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Discovery’s Edge: The power of patents
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Inventors and their breakthrough ideas are popular cultural touchstones in America’s history: Benjamin Franklin’s lightning rod; Thomas Edison’s light bulb; the Wright brothers’ first byplane; and Steve Jobs’ garage-built computer. The stories we hear usually celebrate the inventor and the invention, but give little clue to the hours of scientific study that led to the invention. In the medical world, people who make important advances are usually portrayed as brilliant scientists who may make an exciting discovery but rarely follow its subsequent progression through invention and commercialization.
But Richard L. Ehman, M.D., Mayo Clinic physician and scientist is an advocate for physicians and scientists who become inventors and perhaps even entrepreneurs. His advocacy comes with experience. With a long career of research, Dr. Ehman holds more than 40 U.S. and international patents for inventions that have advanced medical imaging.
One of these inventions is a called magnetic resonance elastography (MRE). Dr. Ehman and his team developed this unique technology to solve a problem that they saw in existing medical imaging tools like magnetic resonance imaging (MRI), computed tomography, and ultrasonography. While these techniques can reveal many diseases, they are not capable of demonstrating the stiffening of tissue that can be the earliest sign of important diseases such as fibrosis and cancer. He and his team discovered a way to use low frequency mechanical vibrations in combination with MRI to quantitatively image the mechanical properties of tissue. MRE is now used as a more comfortable and less expensive alternative to needle biopsy for diagnosing chronic liver disease at Mayo Clinic and other major medical institutions throughout the world.
Researcher to Inventor to Entrepreneur
Applying scientific rigor to the hypothesis behind MRE ultimately led to the actual invention. But Dr. Ehman soon found that the development of the MRE led to a new phase to his career: entrepreneur. And timing was definitely on his side.
Like most other academic medical institutions, during much of the 20th century Mayo Clinic did not pursue patents on advances in patient care developed through research and practice. “The invention of cortisone is often cited as an example”, Dr. Ehman notes.
The discovery of cortisone from a substance known as “compound E” was an effort that spanned many labs and researchers, but ultimately was credited to Mayo Clinic colleagues Edward Kendall, Ph.D., and Philip Hench, M.D., along with Swiss chemist Tadeau Reichstein. They won the 1950 Nobel Prize in Physiology or Medicine for demonstrating how cortisone was capable of reversing inflammation. As a drug, this was a breakthrough treatment for patients with rheumatoid disease. Five groups, including Mayo, held patents for some part of the process. They were able to come to an agreement that allowed manufacturing of cortisone by employing a third-party, non-profit entity. But Dr. Kendall and his lab were also patent holders. They were awarded patents for the steps involved in taking compound E on its journey to cortisone. At the time, Mayo physicians were not allowed to profit from any drug, vaccine or device they helped invent. However, Mayo did want to retain some power to advocate for its principles and the medical profession. So, Dr. Kendall, who fully supported this policy, signed over his patents to Mayo, and Mayo in turn gave them to the third-party that managed the manufacturing agreement of cortisone. Key to Dr. Kendall’s decision was that colleagues in fields other than chemistry didn’t have the opportunity to patent their work in the same way, and therefore profit from it despite the fact that all had the same level of devotion. He writes in his book on the topic, "Cortisone", that, “In the long run, teamwork is of more value than solo performance.” **
That idea, though, shifted slightly in the early 1980s with a new federal law called the Bayh-Dole Act. This legislation was designed to encourage academic institutions like Mayo Clinic to pursue patents for inventions made by employees and to promote commercialization of these innovations as products that could benefit people everywhere. This legislation is regarded as highly-successful, and is credited with sustaining US leadership in the world biotechnology sector. In response to The Bayh-Dole Act, , Mayo established a “technology transfer” office, now known as Mayo Clinic Ventures (MCV). Through MCV, the Mayo Clinic has become one of the most successful US academic medical organizations in identifying important inventions, patenting them, and then making these advances available to patients everywhere through licensing and commercial ventures.
According to Dr. Ehman, “in 2012, the leaders at Mayo Clinic recognized that while the organization was doing a great job in supporting the innovation talents of its employees, more could be done to encourage individuals who wished to contribute through entrepreneurship.” New policies were developed to expand the options for Mayo employees to be involved in start-up companies, often based on Mayo inventions.
In 2013, MCV formed a company called Resoundant, Inc., dedicated to making MRE technology available to patients around the world. Mayo Clinic owns the majority of the company, but consistent with Mayo policy, more than a dozen Mayo inventors also participate in ownership. Dr. Ehman serves as Chief Executive Officer and member of the Board of Directors of the company. In its first two years of operation, the company has been extremely successful, making MRE technology available to patients at more than 500 locations on five continents.
The company is based in Rochester, Minnesota, - a perfect location according to Dr. Ehman. Mayo Clinic and the city are actively encouraging the development of local start-up ventures to help deliver Mayo innovations to world, and to contribute to a healthy regional economy. Resoundant is investing heavily in research and development, and according to Dr. Ehman, Rochester is an ideal place to do this because of access to tremendous expertise at Mayo Clinic. “Another key advantage is that Mayo has comprehensive policies governing commercial relationships that provide a basis for industry collaborations within a very strong ethical framework.” says Dr. Ehman. “And since Resoundant is based on technology that was first introduced at the Mayo Clinic, future advances should always be available to patients at Mayo first.”
The specialized hardware that is used in every MRE-equipped MRI scanner is manufactured in Rochester. “By locating our business operations, manufacturing, and research and development programs here, we are making a contribution to a growing and vibrant start-up scene in the ecosystem around the Mayo Clinic.”
How is an invention commercialized? The Importance of Patents
The historical purpose of the patent system is to encourage the development and public disclosure of new inventions by providing the patent holders with exclusive rights to the invention for a period of time (typically 20 years in the U.S.). Abraham Lincoln, the only US President to hold a patent, once said that the patent system “added the fuel of interest to the fire of genius.”
That “fire of genius” resulted in the the U.S. Patent and Trademark Office awarding more than 325,000 patents in 2014. This activity provides fuel for the economy as well. According to the Brookings Institute, the Washington, D.C. think tank, “Inventions, embodied in patents, are a major driver of long-term regional economic performance, especially if the patents are of higher quality. In recent decades, patenting is associated with higher productivity, lower unemployment rates, and the creation of more publicly-traded companies.”
The medical innovation community contributes to this economic performance. According to Dr. Everett Ehrich, who wrote “NIH’s Role in Sustaining the Economy,” approximately one million people are working on medical innovations, and this creates about $84 billion in wages and salaries. The goods and services generated by this industry account for another $90 billion in exports.
Studying Patents in NIH-Funded Research
Dr. Ehman began a two -year term in 2013 as president of the Academy of Radiology Research (ARR), a Washington-based organization dedicated to advocacy for Federal funding for research in imaging science. He found that Michael Kalutkiewicz, senior director for Government Affairs at the ARR, shared an interest in the significance of medical inventions, and they began a collaboration to explore patent productivity as a potential metric for assessing the return on investment for NIH-sponsored research.
They quickly realized that focusing on patent volumes was not sufficient because inventions can vary widely in significance and value. With this in mind, Kalutkiewicz and Ehman examined another metric: the number of “forward citations” associated with each patent, which is a measure of quality or impact. They tapped databases at the NIH and the U.S. Patent office to study the “invention productivity” of NIH-funded research from 2003 to 2012. They found a wide range of invention productivity between the institutes, but on average, patents resulting from NIH-funded research had nearly double the number of forward citations of patents from the US private sector and nearly six times that of the European biotechnology sector. They published their results in an article entitled “Patents as Proxies: NIH Hubs of Innovation”, in Nature Biotechnology (June 2014).
National Policy Implications
At a time when the NIH has experienced more than a decade of diminished appropriations from the federal government, both Dr. Ehman and Kalutkiewicz believe this hard evidence could help persuade U.S. politicians to look at increasing funding to the NIH. It saves lives—and it creates jobs.
“Legislators are asking for more evidence to guide the federal R&D portfolio – introducing somewhat of a “moneyball approach to science policy,” says Kalutkiewicz. “Patent production only seeks to examine one aim of research, but it’s particularly important at the moment: fueling our innovation economy, which will be critical for this country moving forward.”
“Although the core mission of the NIH is to improve human health through medical research and discovery,” adds Dr. Ehman, “legislators on both sides of the political aisle often point to the NIH as an engine for innovation and economic growth. We think this analysis shows that it’s a good investment for the American taxpayers.”
How Do Other Organizations Compare?
To further validate the approach, Kalutkiewicz and Ehman applied the same analysis to NIH-funded research by investigators who received Nobel prizes for their work. As expected, the volume and quality of patents reported by these investigators was much higher than the overall NIH average.
And Mayo Clinic? In 2013, the U.S. Patent Office approved 66 patents registered to Mayo. With a total research budget of $646 million for that year, Mayo averaged 10.2 patents per $100 million of funding, which is approximately twice the productivity of the NIH in this regard. From 2003-2006, Mayo patents averaged nearly 12 forward citations per patent, nearly four times the rate in the US private biotechnology sector.
Pasteur’s Quadrant
Dr. Ehman believes there’s a reason for Mayo Clinic’s high performance. That reason - and Mayo’s research - both reflect what has been called “Pasteur’s Quadrant”.”
In the 1990s, political scientist Donald Strokes from Princeton University, published a book exploring the history of scientific research and in particular, the often sensitive debate about the merits of basic and applied research and the accountability of researchers for their resources that support their work. Stokes characterized research according to a two by two diagram in which one axis divided the work according to whether or not it was inspired by a quest for basic understanding (so-called “basic” research) or whether or not the work was motivated by a practical problem (so-called “applied” research). He referred to the part of the diagram that represented research seeking new knowledge, without consideration for usefulness, as “Bohr’s quadrant”.” He designated research that is completely focused on finding a useful solution to a problem as “Edison’s quadrant.” For Stokes, the sweet spot of the diagram was where basic research was inspired by real world needs. He called part of the diagram “Pasteur’s Quadrant”, after Louis Pasteur, the French chemist and microbiologist who brought the world such life-altering ideas as safe preservation of foods and the principles of vaccination. Stokes emphasized that research in Pasteur’s quadrant, harnessing the power of basic research to address real world problems has not only been extraordinarily successful but compared to the usual sequential approach of basic followed by applied research, it is often more efficient.
“It is tempting to think that to some extent at least, the axes in our figure may correspond to the axes in Stoke’s diagram”, says Dr. Ehman.
The challenge of working in Pasteur’s quadrant is that it requires the combination of practical experience with real world problems and multidisciplinary scientific expertise. That can prove daunting if you are a solo investigator. “At Mayo, we work in teams”, says Dr. Ehman “We can easily assemble teams with extraordinary expertise in diverse areas of basic science, mathematics, and engineering.” And since our research is inspired by our mission of patient care, our teams have no trouble identifying the most important opportunities. It is a powerful model.” “When teams create inventions that are proven useful and used in patient care at the Mayo Clinic, then we know that they will work and should be shared with the rest of the world.”
Economic Impact
Both Kalutkiewicz and Ehman emphasize that there are many valid criteria for assessing medical research, the most important of which is advancing human health. The value of medical inventions that improve patient care goes far beyond any consideration of commercial potential. However the economic value of medical innovations is an important factor in mobilizing the support of policy makers for public investment in medical research.
“Our mission at Mayo is to take care of patients,” says Dr. Ehman. “That mission also directs the focus of our research. Through our team approach, the scale of our practice and our constant focus on the needs of our patients, we can achieve things that other organizations cannot.”
And that’s what this radiologist turned inventor turned entrepreneur would call the best discovery of all.
-- Jeffrey Briggs
November 2015
**Update, March 2020: Text in this paragraph has been updated. The development of cortisone is a long and nuanced story. For more information consider reading Dr. Kendall's book, "Cortisone," or one by Thom Rooke called, "The quest for Cortisone." Another publication that mentions Dr. Kendall and cortisone is, "Rheumatic Disease Clinics of North America" by Marcy Bolster. Original text read: When Mayo Clinic colleagues Edward Kendall, Ph.D., and Philip Hench, M.D., along with Swiss chemist Tadeau Reichstein, won the Nobel Prize for Physiology or Medicine in 1950 for demonstrating how cortisone was capable of reversing inflammation, Mayo Clinic did not patent this discovery nor participate in its commercialization. The invention was a breakthrough in treatment for patients with rheumatoid diseases, but Mayo Clinic did not receive a share of the revenue generated by pharmaceutical companies from this innovation. If Mayo had received such funds, they could have been used to further research to benefit patients.
