In December 2019, the first cases of a respiratory disease caused by an unknown infectious agent were reported in the city of Wuhan in Hubei Province, China. Over the next few months, the disease spread around the world, causing widespread illness and death. The numbers “are staggering,” said David Walt, the Hansjörg Wyss Professor of Biologically Inspired Engineering at Harvard Medical School, during his plenary presentation at the 2020 annual meeting of the National Academy of Engineering. “Every time I update [the numbers], I am saddened by how many more people have been infected and how many more people have died.”1
The virus that causes the disease, which was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the seventh member of the coronavirus family that has been reported to infect humans, Walt explained. Four of the seven cause mild symptoms in humans, but three produce more severe symptoms. The first SARS coronavirus, which also was first detected in China, caused just over 8000 confirmed cases across 32 countries in 2002–03 and nearly 800 deaths—a mortality rate of approximately 10 percent. The Middle East respiratory syndrome (MERS) coronavirus, which was associated with an outbreak of disease in Saudi Arabia and other countries in 2012, caused about 2500 cases and 858 deaths, resulting in a much higher fatality rate of approximately 33 percent.
Though the fatality rate for the disease caused by the newly identified SARS virus, named coronavirus disease 2019 (covid-19), is lower than for the earlier SARS virus, the new virus has infected many
thousands of times more people. As a result, said Pam Cheng, executive vice president of global operations and information technology for AstraZeneca, during her plenary presentation, the pandemic has posed more than a health crisis. Jobs were lost and workforces slashed. Schools went online and childcare centers closed. Panic buying and hoarding of basic necessities led to shortages of essential items. The stockpiling of medicines and medical supplies threatened shortages across the globe. “No part of the world has been left untouched,” said Cheng. “We have all underestimated the complexity of the issues.”
Coronaviruses consist of a protein envelope surrounding their genetic material, which is the molecule RNA in coronaviruses rather than the DNA in human cells. The protein envelope is covered by spiky proteins that resemble the protrusions on a crown, thus giving the viruses their name. When the spike proteins bind to receptors on human cells, the virus injects its genetic material into the cell, where the RNA highjacks the cell’s biochemical machinery to produce new copies of the virus.
Just a few weeks passed between recognition of the new disease and the sequencing of the virus’s genome. “Twenty years ago, this would have taken at least six months, perhaps longer,” Walt said. The sequencing of the first human genome cost over $3 billion and took more than a decade. Today, benchtop devices can simultaneously sequence nearly 50 human genomes for less than $1000 each. “That is six zeros taken off the cost alone.”
Engineers were pivotal to this technological revolution, said Walt. Bioengineers designed enzymes to perform the biochemical sequencing steps. Mechanical engineers developed fluidic systems to move nanoliters of material deliberately and accurately. Optical-electrical engineers provided the sensors that detect faint light signals emitted by the sequencing reactions. Materials scientists and engineers helped create the integrated solid state circuitry that could work in aqueous environments. Computer scientists and engineers developed the computational hardware and informatics needed to analyze the terabytes of data generated during a single sequencing run.
Engineering has also been essential in many of the other responses to covid-19, Walt observed. As biomedical researchers began working with clinicians to overcome the problems arising in clinics and hospitals, both groups “partnered with engineers to help find scalable solutions.” Engineers developed ways to produce needed supplies, such as nasal swabs, through 3D printing. They repurposed equipment designed for other uses, such as anesthesia gas delivery systems, as ventilators. They even produced devices such as shirts with which family members and healthcare providers could give virtual hugs to patients in isolation.
Cheng, too, highlighted the importance of engineering in responding to the epidemic. For example, when AstraZeneca needed to repurpose a sterile powder-filling facility into a biosafety containment facility dedicated to the formulation, filling, and packaging of a vaccine for the virus, engineers redesigned the ventilation system and facility flows, reengineered the filling line, installed vial labeling equipment, and automated visual inspection equipment. The project went from concept to construction in 2 weeks, construction was complete in 10 weeks, and the facility was ready for qualification in 21 weeks, all while continuing to produce the medicines provided previously from the site.
“I have never seen a group of people more passionate, more committed, and more happy to be working so hard,” said Cheng. “It was absolutely fantastic to see what smart and passionate engineers can do.”