Medical technology advancements are coming now that enable disease prevention—but, continued innovation is necessary.

Biomedicine has undergone a recent revolution that transformed our ability to identify and characterize a virus—that is, detection—as well as our ability to treat and prevent it—that is, countermeasures. One of the key technologies that underlies this revolution is genome sequencing, which allows us to detect and characterize novel threats and informs the design of targeted diagnostics, treatments, and vaccines.

Detection Technologies

When a virus first enters a human population, containment hinges on rapid and accurate detection. Once it is detected and characterized, a distributed and reliable diagnosis is the foundation of pandemic preparedness and response. This is partly because many infectious diseases present with overlapping symptoms, so precise, an early diagnosis is necessary to prescribe appropriate clinical or public health measures. It is also because some infectious diseases spread through asymptomatic or presymptomatic carriers, like COVID-19, of which 20 percent of transmission comes from cases that are asymptomatic and 30–40 percent from those who are presymptomatic, meaning that those infected may spread the virus without knowing. Thus, widespread early detection efforts are critical to containment.9, 10 Moreover, early detection can reverse the course of a disease by signaling the need for lifesaving treatment, like in the case of Lassa fever, where early treatment has reduced case fatality from 55 percent to 5 percent.11

The first major breakthrough in our ability to detect viruses is genome sequencing, which allows us to identify and characterize the genome of viruses circulating in clinical and environmental samples and to gain continual insights into their genetic diversity, evolution, and transmission. For example, within a month of COVID-19 entering the human population, genome sequencing allowed Chinese scientists to identify and characterize SARS-CoV-2—the causative agent. Since then, there have been over 3.4 million genome submissions and counting, as of September 2021, to GISAID, the publicly accessible global database, which have helped uncover patterns of transmission (for example, super-spreader events, increases in virus transmissibility) and identify variants of concern.12

Traditionally, scientists have relied on two kinds of diagnostics—polymerase chain reaction (PCR) and antibody tests. A classic molecular diagnostic, PCR works by extracting genetic material (DNA, RNA) from a sample, which is then copied several times over to confirm or negate the presence of a virus. It is sensitive and specific, suitable for clinical testing, and readily adaptable to new infectious pathogens.13 Alternatively, antibody tests can detect either the virus or antibodies to a virus. This group includes antigen capture tests, often used as point-of-care tests, which use antibodies that bind to viral proteins and other elements to signal if they are present in a patient’s body.14 Another type of antibody test, classic serology tests, determine if a patient is currently mounting an immune response or previously had an infection that left memory antibodies. Both classes face barriers to implementation (see table 2-2). PCR requires sophisticated machinery, thereby limiting its deployability; and antibody tests—like the U.S. FDA- approved antigen test for COVID-19—require bespoke development, which often takes several months.15

New technologies are emerging that have enabled increased diagnostic development and operability in lower-resource settings worldwide. Thanks to genomic advancements and new discoveries around isothermal amplification, CRISPR, and synthetic biology, scientists have developed a range of new, ultrasensitive, low-cost, rapidly programmable, and widely deployable point-of-care diagnostics. Isothermal amplification technologies such as LAMP (Loop-Mediated Isothermal Amplification) operate similarly to PCR, but at a single lower temperature, so that they can be performed with minimal equipment. As a test, LAMP was found to be highly specific, scalable, and cost-effective, and can produce results within an hour (compared to the four to eight hours required by PCR methods).16, 17 CRISPR, which consists of a guide protein and nuclease originally discovered in nature as a bacteria’s immune system to viruses, has been paired with isothermal amplification to enable the development of even more sensitive, fast, and portable diagnostic tests, such as SHERLOCK, DETECTR, and HOLMES.18, 19 The synthetic biology-based INSPECTR—a molecular diagnostics platform—has also enabled accurate and specific viral detection on a portable and affordable lateral flow test strip.20 Meanwhile, efforts to accelerate the development of antibody tests have been underway to prepare for new and emerging threats, and could provide a viable option for household testing kits by 2030.21

Countermeasures

Prior to the genomic advancements described above, the development of medical countermeasures was slower, more experimental, and less precise. Traditionally, therapies were often discovered in nature and had to undergo a long evaluation process to understand effects on patients. Classic vaccines required a complex process of inactivation of the antigen or viral protein—that is, the part of the virus that induces production of antibodies—to trigger a natural immune response, and development generally took up to a decade before safe public deployment was possible.22 Today, with the unprecedented ability to target pathogens based on their genome, countermeasure development has been faster, more innovative, and more specific than ever before. Examples of treatment and vaccines made possible by genomic advancements include monoclonal antibodies, messenger RNA (mRNA) vaccines, and universal vaccines to target all types of flu and coronavirus.