The coronavirus genetic code that causes COVID-19 is only about 30,000 characters long, but what a story it tells.
These nucleotides hide secrets from the virus's past, including its origins, its passage between families and its journey to distant ports. They signal how much time has passed and can be hidden by infecting people who show no external signs of illness. And they can point the way to drugs, vaccines and public health strategies that can control an uncontrolled crisis.
Unlocking all of this requires a combination of teamwork and technology that did not exist when the The SARS epidemic broke out almost 20 years ago. But today, when a deadly virus explodes out of nowhere, geneticists are indispensable players in the international game of whodunit.
"Now we can actually get a much more complete version of this puzzle," he said Dr. Liliana Brown, who heads the office of genomics and advanced technology at the National Institute of Allergy and Infectious Diseases.
For much of the 20th century, the central germ-hunting technique has been a labor-intensive process called contact tracking. It starts with a search for the person or people who were the first to be infected. Then, the research expands to the people with whom the initial patients interacted, then with whom they interacted, and so on.
Hopefully, the result is a map with a date and time for the spread of the germ that includes all cases of illness, death and recovery. These investigations provide inferences and insights into how a pathogen spreads, how deadly it is and what measures – including quarantines, school closures and travel restrictions – could delay its transmission.
A man crosses an empty road this month in Wuhan while the city is quarantined.
However, contact tracking is an imperfect process that is based on people's memories, their sincerity and the absence of casual encounters with strangers. With genomics, scientists can track the progression of mutations from patient to patient and establish relationships between them.
This can fill in gaps left by memory lapses or concealment. It can even signal new and worrying means of transmission between distant strangers – through vents or pipes that connect apartments, for example, or by air particles that remain longer than expected.
"Genomics has completely transformed our ability to track viruses and understand their spread," said Kristian Andersen, a pioneer in this emerging field, headquartered at the Scripps Translational Research Institute in La Jolla. "We are obtaining information not previously possible"
A virus gives up its secrets, one mutation at a time. As it moves from host to host, or population to population, it constantly launches, wins, or just revises the sequences that define it.
Armed with powerful computers and a mature understanding of how genes work and change, geneticists research the needles that will give them an advantage in data haystacks.
To do this, they break the DNA or RNA sequences of viral samples collected from different people or animals. Then they stack these strings on top of each other to see how and where they changed. With enough samples, they can reconstruct a “tree” of viral descent.
Patient samples are prepared to be tested for the new coronavirus.
(AFP / Getty Images)
Looking around the tree trunk – the common ancestor of all samples – they can find the first patients in an outbreak. This can help scientists determine when the virus first colonized humans and narrow the list of animal species that may have incubated the virus.
They can peek further into the branches for information on who infected whom, how quickly transmission occurred, and whether mutations along the way made the virus more infectious or more lethal.
When the genetic diversity of the samples seems unlikely to be broad, researchers need to explore new possibilities about the virus they are dealing with.
It may have infected many more people than initially thought, but it spread without causing symptoms. Perhaps it launched several attacks against humans from its animal base. Or it could have circulated harmlessly in humans for years and recently acquired a mutation that makes its hosts sick.
In just over a decade, this type of genetic investigation – scientists call it philodynamic analysis – has changed the way disease detectives investigate an outbreak.
Genomic analyzes of the Ebola virus emerged at various points during his three-year reign of terror, when it seemed to improve better from person to person and demonstrated the value of closing the border between Sierra Leone and Liberia.
Studies on the Zika virus revealed that it became harmful to fetuses in 2013 while circulating in French Polynesia, more than a year before triggering a wave of birth defects in Brazil.
Genetic sequencing helped to identify bats as the source of the virus responsible for respiratory syndrome in the Middle East and camels as the animals that transmitted MERS to humans.
So far, Chinese scientists have sequenced the complete genome of at least 115 samples from the COVID-19 coronavirus and shared the details with an international community of geneticists, who scour them for answers.
These sequences have already shown evidence that the virus first appeared in a wildlife host before jumping on humans. Bats are the main suspect, because there is little or no difference between the RNA of viral samples taken from bats in and around Wuhan and samples taken from people hospitalized with pneumonia of unknown origin in the early days of the outbreak.
That same pattern – a tree with bats at the base of the trunk, the first human patients in Wuhan just a step above them and more recent victims in ever-widening branches – allowed scientists to date the virus's appearance in people sometime early December.
A medical worker sees a patient in the intensive care unit of a hospital in Wuhan. The viral samples taken in the first patients with COVID-19 were genetically similar to those of bats.
(Xiong Qi / Xinhua via the Associated Press)
As an incidental benefit, the sequencing work provided scientific evidence of China's claims about managing the epidemic. Chinese officials said they responded quickly to the emergence of a new dangerous virus and that they hid nothing from the Chinese people or the international community. So far, the genetic data they have shared with the world suggests that this is true.
This was not always the case. In 2003, authorities concealed the outbreak of severe acute respiratory syndrome (SARS) in southern China, allowing the virus to spread to 16 other countries and kill 774 people.
Finally, the combination of genetic sequencing technology and outdated disease hunting has given scientists a rare glimpse of evolution in near real time.
Observing it in long-lived organisms, such as humans, would take thousands of years. But viruses change constantly, and by examining samples from a single outbreak, researchers can capture the subtle process of adaptation with surprising clarity.
Passengers at a Hong Kong train station wear masks to prevent the spread of COVID-19.
Even a small change can reveal a crucial moment when the virus mutates in ways that increase its fitness or spell its death, he said. Dr. Marc Suchard, UCLA biomathematician who studied the evolution of HIV and the flu.
Armed with the dynamic details of a virus' life cycle, scientists can do more than confirm their assumptions about how natural selection selects a winner, said Suchard. They can help answer some of the most worrying questions: who should be vaccinated first? Will a quarantine work? When consoling cultural practices endanger the safety of a community?
In a world of relentless viral threats, he said, the results can save lives.