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The Biggest Treasure Hunt You Can Imagine

Inside the digitization of Mayo Clinic's Tissue Registry Archive.

By Kathleen Hull Photography by Matthew C. Meyer

In a vast warehouse on the northwest side of Rochester, Minnesota, a group of skillful robots are hard at work. These custom-engineered creations swiftly and delicately lift glass slides containing patient tissue samples preserved in paraffin and feed them into a scanner, processing tens of thousands of slides each day.

The warehouse, which sits across the street from a quiet row of ranch houses, seems an unlikely hub for the transformation of healthcare. But the work happening within is forging a new future for patients everywhere. The warehouse contains Mayo Clinic’s Tissue Registry Archive, and by digitizing a significant sampling of material from this collection — 13.4 million slides so far and up to 16.5 million by the end of October — Mayo Clinic is unlocking previously unimaginable health insights and creating cutting-edge new treatment options.

“This discovery effort is like the biggest treasure hunt you can imagine,” says Joaquín J. García, M.D., chair of the Division of Anatomic Pathology, which oversees the archive, and medical director of Mayo Clinic’s Digital Pathology Program. Researchers are now able to draw on digitized images and data from slides to develop artificial intelligence (AI) programs that automatically recognize features of various diseases in tissue samples. They’re also working to identify novel biomarkers and treatments for diseases such as cancer.

Serving Patients Across Generations

The unparalleled depth of the archive allows Mayo Clinic to generate insights that no other healthcare institution can. Most hospitals keep tissue samples for only 10 years. Mayo’s tissue archive goes back well over a century.

This practice of preserving tissue samples is rooted in Mayo’s commitment to putting the needs of the patient first. “Mayo Clinic has long viewed itself as the medical home for its patients,” Joseph J. Maleszewski, M.D., the medical co-director of the archive, explains. “And many of our patients’ conditions are genetic in nature, so it’s not uncommon for us to see not only patients but also their family members.” He adds that sometimes, decades after a tissue sample was created, relatives of the patient return to Mayo Clinic with questions about their own health.

“Through the generations, our goal has been to preserve patient tissue so we can return to it should new testing or new diagnostic insights become available,” Dr. Maleszewski says.

He adds that the archive digitization project has been driven in part by a desire to add an additional layer of protection for patients. “We view our role as keeping the tissue safe should our patients ever need it in the future,” he says.

Preserving the Past

In the Rochester warehouse, a dedicated team of archivists work alongside the robots to prepare and digitize the collection. The oldest tissue sample in the archive dates back to 1891 — just eight years after country doctor William Worrall Mayo, M.D., and Mother Alfred Moes of the Sisters of St. Francis famously shook hands and agreed to open a hospital in Rochester. “In terms of medical records, we have tissue from Mayo Clinic patient No. 3,” Dr. Maleszewski says.

Of course, challenges can arise when digitizing slides that are essentially historical artifacts. Dirt and damage are major concerns. Recognizing this, Mayo Clinic partnered with Pramana, a robotics and microscopy startup based in Cambridge, Massachusetts. Working together, Pramana and Mayo developed the first robotic scanner on the market capable of processing these older slides with a high level of quality control. Now, these scanners are powering the digitization project.

Living Forever: The Journey of a Digital Pathology Slide

STEP 1

COLLECTING

A biospecimen is taken from a patient, placed in a chemical solution that protects and preserves it, and sent to the Mayo Clinic Histology Laboratory.

STEP 2

EMBEDDING

After several preparatory steps in the lab, the patient sample is embedded in paraffin wax. Once the wax has solidified, the biospecimen can be cut into very thin sections — usually around 5 microns in thickness.

STEP 3

MOUNTING

These sample sections are placed in warm water. Glass slides are dipped into the water to pick them up.

STEP 4

STAINING

Once a slide has dried, the patient sample is stained so that cellular structures are easier to view, and a cover slip is placed over the sample. The slide is now ready to be examined under a microscope.

STEP 5

ARCHIVING

Once it has been viewed and analyzed, the slide becomes part of Mayo Clinic’s Tissue Registry Archive. Physical slides are stored in a climate-controlled warehouse in Rochester.

STEP 6

DIGITIZING

Each slide is also scanned and digitized, with the images and information it contains entering Mayo Clinic’s digital repository.

STEP 7

PRESERVING

The digitized data from the slide is preserved forever and can be used for a variety of purposes, including algorithm development and the creation of personalized health guidance and care plans for patients.

Supercharging the Future of Care

Meanwhile, in areas across Mayo Clinic, newly digitized data from the Tissue Registry Archive is already driving discoveries as researchers embark on Dr. Garcia’s “treasure hunt.”

For example, data from the archive is boosting research on one of the deadliest types of cancer — pancreatic cancer. Ryan Carr, M.D., Ph.D., a Mayo Clinic oncologist specializing in gastrointestinal malignancies, turned to the archive when he began work on an algorithm that will predict how different types of pancreatic tumors respond to treatment after surgery. Despite major advances in surgical techniques, a significant risk of cancer recurrence remains, so having new information to guide treatment decisions post-surgery will be transformative.

Using slides from as far back as 1991, Dr. Carr looks at factors such as the location of cancer cells and their relationships with other cells, including immune cells and cancer-associated fibroblasts.

Mayo Clinic technicians prepare slides in a histology laboratory in 1933 (below) and 2020 (right), ensuring that the health information of Mayo patients will be preserved into the future.

Photography by Leonard Julin (above) and Matthew C. Meyer (right)

“Using this data, the algorithm can predict sensitivity to particular chemotherapies that we can then apply,” he explains. Mayo Clinic teams can then create individualized care plans for each patient. This new treatment pathway promises to offer hope and targeted solutions to patients struggling with a difficult diagnosis and challenging treatment process.

Having access to the vast collection of assets in the Tissue Registry Archive is also changing the nature of pathology itself. Already, biopsies from current patients can be processed instantly and added to Mayo Clinic’s digital repository. With more data at pathologists’ fingertips, diagnoses and analyses can take place in hours or even minutes, not weeks. And patients are being empowered to learn more about their condition and make data-driven decisions about the types of treatment they would like to pursue. Dr. Garcia offers the hypothetical example of a patient facing a colon cancer diagnosis.

"In the future, when that patient decides they want a second opinion, they’re not going to jump through the hoops of the clinic or hospital,” he explains. “They can seek that extra opinion, and if they want someone to assemble it based on 50 colon biopsies over the last 30 years and assimilate that with 50 additional biopsies from their siblings, they can. That future is right around the corner with digital pathology.”

As the Tissue Registry Archive team approaches its goal of scanning and digitizing Mayo Clinic’s rich collection of material by the end of 2024, Dr. Garcia is reflective about the way this work bridges Mayo Clinic’s past and future — and furthers its legacy of serving patients.

“When we place tissue into paraffin wax, whether it’s in 1891 or today, we regard it as immortalized,” he says. “And we now have over a century’s worth of this tissue. We’re going to be able to piece together stories and predict new treatments for patients in ways we never imagined."