Q&A: Dr Robert Langer

Q1: Who is Dr Robert Langer?

Dr Robert Langer FREng is an American engineer at the Massachusetts Institute of Technology and winner of the 2015 Queen Elizabeth Prize for Engineering. He is the most cited engineer in history, having been cited nearly 170,000 times. He has an H index of 210.

Dr Langer is an internationally acclaimed inventor and engineer, with over 1,000 issued and pending patents and 1,300 published articles. His work as a chemical engineer in the medical and surgical fields made him a pioneer in bioengineering, drug delivery, tissue engineering, and nanotechnology.

Dr Langer has won a dizzying array of prizes and awards, was named as one of the 25 most important individuals in biotechnology by Forbes Magazine and CNN (1999) and Bio World (1990), and as one of the 100 most influential people in America by Time magazine (2001).

Q2: What was Robert Langer like before he became an engineer?

Langer’s interest in chemistry was sparked at a young age, when his parents bought him a Gilbert chemistry set. As an 11-year-old he set up a small laboratory in the basement of his house in Albany, N.Y. In high school, he was the top runner on his varsity track team, and he continues to exercise extensively today.

While completing his education, Langer helped start a school, the Group School, which was based on democratic educational principles. In the 1970s, the town of Cambridge, MA was a study in contrasts. It had world-class research institutions, but it also had the highest high school dropout rate in America for a city of its size. Langer’s experience at the Group School, which aimed to reach those who had dropped out, led to him to create new science curriculum that was accessible, motiving, and enjoyable for his students.

Q3: How did engineering impact Robert Langer’s life?

Langer studied chemical engineering at Cornell University and received his Sc.D. in chemical engineering from the Massachusetts Institute of Technology in 1974. He was driven by a desire to use his chemical engineering background to directly improve peoples’ lives, so he took a job as a postdoctoral fellow in a hospital. In the 1970s, this was a very unusual route for a chemical engineer. This experience, coupled with his engineering training, set the stage for his ground-breaking advances in bioengineering.

Q4: Who did Robert Langer learn from and work with early on?

As a postdoctoral fellow, Langer worked for cancer researcher and surgeon Dr Judah Folkman at the Children’s Hospital Boston and at Harvard Medical School. Folkman was a visionary and an excellent role model for Langer. As a student in Harvard Medical School, Folkman developed one of the earliest pacemakers. In the early 1970s, he hypothesized that controlling the way blood vessels form in tumours could yield new ways to treat cancer. Working from this basis and with Folkman, Langer developed new and innovative technologies, focusing on restricting tumour growth and on developing controlled-release drug delivery systems.

In the 1980s, Langer worked with Harvard surgeon and transplant researcher Jay Vacanti. They discovered that tissues and organs could be produced from cell cultures on three-dimensional polymer scaffolds. This work helped lay the foundation for the field of tissue engineering.

Q5: How has Robert Langer used engineering to change the world?

In his early research, Langer encountered a great deal of scepticism; this led to the rejection of his nine initial research grant applications. However, he persevered. The FDA approved his polymer-based treatment for brain cancer in 1996, and many other products have since matured from the lab to the public. Following this approval, Langer participated in the founding of multiple technology companies, including Enzytech (which merged with Alkermes), Momenta Pharmaceuticals, T2 Biosystems, and Moderna Therapeutics.

He has also directly changed the lives of over 800 students in fields ranging from medicine to electrical and chemical engineering to physics and chemistry. Nearly 300 are professors; and many lead companies around the world. Langer’s research laboratory at MIT is the largest academic biomedical engineering lab in the world, maintaining over $15 million in annual grants and over 100 researchers. 14 of his trainees are in the National Academy of Engineering or in the Royal Academy of Engineering.

Q&A: Controlled-Release Large Molecule Drug Delivery

Q1: What is controlled release drug delivery? Why is it important?

The judges have awarded the QEPrize for a technologically disruptive change in controlled-release drug delivery systems. Controlled release in drugs is important because a dose that is too high could be toxic, but a dose that is too low will not be effective. Controlled release drug delivery gives a patient the correct dose over a long period of time but requires much less frequent doses. For example, Bydureon® is the first weekly treatment for Type 2 diabetes.

Q2: What’s the difference between small molecules and large molecules?

In the area of pharmaceuticals, small and large molecule drugs are nominally differentiated based on their weight, with small molecules generally placed at less than 300 atomic mass units. However, they have many more differences. Because of their size and chemical properties, small molecules are relatively stable in the body and can cross cell membranes quickly and without assistance, easily reaching the active areas inside cells. Furthermore, some small molecules can cross through solid polymers. They stay confined and slowly leak out, leading to a steady dose over a long period of time. In contrast, large molecules are too big to do this and simply get trapped inside. Aspirin, with 21 atoms and a low molecular weight , is a conventional small molecule.

Small molecules are incredibly useful and make up the majority of available drugs. However, large molecules hold the key to tackling long-standing problems like cancer, mental illness, and diabetes. Unlike small molecules, they can attack specific cells and react in tailored circumstances, acting in the same ways as the body’s own proteins. Large molecules also have different chemical properties; they might have 20,000 atoms and be over 800 times heavier than aspirin. Furthermore, aspirin always has the correct structure. In contrast, the structure that a large molecule takes is vital to its function, and large molecule drugs are vulnerable to degrading and deforming when exposed to the body’s environment.

Q3: Why was Robert Langer’s work innovative?

Dr Robert Langer was a founding figure in the field of large molecule controlled drug delivery. His training as a chemical engineer and fundamental understanding of the sciences enabled him to make advances at the intersection of new materials synthesis and applied engineering. In a time when few, if any, engineers worked in experimental medical research, Langer’s perspective on medicine was unique: he saw surgery problems but created chemical and engineering solutions. Medicine at the time relied on existing, analogous materials. For example, dialysis tubing was made of cellulose acetate, inspired by its use in sausage casings. Polyether urethane, commonly employed as girdle elastic, was adapted for artificial hearts.

Langer turned this approach on its head. Instead of using what seemed convenient, he asked the engineering design question: what do you really want, from an engineering, chemistry, and biology standpoint? His answer was to synthesize exactly what was needed to solve problems. Not only did he solve the problem of large molecule drug delivery, he fundamentally changed the way that we use materials in medicine.

Q4: How is this innovation engineering?

Robert Langer translated engineering principles into human beings. He instituted a new, systematic, and rigorous engineering approach in medical material design. Starting with the engineering design question flowed naturally into considering and using engineering principles. The controlled delivery of large molecules in the complex environment of the human body relies on a thorough understanding and the precise application of engineering techniques and principles, including time-dependent design, modelling, reaction theory, and mass transfer.

Perhaps even more fundamentally, engineering is about two things: ingenuity, and problem solving. Experts and companies had dismissed this problem, but its solution needed real creativity and interdisciplinary collaboration. Ultimately, the clever solution lay at the intersection of many fields. Langer always kept the final goal in mind – as in much of engineering, he did exactly as much as was needed to solve the problem.

Beyond this, engineering is often called “the science of scale-up.” Langer started companies to see his ideas through from the lab to the patient. Without engineering, and its combination of new ideas and business savvy, these ground-breaking ideas would never have reached the people they were intended to help.

Q5: How did Dr Langer develop controlled release drug delivery for large molecules when so many people thought it was impossible?

Drug distribution systems existed prior to Langer’s innovation, but it was believed that slow, timed drug release was limited to small molecules. This was the standard view in fields ranging from medicine to polymer science.

Langer created a polymer and a system that overcame all of the long-standing challenges. Incorporating biomolecules into the creation of his polymer resulted in one that contained water-filled channels through which the large molecules could travel. Scientists were correct in believing that large molecules could not travel directly through polymers; but Langer gave them another path by applying an understanding of engineering phenomena. By engineering the channels such that they wound around in long, precise pathways, Langer could control the amount of time it took to disperse the large molecules. Faster systems are like walking through a park where the trees have all been planted in rows. Finding a way out is quick because the path is direct. In contrast, Langer’s paths are like trying to hike out of a forest filled with many, winding trails. He could design each path to take a certain amount of time. Additionally, the polymer itself broke down in a controlled fashion. It was another way to protect the fragile large molecules and release them at the correct rate, over as much as five years.

Q6: What else can be done with Robert Langer’s QEPrize-winning innovation?

Langer’s work was the basis for, among countless other innovations, long-lasting treatments for brain cancer, prostate cancer, endometriosis, schizophrenia, diabetes, and the drug-coated cardiovascular stents that alone have benefited 10 million patients.

Langer and many other researchers have extended his founding work into nano-medicine, tissue engineering, and to fields as diverse as agriculture and cosmetics. The 1000 patents that carry his name; the 300 pharmaceutical, chemical, and biotechnology companies that use his technology; the hundreds of his former students in engineering, chemistry, biology, physics, and medicine who now lead companies and labs around the world; and the 2 billion lives improved by the technologies that his lab has created serve witness to Langer’s unchanging goal of helping people, with engineering and science.