An Irish invention that has tracked viruses and scaled Kilimanjaro

We are not always good at telling the stories of Irish scientists and the impact of their work. One of these stories concerns the extraordinary impact of Prof Des Higgins of University College Dublin.

To understand this impact, we need first to remind ourselves of the biological revolution that started with the discovery of the structure of DNA and the genetic code and entered a new phase with the mapping of the human genome 12 years ago. This has provided us with a vast library of information with the potential to revolutionise our understanding of health, disease and much more.

The genetic code is enormously complex. This presented a major challenge for biologists as they tried to decipher the meaning of the mountain of information contained in the code. New tools were needed to mine the data for the valuable nuggets of insight that existed within.

Fortunately, advances in computer technology facilitated the development of these tools, and the new field of bioinformatics was born.

Higgins was a pioneer in this field. In the 1980s he developed a computer programme called Clustal, which takes sections of DNA or proteins and tries to align them to see what they have in common or how they differ. He wrote the first version on an IBM PC with an 8088 processor and very little memory, largely for use in the lab in which he was working.

As word spread, he sent it out on floppy disks to other researchers.

Gradually, the value and power of Clustal’s capabilities became apparent to a much wider community of users. Successive versions of the programme, which were developed by Higgins and a number of key colleagues, became more powerful and user-friendly.

Clustal became a global standard. It is now applied in laboratories and companies around the world in multiple and varied applications. One example is in tracking the behaviour of viruses such as influenza and HIV. These viruses are constantly changing in order to maintain their virulence.

Clustal is now used to compare different strains in order to track disease outbreaks and cluster the major virus types. This is essential for monitoring the progression and nature of outbreaks and informing the best approaches to containment.

Another application lies in developing our understanding of evolutionary trees based on differences in protein sequences between species. This helps us to understand the nature of evolution.

Highly cited papers

One way to understand the immense impact of Clustal is to look at its citations. These are the subsequent scientific publications whose authors made use of Clustal in their work and cite it as a reference. Very highly cited papers are ones that have been very widely used by other scientists.

Last year, the journal Nature published a list of the most highly cited scientific publications of all time. Higgins has one Clustal paper in the top 10 and a second in the top 30. This makes him one of the most highly cited scientists worldwide.

To put this achievement in context, Nature explained that if you took one page from each of the scientific publications in the database that it examined and stack them one on top of another based on the number of citations they generated, the resulting pile would be about as high as Mount Kilimanjaro. The top 10 most highly cited publications account for the top millimetre. Higgins, by this measure, has one paper in the top millimetre of Mount Kilimanjaro and a second within three millimetres of the top. This is an extraordinary achievement.

Looking at the citations, we see that Clustal has been used to address some of the major global challenges of our time. More than 5,000 publications describe how Clustal was used to advance understanding or control of the HIV virus. Others describe its use in determining the origins and evolution of the swine flu virus or understanding drug resistance in cancer treatment.

The impact has been felt in industry. Clustal has been referenced by more than 27,000 patents issued to companies such as DuPont, Bayer, Pfizer and Toyota. These patents address a range of global problems such as controlling disease, improving plant yield and the production of biofuels.

Excellent research can have an impact far beyond that originally envisaged. The work of Higgins is a great example of this.

• Orla Feely is vice-president for research, innovation and impact at University College Dublin