Google+ Facebook Twitter Twitter

Figuring out the threats: Problem-solving with genomics

As the COVID-19 enquiry continues to unpick the tangled threads of the pandemic response, little has been said about one of the most effective weapons against the SARS-Cov-2 virus – pathogen genomics.


Since 1995, when the first sequencing of the genome of a living organism, the bacterium Haemophilus influenzae, was completed, the technology has developed rapidly, pushed along by the mushrooming processing power of computers, allowing faster analysis of ever-greater numbers of genetic samples. Come 2020, with the sudden emergence of the novel COVID virus and the speed with which it spread around the world, the stage was set for pathogen genomics to show just what it could do.

In being able to decode the biological blueprint of the SARS-Cov-2 virus in real time, and when viewed alongside other relevant data and research, genomics threw a forensic light on the potential origin of the pathogen, its diversity and its evolution. Any mutations in that blueprint or changes in the trajectory of infection could be tracked as they happened, nationally and internationally. This constant monitoring of the COVID genome data, taken from millions of samples from around the world, was critical to the development of the rapid diagnostic tests, the adjustments to the treatment options, and the production of the vaccines that did so much to halt the further spread and mutation of the virus.

Tracking threats

With the pandemic, the real-world application of genomics had come of age. Now, having absorbed the lessons of COVID and the contribution of genomics, the UK Health Security Agency (UKHSA) has launched its Pathogen Genomics Strategy. This five-year plan seeks to establish a unified UK-wide programme that will track the threat from infectious diseases and drive the response to them.

Dr Meera Chand, Deputy Director for Emerging Infections and Clinical Lead for the Genomics Programme at UKHSA, says: “Pathogen genomics is an essential component of the world’s ability to respond quickly to infectious disease threats, whether by increasing the speed at which we can identify emerging pathogens or control outbreaks, or by improving our understanding of what treatments or vaccines might be effective”.

Professor Dame Jenny Harries, UKHSA chief executive, adds: “We know it will become even more important in the years to come, and our new strategy will ensure that UKHSA continues to be at the forefront of implementing this technology.”

The UK’s capacity in genomics was underscored during the pandemic when its labs supplied more than three million sequences of the SARS-CoV-2 virus to the international GISAID database – a quarter of the global total. Broadly, the new strategy aims to build on the UK’s existing expertise and by developing an integrated genomics system that further enhances the capacity of UKHSA to detect pathogens as they emerge, decode their genetic makeup, and put the necessary controls in place to prevent the spread of the infection.

Building on the legacy

As always, the devil is in the detail, and the 11-page strategy document only skims the surface of how a unified and highly responsive national system is going to emerge from the current infrastructure. Nevertheless, the launch of the Pathogen Genomics Strategy has stirred enthusiastic, but cautious, feeling within the biomedical community. 

“It’s incredibly exciting,” says Phillipa Burns, Consultant Clinical Scientist at Hull and East Yorkshire Hospitals NHS Trust. “The genomic monitoring of COVID showed how this type of data can be used to influence the management and containment of outbreaks and it is wonderful to see that we are building on the legacy of COVID.”

Matt Griffiths, School Standards and Quality Manager for the School of Science and Technology at Nottingham Trent University agrees that the strategy is a step in the right direction. “Clarity around the goals and expectations for genomics gives us the ability to plan workforce development and work with colleagues to ensure maximum positive patient impact from the knowledge derived from genomic systems,” he says.

For Burns, the key benefit of the strategy is the promised national system: “A connected and dynamic pathogen genomic service will allow early detection of new infectious disease threats and will enable outbreaks and transmission events to be rapidly identified. We can move to a model of preventative rather than reactive management by understanding and disrupting transmission events.”

Griffiths adds that the international dimension, to which the strategy clearly commits, could be just as transformative. “Developing a proactive approach to the development and implementation of effective, evidence-based policy to deal with emerging outbreaks is a huge benefit to the population as a whole,” he says. “For example, WHO has a target to eliminate cervical cancer worldwide, based on the importance of HPV as the causative agent. The same will be seen for other targets. While the UKHSA is focusing on the UK, the knowledge will be worldwide, with sharable policy that can benefit everyone.”

The seven aims of the Pathogen Genomics Strategy:

pathogenspreadhr - CREDIT - spooky-pooka
  • Use pathogen genomic data to optimise clinical/public health decision-making
  • Use pathogen genomic data to drive improvements in diagnostics, vaccines and therapeutics
  • Provide a nationally coordinated, scaled-up pathogen genomics service
  • Support a pathogen genomics workforce transformation within and beyond UKHSA
  • Commit to pathogen genomic data sharing and global collaboration
  • Drive innovation in pathogen genomics
  • Build high-impact pathogen genomic services that are good value for money.

Proactive surveillance

While the impact of genomics during the COVID pandemic was evident, might there be a danger that the strategy points to an over-reliance on the technology? “We saw from the COVID dashboards that data outputs from labs can be used to influence individuals to perform their own dynamic risk assessments and to take steps to manage their own risk of exposure to a pathogen,” says Burns. “I don’t think we were over-reliant on the genomic data, but we certainly missed the connectivity when they were stopped.”

Griffiths believes it could be perilous to expect too much from a single approach. “Genomics is a hugely powerful tool, and it is one of many available to us. Focusing on specific markers for detection has a risk if those markers change – a proactive surveillance approach to pick up any drift, to find any newer emerging markers, is needed. This is one part of a wider strategy and should be regarded as such, not as a holy grail.”

As part of the strategy’s overarching objectives, it sets out the intention to use pathogen genomic data alongside other epidemiological information and to integrate the technology into the existing public health structure. It also aims to establish best practice guidelines for the use of genomic data, and to work with NHS England to explore the potential application of metagenomic analysis.

While the ambition for the service is clear, it does raise the question of infrastructure and resources. Underpinning the establishment of a unified high-throughput genomics service will be “scalable, robust and standardised laboratory services, bioinformatic analysis pipelines and translational services”, and a system of labs and services that are “resilient and rapidly adaptable” and consistent across the whole of the UK. Allied to this is the aim of transforming the genomics workforce inside and outside UKHSA, with “clear pathways for the development of specialists in all aspects of pathogen genomics”.

The workforce

Phillipa Burns believes the workforce issue will be fundamental. “We need to recognise that genomics and bioinformatic skills will be needed by future biomedical scientists and start to build up those skills now.”

Matt Griffiths also feels the change will need to be managed. “Practitioners are fully stretched dealing with the existing workload, and bringing about change requires staff time. Also, this has the scope to impact many areas of healthcare, so ensuring that practitioners understand the impact of the strategy, how it relates to their roles and their patients, will be very important.”

The strategy’s intention to “leverage” existing capacity might also raise an eyebrow or two. “There is no space to be ‘leveraged’,” says Griffiths. “While there is the opportunity to make effective use of existing facilities, it would be at the expense of current capacity. So real investment is needed to make this a reality.”

What, then, of the strategy’s three priority areas: antimicrobial resistance, emerging infections and biosecurity, and vaccines for preventable diseases. Are these the right points of focus? “Yes, at the moment,” says Griffiths. “However, there is scope for other areas. The knowledge we gain from the implementation of this strategy should be able to offer insight into other non-transmissible diseases and provide scope to move forward with other treatments based on genomic data.”

Pointing to recent data that suggest deprived and vulnerable patients have poorer infection outcomes and carry a higher AMR burden, Burns would also like to see a focus on understanding transmission within those populations: “Other countries have reported the transmission of penicillin-resistant Streptococcus pyogenes within homeless populations, people who inject drugs and people who have spent time in prison. We need to understand transmission and build a strategy to disrupt it and develop vaccines. We also need to understand the burden of drug-resistant infections on those with chronic long-term health challenges.”

New opportunities


For an ambitious, forward-looking piece of work that centres on public health, a role for the public is not mentioned. How far do people need to be aware of the impact genomics could have on their health and wellbeing? “We need to sell

the potential of this technology by using terms that help the public understand,” says Burns. “Spending money on genomics now will help to preserve antimicrobials for future generations. It is an investment with the potential to return whole population-level improvements in health.”

Matt Griffiths says that while an informed public is a good thing, it’s difficult to realise. “It is important that there is transparency, so that people can see work is being undertaken for their benefit. Public buy-in is mainly important in terms of funding and providing informed consent for clinical samples to be used for wider testing. That will rely on them supporting the underlying principles.”

One group of people whose buy-in is required is the biomedical scientist community. What might the next five years and the implementation of the strategy entail for the profession? “This is an opportunity for us to evolve,” says Phillipa Burns. “We have always adopted innovative technology to ensure that we provide excellent diagnostic services but we will have to ensure that we are confident and able to work with genomic pipelines.”

Matt Griffiths thinks it is too early to say. “But it will bring more work, as most new initiatives do. However, it may also bring new career pathways, opportunities to develop, growth of the profession. The opportunity is there to do more for our patients and the population.”

Image credit | Spooky Pooka



Related Articles

The lesser horseshoe bat (Rhinolophus hipposideros)-Image Credit | istock-816193242

Bat swarming and immunity

Bats carry some of the deadliest zoonotic diseases that can infect both humans and animals, such as Ebola and COVID-19.

Pancreas or pancreatic cancer with organs and tumors or cancerous cells 3D rendering illustration with male bodyImage Credit | istock-1467893187

Fibroblast cells and pancreatic cancer growth

Older people may be at greater risk of developing pancreatic cancer and have poorer prognoses because of age-related changes in cells in the pancreas called fibroblasts, it is claimed.

brain tumour CREDIT_science photo library

Pores for thought

A team from Nottingham looks at intraoperative molecular diagnosis of brain tumours using nanopore sequencing.

CRISPR-Cas9 gene editing complex, illustration.Image credit - Science-Photo-Library-f0248864

Activating genes using CRISPR technology

There are over 7000 different rare genetic diseases, and often it can be a significant challenge and take a long time to receive a correct diagnosis.