by Eleni Apostolatos
“There’s no gene for fate,” declares Vincent, the main character of the 1997 science fiction thriller, GATTACA, after he decides to disguise his imperfect DNA and assume the genetic identity of Jerome Morrow—a man whose flawless genetic makeup makes him apt for space travel. While Vincent’s argument that genes do not necessarily determine fate is valid, we are entering an age in which Vincent’s statement can be interpreted in a new light: in healthcare, the study of genes is reshaping patients’ fates.
The correct identification of genes linked to diseases and the prescription of tailored prevention mechanisms and treatments to meet specific needs—a practice known as precision medicine—can alter patients’ futures. Physicians involved with precision medicine aim to redefine the use of personal genomics, the study of individuals’ DNA, in healthcare by detecting genetically rooted illnesses and predicting personalized responses to potential treatments. In recent years, precision medicine has gained increasing public attention and support. The emerging question is: how will the surge of genomics impact the medical field and the health arena, as our society’s emphasis on genomics draws closer to that of GATTACA´s genetically-oriented society?
Precision Medicine from the Start
“It’s far more important to know what person the disease has than what disease the person has.” – Hippocrates
The notion of personalized medicine can be traced back several centuries to the time of Hippocrates. Some 2,500 years ago, Hippocrates wrote about the importance of presenting “different [drugs] to different patients, for the sweet ones do not benefit everyone, nor do the astringent ones, nor are all the patients able to drink the same things”.1 He arrived at the remarkable notion that every human is biologically unique. However, this notion was not significantly put into practice until much later, in the 20th and 21st centuries.
The traditional standardized care relied on a “one-size-fits-all” approach that proved to be ineffective in the treatment of many diseases, including diabetes and cystic fibrosis. In standardized care, doctors are less prepared to anticipate their patients´ susceptibility to certain diseases and their responses to prescribed treatment. Doses are prescribed on the basis of statistically gathered data and later adapted to each patient´s specific response.2 As Dawn McMullan wrote in her article, this form of care “doesn’t have all that much to do with you specifically”3 —the diagnosis is a general one that is usually met with a pre-constructed and impersonal treatment. And even though for almost half a century “scientists and clinicians suspected that a person’s genes could play a vital role in the response to medicines, genetic technology was not advanced enough to reveal which genes and which variations of those genes were relevant,”2 as claimed in the study “Personalized Medicine versus era of ‘Trial and Error.’”
In the 20th century, developments in science and technology enabled more focused healthcare; with the emergence of genetics, imaging and data mining, the medical device and pharmaceutical industries began to critically grow. The sequencing of the human genome at the outset of the 21st century made way for the sustained growth of personalized medicine: from being a theory that doctors tried to understand, personalized medicine began to be practiced. While scientists today still can’t pin down the reasons why patients have different manifestations of disease— in particular, of cancer and autoimmune illness—recent developments in genomics and in genetic technology have allowed for more personalized diagnosis and treatment, and have eased the way for precision medicine and its revolutionary approach to personalized healthcare. The National Academy of Science (NAS) defined “personalized medicine” as “the use of genomic, epigenomic, exposure and other data to define individual patterns of disease, potentially leading to better individual treatment”4. The momentum in genomics research has increased drastically in the past thirty years—when compared to its pace in the last four centuries, as visually depicted in Figure 1—with the invention of Polymerase Chain Reaction (PCR), an incredibly useful technique that is often considered to be, as written by Stephen A. Bustin in his book The PCR Revolution, “the defining technology of our molecular age”.5
Through PCR, researchers can amplify select sequences of DNA; metaphorically, “the needle-in-a-haystack stumbling block is magically recast as a solution that creates a haystack made up of needles”,5 enabling scientists to construct multiple copies of desired segments of DNA for use in lab. PCR thus allowed for the detection of single nucleotide changes in DNA, and paved the way for the Human Genome project— which was launched only five years later in 1990.
The Human Genome Project was an international project carried out to identify the sequence of the chemical base pairs that compose human DNA. Today, we are surrounded by the fruits of the Human Genome Project, which are some of the most promising discoveries in the history of humankind. Scott T. Weiss, the scientific director at Partners HealthCare Center for Personalized Genetic Medicine at Harvard Medical School, commented about the Human Genome Project: “Probably at no time in the history of medical research…has there been more potential and promise for discovery that will benefit mankind in terms of the health of the species as where we are right now as a result of the Human Genome Project”.3 In 2015, BioMed Research International revealed the growing impact of the Human Genome Project: “Currently, more than 1800 disease genes have been identified, more than 2000 genetic tests have become available, and in conjunction with this at least 350 biotechnology- based products have been released onto the market.”6
As a result of technological advancements that followed PCR and the Human Genome Project, physicians can now practice personalized medicine and provide “the right patient with the right drug at the right dose at the right time”,4 as the U.S. Food and Drug Administration indicates. This new form of medical treatment aims to tailor all stages of care—prevention, diagnosis, treatment and follow-up—to a patient’s specific needs.
Precision Medicine and Cancer
The advancements of precision medicine have been most noteworthy in the detection and treatment of cancer. Patients’ and tumors’ DNA are helping researchers and physicians determine the ideal treatment pathway for cancer patients. Patients with cancers such as melanomas, leukemias, breast cancers, and lung cancers, go through molecular testing and provide physicians with sufficiently specific details about their condition to enable personalized and precise treatment, generally minimizing adverse side effects and unnecessary exposure to certain treatments.7
“If you didn’t know what happened to her, and you saw her now, you would have no idea what she has been through,” says Emily Whitehead’s mom of her daughter’s formidable recovery. After being told by doctors at age 6 that she could no longer go through any more aggressive chemotherapy treatment as it would no longer help her acute lymphoblastic leukemia (ALL), Emily was enrolled into a phase 1 clinical trial at the Children’s Hospital of Philadelphia, where she was the first pediatric patient to be treated with a novel type of cancer immunotherapy: genetically modified T-cells, taken from her blood and re-engineered to detect a protein on her leukemia cells, were used to fight her specific leukemia condition.8 Recognized as a 2013 Breakthrough of the Year by Science Magazine, the genetically engineered T-cells, which Emily aptly dubbed “ninja warriors,” successfully treated the type of leukemia Emily had. After only 28 days of treatment, Emily recovered, and was in remission—and has been for the past three years. If she had stayed with chemotherapy, the more general form of cancer treatment, these results wouldn’t have been possible.8
Precision medicine has revolutionized diagnosis in a number of cancers. For instance, physicians used to diagnose non-small-cell lung cancer by simply assessing the tumor’s location. However, due to advances in precision medicine, physicians can also use genetic mutations in the tumor to determine a diagnosis. More specific diagnosis due to precision medicine also helps personalize therapy for increased effectiveness. An example is non-small-cell lung cancer: a driver mutation occurs in the gene encoding the signaling protein EGFR, which normally promotes cell proliferation; this driver mutation causes the EGFR to have increased activity and tumors to have unrestricted growth. Gefitinib and Erlotinib are drugs that block the abnormal activity of the EGFR that are inflicted with the driver mutation in non-small-cell lung cancer. These two drugs, however, are only useful in about 10 percent of patients with non-small-cell lung cancer because they only help the patients who have the specific EGFR driver mutation.9 Consequently, diagnosis of this type of disease can facilitate its treatment, as confirmed by the National Academy of Science (NAS) who, in their report “Improving Diagnosis Through Precision Medicine” prove how useful and efficient it is to focus on the molecular profile of each individual patient as opposed to only assessing the general characteristics of the disease or location of the cancer.9 By arriving at more specific diagnosis, treatment is more effective. Currently, specific mechanisms that detect the “molecular signatures” of individual manifestations of cancers are replacing traditional tools for diagnosis.9 While “this knowledge is starting to revolutionize the way medicine is practiced and is most vividly seen today in the diagnosis and treatment of patients with cancer,” there is great faith that “where we have yet to go next may prove the most useful and transformational development in medicine to date”,10 as elucidated in Davos 2015: The New Global Context.
How Precision Medicine is Already Changing the U.S. Healthcare System
In his State of the Union Address on January 20th, 2015, President Obama supported precision medicine. He announced the new Precision Medicine Initiative, that aims to provide correct personalized treatment to patients and families and promises to provide physicians with the necessary resources to treat the specific illnesses of their patients.
President Obama’s 2016 Budget dedicates $215 million to the National Institutes of Health (NIH), the Food and Drug Administration (FDA) and the Office of the National Coordinator for Health Information Technology (ONC) to increase research in precision medicine. The Precision Medicine Initiative plans to put together a comprehensive database of research findings, with genetic information and medical data from about a million Americans.11 The FDA has assigned the largest fraction of the investment, $130 million, to NIH for national research that hopes to increase understanding of disease and health with volunteers. Additionally, the FDA is investing a large sum of the money in the National Cancer Institute (NCI), in order to increase knowledge of genomic drivers and produce effective treatments for cancers.2
The White House’s website states that “America is well-positioned to lead in a new era of medicine, as the country that eliminated polio and mapped the human genome”.2 This heralds the question: is the rest of the world on board, or is only healthcare in the U.S. undergoing the change towards precision medicine?
Currently, the U.S. is the country that promotes precision medicine and its research the most, but this personalized outlook on medicine has the potential to catch on elsewhere. The main difficulty posed by precision medicine in the global scene is the sharing of knowledge and procedures. As written in Davos 2015: The New Global Context: “Today, two people receiving world-class care in different parts of the world, both suffering from a known and identifiable cancer, may experience two very different outcomes. One person will succumb to a cancer for which the other has been successfully treated.”10 This is unfortunately “a tragedy of modern medicine, made even worse since this disparity may often be solvable, the information to do so is at hand.”10 Discussions and conferences are taking place to resolve the issue of shared information—such as the 2nd Precision Medicine Congress that will be held by Global Engage later this year in London.
Projections to the Future
While the cost of performing gene mapping is steadily decreasing , its feasibility and accessibility increase. “It cost us $400 million for that first genome,” Dr. Francis S. Collins, the director of the National Institutes of Health, claims. “Now a genome can be sequenced for a cost approximating $1,000”.12 Not only is the cost for DNA sequencing decreasing—with many companies in the market already offering services related to sequencing for around $100—but also, “it is argued that, by increasing treatment effectiveness in specific individuals and reducing risk and expenditure associated with treating patients with an inappropriate drug, such approaches herald a new era of cheaper, more effective healthcare”.13
Additionally, precision medicine can also be used as a preemptive mechanism. Through precision medicine, healthcare can be veered more towards prevention than treatment, as indicated by the European Science Foundation: “Personalised medicine has the potential to embrace a truly pro-active and preventive approach to the health and wellbeing of all citizens”.13
However, some fears about precision medicine are also being put to voice. “I don’t think anybody disagrees with the fact that we [patients] are different and we respond differently. But it’s hard to make changes,”3 explains Edward Abrahams, the president of the Personalized Medicine Coalition in Washington, D.C. “You want to see evidence before you’re willing to move away from one-size-fits-all traditional medicine.”3 What frightens some is precisely that precision medicine is tailored for them, and thus few people have tried the exact prescribed treatment.
Additionally, the public is expressing ethical concerns with the privacy of genetic profiles. What exactly is done with the genetic information? How will it be stored—- and who will have access to it? These are some of the questions that are currently being asked. Some patients are concerned that insurance companies or employers might genetically discriminate. Also, genetic correlations indicating increased intelligence or better behavior might affect individuals’ identities. Maintaining privacy is an ongoing issue: GATTACA displays the potentially stifling effects of genomics; in its fantastical world, the privacy of the citizens is completely infringed.
Yet, despite the fears and concerns, many believe that precision medicine will continue to grow in popularity, as Ralph Snyderman, M.D., Chancellor Emeritus at Duke University relates in the The Case for Personalized Medicine 2014: “Health care today is in crisis as it is expensive, reactive, inefficient, and focused largely on one-sizefits- all treatments for events of late stage disease. An answer is personalized, predictive, preventive, and participatory medicine.”14 Similarly, both Margaret Hamburg, M.D., Commissioner of the U.S. Food and Drug Administration, and Francis Collins, M.D., Ph.D., Director of the National Institutes of Health, jointly commented optimistically in The Case for Personalized Medicine 2014, “As the field advances, we expect to see more efficient clinical trials based on a more thorough understanding of the genetic basis of disease. We also anticipate that some previously failed medications will be recognized as safe and effective and will be approved for subgroups of patients with specific genetic markers.”14
How will precision medicine develop in the following years? Will Obama’s Precision Medicine Initiative revolutionize healthcare in the United States? While current opinions and projections give us an idea of precision medicine’s promising future, only time will tell the role precision medicine will actually play in healthcare and society.
Eleni Apostolatos ‘18 is a freshman in Greenough Hall.
- Holst, L. “The Precision Medicine Initiative: Data-Driven Treatments as Unique as Your Own Body.” The White House. The White House, 30 Jan. 2015. Web. 7 Apr. 2015.
- Najeeb, Q et al. “Personalized Medicine versus Era Of ‘Trial and Error.’ ” Journal of Pharmaceutical and Biomedical Sciences, 2012. Web. 13 Apr. 2015.
- McMullan, D. “What Is Personalized Medicine?” Genome Magazine. N.p., n.d. Web. 5 Apr. 2015.
- “Paving the Way for Personalized Medicine.” (2013): n. pag. ES U.S. Food and Drug Administration, Oct. 2013. Web. 5 Apr. 2015.
- Bustin, S.A. The PCR Revolution: Basic Technologies and Applications. Cambridge: Cambridge UP, 2010. Web. 13 Apr. 2015.
- Durmaz, A.A. et al. “Evolution of Genetic Techniques: Past, Present, and Beyond,” BioMed Research Intl, vol. 2015, Article ID 461524, 7 pages, 2015. doi:10.1155/2015/461524
- “FACT SHEET: President Obama’s Precision Medicine Initiative.” The White House. The White House, 30 Jan. 2015. Web. 2 Apr. 2015.
- “About Emily.” My Journey Fighting Leukemia. N.p., 2015. Web. 4 Apr. 2015.
- Insel, T. “Director’s Blog: Improving Diagnosis Through Precision Medicine.” National Institute of Mental Health. U.S. Department of Health and Human Services, 15 Nov. 2011. Web. 5 Apr. 2015.
- Pellini, M. “Not Knowing the Knowable.” Davos 2015: The New Global Context. World Economic Forum, 23 Jan. 2015. Web. 4 Apr. 2015.
- Powledge, T.M. “That ‘Precision Medicine’ Initiative? A Reality Check.” Genetic Literacy Project, 3 Feb. 2015. Web. 5 Apr. 2015.
- Pear, R. “U.S. to Collect Genetic Data to Hone Care.” The New York Times. 30 Jan. 2015. Web. 4 Apr. 2015.
- Look, E.F. “Personalised Medicine for the European Citizen.” European Science Foundation (2012): n. pag. European Science Foundation. Web. 5 Apr. 2015.
- The Case for Personalized Medicine (2014): n. pag. Personalized Medicine Coalition. Web. 7 Apr. 2014.