Daniel Blanco-Melo, the evolutionary virologist, searches for ancient pathogens

Smallpox, measles, and mumps are among the infectious diseases European settlers likely introduced to the Americas at the dawn of the 16th century, leading to a devastating decrease in Indigenous populations. However, the precise nature of the viruses accountable for these millions of deaths is still unknown.

Daniel Blanco-Melo attempts to uncover this historical mystery. Blanco-Melo is an evolutionary virologist at the Fred Hutchinson Cancer Center in Seattle who utilizes advanced scientific investigation to study archaic viruses and reveal their role in shaping human evolution and history. Recently, Blanco-Melo and his team reconstructed two viruses found in Mexico during the European colonization period.

Blanco-Melo declares that "Our research on ancient viruses is very appealing due to its connection with history." Blanco-Melo's work has personal significance, as he hails from Mexico. Using genetic detective work, he delves into a topic close to his heart: understanding important historical events through the lens of molecular biology.

Blanco-Melo's fascination with viruses began in high school after coming across Matt Ridley's book Genome. Initially intended as a Father’s Day present for his father, Blanco-Melo ended up immersing himself in the book. Encouraged by his biology teacher, he started studying genomics at the National Autonomous University of Mexico, in the Cuernavaca campus.

As a Ph.D. student at the Rockefeller University in New York City, Blanco-Melo had his first exposure to ancient viruses. His research revolved around specific viruses, referred to as endogenous retroviruses, which are traces of earlier infectious viruses incorporated into a host's genetic code.

Blanco-Melo successfully traced the genetic remnants of an ancient retrovirus, called HERV-T, which proliferated among our primate ancestors millions of years ago. Upon further investigation, he discovered that a particular gene, responsible for creating the virus's external envelope, survived throughout primate evolution. Modern humans even retain an inactive version of this gene, which codes for the envelope protein that enables viral entry into a cell via cell-surface protein interaction.

Blanco-Melo questioned why such a viral gene would be so well conserved and what potential evolutionary benefit it could offer. Based on laboratory studies, he theorizes that ancient primates might have exploited the viral gene and used the associated protein to block viral entry into cells by eliminating the cell-surface protein.

This case underscores how viruses' genetic material, in the course of evolution, can be utilized against them. Blanco-Melo says that "This project not only sated my curiosity, but we were also able to develop a comprehensive narrative of virus evolution, emergence and extinction."

He suggests that modern researchers could employ similar techniques to fight against present-day retroviruses, with HIV being the ultimate goal.

Blanco-Melo recently partnered with evolutionary geneticist María Ávila-Arcos from the UNAM to study viral epidemics that decimated Indigenous populations in the Americas.

Blanco-Melo, Ávila-Arcos, and their research team extracted and isolated viral DNA from skeletal remains dating back to the 15th and 17th centuries. These remains were found in mass graves at a colonial hospital and a chapel in present-day Mexico City. Archaeological artifacts and hospital records indicate that the remains are of Indigenous peoples and enslaved Africans who succumbed to epidemics in the 1540s and 1570s.

The team reconstructed the genomes of two unknown viruses at that time, human parvovirus B19 and a human hepatitis B virus, based on these findings.

Jesse Bloom, a virologist at Fred Hutch not involved in this project, says that the team's study, published in the eLife journal in 2021, might be the first to recover ancient viral sequences from the Americas, denoting its global scientific and historical importance, particularly the Americas.

The research team discovered that these ancient viruses are similar to modern African strains. Blanco-Melo elaborates, "These viruses appear to have reached Mexico shortly after the arrival of the Europeans. However, they did not originate from Europe. Instead, they were brought from Africa, basically through the transatlantic slave trade."

Through the collaboration, Blanco-Melo has been careful to avoid helicopter research, where outsiders come to a place, get the data and take credit for the resulting work. “These samples should stay in Mexico, should be analyzed by Mexican researchers … and all those results are, of course, going to be communicated back into the communities. That’s our goal,” he says.

Though the two viruses the team identified aren’t likely to have caused massive epidemics, they could have exacerbated some of the symptoms of other diseases. Ongoing projects based on the same samples from Mexico are looking for other viruses and even peptides to get a fuller picture of the viruses from that time — and perhaps pin down big culprits. “There’s a lot more research that needs to be done in order to capture those other causative agents,” Blanco-Melo says.