At first glance, the idea of personalized medicine may not seem that new.  After all, haven’t physicians always given personalized care?  They ask about your health, take your blood to measure hormones and cholesterol, and look at the numbers and types of cells in your blood. If a prescribed drug doesn’t effectively treat a disease they switch you to a different one.  Isn’t that personalized medicine?    Maybe—but not in the way it could be.

Today, when people refer to “Personalized Medicine” it is generally in the context of using genomics, the science of looking at all of the information in the human genome, to tailor medical care to individuals based on their genetic makeup. The DNA in the human genome encodes the information that provides our biological machinery with the instructions for all of the molecular parts of that compose the human body.  Overall there are about 3 billion letters in that set of instructions.  When the 3 billion letters of one individual human are compared to those of another, unrelated person, there are something like three million differences. Those 3 million differences contribute significantly to what makes those individuals unique. One very tangible example of this is the physical similarities that are often seen between parents and their children, because children share much of their genetic variation with their parents.  This is also why some diseases run in families.

One of the promises made when the human genome sequencing project was started was that it would lead to treatments that could be better tailored to the individual.  The idea is that by “reading” the sequence of an individual’s DNA it might be possible to predict whether or not that person would respond in the expected way to treatment with a particular drug.  That information would then be taken into consideration when a drug is prescribed as a treatment.  So, rather than a “one-size fits all” treatment for a disease or condition, treatment would be based on additional information about the individual’s genetic makeup. For example, specific drugs such as Gleevec, Herceptin, Iressa and Tarceva, have been used over the past several years to treat leukemia, breast cancer and even lung cancer, and they’ve been shown to be most beneficial in a subset of patients with specific genetic variations. In these cases patients are tested prior to prescribing the drug.  Patients who would be unlikely to benefit are saved the expense of the drug, which can be tens of thousands of dollars, while those who will likely benefit from treatment have higher confidence of a good outcome.

Just as genetic variations can affect how patients respond to treatment, they also affect the way drugs are metabolized, or processed, by the body. For example, genetic variation is known to affect the pain-killing ability of codeine.  If you have one variation codeine is an effective painkiller, but if you have a different variation it is not.  As we learn of more examples of genetic variation altering individual response to drugs, we will start to see more examples of genetic tests being given to determine how much of a drug will successfully treat a particular individual.  This is already done in cases of childhood leukemia to determine what dose of medicine a particular patient should be given.  If the child suffering from leukemia has one genetic variation, they tend to metabolize the drug more quickly, so they require a much higher dose than if they have a different variation that results in slower breakdown of the drug.  If you give the high dose to a person with the genetic variation that would be appropriately treated with a lower dose, they are at risk for very severe side-effects.

This approach could even allow drugs that might normally be taken off of the market because of side effects to be safely given to those who would be unlikely to suffer an undesirable side effect. It has been estimated that there are more than two million occurrences of serious side effects from drugs each year in the United States, which may lead to more than 100,000 deaths per year. If the genetic variation responsible for the unwanted side effects of a drug can be identified, a test for those variations could be given prior to treatment.  This would prevent individuals at risk of undesired side effects from receiving that treatment, allowing drugs that would otherwise pose a liability to the manufacturers but which could also benefit a large number of people to be safely available.

This knowledge of the contribution of genetic variation to effective drug therapy is also likely to impact how drugs are developed and marketed.  Currently, drugs must be tested in large and varied populations that include individuals who would respond well to the drugs as well as some who might not.   This often creates the possibility that the effectiveness of the drug is underestimated because of those that did not respond well to the drug.  However, if drug developers understood the contribution of genetic variation to the effectiveness of the drug, they could test the drug in a much smaller group, comprised of people would likely respond to the treatment with minimal side effects.  While the drug in question might not treat everyone with a particular disease, it would very effectively treat a subset of those patients.  This could make drugs that otherwise would not be seen as valuable available to those who need them and potentially reduce the costs of drug trials.

Improved diagnosis of disease is another benefit of personalized medicine.  The first example of great success was the ability to divide the disease B-cell lymphoma into two different diseases based on patterns of gene expression displayed by the cancer cells.  By having the sequence of the human genome and knowing what genes are present in human DNA, researchers were able to produce a “gene chip”—a glass slide that has a test for every gene in the genome on it.  The researchers could then ask which genes, which of those 22,000 instructions in the DNA, were actually used to produce a particular tissue—in this case a B-cell in the blood. They were able to compare the genetic instructions used in normal B-cells to those used in B-cells in patients with leukemia.  It turns out that there are some key differences in the instructions, or genes, used in the disease.  Those differences in gene expression can be used to diagnose the disease.  Using this approach, two distinct gene expression signatures were observed in different leukemia patients, leading to the conclusion that rather than being a single disease, the patients with different signatures had different diseases.

More recently it has been shown that it is possible to distinguish between metastatic breast cancer and non-metastatic breast cancer by comparing the levels of expression of only seventy or so genes.  Metastatic breast cancer spreads more rapidly, has a much worse prognosis and requires much more aggressive treatment than does non-metastatic breast cancer, which tends to spread much less. The ability to distinguish them provides valuable information that can be used to tailor treatment to that particular tumor type.

Since genetic variation also has a significant impact on disease risk, an important feature of personalized medicine will be preventive.  By having knowledge about the genetic predispositions of a particular individual for a particular disease, their physician will be able to focus on prevention and screening for those conditions.  Predisposition based screening should lead to earlier intervention in disease if it does occur.  In general, earlier diagnosis maximizes both successful treatment and often reduces the costs associated with treatment compared to later diagnosis, which often requires more costly treatments.

These advances, all based on the human genome sequence and our ability to measure natural genetic variation, will produce more effective treatments, more effective diagnoses and may contribute to reducing health care costs.  Most importantly it will enable our physicians to provide an even more personalized approach to our healthcare – one informed by the ability to read our DNA.