The California Cure Making Medicine Personal

by Robin Mejia

If you hear the term personalized medicine, it doesn’t mean your doctor has your phone number and likes to call you and meet for coffee. The “personal” part of this phrase has to do with genes—after all, our genes are what make each of us unique. And the science emerging from our burgeoning knowledge of genes is already having an impact on everything from targeted drug treatment to prevention to genetic testing. Essentially, the future is now.

The sequencing of the human genome was a 13-year project and one of the more entertaining scientific races of its time. This summer, Stanford researcher Stephen Quake reported he’d sequenced his entire genetic code in about a month. At the same time, scientists have made considerable progress identifying what different genes actually do, including finding genetic mutations that can lead to disease. Scanning a genome for known risks is becoming increasingly common.

Experts believe these changes are ushering in a new era of medicine. Essentially, researchers can now compare the genetic maps of hundreds of people who have a disease with hundreds who don’t to figure out what genes are different in those who are ill. Then they try to determine what those genes do and how that function has been compromised. Next comes the exciting step: creating targeted treatments that fix the problem.

Of course, getting through all those steps takes time and money. The new director of the National Institutes of Health—Francis Collins, who led the Human Genome Project—has promised a renewed focus on such research. Similarly, the genetic underpinnings of disease can help patients avoid unnecessary treatments. Currently, many people take drugs that don’t actually help them, either because their bodies don’t process them correctly or because they have a form of a disease that doesn’t respond to the most common treatment. And many of those drugs have side effects the patient has to manage for what turns out to be no medical benefit. “What’s evolving is the attempt to find the right drug for the right person with the disease,” says Stephen Forman, chair of Hematology and Hematopoietic Cell Transplantation at City of Hope. “The more we understand about a cancer, the more drugs will be tailored to the cancer and have a less adverse effect on the person.” Researchers call this personalized medicine, a phrase making its way into the modern lexicon.

Test Case

The first private genetic testing firm—23andMe—was launched in 2007. Founded by Linda Avey and Anne Wojcicki (wife of Google cofounder Sergey Brin), it offered to scan the DNA of anyone who asked. The company was soon followed by others. At first the services sounded faddish—ads highlighted “ancestry” services offering to help people find their genetic roots. Today, the companies generally focus on more practical applications of genetic testing.

“One of the things we are trying to do is change consumer behavior so that people really take ownership of their own information,” says Wojcicki. “If I’m a carrier of the Parkinson’s mutation, then I want to know what I can do to prevent it.” For somewhere between $99 and $999, you can chose from an array of services that will take a swab of saliva from your inner cheek and give you your genetic-risk profile.

What does this actually mean? Well, say your dad had a heart attack at 50. Normally, your doctor might ask whether anyone else in your family has heart disease and warn you that you’re a likely candidate yourself, so you ought to eat right and stay fit. But neither you nor your doctor knows whether you inherited any risk factors. 23andMe can actually read through your genome and tell you whether you have genetic mutations known to contribute to heart disease. The test can also tell how your particular genetic makeup will affect your response to medical treatments.

“Or let’s say you are a patient with MS,” says Wojcicki, “and you participate in a trial at UCLA. UCLA is the only one using your data. But if you work with 23andMe, your data will be disseminated to UCLA and Pfizer. We want to put you in control of your data, rather than having it owned by the institution. It is a fundamental shift from today, where if you participate in a clinical trial with Amgen, you do not have access to your own data.”

There is also a larger goal at hand, she says. “For example, 23andMe gets everyone’s genome data in an area like Santa Barbara. What we do is put out a survey that asks, ‘Who, when they take Benadryl, gets sleepy, and who, when they take Benadryl, gets hyper?’ ” By combining that information with all of the genomes, we can do a genome-wide association study, where we look at all of the data points in the genomes and look at the answers to the questions and find a correlation. That is how you, the citizen, participates in research.”

Mike Godfrey, director of corporate communications at Scripps Health, couldn’t resist when his employer offered a discount on DNA analysis from Navigenics, another genetic-testing firm, that would examine his risk for a list of diseases. The five-foot-nine 47-year-old gives his weight as “under 200.” Four years ago, he started seeing a trainer in order to regain some of the athleticism he let go dormant during his kids’ younger years. But with diseases like Alzheimer’s running in his family, barbells and cardio could only get him so far.

When he got the email from Navigenics that his results were ready, Godfrey clicked through to the site. A list of 22 diseases ran down the left-hand side of the screen. Across the top were columns denoting his lifetime risk of contracting each one. Eleven of the 22 boxes on Godfrey’s screen were orange, showing he was at higher-than-average risk.

“I looked at it and said, ‘Oh my God,’ ” he recalls. Then he put it out of his mind. “I’m busy, just like everyone else.”

But a lot of his coworkers at Scripps had also been tested. Talk kept circling back to the results and what people were doing about them. Eventually, Godfrey succumbed to curiosity and began reading. (The Navigenics Website provides information on each of the diseases the company tests for.) In many cases, Godfrey’s risks turned out to be minimal, even if they were elevated. The chance that any one of us will suffer a brain aneurysm during our lifetime is 0.64 percent. Godfrey’s risk is 0.81. Higher, yes, but not worth losing sleep over. For some of the other problems, he felt like he was already on the right track.

And what about the disease that sparked the decision to be tested? His mother, it turns out, has a perfectly average risk for Alzheimer’s. Godfrey, on the other hand, carries a gene that nearly doubles his risk for the disease. So he has asked his trainer to change his exercise regimen to include more activities that require “balance and forethought” in the hopes of stimulating different brain pathways.

Godfrey is not sure whether the changed regimen will make any difference, but he did find other risks he can do something about. Macular degeneration is a disease marked by blurred vision and blind spots. According to his genes, he has a 9 percent chance of suffering from it before he dies. “I’d never even thought about that before,” he says. “Is that a life-threatening disease? No, but it’s certainly life changing.” It turns out macular degeneration can be minimized through lifestyle choices like wearing sunglasses. “If doing this can help me prevent getting that alone, it was worth the $150.”

On Target

Joe Ford is a program director at Five Acres, a nonprofit that works with families to prevent domestic violence. His wife, a former teacher, works for another youth and family services agency. A little more than a year ago, the two of them were having a typical evening. After dinner, they were sitting on the edge of their bed talking about the day’s events, Ford recalls. For the past week, his side had been hurting, and it was getting worse. His wife wanted him to go to the hospital, an idea he’d nixed. But as the pain worsened, he acquiesced.

At the Huntington Hospital ER, doctors ordered several blood tests. “When they brought the results, I could see the nurse’s expression change,” Ford recalls. Then the doctor came in and told him the tests uncovered an advanced case of chronic myelogenous leukemia. “They were pretty much telling me this was it.” The cancer was so far along that the only chance, it appeared, was a bone-marrow transplant.

Ford stayed upbeat. His wife and son were in the room, and he felt it was his job to set the tone for their response. When he got home, he prayed. “This is the purpose of faith,” he says. “You’ve got to keep your energy positive. Worry doesn’t add anything.”

He made an appointment at City of Hope, a nationally recognized research hospital in Duarte. Ford’s youngest son, who’s now 21 and starting Saint Thomas University in Miami on a basketball scholarship, has sickle cell anemia and had been treated there throughout his childhood. Ford trusted the City of Hope doctors. At his initial appointment, his doctor had good news. He’d reviewed Ford’s test results and determined that the leukemia was not quite as advanced as the ER doctor had indicated. They could try treating it with Gleevec—no bone marrow transplant.

In 2001, when Gleevec was first released by Novartis, it made national headlines. One magazine cover called it “a cure for cancer.” That ink has turned out to be a bit hyperbolic. Patients have to stay on Gleevec indefinitely or the leukemia will return, and in some rare cases, the cancer develops resistance and comes back even if they stay on the drug. Still, the hype was right about some key points. Gleevec targets a very specific chromosomal mutation, unlike most traditional chemotherapy agents that kill off cells both bad and good. Hence, Gleevec has far fewer side effects. And the drug opened research into what scientists call “targeted therapy.” This ability to identify the genetic mutations behind a disease is enabling researchers to develop more drugs like Gleevec.

“That first part [identifying the genetic mutation] used to take 5 to 10 years,” says Brian Druker, director of Oregon Health & Science Uni­versity’s Knight Cancer Institute, who helped developed Gleevec. “You can do a whole cancer genome in weeks now...There are already a dozen drugs on the market, FDA approved, that follow the Gleevec model.” His lab is working on targets for types of melanoma, and he notes he recently saw presentations on ongoing trials for new compounds targeting some types of lung cancer, including advanced metastatic cases. “We’re opening up a whole new era of how we treat cancer.”

Ford, who was already on Gleevec, was keen on the idea of trying multiple targeted therapies after speaking with his doctor—with the goal of trying to beat back his leukemia permanently. So he started looking for clinical trials to see if there was any new research that might yield additional treatments. It turned out there was one, and City of Hope was testing it. This summer, Ford added the experimental drug currently known as LBH589 to his treatment regimen. As a result, he’s been able to dodge the devastation of conventional chemotherapy. He has a full head of hair, and the disease is not winning.

Just Getting Started

“Cancer is the best understood of the chronic diseases, but researchers are making advances in many fields, in large part due to the millions of genome scans that have been done in the past couple years,” says Eric Topol, a cardiologist and director at Scripps Translational Science Institute. “From April 2007 to August 2009, there’s been more learned about the root causes of disease than in the history of mankind. I’ve been a scientist and researcher my entire life—that’s 30 years—and I’ve never seen anything like this.” A fairly sober guy, he immediately backs up the claim by citing recent scientific papers. “This week, it was hepatitis C and childhood leukemia. Two weeks ago, we had genes for pancreatic cancer, ovarian cancer, bladder cancer and short sleep.” He pauses to look up earlier papers. July 7, there were papers on melanoma and brain cancer. July 2, schizophrenia.

The hope is to eventually have targeted treatment—à la Gleevec and LBH589—for all of these conditions. That’s a long-term goal, but in the meantime, genetics are providing clues that some researchers believe could soon dramatically change treatment protocols. For example, people who have been prescribed statins to lower their cholesterol may have such severe side effects—cognitive changes, muscle aches and damage—that they go off the drugs. “For some, it can be really profound, and they don’t get back to work for a week,” says Topol.

“Recently, one particular gene was identified, and the variations in it increase the risk of muscle toxicity almost 20-fold,” says Prediman Shah, director of cardiology at Cedars-Sinai. If doctors tested for that gene before writing the prescription, they’d avoid those bad reactions.

Then there’s the anticlotting drug Plavix, which simply doesn’t work in roughly a third of the population, say cardiologists. Once again, there’s a genetic test doctors can request before Plavix is prescribed that can tell whether a person will respond to it.

So why aren’t these tests being done today? Shah says he’s waiting for the completion of clinical trials before promoting widespread use of genetic testing, as history has shown not every medical intervention that sounds logical ends up promoting health and saving money—think hormone replacement therapy for postmenopausal women.

Topol, meanwhile, feels the data behind the Plavix test is “incontrovertible” and says Scripps has already implemented it. In addition to avoiding potential side effects from a drug he knows won’t help certain patients, there’s a financial argument. “It costs $2 or $3 a day. Why are we giving them this [if it won’t work],” he asks, arguing tests like these could avoid unnecessary medical treatments. “There’s cumulatively hundreds of billions in savings if we apply medicine appropriately.”

Looking forward, Topol envisions a day when each of us will carry our genetic code with us in our cell phone, letting us check each and every prescription against our own innate makeup. Surely, there’s an iPhone app on its way.