Delivering impact to support AIDS research

LGC is helping to ensure that research into a cure for HIV is based on sound fundamental measurements.

Over 36 million people currently live with HIV, with approximately 2 million becoming infected each year (WHO 2015). Although HIV can be successfully managed with combination antiretroviral therapy (cART), the therapy must be continued indefinitely as no cure presently exists. This can be challenging in regions with high HIV prevalence and long-term use can potentially have toxic side effects.

One barrier to curing HIV is the presence of infected host cells that are not targeted by current therapies but lay dormant (so-called ‘viral reservoir’). These cells have the potential to become re-activated so novel strategies to cure HIV aim to target this reservoir. To determine whether these new approaches are successful, accurate and robust, methods for measuring HIV DNA are required.

The Molecular and Cell Biology team at LGC perform research to support accurate and reliable measurement as part of our National Measurement Laboratory (NML) role. Recent work by NML scientists comparing different molecular methods (qPCR, digital PCR) for quantification of HIV DNA has raised some concerns around the current popular choice of calibrator used to compare results between HIV clinical studies (8E5, ATCC® CRL-8993). It appears to lose HIV DNA copies during cell growth, potentially producing misleading estimates of how much HIV DNA is present and affecting whether novel strategies towards curing HIV are deemed successful or not.

Based in part on our work, the NIH AIDS Reagent Program, which provides critical reagents and resources to support research in the areas of AIDS therapeutics and vaccine development, has recently highlighted the potential instability of the standard on its reagent database to support the research community and enable the best chances of success.

 

 

Citation:

Busby E et al. Instability of 8E5 calibration standard revealed by digital PCR risks inaccurate quantification of HIV DNA in clinical samples by qPCR (2017) Sci Rep 7(1):1209. doi:10.1038/s41598-017-01221-5

Rediscovering the lost soldiers of Fromelles

The Battle of Fromelles took place on 19-20 July 1916, and is still known as “the worst 24 hours in Australian history,” as 5,533 Australian soldiers lost their lives in the battle. Most of the men were reinterred after the war, but in 2006, the remains of two hundred and fifty soldiers were discovered in unmarked graves near Fromelles.

In 2009, our specialist DNA team began to work with the Australian and British governments, as well as the Commonwealth War Graves Commission to help identify these soldiers using the most current DNA methods. Using DNA extracted from remains, like teeth, we can compare samples from the remains to living relatives of World War I soldiers with a combination of mitochondrial and Y-chromosome DNA.

Earlier this week it was announced that nine more Australian soldiers who had fallen at Fromelles have been identified using advanced DNA analysis. This is a huge moment for the families of the men and all those involved in the work for the last nine years.

Vic Moore, one of our DNA experts, has worked on the project since the remains were excavated. She said, “This year we have been able to provide closure for nine different families, bringing the total number of soldiers identified at Fromelles to 159 from the 250 soldiers originally recovered.”

The battle, discovery and research is a fascinating story which also caught the attention of playwright and author Lynn Brittney, who wrote ‘Dig for the Diggers’ in 2010, just after the work had begun. The play recounts the story of the fictional Mick Feeney while two forensic scientists examine his bones.

“I got the idea for ‘Dig for the Diggers’ after reading a piece in the paper about the War Graves Commission finding more bodies and the DNA testing started on the Australian relatives. I thought it was so fascinating and then I read up about the Battle of Fromelles and was so appalled by the disaster that I felt I had to write something about it,” said Lynn. “I am deeply impressed that the scientists in your organisation were involved in the forensic work on the soldiers from the battle.”

After researching the battle and the present day research, Lynn was moved by the story of the brave men who were getting their names and identities back. She explained, “I chose to write about the ‘ghost’ of the first body to be disinterred and how he viewed what was happening to his remains. It told the story of Australia’s involvement through his eyes and how ‘the worst 24 hours in Australia’s history’ panned out.”

The play has been performed extensively in Australia and was even performed last week as part of this year’s One Act Play Festival as drama groups commemorate the First World War. Director Christine Mace, whose group The Athelstan Players performed the play last week, called it “very emotional and moving”.

Captain Kenneth Mortimer, one of the nine soldiers identified. Image via Australian War Memorial

It’s easy to imagine that the nine men who have been identified had much in common with the play’s fictional protagonist. One of the men, Alexander McCulloch was 35 years old at the time of his death, while Captain Kenneth Mortimer was only 20 years old.

The men will be honoured at a commemoration ceremony this July on the 102nd anniversary of the battle, and new headstones will replace the old anonymous ones, marking their identities for the first time in over a century.

“Even after 102 years, being able to provide a name to an unknown grave can have a massive impact to the families, as it allows them to finally know what happened to their loved ones, and know where their final resting place lies,” reflected Vic.

Work continues to identify the remaining 91 soldiers with the aim that one day, each of the recovered diggers will be laid to rest. Read more about the identities of the soldiers here.