I’m only here because it didn’t work. I’m happy to be here, but it’s uncomfortable to follow this joy back to its logical source. It’s all kinds of inappropriate to derive pleasure from the stumbling blocks of anybody’s project, even more so when that project is an HIV vaccine.
Spelunking With a Laser Pointer
Any vaccine we desighas to account for the incredible amount of variety in viral genetics as well as the multiplicity of human genetics. The latter has been long overlooked, but its implications are grave. Just as humans have genetically determined blood types that determine what kind of blood you can receive if you need a transfusion, humans have different serotypes or HLA types (Human Leukocyte Antigen, if you care), that are roughly the same phenomenon applied to your immune system. Whether a donated organ is accepted or rejected is dependent on a match in this serotype. In the context of infection or immunization, different serotypes respond to different antigens, so one person may respond to a particular part of a bacteria or virus, while someone else may respond to a completely different part. When designing what parts to include in a vaccine, we need to take into account not only that the vaccine needs to enable people to shoot at a moving target, but also that many people are shooting from different distances and vantage points. Therefore, we need to test our individual vaccine components many times, each time against people with different serotypes. We tested the B7 serotype in Providence, and we’re testing A2 in Bamako.
The person that has been running the experiment here in Bamako is Kotou Sangare, a Master's student at the University of Bamako. Kotou is, in every respect, a character. He looks like Marlo Stanfield and acts his opposite. Kotou is a man whose smile starts somewhere behind his eyes and radiates out across his face and out into the world. He walks around like he has “Sir Duke” playing in his head on a loop. He will often abstain from eating or drinking for twelve hours at a time to be closer to Allah, but he never mentions his faith unless pressed and has vehemently nixed the idea of ever sending his children to a Madrassa. He knows his way around the lab, he’s quick, thorough, patient and precise.
The impression that we were under as we prepared for this trip was that Kotou, for all his personable qualities, was the problem. He doesn’t know how to ELISpot tests, claimed the project manager. That would indeed be a problem, given that those tests comprise about 95% of our project. He can't manage his lab, it seemed. They had sent chemical reagents to Bamako, which had disappeared. He claimed to have followed protocol, but the cells died and the data were lost. It took him four months to even get started. That’s why the project stalled.
Lauren and I were sent to Bamako to confirm those suspicions and to pick up the slack. We have been sent here by the various business and academic tendrils controlled by Anne De Groot, a brilliant immunologist and intensely driven doctor, the brains behind this potential vaccine. Lauren works for Epivax, the biotech company Annie runs, and I work for the department she chairs at URI. The project is under the purview of GAIA vaccine foundation, and NGO of which she is the founder and scientific director. GAIA works at a clinic in Bamako providing HIV care and treatment, TB treatment and maternity ward support while building out the required infrastructure that will be necessary to do clinical trials of that the completed vaccine.
However, GAIA is short-staffed, and much of the project management has been shoved over to people at EpiVax, who do all sorts of other work and may or may not necessarily care about the vaccine project, which is unfunded and time-consuming. They are busy people who have had extra work thrust on them by their boss, so they are unlikely to go digging for any unlikely answers where Occam’s razor will do. Moreover, they don’t speak French, and Kotou’s English is mediocre, so communicating about obstacles would be a problem if they were even inclined to do so. Technical minds gravitate towards technical solution, and the conclusion reached in Providence was that what held these experiments back was in the lab, a single, smiling weak link.
The Best Laid Plans of Lab Mice Usually Involve Survival
Vaccine research requires expensive equipment, a steady supply of disposable tools and chemicals, refined technique, and an infrastructure that guarantees things like a steady supply of electricity and clean water. Mali is the fourth least developed country in the world. The conflicts here are obvious. Luckily, the lab we work in is the beneficiary of a multimillion dollar grant from the US government, which facilitated its pimpification, whereby the lab was taken away from the hard-working, noble researchers, worked on by a former rapper and his team of sassy and zany technicians, who installed multiple incubators, sterile hoods, centrifuges, and put plasma screen TVs in the gene sequencer.
It is a far cry better than the lab at the Bamako Med School - a typical lab in Bamako left to fend for itself - which has no reliable source of water, little gas and no chemicals from this century. Even with our advantages, it is difficult to run two-day experiments when you never know that there will be electricity available for the duration of the period. Not to mention the vulgarity of the amount of waste that goes on in a lab, compared to the pinching resourcefulness of poverty. Tubes that cost the equivalent of a family’s weekly income are used once and tossed. According to the doctrine of sterile technique, which dictates cleanliness in much the same way that Leviticus does - everything that could have possibly touched anything that was ever in the vicinity of any chemical at all is unclean and has to be thrown away. It’s not unreasonable, we are working with HIV-positive blood after all, but the island of sterility in our lab seems about as far from Bamako as you could possibly be.
We came here full of piss and vinegar and with two suitcases brimming with over a hundred pounds of equipment and reagents, to fix the problems in the lab. We spent a week ironing out supplies and fending off the demands of clinic politics, and still no results. We learned that Kotou knows exactly how to do ELISpots, but he was given inactivated chemicals and instructed to follow a dead-end protocol. It turns out that our hypothesized quick fixes failed to account for one thing. The limiting reactant here is HIV-positive blood from Sikoro, and we're not getting it. None of the HIV-positive patients come into the clinic to donate blood. The problem is not at the lab, but at the clinic.
“Are we calling them?”
“Yes, we’re calling them. They schedule an appointment but don’t come.”
“Are we telling them why this study is important?”
“Of course. ”
“Are we telling them they will be compensated”
“Yes. 2000 CFA ($4.50)”
“Maybe the doctor is keeping the money?” A week of investigation reveals that he is not.
“Why don’t they come?
“They just can’t.”
“How do we fix it?”
“Education campaigns in schools and the village for a few months or years.”
HIV, Syphilis and Nuremburg
Our study critically depends on HIV-1 positive blood from otherwise healthy, non-pregnant patients who have been infected for more than a month but are not under treatment. We are expected to get this blood from the 100-200 HIV-positive patients in our catchment area, most of whom we diagnosed as HIV-positive when we tested them because during pregnancy. Our work serves to find patients that are almost universally ineligible for the study. When we find someone that by chance, or when we wait out a pregnancy and early childcare and ask the patient to come in to give blood, we have to compete with all of the other stresses and strains of a new HIV-positive mother. Taking care of the household, manning the stall in the market, cooking meals, and the other tribulations of life in Sikoro.
This brings us to the problem of medical ethics. This is an all-important part of research, borne of the need to prevent the atrocities of human subject research in Nazi concentration camps and the famous Tuskegee trials where men with syphilis were denied treatment and forced to die heinously as bacteria made their way into the brain and subjected it to a game of Worms Armageddon. Reports recently came to light of an even worse trial perpetrated by American researchers in Guatemala in the 1940s, whereby subjects were actively infected with syphilis. From a sociopathic data-seeking point of view, the researcher benefits from sick subjects. Obviously, to act on this is disgusting and inhuman and not only violates public trust in science, but violates the purpose that science serves. Ethical review boards are charged with litigating against the temptation to cut corners and exploit the grey areas that pop up in the complexity of real life.
Modern research ethics abides by three main principles. First, the fate of each and every individual subject is unequivocally more important than all of the research. If the study concerns acquisition of disease, everything attempt must be made to prevent subjects from getting sick. In the case of an HIV incidence study, this means providing counseling on risk reduction, free condoms, and free testing to all subjects, which requires a larger number of subjects, increases the cost, necessarily reduces the broad applicability of the data, because it cannot represent those who were not study subjects and did not receive counseling, condoms, testing, etc. Second, there can be no undue coercion of any kind. You may not force subjects to participate or restrict their rights to end their participation at any time. Undue coercion includes things that might be seen as beneficial, such as providing preferential treatment or excessive payment that may cause the patients to participate for the sake of the money or status. Study remuneration is fair compensation for time and expenses, not payment for a service. Third, complete confidentiality must be maintained.
In our case, the first is not limiting, as there is no conflict between our research and the health of the patients. The third only complicates matters insofar as only Doctor Koné can contact the patients. We can’t, for instance, have our Peer Educators go visit a patient before the appointment to remind them of their appointment or escort them to the clinic. It is the complexities of the second criterion, the absence of any coercion, that hinders the study, insofar as it makes it economically near-impossible for poor Malians to participate. We can subsidize transport, but we can do nothing to cushion the opportunity cost of a day’s work as well as the extra expense of food, neither of which are trivial. In our ethical vigilance, we make sure that the donor gets a raw deal in order to make sure they are not giving blood for any but the most honourable reasons.
Blood is sacred in Malian society. I have already mentioned this, but it bears repeating. Blood is your very essence, and giving it up is a profound act. Blood drives are difficult, people give blood if and only if a neighbor or relative needs it, in which case the mother mobilizes the entire family to give blood at once. Giving blood because you have HIV and it would be useful to some Toubabus up on a hill is a different story, and entails opening yourself up to the full brunt of stigma.
So we have both willingly and unwillingly stacked the deck against our own success. The people that manage our project didn’t know this when they sent us out here, assuming that what could be done in Providence could just as easily be done in Bamako.
Stuck In A Rut
This is in some ways a typical story of NGO work in the developing world, especially technical work. Technocrats design the operation, and when it doesn’t go to plan, assume it is because of a paucity of technical knowledge on the other side. They don’t have the insight, experience, interest or time to ask the right questions, so they provide their own answers. The wholesale difference of life and business between Providence and Bamako. Science in general, and vaccine development especially, is implicitly built a modernistic conceit that assumes away any inconvenient human strata. If we develop the right vaccine, it was thought, we will defeat the disease. Period. Reality tells a different tale – Measles kills 300 000 children annually and is the leading cause of blindness, but we’ve had a vaccine for that for years. Whooping cough kills kids all the time. Polio still cripples people in India, Afghanistan, Pakistan and Nigeria (Aside to India: You can have a space program or you can have polio. Not both). Measles in Niger does vastly more damage than HIV in America. These plagues are diseases for which we have had vaccines for half a century, but science as a whole considers the human application and implementation of its fruit to be an afterthought. Not coincidentally, science has a hard time believing that the human element may entail some cultural, social, and other non-technical problems that are not immediately surmountable. What we do in the lab is inseparable from what we do in the clinic, and what we do in the clinic is firmly embedded in how life works and doesn’t work in Sikoro.
We arrived in Bamako worried about what we would do when we ran out of reagents – what would we do about the 13th patient, for whom our calculations left only half a test-kit? In just over half the allotted time, we have received donations from three patients, and I was at the clinic to witness the most recent one. She looked, as most HIV patients do for most of their lives, strong and healthy, there was nothing about her that betrayed her status. Normally we need 5 test tubes (50 mL) of blood. After two tubes, filled drip by tedious drip, and she started to swoon, then moan, and began to fade. The sight of her own blood leaving her body was too much. As soon as it was clear she was fainting, it was a mad rush to remove the needle, clear the bed, get her off the chair and onto the bed, and to free her from the tubing that bound her arm. The latter was my job, and is I reached up her arm, avoiding like the plague the inside of her elbow where the needle had been, wrestled with the surgical tubing that restrained her circulation, pulled it free and let her lie down as she let delirious groans escape her throat. And as I stood up, I saw Awa, just to my left, holding the last tube of blood at her hip, with the ruddy glint of the syringe tip still pointing up and vaguely in my direction. It must have been a foot away from me, and I know that even if I get stuck, proper treatment gives me a 99% chance of safety. But still I could have sworn that the needle was, or seemed like, millimeters away from my skin. It might as well have grazed the hairs on my forearm, I thought. And it was very nearly my turn to swoon and faint, as I contemplated the glinting possibility of a new biological condition, one that I would share with this woman and the others upon whose broad backs our study is built. It is a very odd feeling indeed to look at someone like that and think "your life is my worst-case scenario, and I have never come closer to it than just there", and then to realize that we need her to make sacrifices for us.
We whisked the blood off to the lab and performed a successful ELISpot test, with Kotou’s capable help. We are closer to completing our study, and therefore closer to an HIV vaccine, than we were that morning. Despite the problems and our inability to grasp them, we are pushing forward, largely on the strength and spirit of the weakest and sickest here.
As we left the clinic, we walked past the woman one more time. The last time I will ever see her, though she will continue to exist in my life as a data point. I looked at her and she returned a look, gaunt and deflated, incongruous with the proud black and gold Malian batik that wrapped her from head to calf. My muscles congealed and my throat thickened, as my relief at having a test subject was suddenly saturated with a feeling something like shame and a lot like inadequacy, knowing that while my Bambara is abysmal, that has nothing to do with why I can’t begin to know how to thank her.
