Notes on Catalyzing Health, January 2024: Notes on The Importance of Translation

Geoffrey W. Smith

Geoffrey W. Smith

January 9, 2024

Welcome to the first edition of Notes on Catalyzing Health, the newsletter of Digitalis Commons. Digitalis Commons is a not-for-profit organization that seeks to catalyze frontier-advancing, scalable, public good-based solutions to fundamental problems in health.

In this edition of the newsletter, we define and motivate the importance of translating inventions into innovations. In subsequent editions of the newsletter later this year, we will take on the importance of being driven by well-defined problems, why public goods are under-produced but vital, the definition and importance of technologies and entrepreneurship, and the impact of mission, margins, and mandates on organizations.

The Importance of Translation

What is Translation?
In addressing important unresolved problems in health and health care, Digitalis Commons is engaged in a form of innovative action involving the translation of findings in basic research and discovery into applied practice… (see Figure 1).

Figure 1
Digitalis Commons is focused on moving use-inspired basic research forward through applied research and ultimately into the commercial market. (figure modified from Stokes, Pasteur’s Quadrant).

Translational work in health and healthcare sits at the intersection of biological sciences, engineering, and social sciences relevant to technology development (see Figure 2). The goal of translation is to harness technical expertise and practical experience to drive use-inspired basic research from original insight all the way through the commercial development process.

Figure 2
Translational work involves combining a wide-range of technical and practical knowledge and experience. (figure modified from Neal Simon, Lehigh University).

Invention versus Innovation

In loose terms, translational work is often described as involving inventions.

Consider these three (at least semi-) famous inventors: Douglas Englebert, inventor of the computer mouse; Laszlo Biro, inventor of the ballpoint pen; and Daisuke Inoue, inventor of the karaoke machine. Englebert first came up with the idea for the computer mouse in 1968. But, while he did patent the invention, the patent ran out in 1987 before the technology became widely used. In the years since 1987, at least one billion computer mice have been sold.

In 1938, Laszlo Biro patented the invention of the ballpoint pen after becoming fed up with leaky fountain pens. But having taken out a patent for his invention, Biro sold it to Marcel Bich in 1945 for $2 million which, while a reasonable amount of money at that time, meant that Bich and his company Bic pocketed the majority of the cash from the 100 billion ballpoint pens that have been sold since the exchange of the patent.

Daisuke Inoue came up with the idea for the karaoke machine as a way for musicians to perform in bars without live back-up musicians. He failed to patent his invention, and thus failed to directly profit from its popularity. He did, however, manage to patent a pesticide for karaoke machines, a somewhat less lucrative invention.

While each of the men described above were clearly talented inventors (though perhaps at least some of us could do without the karoke machine), none of them were actually particularly good at innovation.

As far back as 1939, economist Joseph Schumpeter made a clear distinction between invention and innovation:

“The making of the invention and the carrying out of the corresponding innovations are, economically and sociologically, two entirely different things. They may, and often have been, performed by the same person; but this is merely a chance coincidence which does not affect the validity of the distinction. Personal aptitude—primarily intellectual in the case of the inventor, primarily volitional in the case of the businessman who turns the invention into an innovation—and the methods by which the one and the other work, belong to different spheres.”

Thus, while invention is a necessary step in the translation process and often the step that gets remembered and credited with patents and prizes, it is actually the hard, detailed work of innovation that ends up creating a tangible effect on welfare by solving regulatory approvals, go-to-market strategies, pricing, and the other myriad details that result in the introduction of new products and services, as well as the continual improvement of existing products and services.

ARPA-H + Digitalis Commons
In 2022, the Advanced Research Projects Agency for Health (ARPA-H) was created as a funding agency to support high-impact research capable of driving biomedical and health breakthroughs that can deliver transformative, sustainable, and equitable health solutions for everyone. ARPA-H’s mission focuses on leveraging research advances for real world impact—which is to say in another word, translation.

Digitalis Commons is privileged to be the first organization to formally partner with ARPA-H with a mandate to provide translational services to ARPA-H aimed at speeding and smoothing the process of getting breakthrough innovations in health to the American public. The Commons brings particular expertise in navigating through the regulatory, intellectual property, and market hurdles that can slow the delivery of innovative solutions to patients who need them. Through our collaboration with ARPA-H, the Commons harnesses its extensive network in the field of human health, technological proficiency, and market insights to expedite the transition of groundbreaking discoveries from the lab to the real world.

Digitalis Commons was founded in part on the idea that supporting the translation of basic research is hard, but crucially necessary. This is particularly true for problems in health and healthcare. And ARPA-H is a unique, scaled opportunity to make fundamental progress against a wide-range of unmet needs.

Notes on Catalyzing Health
We look forward to continuing to share our thoughts and translational projects with you through this website and our newsletter. And we hope that you will reach out with important problems and ideas that we can work on together.

– Geoffrey W. Smith

First Five
By Lara Mangravite

First Five is a curated list of articles, studies, and publications on that have caught our eye on the topics of public goods and emerging applied technologies.

A commons for quality improvement of research tools
Scientific knowledge advances one experiment at a time—and each experiment is only as good as its reagents. Many commercially available reagents, like antibodies, are highly variable in quality and specificity.  Use of low quality antibodies create erroneous experimental results and cost the research community an estimated $1 billion annually. How might we address this problem at the systems level? A nonprofit laboratory has taken on this problem by partnering with commercial antibody vendors to perform and openly publish a quality assessment of available antibodies. To date, vendors have contributed 614 antibodies targeting 65 neuroscience-related proteins for evaluation.  Antibodies failed quality and specificity criteria 50% of the time. Low-quality antibodies were used in 20-30% of relevant published experiments. Over half of these underperforming commercial antibodies have already been removed or relabeled. While it will be difficult to retrospectively address the estimated 20-30% of published experiments that used these low-quality antibodies, the creation of this open “Validation Commons” is actively improving reagent quality in the hopes of diminishing the scale of this problem over time.

Open resource for neuroscience
Focused research organizations (FRO) are an increasingly popular strategy to address key problems in science. These are typically organized as limited-term institutes dedicated to advancing emerging scientific domains by developing open research tools and resources to overcome existing research barriers. The Allen Institutes have operated under this model over 20 years. The Allen BRAIN Institute announced the first version of the Allen Brain Atlas, conceived as a 3D map of gene expression across the mouse brain, in 2006. Over the years, this team has expanded their work across species, contextualized it to both developmental and disease brains, and updated the framework as technologies have advanced. Last month, the Institute published the completion of the first high-resolution cellular map of the adult mouse brain using single-cell RNA-sequencing and spatial transcriptomics.

Taming the wild
Agriculture faces the continuous challenge of increasing food productivity to meet global demand. Breeding programs in recent history have focused on increasing yield of existing crops in a manner that is now reliant on fossil fuel products and intensive irrigation. Public investment into research tools—including development of well-annotated reference genomes for an array of wild plants - has opened an exciting alternative. As described in a recent commentary, these resources enable new breeding programs to re-domesticate wild crops aand de-novo domesticate alternative plants. Such strategies would allow for seletion of high-yield plants that are both self-sufficient growers and resilient to emerging climate conditions. Initial efforts have successfully bred stress-tolerant wild tomato, groundcherry, and wild rice.

Integrating innovation and invention in cancer diagnostics
One simple way to ensure your idea turns into a useful product is to design it that way. Because public research funding is designed to incentivize invention, innovation is frequently left till later. But designing inventions with market needs in mind can lead to faster development cycles and more commercial partners. One emerging technology that many people are watching is the use of synthetic biology for early cancer detection. A recent study has reported an inhalable nanosensor that could detect early-stage lung adenocarcinoma in a mouse model with high sensitivity and specificity. They caught our eye by intentionally designing their detection strategy to provide rapid results at room temperature, opening the potential for the test to be used at point-of-care in a broad range of clinical settings.

Viral protection in a single breath
Vaccines are a powerful, if controversial, tool used to combat viral infections including SARS-CoV-2, the virus that causes COVID-19. Vaccines work by boosting our bodies’ ability to mount an immune response following infection. Despite popular belief, they do not protect us from getting infected. But what if they could? A recent study in primates suggests that achieving viral immunity may be as simple as changing the way that the vaccine is administered. Macaques that inhaled a SARS-CoV-2 vaccine booster into their lungs could block infection in a manner that was not possible when the same booster was administered using the standard intramuscular administration or an intranasal administration. Could there be a future where vaccines are taken by inhaler instead of by needle?