The Past Half Century of Engineering--And a Look Forward: Summary of a Forum (2015)

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Engineering and Medicine

Roderic Pettigrew went to graduate school at the Massachusetts Institute of Technology to work on a specific project that fascinated him: a treatment for a highly lethal form of brain cancer, glioblastoma multiforme, based on an idea that was “something out of Star Trek.” The treatment involved loading the stable isotope boron-10 into cancer cells and then exposing the cells to low-energy neutrons. The isotope captures neutrons and becomes boron-11, which rapidly fissions into a high-energy alpha particle and lithium. The range of these fission products in tissue is so small that their energy is delivered in a volume that is about the same size as a cell. In this way the treatment delivers “very focused radiation damage and death specifically to cancer cells and not the healthy surrounding cells,” Pettigrew said.

Pettigrew’s work at the interface of engineering and biology eventually led him to be named director of the NIH National Institute of Biomedical Imaging and Bioengineering. The institute was based on the idea that “biology and engineering were beginning to cross paths,” he said, which promised a transformative impact on the understanding and treatment of disease. This observation was underscored by a survey of physicians on the relative importance of 30 medical innovations in the last three decades of the 20th century. Engineering and imaging claimed the top innovation and played a major role in three of the top five—MRI and CT scanning (the top innovation), balloon angioplasty, and mammography—and was critical in more than half of the top 15.

The development of MRI is “an exemplar of this process,” said Pettigrew. In 1973 Paul Lauterbur, a professor of chemistry at the State University of New York at Stony Brook, published a paper in the journal Nature that arose from a “eureka moment.” The phenomenon of nuclear

magnetic resonance was well known but had not been used for imaging. Lauterbur realized that if a magnetic field were varied spatially it would produce a signal that corresponded to a location. The English physicist Peter Mansfield showed how to efficiently analyze these signals to produce an image and developed a way to do very fast imaging. For their discoveries, Lauterbur and Mansfield received the 2003 Nobel Prize in Physiology or Medicine.

“The point here is that there is no limit to imagination,” said Pettigrew. “Decades of continuous imagination and innovation led us, just 30 years down the road, to the ability to produce exquisite images of the human brain and some of its biological processes without harm.”

PATHWAYS IN THE BRAIN

As another example of the intersection of engineering and biology, Pettigrew briefly described neural tractography, the use of imaging to trace neural tracts in the brain in three dimensions. These pathways are not directly visualized, he explained. Rather, they are computed based on the diffusion of water along axonal pathways that are quantitatively resolved in 300 isotropic directions.

The technique has “rocked the neuroscience community” by revealing the detailed wiring patterns of the brain, said Pettigrew. For example, it has revealed orthogonal wiring patterns within sheets of neurons, which Van Wedeen, the discovering neuroscientist, speculates make it easier for developing neurons to navigate through space. Such studies also may provide insights into brain plasticity when one part of the brain becomes dysfunctional and adjacent areas of the brain are enlisted to serve a lost function.

Beyond the tracking of neural pathways, reverse engineering of the brain is a “daunting challenge,” said Pettigrew, but it is a challenge where engineering will continue to make progress.

CURRENT TECHNOLOGIES THAT POINT TO THE FUTURE

Pettigrew concluded by citing six current technologies (illustrated in a video¹) that demonstrate the incredible promise of engineering to improve health:

• Regenerative medicine makes it possible to grow human liver tissue in a mouse, which then can be tested for drug toxicity to avoid the need for human testing.
• Biodegradable stents can dissolve and resorb into the body, greatly reducing the body’s negative reactions to the implants.
• Tiny MRI devices combined with analytic chemistry platforms can probe virtually any biological target, including bacteria, viruses, and drugs, at very high sensitivity.
• A portable Doppler ultrasound device can be carried in the pocket and transported anywhere in the world, including disaster sites or remote regions.
• A bilayer polymer that changes shape as it absorbs moisture can be used as an energy source.
• An epidural spinal stimulation technique can return some voluntary motion to individuals who are completely paralyzed.

Pettigrew quoted Robert Goddard to make his final point: “It is difficult to say what is impossible, for the dream of yesterday is the hope of today and the reality of tomorrow.” Engineers and engineering make this

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¹ The video of his presentation is available online at www.youtube.com/watch?v=Vw-kIiHhMn8.

statement true, said Pettigrew. “Engineers are in the practice of dreaming, harnessing those dreams, and turning them into a reality, giving all of us real hope for a better and brighter future.”