OP-ED: A molecular tale

Important branches of the biological sciences arose to find solutions to medical problems at the molecular level in the early 20th century. Medical doctors were treating the symptoms of organ and tissue level dysfunction without being able to locate or cure the causes of the maladies. 

Initially, the discipline of biochemistry was able to establish the cause of organ-level malfunction by looking at the activities of specific enzymes, specific metabolites, or alteration in cell count or shape. These were helped by advances in chromatography, spectroscopy, and other instrumentation which helped in studies of molecular dynamics. 

With the discovery of the DNA structure in the 1950s, and the subsequent sequencing of the human genome in early 2000, the disciplines of biochemistry, molecular biology, and other related areas like genetic engineering became essential to fill the gap in knowledge for medical diagnostics and treatment. 

Microbiology also became more sophisticated as the range of microbes increased almost in competition with the growth of the human population. The discipline of bioinformatics had to be given birth to as well in order to handle the huge amount of sequence and other related data that started becoming available from the start of the 21st century. So, molecular knowledge and the means to handle gigabytes of data has become essential not only in the medical discipline, but also for health, agriculture, and the environment. 

The role of a biochemist and molecular biologist and related disciplines is therefore clear-cut and defined. They are experts at molecular level studies and diagnostics as was proven time and again from the start of the Covid-19 pandemic. Biochemists and molecular biologists as well as scientists from related disciplines were engaged in setting up the gold-standard RT-PCR tests not only in Dhaka, but all over the country. 

They are still engaged in this manner. This was not only to run the tests, but to explain the analysis of the results to the doctors who were in charge of treating patients and organizing sample collection as appropriate. In other words, cooperative and collaborative action among both biochemists, molecular biologists, as well as medical doctors were needed (as it should) to handle the crisis generated by the Covid-19 pandemic. 

Biochemists are experts by training and learning at most molecular diagnostics, and the results they produce should not need to be counter-signed by a doctor. This is simply because the doctor does not study the intricacies of the molecular diagnostic test even though s/he is the only one who knows what to prescribe as a consequence of the test result. 

Counter-signature by a doctor for a molecular diagnostic test like the RT-PCR or other sophisticated tests for cancer which need critical analysis by trained experts like biochemists, molecular biologists, and other related disciplines is not only unnecessary, but can be counter-productive. This is plainly because a medical doctor has never trained in these tests before! Doctors deal with the symptoms of a disease and biochemists, molecular biologists, et al look at the root cause through clinical, molecular, and genetic tests for which they have been trained over a period of four to five years. 

Just like an individual’s reaction and defense to the Sars-Cov-2 virus has many different shades, which a doctor can only define, the biochemists confront a range of quantitative results in an RT-PCR test for the same virus. The RT-PCR test quantitatively estimates the real-time concentration of the Sars-Cov-2 virus which varies from the start of infection to the shedding stage and recovery phase. 

Then again, the different strains of the virus achieve differing loads in the patients. For example, the viral load of the delta variant is 1,000 times greater than that of the original alpha variant. Then there is the Ct value, which calculates how many cycles of the reaction is needed for the viral copied DNA to reach a specific observable concentration. The reaction is also duplicated with two different primers. 

A biochemist will take all of this into account when analyzing the result, and call a result outcome negative or positive. This includes analysis of the reaction curve as the copied virus DNA is amplified in real time. Due to all these variations, it is possible that a negative test may become positive when sampled the next day or vice versa, depending on the stage of infection, the patient’s antibody response, and the viral load. This is the reason why WHO has recommended two back-to-back Sars-Cov-2 tests 10-14 days after a person recovers from a Covid-19 infection. 

Most solutions to problems need a multi-disciplinary approach -- this is particularly so for scientific and biological problems because of the complexity of their nature. We not only need to work together in a collaborative fashion, but to start understanding and respecting each other’s disciplines for the insights and approaches each has to offer to find successful and workable solutions to problems confronting our country.   

Zeba I Seraj is Professor at the Department of Biochemistry and Molecular Biology, University of Dhaka.