The story of how the deadliest virus to humans was revived

General Studies Paper 2

Introduction

• Scientists routinely engineer new viruses in the laboratory. They make changes to the genetic material (DNA or RNA) of existing viruses to create new variants that may or may not exist naturally. Doing so allows scientists to compare the properties of the edited variants to their natural counterparts and infer the role of the changes that they made.

Virus from scratch

• For example, if they observe that some patients have a higher viral load in their blood for a given disease, and a particular mutation is observed in the DNA of viruses isolated from those patients, they can introduce that mutation into the DNA of viruses that don’t naturally harbour it, to see if it improves the viral output in the laboratory.
• But while scientists can easily introduce changes to the genetic material of a virus, they can’t create a virus from scratch. They have to rely on nature to do this.
• So, scientists take samples from patients, make more copies of the genetic material using a technique called a polymerase chain reaction, and use it to understand the sequence of bases that makeup its genetic material. Once they have the sequence, they can tweak it.

Meet H and N

• Researchers designate influenza strains using the types of two genes that the virus contains, named haemagglutinin and neuraminidase, designated ‘H’ and ‘N’.
• There are 18 subtypes of haemagglutinin, labelled H1-H18, and 11 types of neuraminidase, N1-N11, in nature. An influenza virus contains one of each and is classified accordingly.
• For example, the 1918 epidemic was caused by the H1N1 variant; the 1957 Asian flu was caused by H2N2; and the 1968 Hong Kong flu was caused by H3N2.
• There exist further sub-variations of these primary classifications, where different mutations exist in the ‘H’ and ‘N’ genes and which can further modify a virus’s properties.
• The 1918 flu and the 2009 swine flu were both caused by H1N1 – but they varied in disease severity due to the presence of changes on the H1 and N1 genes.

Full genetic sequence

• Scientists get to study the deadly 1918 H1N1 influenza virus. The samples allowed Taubenberger and Reid to determine the virus’s full genetic sequence.
• The sequence allowed other scientists to unearth insights into the virus’s beginnings.
• It appeared to have an ancestor that was avian in origin. But there were also tell-tale signs that the virus had adapted, by evolving, to infect mammals.
• In other words, the ancestral virus that infected birds had switched to infecting humans or swine.
• It had also been circulating for a few years, getting better at its job, before it vanished. Sometime later, it reemerged as one of the deadliest pathogens ever to afflict humankind.

Conclusion

• But for all these remarkable insights, the virus’s genetic sequence revealed nothing dramatic about the virus itself. It failed to explain how it could infect people so quickly or why it killed millions. There were minor variations in the genetic material but this is to be expected for RNA viruses. There remained but one way to answer that question: to recreate the virus itself.