By DR. SURI SEHGAL
Many of us had assumed that the controversy on the origin and spread of coronavirus had died down, but apparently it is not so. I was asked by a friend what I thought of it, and to give my technical opinion, since my background is in genetics and molecular biology. The request was to write it out in simple language so a layperson could understand.
The US is fortunate to have a scientist of the caliber of Dr. Anthony Fauci, who has guided several past administrations and remained at the forefront of US efforts to contend with viral diseases such as HIV/Aids SARS, the Swine flu, MERS, Ebola, and now COVID-19. His advice over the years has always been based on solid scientific data and sound judgment.
A current controversy is about whether the COVID-19 coronavirus was intentionally made and escaped from the Chinese Wuhan laboratory, or has it spread naturally like other viruses, including other coronaviruses. The commonly accepted hypothesis was that COVID was transmitted from bats to humans through an intermediary wild animal, some of which are unfortunately sold commonly in the Wuhan wet market.
There is still no actual evidence that COVID-19 was made and escaped from the Wuhan virology laboratory. Maybe the first infected person was a researcher collecting or handling samples collected in the wild, which remains hard to exclude, but is less likely.
People all over the world are upset about this new controversy, and rightly so because of the social and economic havoc it has caused—first in the developed countries, and now in the developing world. The intentional escape hypothesis is merely speculation; and, in my humble opinion, pure fantasy.
The technical facts about COVID-19 are these: We should be grateful to the Wuhan Chinese researchers who immediately published the genetic structure of the new coronavirus soon after it was completed by them in early January 2020. It was first named COVID-SARS-2. Within a few days of the Chinese publication (probably within just a few hours), scientists in the West began the designs for what would eventually become the BioNTech (Germany) and Moderna (US) vaccines.
The only molecular biology one needs to know to understand this, is this: in nature, DNA molecules carry the genetic information that is embedded in the genetic letters of a sequence. The genetic unit is a “gene” that encodes the protein. The DNA of a gene is “transcribed” in a cell’s nucleus where enzymes produce a copy of the sequence as mRNA (the messenger RNA).The mRNA is translated by the cell’s machinery into a protein.
To start, western scientists designed a DNA sequence that encodes the COVID “spike” protein in bacteria. The DNA sequence was chemically synthesized and multiplied in standard microbes. Small quantities in grams of spike genes are produced and purified by growing the bacteria in fermentation vessels. From this, trillions of copies can be made as needed to produce the final vaccine.
From studies of other coronaviruses, it is already established that the spike protein is a major antigen. \Therefore the spike protein was an obvious target for the vaccine development.
These spike DNAs are used as templates to be transcribed into mRNA molecules. Specific enzymes carry out this assembly in vitro.
The mRNA is translated by the cell’s machinery into a protein. Lots of optimization is then incorporated by design in the DNA to increase the stability of the mRNA, or to increase its translatability to human cells.
The mRNA is finally incorporated in microscopic particles made of highly sophisticated lipids (like oil droplets) called nano lipid carriers. This formulation step is crucial to preserve the mRNA. The mRNA is now ready to transfer to vials for shipment and for vaccination.
BioNTech joined hands with Pfizer of the United States, because Pfizer has the world-class manufacturing capacity, the worldwide distribution network, and the financial depth to build additional facilities that might be needed for manufacturing and warehousing the vaccine. Strict quality control measures are followed at all key steps.
Upon injection into human tissue, the nanolipids fuse with the lipids of human muscle cells and deliver the mRNA into the cells, where it remains for a few days. The cells translate the mRNA into spike protein, which is exported from the cells. This triggers the immune response, as our body creates antibodies that recognize the spike protein, and when confronted with the COVID virus, they neutralize it.
Just 30 µg ( 0.000030 gram) mRNA is in a vaccine dose!
Viral vector vaccines
This same technology has already been used in the development of vaccines against Ebola, Zika, and others.
The key principle is that a functional spike gene itself is used to vaccinate. To deliver the spike gene, it is engineered within a harmless adenovirus that causes the common cold. Oxford University, where AstraZeneca vaccine was developed, uses an adenovirus that infects chimpanzees (and to which humans do not have a preexisting immunity). Johnson & Johnson uses a rare variant of the cold virus as a carrier.
The vector’s DNA and the gene-encoding spike are stitched together by genetic engineering. The recombinant (naturally occurring recombination) virus is multiplied by infecting large batches of a cultured human cell line.
AstraZeneca uses a cell line grown from lung or kidney cells. The vaccine only contains purified recombinant adenovirus with the spike gene. The virus DNA is transcribed in the nucleus, where spike mRNA is produced and translated into spike protein. The protein translocates to the outside of the cells, and triggers the immune response, leading to COVID immunity.
Looking ahead
The four vaccines on the market (Pfizer BioNTech, Moderna, AstraZeneca, Johnson and Johnson) are the first of a long series of vaccines to come. Some are based on other technologies. More than 50 candidates are in clinical trials.
A lot of research now focuses on dealing with present and future variants of the virus and on reducing production and distribution costs.
There is no longer a technical impediment to produce. Before the end of 2022, the 10 billion doses of vaccines needed to protect the global population from COVID-19 will be available. The current global population stands at 7.9 billion and projected by the UN to be 10 billion by year 2057.
The science behind this technology goes back to 1953 when Watson and Crick first published the double helix structure of DNA for which they won a Nobel Prize. Since then, billions of dollars have gone into biotech research mostly by the public sector to advance the science. Yes, the vaccine was developed in one year, but the science behind it has a long history.
Costs/benefits
Johnson & Johnson and AstraZeneca both vowed to sell their vaccines on a nonprofit basis during the pandemic. Moderna, which has never made a profit and has no other products on the market, decided to sell its vaccine at a profit.
Unlike Moderna’s vaccine, Pfizer’s shot is not crucial to the company’s bottom line. Last year, Pfizer earned $9.6 billion in profits before the COVID vaccine had any discernible impact on its results.
Pfizer frequently points out that it opted not to take federal funds proffered by the previous administration under Operation Warp Speed, the initiative that promoted the rapid development of COVID-19 vaccines.
BioNTech received substantial support from the German government in developing their joint vaccine. And taxpayer-funded research aided both companies: The National Institutes of Health (NIH) patented technology that helped make Pfizer’s and Moderna’s so-called messenger RNA vaccines possible. BioNTech has a licensing agreement with NIH, and Pfizer is piggybacking on that license.
Pfizer has kept the profitability of its vaccine sales opaque. The United States, for example, is paying $19.50 for each Pfizer dose. Israel agreed to pay Pfizer about $30 per dose, according to multiple media reports.
The benefit can be summarized in one sentence: Success of the vaccine has saved humanity from prolonged suffering and saved the economies of the world.
I am grateful to Dr Jan Leemans, my friend and former colleague at Plant Genetic Systems in Belgium, for his expert technical input in writing this article.
—Suri Sehgal
(Dr Suri Sehgal, PhD, leading international crop scientist; chair of the Board of Trustees of S M Sehgal Foundation and Sehgal Foundation, USA)
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