STRIDES IN SCIENCE

STRIDES IN MEDICAL

The world health community takes on a new pandemic

BY JOHN D. LOIKE & SALOMON AMAR Guest Columnists from 'The Scientist' magazine

hile scientific misinformation from so- cial media and from high-profile pub- lished papers has spread like wildfire in these past four months, there has also been an astoundingly rapid dissemination of validated scientific research published since the first case of COVID-19 was reported. Under normal conditions, scientific research is meant to be a slow, peer-reviewed, and calculated process of developing and testing a hypothesis, reporting the answers, and, finally, waiting for the scientific community to corroborate or disprove the findings. We are experiencing unprecedented times, and the scientific community has stepped up to address this pandemic. There are many critical research milestones that have been either achieved or in active development and reported in thousands of papers published about the coronavirus pan- demic. These include: 1) deciphering the ge- netic code of the virus and how it infects cells; 2) developing accurate assays to detect the vi- rus in people; 3) developing accurate assays to measure the level of antibody titers that should protect individuals from infections; 4) testing treatments and cures; and 5) conducting clinical trials of vaccines. In an incredibly short time, scientists at re- search universities and biotech companies have achieved remarkable successes regarding the first three milestones and have made im- pressive achievements in the latter two milestones that will hopefully lead to cures and vaccines. Despite the parallel dissemination of scientific misinformation, this progress is still a testament to the machinery of science and the passion of scientists. Comparing the timelines of COVID-19 accomplishments to those of previous RNA virus pandemics highlights just how rapidly research has moved.

For example, acquired immune deficiency syndrome (AIDS) was a term first used by the US Center for Disease Control on September 24, 1982, almost 18 months after the first cited report (June 5, 1981) of five AIDS patients. And

it wasn’t until 1984—almost four years after the first the potential efficacy of treatments in randomized case—when Pasteur Institute and National Institutes or open-label clinical trials. The FDA issued its first of Health scientists independently reported the disemergency use authorization (EUA) of a real time covery of a retrovirus (HIV) that caused AIDS. Two RT-PCR diagnostic test in early February. There are years after that, the US Food and Drug Administranow scores of RT-PCR assays with high accuracy and tion (FDA) licensed the first commercial blood test few false-positives with other human coronaviruses to detect HIV. A year later, in March 1987, the FDA or common respiratory pathogens.The FDA issued approved the first anti-retroviral drug for AIDS, zithe an EUA to Abbott for an assay to detect antiboddovudine (AZT), in a record 20 months. Finally, the ies against this virus in March, and now lists more first clinical trial for a vaccine began in August 1987, than a dozen serology tests given EUA. and VaxGen launched the large-scale trial in 1998. These clinical trials failed, leading this nowmerged company (Diadexus Inc.) to bankrupt- cy in 2016. To date, there are only a few ongoing clinical vaccine studies, but no FDA-approved HIV vaccines. Vaccine development for COVID-19 has been similarly rapid and ro- bust, with dozens of companies and collab- orators developing and trialing both convention- al and innovative technologies. Traditional methods include designing a vaccine with an inactive or at- tenuated virus that will not infect the recipient but THE RAPID PROGRESS TO ACHIEVE SCIEN- TIFIC MILESTONES IS BEING SEEN IN REAL TIME WITH COVID-19. By comparison, scientific milestones were significantly accelerated in response to the SARS epidemic of 2003. On November 16, 2002, the first case of atypical pneumonia, probably caused by the SARS-CoV virus, was reported in southern China. Less than five months later, the US Centers for Disease Control and Prevention published the genetic sequence of SARSCoV. By May and December 2003, two articles in trains the immune system to prevent viral infectivity. New technologies include one that introduces a mes- senger RNA into an individual so that it can direct cells to make critical COVID-19 viral proteins that are viewed by the immune system as “foreign” and enable the body to build effective immunity. This approach, used by Moderna in partnership with the National Institute of Allergy and Infectious Dis- eases (NIAID), has not been used in any approved the New England Journal of Medicine described the vaccines to date. On May 22, 2020, NIAID Director application of real-time reverse transcriptase PCR Anthony Fauci said it’s still possible that a coronavi- (RT-PCR) to accurately detect SARS-CoV in human rus vaccine using classical or innovative technologies blood or tissue. Real-time RT-PCR is a very fast and will be available in the US by December. There are precise method to amplify viral RNA that quantifies now more than 100 potential vaccines in clinical tri- viral particles in human biological samples (that is, als running at an unprecedented pace. blood or a nasal swab), and it is extensively used in the COVID-19 pandemic. Still, the response to the SARS outbreak did not deliver the milestones we’ve seen in just a few short months with COVID-19. Currently, there is no medication that is known to effectively treat SARS. Treatment is only supportive. In part because the SARS pandemic subsided within a few years, there are no listed clinical trials for SARS and no FDA-approved vaccine for this virus. The rapid pace of publishing scientific preprints and peer-reviewed articles during this pandemic is bound to result in some mistakes from inaccurate data or poor analyses, but this casualty is worth it in light of the astonishing progress that has been made and will continue to be made in the face of this global threat. History has shown that the scientific commu- nity takes full advantage of peer review, collabora- tions, confirmatory studies from other scientists, and The rapid progress to achieve scientific milestones is being seen in real time with COVID-19. On Dec 31, 2019, China reported a cluster of cases of pneumonia in people at Wuhan, Hubei Province that later became known as SARS-CoV-2. Less than two self-assessment to correct scientific mistakes. The rapid pace of scientific research in its ongoing search for truth is not perfect, but the accelerated response has great merit and potential to be used for current and future pandemics. weeks later, on January 12, the first genomic characterization of the virus was reported. Across the Original article: J. D. Loike and S. Amar, “Opinion: Don’t Disparage the Pace of COVID-19 Research,” The Scientist, the-sciglobe scientists quickly launched trials to examine entist.com, June 22, 2020. Used with permission.