CEO SUMMARY: Evidence is accumulating that tissue banking may be where the “rubber meets the road;” where pharma money funds technology enhancements that directly benefit the profession of pathology. Without question, the need by pharma, biotech, and genomic companies to access, analyze and understand the tissue of targeted subpopulations is creating an opportunity for savvy pathologists to make money by aiding in the identification and collection of such tissue specimens.
TISSUE BANKING MIGHT BE RIGHTLY called the new frontier of the anatomic pathology profession. It sits at the convergence point for a variety of medical disciplines, of which genomics and proteomics are only the most publicized.
For local anatomic pathology group practices, tissue banking is now beginning to offer specific, but limited, revenue opportunities. However, during the next decade, tissue banking has the potential to stimulate immense changes to the profession of anatomic pathology.
One pioneering company in the emerging field of tissue banking is
TissueInformatics.Inc, based in Pittsburgh, Pennsylvania. Founded in 1997, it has attracted investment capital from such credible corporations as Motorola. Its mission is comprehensive.
Five Basic Functions
“Think of us as a company organized around five basic functions,” stated Peter C. Johnson, M.D., Chairman and CEO of TissueInformatics. “One, we acquire tissue. Two, we develop proprietary imaging technologies. Three, we develop proprietary software to analyze tissue. Four, we build databases from these analyses, and five, we mine that data and can do so with respect to associated genomic and clinical data.”
The short term business priority is for TissueInformatics to acquire relevant tissue specimens needed to build its tissue bank. Here is where the business interests of TissueInformatics, hospitals, and local pathology group practices intersect. But more on that later.
In the long term, the demand by customers of tissue banking services will stimulate development of proprietary technologies for tissue imaging and analysis. As a result, anatomic pathologists will be armed with new tools for diagnosing disease. As that happens, pathologists will enjoy increased value and utility to referring clinicians.
This change curve in pathology will parallel that of radiology. Two decades ago, the radiologist’s primary role was to read simple X-rays. But in a steady, evolutionary process linked to technologies such as CAT, MRI, and PET, radiologists now enjoy a more complex, interactive relationship with referring clinicians that involves patient diagnosis and ongoing patient monitoring.
Such a “brave new world” for pathology still awaits the future. But basic tissue banking functions are currently expanding in the marketplace. As Dr. Johnson notes, “We are actively working with healthcare institutions to legally and ethically obtain human tissues, which we then microscopically analyze digitally. We use this information to create databases of tissue structure and function.”
Two Business Services
Dr. Johnson points out the current market for tissue banking is divided into two primary business services. One group of organizations banks tissues for human and clinical use; these would include cornea banks, bone banks, and eye banks. The other group of companies primarily wants to acquire tissues: 1) to test for specific gene expression; and/or 2) to use tissues as a platform for biochemical analysis.
TissueInformatics falls into the second group. “We are not a supplier of tissue for therapeutic use,” explained Dr. Johnson. “We are not organized to support human use of the tissues. We won’t transfer a tissue if it’s going to be used for placement in a human.
“Our business is to support pharma, biotech, genomics, and research enterprises,” he continued. “We obtain our tissues fresh, preserve them in an appropriate fashion, then take part of the tissue for our own digital analysis while making the remainder available to the pharmaceutical industry for research purposes only.”
TissueInformatics’ primary customers are pharmaceutical and tissue engineering companies. “These companies want targeted tissue types that may only be available in smaller population areas,” explained Dr. Johnson. “That’s why local hospitals and pathology groups can be contributors to a tissue banking program.”
In its early stages, companies like Pharmagene and LifeSpan are driving this market. Once these companies acquire tissues, they do biochemical assays and extract DNA, RNA, and proteins. This information is sold to pharmaceutical companies to help them in their drug discovery process. It’s an outsourcing type of business arrangement.
“Two things make us different at TissueInformatics,” Dr. Johnson stated. One is our emphasis on anatomic pathology. The other is our comprehensive data sets, with the ability to incorporate a wide range of data on individual tissue specimens.
“First, we look at tissues in the same way as pathologists, when they form an opinion about whether the tissue is normal or abnormal. That’s the key to understanding our proprietary imaging and analysis technologies,” observed Dr. Johnson.
Automate The Analysis
“Second, our software allows researchers to break tissue down into all of its components. It supports the diagnosis by including all of the tissue’s mathematical subcomponents,” he continued. “This also allows us to automate the analysis and quantitate anything that can be made visible.
“This includes any probe-based assessment of tissue, whether its immunohistochemistry, in situ hybridization, metabolic probes and the like. If it can make the tissue appear different, we can quantitate and develop an information reserve from that,” added Dr. Johnson.
“In a literal sense, other companies in this field are grinding up tissues to run biochemical experiments,” he added. “In contrast, anything which can be made visible to the pathologist can be digitalized and archived. We can perpetualize the value of that and put the data in a form that lets us leverage associated genomic or clinical data in a quantitative, correlative way.
“We’re primarily interested in amassing enough tissue information from distinct subpopulations to allow us to determine the degree of variability in tissue structure and function throughout these subpopulations,” observed Dr. Johnson.
“If we can we extract this information at the same time that genetic information is extracted or proteomic information is accessed, that will yield the most value,” he said. “We believe the greatest added-value service in bioinformatics today does not come from expertise exclusively in tissue information, genomics, cellular information, or similar fields. Rather, the greatest added value will come to those companies which build a bridge between these disciplines to create useful knowledge that was previously unavailable.”
The need to accumulate tissue specimens from specific subpopulations offers local hospitals and pathology group practices a strategic role in the tis- sue banking market. “Researchers and pharma companies are interested in looking at subpopulations representative of specific disease states,” Dr. Johnson declared. “For example, one study might look at the lung tissue of men who had smoked for 5, 10, 15, or 20 years. Appropriate subjects must be identified at the level of the local hospital.”
Dr. Johnson says that biotech, pharmaceutical, and genomics industries currently need improved methods to perform a high-throughput analysis of multiple tissue images that have either been stained with antibodies for presence of specific proteins or with in situ hybridizations. The goal is to shorten the time and reduce the cost needed for target identification.
This is why the biotech, pharma, and genomics industries are funding the research and development of new technologies that will benefit the pathology profession. But the immediate and primary use of these technologies lies outside general clinical use.
“Technologies under development and refinement at Tissue Informatics are not targeted at replacing pathologists,” noted Dr. Johnson. “To the contrary, our efforts are to create new tools which make pathologists both more productive and more valuable.
“We’re targeting unique niches, primarily in corporate pathology, where pathologists are faced with the drudgery of looking at thousands of the same kinds of slides over and over,” he added. “For example, we’re building a package for toxicology that automates the analysis of liver tissue. It will enable a pathologist to spot tiny changes without having to review the entire population for quality control in order to find outliers and classify them outside of what is considered to be the normal database.”
How Tissue Informatics was Formed
ACTIVITIES IN TISSUE ENGINEERING led to the creation of TissueInformatics.Inc, based in Pittsburgh, Pennsylvania.
It was founded in 1997 by four individuals: Dan Farkas, Ph.D.; Peter Johnson, M.D.; Michael Becich, M.D., Ph.D.; and Mary Del Brady. Dr. Johnson was a reconstructive plastic surgeon at the University of Pittsburgh Medical Center. He was an organizer of the Pittsburgh Tissue Engineering Initiative and served as its President for two years.
Dr. Johnson left surgical practice in late 1997 and became a full-time employee at TissueInformatics in early 1999. At that time, the company had six employees. It has since grown to 38 employees. During the past four years, TissueInformatics developed five different software analysis packages for tissue analysis, including specific modules for in situ hybridization and high capacity antibody screening.
“All our basic business services are in place,” stated Peter C. Johnson, M.D., Chairman and CEO of TissueInformatics. “We have teams ready to do tissue procurement, tissue imaging, and tissue information management. We are actively generating revenues and ramping up our business services. The company is pursuing additional capital and, on two previous rounds of financing, Motorola Corporation invested funds.
“Motorola was interested in Tissue-Informatics because of its activities in bioinformatics,” noted Dr. Johnson. “It’s developing a biochip system that automates genetic analysis.
“That functionality dovetails with our capacity to automate tissue feature assessment,” added Dr. Johnson. “Both companies want to eventually correlate those two unique data sets. That would produce an entirely new dimension of useful information.”
Similar Technology Curve
Dr. Johnson points out that a similar technology curve has been under development in cytologic analysis. “Imagine the day when Pap smears can be accurately, speedily, and inexpensively screened by automated systems,” he postulated. “When that day arrives, there will be many clinical pathologists who say ‘Hooray! The drudgery of looking at large numbers of specimens each week has been eliminated’.”
Dr. Johnson is obviously excited about the future of pathology, given the technologies and methods he’s observed under development in his company. “To some extent, I think pathologists are currently tethered to the microscope because automated analysis systems are not yet available to them.
Pathologists Interpret Data
“But I think the day is fast approaching when pathologists are worth far more if they serve as ‘meta-pathologists,’ where their time is spent, not just doing pattern discrimination work, but interpreting the data,” offered Dr. Johnson. “They’ll have the capability to aggregate large quantities of clinical and behavioral information and make better projections of patient health on the basis of what’s known about the tissue!”
In Dr. Johnson’s view, the digitalization of images, combined with software tools that can analyze more information than is present in the image alone, will give pathologists new tools for evaluating specimens. “When such data is networked and available across systems, pathologists will be able to make correlations that were impossible in a ‘microscope-only’ type of setting,” said Dr. Johnson. “It will be a direct consequence of the digital revolution.”
Issues Yet To Be Solved
In Dr. Johnson’s view, this pathology utopia is probably ten years from becoming reality. “There are a lot of issues yet to solved,” he said. “Developing the technology to accomplish this is only the first step. Gaining FDA approval for clinical applications will certainly be challenging, as will liability and subpopulation issues. But this is not pie-in-the-sky. There are compelling reasons why both the research and the clinical markets will embrace these types of enhanced pathology services.”
That future will unfold based on trends already under way in today’s marketplace. Whereas a company like TissueInformatics has systems to do proprietary tissue analysis and the database capability to store and study that information, it is local hospitals and pathology group practices which have direct and intimate access to patients, the ultimate source of the tis- sue specimens.
“We have contracts with hospitals that participate in our tissue banking program. Their consent forms cover this kind of procurement,” stated Dr. Johnson. “Based on the types of tissues we need to accumulate, the hospital works with the pathologists and the OR teams to identify and obtain consent from the best sources for such tissue. In many instances, such specimens might ordinarily be discarded.
Information Is Shared
“It’s not expensive for hospitals and local pathology group practices to work with us,” he added. “We support the technicians involved in collecting specimens. There’s also a certain amount of money that can aid internal research processes. But most important for the hospital, we share the information we obtain from the tissue it provided.
“This is a critical part of the relationship between TissueInformatics and contributing hospitals,” continued Dr. Johnson. “The information we return back to them is available for non-commercial use by their researchers. Because it’s been stripped of identifiers, patient confidentiality is protected. That fact helps a non-profit institution deal with the transfer of tissues. It allows them to access the information [from specimens] they need to advance their research, while answering concerns by patients and the community about disclosure of personal information.”
Importance Of Tissue Banks
THE DARK REPORT believes that tissue banking is an emerging field that provides forward-looking pathologists with revenue opportunities in the short term, but may have far-reaching consequences to the entire profession of anatomic pathology in future years.
In the current marketplace, funding for tissue banking activities is coming almost exclusively from pharmaceutical companies, tissue engineering firms, and biotech research companies. The motive is to use a variety of emerging technologies in genomics and proteomics to unlock knowledge on how gene expression affects disease.
However, the ultimate goal is to use this knowledge to develop commercially viable products for diagnosing disease, treating patients, and monitoring their progress. As Dr. Johnson points out, pathology lies at the nexus of matching tissue image analysis with the information generated by various profiling tests.
Molecular And Genetic Path
In fact, it is this type of service mix that academic center labs and companies like IMPATH, Inc. now offer to the clinical marketplace. They blend molecular and genetic pathology with the traditional science of anatomic pathology.
From that perspective, the business model of TissueInformatics.Inc. illustrates how the large amount of research dollars funded by pharma, biotech, and genetic-based companies will directly improve the capability of pathologists to make rapid, highly-accurate, and comprehensive diagnoses from a full range of data sets, which include image analysis, genotypic testing and phenotypic testing.
Maybe tissue banking is the place where “the rubber meets the road;” where pharma company money stimulates the creation of new technology that directly benefits the pathology profession. If this happened, it would certainly be logical that breakthroughs in therapeutic technologies would also trigger breakthroughs in diagnostic technologies which find widespread application in the field of anatomic pathology.
Tissue Engineering Advancing Rapidly
“TISSUE ENGINEERING TECHNOLOGY is making rapid progress, in part because of the research funding by pharma, biotech, and genomics companies,” said Peter C. Johnson, M.D., Chairman and CEO of TissueInformatics.Inc.
“If you follow the trajectory curve, we are moving to a point where medical science can manufacture specific tissues tailored to specific individuals,” explained Dr. Johnson. “For example, let’s say that a patient is going to have surgery that will require skin to be removed and this patient does not want skin for the replacement graft to be removed from another part of his body.
“Technology is taking us to the point where it will be feasible to take a tiny biopsy of skin from this patient and have it histologically analyzed,” he continued. “This patient’s pattern would be ‘fingerprinted’ for a subpopulation. Tissue for his skin graft could actually be manufactured to those specifications. Moreover, it would be tested to insure the final product had the proper hue and texture to match the patient’s existing skin at the site of the proposed skin graft. In a true sense, it will be ‘made-to-order’ tissue fabrication!”