Pictures of the Future    Spring 2007

The Right Mix

A vision of a radically different healthcare future is transforming Siemens Medical Solutions (Med). That vision, which is based on linking the data that comes from lab tests—in vitro diagnostics—with in vivo data from medical imaging, took a giant step toward realization on January 1, 2007. On that date, Diagnostic Products Corporation (DPC), headquartered in Los Angeles, California, joined with Bayer Diagnostics, headquartered in Tarrytown, New York, to form Siemens Medical Solutions Diagnostics. The new unit—a subsidiary of Siemens Medical Solutions USA—employs about 8,000 people, approximately 1,000 of whom are involved in R&D.

Thanks to the addition of this new unit, Siemens Med has become the world’s second largest immunodiagnostics company. With a total of 41,000 people worldwide and sales of 8.23 bill. € in 2006, Med is one of the major players in the worldwide healthcare market. With over 2,500 employees (440 in R&D) and $481 million in 2005 sales, DPC is known for its IMMULITE series of analyzers, wide range of immunoassays, and spectrum of allergy panels. The company includes an assay R&D center in Los Angeles and a systems and software R&D center in Flanders, New Jersey.

Bayer Diagnostics, on the other hand, which had sales in 2005 of 1.4 bill. €, adds some 5,400 employees (more than 600 in R&D) to Siemens, as well as a number of R&D centers, including instrument and reagent development in Tarrytown, New York; Molecular R&D in Berkeley, California; basic research in cancer prognostic biomarkers in Leverkusen, Germany; and oncology testing development in Walpole, Massachusetts. The company offers a wide range of lab automation systems, including its ADVIA families of clinical chemistry and immunoassay systems, as well as hematology, urinalysis, blood gas, diabetes, and molecular testing systems for hospital and dedicated laboratories and physicians’ offices.

Valued at a total of 5.7 bill.&nsp;€, the acquisitions have turned Siemens into a major player in the $32 billion in vitro diagnostics (IVD) market (see In Vivo Diagnostics). "Siemens Medical Solutions Diagnostics competes in about two-thirds of that market," says Chief Executive Officer Tony Bihl. "The merger creates synergies that will allow us to be much faster than our competitors in meeting customer needs. It also coincides with the growing need for conventional and genetic testing, which is driven by an aging population and steadily increasing demand for improved healthcare in developing countries."

Healthy Synergies. To understand what the new diagnostics subsidiary means for Med, consider this: Seventy percent of all medical diagnoses are based on the results of lab tests. Lab tests play a crucial role in determining whether imaging tests, which are much more costly, should be ordered or not. But the connection between in vitro (lab) tests and in vivo (imaging) goes well beyond economics. Tomorrow’s lab tests will move increasingly to a molecular level of analysis. If indications of cancer, for instance, are detected in an initial test, more detailed lab tests could identify the cancer cells’ genetic qualities, thus indicating the best medication for controlling it. Imaging would then be ordered to precisely track the tumor’s response over time. (see Knowledge-Based IT). "I think there’s great potential for linking in vitro and in vivo information on patients," says David Okrongly, PhD, who heads the Diagnostics unit’s new Molecular Business. "This will drive workflow on each patient around a combination of laboratory and in vivo imaging results that will help to move patients through the healthcare system with increasing efficiency."

As in vitro and in vivo diagnostics come closer together, a third element—knowledge-based information technology—will become the key to new applications in molecular medicine (see Knowledge-Based IT). For instance, diagnostic medicine is already benefiting from a growing population of computer-aided diagnostic in vivo image screening systems—systems that can sift through thousands of lung or intestinal CT or MR slices in minutes and draw a radiologist’s attention to the one image that may indicate the presence of a cancerous node or polyp. "What all these systems have in common is the need for pattern-matching algorithms and data integration," says Lance Ladic, PhD, strategic development manager at SCR. "That will be all the more so as we integrate biomarker pattern signatures and genetic information into the larger clinical picture."

Molecular Future. Considering the breadth of activities at Siemens Medical Solutions Diagnostics, it’s interesting that its molecular business segment, which accounts for just a few percentage points in sales, happens to be where about 20 % of its R&D employees have landed. But although gene analysis and molecular diagnostics represent a mere $1.5 billion market within the vast IVD spectrum, they clearly represent one of the most exciting growth opportunities in the entire field. "Want to know where the future is?" asks Okrongly, "Genomics. Advances in gene analysis will give us the ability to identify each person’s predispositions to disease; and advances in molecular diagnostics will give us the tools with which to identify the presence of disease and decide which medications a patient will respond to."

The Diagnostics unit’s Molecular Business segment is divided into two major areas. The first, infectious disease testing, enjoys a five to six percent annual growth rate and is currently the biggest part of the molecular market. Here, the Diagnostics unit focuses on monitoring major infectious diseases, such as human immunodeficiency virus (HIV, see image right) and the hepatitis B and C viruses (HBV and HCV). In this area, exciting monitoring systems, such as the Versant 440, have recently been released in Europe and are in the approval process in the U.S. About the size of a professional desktop copier and designed to process dozens of samples simultaneously, the Versant 440 uses a technique called branched DNA (bDNA)—so called because chemical branches attach to the sample, thus allowing probes (think of ornaments on a Christmas tree) to fasten themselves in enormous numbers to the original nucleic acid target. The result: amplification of the signal from the viral RNA or DNA with an unparalleled level of accuracy and automation.

Of particular interest for large laboratories is the unit’s new Phoenix technology. The Phoenix system is designed to process two separate targets of up to 96 samples simultaneously in about three hours. Currently in development and expected to enter the market in 2008, Phoenix will not only offer industry-leading automation, sensitivity and speed, but is also designed to allow customers to run assays they themselves develop. As with bDNA, Phoenix isolates viral RNA and DNA from a serum sample using chemicals that open the target cells. "But instead of amplifying the target’s signal, Phoenix uses an established process called quantitative real-time polymerase chain reaction to amplify either the RNA or DNA target," says Dr. Norbert Piel, Vice President for Global Molecular R&D at Siemens Medical Solutions Diagnostics. For RNA targets, it does so by ‘transcribing’ a section of viral RNA into so-called complementary DNA (cDNA). "Here, the DNA is exposed to an enzyme that makes millions of copies, and a probe that includes a fluorescent dye is added," explains Piel. "Then, if you excite the dye with light, you get a fluorescent signal that can tell you the concentration of the virus in the blood."

The new level of flexibility created by Phoenix is particularly important for the Diagnostics unit itself because, according to Piel, "the same technology that will be used for the detection of infectious diseases can also be applied in oncology and cardiology, as well as to emergency conditions, such as septic shock, and hematological conditions such as leukemia. In short, Phoenix will open up entirely new lines of business."

Emerging Markets. And that takes us to the second, but most exciting segment of the Diagnostics unit’s molecular business, which is the emerging oncology and cardiovascular testing market. "This is a market that represents only about $400 million worldwide today. But it’s growing at 20 to 25 % per year," says Bihl. "As more and more new disease markers are identified, demand for reliable tests to detect them is growing. And as those tests come to market, they create tremendous growth." Indeed, the Diagnostics unit has already discovered a handful of biomarkers unique to breast cancer, and has patented associated tests that are planned to run on the Phoenix platform. "What we propose to do," says Okrongly, "is to take a small tissue sample, process it on a molecular instrument like Phoenix, and provide an assessment of low, medium, or high risk for a particular tumor."

"The vision is clear," sums up Bihl. "As we move toward improved understanding of the human genome, we will be able to identify people with a predisposition to certain diseases. Regular monitoring of those potential conditions will follow. Then, if a condition does arise, it can be quickly identified through specialized in vitro and in vivo tests and associated, targeted therapeutics. The entire process will be integrated and brought together in a workflow-optimized electronic patient record. What we’re talking about—if we can do it cost-effectively—would be revolutionary."
                                                                                                              Arthur F. Pease