The 2007 HIV/AIDS study that mentioned Haiti and Haitians

[Gelin*]

Here is the title of the paper:

<b>The emergence of HIV/AIDS in the Americas and beyond </b>
M. Thomas P. Gilbert*†, Andrew Rambaut‡, Gabriela Wlasiuk*, Thomas J. Spira§, Arthur E. Pitchenik¶, and Michael Worobey*


*Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721; †Ancient DNA and Evolution Group, Centre for Ancient
Genetics, Niels Bohr Institute and Biological Institute, University of Copenhagen, DK-2100 Copenhagen, Denmark; ‡Institute for Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom,; §Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333; and ¶Department of Medicine, University of Miami, Miami, FL 33125

Edited by John M. Coffin, Tufts University School of Medicine, Boston, MA, and approved September 17, 2007 (received for review June 6, 2007)

Source: Proceedings of the National Academy of Sciences, PNAS November 20, 2007, Vol. 104, no. 47, pp. 18566-18570
www.pnas.org/cgi/doi/10.1073/pnas.0705329104

It's always good to go to the source - whenever possible...

gelin

[Gelin*]

If you had not taken the time to go through the above article, why not give it a try? Even if you are not familiar with the scientific jargon and all the big and scary words used by the authors, I guess we can spend some time looking at the major weaknesses of this ' study ', the title of which reminds me of the movie Toy Story in a strange way <i>"...to infinity and beyond..."</i>

gelin

[Gelin*]

The study in question tried to revive the ancient rumor that somehow Haiti was “the stepping stone” for HIV/AIDS to enter the American continent and spread throughout the world, thereby serving as a sort of trampoline for the old fable to bounce back from its grave and enter the public discourse – again.

Science deals with facts, events, and things that can be observed, and observation is the first step of the scientific method. Science cannot deal with rumors although the means by which rumors are created and spread (the reasons as well) can become the object of a scientific inquiry. While reading this report I have made a few observations that I intend to list here for all of you to join in and discuss. Here is the first one:

Obs # 1: The authors appear to try to reinvent the wheel.

...<b>Some researchers</b> have noted that Haitian HIV-1 sequences tend to occupy basal positions on the subtype B phylogeny, suggestive of the epidemic originating there (9–11). <b>Others argue vigorously</b> that the Haitian HIV/AIDS epidemic was seeded from the United States, perhaps after Haiti became a popular sex tourism destination in the mid-1970s (12–14). <b><u>However, these competing hypotheses have never been rigorously tested...</b></u>

Is it true that these so-called “competing hypotheses have never been rigorously tested”? I don’t think so. Numerous studies have demonstrated how HIV/AIDS conquered the world without implicating Haiti as a “stepping stone” because that’s simply not the case. And in the late 70’s the general observation in the country was that the new disease was being propagated by infected tourists and Haitians from the diaspora. The authors did try to reinvent the wheel but their masterpiece won’t turn because of flaws in the design: The spokes don’t match up!

gelin

[Guysanto]

Gelin, I thank you first of all for paying attention to this important issue and for your attempts to engage us in discussing it. While it is of enormous interest to Haitians who bristle when a foreigner or team of foreigners tarnish our national image, I have suspected for a long time that the reactions it provoked would be short-lived and only skin-deep. Why?

- we are here concerned with the publication of a "scientific" paper (apparently of dubious value), written by previously unheard-of authors. In other words, who the hell are "M. Thomas P. Gilbert, Andrew Rambaut, Gabriela Wlasiuk, Thomas J. Spira, Arthur E. Pitchenik, and Michael Worobey " ? What credibility, if any, do they have in scientific or medical circles?

- is the response to their study best met by a surge of nationalist sentiment or by critical peer-review (that is from biologists, epidemiologists, and seasoned professionals from related fields of scientific inquiry)

- it seems to me (and I say this without malice or offense) that this paper is much like creationism, "bad science". In creationism, the so-called scientific theory is driven by the urgency to defend "the literal truth of the Bible". This in turn lends to biased methods of selection/rejection of evidence, maximization/minimization of logical argumentation based on how well it fits "The Word" which of course is "infallible" by its very definition. The overriding interest of creationism and the push behind it is to show that "God created the world in six days", period. In "Worobey's study", the overriding interest is to show that the most vulnerable segments of the world's population must somehow be responsible for its worst ills. Hence the wholesale discarding of all other possibilities from the nearly infinite human interactions that could have led to the propagation of the AIDS virus, to focus on a particular set: "the African-Haitian-US diaspora" connection. I wonder which ones of the researchers woke up one morning, hit their forehead, and exclaimed "Eureka! I got it! Why didn't I think of that before?"

Could it have happened the way they said it did? Yes, of course. It is equally possible that we have been invaded by aliens who secretly run the world or that we are simply in the midst of a bad dream, à la Bobby Ewing in "Dallas". We might just wake up to reality some day, and the world will be a far better place to live (...without Haitians?)


I must thank you and Shelony, on the Ann Pale forum, to have tried to address this issue on the basis of its lack of rationality, even when the forum appears to be void of serious human interest at this time. But if we keep on keeping on individually, perhaps one day Ann Pale will return to its days of pioneering a dialog of substantive exchanges between Haitian nationals and Haitianists on the Net. A dialog that will make us less vulnerable to attacks directed at us, based on our perceived inability to effectively defend ourselves.

[Gelin*]

Guy, thanks for noticing. As I said earlier I have read the paper and to me it's not that good. Far from it! My intent here is to bring some of my observations one by one so we can hopefully discuss them. In the process, we will see that the whole issue is full of holes and does not deserve all the attention it got - except when it comes to the untold possible consequences for Haiti, Haitians and Haitian-Americans - again!

I believe, as you said, that a critical review is the way to go. After all, if it could be proven that Haiti was the stepping stone for the spread of HIV/AIDS then everybody would have to accept it as fact and no surge of nationalist sentiment would be able to change it - because a scientific fact is a scientific fact. But it's not the case here, the way I see it.

I'll bring my second observation later on. No hurry.

gelin

[Gelin*]

Obs. # 2: The authors associate one right idea with a wrong one in a subtle way.

...However, these competing hypotheses have never been rigorously tested, <b>despite their importance for understanding the global spread <u>and</u> vaccine-relevant genetic diversity of HIV-1...</b>

The authors are right in stating that these two hypotheses can help understand the global spread of HIV-1, simply because they deal with whether or not HIV/AIDS came to Haiti from the United States. That’s the first part of their claim. The second part is wrong when they state that there is “vaccine-relevant genetic diversity of HIV-1” associated with their study – and here is why:

1) The production of vaccines is related to the strict existence of variants (genetic diversity) of the virus AND has no connection whatsoever with the above hypotheses that deal only with how the virus moved from one place into another (from US to Haiti or vice versa).

2) Vaccines already exist and have been used for many years to control HIV/AIDS in the US, Haiti, Africa and around the world. If the authors had made that statement in the early 80’s, perhaps some people would have believed it because not much was known on the subject at that time. The authors are late by at least 2 decades! All of them together! Science is good very good, but scientists can be funny at times.

I have a few more observations...

gelin

[Dr Roger Malebranche]

Dear Guy:
My son who is an internist at the Emory University in Atlanta called to warn me about the so called scientific study linking AIDS in the USA to Haiti and Haitians. ( He knows how defensive I am about our country ). David is an infectious disease specialist in charge of the Aids program. He has never been to Haiti because of our political situation but loves the country because his father is from Haiti. As he said and as I already knew from my life in Medicine, doctors have to write papers in order to get their names in print and justify the grants that pay for their salaries. The more papers you write, however stupid and harebrained they may be, the better your CV appears. The more controversy you ignite the more money you stand to make on the medical speaking circuit . It is a bad setup but as physicians we realize that it is the medical world is.

Those so called scientists ( they are in fact morons ) used a very limited unscientific study on 5 Haitians living for years in Miami ( Go figure ), to derive sweeping conclusions about a disease affecting the world. The way they have it, a few Haitians (perhaps a few dozens) went to Congo in the 60s as teachers, doctors, engineers, the elite of Haiti mind you... to help in the post colonial period. They either ate chimpanze meat or got scratched by primates or had sexual relations with some chimpanze hunters. What a life! They then contracted some form of previously unknown ? animal virus, the forerunner of our actual HIV-1 subtype B. (note that the subtype C is the dominant one these days in Africa and India). Those early HIV carriers then moved back to Haiti. Absolutely no proof of that sequence is given. Some mutations then took place... Again no proof given and somehow those nasty Haitians gave the disease to other Haitians and to innocent American tourists. ET VOILA. Case solved!

I have some questions. Were Haitians the only people traveling to Central Africa in those days ? What about Canadians, Europeans, Indians, Cubans, Dominicans, other Caribbeans, Latin Americans, North Americans etc...What happened to the travelers of all those countries ? Haha! They did not like chimpanze meat, nor primates hunters.

Did the virus have a special calling for Haitians and decided to make them the chosen ones ?

This article : "The emergence of HIV-AIDS in the Americas and beyond" would be laughable if it did not appeal to the deeply rooted prejudices in the white and Asian worlds. I have lived through that infamy before when Haitians were excluded from the group of blood donors (condemnation by blanket). Haitians at every turn have to defend themselves against false accusations. We torture children, we gave Aids to the world, we drink chicken blood, we practice cannibalism and the list goes on. If I was not born and raised in Haiti, if I did not know Haiti and the Haitians, I could easily conclude that the world would be a better place without Haiti. And this is the sadness of the whole thing. Haiti is a gift to the world.

[Gelin*]

Thanks for joining in, Dr. Malebranche.

I agree, the whole article is a funny joke, but the sort of jokes that can't make Haitians and Haitian-Americans laugh. It's a kind of 'parascientific' study published just a few weeks before the attention of the entire world turned toward the issue of HIV/AIDS: AIDS day was on the horizon! As you can imagine the timing of their publication gave maximum exposure to these authors, which can only help them and them only. The paper does not help science one bit.

gelin

[Dr Roger Malebranche]

Gelin :
You have been carrying the fight all by yourself, with Guy's help, and that is not fair. I retired from the practice of surgery 8 years ago but I still remember the stigma attached to ALL Haitians when the Aids bomb hit the world. The fact that a Canadian airline worker was in the forefront of the disease ( the San Francisco gay baths ) did not do any damage to Canada but the white world needed a scapegoat and Haiti was chosen. For a long time I felt like a leper, a pariah, despite my position in the American medical community. Since internship's days I always gave blood because I have a rare type but I was told by my hospital friends at the Lab that the Center of Disease Control had excluded Haitians from their list of potential blood donors. You can imagine my shame.
It took a long time to reverse that situation and even today there is a stigma attached to Haiti concerning Aids. In view of the experience of the past I thought my medical Haitian colleagues and the Haitian community were going to raise a storm of protests, even threaten legal action on the medical journal which published the article and the writers but I won't hold my breath.
You have been one of the few voices in the wilderness and I greatly commend you. Haiti needs help. Keep the good fight.
Roger.

[Gelin*]

Dr Malebranche,

I have seen many responses to this study and some writers have made the mistake of asking for the name of this single hypothetical Haitian carrier. Well, if that's the basis for any response, it will fall down the moment a name is produced. And this can be done easily, in no time at all! Every time I post an observation here I feel I am preaching to the choir, but that's ok.

I don't know if you have read the article in question but the link above should work fine, I hope. I would encourage others on the forum to take a look at it as well. My general impression is that the whole thing is based L-A-R-G-E-L-Y on assumptions/presumptions coupled with computer modeling (with additional assumptions). Isn't it how movies are made for Cartoon Network or the SciFi channel? ....♪ to infinityyyyyy...and beyond...♪ :roll:

gelin

[Gelin*]

Obs # 3: The authors use an imbalanced approach to conduct their study

<b>To test these hypotheses</b>, we recovered complete HIV-1 env and partial gag gene sequences from archival specimens collected in 1982–1983 from five Haitian AIDS patients, all of whom had recently immigrated to the United States and were among the first recognized AIDS victims...

What do these scientists tell us (readers) they want to do? They want to test their TWO “competing hypotheses”. How did they do it? To test their TWO hypotheses (as they claim), the authors adopted a methodology slanted heavily toward just one of them. They recovered blood samples from Haitian immigrants collected over 20 years ago and worked with them to build their case. The above section shows that the authors used a research methodology that is obviously imbalanced. Apparently, they were primarily looking for any evidence that could offer some sort of support for the second hypothesis (from Haiti to the US).

But is there a way they could also test the first hypothesis (from the US to Haiti)? Absolutely! There are other archival blood samples and DNA sequences available that they could use. The only “scary” thing is that they were NOT collected from Haitian immigrants! Please read the following:

<i>“The data presented above allow us to sketch a tentative scenario for the introduction of HIV-1 into the Western world. Based on the available data, the most plausible scenario seems to be that the subtype B virus was carried out of Africa and introduced into the Western homosexual community by one person. There is some other evidence for this in the form of the notorious “patient 0,” a gay airline steward who was infected in the late 1970s and allegedly infected a number of his sex partners (63). A sequence of this patient’s virus is available; it is of subtype B and has the homosexual characteristics. However, patient 0 probably was not solely responsible for the initial spread of the virus in the United States; anecdotal evidence shows that he was part of a cluster of homosexual men who traveled frequently, were extremely sexually active, and died of acquired immunodeficiency syndrome at a very early stage in the epidemic (around 1980–1982) (64).</i>

Source: Carla Kuiken, Rama Thakallapalli, Anne Eskild, and Anthony de Ronde. 2000. Genetic Analysis Reveals Epidemiologic Patterns in the Spread of Human Immunodeficiency Virus. Am J Epidemiol Vol. 152, No. 9, 2000 pp. 814-822.

Link: http://aje.oxfordjournals.org/cgi/repri ... type=HWCIT

Ladies and Gentlemen of the Forum (…and beyond…of course :-), try to imagine with me what whould have happened to their study if our scientists had decided to investigate the above fact!!!

gelin

[Gelin*]

Obs # 4: The authors may have used blood samples of questionable quality.

One of the six PBMC samples obtained for this study <b>failed to yield any amplifiable HIV-1 PCR products</b>.

One blood sample out of six failed to yield PCR products for the virus and the authors did not even bother to offer some explanation. Is this due to the age of the samples? Remember they were collected in the early 1980’s. Is it possible that the samples were contaminated, mishandled or inadequately stored for all these years? The least the authors could do would be to offer some related insights based on their experience in working with ancient specimens. At least one of them is part of an “Ancient DNA and Evolution Group”! They just went over it as if it was meaningless. Well, it’s not.

gelin

[Gelin*]

Obs # 5: The authors use presumptions to help their data

…all of the patients were Haitian immigrants who had entered the United States after 1975 and progressed to AIDS by 1981 <b>and hence were <u>presumably</u> infected with HIV-1 <u>before</u> entering the United States.</b>

There is no indication anywhere in the study that the Haitian immigrants were infected with HIV-1 BEFORE entering the United States and progressed to AIDS afterwards. It was necessary for the authors to use the word “presumably” before making their inference because they simply do not know. It must be equally important for the readers to understand they can reject that presumption entirely, as easily as it was made. If they wanted, they could have easily produced statements like:

…and hence were presumably infected with HIV-1 shortly after entering the United States.

Or

…and hence were presumably infected with HIV-1 during the first 24 months after entering the United States.

You see, the authors have no way of knowing if the Haitian immigrants were not infected with HIV-1 only AFTER entering the United States and progressed to AIDS soon after. This scenario is very likely given that some reports indicate the virus may have already been present in the United States at that time. To base a study on presumptions is simply to go beyond science.

gelin

[Gelin*]

Before I continue with more observations, here is another link for a pdf version of the article:

http://www.eebweb.arizona.edu/nachman/p ... l_2007.pdf

Enjoy! And if it turns out that I'll have to play solo for some time, well, I'll play solo. Some songs are so enjoyable that you have to keep singing even when just a few on the forum here seem interested to join...<i>Hmm! ♪ Hmm1 ♪ ♪ Bababeda ♪ a a♪ </i> :-)

gelin

[Gelin*]

Obs # 6: The authors failed to report critical sequencing information

Each sample was extracted, PCR amplified, <u>and sequenced twice to ensure</u> that the sequences generated were not modified through low template copy number. <u>We recovered five full-length env sequences and five partial (0.7- to 1.2-kb) gag sequences.</u>

There are a number of things not clear with the above statement. Before I address some of them, I think it’s important to clarify a few point about DNA itself.

DNA consists of a sequence of subunits called nucleotides. Each nucleotide consists of a sugar, a phosphate and a base. In a given stretch of DNA, the following 4 bases are found: Adenine (A), Cytosine (C), Guanine (G), and Thymine (T). To sequence a piece of DNA, a gene, a chromosome, or an entire genome means to find the order in which these bases are organized. An example of a DNA sequence is ATCGAATTGCCG. And that sequence, if found in a DNA sample that is adequately stored, will be the same no matter of often one may want to look at it. Given that, I understand that our story tellers failed to report critical sequencing information in their study:

a) How much similarity did they find in their various sequences?

The authors started with 6 blood samples and one of them did not give any PCR product (Obs # 4). If we call the first one “Sample A”, that leaves us with 5 samples (B, C, D, E, and F). Considering that each sample was sequenced twice, we would have something like this: B1 (1st sequence from Sample B) and B2 (2nd sequence from Sample B), C1 and C2, D1 and D2, E1 and E2, and F1 and F2.

As readers, we would like for instance to know if B1=B2, C1=C2 and so on…And since we are dealing with the same virus and the same pair of genes (env and gag), perhaps it would be even good for us to know if B1=D2=F2 for each gene. In other words, we would like to know if experimental or human error was large or small. Was there significant variation within samples (a different sequence for each replication in the same sample) or among samples (a different sequence for each sample)? Basically, the authors failed to tell us if the sequences generated by each replication were identical, completely different, or partially similar. As a result, when they talk about sequence alignment throughout the paper, we simply can’t know what they really mean. And that’s not good for us. For them, maybe; but not for us!

b) How can they use both full and partial sequences?

The authors told us they recovered full sequence for the env gene but only partial sequences for the gag gene from each of the five samples; and they kept going as usual without even attempting to offer an explanation. Is it because they simply could not recover a full sequence after repeated attempts? Or is it because for their purpose a full sequence of the gag gene was not necessary? Your guess is as good as mine.

c) Why did they pick only “two” gene sequences among the many that are available?

I do not find a solid justification for their choice of just the env and gag genes anywhere in their paper. Perhaps they did not see this as an important point, but we are talking science here, not mere propaganda. There is much more that is known about the HIV virus.

gelin

[Gelin*]

Has anyone here in the forum (and beyond :-) taken the time to read the paper or just look at it? It's worth a try...

gelin

[Gelin*]

Take about 5 minutes to follow this link and listen to a few words from Dr. Warenn Johnson who has been working in Haiti long before HIV/AIDS showed up there. Although brief, his comments are in ligne with some of my observations:

http://www.npr.org/templates/story/stor ... d=16223498


gelin

[Gelin*]

By the time our story tellers had decided to publish their “tale from the lab” portraying Haiti as a stepping stone in the worldwide spread of HIV/AIDS, a lot of genetic information had already been collected on the virus. If you are interested, click on the link below to see some of what’s available today:

http://www.hiv.lanl.gov/content/sequenc ... dmark.html

Remember, they did not say much to explain why they picked only two genes, and they did not explain why they used only partial sequences of one of them.

gelin

[Gelin*]

Obs # 7: The authors applied arbitrary measures to downloaded sequences.

Until now, I have paid a particular attention to what our story tellers have produced themselves, that is, their rationale for the study, their methodology, and the DNA fragments they were able to collect (or not) from relatively old blood samples. In all of these areas they were funny, at least. Now, let’s turn our attention to DNA sequences produced by others to see what they did with them:

<b>Sequence Alignments.</b> We used the Los Alamos National Laboratory HIV sequence database (29) to download all full-length published env and gag gene sequences of subtypes B and D. We then subjected the resulting sequence set to strict quality control measures to remove (i) incomplete sequences; (ii) sequences not published in a peer-reviewed journal; (iii) multiple sequences from the same patient; (iv) sequences suspected a priori of possibly anomalous evolutionary patterns (from long-term nonprogressors with nef deletions, laboratory workers infected accidentally, sequences exhibiting evidence of hypermutation, etc.); (v) sequences with midpeptide stop codons, frame-shift mutations, or nonnucleotide characters; or (vi) sequences for which there was any uncertainty regarding which subtype they belonged to.

There is no need for me to go over every point of their so-called ‘strict quality control measures’, which consists ONLY of removing elements of the downloaded sequences. But consider for a moment one of the things they removed: (i) incomplete sequences;

The first thing our story tellers did with the data they downloaded from Los Alamos was to remove incomplete sequences. Why? They would not say. What’s wrong with incomplete sequences? Have they all of a sudden become afraid of incomplete sequences? Well, whatever their thinking was at that time, they apparently have forgotten that the only thing they could get for the gag gene was PARTIAL SEQUENCES! Perhaps they should have also removed the gag (partial) sequences from their analysis, and that would have left us with only the env sequences to work with. That could be a good place to start. And I wonder if their so-called phylogenetic tree would then have turned into a crooked twig!

I don't believe their story one bit.

gelin

[Gelin*]

<i>…Et le spectacle continue…</i>

What else did our story tellers remove with their so-called ‘strict quality control measures’? They removed: (ii) sequences not published in a peer-reviewed journal;

Oh Yeah…You got it right. After removing “incomplete sequences” for the set of sequences downloaded the Los Alamos Lab, the authors went ahead and removed any sequence published by Las Alamos but not published in a peer-reviewed journal. Do you see what I see? Let’s take a closer look at their game:

a) Didn’t they use “the Los Alamos National Laboratory HIV sequence database to download all full-length <u>published</u> env and gag gene sequences of subtypes B and D”? Now they want us to believe that if a sequence is not published in a peer-reviewed journal it’s no longer valid. Don’t they trust the lab? Does that mean that in their eyes sequences published by the Los Alamos Lab are not that good?

b) What about their own complete env and partial gag sequences? Were these sequences published elsewhere before our authors generated them? And it appears that if you want to see their sequence alignments you’ll have to address a special request directly to the authors. Why couldn’t they just go ahead and publish them if they are so concerned about sequences “published in a peer-reviewed journal”?

Well, considering that our story tellers seem to have issues with sequences NOT published in a peer-reviewed journal, and since they did not publish their own sequences “in a peer-reviewed journal”, would it be ok if I decide to apply “strict quality control measures” to the literature available and JUST DISCARD THEIR PAPER? That would be fair, don’t you think?

gelin

[Gelin*]

...I will stop soon...

And the kept on purging the data set by removing:

(iv) sequences <b>suspected a priori</b> of possibly anomalous evolutionary patterns (from long-term nonprogressors with nef deletions, laboratory workers infected accidentally, sequences exhibiting evidence of hypermutation, etc.);

I will not say much here, but consider this. Our story tellers are so good (at least in their own eyes) that they can just look at some sequences and SUSPECT that they came from “laboratory workers infected accidentally”. And that’s why they were removed. Ah Ah…yep! They can suspect those things a priori!! And that makes me wonder if the archival blood samples collected from those Haitian patients were not accidentally contaminated in the lab. That could perhaps explain why one sample could never yield PCR products…

But we have not seen the really fun part yet…

gelin

[Gelin*]

Here we go again....

Obs # 8: The authors used strange ways to adjust their sequence alignments

The resulting data sets were codon-aligned and then adjusted by eye in Squint Ver. 1.0 (M. Goode, University of Auckland, Auckland, New Zealand), and regions of ambiguous alignment were removed.

Let’s look at one thing here. After removing all sorts of sequences from the data set published by the Los Alamos Lab, our story tellers did something funny: they did their sequence alignments by eye using “something” called Squint Ver. 1.0. Yep, they squinted at the data!!!! And it makes me smile to imagine them in their white lab coats doing nothing more at this point than squinting at their sequences. As I think of this part of their story, a number of questions come to my mind:

a) If to squint means to narrow your eyes, to strain to see, or to look sideways, what in the world is Squint Ver. 1.0?
b) Is there a sort of training one must go through in order to learn how to use that tool or to learn how to squint scientifically?
c) Do they offer a certificate in squinting so one can become a certified squinter?
d) Was there ever a 0.5 version of the Squint thing?
e) Does their tool require closing entirely the left eye to squint at the data with only the right one?
f) If M. Goode is the Master Squinter who developed the tool where is that listed so people can go check it out?
g) <i>…at this point feel free to include your own questions…</i>

The more I squint at the study, the more ridiculous it appears to me. Perhaps I squint too much…

gelin

[Guysanto]

Today is Windows on Haiti's anniversary and I want to use this occasion to express my great admiration for Gelin as he has singlehandedly taken on his broad shoulders the responsibility of debunking this pseudo-scientific theory which allegedly demonstrated that the AIDS virus first appeared in the U.S. via a case of African-Haitian migration. I thank Gelin for using the pages of the Ann Pale Forum (5th anniversary) of Windows on Haiti (10th) for such a systematic deconstruction of the authors' fallacious arguments and suspect methodology.

Frankly, no one could have done it better than Gelin in the space of a few concise observations. That's probably why most of us were content to keep silent, something that could have been most discouraging to Gelin and might have prompted him to stop along the way. I am glad he did not.

Respè ak Onè, Gelin, for the faith you have in us, the capacity of these archives, and Ann Pale's potential to contribute to our people's education and national consciousness.

[Shelony]

Gelin, we missed you yesterday.

I just want to join my voice with Guy to compliment you for taking the time to address the numerous issues of the article. To tell you the truth, I read the article numerous times to try to see if it has any scientific merit or if it could be easily refuted. I even attempted to contact a Haitian scientist I know who could be better than me in the field of virology and HIV evolution but found his research in the field was really brief and not deep enough to address certain techniques used in the field. But I am happy to see that you have taken the time to address a lot of issues in the article when we all stayed silent.

I don't know if you read the articles mentioned in references 9-11 (observation # 1), I read them and I feel that all these articles reach about the same conclusions regarding Haiti and HIV although in a more subtle way than Worobey. I feel that this is something that our (Haitian) scientific community should have addressed a long time ago. For taking the time to do what is long overdue, I command you again.

However, there is one thing I would like to ask you and one thing I would like to clarify about the observations that you have made.

The first one, you can email me with the answer or post it if you want. It's about observation # 2

Obs. # 2: The authors associate one right idea with a wrong one in a subtle way.

Quote:
...However, these competing hypotheses have never been rigorously tested, <b>despite their importance for understanding the global spread <u>and</u> vaccine-relevant genetic diversity of HIV-1...</b>

The authors are right in stating that these two hypotheses can help understand the global spread of HIV-1, simply because they deal with whether or not HIV/AIDS came to Haiti from the United States. That’s the first part of their claim. The second part is wrong when they state that there is “vaccine-relevant genetic diversity of HIV-1” associated with their study – and here is why:

1) The production of vaccines is related to the strict existence of variants (genetic diversity) of the virus AND has no connection whatsoever with the above hypotheses that deal only with how the virus moved from one place into another (from US to Haiti or vice versa).

2) Vaccines already exist and have been used for many years to control HIV/AIDS in the US, Haiti, Africa and around the world. If the authors had made that statement in the early 80’s, perhaps some people would have believed it because not much was known on the subject at that time. The authors are late by at least 2 decades! All of them together! Science is good very good, but scientists can be funny at times.

It's more specifically about part 2 of your comments. can you please direct me to some sources where I can find evidence of vaccine used for HIV? I just want to compare that to something I read recently in JAMA and my email is ssf224@med.nyu.edu.

The comment is about the last observation (# 8)

Obs # 8: The authors used strange ways to adjust their sequence alignments

Quote:
The resulting data sets were codon-aligned and then adjusted by eye in Squint Ver. 1.0 (M. Goode, University of Auckland, Auckland, New Zealand), and regions of ambiguous alignment were removed.

Let’s look at one thing here. After removing all sorts of sequences from the data set published by the Los Alamos Lab, our story tellers did something funny: they did their sequence alignments by eye using “something” called Squint Ver. 1.0. Yep, they squinted at the data!!!! And it makes me smile to imagine them in their white lab coats doing nothing more at this point than squinting at their sequences. As I think of this part of their story, a number of questions come to my mind:

a) If to squint means to narrow your eyes, to strain to see, or to look sideways, what in the world is Squint Ver. 1.0?
b) Is there a sort of training one must go through in order to learn how to use that tool or to learn how to squint scientifically?
c) Do they offer a certificate in squinting so one can become a certified squinter?
d) Was there ever a 0.5 version of the Squint thing?
e) Does their tool require closing entirely the left eye to squint at the data with only the right one?
f) If M. Goode is the Master Squinter who developed the tool where is that listed so people can go check it out?
g) <i>…at this point feel free to include your own questions…</i>

I just want to include some information about SQUINT ver 1.0
It is a software developed by Matthew G. Goode and Allen G. Rodrigo. There are different versions of it. It stands for SeQUence alIgnmeNT (SQUINT). It is a software that allows scientists to align multiple sequences of nucleotides (DNA or RNA) or/and amino acids (protein). It is supposed to be a powerful tool allowing the scientists to do sequence editing. It also helps seeing different type of mutations and is very helpful in the creation of phylogenetic tree. The original article about its development and features can be found in the journal Bioinformatics 2007, 23: p 1553-1555. Information can also be found at the site of the bioinformatics department of the university of Auckland in New Zealand. The website is www.cebl.auckland.ac.nz. From there you will click on the link "software" and you will get some basic information. I don't think there is anything wrong with using that particular method. It just simplifies the work of the authors because it allows them to do multiple things at once while still allowing them enough freedom to check and adjust by eye.

Sorry for being that long I know you don't like that. But I just wanted to clarify this issue and ask you for this specific information. Hope to read you soon.

Shelony

[Gelin*]

Shelony, I will come back to your observations about my observations. Actually I am glad you decided (finally) to jump in and bring some balance to my position. Feel free to disagree or bring more light wherever applicable. Later this week I will post some answers to your points. In the meantime, let's keep squinting....:-)

gelin

[Gelin*]

Shelony,

I'll be brief today but I'll come back soon. Nèg onjan bizi...

Obs # 8 has two parts and I have underlined a few words as a hint. For the first part about squinting, I wanted to have some good fun because I have been serious for too long in this series. I did laugh and hope some other squinters on the forum (and beyond.. had some good time as well.

I knew Squint was a software and that's why I asked a question about an earlier version. But you see, it's not up to the reader(s) to guess what anything is in a paper published in a peer-reviewed journal! And if details cannot be provided because of lack of space, at least the references should make it possible to dig deeper. All the information you provided in your post should have been made available by the authors themselves, or that lack should have been picked up by the reviewer(s) and editor in chief. Look how much space they took to talk about those Haitian immigrants...and see how many times the words Haiti or Haitians show up in their paper. Even some headings are potentially misleading (I'll come back to that one later on)

I kept squinting, hoping that someone would decide to take a walk through that open door. I am glad you did. One thing: I won't feel discouraged or upset if you disagree with some of my points. Far from it! I am sharing what I see and think, feel free to do the same. And I have a couple of more observations to post here before I stop. I guess I'll stop at 10, but there is more. Isn't squinting a good thing...

gelin

[Gelin*]

....Just a few more posts and I'll stop...

Shelony asked the following questions:

...I don't know if you read the articles mentioned in references 9-11 (observation # 1), I read them and I feel that all these articles reach about the same conclusions regarding Haiti and HIV although in a more subtle way than Worobey...

and

...you please direct me to some sources where I can find evidence of vaccine used for HIV? I just want to compare that to something I read recently in JAMA...

I'll try to address the second one first. HIV is an acronym for Human Immunodeficiency Virus, and AIDS stands for Acquired Immune Deficiency Syndrome. We all know that here but it doesn’t hurt to say it again since that difference is somewhat important for what I am going to say.

Our story tellers want us to believe that it’s important to know if the virus came to Haiti from the U.S. (or vice versa) because of so-called “vaccine-relevant genetic diversity of HIV-1.” associated with their study. I say, nope!

In Point 2 of Obs # 2 I say that vaccines already exist and have been used for some time for HIV/AIDS control. And that seems to be a bit unclear since you asked me to point to “evidence of vaccine used for HIV”. Let me explain what I meant.

Do we have good HIV vaccines? No, and apparently it will take a few more years. But have vaccines been used to control HIV/AIDS? Yes. The reason is that opportunistic infections and diseases usually invade the body following HIV infection. For these opportunistic diseases vaccines exist and have helped many carriers stick around above ground a bit longer. Here is one link:

http://aidsinfo.nih.gov/contentfiles/up ... _FS_en.pdf

When I talked about vaccines, I meant for HIV/AIDS but not for HIV itself. I meant vaccines to fight the syndrome and not the virus. I don’t know if my explanation helped a little bit. Please feel free to add, subtract or multiply. But please, no more squinting….:-)

gelin

[Shelony]

Gelin,
Thank you for the answer. I thought you were referring to anti-HIV vaccine. Not too long ago, I read about the failure of HIV vaccine research in the news and in details in JAMA and I felt that there was a feeling of disappointment in the scientific community because to date every attempt at generating an effective vaccine has failed. I wanted to see if there was another view on the subject or if there was a vaccine against a different subtype of HIV other than the one which has been in the news lately.

But you say,

Our story tellers want us to believe that it’s important to know if the virus came to Haiti from the U.S. (or vice versa) because of so-called “vaccine-relevant genetic diversity of HIV-1.” associated with their study. I say, nope!

In Point 2 of Obs # 2 I say that vaccines already exist and have been used for some time for HIV/AIDS control. And that seems to be a bit unclear since you asked me to point to “evidence of vaccine used for HIV”. Let me explain what I meant.

Do we have good HIV vaccines? No, and apparently it will take a few more years. But have vaccines been used to control HIV/AIDS? Yes. The reason is that opportunistic infections and diseases usually invade the body following HIV infection. For these opportunistic diseases vaccines exist and have helped many carriers stick around above ground a bit longer. Here is one link:

http://aidsinfo.nih.gov/contentfiles/up ... _FS_en.pdf

When I talked about vaccines, I meant for HIV/AIDS but not for HIV itself. I meant vaccines to fight the syndrome and not the virus. I don’t know if my explanation helped a little bit. Please feel free to add, subtract or multiply. But please, no more squinting….

Although now I understand your point, and agree with you that the result of Dr Worobey study (which is inconclusive at best) doesn't help a bit in controlling the spread of the virus understanding its genetic diversity, I agree with him that understanding genetic diversity of a microbe is important in order to develop effective vaccine.

Vaccines are designed to help the immune system mount an effective and fast response to either prevent or control an infection. High rate of mutation and genetic diversity in the microbe is not good for the development of effective vaccine unless one can predict the rate and the type of variation. This is the reason we get vaccinated once (or maybe once every 5 or 10 years) against certain microbes but have to be vaccinated annually for others. The flu vaccine is an example which falls in the second category because of the high mutation rate and genetic diversity of the causative agent. Every year, scientist have to make prediction based on the current forms of the virus and past pattern of mutation to determine what type of vaccine to make. Because it is based on prediction (has to be made before the actual strain exists), the vaccine is not always effective. Therefore, one could conclude that genetic diversity and even more so a lack of its understanding would make creating effective vaccine a challenge.

For the other vaccines that are used against the opportunistic infection that characterize AIDS, I would not consider them as AIDS vaccine but rather as hepatitis, tetanos, diphteria... vaccines for the reason the they do not do anything to the causative agent of AIDS which is HIV. Beside, their safety and effectiveness depend on how much damage that HIV itself has caused to the immune system that those vaccines suppose to modulate.

Also, if you get a chance to read reference 9-11 let me know what you think.

You say no more sqinting... but on squinting, don't you think that the information provided in the paper was sufficient (name, version, developers, affiliation). Also the original paper for the software was published the same year as the AIDS paper, could it be that they could not have given more details because the software paper was not accepted yet. Isn't it weird that I am making more excuses for them, but anyway, it is apparent the software was refinement (such a word does exist?) of a feature of another sofware developed at the same place; may be the reviewers and the editors were familiar with the previous one and did not ask too many questions.

One last thing; have you looked at the phylogenetic trees in the paper? Given your background in genetic, and let's forget for a moment that there are flaws in the experimental methodologies used, do you think that the result as is really prove at 99.9 percent that HIV came to the US from Haiti?

Shelony

Shelony

[Gelin*]

...Although now I understand your point, and agree with you that the result of Dr Worobey study (which is inconclusive at best) doesn't help a bit in controlling the spread of the virus understanding its genetic diversity, I agree with him that understanding genetic diversity of a microbe is important in order to develop effective vaccine.

We can agree on that one BUT it must be made clear (as clear as we possibly can) that understanding the genetic diversity of HIV-1 has NOTHING to do with whether or not it came to Haiti from the US (or vice versa). And that's exactly what our story tellers want to imply in a very sublte way. It's a fine line.

gelin

[Gelin*]

...Given your background in genetic, and let's forget for a moment that there are flaws in the experimental methodologies used, do you think that the result as is really prove at <u>99.9 percent</u> that HIV came to the US from Haiti?

No, I don't think our story tellers proved that the virus came to the U.S. from Haiti. Probability values depend primarily on two things: a) the type of data submitted for analysis; c) the type of analysis performed (not to mention the tool used for the analysis).

If I see a 100% P-value in a study (basically that's what they say), two things come to my mind: a) this research team is extremely lucky; b) there is something very funny in the study. Well, to tell you the truth, I don't think our guys were lucky at all; I think their study is simply funny. And that's why I reject it.

gelin

[Gelin*]

...You say no more sqinting... but on squinting, don't you think that the information provided in the paper was sufficient (name, version, developers, affiliation). Also the original paper for the software was published the same year as the AIDS paper, could it be that they could not have given more details because the software paper was not accepted yet. Isn't it weird that I am making more excuses for them, but anyway, it is apparent the software was refinement (such a word does exist?) of a feature of another sofware developed at the same place; may be the reviewers and the editors were familiar with the previous one and did not ask too many questions.

Not really, Shelony, we can keep squinting as long as we need to...:-) and all you say here makes sense. But , here is what we have on this issue:

a) Matthew G. Goode and Allen G. Rodrigo. SQUINT: a multiple alignment program and editor. Bioinformatics Advance Access published on <b>May 7, 2007.</b> Bioinformatics 2007 23: 1553-1555; doi:10.1093/bioinformatics/btm128

b) For the story in question: Edited by John M. Coffin, Tufts University School of Medicine, Boston, MA, and approved September 17, 2007 <b>(received for review June 6, 2007)</b>

It appears that our story tellers submitted their document roughly one month <u>after</u> the software was published (online). Did they know? The information they provided can be sufficient when there is nothing else availabe. I have seen examples where the phrase "In Press" was used following a reference just so the reader can know that it's coming out soon. Also, if there are many versions of the thing each may (or may not) carry features that influence the analysis output (trees, p-values...). But to tell you the truth, being a bit vague about Squint is just a minor weakness of their story - and something I wanted to laugh about...

Happy Mother's Day to All...

gelin

[Gelin*]

...Also, if you get a chance to read reference 9-11 let me know what you think.

I have a copy of two of them but never really had time to read them carefully. If I get a chance to do that I'll let you know what I find. Do you have anything specific that you can share from these studies?

gelin

[Gelin*]

Earlier I promised to stop after posting 10 obs but I guess I will stop with this one: Part 2 of Obs 8...

The resulting data sets were codon-aligned and then adjusted by eye in Squint Ver. 1.0 (M. Goode, University of Auckland, Auckland, New Zealand), <b>and regions of ambiguous alignment were removed.</b>

Here we go again. Our story tellers kept on REMOVING sequences but this time their eyes were on "regions of ambiguous alignment". What they failed to tell us is: a) how they decided that some alignments were ambiguous; b) what was the frequency of "ambiguous alignment" given that alignment was done only after their so-called "strict quality control measures"?

As usual they just kept going hoping that people will buy into their story simply because it was published in a peer-reviewed journal. There are too many holes and too much critical information is lacking for people to take them seriously. Of course they have now made a name for themselves and people will talk about them every time the subject of HIV/AIDS spread is discussed, even if later on they or PNAS would be forced to retract the paper...

Nap swiv!

gelin

[Gelin*]

"When HIV Spread Afar" was published by PNAS last November to help <u>spread</u> the (pseudo-scientifc) rumor that the AIDS virus came to the West via Haiti. The link is here: http://www.pnas.org/content/104/47/18351.full.pdf+html , and this kind of support will make it difficult for the myth to dissipate. All this fellow did was to join the band and repeat the claims of the previous report - no more no less. A weird sort of echo for a scientific paper! But that does not change the fact that the previous report reads like a joke, a sort of gossip wrapped in scientific and technical jargon. I don't believe it.

gelin

[Gelin*]

Earlier, I promised (Shelony) I'd take a look at a couple of references cited in the 2007 report we have been discussing above. Here is one of their claims:

...The phylogenetic tree <u>inferred suggests</u> the following evolutionary history: divergence among the Zairian isolates was the earliest event; the Haitian sequences (RF and WMJ*) were derived from the African sequences; and the American sequences were later derived from the Haitian sequences. It is interesting to note that all the non-African sequences are monophyletic, suggesting a single introduction of the virus into North America...

Source:

<b>Rates and Dates of Divergence between AIDS Virus Nucleotide Sequences</b>
Wen-Hsiung Li, Masako Tanimura, and Paul M. Sharp
Center for Demographic and Population Genetics, University of Texas
Mol. Biol. Evol. 5(4):313-330. 1988

I will come back later to address what I think is wrong with this statement.

gelin

[Gelin*]

It's clear to everybody that the above statement IS NOT BASED on data at all. If that were the case then we would have to agree. Its only basis is what the authors produced themselves with the available data, that is the phylogenetic tree; their approach amounts to circular reasoning. They started with the idea that the virus came from Africa to Haiti and then from Haiti to the U.S., produced a phylogenetic tree that fits this pattern, took a good look at their own tree and cried " Voilà! ". In Haitian we say "Yo bat tanbou yo epi yo danse l ankò" ( they dance to the beat of their own drums).

Phylogenetic trees can be deceptive if the amount and quality of the input data are less that adequate, AND - above all - because the parameters that lead to the tree can be manipulated and changed almost at will.

But isn't it interesting that 20 years after this story, the 2007 report we have been talking about was published almost as a carbon copy of this one? Some people are bent on "proving" that Haiti somehow played a role in the global spread of the AIDS virus, but there was NO DATA in 1988 and there still is NO DATA in 2008 to support that view. That's why they keep hanging on to their trees...that's all they have!

gelin