Millennium man

Prof Robert Langer, latest winner of the Millennium Prize, is a pioneer of biomaterials for controlled drug release and tissue regeneration but sees himself as primarily as an engineer. Berenice Baker reports

In today’s rapidly evolving technological landscape, identifying a single innovation that has greater potential than any other to improve the quality of human life is a daunting task.

Yet that is the duty that befalls the committee of the Millennium Prize, the technology-world’s equivalent of the Nobel. Established by Finland in 2002, the biennial award has previously gone to Prof Tim Berners-Lee, the inventor of the World Wide Web and Prof Shuji Nakamura, inventor of the blue LED.

This year’s winner, announced at a glitzy ceremony in Helsinki last month, is the Massachusetts Institute of Technology’s (MIT) Prof Robert Langer, a pioneer of a branch of engineering that straddles biology and materials science: biomaterials.

Langer’s work in developing biomaterials for controlled drug release and tissue regeneration has informed treatments for conditions including cancer, schizophrenia and blindness-causing macular degeneration and helped regrow tissues, including skin and cartilage.

He sees himself primarily as an engineer. ‘I really want to do things that will help people,’ said Langer, talking to The Engineer before being announced as this year’s winner. ‘I also have a very interdisciplinary laboratory with wonderful people in it, and we’re all thinking, “How can we do things that will lead to new improvements?”’

After graduating with a chemical engineering degree in 1974 at MIT, Langer was determined to do ‘some good’ and, after he was turned down for some 30 jobs with colleges, hospitals and medical labs, his supervisor encouraged him to write to famed cancer researcher Judah Folkman, who had a reputation for taking on ‘unusual’ people.

‘He had this idea that tumours don’t grow beyond a millimetre without nutrition from a blood supply,’ said Langer. ‘They emit a substance called TAF (tumour angiogenic factor), which calls surrounding blood vessels to grow towards the tumour to supply nutrition and get rid of waste — angiogenesis. The first job was to isolate the angiogenesis inhibitor, so without TAF the tumour would wither and die.’

As cartilage has no blood vessels, they used some to extract a blood vessel growth inhibitor on which to carry out a bioassay. ‘We needed to study tumour growth in the absence of blood vessels, so we put a tumour in a rabbit eye as the eye is an unusual organ in that there are no blood vessels inside,’ said Langer.

Normally, TAF would cause blood vessels to grow towards the tumour where there are usually none, and the researchers wanted to prove the inhibitor would prevent this. ‘As blood vessel growth takes several months, we developed a polymer to slowly release the substance being tested,’ Langer said.

That was the Eureka moment that defined Langer’s career. ‘This was a revolution in bioengineering. You can’t swallow or inject large molecules such as the inhibitor as they get destroyed and have a short active life.’

Macromolecules such as the inhibitor could not be released through regular polymers due to their extremely limited release rate through polymers. So the researchers developed microspheres of polymers, which allowed a constant steady release.

So radical was the breakthrough that Langer and Folkman faced doubts from the scientific establishment when they described their work in 1976. ‘When we made the discovery that we could get molecules past a certain size through polymers, a lot of people didn’t believe it was possible, so there was a lot of scepticism and it had effects on my professional life.

‘When we figured out the science, and because other people could repeat what we did, that’s when things got better.’

Explaining the challenges of designing medical polymers, Langer said: ‘For molecules with a molecular weight of 300 or greater, they leave through interconnected pores in the polymer and take a long time to get through. The size of the pores defines the speed they leave according to the length of treatment needed. They could take a day or three years — the greatest problem was finding a grad student prepared to stay long enough to see the three years out!’

Langer showed his technology could work in live animals by slowly releasing insulin in diabetic rats. Medical science moves slowly, however, and it took 28 years from the discovery of the angiogenesis inhibitor to the approval of a treatment using it for cancer and macular degeneration — one of the biggest causes of loss of sight in older people, where blood vessels grow over the back of the eye. It can also be used in interventional cardiology — a polymer coating with anti-cancer drugs stops blood vessels and clots.

Another cancer treatment known as BCNU that is used to treat fibroblastoma only lasts 12 minutes outside the body. But by being distributed through a biodegradable non-toxic polymer, it can be used in localised chemotherapy by implanting wafers of the substance in the brain after surgery. Slow release polymers developed by Langer have also been used to treat prostrate cancer, schizophrenia and alcoholism.

‘In the past, scientists would take the materials used in household objects as inspiration for medical polymers,’ said Langer. ‘The strength and flexibility of a ladies’ girdle inspired clinicians to use polyether urethane in artificial hearts, Dacron fabric from clothing was used in vascular grafts and lubricating silicone inspired breast implants for example. Our approach was to create the polymers from scratch to exactly fit the purpose.’

Langer’s laboratory has also worked on memory metal for minimally invasive surgery. Wires, which are straight and easy to insert at room temperature, can form stents for gall bladder or cardiac operations at body temperature, or even form a self-tying knot.

He has also applied his unique skills to inhaled drugs, which are often inefficient as the powdered drugs tend to aggregate in the inhaler and on delivery, especially in granules two microns or less in size. ‘We decided to make the aerosols big but light and porous,’ he said. ‘This way it floats into the deep part of the lung, the bigger particle doesn’t aggregate, and the phagocytes which destroy drugs in the lung don’t eat it as fast.’

Langer’s polymers are also used as a scaffold on which to grow body tissues in a culture then transplant. ‘There is a donor shortage,’ said Langer. ‘Our method can be used to deliver liver, bone, cartilage, liver, intestine, heart muscle and urethra tissue. In the future we could rebuild an entire nose using cartilage cells from the ear. Initially, it could only be used for cosmetic purposes, as grown cartilage is not strong enough for knee injury. But we can grow a replacement outer ear for soldiers who have lost one in battle, for instance.’

Elsewhere, Langer’s technology has already helped a child with severe burns on his chest heal without scarring by putting on a skin cell polymer scaffold at the time of injury.

Other work that is in an early stage is using a polymer scaffold to build a new spinal column in people disabled through spinal damage. ‘We’re carrying out animal trials, but there are great steps ahead of us before we can treat humans,’ said Langer.

‘Our technologies raise principles in engineering and biotechnology that can relieve suffering and prolong life,’ he said, but admits there are limits. ‘Skin is an easy tissue to grow — it is thin and sloughs off. A liver, however, is made of five different cell types and is vascularised, so we can’t yet grow a whole one.’

Langer is co-director of a major nanotechnology grant, and his laboratory is to use the new technology to deliver drugs and genetic material such as SRNA and DNA right to the cells that need them.

And the next big thing in bio-engineering? Langer said: ‘The three areas we’ve done a lot of work in are new materials, growing new tissues and organs and drug delivery. I think nanotechnology is a cutting-edge area, which could be combined with other areas such as stem cell biology.

‘We also want to get a better understanding of the immune system and the brain from the perspective of engineering — immuno-engineering or neuro-engineering, if you like. I think those areas could be new frontiers, and very little has been done to date.’