“We live in absolutely extraordinary times,” says Antony Rosen, M.D., Vice Dean for Research and Director of the Division of Rheumatology. What makes our time particularly remarkable, he adds, is our ability to analyze huge amounts of data, to recognize patterns, and to absorb new information very quickly. “That’s a big change, and a powerful force.”
So is our connectivity – humans with humans, and devices with devices. “This enormous web of interconnected things is changing the way that we generate, capture, aggregate, analyze, and deploy data, and it’s changing the way we’re making decisions.” There has also been what Rosen calls a revolution in measurement. “Even 10 years ago, to measure and analyze tissue, blood, cells, DNA, RNA, protein, lipids, or metabolites – that required large amounts of material, and was very labor-intensive.”
When scientists look at something and study its chemical makeup, the object of study is called an “analyte.” And not too long ago, scientists could only investigate one or a few analytes at once. No more: Now they can measure almost any analyte – and not just a paltry one or two, but tens of thousands all at once – and sample sizes are tiny; Rosen calls them “vanishingly small,” in fact.
“That remains our calling, to bring science to the caring practice of individuals with disease, for prevention, and monitoring, and therapy, and cure. The tools of the modern era are greatly affecting our ability to accomplish those goals, and that’s what we are calling Precision Medicine.”
Now hang on just a darn minute, you may be thinking: This is the Center for Innovative Medicine, where the patient is the top priority, and here we are talking about the super powers of machines in a way that might even sound creepy if you’re the kind of person who prefers to keep technology at arm’s distance. What does this fancy science have to do with people?
Everything.
This is why Rosen is so excited. For starters: “Instead of needing large amounts of human tissue to make diagnoses, we can get away with tiny amounts of tissue. Instead of needing to cut into someone do a deep biopsy, we can sometimes access the same materials in the blood.” This is called a “liquid biopsy,” and for anyone who has endured a painful biopsy or spinal tap, the idea of getting information from blood or maybe even urine sounds like a big improvement.
So we’re looking at a revolution in precision diagnosis. Even better: we’re also looking at a new era of precision treatment. David Hellmann, M.D., founder of the CIM, “likes to say that when Johns Hopkins began, it unified the brain and the heart of medicine,” says Rosen. “That remains our calling, to bring science to the caring practice of individuals with disease, for prevention, and monitoring, and therapy, and cure. The tools of the modern era are greatly affecting our ability to accomplish those goals, and that’s what we are calling Precision Medicine.”
It’s the anti-cookie cutter approach.
Rosen, who has been part of the CIM since it began, has been a leading advocate for precision medicine; he pioneered it in Rheumatology, with the goal of expanding it – and it’s happening. With the partnership of Scott Zeger, Ph.D., professor of biostatics and medicine, and with funding from Johns Hopkins University President Ron Daniels, he has developed a new program called Hopkins InHealth, with the goal of delivering “medicine that’s precisely for you.” Also, with funding from Hopkins Dean and CEO Paul Rothman, M.D., and Johns Hopkins Hospital President Ron Peterson, Johns Hopkins Medicine is establishing Precision Medicine Centers of Excellence (PMCOEs) throughout the institution. Rosen sent out a call for proposals and was “blown away” by the number of high-quality ones he received. So far, he has identified eight new PMCOEs, with plans to fund another 10 in the near future.
It’s the anti-cookie cutter approach, and for the first time, thanks to new technology, it is possible on a wide scale. Here’s an example: we know that not all prostate cancers are the same – even if the cancers are technically the same stage and grade. At last count, there are, in fact, 27 different varieties of prostate cancer, depending on which particular genes are involved. This doesn’t matter so much if the cancer is caught early and is curable with surgery or radiation. But with metastatic cancer, precision treatment matters a great deal. Some prostate cancer involves the same faulty genes that are involved in breast cancer; other varieties have more in common genetically with colon cancer. It makes sense, then, that to tell a patient, “Here’s your chemo,” as doctors used to do, would be to do that man with prostate cancer a huge disservice. Some men will be helped by the chemotherapy, and some won’t. Now we know why: because they don’t all have precisely the same disease.
To tell a patient, “Here’s your chemo,” as doctors used to do, would be to do that man with prostate cancer a huge disservice. Some men will be helped by the chemotherapy, and some won’t. Now we know why: because they don’t all have precisely the same disease.
This scenario repeats itself throughout medicine. “We know that even though you can aggregate diseases together under one label, many diseases are heterogeneous,” says Rosen. “If you have a group of 100 people with the same disease, they really should be divided into homogeneous subgroups. It’s important to identify these subgroups and understand what the disease mechanisms are that impact them in specific ways.”
Picture, if you will, a box of crayons. In your basic Crayola 64 pack, you might have 10 crayons that could be considered blue. But some of them, like teal and turquoise, are also part of the green family, and cadet blue actually looks pretty gray.
Understanding which shade of blue, or which subtype of disease a patient has, will lead to custom-tailored treatment. This idea, Rosen points out, is not new at Hopkins. “The way that’s been manifested here has been that wise, experienced clinicians who take great care of their patients know intuitively that not all of these patients with certain diseases are alike. They start recognizing subgroups of people who are homogenous based on phenotype – how the disease presents – and trajectory – what it looks like as time goes by.”
Picture, if you will, a box of crayons. In your basic Crayola 64 pack, you might have 10 crayons that could be considered blue. But some of them, like teal and turquoise, are also part of the green family, and cadet blue actually looks pretty gray. Understanding which shade of blue, or which subtype of disease a patient has, will lead to custom-tailored treatment.
At multidisciplinary Centers of Excellence (Hopkins has many of these), clinicians not only recognize these subgroups of patients but study their blood and tissue samples; the patients are also partners in research. “In the context of great, patient-centered medical care, these centers are excellent frameworks for discovering subgroups and the mechanisms that underlie their disease, with the hope of finding targeted treatment,” says Rosen. “We already have many centers, informally organized, but we recognize the opportunity to formalize what we really do well, and provide resources to enable these centers to form a learning health system.”
If these new PMCOEs live up to their promise, they may also offer proactive medicine. “Clearly, as medicine evolves over the next decade, not only are there going to be people who have a disease now, but we will have a better understanding of who’s at risk to get it, who’s already in the process of getting the disease – and intervening, perhaps before the disease causes damage. The way to do that is to follow patients in partnership, in a learning health system, to collect their data, to follow their trajectories over time, find the tools that will help us predict the course of their illness, and intervene appropriately.”
