The Promise of Precision Medicine

By Catherine
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By Catherine Bolgar

Medicine is moving away from a one-size-fits-all model.

Precision medicine, sometimes called personalized medicine, holds so much promise that the U.S., China, and France have announced massive investments in this field over the past year.

“Precision medicine, we contend, has the potential to result in systemic savings,” says Christopher J. Wells, communications director at the Personalized Medicine Coalition (PMC), a Washington nonprofit organization representing scientists, patients, providers and insurers. “Now, medicine is by trial and error. You try one treatment and if doesn’t work, you try another.

The power of precision medicine is that if you get it right the first time, everybody benefits.”

IV solution in a patient hand and IVS machinePrecision medicine has made the biggest strides in oncology, where time is of the essence and chemotherapy drugs have strong side effects. For example, some breast cancers may be resistant to treatments such as trastuzumab. But that chemotherapy drug is very effective for breast cancers caused by the HER2 mutation.

No two cancers are the same,” says Susanne Haga, associate professor of medicine at Duke University in Durham, N.C. “They may be the same with respect to their tissue origin. But each person has a unique set of mutations that give rise to uncontrollable cell-division cycle, or cancer. With that in mind, each person would have some commonalities with other patients but also some unique qualities.”

However, the majority of patients still don’t receive personalized care, notes Mr. Wells. The PMC notes that a previous study has demonstrated chemotherapy use would drop 34% in women with breast cancer if they had a genetic test of their tumor before treatment.

With cystic fibrosis, “we thought it was one disease,” says Euan Ashley, associate professor of medicine at Stanford University in Stanford, California. “But as we dig deeper with genetic sequencing, we find it’s many diseases. If you can subcategorize patients, you can treat a disease much more effectively.”

Dr. Ashley’s specialty, cardiovascular disease, is the leading cause of death globally. “So we tended to do very large population studies, giving the same drug to everyone,” he says. “But if you study closely afterward, you see that a small number of people drive the effect—they get a significant benefit. Many get no benefit. And a few get significant harm.”

Precision medicine is prompting different ways of thinking about populations and individuals. “The answer has to be to measure people in as high a resolution as we can and work out who is responding and why,” he says.

With the cost of developing a prescription drug at about $2.6 billion, pharmaceutical companies have a big interest in seeing that the drugs they make get tested on the right segment of patients. A drug could appear to have no effect, when in fact it’s highly effective but only for a smaller number of patients.

Scientist woman“Drug companies now are building precision medicine into their research-and-development strategies,” says Mr. Wells. Personalized medicines accounted for 28% of novel new drugs approved by the U.S. Food and Drug Administration in 2015, and for 35% of novel new oncology drugs. Novel new drugs go beyond improved formulations or new dosages to deliver truly innovative advances.

Meanwhile, pharmacogenomics looks at how different people metabolize drugs. “There are a number of genes that are particularly active in the liver,” says Dr. Haga of Duke, adding that there are many variations of these genes among people. “We can test whether a patient metabolizes fast or slow and, if necessary, can prescribe a different drug that goes through different pathways so the affected genes aren’t involved.”

This test is valid for life, because one’s genes don’t change. Some institutions are trying to incorporate the information into electronic medical records, so all the different doctors and specialists one might see—as well as pharmacists—would be more knowledgeable, for prescribing drugs.

Because the cost of genetic sequencing has fallen dramatically, to about $1,000 today for a genome from $100 million in 2001, some are asking why everybody doesn’t get tested. It could speed up treatment for cancer patients or could allow for early intervention to arrest development of certain other diseases.

The U.S. National Institutes of Health devoted $25 million to four projects of genetic sequencing in newborns over five years with the goal of diagnosing conditions at the start of life. China just launched a project to do genetic tests on 100,000 newborns over the next five years, to improve treatment strategies and patients’ quality of life.

“The technology is going to continue to improve,” Mr. Wells says. “But already we’re at a point where the scientific advances are incredible.”



Catherine Bolgar is a former managing editor of The Wall Street Journal Europe, now working as a freelance writer and editor with WSJ. Custom Studios in EMEA. For more from Catherine Bolgar, along with other industry experts, join the Future Realities discussion on LinkedIn.

Photos courtesy of iStock

Calling in Sick

By Catherine
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Written by Catherine Bolgar

One day, your phone might detect that you have cancer and alert your doctor. It’s among the new diagnostics being developed to spot health problems faster.

Cancer cells, bacteria and certain non-infectious diseases give off volatile organic compounds which the blood eventually transports to our lungs to be expelled into the atmosphere, explains Hossam Haick, professor at Haifa’s Israel Institute of Technology. He is part of a team developing a handheld device with gold nanoparticle sensors that can detect volatile organic compounds in breath samples.

Each disease has a unique breath print, he says. The team’s sensors can detect 23 diseases, including cancers of the lung, breast, ovaries, head and neck, lung, stomach, kidney and prostate, as well as pulmonary hypertension, tuberculosis, and even Parkinson’s disease and Alzheimer’s disease.

Cancer “exists in humans for five to 15 years before we start to see its effects,” Dr. Haick says.

If we want to detect cancer early, we have to do it when people feel good. That’s why we want to detect it by exhaling. It’s painless, so people will be willing to do it.”

Dr. Haick started with lung cancer in 2007. “If you detect lung cancer early, the survival rate is 70%,” he says. “If the cancer is at advanced stages, the survival rate is 9%-15%.”

Today, X-rays and computerized tomography scans detect tumors, but only a biopsy (i.e surgery) can determine if they are malignant—and 96% are not, Dr. Haick says. The sensors can distinguish between benign and malignant cancer, thus reducing the need for biopsies.
Dr. Haick hopes to produce a handheld device for around $800, affordable for clinical doctors. He’s also working with a European consortium to integrate the device into smart phones. “When we speak on the phone we exhale a lot of breath, and we can use that to monitor disease,” Dr. Haick says. The phone would alert the owner’s doctor, who would decide how to manage the results.

Similarly, a team at the Mayo Clinic in Rochester, Minn., is working on a noninvasive screening for several cancers simultaneously, by detecting DNA markers in a blood or stool sample.

While cancer lurks for years, infections can become serious in hours. On TV dramas, doctors examine samples under microscopes and find the solution in minutes. In reality, samples are sent to a lab where they are cultured—which can involve growing bacteria or viruses for six to 24 hours—or undergo polymerase chain reaction (PCR), a complex process that takes about six hours.

Emergency room patients with an infection can’t wait that long, so doctors immediately administer a range of antibiotics. But overuse of antibiotics has led to resistance, and in any case the drugs don’t work on viruses.

Jeong-Yeol Yoon, professor of agricultural and biosystems engineering and biomedical engineering at the University of Arizona in Tucson, has found “a whole new way of doing PCR” utilizing interfacial effects, that’s cheaper, easier and much faster—the whole process takes less than 10 minutes.

Normally, PCR identifies the pathogen by looking at the DNA in the sample. The DNA is first extracted and purified, which can take three or four hours. The amount of DNA is tiny, so it’s amplified by an enzyme and heated and cooled repeatedly. Each cycle doubles the DNA, so “if you repeat the cycle 30 times you’ll have about a million copies, theoretically,” Dr. Yoon explains.

Dr. Yoon’s team instead uses an approach called droplet-on-thermocouple silhouette real-time polymerase chain reaction (DOTS qPCR). The method can identify infection after just three to eight cycles. And the process uses water droplets, which separate contaminants, eliminating the time-consuming step of purifying the sample. The entire process, from sample to answer, can take just five to 10 minutes.

Regular PCR requires expensive equipment and trained lab personnel. But Dr. Yoon hopes to make a fully automated DOTS qPCR device for under $1,000, so it can be used in poorer countries where diseases such as Ebola, MERS, SARS and bird flu require speedy quarantines to prevent epidemics.

Genetics play a key part in other new early diagnostics methods. For example, Stanford University researchers have identified a pattern of gene activity that could lead to a quick blood test for sepsis, which kills 750,000 people annually in the U.S. alone. Meanwhile, a University of Utah team has found DNA anomalies that predict how an ovarian-cancer patient will respond to platinum-based chemotherapy. And scientists at the University of Toronto are using next-generation sequencing to match a sample against a database of thousands of bacteria and viruses, eliminating the need to test one by one.


Catherine Bolgar is a former managing editor of The Wall Street Journal Europe. For more from Catherine Bolgar, contributors from the Economist Intelligence Unit along with industry experts, join the Future Realities discussion.

Photos courtesy of iStock

The Secrets of Protein

By Catherine
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Written by Catherine Bolgar

If genes are our bodies’ architectural plans, then proteins are the internal devices that make decisions, send signals and ensure that our metabolism operates properly. The study of proteins in our cells and tissue is known as proteomics, a term coined in 1994 by Marc Wilkins, now professor of systems biology at the University of New South Wales in Sydney.

Proteomics began with a lofty goal: to “figure out what all the proteins are inside cells,” Dr. Wilkins recalls. Two years ago “we could say we had found all the proteins one would expect to find inside a bacteria cell or yeast cell.” Last year, two research groups declared that they had found 85%-90% of the proteins inside the human cell. Another expects to publish a list of all human proteins later this year—a milestone as important as sequencing the human genome.

Proteins are responsible for the basic aspects of metabolism: they convert food into amino acids, sugar or other states that the body can use. Proteins are also the functional molecules inside systems. Like antennae, they sense what’s happening outside the cell, and transmit signals inside the body.

Some proteins are decision makers,” Dr. Wilkins explains. “There are not that many of them in a cell. But there are lots of copies of ‘worker’ proteins. It’s like corporate organization, with executives and workers.”

Scientists have long understood what ‘worker’ proteins do, but for years, “it was hard to get good data on proteins that pass information to each other (known as signal transduction) and transcription factors that decide what proteins are made inside the cell, which have a big influence on what cells are doing. They’re important for the specialization that happens in all cells; regulating a kidney cell is very different from a brain cell,” Dr. Wilkins says.

iStock_000014137699_SmallSignal transduction proteins are the “middle-men” that connect cell receptors on the outside of cells to proteins in the cell nucleus. They sense and integrate information, and decide which proteins need to be made, Dr. Wilkins explains. For example, human growth hormone, or erythropoietin, produced by the kidney, is a protein that tells bone marrow to make more red blood cells.

Recent advances in mass spectrometry, coupled with faster computers, now allow scientists to analyze all the rare proteins inside the cell.

There are 20,000 proteins inside the human body,” Dr. Wilkins points out. “We have good information on what 11,000 to 12,000 of the proteins do. But for a third to half of the human proteins, we have very little idea of what the function is.”

A better understanding of these lesser-known proteins would aid research into many health issues. In particular, proteomics could tell us which signaling and decision-making proteins are associated with cancer, and help in its early detection, by discovering protein biomarkers. We know, for example, that some breast cancer cells make too much HER2 protein, which can then be targeted by biopharmaceutical drugs that include monoclonal antibodies (themselves proteins).

But the process is far from straightforward. “The challenge with biopharmaceuticals is you don’t synthesize them chemically,” Dr. Wilkins says; they’re made by other cells such as bacteria, yeast or mammalian cells. “When you use cells to make proteins… the cell is also making all its usual other proteins. So when you go to purify the drug, the protein of interest is there but with thousands of others,” he says. “Also, you have to make sure all the decorations on the protein are accurate for it to be effective …[or] it can set off a patient’s immune system and have disastrous results.” Proteomics and better instrumentation can resolve these quality-control issues.

Proteomics’ potential extends far beyond a cure for cancer. It’s “a general technology platform, so it can be applied to the analysis of every living thing in biological sciences,” Dr. Wilkins says. Viruses, bacteria, yeasts in bread, wine or beer, enzymes in laundry soap, animal and human food supplements, and more, all involve proteins.

“We are just now starting to identify all the proteins in cells,” Dr. Wilkins says, “and so must now tackle the next challenge: to understand how these interact with each other to form all the hundreds of molecular machines inside the cell, and how these function in the normal cell and change in disease.”


Catherine Bolgar is a former managing editor of The Wall Street Journal Europe. For more from Catherine Bolgar, contributors from the Economist Intelligence Unit along with industry experts, join the Future Realities discussion.

Photos courtesy of iStock