By William Ray
Assistant Professor of Pediatrics, The Battelle Center for Mathematical Medicine

By their nature, two-dimensional images offer incomplete views, leaving that third dimension to speculation. In non-technical applications, it’s not critical to know what’s on the other side. But in medical research, when doctors are trying to find big answers that lie hidden in small organisms, the failure of two-dimensional images can multiply the difficulty of finding cures.

To combat the problem, we used 3D printing for visualization in our study of the Respiratory Syncytial Virus (RSV). By 3D printing large physical representations of proteins and organisms, we were able to break away from flat microscope images and see these structures in full view.

We continue to conduct this work at the Research Institute of Nationwide Children’s Hospital, located in Columbus, Ohio.

RSV is the leading viral cause of lower respiratory tract infection in infants and children worldwide. RSV has an estimated annual global disease burden of 64 million cases and 160,000 deaths. It is the most common cause of bronchiolitis and pneumonia in the United States for children under one year of age, and each year 75,000 to 125,000 children are hospitalized due to RSV infection, most under six months. It is estimated that more than 8.5 million adults (including those over age 65) are also infected annually. In the United States and Europe, approximately 900,000 hospitalizations result from RSV each year. Taking hospitalizations, lost workdays and mortality into account, this virus costs billions of dollars annually, yet there is currently no approved vaccine for its prevention.

One problem we face is that no one is sure how RSV actually works. What has become evident about the virus, however, is that a critical part of its lifecycle involves a molecular machine (the “F protein”) that is used to stir together the viral envelope and the targeted cell membrane. This results in the deposit of a viral payload into the cell.  Putting a wrench in the gears of this machine would stop the infection process, but because the gears of this metaphor have not yet been located (we still do not know how it works), past attempts to find a vaccine have failed.

To determine the true colors of this machinery, we set out to study the F protein using 3D printing. With a background in computational graphics, we knew relying on two-dimensional pictures would not yield the degree of insight required to solve the challenge of RSV, but we believed color 3D printed representations of the virus would benefit our research. Thus, when our center was awarded funding to invest in new technology to support its research, we jumped at the chance to obtain full color ProJet 3D printers from 3D Systems.

Our team, including noted virologist Mark Peeples, as well as my wife and longtime collaborator, Joan Ray, modeled RSV using computer graphics and computational physics tools. We then 3D printed models of the F protein, so we could hold it in our hands and gain visual access to the elusive third dimension of its molecular machinery. This has helped us see RSV in enough detail to formulate new intuitions about how it works and how it does not. This third dimension provides us with critical information. Even with prior access to stereo-3D monitors and professional graphics cards, nothing compares to a full color, physical 3D model.

Though a cure for RSV is still a ways off, ready access to color 3D models has moved research substantially forward and inspired new ideas about how it functions. 3D visualizations have also been instrumental in debunking former disruptive myths about the virus that had been leading researchers down unproductive paths.

Yet even for sophisticated users with extensive experience in photoreal graphics, 3D visualizations can do a poor job of conveying uncertainty. Though portions of models containing calculation error may be colored differently to indicate this distinction, uncertain parts are still just as real on the screen as the parts that are certain. This disconnect is exacerbated with solid 3D prints, as speculative parts of the model are just as solid in your hand as high-confidence portions. Therefore, at least until new technology allows us to print models with variable flexibility to tactilely represent uncertainty, the knowledge-transfer benefits of 3D printing are paired with the responsibility to remain ever cognizant of the reliability limitations of our current models.

This realization notwithstanding, the research community now has another tool in its arsenal to assist it in its quest to isolate, understand and resolve harmful pathogens and threats to our health. Full color 3D printers can cost between $25,000 and $70,000, but for the advance of our physical wellbeing and the knowledge of modern medicine, the investment is well worth it. After all, if a picture is worth a thousand words, a full color 3D model is all but priceless.

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