Personalized medicine is alive and growing in the local bioscience community.
Dr. Shirlean Goodwin, a research assistant professor in the University of Memphis' biology department, holds a chip containing a genetic sample.
photographs by Lindsay Jones
It’s a hot summer afternoon and rain is falling on the University of Memphis campus. If it were possible for droplets to sizzle on contact, steam would be billowing off the pavement on its way back to heaven. But apart from this gray outer world, a microcosm of discovery is at work inside the university’s W. Harry Feinstone Center for Genomic Research. There, students tap away at computer terminals, analyzing genetic data to understand more about diseases and other intricacies of the human genome.
The center is a place Dr. Ramin Homayouni knows well. Homayouni heads the university’s bioinformatics program and is a co-founder of Computable Genomix, a Memphis Bioworks incubation company that helps scientists make sense of genetic data. Homayouni’s work is one of the many planks that undergird the growing field of personalized medicine, or tailoring therapies around individual genetic mutations that cause illnesses or adverse reactions to drugs.
The field has been burgeoning for the past three decades, but it has gained particular momentum since the human genome was sequenced in 2003. The genome is known as the blueprint for human life. It contains 3 billion DNA subunits, or base pairs.
“Some people have said that personalized medicine is just an extension of current medical practice,” Homayouni says. “It’s just more precise.”
Instead of expecting a certain drug to work on every patient, doctors — albeit slowly — are moving from traditional methods to treating patients on the cellular and molecular levels. The biochemistry involved can range from the relatively simple to the highly complex.
“The best example is sickle cell anemia,” Homayouni explains. “A single [genetic] mutation can cause sickle cell. But what we’re finding now with a lot of modern diseases is it’s a combination of genes, and a mutation isn’t a sledgehammer like it is with sickle cell. When you put a bunch of genes together, then you have Alzheimer’s disease, for example.”
Alzheimer’s, he says, is a multigenic condition: multiple things happening to multiple genes. “The gene really defines what protein is being expressed, and if you get a faulty protein, or mutation, then the problem appears.”
The trick either is to eliminate the problem before it manifests itself or figure out how best to treat it once it does. As Homayouni asks, “Can we use genetic information to better fine-tune the drug?”
The answer, of course, is yes. Since that first decoding of the genome, which took 13 years, $3.8 billion and involved regulatory behemoths such as the U.S. Department of Energy and the National Institutes of Health (NIH), technology has progressed to the point where a person’s genetic sequence can be mapped in a single day for less than $3,000. Such rapid advancements are opening a realm of possibility that didn’t exist before.
“Imagine there are 12 million known mutations that we’ve catalogued so far in the human genome, and those are all opportunities, whether their effect is large or small,” says Brad Silver, CEO of Computable Genomix. “Then, to think that there are more than 12,000 known diseases, and almost 12,000 drugs, you start to get a feel for the immense complexity of making these observations.”
After a year of selling the company’s software, GeneIndexer, to institutions such as the NIH and St. Jude Children’s Research Hospital, Computable Genomix executives decided their best strategy would be identifying gene mutations that predict predispositions to diseases or adverse reactions to drugs. Or, by extension, learning how to minimize side effects based on a person’s genes. The potential of such predictions lies largely in making sure patients receive the correct treatment the first time around. Finding influential biomarkers is central to this idea.
Genome Explorations Inc., founded in 2001 by Dr. Divyen Patel, uses microarray technology, genotyping, and miRNA interactions to identify useful genes and corresponding proteins.
“Our ambition is, in essence, molecular assessment for individuals,” he says.
Microarrays allow scientists to zero in on the genes that differentiate from normal tissues to form diseased ones. Once a biomarker is identified, it’s possible to hinder any rogue behavior on the molecular level.
Genotyping, on the other hand, determines inherited traits, or polymorphisms, that make a person more or less susceptible to disease. It’s only a matter of time before such testing is available on a wider scale.
Says Jan Bouten, a partner at the Memphis Bioworks Foundation’s subsidiary Innova: “A lot of attention in the media might make people believe [personalized medicine] is something new, but the current market is driven by diagnostic tests that help providers select the most effective drug for a patient. This can either be a choice between different alternatives treating the same indication, or a yes/no decision when there’s only a single drug available for treatment.”
Bouten estimates diagnostic tests netted $10 billion in 2010. He expects them to reach $20 billion by 2014.
“Today, many thousands of patients have been getting genetic tests, and through this have received the benefits of improved care,” says Dr. Felix Frueh, vice president of personalized medicine for Medco, the parent company of Accredo Health Group Inc. One thing Frueh and his colleagues have been working toward is finding ways to make personalized medicine more widely accepted by clinicians.
“What we’re struggling with is bringing this technology to market,” he says.
Even so, the pharmacy benefits provider has more than 300 clients offering genetic testing and millions of patients with access to it. Affordability will be critical in helping push personalized medicine into the mainstream, he says, but right now not all the pieces of this broad field have been connected.
“Multiple things need to come together in order to make this successful,” he says.
Meanwhile, Austin B. Byrd, senior vice president of Smith & Nephew’s InVentures Program, points to the company’s Visionaire line as something that’s helping personalized medicine along. The product allows artificial knees to be matched to each patient’s anatomy, reducing surgery time and increasing long-term success.
“Our company, over the last three or four years, has invested a lot of time and energy in creating patient-specific products,” Byrd says, “in particular, cutting instruments or cutting blocks that enable knee surgeries to be pre-planned and customized for patients one at a time.”
These templates are anatomically correct — again, not the traditional one-size-fits-all approach — based on a patient’s MRI scans and X-rays. “The [bone] dimensions are infinitely variable [from patient to patient],” he says.
While he declined to say how much surgery with Visionaire costs, he did stress that such an advance should be viewed less as an expense and more as an investment.
Dr. Ronald Morton, chief medical officer of Memphis-based GTx, says costs will go down as more advancements are made and technology becomes more accessible.
“I think that down the road, as we further refine our ability to predict the pathology of disease, we will further understand how to treat it,” he says.
As far as he is concerned, genetic testing will become as prevalent as blood work in the average medical practice.
“That’s going to dictate how you’re treated,” Morton says. “That was something that was just hypothetical during my training and now it’s very real.”
If any area of personalized medicine is more fully developed than others, it’s oncology. The discipline has a long history of classifying subtypes and stages of tumors. In blood cancers alone, 38 types of leukemia and 51 types of lymphoma have been identified, and survival rates for many subtypes of blood cancer have improved drastically in recent years.
“It’s taking the individual specifics into a new era, making our cancer management more robust because we have a greater understanding of the individual cancer traits. The more we find out about how different cancers act in an individual, the better we can treat that patient for their specific disease,” says Dr. Sylvia Richey, a hematology oncology specialist at The West Clinic.
Analyzing individual subtleties has proven that genetic variations can’t be ignored.
“Now we know all breast cancer is not the same, all lung cancer is not the same, all colon cancer is not the same,” she says. “We’ve completely changed the way we treat breast and colon cancer because of biomarkers, no question.”
Richey divides genetic markers into four basic categories: detection markers that aid in cancer identification, diagnostic markers that signal the presence of a cancer or its risk, prognostic markers that relay the long-term outcome of a cancer regardless of therapy, and predictive markers that act as targets for drug development.
She looks to advances in breast cancer because it is now possible to obtain genetic profiles for different subgroups of patients, and drugs have already been developed around certain biomarkers. For example, about 20 percent to 30 percent of breast cancer patients over-express the marker HER-2, a protein on a cell’s surface that helps cancer grow. The new drug blocks that mechanism, giving these patients an improved chance of survival.
“We’re also finding a lot of women with earlier-stage breast cancers, and if they’re at a low risk of recurrence, they don’t even necessarily need chemotherapy. Saving somebody from the toxicity of chemo, that’s huge,” says Richey.
Anything specific is expensive, however, and that’s one of the major issues in personalized medicine. By knowing more about an individual cancer, ultimately, money can be saved. But for now these therapies and tests can be costly upfront; not everyone can drop $3,000 on genetic sequencing, let alone $500 for a spot check of their biomarkers. The other hurdle doctors are trying to overcome is not having widespread access to testing.
The West Clinic champions clinical trials and studies designed to evaluate new cancer prevention and treatment options. It also helps other oncology practices participate in clinical trials through ACORN, the national Accelerated Community Oncology Research Network. The clinic itself is participating in 35 separate trials. That compares to the more than 400 cancer-related clinical trials happening throughout the U.S.
“In streamlining therapy for individuals overall, you wind up being much more cost-effective than trying multiple things, not knowing what’s going to work and what isn’t,” Richey says. “I think the regulatory and financial systems that are ultimately going to support [personalized medicine] are not really in place yet; the technology has sort of preceded the infrastructure.”
Although personalized medicine is still in its infancy, support systems are in place. FedEx is one of them.
“As Memphis is America’s Aerotropolis, I would argue that there is no better place in the United States for a company that trades in high-value goods to locate for distribution purposes,” says Richard Smith, managing director of Life Sciences and Specialty Services for FedEx.
This kind of access is significant for companies with “mission-critical” goods such as blood or tissue samples, perishable drugs, or surgical equipment.
“Having the world’s largest all-cargo airline puts us in a unique position in terms of being able to meet these needs,” Smith says.
The company offers specialized packaging and containment for any temperature range, from deep-frozen samples to controlled room temperatures. It also provides special handling services like FedEx Priority Alert, which monitors items throughout a shipment cycle.
FedEx’s SenseAware technology — a sensor-based system with almost-real-time awareness of a package’s GPS location, integrity, and temperature — issues an alert if any of these parameters are compromised. The information such services provide also can be crucial to regulatory agencies by generating compliance reports. Yet another service, FedEx Custom Critical, offers temperature-controlled trucks or specialty aircraft chartering for life-science businesses.
“When samples arrive viable and intact, medical research can advance more rapidly,” Smith says. “Otherwise samples have to be redrawn, which causes delays and increases costs.”
And perhaps someday genetic testing and shipping will be even less complicated and more ground-level than they are now.
“I would love to be able to say that in the future we should be able to have a chip or data set that we could walk around with in our pockets and take to our clinician or pharmacist,” Patel says. “The pharmacist would then have a data reader that allowed them to determine exactly the drug that will work for a person’s particular ailment, whereas it won’t work for 2,000 others.”
The possibilities are as vast as the human genome.