Trailblazing Genomics

In November 2022, a review published by Nature ranked the most innovative countries worldwide, identifying top academic innovators in each. The UK, ranking third in Europe, saw the Wellcome Sanger Institute as head of the list. 

Dr Emmanuelle Astoul, Head of Translation at the Sanger Institute welcomed the news as a ratification of the Institute’s mission: “This recognition shows how foundational our work is, enabling others to advance on our science and develop products or services including therapeutics stemming from our research. We work with partners, including investors, to apply our own science to solve real-world problems, but we also maximise our impact by enabling others to innovate by sharing the resources we create.”

Dr Julia Wilson, Associate Director at the Sanger Institute, says: “We do not have the skills or resources to progress our science into the clinic, that is not our strength. Hence, we pass the baton on to others who can create diagnoses and treatments based on the data we openly share. We welcome the fact that this is happening and that our ambitious science is underpinning these efforts.” 

The review takes into account patent scholarly citation - how many times a scientific research paper is cited in patents - as well as academia-industry collaborations, among other parameters. Taking a glance at these data, it comes as no surprise that among the most cited papers in patents are the results of the international collaboration of the Human Genome Project, which is considered the biomedical research achievement of the 20th Century.

Professor Sir John Sulston, the Sanger Institute’s founding Director and partner of the Human Genome Project, was present at the 1996 summit in Bermuda, where leaders of the scientific community agreed on a set of principles, (known as the Bermuda principles), requiring all DNA sequence data to be released in publicly accessible databases. This was endorsed by funders, thus becoming a norm in genomics. As Dr Julia Wilson puts it: “Genomics was founded on open principles from the outset, and this has continued today.”  

In the top five papers, there is also a 2002 paper on the discovery of the mutations of the BRAF gene and how these relate to skin cancer, one of the landmark papers of our previous director, Professor Sir Mike Stratton. His work and discovery were instrumental in the development of small molecule drug inhibitors targeting mutated BRAF genes, which radically changed the clinical treatment of melanoma and improved patient outcome.

Advancing healthcare & biodiversity with ambitious projects 

The Sanger Institute’s ability to undertake large-scale initiatives due to its people, infrastructure and open-access culture enables us to manage projects that cannot happen anywhere else. International efforts and collaborations such as the Human Cell Atlas, HipSci and the Cell Model Passports platform are examples of the ambitious science that takes place at the Sanger Institute in collaboration with colleagues all around the world.  

The Human Cell Atlas (HCA) is a global collaborative consortium spearheaded in 2016 by Sarah Teichmann (Sanger Institute) and Aviv Regev (then at the Broad Institute) with the aim of charting the cell types in the body, across time, from development until old age. The consortium launched with nearly 100 people and has now grown to 3,089 members from 97 different countries. This titanic undertaking aims to transform the understanding of the 37.2 trillion cells in the human body. 

The Sanger Institute also played a major role during the COVID-19 pandemic, sequencing 20 per cent of all virus genomes worldwide - handling more than 27 million samples in total. During the peak of the pandemic, there were over ten million SARS-CoV-2 samples at the Institute, with hundreds of thousands arriving each week. Dr Sara Stott, Senior Scientific Manager at the Genomic Surveillance Laboratory Platforms at the Sanger Institute states that her team was sequencing almost 70,000 viral genomes a week. The genomic data were provided in near-real time to the UK Health Security Agency, giving information on the spread of the virus. It also helped other health authorities make informed decisions, such as by improving infection control in dialysis units where vulnerable individuals were at greater risk.

Sharing the data

“A key factor in ensuring other scientists and organisations can innovate on our foundational work is to make sure the data we share are organised and standardised,” says Dr Emmanuelle Astoul, Head of Translation at the Sanger Institute. 

“Sharing data is not just putting all the raw data out there, we need to make it useful for the community. That means including rich metadata, which make the data we share findable and reusable” adds Dr Mate Palfy, Open Science Lead at the Sanger Institute. 

“We would not be able to do this without EMBL's European Bioinformatics Institute (EMBL- EBI), which sits right next to us in the Wellcome Genome Campus,” says Dr Julia Wilson, Associate Director at the Sanger Institute. “We’ve been partner organisations for almost 30 years now, and our data flows are well established. EBI has the capacity to take the data at scale that we produce, aggregate and improve it and serve it to the world.”

Into the Future

The Sanger Institute has recently embarked on a gargantuan project, the Darwin Tree of Life, which aims to sequence the genomes of all animals, plants, fungi and protists in Britain and Ireland - an estimated 70,000 species in total. As a collaboration of ten equal partners, the Sanger Institute is working alongside the Natural History Museum in London, the botanic gardens at Kew and Edinburgh, the Earlham Institute, Marine Biological Association, EMBL-EBI, and the Universities of Oxford, Cambridge and Edinburgh. The project is playing a leading part in a global effort, known as the Earth BioGenome Project, to sequence and assemble genomes for every eukaryotic species on the planet.

This had been a distant aspiration since the discovery of the structure of DNA and the invention of DNA sequencing technology - that there would ultimately be a reference genome sequence for all species on Earth. The Darwin Tree of Life is certainly a step in that direction. 

Samples from more than 4,800 species have already been collected and sent to Sanger for whole-genome sequencing. Of those, Sanger’s Tree of Life programme has released over 1,000 genomes to public scientific databases, freely available to researchers worldwide, with a further 2,500 genomes being actively sequenced and assembled at the moment. The study of these data is expected to have a profound effect on agriculture, biodiversity and conservation, new medicines and even in industrial materials and techniques.

“The aim of the Darwin Tree of Life project is hugely ambitious, and deliberately so. We want to ensure the next generation of scientists have the top-quality genomic data critical to carrying out the research needed to safeguard the future. As part of a global network of biodiversity genomics projects, known as the Earth BioGenome Project, we are on the cusp of changing biology forever,” says Dr Mark Blaxter, Head of the Tree of Life Programme at the Sanger Institute.

Another, more incipient project, is the Atlas of Variant Effects. Sanger scientists have taken a leading role in this internationally collaborative initiative to generate all possible mutations in protein coding genes and regulatory sequences of the genome and to create an Atlas of Variant Effects. During its early stages approximately 11 million total variants have been studied, which are already informing interpretation of clinical genetic tests, albeit thus far covering less than one percent of the relevant human genome. 

The underpinning philosophy for innovation at Sanger combines the mission of making an impact from our science with nurturing the next generation of scientific leaders. Looking into the future, we're exploring ways of unlocking the innovation and entrepreneurial potential of our scientists, especially those earlier in their careers to enable them to make a difference with their science in ways we've yet to imagine,” says Dr Joanna Mills, Head of Entrepreneurship at the Sanger Institute. 

Nature’s recognition is a validation of Sanger’s mission - to apply and explore genomic technologies at scale to advance understanding of biology and improve health. Dr Emmanuelle Astoul says, “By undertaking grand scientific challenges and creating shared resources at a scale few could aim for, our ambition is to generate insights and technologies we and others can apply to benefit society.”