The Birth of Ebola

May 1, 2015

By Medical Discovery News

Colorized micrograph of Ebola by Dr. F.A. Murphy

For most Americans, the Ebola scare seems to have come and gone, but that doesn’t mean the outbreak is over in Africa or that we’ve seen the last of the virus, especially considering its history. Scientists believed that Ebola is relatively new as far as viruses go – only 10,000 years old. However, ancient animal bones show that Ebola appeared between 16 and 23 million years ago, perhaps even earlier.

The Ebola virus was discovered in 1976 during two outbreaks in what was then called Northern Zaire (now the Democratic Republic of the Congo) and Southern Sudan. The outbreaks were actually caused by two different strains of the Ebola virus named Zaire and Sudan, with 90 and 50 percent mortality rates respectively. Since then, three other strains have been identified: Tai Forest, Bundibugyo, and Reston, which is the only one that doesn’t affect people. Overall, there have been 27 outbreaks, but the current outbreak that started in March 2014 is by far the worst, infecting almost 25,000 people and killing over 10,000, thereby making it the world’s first Ebola epidemic.

Ebola is a member of the filovirus family, which also includes the Marburg virus discovered in 1967. Filoviruses are zoonotic, meaning they replicate in other animals, their natural reservoirs, before transmitting to humans. The Ebola virus’s natural reservoir is African fruit bats, so it can transfer to humans who come into contact with an infected bat or another species that has been infected, such as chimpanzees, antelope, and porcupine. Then the virus can spread from person to person.

New research into the origins of filoviruses shows that they have evolutionary ties that go back millions of years. Scientists tracked the viruses’ origins by looking for pieces of their genetic information in fossilized animal bones. While using the bones to study the genomes of ancient voles and hamsters, they found the same pieces of the viruses’ genetic material in the same locations in both rodent species. This suggests that the viruses have existed at least as long as the two species have.

Given the billions of bases each animal has in its genome, it is highly unlikely that these fragments of viral genetic information would have been inserted in exactly the same locations during different infections. Scientists therefore concluded that the virus had infected a common ancestor of these two rodents sometime before the Miocene Epoch, 5-23 million years ago, around the time the great apes arose. Furthermore, the viral genetic elements more closely resemble Ebola than Marburg, meaning the two viruses had already diverged from each other. Sometime before then, the two viruses shared a common ancestor that has not yet been identified.

This means that these viruses have been coevolving with mammals for millions and millions of years, much longer than previously believed. An understanding of the origins and evolution of filoviruses could help us better prevent outbreaks of them and hopefully even create a vaccine that would be effective against all of them.

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Richard III Rises Again

Aug. 15, 2014

By Medical Discovery News

Richard III at Bosworth

One of the literary world’s most despicable villains, William Shakespeare portrayed Richard III as a clever, ruthless murderer obsessed with ascending to the throne of England. Historical accounts of this last king of the Plantagenet dynasty are more kind and describe a complex figure, who during his brief reign instituted reforms beneficial to the common man. For example, he started the Court of Requests where common people’s petitions could be heard, instituted the practice of bail for citizens, and banned restrictions on printing and selling books. While these historical accounts provide some good information about Richard III, new forensic science reports can give us an even more extensive view of this historical figure.

When King Edward IV died in 1483, his 12-year-old son Edward V inherited the throne while Edward’s brother Richard was named Lord Protector. Soon after, court gossip perpetrated by Richard resulted in Edward V and his siblings being declared illegitimate; therefore Edward V could not assume the throne. Richard was crowned king. Edward V, who was in the Tower of London, was presumably killed. Edward’s supporters then tried to unseat Richard III and replace him with Henry Tudor, who was living in exile.

This effort culminated at battle of Bosworth Field. Accounts of the battle indicate that Richard led a cavalry charge that almost killed Henry Tudor but fell short and Richard was surrounded and killed. Here the story becomes murky, with accounts differing on what happened to Richard’s body. 

Fast forward to 2012, when the City of Leicester and the University of Leicester began searching for Richard’s remains. They started at the site of the long-destroyed Church of the Grey Friars, where some say he was buried. The most likely spot for the church’s burial ground was beneath a parking lot, and they did discover human remains there.

Forensic science then played a major role in identifying those remains as Richard’s. The skeletal remains were those of a male who clearly suffered from spinal scoliosis or the curvature of the spine. The man would have had one shoulder higher than the other, giving him a hunched appearance, which fits Richard’s descriptions. Next, the remains showed multiple wounds to the head, which also coincide with accounts of Richard’s death on the battlefield.

Strong evidence came from mitochondrial DNA, which is always inherited from the mother and is therefore an accurate way to tell whether people are related. Using a DNA sample from a modern-day descendent of this once-royal family, the DNA analysis showed a clear match between the modern relative and Richard. Together, all the evidence points to Richard. Recently, 3-D mapping of the skull created a forensic reconstruction of his face.  

Richard’s remains will receive a dignified interment in Leicester’s cathedral next spring, although descendants of the Plantagenet family fought and lost a court battle to have him re-buried in York. In the meantime, scientists at the University of Leicester plan to sequence Richard’s whole genome, which would provide an unprecedented look at his ancestry and health. He will be the first prominent historical figure to have his total genomic sequence determined.

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The Human Genome Revisited

March 1, 2013

By Medical Discovery News

When scientists sequenced the human genome in 2000, it revolutionized biomedical research, much like the invention of the Internet forever changed communications. The project aimed to identify all the genes in the human genome.

At first, they estimated that humans had less than 100,000 genes, then improved methods lowered that to 35,000, and a new analysis suggests that humans have no more than 21,000 genes. When considering the complexity of a human being, that number does not seem very high.

However, even the highest of those estimates accounted for less than 20 percent of the DNA sequence in the human genome. The rest of sequence did not appear to encode genes that led to proteins and was therefore considered non-functional or “junk” DNA.

Now a recent study by more than 400 researchers at 32 institutions costing almost $300 million challenges that notion and suggests that more than 80 percent of the human genome is indeed utilized and therefore important in the overall biology of each person – so much for “junk” DNA. The Encyclopedia of DNA Elements (ENCODE) project concluded that 20,687 genes produce proteins and an additional 18,400 genes produce RNA involved in coordinating the activity of the genes that produce proteins. 

This extensive effort originally focused on the genomes of a small number of human cells but later expanded to include almost 150 different cells, including immune, embryonic, liver tissue, umbilical cord, and cancer cells. Specific genes produce proteins for different tissues at different stages of human growth, so using this wide array insured that the analysis included all active genomic regions and gave a broader view of the genome. 

The analysis also identified genome regions associated with specific human diseases, creating an opportunity for better understanding these diseases and treating them. In addition, the ENCODE project revealed just how different humans are from other mammals like monkeys, dogs, or dolphins. While previous estimates suggested that just 5 percent of the human genome is unique from other animals, ENCODE’s research doubled that estimate to almost 10 percent. Another revelation showed just how complex the control mechanisms of the human genome really are. They signal almost 20,000 genes at the exact time and location to allow a fetus to develop normally and instruct the specific workings of tissues, like in the kidneys, lungs, or brain.

So the action of genes is controlled by layer upon layer of interacting and intricate controls that make each person who they are. Homo sapiens are a species of biological wonder and will require many years of intense study to even begin to understand the mysteries of how genes are regulated to make a human being. 

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