Consider the ways humans differ from one another and what characteristics make us unique individuals. We differ by sex, age, size, and shape. Our diets are different, the environmental factors we are exposed to vary, as do our general lifestyle choices. And even though we are extremely similar at the genetic level, there are differences in our genetic makeup that make us unique as well. Scientists are beginning to understand how these small differences in our DNA contribute to health, disease prognosis, progression, prevention, and response to treatments. And these small differences between us are making it clearer to physicians why the “one size fits all” approach to healthcare is not as accurate or safe as it could be.
The underlying idea behind “personalized medicine” is that an individual patient’s healthcare can be customized and optimized by taking into account their specific genetic and environmental profiles. Scientists and physicians see great potential in the ability of personalized medicine to provide customized preventive, diagnostic, and therapeutic interventions to optimize healthcare. Many of the world’s leading academic institutions and pharmaceutical companies see the potential in this line of research and are investing heavily in personalized medicine programs because it is strongly believed that personalized medicine will improve health outcomes and transform the medical system.
So what does personalized medicine have to do with the mission of NAVS – to advance science without harming animals? How are these topics related? It comes down to this – if subtle genetic differences among human beings can have not-so-subtle effects on our health and response to drugs, how can scientists expect an animal, with a significantly different genetic profile, to predict what happens in people? Knowing what we now know about differences between species, it should come as no surprise to us that animal models cannot predict what happens in people, and continued reliance on them may mislead researchers and delay advancements in science.
With personalized medicine, we can start to appreciate what the differences in human DNA mean for people and start to understand how our genetic variants can be used to make predictions about our health and well being. We can begin to more thoroughly understand the genetic profile of diseases, and why disease risk, progression and treatment response differs among different people. We are able to ask new, human-relevant scientific questions that could not have been answered just a few years ago—but are answerable now based on advances in science and technology.
Let’s consider the ways that personalized medicine has advanced over the years and what kind of information we can learn from it. On some level, physicians have tried to personalize medical treatment by asking about family history, social circumstances and environmental exposures during regular check-ups. However, advancements in science are allowing us to personalize medical treatments to a whole new level. Understanding the effects of specific genetic differences between individuals can provide important information for a physician. Because some of our genes encode for enzymes, differences in gene sequences can affect the activity of enzymes. Since some enzymes play an important role in the way our bodies process drugs, and because this variation in genes exists, some people may metabolize drugs more quickly or slowly than other people. This means that different people may need different doses of a drug for it to be effective in them. And using genetic information, it is now possible for doctors to personalize and customize dosage of some drugs based on how well your body can process the drug, based on your genetic profile. That way, your chances of receiving an optimal therapeutic dose of a drug can improve from the start, rather than selecting a dose based on a general trial-and-error approach, which can save time, money and negative side effects.
A good example of how a person’s genetic makeup can be used to predict their response to drugs can be seen with dosing of the blood-thinning drug warfarin (coumadin). It is estimated that about two million people in theU.S.start taking warfarin every year for prevention of blood clots, heart attacks, and stroke. A trial-and-error means of prescribing warfarin is particularly dangerous, because individuals who take more of the blood thinner than they can tolerate risk life-threatening bleeding. On the other hand, individuals that do not receive a high enough dose run the risk of forming blood clots. Because of these factors, warfarin is one of the most common drugs that is implicated in emergency room visits due to adverse drug reactions. Ever since 2007, the Food and Drug Administration (FDA) has recommended that healthcare providers use genetic tests to help them determine their initial estimate of warfarin doses for individual patients because studies have shown that patient responses to warfarin can be explained in part by variations in specific genes. Although it is not common practice for patients to be screened for these genetic variations yet, it is anticipated that such tests will become a routine part of clinical practice in the future.
Experts in personalized medicine acknowledge that it will take time to see breakthroughs in personalized medicine and for the medical system to change in light of these advances. While it is important to understand the inherent challenges that come with personalized medicine, we should not be discouraged by them, as a number of impressive advancements have been made in the field in just the last few years.
Sequencing genomes is faster and cheaper than ever
Many experts predict that we may soon see more rapid advancements in personalized medicine because it is becoming much less expensive to sequence the human genome. The thought is that when the cost of sequencing a human genome drops to about $1,000, that it will be become more widely adopted in clinical practice. In just the last decade, we have witnessed a dramatic decrease in the cost of genome sequencing, from $300 million in 2001, to $5,000 in 2011, to $3,000 today in 2012. We are well on our way to reaching the goal of the $1,000 genome. In fact, two biotechnology firms announced earlier this year that they would be able to offer machines that could sequence a human genome in about one day for less than $1,000.
We are able to better classify human diseases by understanding what is happening at the molecular level
Just this year, researchers realized that there is a better way to identify the kind of breast cancer that a patient has by analyzing genetic material rather than just focusing on the presence of a few biomarkers, like hormone receptors ER and Her-2. Based on the genetic analysis, 10 subtypes of breast cancer were identified. This reclassification means that doctors can better diagnose what kind of breast cancer a patient has and prescribe treatment that is most likely to work for them.
We have seen major growth in the number of personalized medicine products that are commercially available
In 2006, there were 13 well-known examples of personalized medicine drugs, treatments and diagnostic products available, including Herceptin, an antibody used to treat HER-2-positive metastatic breast cancer and Gleevec, used to treat patients withPhiladelphiachromosome-positive chronic myeloid leukemia. At that time, scientists were also aware that targeted dosing of some drugs, like warfarin and 6-mercaptopurine, a chemotherapeutic drug, could be guided by an understanding of a patient’s genotype for relevant genes. Just 5 years later, in 2011, there were 72 prominent examples of personalized medicine drugs, treatments and diagnostic products available. That’s a 5-fold increase in just a 5 year time frame! Because an individual’s response to drugs can be accurately predicted for some medicines, the FDA now includes information about genetic biomarkers for a large number of FDA-approved drugs. In time, we will see that our genetic information will be utilized by physicians to help them make decisions about our health care.
Of course, to continue making progress in personalized medicine, time and resources will need to be allocated for identifying genetic variants and environmental risk factors and determining how to translate this information to human health and well being. Researchers and doctors will need to understand how to sift through the enormous amount of data that can be collected from each patient – a combination of our molecular data and our lifestyle and environmental exposures – to identify meaningful information that can impact our health and well being. This is obviously a complex problem, as we are complex organisms. But scientists are up for the challenge and are developing and applying analytical tools to approach this problem in a logical way. With continued investment from pharmaceutical companies, prestigious academic institutions, venture capitalists, and the government, we will really begin to more fully recognize the vision of personalized medicine. As Dr. Francis Collins, Director of the NIH stated, “Genomics has had an exceptionally powerful enabling role in biomedical advances over the past decade. Only time will tell how deep and how far that power will take us. I am willing to bet that the best is yet to come.”
Personalized Medicine is beginning to reshape the way we think about health and well being. The following studies provide just a few examples of the way that personalized medicine is changing how physicians approach a number of different diseases and conditions.
- Genetic variation can impact the efficacy and risk of adverse reactions to commonly used oral agents in diabetes
-Pearson ER. Pharmacogenetics in diabetes. Curr Diab Rep. 2009 Apr; 9(2):172-81.
In individuals with HIV:
- Genetic testing for a genetic variant associated with hypersensitivity in HIV treatment with abacavir
Phillips E, et al. Drug hypersensitivity in HIV. Curr Opin Allergy Clin Immunol. 2007; 7(4) 324-30.
In the Dosing of Blood Thinners:
- Use of clinical and genetic data to estimate the appropriate initial dose of warfarin (coumadin), a drug used to prevent formation of blood clots
-The International Warfarin Pharmacogenetics Consortium. Estimation of the warfarin dose with clinical and pharmacogenetic data. New England Journal of Medicine. 2009; 360(8): 753-64.
In the Management of High Cholesterol Levels:
- Genetic variation can impact the efficacy of statins, drugs used to lower cholesterol levels
-Chasman DI, et al. Pharmacogenetic study of statin therapy and cholesterol reduction. Journal of the American Medical Assocation. 2004 Jun 16; 291(23): 2821-7.