September 2008 Archives

I have been on 8 airplanes in the past week. When I travel, I pass the time with a combination of crossword puzzles, books, my iPod and the latest issue of Scientific American (yeah, yeah I know I am a dork).

One of the first things I look for in any issue of SciAm is Michael Shermer’s ‘Skeptic’ column. I genuinely appreciate his critical eye and steadfast rationalism. His most recent column has been giving me fits.

He wasn’t really writing about statistics, but something he calls the ‘middle land’ that we live in- where our brains are quite adept at perceiving phenomena of a middle scale- for example we are wired to understand time on the scale of seconds to decades, but nanoseconds or geologic time intuitively baffle us.

He opened the column with a retelling of what is known as the ‘Monty Hall Problem’:

Imagine you are on Let’s Make a Deal, there are three doors, behind one door is a new car, behind the other two are goats. You pick one. Knowing what is behind each door, Monty opens one of the doors with a goat behind it. He then offers you the opportunity to change your pick. Do you? Does switching from your original choice change your chance of winning that coveted new set of wheels?

Like most people my answer is that it doesn’t matter. There are 2 doors, so I have a 50/50 shot at being right- right?

Uh, no.

Turns out, like most people I am wrong- you should switch doors, because it doubles your chance of being right.

Huh?

Let me see if I can explain this to myself: There are 3 doors- A, B and C. I pick door A. I have a 1 in 3 chance of being right. Hall, knowing what is behind each door opens one with a goat behind it.

Now you have only two doors. Most of us- including me- now recalculate our probability as being equal, but it isn’t. Each door had a 1/3 chance of having the car behind it- meaning I had a 1/3 chance of being right and 2/3 chance of being wrong. He knows where the car is, forcing him to pick a door with a goat. Your original 1 in 3 odds haven’t changed, he has just reveled that one of the other doors has a goat behind it. There was a 2 in 3 chance that the car was behind one of the doors I didn’t choose. That is still true, meaning that I double my odds of winning the car if I switch.

Wikipedia offers some help in explaining this. Instead of just three doors, imagine 1 million doors. You guess one door. He goes down the line opening every other door but yours and one other- and offers you a chance to switch. You have seen 999,998 wrong doors, and have two possible right doors. Did your original odds of being right (1 out a million) change? No- so you switch.

There- do you understand? I don’t for what it is worth, but I accept that it is true. I have to do that a lot in my work. I have never been really good with math, yet my work requires looking at statistics. Concepts like confidence intervals and power equations are beyond my ability to truly understand- but I look at them and use them in my work all the time. Is that a weakness for me as an treatment activist- probably.

And that is why I hate statistics.

I jealously guard my evening free time. So, however much I am an AIDS activist, I was not happy to find myself in the back of a nearly empty room at the SF LGBT Center, harrumphing and scoffing my way through an evening presentation by one of Dr. Matthias Rath’s soft-denialist henchmen. But I pulled my cranky pants on, and soldiered over to the Center to fight the good fight.

Why would a sane and perpetually busy AIDS activist like myself spend his evening with a dozen or so folks listening to a kindly-seeming gentlemen extol the virtues of vitamins and other micro-nutrients? Because denialism equals death.

Dr. Matthias Rath is what I call a soft denialist. Unlike their harder kin like Duesberg and Maggiori, Rath doesn’t outright deny either the existence of HIV nor its role in HIV disease and AIDS. Rather, he and his ilk take a more insidious, and probably no less harmful tack of championing the potential of ‘natural molecules’ over ‘toxic anti-retrovirals’ to treat HIV.

You would think I would be fairly sympathetic to this sort of thinking- I am a vegetarian after all, and as I wrote about here , my dearest friend is an acupuncturist. Indeed my friends are more prone to boil pots of noxious eastern herbs, or swallow droppers full of tincture of whatnot than to crack open a pharmaceutical pill bottle.

And in fact, I do not discount the healing power of plants. The other night, my roommate David and I were recounting the moment when he fully grasped the medicinal value of marijuana. It was back in 1996 or 7, and we were on a camping trip with my daughter and her Mother. We were on our way home, and stopped near a stream to have lunch. I was hurting. These were my Crixivan days, full of nausea, vomiting, and general feeling ickyness.

I snuck away from my young daughter down the stream a bit, and took a couple of puffs from a pipe. A few minutes later, my color was normal, and I was able to eat. My daughter’s Mom, Kim had reason to be quite skeptical of marijuana, having seen it suck much of the life out of her sister. But she, and David were simply struck my the stark difference the plant made.

Plants were the first pharmaceuticals, and many drugs in wide use today have their origin in the earth’s flora. And as someone who struggled to hold down food for years on end, I viscerally understand the effects of malnutrition.

But I didn’t go to see Rath’s acolyte to learn- I went to challenge and even to disrupt. Rath is a sworn enemy of South Africa’s Treatment Action Campaign, the worlds most important AIDS activist organization. He and his henchmen tell people that anti-retrovirals are toxic, and unnecessary- that to be well all you have to do is, you guessed it, take their magic formula of vitamins and other micro-nutrients.

Rath himself wasn’t there, but one of his ‘researchers’ was. He was a bit of a stumblebum, possessing neither charisma nor scientific acumen.

He presented a hodgepodge of data purporting to illustrate the power of micronutrients. Most of the data were reasonable, but few of the conclusion he drew were. For example he cited a interesting little study about selenium supplementation. The study showed that giving people with low blood selenium labels daily supplements led to a stabilization of HIV levels and a modest increase in CD4 count. His slide said that daily selenium supplementation was proven to lower viral load and increase CD4 count.

I repeatedly challenged him throughout the night. At one point, a woman sitting close to the front of the room turned to me and told me to shut up. “He is doing great work” she said, and raised he hands over head and applauded- a few in the audience joined in. I asked her why she thought he was doing good work. She said that it was because we are all brothers and that eating poorly and improper nutrition is the cause of all disease. I asked her point blank- do you mean that if people with HIV- like myself- were to stop taking our meds and just eat right (and I presume take Rath’s special vitamins) we would be better off. She said yes.

There are many other examples of similar numbskullery I could recount, but there is no need. There are two simple points for me. First, as I wrote about recently there is no such thing as alternative or holistic or western or eastern or natural or allopathic medicine- there is simple proven and non proven medicine. If scientifically sound, reproducible studies showed convincingly that rubbing mugwort on my pinky toe under a new moon reduced HIV levels by 1.9 logs, I would do it. Likewise, if there weren’t compelling evidence that convinced me that swallowing thousands of dollars worth of pills each year was keeping me alive, I wouldn’t do it.

My second point is that science can not be entrusted to true believers. People who have a vested interest, whether it be financial or intellectual, in the outcome of research can not be the final word on the subject. Speaking broadly there are two types of research- discovery and confirmatory. True believers can and often do perform solid discovery research- the type that illuminated a previously unknown piece of information. What happens then is that others need to come in and test the findings- people who do not have the same kind of interest in the outcome.

When the oil industry shows us research that exonerates them from any role in global warming, we are naturally skeptical. When a pharmaceutical company shows us research supporting one of their products, we are properly skeptical. The same skepticism should be aimed at the world of vitamins, herbs, and the rest of it.

Hank Wilson, an old school AIDS activist sat next to me throughout the talk. At one point he reminded the audience that prior to HAART, many people with HIV in San Francisco tried every kind of natural approach to HIV. In fact we had a vibrant and bustling buyers club (the Healing Alternatives Foundation) and virtually a week didn’t go by without a talk on some sort of natural approach to combat HIV. He also reminded the audience that what changed the game was anti-retrovirals.

If I was writing the script, believe me the heroes wouldn’t come from big pharma. It would have been great if an herb, or a combination of vitamins had proven truly effective in reversing the course of HIV disease. Outside of the investment community, big pharma has few true admirers and I am not one of them.

The truth is however the truth. It was big pharma that got the job done, and for that I am grateful. The beautiful thing about science is it cares not who you are- proof is proof. That isn’t to say that the playing field is level- clearly big pharma has resources that the rest of the world doesn’t. But lest you think that there is a heroic battle going on between the forces of good (the vitamin folks) and evil (big pharma), remember- the vitamin and natural medicine industry is a huge, largely unregulated cash machine.

Back to my original point- denialism equals death. Rath and his cronies are wreaking havoc in South Africa. The have run illegal clinical trials and fought tooth and nail against TAC and others who would dare question their validity. Rath is a very rich man, who is contributing to the suffering and needless of death of many in the area of the world that can least afford it.

That is why I spent my precious free time being a gadfly.

On a related note: Mbeki’s days are numbered- according to the newspaper exactly 2. The harm cause by his dalliance with denial is profound. I only wish his downfall had come much quicker.

and one last note: lest anyone think that natural medicine is harmless see this story below:

(09-22) 11:42 PDT JOHANNESBURG, South Africa (AP) --

Many South Africans use herbal medicine and consult traditional healers in addition to Western style doctors.

People with HIV, even more so than the general population, are quite likely to use what is ‘complimentary’, ‘alternative’ or ‘holistic’ medicine. Project Inform’s Hotline LINK receives a fair number of calls about the safety and utility of such interventions, and I am asked my opinion rather frequently.

Project Inform takes a skeptical, but fairly hands off approach to what I will call alternative medicine. We make the following points 1) little reliable, reproducible evidence exists to back up most types of alternative medicine, 2) the ‘decision to use’ is most often based on anecdote and word of mouth recommendation 3) most interventions are viewed as safe (most often true) and non-corporate (less often true) and 4) tell you doctor everything you are doing.

Personally, I have a bit harsher take on this question. Full disclosure: Back in the 1990s, when I was sick I went to acupuncture regularly, and took heroic handfuls of various herbs and supplements in a kitchen-sink effort to support my flagging immune system. As I recently wrote about, one of my dearest friends is the clinical director at an HIV focused acupuncture clinic. Most of my friends are more likely to take an herbal tincture or homeopathic sugar pill than a course of antibiotics.

While I won’t be as provocative as Penn and Teller recently were and call the lot of it ‘Bullshit,’ I will say that I am quite skeptical about most of it.

I don’t think of medicine in terms of ‘western’ or ‘eastern’ or ‘allopathic’ or ‘holistic’ or ‘traditional’ or whatever. I only see two categories: proven and unproven. I don’t care a wit if a treatment comes from the bark of a tree or the inside of a beaker- what matters to me is proof.

Aren’t I a bit of a hypocrite? Didn’t I use Chinese herbs and moxabustion when I was dangerously sick, and now am trashing it? Well yes and, well yes.

When I was sick, I was willing to try almost anything. There were programs that helped pay for acupuncture and herbs, so I tried it. Some of it helped- especially the herbs. What really improved my health however wasn’t herbs, wasn’t massage, wasn’t yoga, wasn’t prayer, wasn’t tweaking my chi- it was stavudine, lamivudine and indinavir- nasty, harsh and altogether life saving chemicals.

I think there is something to be said for herbs. To this day many of the drugs we take have their origin in plants of various types. It isn’t hard for me to understand how a plant- a complex of biologically active compounds- could have physiologic effects.

But it is folly to assume that nature is more gentle or healing than chemistry. The analgesic properties of willow bark were long known, but its bitterness and propensity to shred people’s stomachs limited its utility. When chemists were able to isolate, synthesize and manufacture acetylsalicylic acid- aka aspirin- the world became a better place.

As for things like healing touch, acupuncture, chakra balancing and so on and so forth, I just don’t see it. Just because I don’t understand it, doesn’t mean it isn’t true of course- but the burden of proof is on the supporters, not the skeptics.

There are some supportive data on acupuncture for example, and more equivocal to negative data. It isn’t proper to cherry pick supportive data and ignore the rest. When pharmaceutical companies do that we yell and scream (rightly). When scientists do it, they ruin their careers. When politicians do it, we call them Karl Rove.

One of the most egregious examples of this in HIV tainted Project Inform and literally scarred me. Back in the pre-HAART days, I attended a talk on DNCB- a photochemical that its supporters claimed stimulated a part of the immune system. You bought these little brown vials of the chemical and rubbed them on your skin.

Project Inform supported research on DNCB. The initial data looked promising- people in the intervention group seemed to be doing better than the control group. Turns out the scientist doing the research took everyone who was getting sicker during the study (non-responders) and called them the control group. Project Inform discovered what was going on and immediately distanced itself from the whole thing. However, DNCB was still being sold for years after that.

The DNCB left its mark on me- literally and figuratively. I still have a faint scar on my arm where I used to rub the stuff on. It helps remind me that my job is to be skeptical- to look at all HIV medical claims, whether they come from Pfizer or Andrew Weil.

On that episode of Bullshit, they talked about this 9 year old girl (forget her name) who holds the record for being the youngest person ever to have a paper published in a peer reviewed medical journal. She did a simple, elegant experiment to test the concept of healing touch. Proponents of this misnamed practice believe that you can help heal someone by moving your hands above a person’s body and manipulating their energy fields. This brilliant pre-teen skeptic got together a group of healing touchers and had them put their hands through a cardboard shield to see if they could feel- without looking- whether her hand was there or not. Surely if they can sense and manipulate a person’s energy field, they should be able to tell if their body is there or not without looking. Pure chance would give them a 50/50 shot- they got it right around 40% of the time- less than pure chance.

Like I said- there is only proven and unproven.

Here is a comment from my last post:

I do believe that profit is the Pharma companies motive. Take for instance T-20 was developed by a small pharma company called Trimeris and it's discovery was taken over by one of the "big players" Roche.And I noticed TNX-355 (a co-receptor independent inhibitor) being studied by Tanox has been taken over by Genetech which has subcontracted the work out to a Taiwan company TaiMed. All this juggling is can not benefit HIV development.

And here is my response:

I don't think that anyone would dispute that the pharmaceutical industry is motivated primarily by profit. I think that the Tanox and Trimeris situations are not the same however. In the case of Trimeris- Roche came in late in the game, mostly to assist with manufacturing and marketing. That is a model that I think makes a fair bit of sense- Trimeris didn't have the resources to really bring the product to market and Roche certainly did.

Tanox was bought out by Genentech- a company that has publically stated a total lack of interest in the HIV market. They bought Tanox not for TNX-355. but for other mAbs they have or are developing. Due to their lack of interest in HIV, Genentech has farmed out work on TNX-355 to the Taiwanese company you mentioned, which I agree will slow down the already uncertain development of the drug.

To me this points out the importance of judging each of these situations on their own merits. As a rule, pharma consolidation is very bad news for HIV, but not always. Trimeris maintained their independence from Roche, and have been able to move ahead with their second generation fusion inhibitor without Roche. Tanox is not independent from Genentech leaving the future for their product murky at best.

One of the more common sentiments I hear from people living with HIV is that the pharmaceutical industry will never cure HIV because they make too much money treating the disease. In some versions people go as far as to say that industry will actively thwart any potential cures to ensure their uninterrupted profit streams.

What is my opinion of this line of thought?

In the spirit of full disclosure, I am a card-carrying anti-capitalist. In my word view, profit is a politically correct word for theft. I very much want to get the profit motive out of medicine, and everything else for that matter.

But in my work as an AIDS activist, my focus is not on overthrowing the world, but advancing the fight against HIV. I work closely with drug companies, meeting with them, sitting on advisory boards, reviewing research programs and even occasionally breaking bread with them.

The ultimate aim of my work is to help in some small way to get us to the cure. So I have given a good amount of thought to this question, and as much as it pains me to say it, I do not think that the pharmaceutical industry is conspiring to keep the cure from us.

To begin, as a whole not that much money is being made in HIV treatment. In the US, where the companies make the most money off of their drugs, HIV is a relatively small and quite crowded market. The long term nature of HIV treatment makes it a somewhat attractive market, but that is balanced our by the relatively small number of people taking HIV drugs, and the large number of products competing for those people.

If the companies were making money hand-over-fist off of HIV drugs, why would they be abandoning HIV research in droves? While I am no expert in the way that companies make investment decisions, if HIV were the plum market so many seem to think it is, I suspect companies would be aggressively moving in to the market, not away.

In fact, only Gilead Sciences makes the bulk of its money off of HIV. The other big players, GSK, Abbott, Roche, Tibotec (Johnson and Johnson), Merck, Pfizer- HIV is a small niche within a vast juggernaut.

Now that is not to say they aren’t making money. They are in the business of making money, and they do this by selling drugs. If they weren’t making money, they wouldn’t be doing it. It is a matter of scale and perspective.

The biggest problem with this line of thinking though is that it treats pharmaceutical companies like a caricature: a cabal of conniving fat cats, secretly conspiring in smoke filled rooms.

In reality they are like any other business people- cut throat competitors. While they will work together on mutually beneficial efforts through their lobbying arm PHARMA, I just don’t see the folks at J and J thwarting one of their own scientists to protect the GSK’s profits.

In fact, there is a powerful economic incentive to cure HIV disease. If a pharmaceutical company develops the cure, they aren’t going to give it away, they will sell it. They will make lots and lots of money off of it. Their competitors won’t. They will also reap a public relations bonanza more valuable than any single drug.

Pharmaceutical companies are made up of regular people- some good, some bad, most somewhere in-between. I don’t work much with the proverbial bean counters, so I fully acknowledge my perspective is incomplete. The folks that I work with are either sales people (often called community relations, but…) or scientists. They are a perfectly ordinary group of people- the sales people are not different than other types of sales people, nor are the scientists substantially dissimilar to their counterparts at NASA or in academia. To a person though they have a sense of the human cost of HIV, and are working if imperfectly on ameliorating its damage. And getting paid to.

When I think about the net effect market capitalism has had on HIV drug development (and trust me I do), I end up agnostic on the question. On one hand I note the tremendous volume of drug development- far outstripping pure market forces- and the overall product improvement, which I know to be in part the result of market forces. I also see how companies jealously guard their products and technologies, effectively slowing and at times thwarting scientific advances.

What I don’t see is conspiracy to keep us on HIV drugs for the rest of our lives. Even Gilead I suspect would be happy to sell us the cure, and go on to making money in other areas. As for the Merck’s and GSKs of the world, they already have their diabetes, high blood pressure and erectile dysfunction drugs to keep separating us from our money for the rest of our lives.

Two of my closest friends are grappling with very different problems- both HIV related.

I went to a concert on Sunday with J, a woman living with HIV and fellow metal head. We were getting ready to go see Judas Priest, Heaven and Hell (Sabbath with Dio), Motorhead and Testament. I asked her how life was treating her.

Her face told me immediately all was not well.

‘I have a lump on my breast,’ she shared.

She is in the midst of figuring out what is going on, but the signs aren’t good. She is set for some more tests- and is expecting a cancer diagnosis. Already struggling with lipodystrophy, she is now wondering if more body changes are on the way.

Last night I got a call from another friend N, who is acting co Executive Director of a small, HIV focused acupuncture and herbal clinic in SF. Without dishing dirt here- she is only acting as ED because of the mess left behind by others- and from what she said the mess is big. They are spending much more money than they are bringing in, their government funding has been slashed, and their line of credit is maxed out.

I love both of them and their struggles are very personal. They also seem somewhat emblematic of the epidemic these days. Non-HIV specific health concerns grow increasingly important. Data were presented in Mexico City showing an increased risk of non-HIV cancers for HIVers. HIV service agencies are struggling to raise money, and even keep their doors open as donor fatigue and flat-to-declining government funding results in a shrinking pie being divided in to smaller and smaller pieces.

I didn’t have much to offer either of them. I know next to nothing about fund raising or running an agency. I know something about breast cancer (my Mom is a survivor), but much less than Jen does. In both cases, all I can do is be there.

In the bigger picture though, the work of AIDS activism is these problems. We work for better funding of AIDS agencies, and better understanding of HIV and health. We struggle against disease and for wellness.

Their struggles are both personal and professional to me. They are first and foremost loved ones- people who I care deeply for who are facing their own struggles. They are also examples of the need to keep suiting up for the fight.