Pictures of the Future      Fall 2008

Patterns in the Puzzle

In northeastern Germany, medical researchers are examining thousands of subjects in one of the world’s most comprehensive health surveys. Together with Siemens, they hope to gain insight into the origin and treat­ment of the most common illnesses.

Susan is being examined in a Siemens Magnetom Avanto magnetic resonance imaging (MRI) scanner at the hospital of the University of Greifs­wald, in Germany. Within minutes, the scanner has divided her entire body into thousands of virtual millimeter-thin slices, producing a huge volume of data. Beforehand, she had an ECG scan, her retinas were examined, and she submitted blood and urine samples that were used for a number of laboratory tests. Her DNA was examined with a gene chip, and the condition of her teeth was recorded. Susan, who is 40, will also spend a night under observation, in the hospital’s sleep laboratory. In addition, during a meeting with university staff, she reported her dietary habits, whether she smokes, how much alcohol she drinks, how often she’s been ill, and what medications she is taking.

This is the third examination of her state of health in the last 11 years, and this time the exam encompasses almost everything. At present, Susan feels fine.

Like more than 4,000 other residents of the Germany state of Mecklenburg-West Pomerania, Susan is a test subject in the Study of Health in Pomerania (SHIP), one of the largest studies anywhere of the relationships between illness, living conditions and genetic predispositions. Are there specific circumstances in life that make women more susceptible to breast cancer? Is there a genetic predisposition to diseases of the liver and kidneys? Why are gallstones significantly more common in Mecklenburg-West Pomerania than in the world as a whole, with the exception of one group of indigenous people in Chile? Do poor teeth exert an influence on growth during childhood—or on the risk of a heart attack during adulthood? These are the kinds of questions SHIP wants to answer. The objective is to lay the foundations for new treatment strategies. "Medical treatments have made considerable progress in recent years, but at the cost of becoming largely standardized. The effects of multiple illnesses are frequently not taken into account adequately—and the same goes for the specific characteristics of patients," says Prof. Wolfgang Hoff­mann, director of the Institute for Community Medicine at the University of Greifs­wald. The standard guidelines often enough reach their limits, particularly in the case of older persons with multiple illnesses. "We need innovative research that quickly and efficiently shows how best to treat such persons in accordance with their specific conditions," says Hoffmann. This new, individualized vision of medicine confronts physicians with major challenges, since it does not rely on generally-applicable norms. On the contrary, in personalized medicine, decisions are based on complex combinations of diagnostic data. The job of the Greifswald project is to filter out these combinations for each patient.

Genetics, Imaging and Metabolism. In March 2008, the Community Medicine research association, which includes a number of departments of the medical faculty at the University of Greifswald, launched the third stage of examinations. It all began in 1997. At that time, the researchers randomly selected 4,310 test subjects between 20 and 79 years of age as a representative cross section of the approximately 200,000 people living in the communities of Stralsund, Greifswald, and Anklam. More than 3,300 of them are still available for examinations today. When the current series of exams has come to an end, the researchers will have three sets of records for each person: genetic, imaging, and metabolic. The latter encompasses a large variety of metabolites that are dependent on enzyme activity, metabolic conversion rates, nutrition and the ingestion of medications, among other factors. When all of this data is compared, the result amounts to over 150 million variables for each person.

In the spring of 2008, project researchers began another study called SHIP Trend, for which approximately 5,000 representative test subjects are being examined. With this new series of exams, the research group intends to ensure that the study remains up to date. "The cross-section of the population has changed in the last ten years. Young people who are 20 years old today have a different diet and lifestyle from their counterparts of ten years ago," says Dr. Matthias Nauck, director of the Institute for Clinical Chemistry and Laboratory Medicine at the University of Greifswald.

Customized Therapy. Siemens has participating in SHIP since the third series of examinations. "In the future, it will be vital to provide physicians with decision-making tools that are based on a large amount of medical data," says Dr. Jürgen Simon, director of Healthcare Strategy, who is coordinating the project for Siemens Healthcare. This is the only way to adapt therapies much more closely to the specific characteristics of the patient. "Through SHIP, we can find out how an individual’s metabolism reacts to medications, for example," says Nauck.

Typically, patients receive standardized doses of medications—a strategy that fails to take individual characteristics into account. Often, for instance, a medication has no effect, because the patient lacks the enzyme needed to metabolize it. If this were known, the doctor could choose a different medication.

Together with the University of Greifswald and other clinical partners, Siemens is therefore researching algorithms that identify relationships in millions of pieces of data. For instance, Siemens researchers in Malvern, Pennsylvania, are combing medical data for patterns based on medical hypotheses and statistical discrepancies. The SHIP study is the most comprehensive of these research projects, because it is the only one that also includes detailed data from medical imaging. Thanks to the MRI equipment provided by Siemens, researchers can, for instance, record even the smallest changes in vascular structures. "This means that, for the first time, our researchers can identify a number of illnesses at a very early stage," says Dr. Henry Völzke, director of the SHIP study. Researchers can also analyze whether common exams such as those for breast and cervical cancer are sufficient, or whether detection rates can be significantly improved by adding an MRI scan.

The results of the first two series of studies are about to be published and will have a broad impact. "We’re doing research on illnesses that are relatively common, like heart attacks and strokes," says Nauck. Epidemiology, the study of the causes, consequences and spread of illnesses in populations, is acquiring increasing importance because the population of the western industrial nations is aging rapidly and therefore becoming increasingly illness-prone.

Many of these general demographic processes are at work in the region selected for the SHIP study. In the economically underdeveloped region around Greifswald and Stralsund, for instance, the average age of the population has risen dramatically in only two decades because of migration and falling birth rates. Beyond its healthcare implications for the region, the SHIP study is there­fore also investigating a general problem faced by industrialized countries.

Blueprint for Early Diagnosis. The SHIP study will lead to changes not only in therapies but also in preventive care. For the most common illnesses, such as certain types of cancer, high blood pressure and diabetes, researchers want to create information clusters with a manageable number of relevant parameters. Then, instead of comparing millions of pieces of data for each patient, it will suffice to review an estimated 50 to 100.

"If we can clearly identify certain predispositions and causes of breast cancer, for instance, women who are in high-risk groups can take advantage of more thorough monitoring," says Hoffmann. The patterns for many other common illnesses are likewise being identified by sifting through billions of pieces of data.

SHIP’s first results are expected in two or three years. At that point, physicians may start to have the information tools they need to determine the right therapies faster and more effectively—thus setting the stage for lowering public health expenditures.
                                                                                                              Katrin Nikolaus