You have received numerous awards, including the Breakthrough Prize in Life Sciences, for your wide-ranging scientific contributions. Can you briefly tell us how your interest in angiogenesis and in tissue engineering emerged and how it has benefited the investigation of cell-cell communication? We will provide references for those that want more details.
My first important scientific work was actually in the field of cell-cell communication, more exactly in the study of the signals regulating angiogenesis.
After obtaining my degree at MIT, in chemical engineering, I received many jobs offers to work in the oil industry, however I realized that I wanted to use my knowledge to make a scientific impact that would help people. I therefore started to apply for jobs in medical research but initially no one was interested in someone with my skills. I eventually was able to get a job in the lab of Judah Folkman, at Boston Children’s Hospital. Dr Folkman thought that stopping the growth of blood vessels could be a new way to treat cancer. Many were skeptical but we were eventually successful in establishing proof of principle of the approach and in developing novel vascular growth assays and delivery methods, which were published in Nature and Science in 1976. This work established a foundation for this field that later was built upon by the pioneering work of Napoleone Ferrara and others at Genentech and lead to the development of widely used anti-angiogenesis drugs against cancer and eye disease.
I was the only engineer in the hospital at the time of my work with Folkman and we were able to see things in a novel way combining knowledge of chemical engineering and medicine. This novel approach encountered initial resistance from colleagues and my first nine grant applications were rejected. Later, when the pharmaceutical and therapeutic applications started to be successful, our work was however widely accepted.
Two broad interests in my lab have been tissue engineering and drug delivery systems.
The work on tissue engineering started as a collaboration with Jay Vacanti, with the aim of making tissues and organs from scratch. We have been using combinations of polymer scaffolds and cells, with the addition of the right signaling molecules and bioreactor conditions. Among the most successful applications are those to skin and blood vessels. We have also used stem cells, for example in a collaboration with Evan Snyder for the treatment of spinal cord injury. Another related line of research is the development of organs-on-a-chip, which can be used to test drugs and investigate cell-cell communication in vitro.
Our other main research interest, drug delivery technology, has already resulted in many clinical applications. One of the most notable is the use by Moderna, a company I co-founded, of nanoparticles for the delivery of the COVID-19 vaccine. One of the reasons Moderna was able to develop this vaccine so rapidly was the infrastructure it had already in place for RNA-based drugs and vaccines and for nanoparticles. These and other drug delivery systems can be used to turn genes on and off and can play a role in the in vivo investigation of cell signaling.
More generally, what could we do to advance the understanding of cell-cell communication, and would this knowledge produce large medical benefits?
Cell-cell communication is incredibly important, and the mentioned development of anti-angiogenesis drugs is only one of the many medical benefits that have already originated from the study of these processes. The work we and many others have done over the last decades shows how engineering can contribute to an interdisciplinary investigation of this fundamental aspect of biology.
Langer, Robert, and Judah Folkman. "Polymers for the sustained release of proteins and other macromolecules." Nature 263, no. 5580 (1976): 797-800.
Langer, Robert, Henry Brem, Kenneth Falterman, Michael Klein, and Judah Folkman. "Isolations of a cartilage factor that inhibits tumor neovascularization." Science 193, no. 4247 (1976): 70-72.
Lanza, Robert, Robert Langer, Joseph P. Vacanti, and Anthony Atala, eds. Principles of tissue engineering. Academic press, 2020.
Teng, Yang D., Erin B. Lavik, Xianlu Qu, Kook I. Park, Jitka Ourednik, David Zurakowski, Robert Langer, and Evan Y. Snyder. "Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells." Proceedings of the National Academy of Sciences 99, no. 5 (2002): 3024-3029.
Vacanti, Joseph P., and Robert Langer. "Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation." The lancet 354 (1999): S32-S34.