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by 3dRevelation
Fri Feb 14, 2014 6:00 am
Forum: Full Reviews
Topic: Dallas Buyers Club (2013)
Replies: 10
Views: 2740

Dallas Buyers Club (2013)

*Some Spoilers will follow*

I normally don't write longer reviews (on criticker at least), but I feel that I should in this case. As a Biologist (and one who knows a few things about HIV, although I'm not an expert), the story of the film is kind of baffling. I expected the film to take some shots at the FDA, but going so far to almost portray the FDA as murderers was kind of dramatic. I'm not going to sit here and vouch for the FDA though, because I'm sure they could have done things better in response to the AIDS crisis. My main focus here will be the drug, AZT, that Ron Woodroof and others took (or didn't take) as part of a clinical trial. I took offense to the way that AZT seemed to be treated as a cyanide pill. Here are some facts:

-AZT was the first medicinal breakthrough in the treatment of HIV. AZT (short for Azidothymidine) is a nucleoside analog. HIV (Human Immunodeficiency Virus) is a retrovirus. Simply, this means that the viral genome in HIV is RNA-based (instead of DNA). HIV also uses an enzyme called reverse transcriptase to convert this RNA genome into DNA. For those who may not remember some basic biology, RNA and DNA are made up of 4 bases: A,T,G,C in DNA, and A,U,G,C in RNA. In the process of reverse transcription, the RNA is used as a template and DNA bases are added based on the template. Normally, whenever an A is found in the RNA template, a T is added to the growing DNA strand. AZT is an analog of T, so in patients treated with it AZT is used by the reverse transcriptase. AZT inhibits the reverse transcriptase and thus prevents the RNA conversion into Double Stranded DNA and its subsequent integration into the host DNA. Because viruses require a host and use the host machinery to replicate, this slows the replication of the viruses, but does not completely stop it. For those that are visual learners, here's a pretty good picture:
Image

-Obviously from the above information you can probably understand why AZT was effective. Unfortunately, the success of the drug is short-lived. As AZT does not completely stop all virus replication and the fact that genetic variation exists, some viruses could withstand the AZT treatment better than others. That is where evolution kicks in. The viruses that can survive live on to replicate and over time the viral population within a patient becomes mostly resistant to AZT treatment. At this point, AZT dose is increased or the treatment is stopped (as obviously there is a threshold for dosage). Ultimately, because of these facts, AZT treatment which had at the beginning seemed a promising cure to HIV became a treatment that lengthened the life of HIV patients instead of saved it.

-Today the treatment (not cure) for HIV is HAART (Higly Active Anti-Retroviral Therapy). HAART is a cocktail of drugs that include drugs that are nucleoside analogs (AZT included), and drugs that target other parts of the HIV virus. The aforementioned reverse transcriptase is not infallible so during the process mistakes are made. We call these mutations. These mutations result in genetic variation that can result in viruses that react differently in different environments (as is the case with the AZT resistance). The idea behind HAART and using a cocktail of drugs is that adding more drugs that disrupt HIV decreases the probability that mutations will occur that will allow the HIV virus to survive in this HAART environment. For example, I will use some fake numbers to illustrate this point. If the chance of mutation in AZT treated patients is 1/1000 and you add a 2nd anti-retroviral, then the chance of mutation that garners survival becomes 1/1,000,000. Adding a 3rd drug would decrease the chance even more, and so on. This does not completely eradicate the virus, which is why I use the term treatment instead of cure, but it allows HIV patients to live fairly normal lives with hardly no decrease in life expectancy compared to non-HIV patients.

-AZT did have side effects. I'm not denying that. They just weren't as severe as the film made them out to be. I would think we would all agree that taking AZT and enduring the side effects would be better than dying a faster death from AIDS.

Now I will discuss some of the things that the film shows about Ron Woodroof and his struggle with HIV (this is where most of the spoilers will come in):

- Ron was a drinker and drug user. I mean there is even a scene where we see McConaughey wash down his AZT pills (which he has illegaly and has no idea how much to take) with some booze and follow that with a line of coke. Later after he stops taking the "poison" (AZT), he gets different medication from an unlicensed doctor in Mexico, and he starts to feel better. At the same time we also see Ron seemingly discontinue his alcohol and drug use. He also eats better which is exemplified by his scolding of Jared Leto for trying to buy processed foods when they go shopping. So I ask: why does Ron feel better? Is it because of the new medication? Or is it because he starts to take better care of himself? This is afterall the reason why clinical trials include a placebo: to show that the drug is causing the better health, not an different environment or the placebo effect.

- How about the drugs that the unlicensed, exiled doctor gives Ron? I believe they were vitamins, ddC and peptide T. Can anyone guess what ddC is? Yes, it's short for dideoxycytidine and it is a nucleoside analog. It works through the same damn mechanism as AZT. In fact, ddC would later be approved by the FDA. There is a couple things though: ddC is less effective than AZT and also has worse side effects. ddC itself hasn't been used since 2006, wheras, AZT is still used as part of HAART. As for peptide T? I don't know much about it, but I haven't been able to find anything that conclusively states that it was super effective in treating HIV.

-You might ask then, if those drugs didn't really do much for Ron Woodroof, then why did he live 7 years after his diagnosis? It's a perfectly reasonable question. It is possible that Ron Woodroof may have had a genetic variation that slowed down the progression of AIDS. CD44 is a receptor on T Cells (which are the cells HIV infects and destroys ultimately leading to AIDS) that HIV exploits to gain entry to the T cells. There is a portion of the human population that contains a mutation on the gene that encodes this receptor. A person who has inherited this mutation from both their mother and father CANNOT be infected with HIV. They are resistant to infection. A person that has inherited one copy of this gene from either their mother or father is not resistant, but they will better survive their fight with HIV than people that have the wild-type gene. This adaptation is most concentrated in the populations of Northen Europe. The theory is that this adaptation evolved as a defense mechanism to smallpox, but also slows or stops HIV entry into cells. Ron Woodroof, as a white male, could have very well had one copy of this mutation. This would explain why he lived for 7 years.

The film obviously doesn't give you the whole picture. It wants you to see Ron Woodroof as some hero that fought the FDA and the "poison" it was peddling, and who went and found alternative medicine (even if that medicine was inferior to what the FDA had approved). It's a shame too, because it's an interesting story. McConaughey and Leto both give good performances. I just wish the writers had been a little more truthful with their treatment of the FDA and AZT. Most people probably didn't notice, and hopefully I haven't written this all for naught.

TL;DR: This has been science with 3dRevelation.