publication date: Nov. 13, 2020

An Appreciation

David A. Ahlquist, pioneer of cancer screening, dies at 69

With unwavering positivity and unquenchable curiosity, David A. Ahlquist, MD, turned complex challenges into addressable opportunities, and audacious ideas into achievable realities.

Dr. Ahlquist, who died Nov. 1 due to complications from amyotrophic lateral sclerosis, was a visionary leader, compassionate clinician, dedicated mentor, and tireless innovator. He dedicated his research to meaningful change in the prevention and early detection of cancer, recognizing profound opportunities in unexpected places. He was 69. 

Dave’s long list of accolades includes Investigator of the Year and Distinguished Inventor Awards from Mayo Clinic, the William Beaumont Prize for practice impact from the American Gastroenterology Association and Fellowship in the National Academy of Inventors.

His scholarly productivity includes more than 25 years of continuous funding from NIH, more than 200 peer-reviewed manuscripts and book chapters, and over 80 issued patents. Dave mentored over 40 trainees, and further served the Mayo Clinic community through innumerable clinical, educational and research leadership positions, including directing the GI Fellowship program, the GI Endoscopy unit, and the GI Neoplasia clinic, before taking on broader leadership roles at the institutional level, including president of the alumni association, president of the staff, and director of the Department of Development.

He was masterful in building meaningful relationships, inside and outside of Mayo Clinic, that celebrated diversity in the collective approach to achieve common goals.

Dr. Ahlquist’s professional career was guided by his north star of reducing the cancer burden, fueled by his creativity, humility, and mission-driven entrepreneurialism. As a gastroenterologist, Dave was convinced that the biggest impact he could make on colorectal cancer was through improved early detection.

He and his scientific team dedicated their talents to the discovery of tumor-associated molecular markers that could be applied to screen-detect localized cancers and advanced precancerous neoplasia.

To solve the obvious dilemma of “finding a needle in a haystack” in stool, the Ahlquist team defined and optimized their molecular probes to separate the relatively rare fragments of human DNA from the massive amounts of bacterial DNA, to maximize performance and efficiency of the resulting assay.

Dave’s seminal laboratory observations were ultimately translated into the FDA-approved, multi-target stool DNA (mt-sDNA) test, commercially marketed as Cologuard, through his deep partnership with Exact Sciences.

To date, the mt-sDNA test has been used to screen for colorectal cancer by more than 4 million people, thereby preventing morbidity and mortality for thousands of patients.

Ironically, one of the biggest obstacles that Dave and the team from Exact Sciences faced in commercializing the mt-sDNA test was overcoming reservations among his fellow gastroenterologists, that a noninvasive test such as Cologuard deserved a place in the average-risk screening armamentarium.

In the end, their test added another option, and a scientifically elegant one, to the list of early detection methods that patients and providers can choose to best meet their screening needs.

Building from successful development of the mt-sDNA assay for colorectal cancer screening, Dr. Ahlquist expanded his research to pursue novel assays for other early detection opportunities. Dave was among the first to recognize that tissue-specific DNA methylation patterns in health could inform tissue-specific DNA methylation signatures in cancer.

Though this concept had been previously proposed by other thought leaders, meaningful advances were hindered by the lack of compelling candidate markers. To discover methylated DNA markers unique to the site of cancers arising in different organs, Dave directed his team to explore a then emerging tool, next-generation DNA sequencing.

In contrast to existing hybridization arrays, next-gen sequencing provided huge amounts of information without bias to known markers. This insightful approach is now widely applied in molecular tests for cancer screening, treatment response, and post-treatment monitoring.

This new investigation was coupled to his rational and scientifically justified hypothesis that biomarkers could be used to efficiently screen for multiple cancers in a population. This sharp departure from the traditional practice of single-organ screening has been the cardinal focus of Dave’s later career, along with the researchers he recruited and mentored over the last decade.

Single organ cancer screening is practiced at a population level for the few malignancies that are not only highly prevalent, but can also be found at early stage or pre-cancerous state and can often be treated with minimally invasive means. Currently, cancers of the breast, uterine cervix and colorectum meet all these conditions.

However, the unscreened solid cancers in the general population, such as lung, esophageal, gastric, liver, pancreatic, and ovarian, account for a majority of fatalities each year when counted together.

Dr. Ahlquist raised international consciousness of the transformative concept that a non-invasive biomarker might be capable of screen-detecting several of these diseases at the same time. If screened in aggregate using a multi-cancer test, the low prevalence of each individual target condition would no longer pose a major barrier to clinical application and adoption.

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Ahlquist with daughter Brooke Carlson

 

Along with his stellar reputation as a cancer screening specialist, Dr. Ahlquist was a recognized expert in occult gastrointestinal bleeding. In the mid-1990s, Dave was contacted by the Centers for Disease Control and Prevention to assist with an investigation of pervasive, unexplained, iron-deficiency anemia in the Alaska Native population.

Through a series of collaborations with arctic investigators, tribal elders, and dedicated study participants, Dave and his team identified hemorrhagic gastritis, an atypical manifestation of Helicobacter pylori infection, as the etiology of this longstanding medical mystery.

This experience marked the beginning of a deep connection Dave developed with the Alaska Native population, which is also at higher risk for colorectal cancer than other major race/ethnicity groups in the United States.

Over more than two decades, Dave stayed actively involved with Alaska researchers, including visits to remote outposts to learn from, and work with, the indigenous peoples. Not surprisingly, Dave was quickly welcomed into these traditionally tight-knit communities as a trusted colleague.

Alaska’s environmental splendor and ecological diversity also had a tremendous impact on Dave, prompting several memorable trips with family and friends to share in the beauty of “the last frontier.” 

Beyond Alaska, Dr. Ahlquist’s wanderlust took him to spectacular places, including Greenland, Ecuador, Patagonia, and Costa Rica.  Yet, despite his extensive travel to exotic locations, northern Minnesota remained Dave’s spiritual center.

He was always a keen observer of the world around him, and a stalwart steward of the environment. For those who had the privilege of taking a walk in the woods or a trip to a trout stream with Dave, his intoxicating sense of nature’s wonders was immediately evident.

While relaxing streamside, Dave would expertly identify the surrounding flora, explain the subtle differences between varieties of nearby spring warblers, and then deftly cast his fly line into a barely visible trout pod lurking just beneath the water’s surface.

While some occasionally find the courage to embark on a “road less travelled” during life’s journey, Dave made it a habit, reveling in every chance to chart his own course, undaunted by the unknown. Whether traversing the forest near his family cabin on the north shore of Lake Superior, or problem-solving a complex conundrum in his Mayo Clinic laboratory, he routinely trail blazed a new path through uncharted territory.

Paraphrasing The Waking, by Theodore Roethke, Dave learned from going where it was he needed to go. Admittedly, not all of his “short cuts” were immediately successful, but Dave always learned from the experience and deciphered a way to achieve his defined goal, pausing only to congratulate those who contributed to the success before moving on to the next quest, whether over the next hill or within the next tumor profile. 

Dr. Ahlquist inspired us, and so many others, to join him in the cancer-prevention mission, moved to think in new ways by his forward-looking yet well-argued and evidence-based vision. He was so skilled in the building and nurturing of his professional relationships, that all personally connected as well.

Dave’s collegial approach and impressive networking have sparked deepening dialogues between bench scientists, clinicians, epidemiologists, patient advocates, industry leaders and regulatory authorities, who are ever-more committed to advancing and accelerating the multi-cancer screening movement, drawing in the horizon so that previously unsolvable problems are no longer out of reach, through innovative experiments and creative collaborations.

Indeed, the enormous potential to meaningfully improve cancer prevention and control through multi-cancer detection has launched entire new commercial and academic programs, which Dave viewed as beacons of a new era in patient-centered prevention, shining more light on the ultimate goal of vanquishing the “emperor of all maladies.”

It’s natural to wonder how one would respond if broadsided by the diagnosis of a lethal disease. Characteristically, Dave Ahlquist did not focus on the progressive limitations imposed by ALS.  Instead, Dave chose to describe his end-of-life journey as an adventure, with intense focus on the beauty found in each moment. He dedicated his time to pursuing extraordinary travel with family and heartfelt conversations with friends, while also continuing to guide and support his grateful colleagues for as long as possible.

Dave was devoted to his family above all else. He is survived by his loving wife Susan, his daughter Brooke Carlson (Bryant), his sons Aaron (Elizabeth) and Daniel (Amanda Flaim) and by many grandchildren.

Now around the last bend, Dave is no doubt waiting, as usual, for the rest of us to catch up. His was a life well lived, and we are all better for it.


Disclosures:

Dr. Limburg serves as Chief Medical Officer for Screening at Exact Sciences through a contracted services agreement with Mayo Clinic. Dr. Limburg and Mayo Clinic have contractual rights to receive royalties through this agreement. Mayo Clinic has an intellectual property agreement with Exact Sciences under which Drs. Kisiel is listed as an inventor and may receive royalties. 


The authors are:

Paul J. Limburg, MD, MPH
Professor of medicine,
Mayo Clinic

John B. Kisiel, MD
Associate professor of medicine,
Mayo Clinic

Richard M. Goldberg, MD
Professor and cancer institute director emeritus,
West Virginia University

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