Robert Langer
Robert S. Langer David H. Koch Institute Professor, Massachusetts Institute of Technology
The programming of AIChE’s Regenerative Engineering Society will feature the Cato T. Laurencin Regenerative Engineering Founder’s Award Lecture — named for that society’s organizer. Robert S. Langer, David H. Koch Institute Professor at the Massachusetts Institute of Technology, is slated to deliver the lecture on October 28.
My Journey in Chemical Engineering: from Initial Struggles to the Development of Drug Delivery Systems and Tissue Engineering and Having Fantastic Students such as Cato Laurencin
Robert S. Langer, David H. Koch Institute Professor, Massachusetts Institute of Technology
When I graduated from MIT, I went to work at Boston’s Children’s Hospital. I was the only engineer there. I began trying to see if I could make tiny particles that could deliver large molecules (e.g. proteins, nucleic acids) that prevent vascular growth to tumors. Over two years, I had found hundreds of unsuccessful methods. Finally, in 1976 I discovered a way to make it work (ultimately published in NATURE).
One of my goals was to move beyond just conducting experiments and publishing the results, to applying that work to helping people. We used the delivery systems to see if we could find substances that could stop blood vessels from growing. I isolated many different substances and tested them in over 100 different studies. We published a paper in Science in 1976, which showed for the first time that inhibitors of blood vessel inhibitors existed, and provided bioassays which could be used and were used to, isolate future inhibitors. Today, many inhibitors of blood vessel growth have been isolated and they are used by many millions of people to treat cancer and diseases of blindness, such as macular degeneration and diabetic retinopathy.
The principles we established for the controlled movement of molecules have been essential to the development of numerous clinically used therapeutics. There are many tiny controlled-release systems used by patients worldwide that continuously release peptides for up to six months from a single injection (Lupron Depot, Zoladex, and Decapeptyl) to treat advanced prostate cancer. Similar microspheres or other polymer systems containing bioactive molecules have led to new treatments for schizophrenia (Risperdal Consta), alcoholism, opioid addiction (Vivitrol), arthritis (Zilretta), controlling bleeding (Floseal, Surgiflo), pituitary dwarfism (Nutropin Depot), type-2 diabetes (Bydureon), heart disease (drug eluting stents) and many other diseases.
The original controlled-release materials we developed were small particles; in many cases, microparticles. However, nanoparticles are often critical for delivering significant payloads of any drug into cells, particularly newer potential drugs such as siRNA and mRNA. Yet, once nanoparticles are injected into the body, they are destroyed almost immediately by macrophages, and are unstable and often aggregate. These characteristics made their use essentially nonexistent. To address these issues, in a 1994 paper in Science, we defined seven characteristics we wanted to build into nanoparticles. We found that nanoparticles composed of a block copolymer of polyethylene glycol (PEG) and any other material and an added drug, could circulate for hours in vivo, be stable on the shelf for years, and not aggregate. Another issue with nanoparticles is that for nucleic acids, it is desirable that they be cationic (positively charged) so they can complex negatively charged nucleic acids. However, charged nanoparticles can cause toxicity. So, Dan Pack, David Putnam, and I added what are called ionizable molecules to nanoparticles that made them neutral at physiologic pH but charged inside the cells. This approach enables endosomal escape inside cells. Another area I worked on, initially with Jay Vacanti, was tissue engineering where Jay and I and my students created many of the principles and techniques in this field that are used today.
I also got involved in helping to start companies to advance our discoveries. The most well known company is Moderna. The company was initially criticized by scientists, stock analysts, and the news media who said the stock was overvalued and that our messenger RNA therapeutics would not work. However, Moderna produced a COVID-19 vaccine that saved millions of lives. Many other new medical treatments for cancer and other diseases are in late-stage clinical trials. Polaris Ventures and Harvard Business Review stated that billions of people are or will be helped by products created by companies I helped start.
I’m also so proud of the students and postdocs who worked in our laboratory. When I turned 70, they had a celebration and over 700 people came. One of the students I’m so proud of is Cato Laurencin. He joined our laboratory in the 1980’s and he has had a magnificent career and is a great person not only is he an outstanding scientist and mentor, he is also my friend. I’m so very honored to receive an award in his name.