“As will have been realized from other excursions of Richard Nixon, the word hubris was not one which made frequent appearances in his vocabulary. This speech, which heralded the Cancer Act and other efforts by governments and charities worldwide, meant more money and resources were spent on cancer than on any other disease before or since. The field was awash with money. It was the time of hope and riches before the oil crisis, the research institutes were buoyant, the manufacturers who supplied them with equipment had full order books, a footnote in the annals of cancer research was a passport to a doctorate, the Nobel Prize glowed in the distance like the sun.”
“The cancer research programme was far from being an overwhelming success. By the mid-nineteen-eighties articles were beginning to appear in major journals such as ‘Progress Against Cancer?’ in the New England Journal of Medicine. Here authors looked dispassionately at the figures and noted that the cancer mortality rate continued to rise slowly from the nineteen-fifties to the nineteen-eighties despite the vast research effort. Moreover, there was no breakthrough just around the corner. The authors bitterly remarked: ‘We are losing the war against cancer. notwithstanding progress against several uncommon forms of the disease, improvements in palliation, and extension of the productive years of life. A shift in research emphasis, from research on treatment to research on prevention, seems necessary if substantial progress against cancer is to be forthcoming.’”
“One of the theories on which fortune smiled was the theory that viruses caused cancer. It had a head start on other theories, because of earlier work in the field, and it promised great things. Consequently some great minds went into the virus cancer research programme. At one time, viruses were being found in almost every tumour, particularly retroviruses. Peter Duesberg, Professor of Molecular Biology at Berkeley, was part of the virus cancer research programme. He said:
‘We know that mice and chickens contain fifty to a hundred retroviruses which never cause disease. Viruses seemed to be at least a plausible cause of human cancer, based on animal work, and that programme has produced a lot of good things for science but has not identified the cause of human cancer.’
“When you’re in the retrovirus business you can detect a retrovirus. When you look at a disease, you can look for the retrovirus. We have done that before with multiple sclerosis, we have done it with leukaemias, we have done it with sarcomas, and in almost all cases a virus was found sooner or later.”
“What was not emphasised by many of these laboratories was that the same viruses were subsequently always found in healthy carriers and that’s why the virus cancer programme is essentially a failure.”
“Most connections between cancer and viruses are mere association: hepatitis B virus is associated with a high rate of cancer of the liver many years after first infection. There may well be an infectious agent in cancer of the cervix and cancer of the penis because a person with one of these is likely to have a sexual partner at a higher risk than average of developing the other.”
“It is possible that a virus challenges a human organ repeatedly, damaging the liver or the cervix in frequent tiny attacks. This means the cells of the organ have to replenish themselves faster than they would in the natural course of events. The greater the number of cells replicating, the higher the chance that one will ‘go wrong’ and start replicating out of control - a cancer. If every hepatitis B infection caused liver cancer, or if every liver cancer was in a person with hepatitis B, it would all be so much easier. It was not to be so; the viruses contribute to the risk of a cancer developing, they do not cause cancers.”
“Robert Gallo and the human retroviruses”
“The only other success story of the virus cancer programme was the announcement of the isolation of the first human retrovirus - human T-cell leukaemia virus, by Robert Gallo, Chief of the Laboratory of Tumor Cell Biology at the National Cancer Institute’ Maryland’ USA.”
“Robert Gallo is seen as the hero and the villain of the AIDS story. He has been described as ‘champion of the single cause theory’ meaning he believes AIDS is caused by a single agent with no co-factors. He is quoted as saying: ‘Who needs co-factors when you’ve been hit by a truck?’ He pursues his theory with a vigour which is impressive even to those who do not like him. He is a skilful communicator, popular with the media and in particular the medical and scientific correspondents who are invited into his confidence; general reporters develop an immunity to charm.”
“Gallo was born in Connecticut in 1937. Much is made of the incident when, at the age of thirteen, he saw his sister dying of leukaemia. He took a medical degree and began as soon as he could to study leukaemia in the laboratory - his nature was too restless to allow him to enjoy work with patients. Within two years of finishing his degree he was working at the National Cancer Institute where he was to stay for more than twenty-five years.”
“The young Gallo was immediately interested in the virus-cancer programme, showing most enthusiasm for the theory that viruses came from outside the body to infect and cause a cancer by some as yet unknown mechanism. There was another theory of endogenous (passenger) viruses which might cause disease in the presence of carcinogenic (cancer-causing) agents, but this theory has fallen into disfavour. Gallo backed the right horse and became deeply involved in the subject of RNA viruses immediately after Temin and Baltimore discovered reverse transcriptase.”
“Gallo describes his own thought processes: ‘In 1970, when Temin and Baltimore came on reverse transcriptase, I was studying DNA polymerases in blood cells. DNA polymerases are enzymes that assemble DNA; reverse transcriptase is a member of this group, albeit an unusual one. Under the influence of Temin’s ideas I decided to search for reverse transcriptase in human leukaemic cells, hoping to find a retrovirus there.’”
“Seek and ye shall find. But it was necessary to use the correct techniques. The electron microscope, which could detect objects thousands of times smaller than those available to an optic microscope, was a cumbersome tool for the purpose, according to Gallo. Moreover, human leukaemic cells had been studied under electron microscopes and no virus particles had been identified.”
“Gallo and co-workers laboured to refine the test for reverse transcriptase until the enzymes could be detected in leukaemic cells. They did find what seemed to be reverse transcriptase but in such small amounts that it could easily have been some other substance mimicking the behaviour of the key enzyme. They needed a much larger supply of the cells with this questionable virus.
“This was where Gallo’s real skill, and that of his colleagues, came into play. In years to come he will be known as a first-class bench scientist who made significant contributions to the development of cell lines in which viruses could be studied. A plant protein, phytohemagglutinin, had been discovered in the nineteen-sixties. It would induce white blood cells to grow in tissue culture. Gallo’s lab noticed that after such stimulation, some T cells released a growth factor. They would culture T cells to harvest this growth factor and would use it to stimulate T cells which were growing with phytohemagglutinin. Gallo now had T cell lines growing and rapidly reproducing - a perfect set-up for any experiment he chose to perform with them.”
“There was something of a diversion on the path to find the cause of human leukaemia.”
“In 1975 Robert Gallo published a paper saying he had isolated a new human virus - human leukaemia virus 23.”
“Gallo was jubilant, it was the justification for years of dedication. ‘We got permanently growing cell lines eventually, and it was a great eureka. We succeeded ten times in ten different cell lines, and we thought we had made the discovery, the genuine article, that retroviruses exist in humans. A year or more of analysis went by. We thought it was a triumph.’”
“This period of research turned from being Gallo’s greatest triumph to date into his greatest disaster. When other scientists looked at this virus they discovered it was a mixture of three animal viruses: from a gibbon, a baboon and a woolly monkey.”
“The term for this is contamination - the human serum from a leukaemia patient had been contaminated by animal viruses. The way this can occur is well-known and laboratories go to great lengths to avoid it. Viruses are worked on in ‘hoods’ which are basically lab benches surrounded by a clear plastic shield in which a fan takes air, which may contain particles of viruses or other material, out of the lab. It is always possible for scientists to bring in contaminants from outside, despite the measures taken to avoid this, or for lab equipment used in the hoods to be contaminated or for material in other hoods in the same room to pass over and contaminate new material. One contamination is probable in a long research period, two is possible, three is unlikely.”
“As Gallo said: ‘I was depressed, dumbfounded, angry. It was the low point of my whole career. It was almost the last nail in the coffin of the field of retrovirology. The programme died, and all the good that came out of it, like interleukin-2, which would be so important in fighting cancers, didn’t seem to matter, to me or to the world. I became more cynical, tougher, less happy. I mean, what could it be but sabotage? One contamination can occur, but three? In fifteen years I had had one contamination from a mouse. But three?’”
“Robin Weiss, another leading cancer researcher who is now working in the field of AIDS, played a leading role in determining the non-human component of human leukaemia 23. He said: ‘In the late seventies everyone was laughing at Gallo, they’d say: ‘There goes Gallo again discovering another human retrovirus.’ When he went to scientific meetings people would laugh at him. Every fashionable lab was going into oncogenes. He said man can’t be the exception, man must be able to be infected with retroviruses too. He proved us wrong, he found a retrovirus which causes leukaemia.’”
“A leukaemia breakthrough?”
“The connection between AIDS and leukaemia is almost nil. There is a slight connection in that Robert Gallo and those who followed his line of reasoning connected the two for reasons which will be demonstrated. In order to render this accessible, it is worth a quick aside to define leukaemia: it is a malignant disease of the blood-forming organs marked by a proliferation of leukocytes (white cells which include all kinds of T cells among their number) and a reduced number of red cells. Leukaemia is classified according to three facts: first the character and duration of the disease; second the type of cell involved; and third the increase or non-increase in the number of abnormal cells - in effect it can be either leukaemic or aleukaemic.”
“Acute lymphoid leukaemia is, therefore, a disease whose onset is fast, which involves lymphocytes and is characterised by a massive increase in abnormal cells in the blood. Heredity is involved in some leukaemias and radiation is certainly a factor in myelocytic leukaemia - the higher the dose, the more likely it is to develop. Acute leukaemia will cause a tendency to bleed, joint pains, enlargement of lymph nodes, liver and spleen and an increased susceptibility to infection.”
“Robert Gallo and his colleagues took cells from leukaemic patients, grew them with phytohemagglutinin and interleukin-2 and managed to produce reverse transcriptase. They had found a retrovirus. They called it HTLV-I: Human T-cell Leukaemia Virus I.”
“They now needed to find the disease which it caused. The patients from whom the virus had been isolated had a cancer of the T4 cells accompanied by skin abnormalities. This was a well described condition (mycosis fungoides or Sezary T-cell leukaemia) and only a small fraction of patients with it had HTLV-I. The quest for the disease led to Japan where in 1977 Kiyoshi Takatsuki of Kyoto University described something he called Adult T-cell Leukaemia which killed within a few months of diagnosis and was characterised by an explosive proliferation of leukaemic cells. It was heavily concentrated in Kyushu and Shikoku, Japan’s southernmost islands. Gallo remarked: ‘Such clustering suggested the disease might be caused by an infectious agent.’”
“It was clear the Japanese were well on the way to describing the virus also. Yorio Hinuma of Kyoto University and Isao Miyoshi of Kochi University had grown a line of cells from leukaemic patients which were releasing retrovirus particles. In a curious dress rehearsal for the AIDS story Gallo and his team had an isolate from a patient which Hinuma and his team also seemed to have. Gallo notes: ‘All available data indicated that the virus coming from Miyoshi’s cells was identical with HTLV-I.’”
“Gallo claims he and his colleagues isolated the first examples of HTLV-I in 1978-9 and that the results were published in 1980 and early 1981. To delay publication for up to three years is uncharacteristic in a man not given to false modesty.”
“Gallo is credited with isolating and describing the first human retrovirus. Japanese and American researchers confirmed by analysing the RNA of both isolates that the Japanese and American viruses were related strains of the same virus. They could never be exactly the same because of the mutations which occur as the virus replicates, but the RNA sequence was close enough in the two isolates.”
“Once the virus had been described, other laboratories looked for it. It was found in black patients born in the US, Caribbean countries or South America; Caribbean-born black people in England, Africans and Japanese. What could tie these disparate regions together?, mused Gallo.”
“The answer he came up with was the slave trade. Miyoshi in Japan found Japanese macaques had antibodies to HTLV-I and he suggested the monkeys had the disease first and infected people. Researchers at Gottingen, Germany, and in Gallo’s lab found that many species of African monkeys had antibodies which reacted with HTLV-I. African green monkey and chimpanzee viruses were most closely related to the virus Gallo had found in leukaemic cells.”
“Gallo suggested:
HTLV-I originated in Africa where it infected many species of Old World primates’ including human beings. It reached the Americas along with the slave trade.”
“ Curiously, it may well have arrived in Japan the same way. In the sixteenth century Portuguese traders traveled to Japan and stayed specifically in the islands where HTLV-I is now endemic. Along with them they brought both African slaves and monkeys, as contemporary Japanese works of art show, and either one or the other may have carried the virus.”
“The discovery of HTLV-I infection on Hokkaido, one of the northern islands of Japan, immediately challenged this view of events but Gallo and his colleagues have remained attached to the monkey-virus theory.”
“So, why is it thought that this virus causes the leukaemia? ‘First because of the coincidence between virus and leukaemia - find one and you will find the other, Gallo says.’”
“The incidence of adult T-cell leukaemia in Japan, Duesberg points out, is estimated to be only 0.06 per cent based on 339 cases of T-cell leukaemia among 600,000 subjects who are antibody-positive for HTLV-I. Why is this?”
“Because of the latency period, responds Gallo. It will cause leukaemia, but it may take as long as forty years.”
“However impressive this lab work was, it was a poor return on the investment of billions by people who felt themselves accountable to the electorate. The discovery of a human retrovirus was the acme of the viral cancer research programme’s limited success. It was the sort of achievement other researchers applaud but in the cold light of a Senate Sub-Committee hearing it doesn’t seem so great. Cancer research funding was in trouble. The cancer laboratories around the world had vigorously pursued every line of research which might conceivably bear fruit. These were still promising and their hands were still outstretched but the situation in the nineteen-eighties was radically different from that in the early nineteen-seventies. A massive budgetary deficit meant public spending cuts in the US and world recession meant similar actions in other countries. Cancer research had had its day. The cancer laboratories hadn’t played a particularly stunning game so the politicians wanted their ball back.”
Sincerely,
Andrew Maniotis, Ph.D.
Program Director in the Cell and Developmental Biology of Cancer
Department of Pathology, and Bioengineering
College of Medicine Research Building
909 South Wolcott Ave.,
University of Illinois at Chicago
Chicago, IL 60607
References:
1. Jad Adams, Virus Hunters, http://www.virusmyth.net/aids/data/javirus.htm, 1989.
2. Nikolas Kotaratos, Dissecting A Discovery,2006.