Qiagen : Looking to the future of missing persons analysis with next-generation sequencing

To the average passer-by, the entrance to the new ICMP headquarters is just another polished door on a pleasant main street in a quiet, neat Dutch city. It would be difficult to guess that the three-storey facility that lies behind will soon host a cutting-edge laboratory, working to bring solace and comfort to families that have lost loved ones through armed conflicts, disasters or migration.

A unique opportunity
On the third floor, ICMP Director-General Kathryne Bomberger sits at her desk in a quiet corner, watching the new offices take shape around her. She is quietly excited by the relocation. 'The Hague is ultimately the ICMP's natural home,' she says. 'It provides a unique opportunity to reinforce the importance of what we do. The proximity of the other peace and justice institutions will enhance the awareness and perception of the ICMP.' She believes this wider recognition will be an important contribution in making the case for a global response to the problem of missing persons.

However, the ICMP is more than an institution of justice. It has built a reputation based on leveraging technology and establishing solid evidence; its new headquarters will build on this. It offers the organization the possibility of developing a new scientific approach to tackling the challenge of missing persons. The new facility will combine the latest in DNA sequencing technology with the ICMP's established knowledge base and expertise in areas such as forensic genetics and the logistical and data handling needs for missing persons investigations.

A definitive center of excellence
Responsible for creating this facility will be Thomas Parsons, the ICMP's Director of Science and Technology. Quiet-spoken and precise, Parsons leads the ICMP's team of experts in forensic anthropology, forensic archeology, DNA profiling, genetic kinship matching and informatics. Although his new laboratory space is still at a very early stage, his vision for it, and what it can deliver, is clear. 'This is the opportunity to establish a definitive center of excellence for DNA-based human identification,' he says.

At the same time, he also wants the facilities in The Hague to benefit from the mindset that helped the ICMP achieve so much in former Yugoslavia. In Sarajevo, Parsons explained, his team pursued a single-minded approach to problem solving. It was this mindset that drove many of the advances that DNA laboratories around the world now benefit from. 'We continuously updated our techniques, with unrelenting focus. We regularly asked ourselves 'What is currently holding us back? How do we address it?' Once we had solved one issue, we would repeat the process to tackle the next.'

Answering fundamental questions
However, Parsons is quick to stress that although the science is important, ultimately it's about the difference that it makes to families and individuals. He and his team are hugely motivated by the consequences of their work for families of missing persons. 'Our efforts bring a degree of resolution for these anguished people. We may not cure anything, but in many instances we can answer some of their most fundamental questions and resolve some of the causes of their ongoing trauma.' But equally importantly, Parsons appreciates what ICMP's work contributes to justice. 'Where perpetrators believed they would be able to remove people from the human experience, we provide irrefutable forensic evidence of identity. This means that perpetrators can be held accountable.'

With the new laboratory in The Hague, Parsons and his team hope to build on these capabilities. He is eager to leverage the potential of next-generation sequencing (NGS), which he believes will address many of the existing challenges in delivering large-scale missing persons identification. Parsons explains: 'There are three problems that currently hold us back; the unit cost per test; the difficulty of working with highly degraded samples and the amount of genetic information needed to confirm identity via distant family members. Advancements in next-generation sequencing clearly offer the potential to address these issues.

» Where perpetrators believed they would be able to remove people from the human experience, we
provide irrefutable forensic evidence of identity. This means that perpetrators can be held accountable.«

Thomas Parsons, ICMP's Director of Science and Technology

Turning the promise of NGS into reality
To turn the promise of NGS into reality, Parsons and his team are focusing on developing novel Single Nucleotide Polymorphism (SNP)-based testing methods. These will identify singular mutations in the human genome and provide greater power for establishing kinship when used in large numbers. The objective is to develop highly homogeneous and cost-effective laboratory mechanisms that can be applied irrespective of the level of sample degradation. Ultimately, he hopes to make this feasible at around one tenth of the current cost by pooling samples using molecular barcoding mechanisms.

Many in the field of forensic genetics foresee that an SNP-based approach may best capitalize on the strengths of NGS, and Parsons believes that with carefully directed effort it may even replace STR analysis as the standard approach in current human ID applications. Certainly, he views NGS as the way forward, not only for the ICMP but also for the entire forensic community, allowing it to address some of the major existing challenges in missing persons investigations.

At the forefront of human identity testing
The new laboratories in The Hague mark another step in the long-standing collaboration between the ICMP and QIAGEN. The relationship dates back to the ICMP's initial work in Bosnia and Herzegovina, where QIAGEN helped the organization implement highly efficient approaches for isolating DNA from bone. The next phase will see QIAGEN provide support in developing SNP-based assays. The new ICMP laboratory will also take delivery of the QIAGEN GeneReader NGS System, the first fully integrated NGS workflow solution.

For QIAGEN, the collaboration with the ICMP is a unique opportunity. 'The ICMP is at the forefront of human identity testing around the world, pioneering methods and principles for analyzing challenging samples,' says Keith Elliott, QIAGEN's Senior Global Product Manager in Applied Testing. 'What makes the ICMP so special is their commitment to leveraging science to uphold basic human rights and justice for missing persons and their families. Working with Thomas Parsons and his team in developing Sample to Insight next-generation sequencing is a huge privilege for QIAGEN.'

Parsons believes that within the next three to five years capabilities will advance substantially from where they are today. He is dedicated to maximizing the impact of these technological advances on the ICMP's mission. 'This is a worldwide crisis on many levels; economic displacement, mass disaster, terrorism, post-conflict, ongoing conflict, all of these. We have already demonstrated some of the possibilities; now we want to expand those as broadly as we can. Our cooperation with QIAGEN is a major benefit for this objective.'

Founded in 1996, since 2001 the International Commission on Missing Persons (ICMP) has provided the benchmark for DNA identification techniques, combining forensic archeological and anthropological techniques with state-of-the-art DNA matching processes. To date, it has assisted national authorities in resolving the fate of some 70 percent of the 40,000 people who disappeared during the war in former Yugoslavia, with DNA assisted identifications of over 20,000 individuals worldwide; an unprecedented achievement. In 2015, the ICMP entered a new phase as an internationally recognized, treaty-based international organization and moved its base from Sarajevo, Bosnia and Herzegovina, to its new headquarters in The Hague in the Netherlands. There, the ICMP will sit alongside other institutions including the International Court of Justice and the International Criminal Court.