Tuesday, March 30, 2010

Continuing Discussion About the Existence of HIV

If anyone is interested about reading about the ongoing discussion I have been having with the Perth Group here are some helpful links.

I initially posted a long message on a Facebook discussion page here. The post is about half way down the page under the name Kevin Sullivan.

The Perth Group sent an official reply to me in a PDF format that can be found downloaded here

It took me a little while (I was pretty busy with other things) but I recently got a repose back to them, and they kindly made the PDF public here.

Monday, March 29, 2010

Saturday, March 27, 2010

Opinion: HPV Policy

With all the HIV talk and my laborious posts on restriction factors I think this article is a good opportunity to branch out a little bit. Lets talk a little HPV policy.

Fighting viruses is tough. They don’t play by the same set of rules that other pathogens play by. At some point during my first semester in gradschool while drinking with fellow virologists we drafted a poem about the epic journey gradschool was going to be (yes ,we really are that lame, please facepalm for us….now). One of the last stanzas is.

For the virus is an awesome foe

Against which mankind has little to show

For how much time must mankind give

To finally kill that which does not live

Although corny, it is true, we have had trouble fighting viruses. The distribution of Cervarix from Glaxo Smith Kline and Gardasil, from Merck are one of the highlights of virology in the last 10 years. Not only is it a vaccine against a virus, it is a vaccine against cervical cancer. The Merck vaccine also has the added benefit of protecting against some types of genital warts, this may not be a lifesaver but from what I have seen in high school health class, that is one hell of a benefit.

Vaccinology can bridge the gap between bench science and public policy. Lets face it, public policy can be a complicated thing. Since men lack a cervix this vaccine was not initially approved for them (in the USA), many doctors do not stress its importance for men and I am not sure if it is even covered by most insurance companies yet. Despite the fact that something that would protect me from warts down there would be much appreciated (yes I had to link it). I am sure the cost benefit analysis has a little something to do with the decision, these vaccines are expensive to make.

It has been my opinon (I am not a doctor) that it is stupid not to vaccinate men. We sometimes forget in our self-centered society that vaccines are not for the individual. Vaccines do not do too well if most of the population is not vaccinated, especially when dealing with pathogens that can mutate quickly. Vaccines work best through herd immunity. Aggressive vaccination and high compliance rates protect the whole population, including those who have not received the vaccine. This is how smallpox and hopefully shortly polio will be eradicated.

Although, men cannot get cervical cancer from HPV 16 and 18, they can carry the virus and not even know it. Unless 100% of women get the vaccine before they become sexually active (putting a good age on this has been problematic) then women will still die from a preventable form of cancer. Things like that really bother me. Now, if you vaccinate both the carrier (men) and the women you lower the chances two individuals will transmit the virus. The occurrence of infection goes down over time in the population and the chances an unvaccinated person becoming infected rapidly decrease. Unfortunately, policy does not always work that way.

It is more unfortunate that the rise of another form of cancer may help me get my wish. It turns out that HPV 16 and 18 can cause another type of cancer, and it is on the rise. This one knows no gender barrier. Rates of HPV positive oropharyngeal squamous cell carcinoma (OSCC), a so called “head or neck cancer” have gone up by 70 percent in Stockholm since the 1970s and by 50-100% in the last 10 years in the United States. Oral sex is thought to account for the increase.

These findings are going to force the policy makers to reconsider a lot of positions. First, they are going to have to decide if men should be strongly encouraged to be vaccinated. They are also going to have to wrestle with the question of at what age the vaccine should be administered to women (hopefully men too) to insure they receive the series of shots before they become sexually active, including oral sex. Many have oral sex before having other more penetrative forms of intercourse. For OSCC prevention it may turn out to be too late for teenage and young adults, particularly men. Hopefully policy goes at a faster pace than science.

Wednesday, March 24, 2010

“What is WRONG with you people!”

So my See no SIV post got some comments on another forum. This is one from Claus Jensen

Kevin Sullivan,

What is WRONG with you people!

You post a couple of EMs, claim that we're looking at "SIV" because they look the same when they are cloned or something like that. Zero references. Montagnier also has an EM of budding "HIV", and you know what, when the genetic material was "cloned" and the particles from transfected cells were EM'ed they looked fairly similar to that original EM.

What exactly do you think are you adding with your SIV analogy ?

Your so-called "SIV" seems to cause disease when it is injected into a different monkey species, "HIV" doesn't seem to do very much when injected into chimps.

How exactly does that support your argument from analogy?
Let me tell you what would be nice: a couple of references where they inoculated a monkey with their deadly "SIV" or better even "SHIV", let him loose in a captive (has to be captive because it doesn't happen in the wild, coincidentally) colony and watched how the new monkey plague spread and decimated that colony via unprotected sex.

Can you do that, master analogist? Then maybe we can finally get somewhere.”

Claus, yes I put a couple of EM pictures of the pre cloned and cloned virus. I am sorry my brief referencing format author’s last name in year. I will gladly give you the pubmed links to the articles you request.

The EM of in the lymphnode of Macaque239 is from this paper titled “Isolation of T-cell tropic HTLV-III-like retrovirus from macaques” Daniel et al. 1985 in the journal Science.

The EM of cloned SIVmac239 is from this paper “The SIVmac239 Pr55Gag isoform, SIV p43, suppresses proteolytic cleavage of Pr55Gag.” Nicholson et al., 2007 in the journal Virology.

I brought up this point because somewhere some of the criteria of the PG called for was that there be an EM before and after isolation and they must look alike. These pictures validating that point. Dr. Turner states the following

“ To prove the existence of a new (“novelty”) retrovirus first you must:

1. Have proof for the existence of particles bearing all the morphological characteristics of retroviruses.

2. Prove the particles have unique biochemical constituents (proteins and RNA but no DNA).

3. Prove the particles are infectious, that is, the introduction of particles into a cell culture results in the appearance of particles with the identical morphology and biochemical constituents (proteins and RNA) as the parental particles.”

Thank you for agreeing that some of this has already been accomplished, particularly part 3. Montagnier also has an EM of budding "HIV", and you know what, when the genetic material was "cloned" and the particles from transfected cells were EM'ed they looked fairly similar to that original EM."

You state “Your so-called "SIV" seems to cause disease when it is injected into a different monkey species, "HIV" doesn't seem to do very much when injected into chimps.”

My argument is not about chimps. I talk about SIVmac in macaques from a virus that has been shown to come from a sooty mangabey, the same monkey that gave rise to HIV-2 in humans. Not all HIVs are the same, hopefully you appreciate this (or at least allow this distinction). I will discuss the macaque data here. I will discuss this topic first and once sufficiently debated by both sides we can move on to the chimps you are so interested in. Mind you I want to finish my longer reply to the PG fist as they are patiently waiting.

“Let me tell you what would be nice: a couple of references where they inoculated a monkey with their deadly "SIV" or better even "SHIV", let him loose in a captive (has to be captive because it doesn't happen in the wild, coincidentally) colony and watched how the new monkey plague spread and decimated that colony via unprotected sex.”

I will provide you with some links to papers for what you request, papers on the natural circulation of SIVmac in cohorts of macaques across the United States. This is from retrospective analysis. Keep in mind since we cannot ask the monkey, I cannot tell you whether transmission occurred through fighting, breast feeding, birth, or sex or any other route. We can show the virus was circulating before it was isolated, even before the discovery of HIV. SHIVs are artificial and do not replicate as well as SIVmac in macaques. There are no free circulating strains because this could cause problems at primate centers. If you want to get into the molecular biology of SHIVs I suggest we do so later as it is a very complex and technical area.

One theory of how SIV from a sooty mangabey got into captive macaques is presented by Christian Apetrei, I would consider him an expert on the free circulation of SIVs in captivity. This is an opinion piece as some important data was not taken or has been lost to time.

Kuru experiments triggered the emergence of pathogenic SIVmac.” Journal AIDS 2006

That hypothesis came from his careful work on the natural circulation of SIVs in macaques and sooty mangabeys. He traced the spread of SIVmac from the Davis primate center across the country. The paper is titled “Molecular epidemiology of simian immunodeficiency virus SIVsm in U.S. primate centers unravels the origin of SIVmac and SIVstm.” Journal of virology, 2005.

Here is a map and timeline of the spread. (for facebook viewers see linked blog at bottom of the post for all images)


Work at tracing the spread of SIV in the cohort of macaques at the New England Primate Center first was done by. Dr. Daniel “Prevalence of antibodies to 3 retroviruses in a captive colony of macaque monkeys.” International journal of cancer, 1988

This was followed up by Dr. Mansfield “Origins of simian immunodeficiency virus infection in macaques at the New England Regional Primate Research Center.”Published in the Journal of medical primatology in 1995. If you want to see the timeline of the New England outbreak I can scan the document and upload it to my blog.

The passage history of the SIVmac251 and SIVmac239 can be found in Ringler et al. “Simian Immunodefficiency Virus-Induced Meningoencephalitis: Natural history and retrospective study” Annals of Neurology 1988 . Again if you are interested in the figure I can put it online.

When you ask “What exactly do you think are you adding with your SIV analogy?”

I am presenting a case where a virus which is strikingly close to HIV-2 causes immunodeficiency in macaques. The sooty mangabey SIVs got into both humans and macaques and caused similar diseases. Your group makes the clam that HIV does not exist, due to the failure of its isolation and a few other sticking points. Animal data clearly proves beyond any doubt that SIVmac239 is an immunodeficiency virus. When similar sequences (coming from the same natural reservoir) are found in humans with the same immune problems your group claims it does not exist. No one has come out and explicitly stated the Perth Group’s opinion on these viruses. I believe that this is because it is a difficult subject to discuss as it forces them to either accept or deny this animal data and commit to a specific point of view. I cannot say that SIVmac is the smoking gun to prove HIV exists. You are right. However examples of the smoking gun in science are rare. Normally theories are built up and refined over time slowly. This is just another piece of evidence to my argument. Is it required, no, but it does help make my point. Hopefully, some neutral bystanders will agree.

Also I hope these links on the natural spread of SIVmac are sufficient. There are a few others. I would suggest using NCBI Pubmed to find others.

Tuesday, March 23, 2010

Don't worry Michael, I would have facepalmed too

I had reservations about watching Nightline's debate, "Does God have a Future?," featuring Sam Harris and Michael Shermer versus Deepak Chopra. The reason being, anytime Deepak Chopra opens his mouth, a frantic word salad of scientific sounding new agey tripe is released. This places any rational listener at risk of severe and permanent brain dysfunction after hearing just a few sentences of this vacuous crap. I'm glad I watched. Not just because Harris and Shermer were brilliant and eviscerated everything Chopra said, but rather because Chopra's composure implodes under the weight of his own massive ego. Shermer especially gets under Chopra's skin which was hysterical to watch. Chopra had to result to talking over everyone with clear indignation and frustration when his arguments were laughed at for what the were, complete bunk.

There was one exchange that literally had me in stitches, and I've taken the liberty of taking screen shots. This is the actual dialouge.
(Discussing how Deepak Chopra hijacks the word "quantum mechanics" to claim everything is connected and everything relies on observer experience, Shermer goes... )
Deepak Chopra has simply outdone himself.

Yellow: its worse than you think

Look around you, do you see something that's yellow? Just on my desk I have: post-it notes, a week old McDonald's coffee cup, a crinkled up Shop-Rite bag and all the pages in my lab notebook. I really dislike yellow too, its loud and obnoxious, but regardless, its all around us. But now, I have a new reason to add to my "why I hate yellow list," it contains PCBs.

Ah crap.

Polychlorinated Biphenyls (PCBs) were produced for roughly 50 years in the making of electrical capacitors and industrial lubricants before they were banned in the late 1970s. During that time, over a million tons of PCBs were produced which has lead to widespread environmental contamination. Due to their persistent nature, they act as a legacy contaminant, remaining in the environment at trace levels and being transported globally. Bad stuff huh? PCBs are also one of the most common contaminants we deal with in environmental toxicology because they are toxic and have the ability to become stored within fatty tissue leading to bioaccumulation within organisms and biomagnification within the food chain.

There are 209 congeners, or forms of the compound, that are classified as PCBs. Our scientific knowledge is mainly concerned with those congeners that were manufactured under PCB's trade name of Aroclor since these tend to be the most environmentally relevant. But in 1998, the NY DEC found a relatively unknown congener, PCB 11, enriched within New York Harbor wastewater. The researchers were able to trace this back to a pigment manufacturing plant which made paints. So it was thought these PCBs were either being released from paint production or from paint vapors.

But it turns out, PCB11 is from a specific pigment, called diarylide which is used to make the color yellow. New research in ES&T shows scientists were able to measure PCB11 in newspaper, yellow shopping bags and cereal boxes; pretty much anything except plain white paper. And its not just limited to physical products, PCB11 is ubiquitous. It is in the air, the water, sediment, and organisms. Things just keep looking worse. Within New York Harbor, it was measured at the part per billion (ppb) level which is quite significant. The same applies for the Delaware River, except, there are no pigment manufacturing plants that discharge into this waterway, meaning PCB11 is leaching from our garbage (paper and plastics) and contaminating the water.

PCB11 may prove to be a major obstacle in environmental remediation of areas effected by PCB contamination. For example the Hudson River which was infamously contaminated by two GE plants has just recently begun dredging of PCB-laden sediments. But in lower Hudson NY/NJ harbor, PCB11 remains both high and variable so even the removal of toxic sediment upstream will not make the Hudson PCB-free as long as there are other congeners being constantly released. Still, little is known about PCB11, including its toxicity, so we really don't know what we're setting ourselves up for in the future.

The story ends with some quotes that pretty much encapsulate the whole struggle of environmental toxicology.

"But PCB 11 is also symptomatic of a larger problem. “There are more chemicals being produced and invented than we’re able to analyze in environmental samples. At some point, you have such a mixed soup that the synergistic effect is greater than the individual chemical effect,” says Glenn Milstrey, director of the New York State Department of Environmental Conservation’s Bureau of Water Assessment and Management. “We are addressing legacy pollutants [such as dioxins and PCBs] that were discharged a generation ago,” says Scott Stoner, who heads the department’s Pharmaceuticals Work Group. “Let’s not let today’s emerging contaminants become the legacy pollutants that we leave to our children.”"

Monday, March 22, 2010

Words of Wisdom

So today I am sitting in my office with not much real science to do. Hopefully my cells are busy cranking out tons of HIV for later in the week. While talking to a post doc in the lab on an equally slow day he provided me with some words of wisdom, "science is like a pregnant woman, it takes so long to deliver." And there you have it, I think this best describes science. I can be fun to start, then you may regret it, you have to gut it out for a long time before you reach the end. Thats deep.

Sunday, March 21, 2010

Shark-Bitten Crocodile Poop Fossils Found (No, Really)

For the most part I think that this blog sticks to pretty defined areas of interest, mainly HIV/viruses and pollution/marine science. However, a science story comes about that just need to be told, this is one of those cases. Thats right, although highly improbable someone found a fossilized crocodile poo that bears the wounds from an encounter with an ancient shark. Lets think about this, first someone had to find a rock that had a strange pattern of holes it it. See below.



Then they had to bring it to someone to ask about them. That person had to have been bored enough to take a casting of those holes and then compare those to castings of modern day shark teeth. The conclusion, these holes were made by a shark that was a decedent of modern tiger sharks. Against all odds, this story is turning out to be pretty neat.

This discovery leads to many interesting questions. The one that came first to my mind was "what was an ancient shark doing munching on poop?" Followed by, "no wonder this species of shark went extinct". Fortunately, my burning yet sophomoric questions were answered by SCIENCE! It turns out the depth of the tooth holes are not even. This lead the team doing the investigation to speculate that this piece of preserved fecal matter was originally in the colon of some poor crocodilian that was attacked by shark. First, this is why I <3 science. Second, I felt satisfied with this answer. Third and most importantly, I wish I could have seen this prehistoric battle royal go down. Luckily for us all of us, this article included an artist's representation of what this battle may have looked like.





All I can say is badass \m/, I wish this picture was on a T-shirt

Wednesday, March 17, 2010

The Gasm

Breaded chicken, mozzarella, thick-cut bacon, cole slaw and Russian dressing. Coupled with half iced tea/ half lemonade.

Fuck yeah.

Two drunks drinking from the same cup of stupid

Sean Hannity is anti-science. I know, this will read like a story that ends with the punchline, "in other news, dog bites man," because its so damn obvious. But thanks to Sean Hannity's brave mavricky investigation, him and his lapdog Tucker Carlson can now report that stimulus money given to the NSF, is now being used for...get ready for it...grants! I'm sure when this story aired on Fox News this week, many a pearls were clutched and fainting couches were quickly deployed. But to everyone else in the reality based community, these two just look like a couple of fools who fell from the top of the stupid tree and hit every branch on the way down.

So what was the big deal here? The NSF granted Michigan State University over $187,000 to build new storage systems for their famous arthropod collection. Their old storage units were inadequate and were in danger of losing their specimens to other insects. Trying to save dead bugs from bugs. Hilarious right? Carlson sure thought so. He yipped with glee as he reported back to his owner as if he had exposed some know-it-all scientist. I could easily go through a line-by-line dissection of this since each sentence uttered drips with smug stupidity, but it would just be too infuriating.

You can just read the transcript of the segment here and see what I mean.



There is this part here that deserves some attention:

CARLSON: So four students are working on this collection who would not be working on it otherwise.

COGNATO: Correct.

CARLSON: How much are they getting paid?

COGNATO: They get paid between $8 and $10 an hour.

(END VIDEOTAPE)

CARLSON: So four kids are making eight bucks an hour to move dead bugs from old trays to new trays. This is the job-creation engine of the Obama administration.

An employee of the company benefiting from this grant showed up in the comments:

"My job is one of the many that were either created or saved by this particular grant. I work for BioQuip, the company, based in California that manufactures the drawers and unit trays that MSU purchased with their stimulus money. Our company employs 27 people and we purchase wood and other supplies used to construct said drawers from other American companies and those companies purchase lumber harvested and milled in the United States by still more American workers. There is also the local, US based glass company that manufactures and cuts the glass that we use on the tops of the drawers. All of these materials then have to be trucked to us by still more US workers, employed by US freight companies, and then the finished products have to be shipped to MSU, again, using a US freight company which employs American drivers. I could continue on and include the mechanics who work on the trucks used by the freight companies and so on and so forth but I think you get the idea. When you take the time to really examine the facts, this $200,000 stimulus grant has benefited the US economy, created and maintained American jobs and businesses on a level far greater than 4 jobs at a single university."

So Mr. Hannity, Mr. Carlson, why do you hate America?

Happy St. Patrick's Day

Tuesday, March 16, 2010

Ignorance is fish

So what do you do when the world's largest importer of seafood does not understand the concept of sustainable fishing? Actually, its worse than that. What happens if they are completely unaware of the concept of sustainable fishing? Well, the answer is that our fish stocks look a lot like they do now. Though it may seem obvious, a survey conducted of Japanese shoppers has shown that they haven't heard of sustainable fisheries and show little concern for fishing's environmental impact.

The Japanese are fairly notorious for their ravenous consumption of fish which fuels fisheries in all the world's seas. The spoils are shipped to Tsukiji Fish Market in enormous quantities and fetch unimaginable prices. Whether buying the fattest tuna for status or for food, the Japanese continue to oppose international trade regulations and fishing quotas. Even this week at the CITES convention, Japan stands in strong opposition of a bluefin tuna ban supported by the US and EU. Furthermore, their lobbyists have been threatening developing nations into siding against the ban.

So if the government is willing to stand in the face of all fishery science and international support, what does this mean for the Japanese consumer? Misinformation and unsustainable consumption. There is a dangerous mix of ignorance and hubris involved here. As quoted from the first linked article:

"[Japanese shoppers] were sceptical about how humans could ‘manage’ fish stocks and one woman shopper told researchers: 'There can’t be a shortage of fish – just look at how much there is in the supermarkets.'"

"Associate Professor Yuko Onozak of Stavanger University told the Seafood Summit in Paris: ' The Japanese are not aware of any problems with the sea. They don't see it. They don't hear it. They don’t think it is their problem.'"

These sentiments can also be found in the survey results which looked at the seafood concerns of 3,700 Japanese primary household shoppers. As seen below, less that 7% consider the environmental impact of how their fish was harvested very important. With more than 35% considering it unimportant. There results are similar for traceability, or where the fish came from. This is important for determining whether a fish has come from well-managed stock or not. This is bad news for fish stocks since of those surveyed, more than three quarters purchased fish at least once a week, and over half, multiple times a week.

The survey also showed that there was a lack of information available to Japanese consumers and a lack of understanding of what it even meant to manage fish stocks. Some never thought about it and others were unfamiliar with any of the eco-labels that are used to identify fish caught from sustainable fisheries. The phrase 'eco-' in Japan is only used for pollution and recycling, so for many, eco-friendly fish simply did not make sense. But probably the most frightening finding was that, out of the 3700 surveyed, NONE thought that overfishing was occurring.

Those surveyed did respond well to information that was provided to them with respondents willing to pay more for fish if it carried an eco label. But internationally, there really is no lack of information. The results showed that shoppers were more likely to trust the government regarding seafood information, and least likely to trust an NPO. What this just goes to show is that there really is no hope to change Japanese consumer perceptions untill the government actually acknowledges there is a problem. With the Japanese government strong-arming its way through another international conference, tuna and all other vulnerable fish stocks remain at risk from this arrogant over-exploitation.

Sunday, March 14, 2010

Restriction Factor-Tetherin: Not so fast you little virion

It is time to move on from all things TRIM related and I am going to take things in a different direction. Rather than talking about viruses getting in, I am going to be talking about getting out. BST2/Tetherin has a cool story to tell.

Although, scientists talk a lot of game with our technical jargon we do like to keep things simple (because even simple hardly ever works). For example when you want to know what a gene/protein is doing, the easiest way to figure it out is to get rid of it. When scientists deleted the Vpu gene of HIV-1 they saw something weird. First their cells made less virus. Naturally, they wanted to know what part of the viral life cycle was disrupted. It turns out the virus could do everything it needed to, except new viruses could not detach from the cell surface (see picture bellow from Neil et al., 2008). The conclusion was that Vpu was required for proper budding. The funny thing was that if you put SIVs into some human cells a similar thing happens. No one could figure out why but the story stopped there. Surly some grad students and postdocs got burned on this one.


The answer was only recently revealed. Vpu was not actively involved in the budding process at all, instead it was actively opposing a restriction factor that prevented budding. This factor makes a protein string preventing the new virus from leaving the cell. Previously named BST2 the factor was renamed Tetherin because it could “tether” a virus to the cell surface. The ability of a virus to get around this block is species and virus specific. HIV-like viruses, primate lentiviruses (PLVs) that make a niche in one species have a protein to take care of that specie’s Tetherin. If you put the virus in another species it has trouble getting around it.

If viruses had brains this is the sort of thing that would drive them crazy. Look at it from the virus’ point of view. It flies around an organism till it finds the right receptor. It dodges TRIM, it finds a nice spot to integrate into the genome, it makes all the proteins it needs before the cell kills itself or goes into lockdown mode, and now at the very last step the cell gets the last laugh and says…. gotcha bitch. Tetherin is basically a bungee chord preventing the virus from blasting of from the cell. The cell can then reel the virus back in and destroy it.

Insights Gained from the discovery

When one aligns Tetherin sequences from a few species you notice something very quickly, there is a lot of diversity. This is because this protein has been locked in an arms race against viruses, emphasis on viruseS. This protein is not only active against HIV when it is missing its Vpu, but if it were not counteracted it would work against HIV-2, SIVmac, SIVcpz, many other SIVs, Ebola, Marburg, at least one Arena viruses and KSHV. It is beginning to appear that Tetherin is active against just about any virus with a membrane, which begs the question how do other virus get around it?

The most stunning evidence of this arms race comes from how viruses have adapted to counteract Tetherin. I mentioned before that the effects of Tetherin are only observed either when a virus loses a gene to that takes care of Tetherin, or the virus finds itself in a cell that has a different type of Tetherin. The primate lentiviruses have jumped from species to species and they have utilized many proteins to counteract Tetherin. The Vpu of HIV-1 counteracts human Tetherin, but remember that virus came from a chimp virus SIVcpz. In a chimp the virus uses its Nef protein to do the same job. SIVmac in macaques also uses its Nef protein, while some types of the closely related HIV-2 use their envelope protein. This underscores a fundamental property of the PLVs, they are vey plastic, when presented with a challenge they will find a way to evolve around it. Arguably, solving the same problem independently with multiple solutions is one strong case against intelligent design.

Chimps and Humans are quite similar and the PLVs infecting them only diverged in an evolutionary blink of an eye. So why does one type of virus use Vpu while the other uses Nef? Again the answer is evolution. At some point after the two species diverged the human protein lost 5 amino acids in its tail. The amazing thing is that these amino acids are in the exact spot that some SIV Nef proteins recognize Tetherin. Nef basically grabs the tail of Tetherin, pulls it off the cell surface and marka it for destruction. The missing 5 amino acids protect human tetherin from Nef. Sadly, HIV evolves so quickly that it just switched to Vpu in humans to do the same task. The missing amino acids are common to all humans. The obvious question to ask is what virus selected for this? Was it the same virus that selected for only one version of Trim5 in humans? These are all interesting questions that make me want to build a time machine and find out.

Saturday, March 13, 2010

Interesting Story

Last night I went out to dinner with a few friends. While waiting for a table we got a few drinks at the packed bar. As I was trying to wiggle my up to the bar for a refill, a man struck up a conversation with me, he had more than a few. After a little bit about his life he asked what I did. I told him I was a grad student and it came out I was doing HIV research. His reply was a little unexpected. He gave me a big hug and said thank you. I think this has to be the first thank you I have ever received for doing research. It was totally unexpected and I was more than little taken back. He explained how in his social network, some of his friends had tested positive. He began to tell me how he gets regularly tested and takes all the precautions he can. He recounted how nerve racking the testing processes is every single time he has it done. I tired to tell him that what I was doing was basic research and would likely not amount to much in the way of a cure or treatment. That did not curb his enthusiasm. He was very happy to meet someone that cared and was “doing something about it”

When you are a grad student locked away in a lab somewhere you are not exposed to many people like this. I think it is every easy to isolate yourself behind your bench or stacks of papers. The science is tough enough on you, but when you mix in being stereotyped as the typical egg headed, nerdy, socially awkward science guy by most outsiders and the news have more coverage vocal opponents to science than expert opinions, you sometimes get the feeling that no one appreciates or understands what millions of people around the world are doing. When I wake up tomorrow with one hour less sleep on a cold, wet, stormy Sunday, (the type one would rather lay in bed all day) to put in a full day of lab work, I just may have a little more pop in my step, or at least not hit the snooze more than once.

Maybe we need a national Hug a Scientist day.

Friday, March 12, 2010

Friday Fish Tank - Angel spawn


Ok, not the best picture by any means. My laptop died so I lost all my good fish pictures. Here though is an old pic taken with my cell phone of my blushing koi angelfish pair protecting eggs they had laid on a leaf of java fern. Despite guarding them constantly throughout the day, they were no match for my psycho yoyo loaches. They must have gotten to the eggs at night because I came back to the office the next morning and the yoyo's had some big bulging bellies. Clearly, someone had a midnight snack.

Thursday, March 11, 2010

Hear no SIV, See no SIV, Speak no SIV

It is no surprise that in this blog space, there is absolutely 0 doubt that HIV exists. I think denying something with that much scientific evidence without presenting actual data of your own is a little silly.When asked on a Facebook discussion about where the Perth Group stood on SIVs we were met with this answer from an important player in the group, Valendar Turner (or at least someone claiming to be
him).

"Yes, “SIV is not HIV” and you cannot know how closely they are related unless you first have proof for the existence of both. And you cannot have animal models and all the rest unless you first have proof for the existence of HIV. And to paraphrase Professor Weiss, you don’t prove the existence of HIV by proving the existence SIV.”

Aside from dodging the question about how the Perth Group stands on SIV, and a lot of circular reasoning I can see why they make this point. The problem is that they cannot offer an opinion either way. The virus is trap to their ideology. Saying” yes”” they believe it exists, or “no” it doesn’t will compromise their argument either way. The best they can do is not answer the question. This is because of the history of SIVmac.SIVmac (our HIV/AIDS model in macaques “mac”) came from the cross species transmission from an SIV from a Sooty Mangabey to macaques, in captivity. It is a really cool story I will have to share some time. Most people talk about HIV coming from chimps. This is true of HIV-1, the more common form that has become pandemic around the world. However, HIV-2 arose form the cross species transmission of a Sooty Mangabey SIV to humans. This is more common in western Africa where the Sooty Mangabey’s natural habitat is. The virus appears to be less pathogenic and less easily spread. Nonetheless it is a human immunodeficiency virus that has a brother in macaques. Because of some careful work, SIVmac239 fulfills a lot of the criteria the Perth Group uses to claim HIV-(1?) does not exist. There are EM pictures of the virus budding from a lymph cell of macaque 239-82.


(Daniel et al., 1985)
(Nicholson et al., 2007)

The virus was cloned after culture (sequence here) and the virus by the clone looks the same (above). Furthermore this virus does fulfill Koch’s postulates. Monkeys that were given infected blood from macaque 239-82 (example macaque 316-85) and the virus caused the same immunodeficiency, and the virus was isolated to make the infectious clone SIVmac316. The SIVmac239 clone can also be used to infect other animals, which present the same immunodeficiency symptoms. These experiments could never be done in people. Basically this virus rocks their argument.

The fact that it is so closely related to a similar HIV virus in humans makes the Perth Group walk a fine line. Because of the overwhelming evidence that SIV is a real virus (the animals are not given any drugs so its not the treatments, they are well fed no so starvation or oxidative stress, monkeys are not in any risk group so they are not IV drug users or hemophiliacs and although I never ask I would think most are not gay) so to deny this virus exists just makes them sound crazy. Yet if they do say this virus exists it opens the possibility of saying HIV-2 exists since both viruses have a common not so distant ancestor in Sooty Mangabeys. Now I cannot prove HIV exists by proving SIV does, but its presence cannot be dismissed either.

Monday, March 8, 2010

Whales are the “forests of the ocean”

Well here’s a weird little article from the BBC. Researchers from the Gulf of Maine Research Institute have calculated that a century of whaling has released a large amount of carbon into our atmosphere. The use of whale oil has released equivalent amounts of carbon to burning 130,000km^2 of temperate forests, or running 128,000 Humvees continuously for 100 years. Still pretty small compared to the annual anthropogenic input, but this highlights a larger issue.

From the biggest whales to the huge schools of harvestable fish, they are all made up of carbon, lots of it. And whenever we remove biomass from the oceans for our land use, we are reducing the amount of carbon that would otherwise sink to the ocean floor when the organism dies. Previously unaccounted for, the amount of carbon that can be sequestered to the deep ocean by large organisms may be significant. The new research suggests that megafauna aren’t just important an important flux of organic matter which feeds the ocean’s carbon cycle, but they may also be a manageable global carbon sink.

If the amount of carbon contained within a stock of whales or fish could be calculated, the researchers suggest a carbon credit system could be put in place to encourage nations to not fish. This could work in much in the same way as carbon credits are issued for trying to reestablish forests. Keeping marine carbon in the ocean…seems like an interesting way to address the issues of conservationism, climate change and dwindling fish stocks simultaneously.

Friday, March 5, 2010

Friday Fish tank - Laetacara curviceps


It's ironic. I can't get any eggs in the lab and yet fish in my home tanks are spawning, and the angelfish in my office tank were going at it today. Here is Laetacara curviceps, or dwarf flag acara. An extremely pretty fish with each scale an iridescent green or blue. However, when in spawn mode like above, they turn a dark purple, almost black. Pictured is the female guarding her spawn. They are almost ready to become free swimming fry, with a few hopping up every now and then. The male and female take turns protecting the spawn and will occasionally carry them by mouth to a new location. The brooding behavior has been very entertaining to watch. Hell, I didn't even know I had a male and female, I assumed both were male since they were so colorful.

Since the photo was taken, the pair has moved the free swimming fry into a shallow pit dug out in the substrate and are dropkicking any fish that gets close. Ok, they're not being that aggressive, but everyone else is keeping away from that side of the tank.

Thursday, March 4, 2010

Inspiration

Grad school is a strange beast. Nothing can be more exciting and rewarding while at the same time so defeating as John pointed out. I chose to study virology because I wanted to make a difference. I thought that there was no better way to impact as many lives as possible than working on infectious diseases, especially viruses which lag behind bacteria in treatments. I was young bright eyed and optimistic, probably a little too young, too bright eyed and too optimistic. Many seasoned grad students and PhDs who talked to me would agree. I respected the fact that science moved at a time scale only slightly faster than a geologic one, but I was not prepared for the rollercoaster that is grad school. I have to say through classes and rotations I felt like anther cog in a massive machine. I never saw how anything I worked on could ever make a slight impact on the world or be of the slightest interest to anyone aside from 10 other people in the world. It is really a quite humbling and depressing realization. Scientists are born asking question, so it comes at no surprise that we usually question ourselves, our motives, our skill, our qualifications and our goals and ambitions. If I had a quarter for every time I questioned myself I could fund my lab. The most important and frequent question I ask myself is “is it worth it?” On my worst days when my western blot has failed every day for the second week in a row, I almost say no. Caught in a moment of hopelessness I question how much more failure I can take, how on earth can I continue in a career of failure, and most critically how can I fulfill those wild dreams of making a difference in the world. I refuse to let grad school take that goal away from me. Its on days like that when seeing something like this (see below), makes me proud of what I am doing, strengthens my will, and motivates me to step outside the confines of my lab and actually try to make a difference.

Letter From JW. Tested HIV Positive. What do you suggest I do from here regarding further testing? I don't know what to beli...

Today at 12:01pm

Date: Sun, 31 Jan 2010 07:01:08 -0800
To:
Subject: House of Numbers: Tested Positive - Film Availability

I am a 34 y/o gay male who recently tested positive in December. I had three tests - two rapid (oral and blood) and one Western Blot and they all (shockingly) came back positive. I don't understand how this is possible because I've only had oral sex and never let anyone intentionally cum in my mouth. However, it has happened a couple times. That's the only "exposure" I can assume in my case. However, even then it's very rare according to what I've researched.

I'm supposed to have a viral load test to confirm this is in fact HIV. I just don't trust the process anymore and the "meds" have always been a fear of mine years before testing positive. I just knew in my spirit that they're poison and I believe your film (like the others) confirms that.

I recently watched AIDS, Inc and another similar documentary. They're both dated films but very informative and have led me to question HIV/AIDS diagnosis. More specifically the testing process.

I'm really looking forward to viewing House Of Numbers but unfortunately I discovered your documentary after it already screened in Los Angeles. Is it possible to purchase an advanced copy or screener? Is it available to view (PPV) online?

What do you suggest I do from here regarding further testing? I don't know what to believe anymore and it's very uncomfortable not knowing what to do.

Thank you for your time and your courage in creating this film.

Respectfully,
JW

Updated 9 hours ago · View Original Post · Report Note

Sheila Dvorak If you can send this message to JW - PLease contact the organization Alive and Well. They will be able to help you from here. http://www.aliveandwell.org/

2 hours ago · Report

Andres Marroquin Hi Dear JW, my suggestion for you, is not to rely on beliefs, this is mostly a matter of educating your self about real facts, behind HIV=AIDS hypothesis, I would strongly recommend if you study the scientific literature from great and highly credible people, who spent years, making research on this matter, read Inventig the Aids Virus from Dr. ... See MorePeter Duesberg, also Origins, Failures and persistence from HIV=Aids hypothesis from Dr. Henry Bauer, Goodbye Aids From Aids trap surviver Maria Papagiannidou, go and visit the following websites, rethinkingaids.com, aliveandwell.org. I am sure that you will get a conclsuion after reading this material, stick with that, forget about your test result, there are many conditions well documented that can produce those results, the manufacturers from these kits, recognize that there is no standard to determine based in a serological result the presence or abscence of HIV, and please, do not take ARV therapy, a lot of people die from complications associated with it, specially liver failure. Change your beliefs and fears and make a transition in knowing facts from responsible and well condiucted science, mind is very important on this issue, take care and God bless you, you are fine!

2 hours ago · Report

Lishui K Springford

check out www.newmedicine.ca

about an hour ago · Report

Now, I seriously hope that the letter is from someone trolling instead of someone looking for help during the worst time of their life. Sadly, to think that this is not happening (if not here then elsewhere) would be like denying HIV exists. My work on HIV in lab may never result in a cure, or even amount to a drug that can extend lives. However, all those papers and seminars I attended were not a waste. Knowledge is the currency of science and I have a lot in the bank to fight these dangerous people who call themselves HIV dissidents. I can’t change the minds of hard-core dissidents, but maybe I can prevent needless suffering for people like JW by taking on their campaign of misinformation with real facts. Although, seeing things like this makes my blood boil I will try not to let my emotions get the best of me. That is what these people thrive off of, they want to make scientists throw their hands up in frustration. That is what they get when they argue with a famous and often busy PI. What they forget is that I am a grad student, I have an iron will, and I am not afraid to bash my head against a wall for years to get a result if need be. The internet has given people unparalleled access to information and dissident groups of all types have taken full advantage of it, its time to remind them that the internet works both ways.

Wednesday, March 3, 2010

TrimCyp-Crazy Convergence

A few weeks ago I started a series on host restriction factors. So…the Trim5alpha one may have been just a little too technical, sorry about that, I get carried away some times. I am going to try to increase the awesome evolutionary insight to boring biochemistry ratio in this post.

So last time I mentioned that Trim5alpha was made up of two major units, the recognition domain (SPRY) and the effector domain (TRIM). TrimCyp is a protein where the recognition domain has been replaced with a cyclophilin domain. It is an entire cyclophilin A molecule stuck to the TRIM part. Once HIV-1 gets into a cell it binds to cyclophilin A proteins. The cool part is that HIV actually needs cyclophilins to achieve maximum infectivity. So here we have a case where evolution has taken one of the things a virus like HIV-1 needs and fused it to the thing that helps chew HIV up…genius right! You can’t create a better thing. So how did it get there? A cyclophilin mRNA got picked up by some retrotransposition machinery and inserted it right in the Trim5a locus on the chromosome, poly A tail and all. A few splice site mutations sealed the deal for making a potent new restriction factor. Events like this are quite rare and the fact that it was maintained and selected for is pretty cool.

The really wild part of the story is the fact that it has happened twice independently.....on two different sides of the world....in two totally different species. Talk about convergent evolution. It happened once in South America in owl monkeys and it probably did a good job because all 12 species of owl monkey only have this variant. Who knows maybe it saved the species. The second example is in macaques where it is distributed at different frequencies in at least 3 species ranging from about 10-100% . Again one would like to think this protein must have kicked some ancient viral ass. We know they were independent based on where they inserted into the genomic DNA, the macaque insertion is after the SPRY domain while the Owl monkey one comes before it.

If it is one thing evolution likes to do it is improve upon a good idea. It turns out mutating amino acids near the part that binds to HIV-1 changes its specificity for viruses. In the macaque protein these changes cause the loss of recognition for HIV-1 but the gain of recognition for HIV-2. That is a neat trick. Recent work actually shows that this switch is controlled by a singe amino acid change. One could imagine scenarios where at a population level the protein could flip flop specificities fairly quickly in response to new significant threats. There is a similar pattern of changes in the owl monkey version but no one has attributed any functional differences to it.

Personally I think the coolest part of the whole story is where the in the mutations in macaque and owl monkey proteins fall. The mutations that likely change binding specificity occurred just opposite each other! That was a WOW moment for me. These two species probably were faced with similar threats, solved the problem independently in a similar yet distinctly unique way!


I took this image of human cyclophilin A (same sequence as the macaque one) (PDB C3YS) colored it in PyMOL. Light blue is The cyclophilin A protein. The yellow ring is a drug cyclosporine that is bound to the active site, this is where it also binds to HIV. I colored the changes from human sequence to owl monkey in red. The orange ones are the macaque changes. Think of cyclophilin holding that ring like a whole hand gripping a ball. If you were to hold a ball in your hand and look down at it, the mutations in the owl monkey protein would be in the thumb and the macaque ones on the pinky. If you were to mutate “move” either finger you would change the grip on the ball. How cool is that?? I love evolution.

Atrazine: more controversy and sexually confused frogs

Ooh! It’s not every day I get to see an aquatox issue covered in the news. CNN is carrying the headline “Weed killer 'castrates' male frogs, study says” and before even clicking the link, I knew it was going to be about atrazine. Hmm, this isn’t exactly news to us. Atrazine and endocrine disruption/teratogenic effects have been studied in frogs and fish for over a decade now. Amphibians seem to especially sensitive. So what’s this all about now?

Skimming through the CNN article there is this nice gem,

“Syngenta, a Swiss company that is the largest manufacturer of atrazine, has challenged the validity of Hayes' study.

"We haven't seen these kinds of responses that Dr. Hayes reports," said Keith Solomon, an environmental toxicologist at the University of Guelph in Ontario, Canada, who has served as a consultant to Syngenta. "Some of these studies are poorly conducted and are entirely inconsistent."”

Uh oh, looks like another spat between Hayes and Solomon, who have a pretty good history of butting heads. Solomon says the Hayes’ science is poorly designed, and Hayes says Solomon only finds negative results when his studies are funded by Syngenta. Anyways, ignore the drama for now, let’s see what this study says to warrant its publication in PNAS.

Actually, I guess a little background is in order first. Atrazine, the most commonly used herbicide in the US, with over 80 million pounds applied on the ground yearly. Yikes! It is also the most commonly detected pesticide as a groundwater contaminant. The EU has gone as far to ban its use and while, as mentioned above, the effects are slightly controversial, the new administration’s EPA has ordered a review of atrazine’s environmental impact.

Hayes’ new study started out with a 100% male group of African clawed frogs (Xenopus laevis) and exposed them to 2.5 parts per billion (pbb) atrazine from development through as far as 3 years. So while most previous amphibian tox studies looked at developmental disruption, this new study examines how chronic atrazine exposure can lead to detrimental adult reproductive function.

90% of the males were morphologically male when examined. Wait, only 90% of males were males? The other 10% had become morphologically female. They exhibited a pronounced cloacal labia, and upon dissection, they possessed ovaries and a lack of male features. Figure 1 shows the difference in cloaca in unexposed males compared to a “female.”

Furthermore, those females who were not dissected were allowed to live and ended up reproducing with males (Figure 2), even producing viable eggs which were reared to adulthood! And yet, based on chromosome analyses, these “females” were still genetically male. Ack! It’s quite extraordinary that the degree of hermaphroditism observed led to complete feminization.

Of the 90% of that remained males, what of them? Well, two-thirds of them had become essentially, chemically castrated. This was due to for example, lower testosterone production and underdeveloped testes. And compared to unexposed males, atrazine exposed males had a lower libido and were outcompeted by unexposed males in breeding. The comparison in Figure 3 showing a control frog’s gonads compared to an exposed frog’s gonads.

The results from this study do seem pretty jarring, especially considering the low concentration they were exposed to, which in some areas is environmentally relevant, meaning they are equivalent to a chronic exposure organisms are already experiencing in the wild. It would be interesting to see what the critics have to say regarding this study and whether these results really are replicable. Another nail in the coffin for atrazine? Could be. I eagerly await the EPA’s finding regarding their ongoing critical review of atrazine’s environmental impact.

----

Hayes, T. B., V. Khoury, A. Narayan, M. Nazir, A. Park, T. Brown, L. Adame, E. Chan, D. Buchholz, T. Stueve, and S. Gallipeau. Atrazine induces complete feminization and chemical castration in male African clawed frogs (Xenopus laevis). Proceedings of the National Academy of Sciences. PNAS published online before print March 1, 2010, doi:10.1073/pnas.0909519107