Personalized Medicine

ethics + policy

Personalized Medicine by Caryn Kunz

I

t is estimated that over 106,000 people die every year because they are given the wrong dose of medicine. Adverse Drug Reactions (ADRs) are a significant problem in today’s health care industry, hospitalizing an estimated 2.2 million people each year. It is the fourth leading cause of death in the U.S.—ranking significantly higher than AIDS, pulmonary disease and diabetes. Before you become wary of taking your next medication, there is good news. Scientists have made progress in personalized medicine, the identification of drug treatments based upon an individual’s genetic profile. While revolutionary, personalized medicine has profound ethical implications. Dr. David Magnus, Director of the Stanford Center for Biomedical Ethics, reveals the ethical considerations at stake with personalized medicine.

Trial-and-Error Drug Prescriptions Physicians are never 100% certain that a patient will react favorably to a prescribed drug. Since each patient has a unique biological makeup, a given medication may result in different levels of efficacy and adverse reactions. “Right now, what we do is give patients medication that generally works for their conditions, knowing that there may be a certain response rate,” says Dr. Magnus. “Some of them will respond, some of them won’t, and some of them will have

Armed with a patient’s genetic readout, doctors will soon have the ability to modify treatment on a patient-by-patient basis. really bad side effects. We don’t know in advance which ones are going to be which.” Personalized medicine shows promise of replacing the current system of trial-and-error prescriptions and diagnoses with a more efficacious and safe alternative.

The Science Behind Personalized Medicine “When people talk about personalized medicine, it often means pharmacogenomics, and being able to tailor therapeutics to individuals based on far greater information about their genetic profile,” explains Magnus.

layout design: Stephanie Le

U.S. Department of Energy Human Genome Program, http://www.ornl.gov/hgmis

Personalized medicine utilizes an individual’s genetic profile to identify proper drug treatments

With pharmacogenomics, or the study of how variations in the human genome affect the response to medications, researchers analyze large databases of genetic information to develop effective drugs. This data is also used to determine subsets of disease populations and to predict reactions to therapies. In order to group patients into populations that share a specific disease, researchers compare differences in individual DNA polymorphisms, specific nucleotide variations between individuals. The genetic material in these databases is obtained through the use of DNA microarrays, a technology capable of measuring the expression of genes for each individual. When taken over a large population, data from these microarrays can be compiled to create expression profiles common to certain diseases. These profiles can potentially allow physicians to predict the exact drugs that will prove effective for a given ailment. “The idea of using information to better tailor things is a good opportunity to open up what right now is a black box,” claims Magnus. “The idea that we could open up that black

volume iv 57

ethics + policy

box to be able to make better predictions about what’s going to work for whom could dramatically increase the effectiveness of our therapies.” Armed with a patient’s genetic readout, doctors will have the ability to modify treatment on a patient-by-patient basis. Why has personalized medicine not yet developed into a readily viable treatment? The first answer is that technologically, the technique is far from perfected. Secondly, personalized medicine has the potential to disruptively change our current health care system and the

“These are really tough, tough issues that you have to grapple with before you move forward.” -Dr. David Magnus, Director of the Stanford Center for Biomedical Ethics pharmaceutical industry. Patient privacy, health disparities, the waning of “blockbuster drugs” and drug approval policies represent only a small sampling of the countless looming issues for policymakers and ethicists such as Magnus.

The Promises of Personalized Medicine

Genetic screening also has the potential to predict an individual’s risk of contracting a specific disease long before the sickness manifests. Many predisposed diseases are actually triggered by environmental factors, such as eating and exercise habits. Others commence with age. A foreknowledge of patients’ health risks will allow physicians to guide lifestyle routines or prescribe preventative drugs that inhibit the onset of disease.

The Ethical Issues of Personalized Medicine Patient privacy One of the most pressing ethical controversies surrounding personalized medicine is patient privacy. Currently, pharmacogenomic research is conducted using anonymous genetic material. “The move towards creating more and more firewalls between the researcher and the individual so they can’t do any tracing back has been a way of dealing with some of the consent and confidentiality issues,” says Magnus. Although this method may be effective in protecting the privacy of an individual’s medical information, questions regarding the ethics of obligation arise when researchers discover a correctable condition within the anonymous genomes in the databases. “If you turn your material over, and we now can do something that can actively help you, what do we owe you?” asks Magnus. Should scientists trace the genome back through the anonymity firewalls and contact the at-risk individual? Although the patient may appreciate such communication, Magnus warns, “we also don’t want this tracing back to be done too capriciously, and we especially don’t want it to be done in situations where we don’t know how to interpret the meaning of that information.” The practice of pharmacogenomics is still too new to provide a definitive and complete understanding of the genetic information

Specific drug development Today, therapies are developed to treat large populations of common diseases. Many of these people actually belong to smaller sub-groups, each with a slightly different strain of the disease for which blanket therapies are not effective. Knowledge of patient sub-populations has the potential to alleviate pressures currently experienced by the pharmaceutical industry. The costs of researching and developing a new drug are astronomical; less than ten percent of drugs actually make it to the market. According to Magnus, greater Personalized medicine may improve a patients’s condition. knowledge of sub-populations may help to raise the percentage of marketable therapies: “When people have a drug, and it doesn’t work over the population as a whole, the idea that you would look for sub-populations where it does work will allow you to save a drug that otherwise would be a failure.” Early diagnosis/prevention Detecting a disease in its initial stages reduces difficulties and costs for physicians and patients alike. Instead of running many expensive clinical tests to reach a diagnosis, doctors may soon be able to determine the specifics of an illness much earlier than is currently possible. This ability may allow for intervention at the first manifestation of disease, thereby greatly improving a patient’s chances for a successful recovery.

58 stanford scientific

© stockvault.net/Björgvin Guðmundsson

collected from patients. Even as these primary analyses remain unclear, a myriad of ethical issues are becoming more crucial with each new discovery. Within the context of personalized medicine, patient privacy also begs the question of how much insurers or employers should know about an individual’s predisposition to a disease that may prove debilitating or costly to treat. Will that knowledge prevent someone from being hired? Will

“The idea of using information to better tailor things is a good opportunity to open up what right now is a black box.” insurers require genetic screening before selling policies, and who will be required to pay for expensive screening tests? Will insurers raise premiums or deny insurance to individuals who may be genetically predisposed to a disease that may or may not develop in the future? Health disparities Recently, the FDA approved a heart-failure drug called BiDil—a therapy created solely for African Americans. “There are a lot of critics who say that identifying a drug for African Americans is a dangerous step, because it clumps together individuals who shouldn’t be lumped together,” says Magnus. “What we really want to do is have biological markers, which are more accurate, used instead. Otherwise, it may reinforce views that these populations really are different, and may wind up influencing stereotypes.” BiDil, however, is only a halfway point on the road to true personalized medicine, where individuals will be diagnosed and afforded treatment strictly according to genetic screening, not race or class. “Theoretically, [genetic screening] might actually help alleviate some of those disparities,” Magnus remarks. “What it might produce, however, are new health disparities for groups that are small, and where treatments don’t exist.” Populations with extremely National Institute of Standards and Technology rare diseases may Microarrays are used to identify Single Nucleotide be left without Polymorphisms between patients. treatments because they are not large enough to offset the costs of a needed drug’s development. “It may be that we’ll have to figure out some way of accommodating groups that essentially become identified as genetic orphans,” explains Magnus.

layout design:

“At this point, it’s hard to tell whether [health disparities] would get better or worse.” C r e a t i n g economic incentives for pharmaceutical companies that develop therapies for subpopulations may help to alleviate this disparity, but represents only a small part of the solution. Ensuring that underserved access to the full benefits of personalized medicine will be an important issue in the future.

ethics + policy

Photo by Simon Pyle

Dr. David Magnus, Director of the Stanford Center for Biomedical Ethics

The Outlook on Personalized Medicine Before the road to personalized medicine is full paved, much work remains. Magnus points out, “We act like these things are right around the corner, but what we’re actually getting are surrogates in between.” Eventually, personalized medicine will profoundly connect pharmaceuticals, health care providers, patients, insurance companies, researchers and policymakers. As ethical issues surface, it is critical that policies are devised that benefit all involved parties. Consensus conferences, such as those already being held by Magnus and his team at the Stanford Center for Biomedical Ethics, establish a safe environment for top representatives to debate these guidelines. According to Magnus, “These are really tough, tough issues that you have to grapple with before you move forward.” S Caryn Kunz is a senior majoring in Creative Writing, with a minor in HumBio. In addition to science writing, she enjoys reading, eating, the beach, and spending time with friends and family. To Learn More: Departmental website of Dr. David Magnus: http://scbe.stanford.edu Personalized Medicine Coalition: http://www.personalizedmedicinecoalition.org/ Pharmacogenomics Online: http://www.pharmacogenomicsonline.com/ National Center for Biotechnology Information: http://www.ncbi.nlm.nih.gov/About/primer/pharm.html

volume iv 59