Prof. Gaston Gonnet: when technology holds the key to evolution

In 1857, the evolutionary theorist Charles Darwin wrote to his friend and colleague Thomas Henry Huxley, saying: "The time will come, I believe, though I shall not live to see it, when we shall have fairly true genealogical trees of each great kingdom of Nature." Had Darwin known that a century later scientists had collected enough evidence from a range of disciplines including physiology, biochemistry and DNA analysis to compile it into a 'Tree of Life', he probably would have rejoiced in the confirmation modern genetics has brought to his early stream of thought. The establishment of DNA as a hereditary material opens deep, causal questions: Can ancestry be determined? Is DNA sequencing technology able to track human migration routes? What is the cause of epidemics? Following the pathways of intertwining branches of life has taken humanity on a journey through evolutionary history and launched it forward in its endeavors to unlock the mystery of life.

The United States of America: The 1990s hallmarked a monumental interest in genetics as the Human Genome Project, a massive US government-backed effort to lay out the entire genetic code of 'homo sapiens' - three billion DNA base pairs - was brought to life. A pioneering spirit was evident that aimed at answering questions of global urgency: What if genetic disorders caused by DNA mutation, damage or the influence of environmental factors could be pinpointed? Would it be possible to predict a person’s risk of disease and provide them with personalized medicine to target and stop the disease in its tracks?

Meanwhile, at ETH, Switzerland: a seminar held by Prof. Gaston Gonnet about the New Oxford English Dictionary which sought to create a searchable electronic version by parsing of the source text to enhance the tagging and on building a full text searching system based on PAT trees had been suggested to professor of chemistry Steven A. Benner by assistant professor Beverly Sanders from Prof. em. Niklaus Wirth's group. The seminar immediately caught Prof. Benner's attention: The tools which the group around Prof. Gonnet had developed to organize the dictionary were applicable to manage protein sequence databases, an early computerization of large, biological molecules. Just as the threads of life come together, so did this encounter mark the beginning of a fruitful collaboration: the resurrection of ancestral genes and proteins, the use of evolutionary analyses to predict the folded structures and proteins, and the analysis of the natural history of two families to understand adept, drift, functional change and pathway interactions. Further, the exhaustive matching supported some of the earliest efforts to infer the metabolism of very ancient organisms, including organisms standing at the branch points of three major kingdoms, and organisms that invented protein translation. This work was well underway before complete genome sequences, as delivered by the Human Genome Project, were available. However, it was clear that a large number of these sequences could service the platform for the new field of evolutionary-based functional genomics. These ground-breaking times were leading to a revolution in biology.

Today, Prof. Gonnet leads a young, interdisciplinary field combining computer science, biology, mathematics, chemistry and physics which is answering some of humanity’s most pressing questions. As the earth's population climbs towards eight billion, the world is challenged to find solutions of global importance to ensure the basics of life: food, energy and medicine. How can we improve the human condition by eliminating the threat of cancer, Alzheimer’s and AIDS? Can we reduce our carbon footprint caused by rising greenhouse gas emission? How can we save food crops in developing countries lost to ebola and disease? In short: how is the world going to heal, fuel and feed itself? Bioinformatics, the branch of computing concerned with the acquisition, storage and analysis of biological data, has surpassed all other methods for addressing these questions. Where biology has been an empirical field that featured mostly specimens and Petri dishes, computer science has revolutionized the discipline. Harnessing the data on genetics, processes that took weeks to complete have given way to digital research. In the age of big data, manually collected information has been replaced by zeta byte storehouses of genetic and chemical data. Empirical estimates have been replaced by algorithmic certainty, the mathematical exactness of statistics, and data mining. Huge databases dedicated to all aspects of genetic sequence data, repositories for whole genomes, databases on genetic variations in cancer or inherited diseases, or automated pipelines to establish the position of coding sections in DNA are only some of the efforts bioinformaticians have made to contribute to life sciences but also to computer science itself, by developing efficient algorithms and heuristics. Machine learning techniques play a huge role in prediction methods. In order to manipulate genetic data, DARWIN, a bioinformatics system, was created by Prof. Gonnet. Designed as a programming environment, the system has its own modern language and a growing library of functions for the sequence management and analysis, statistics, numerics, graphics and parallel execution.

Providing the tools to unlock the mysteries of life has allowed researchers as well as business and industry to ask detailed questions and draw valuable information from large sets of data. A strong focus is laid on the field of pharma and biotechnology, where industries such as Novartis and La Roche as well as Mepha Pharma and Sandoz, small to medium-sized generic drug enterprises, see much potential in drug target validation, vaccine design and protein engineering and thus ways to capitalize on the investment in bioinformatics. Prof. Gonnet sees great progress in the development of personalized medicine; the full sequencing of a personal genome or pathogens in the body. Complete "medicals" will be available by touching a sensor, or being scanned by a special light, in a way that these methods will become ubiquitous. However, in Prof. Gonnet's view, the largest impact of molecular biology will be in the understanding of the details of generating artificial organs.

By now, bioinformatics has become a pervasive field. Besides biology and medicine, it is already serving the law (criminal, paternity, enforcement), anthropology (migrations, origins, development), archeology (tracking the origin of maize, for example), trading (AOC specifications at a genetic level), consumer protection (quality and origin of biological goods), environment protection (saving species from extinction), pollution control, agriculture, veterinary science and genetic engineering, to name a few. "Switzerland has done a great deal in the area of bioinformatics and in health care in general," Prof. Gonnet says. "The country is in the privileged position of having created and grown its own research and development ecosystem. We should be very proud of our industry and academia and we are an important, international reference. However, excellence, efficiency and productivity aren’t brought about by miracles. They have to be put in place and fed continuously through valuable education, challenging job opportunities and ongoing encouragement." The potential in the technology has also made scientists aware of how many questions remain to be answered. As Darwin put it: "A man who dares to waste one hour of time has not discovered the value of life."