Mexican Huichols, Tzeltals and Tarahumaras, Peruvian Aymaras, and Costa Rican Chorotegas and Guaymís are all part of a pioneering study on the effects of certain drugs on over 6,000 indigenous people in Latin America. It is the largest cohort and number of ethnic groups ever studied for this purpose. Forty research groups with over 200 experts from various countries have taken part in the study, analyzing blood samples to determine almost conclusively that aspirin doesn’t have the same effect on a Caucasian Norwegian as it does on an indigenous Mexican. All the physical features such as skin and eye color that make us unique come from our DNA, which also influences how a person will react to a drug and how enzymes are metabolized. Pharmacogenetics is a rapidly developing scientific field in some parts of the world, but has so far focused on narrow, mostly white population sectors.
“Ethnic influence is one factor in drug response variability. There is virtually no knowledge of it in indigenous peoples,” said Adrián Llerena, a leading Spanish expert in clinical pharmacology. Llerena is the coordinator of the Ibero-American Network of Pharmacogenetics and Pharmacogenomics (RIBEF), the consortium conducting the MESTIFAR project focused on studying drug interactions in different ethnicities.
The initiative aims to promote the incorporation of ethnic factors in studies on drug safety and to refocus personalized medicine, says Llerena, “which only reaches the wealthiest white populations. Drug studies are conducted in privileged societies and exclude indigenous populations.” Llerena has spent over 30 years analyzing the high level of individual variability in drug reactions — effectiveness and toxicity — which led him to question the adequacy of using standardized doses worldwide.
“Recommended dosage is calculated based on certain patients, but we give them to everyone, often causing adverse reactions. It’s a public health problem,” said Llerena, president of the Spanish Society of Pharmacogenetics and Pharmacogenomics (SEFF). Since 2005, he has been leading an initiative to apply personalized precision medicine to Latin American populations. “We cannot allow medical advances to only benefit the wealthiest among us and widen social inequities and the biotechnology gap.”
The results of the study showed significant differences in the efficacy of drugs for different populations. “Some groups had great difficulty eliminating an administered drug from the body, while others did this with unusual speed. This shows the absurdity of our paradigm of administering the same dose to everyone on the entire planet,” said Llerena.
For over a decade, the research team studied the genetic polymorphisms involved in the principal ways of metabolizing and eliminating drugs such as antidepressants, antihypertensives and antidiabetics. Ancestral molecular markers were analyzed for population classification.
The study’s results underline the validity of the Mérida/T’Ho declaration, which proclaims the need for clinical research to consider the population component, the sociocultural environment and the education of the research team, as well as the relationship with vulnerable populations. The declaration of scientists convened in the Mexican city of Mérida affirmed that research from the exclusive perspective of Western medicine cannot be conducted in populations with a different sociocultural environment.
The Mérida/T’Ho declaration was translated into several indigenous languages of Latin America, such as Mayan, Miskito, Nahuatl and Quechua, and was presented at a recent meeting of the European Parliament. “It was the first time that a declaration in American languages was presented in this setting, which left some people perplexed and annoyed,” said Llerena, who had the idea to form the RIBEF network at an international conference in Geneva.
“We were discussing how to do research on populations with resources when I realized it made no sense for us, a group of privileged white Europeans, to make such decisions about people who have a very different reality,” said Lerena, who began collaborating with Latin American research groups.
That idea led to the first Latin American pharmacogenetics conference in Guadalajara (Mexico) in 2005. Llerena credits Mexican José María Cantú for inspiring his career and laying the groundwork for the current research study. Cantú was a pioneer and leader in human genetics and medical bioethics medicine throughout Latin America, and was named National Researcher Emeritus by Mexico’s National Council of Science and Technology in 2007, shortly before his death from stomach cancer.
To optimize the safe use of drugs in indigenous populations with limited resources, RIBEF scientists say the sociocultural context (beliefs, values, habits and social relations) must be considered. “This is especially relevant since the coexistence of Western and traditional medicine has become more common. New drugs have to converge with a people’s customs. Like it or not, scientists cannot ignore this,” said Llerena. “Knowledge has to be based on principles. Without an underlying code of ethics, science becomes meaningless industrial production… I promised him [Cantú] this before he died.”
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