Milan Severino and Andrea Zhang
Picture from the Duke Center for Applied Genomics and Precision Medicine
Overview
According to the National Human Genome Research Institute, pharmacogenomics (sometimes abbreviated as PGx) uses information about a person’s genetic makeup to determine which drugs will be most effective for their treatment (2016). It looks at each individual’s DNA, also known as their genotype, to predict the treatment outcomes of different drugs. This method combines pharmacology with genomics. Instead of using a “one-size-fits-all” approach to drug prescription, pharmacogenomics supports the idea of personalized medicine. It focuses on the genetic components that influence drug effects. These effects are examined through changes in pharmacokinetics, which refer to the movement drugs in the body, and or changes in pharmacodynamics, which refer to the effects of drugs (Evans and Relling 2015, 343).
Background
Pharmacogenomics is often used interchangeably with pharmacogenetics, and they have a similar meaning. The difference is that pharmacogenetics refers to how variation in a single gene influences the response to a single drug whereas pharmacogenomics is a broader term than encompasses the study of the genome (all genes) and its influences on drugs. Scientists and researchers may use either of them in their discussion of genetic factors in drug response. The field of pharmacogenomics traces back to 510 B.C when Greek philosopher and mathematician Pythagoras noticed that some, but not all, individuals had harmful reactions when they ate fava beans (Pirmohamed 2001). However, back then, people did not know about the concepts of genes or genetic heritability. The field of relating genes to drug responses began in the 1950s with the development of genetic research. In 1959, German scientist Friedrich Vogel coined the word ‘pharmacogenetics’ in his paper, which translates to the “Modern Problem of Human Genetics” (Motulsky and Qi 2006). The term pharmacogenomics began appearing more often in scientific journals around the 1990s (Pirmohamed 2001).
Although the aims of pharmacogenomics are lofty, the field itself is still in its infancy. A number of developments in the twentieth century paved the way for pharmacogenomics, the most notable of which was the Human Genome Project. The Human Genome Project developed the technology necessary to sequence a human genome, and thus enabled the genomics aspect of pharmacogenomics (Hood 2003). Other technological developments in the fields of DNA sequencing and bioinformatics have also enabled research in pharmacogenomics. All of these technologies currently are being used by collaborative organizations like the Pharmacogenetics Research Network, which consists of thirteen interdisciplinary research groups (Hood 2003). This network conducts research in pharmacogenomics and combines their findings into a public database known as the Pharmacogenetics and Pharmacogenomics Knowledge Base, or PharmGKB (Hood 2003).
Currently, genomic information only is being used to inform treatment on a small number of health-related issues, but scientists and pharmaceutical companies hope that it will soon be used to help those suffering from heart disease, asthma, depression, and other common diseases (National Human Genome Research Institute 2016). Cancer is an especially common area of research in this field. Despite these high aspirations, current progress in pharmacogenomics is gradual and irregular (Gabe, Martin, and Williams 2015, 27). There has been a significant increase in the amount of money and time spent on this research in the past decades, and yet actual innovation has been limited. Studies have not produced many positive results regarding the link between genomics and pharmacology. These limitations do not necessarily mean that pharmacogenomics is fruitless, but rather that it will take a long time to actually become useful in a clinical setting.
Despite the inauspicious results of research so far, the drive to continue developing pharmacogenomics stems from people in the Western World’s high expectations of medicine (Gabe, Martin, and Williams 2015). The scientific community has been promising to institute personalized medicine for decades, and pharmacogenomics represents that hope. According to University of Warwick sociology professor Simon J. Williams, “the claims underpinning the biotechnology revolution may best be viewed as rhetorical devices employed to generate the necessary political, social, and financial capital to allow the perceived promise to emerge” (Gabe, Martin, and Williams 2015, 28). The advancement of technology has allowed for the development of pharmacogenomics.
Perspectives and Controversy Regarding Pharmacogenomics
Many scientists believe that targeting drugs to an individual’s genotype will increase its effectiveness. Ineffective drug treatments are a large problem in the medical world, especially when treatment is time sensitive. The goal of pharmacogenomics is to save time, lower costs of drug trials, and reduce the negative outcomes of trial-and-error treatment plans (National Human Genome Research Institute 2016). Adverse drug reactions (ADR) are the 5th largest cause of death in the United States (Hood 2003). Therefore, reducing the frequency of adverse drug reactions will have a huge impact on the mortality rate of diseased people. Advocates for pharmacogenomics argue that it would reduce the number of ADRs due to biological incompatibility with a generic drug and drug development would be streamlined, safer, and less expensive for clinical trials. Only individuals with genetic background better suited for the drug would be included in phase III clinical trials, so the drugs on the market would be safer and easier to access.
While pharmacogenomics may help further the field of personalized medicine, it has also raised ethical questions. It has “inspired concerns over diverse populations, overly-segmented (and thus unprofitable) markets, and the proliferation of genetic testing and racial profiling” (Gabe, Martin, and Williams 2015, 27). Individuals that do not respond to drugs will be stigmatized and may have difficulty obtaining health care because the insurer would not want to spend money on them if drugs do not offer a quick solution for these people. Furthermore, drugs tailed towards individual genomes will have to involve clinical drug trials needing extensive genetic information from subjects. Data about a person’s genetics could be stored and used for later study of genetic factor in a disease. A large collection of people’s DNA leads to several questions. Who owns this genetic information? Who has access to it? The patient has claim to it, but the person’s relatives or descendants may also claim access to it if they want to find out their likelihood of inheriting a genetic disease. Also, health insurance companies may want access to genetic information because they want to determine the risk of the individual if the company decides to insure him or her. Employers may also want to know about a person’s genetic because they can get a better understanding of the costs of hiring that person as well as health insurance costs if the company provides it.
Furthermore, personalized drugs would only be accessible to the rich due to high costs. The drugs require genetic testing and tailor to each person. Insurance companies may be hesitant to pay for the drug therapies. These drugs would benefit Big Pharma because they would gain financial rewards for their investment in pharmacogenomics. While these medicines may be better suited for certain individuals, people from underdeveloped nations would be not able to afford them. In addition, medicine would not be completely personalized to one person, thus limiting the profit of pharmaceutical companies, but drugs would be tailored to certain genes over others, thus perhaps establishing a preference for genes. The personalized medicine drugs would target only diseases that have the largest market potential because large pharmaceuticals would not want to waste their time and energy on diseases that are not profitable. Pharmacogenomics would increase the divide between the haves and have-nots.
Politics of Health
Pharmacogenomics relates to the politics of health because it represents the ultimate extent of pharmaceuticalization: tailor-made drugs for each individual. Pharmaceuticalization is sustained by the drug companies that develop and produce new pharmaceutical products, and those institutions have been changed significantly by pharmacogenomics. The old industry model relied on large, “blockbuster drugs” to generate its profits, fund its research, and treat enormous numbers of people (Hood 2003). This economic model is no longer viable under a pharmacogenomic system, which requires that drugs be available in many different forms for people with different genotypes.
Pharmacogenomics also related to the idea of informed consent. Since lots of information about a person’s genome will be recorded during a study, the information may be used again in the future for studying genetic factors of a disease. The person may have another disease later on, and using data collected from earlier would be more efficient than recollecting the data again. Also, researchers may be interested in observing a disease in a particular area and would like to repurpose data collected earlier. While researchers collected the DNA for one use, they may not have considered other future uses of the DNA. One idea is “reconsent,” which refers to obtaining renewed informed consent each time a researcher uses a subject’s DNA, but the process may be cumbersome or researchers lost contact with the subject.
Furthermore, pharmacogenomics may further contribute to the idea of race as a biological concept rather than a social one. Scientific research has historically focused on white males instead of women and minorities. One example of research that focused on minorities was the Tuskegee Syphilis study, which lead to the mistrust of government and doctors by African Americans. The U.S. Department of Public Health (PHS) wanted to study the natural progression of syphilis in African Americans to see if it was different than the one in whites. The PHS saw race as genetic, and many researchers use this idea as the basis of their studies. In 2005, the US Food and Drug Administration (FDA) approved BiDil as the first race-based drug. It was marketed towards African Americans to treat heart failure. Pharmacogenomics contributes to the assumption that people of the same race have similar genetics.
References
Evans, William E., and Mary V. Relling. 2015. “Pharmacogenomics in the Clinic” Nature 526 (1): 343-350. doi:10.1038/nature15817.
Gabe, Johnathan, Martin, Paul, and Simon J. Williams. 2015. “The Pharmaceuticalisation of Society? A Framework for Analysis.” In The Pharmaceutical Studies Reader, edited by Sergio Sismondo and Jeremy A. Greene, 19-47. New York: John Wiley & Sons.
Hood, Ernie. 2003. “Pharmacogenomics: The Promise of Personalized Medicine.” Environmental Health Perspectives 111 (11): A580-A589.
Motulsky, Amo and Ming Qi. 2006. “Pharmacogenetics, pharmacogenomics and ecogenetics.” Journal of Zhejiang University Science 7(2): 169-170.
National Human Genome Research Institute. 2016. “Frequently Asked Questions about Pharmacogenomics.” National Human Genome Research Institute website, May 2. Accessed March 20, 2017. https://www.genome.gov/27530645/
Pirmohamed, Munir. 2001. “Pharmacogenetics and pharmacogenomics.” British Journal of Clinical Pharmacology 52 (4): 345-347.
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