Walt’s deep expertise in molecular diagnostics and the biotech industry will augment translation-focused medical diagnostics efforts
By Lindsay Brownell
(BOSTON) — After more than 30 years at Tufts University, 300 published peer-reviewed papers, 75 patents, seven professorships, numerous national and international awards, and one multibillion-dollar biotech business, David R. Walt, Ph.D. decided it was time for a change. This month, he moves his lab to the Department of Pathology at Brigham and Women’s Hospital (BWH) and the Wyss Institute for Biologically Inspired Engineering at Harvard University, where he will become the newest Core Faculty member. “This dual appointment at BWH and the Wyss Institute is an ideal combination for me, as it will enable me to expand my work into the clinical/translational sphere while also keeping the bioengineering side of my research going,” says Walt, who is also a member of the faculty at Harvard Medical School in the Department of Pathology and a Howard Hughes Medical Institute Professor.
Walt’s work is widely acknowledged to have enabled the recent boom in genetic analysis based on his 1996 invention of microwell arrays, which allow extremely small volumes of liquid to be isolated in individual microwells for detection and analysis. Walt followed that innovation with the idea of random arrays in which beads containing different DNA-binding sequences were loaded into the microwell arrays to facilitate genetic analysis of DNA samples – an idea upon which he co-founded the company Illumina in 1998. Illumina’s BeadArray platform was the catalyst that enabled completion of the HapMap Project in the early 2000s, which resulted in the large-scale discovery of human genetic variation based on detection of single nucleotide polymorphisms (SNPs) from thousands of individuals. Over 80% of this “once in history” project was performed on the BeadArray platform.
The results of the HapMap project sparked the start of genome-wide association studies (GWAS), which were also made possible by Illumina due to the high densities, reduced cost, and flexibility of the BeadArrays. This technology became the standard for GWAS and has been adopted by all the major genome outfits, enabling the discovery of the underlying genetic causes of numerous human diseases, screening embryos for genetic defects before in vitro fertilization, studying preserved/frozen tissues, improving crop disease resistance, and identifying individuals’ metabolic profiles to ensure proper drug dosage. The microwell array technology is also the basis for most of the high-throughput sequencing platforms on the market today. As a direct result of the higher density of throughput, both sequencing and genotyping costs have been reduced by nearly a million fold in less than a decade. Illumina is now a $26B market cap company and holds more than 90% of the next-generation sequencing market, and was named MIT Technology Review’s “Smartest Company” in 2014.
In 2007, Walt expanded the microwell array technology from DNA to proteins, co-founding Quanterix to commercialize his lab’s Simoa technology for ultrasensitive protein detection. Simoa can detect proteins at 1000 times lower concentrations, providing 100-1000x improved sensitivity over the best commercial protein assays and opening up an entirely new set of proteins that can now be detected in the blood. Researchers are using it to discover candidate markers for a multitude of diseases related to inflammation, oncology, neurology, and infectious disease.
At Tufts, Walt’s group has made significant progress toward developing a blood test for detecting early-stage breast cancer, diagnosing latent tuberculosis, and detecting various infectious diseases using the host response to infection. Additional projects include adapting microarrays for single-cell isolation and analysis, single-molecule enzymology, and nanoparticle catalytic activity characterization, which the group will continue to pursue. “The ‘secret sauce’ my lab brings to the Wyss is our ability to look at single molecules and single cells, which are the smallest functional units of chemistry and biology, respectively,” says Walt. “Being able to count individual molecules in individual cells is the holy grail in terms of really understanding biology. Our goal with this move to BWH and the Wyss is to branch out into collaborative projects that could benefit from using that technology, so we can discover and measure things that have not yet been measured at those fundamental levels and use them to improve human health.”
Additionally, Walt is looking forward to using his years of experience in the biotech industry to inspire scientists at the Wyss and BWH to incorporate translationally-minded thinking earlier in their research process. “My experience with Illumina drove home to me how, when you make a new technology available to the world through translation and commercialization, the impact it has on the world is on an entirely different scale. It requires a switch from an output-based approach to an outcome-based approach, measured not by the number of papers we publish, but what kind of impact we make on improving human health, access to food and security, etc. That’s primarily the reason that I’m so attracted to both the Wyss and BWH: opportunities to get young people involved and thinking about translation from the very beginning.”
“We are delighted to bring David Walt into the Wyss family, as he is an outstanding role model for scientists and engineers who strive to both make fundamental scientific breakthroughs and translate those discoveries into products that can change the world for the better,” says Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences. “David’s deep knowledge of both the academic and commercial sides of science, and his long-standing commitment to collaboration, mentoring, and entrepreneurship, resonate with our own. We are also excited to have him create yet another bridge with Brigham and Women’s Hospital, which will undoubtedly lead to entirely new clinical innovations that will again change the world in ways that we cannot yet imagine.”