Personalized medicine. Predictive medicine. Targeted medicine. These are just some of the descriptors being applied to “genomic medicine,” a field of medical research generating much fanfare and hope for the future.
Genomics, according to the Centers for Disease Control and Prevention (CDC), is the study of all the genes in the human genome – that double-stranded DNA helix that defines who we are and what we’re made of. Building on classical genetics, it focuses on gene variations, the genetic code we inherit, the environment we live in, and the range of diseases we develop.
The promise of genomics is huge. It could someday help us maximize personal health and discover the best medical care for any condition. It could help in the development of new therapies that alter the human genome and prevent (or even reverse) complications from the diseases we inherit.
And while the field of genomics has existed for decades, only recently has it started to receive widespread attention.
Genomics makes its way to the public sphere
In 2000, Bill Clinton and Tony Blair stood side by side at the White House to announce the sequencing of the human genome. It required more than a decade of work and cost over $1 billion.
Today, companies advertise machines that can sequence an entire human genome in just a couple of days for less than $2,000. Those who decide to have their genome sequenced can store the information in the Google cloud for as little as $25 a year. And for just a few hundred dollars and a swab of your saliva, a whole host of companies will analyze thousands of genes and identify potential health risks.
Genomics drew mass media headlines last year when Angelina Jolie underwent a double mastectomy and subsequent breast reconstruction. She had tested positive for a mutation in a gene (BRCA1) that assists in the repair of DNA. Mutations of the BRCA1 and BRCA2 genes can place people at significantly greater risk for developing breast and ovarian cancer. Hers is a story of the possibility of genomic testing. As the cost of sequencing the human genome goes down, we can expect the field of predictive medicine to continue expanding.
Genomics in medicine today
Genomics is changing the practice of medicine. In some cases, it’s helping to identify health risks, susceptibility to diseases and how a patient will respond to certain medications. Genomic medicine is making the greatest headway in three key areas:
Oncology. So far, medical genomics has made the greatest leaps in the study and treatment of cancer. By comparing the abnormal genetic structure of a tumor with that of a patient, oncologists can figure out which mutations have occurred and target their chemotherapy directly at the cancer.
“Cancers arise when cells accumulate some combination of genetic events that serve as ‘drivers’ so that cell division outpaces cell death,” said leading cancer researcher Burt Vogelstein.
The Cancer Genome Atlas project is in the process of identifying these various genomic changes in 20 different types of cancer. This government-funded project, supervised by the National Cancer Institute and the National Human Genome Research Institute, hopes to subdivide cancer types at the molecular level, allowing researchers and clinicians to treat different tumors in a more targeted way based on specific gene mutations. Alterations in a tumor cell’s genome lead to the production of abnormal proteins, which account for much of the cancer’s malignant behavior. Researchers see these proteins as potential targets for chemotherapy.
Take chronic myelogenous leukemia (CML), a cancer of the white blood cells. In the 1960s, scientists discovered that different parts of two chromosomes had merged into a single gene found in the abnormal cancerous cells. They named it the “Philadelphia chromosome.” Imatinib, an inhibitor marketed by Novartis as Gleevec, targets the product of this gene rearrangement. By only killing cancer cells, this targeted medicine has made impressive strides in the treatment of CML. Before Imatinib, people with CML survived an average of five years. Today, the 10-year survival rate is 90 percent.
Prenatal screening. Genomics has also proven valuable in prenatal genetic screening for inherited diseases like cystic fibrosis, Tay-Sachs and sickle cell anemia.
Today, prenatal screenings that detect the risk of certain birth defects are commonplace. In California, they’re offered to all pregnant women. And because pregnant women over 35 face an increased risk of chromosomal abnormalities, physicians often recommend genetic testing while many private insurers pay for some or all of the cost. And for couples who want to know about their personal genetic risks should they decide to have a child, there are companies that can screen for over 100 specific diseases.
Pharmacology. Pharmacogenomics, according to the National Human Genome Research Institute, “takes into consideration a person’s genetic makeup, or genome, to choose the drugs and drug doses that are likely to work best for that individual.”
So, rather than a one-size-fits-all approach to prescribing medications, some physicians rely on pharmacogenomics for a more personalized approach.
The medication trastuzumab, for example, is used to treat breast cancer in women whose tumors have tested positive for Human Epidermal growth factor Receptor 2 (HER2), a protein that promotes the growth of cancer cells. Survival rates have increased significantly for women using this treatment. However, the therapy proves much less effective in women without the HER2 receptor. Knowing this, doctors avoid prescribing the medication to these individuals since the risks of serious cardiac side effects outweigh the advantages.
Similarly, 40 percent of patients with metastatic colon cancer have a mutation in a specific gene and will derive no benefit from the drug Cetuximab. For these patients, genetic testing allows them to be spared the side effects and expense of this particular agent.
Is the cost of routine genomic screening worth it?
Genomics has greatly improved our understanding of disease risk and treatment. But the information hasn’t proven useful for most people. In only a few cases have researchers identified genetic patterns that predict whether a certain disease will occur in a particular individual.
Jolie’s double mastectomy happened because she tested positive for a mutation of BRCA1 gene. In her case, her strong family history for breast cancer pointed to a high risk, making her a candidate for genomic testing. However, the BRCA1 and BRCA2 genes account for only five to 10 percent of all breast cancer occurrences. For most people, this type of testing isn’t recommended.
Clinical recommendations rarely change when doctors learn that a patient is at a slightly higher or lower risk for developing heart disease or stroke. Regardless of what a genomic test may indicate, everyone would be better off eating healthier foods, exercising regularly and getting preventing screenings based on one’s age, sex and medical history.
In other words, the information available through genomic testing has not yet proven effective in helping people modify their personal behavior. Genomics will change the practice of medicine in powerful ways – in the future. What remains to be seen is how quickly the future will come.
Robert Pearl is a physician and CEO, The Permanente Medical Group. This article originally appeared on Forbes.com.
