Sir Adrian Peter Bird (Wolverhampton, United Kingdom; 1947) earned his PhD in biochemistry from the University of Edinburgh in 1972. He then went on to occupy post-doctoral positions at the universities of Yale (United States) and Zurich (Switzerland). On returning to Edinburgh in 1975, he joined the Mammalian Genome Unit (Medical Research Council) where he would remain for eleven years. His next move was to Vienna, where he worked as a senior scientist in the Research Institute of Molecular Pathology.
In 1990, he was appointed to the Buchanan Chair of Genetics at the University of Edinburgh, a position he still holds today and which he combined for a time with the directorship of the same institution’s Wellcome Trust Centre for Cell Biology.
He is a former governor of the Wellcome Trust (among the world’s leading funders of medical research), serving for three years as its Deputy Chairman.
Author of more than 150 publications in international science journals, he is a Commander of the British Empire (2005) and has received numerous awards and honors, including a knighthood in 2014.
Speech
Biomedicine, 6th edition
Adrian Bird has been fascinated by the genome since school age, and the challenge of deciphering the assembly instructions for a human being has accompanied him throughout his professional life: “I am always on the lookout for generalizations that simplify the daunting complexity of the genome,” he affirms. So his discovery of certain key pieces in the jigsaw was the result of a preconceived mission. But what Bird couldn’t have imagined is that his work would ‘come to life’ with a direct bearing on numerous individuals.
The BBVA Foundation Frontiers of Knowledge Award in Biomedicine recognizes both facets of his scientific enterprise: his contributions in epigenetics, a field central to the understanding of how the rules governing our bodies are encoded; and his research into Rett syndrome, a severely disabling neurological condition. For Bird, Professor of Genetics at the University of Edinburgh, the sequencing of our genome at the start of this century was just the beginning of the quest. And many questions remain unanswered. “For instance, what does it take to make DNA alive? DNA is the thread of life but it is utterly dead. We cannot make life, but it would be good to know some of the rules required to do that.”
Epigenetics is part of these rules, but it is not a part of the genome or DNA; for epigenetics deals precisely with factors external to DNA that interact with the molecule to the extent of enabling or inhibiting gene expression. They add, we could say, a further layer of complexity. The genome, DNA, contains the genes, but their activation or otherwise is according to rules that are not necessarily written into DNA. As the jury notes in its citation, Bird has pioneered the study of the epigenetic language: ‘Through his work, he identified specific chemical signatures in the DNA involved in the control of gene.’
But Bird also uncovered a surprise connection between epigenetics and the clinic. He and his team found that by acting on a particular gene involved in the epigenetic control of the genome, it is possible to reverse, in mice, the symptoms of a disease comparable to Rett syndrome. This happened in 2007 and was a milestone event: the first time a neurological disorder had been cured in an experimental setting. Now Bird is on the hunt for an effective treatment for the syndrome, which affects one in every 10,000 girls. “I used to be quite content with myself just pursuing knowledge. But to see that your research can have such practical relevance in people’s lives adds a new dimension, and makes the whole thing more exciting and engaging,” he admits.
His emotion is all the more understandable when we consider how biology has changed since the pre-genome era. When Bird began researching, scientists were still unsure whether all the body’s cells had the same genome — they do. And no techniques were available for sequencing even the tiniest lengths of DNA: “Back then, sequencing an entire genome, even of a bacterium, was an impossible dream,” he recalls today. Now we have mapped the complete genomes of hundreds of organisms, and all a researcher has to do to locate a gene among the billions of base pairs that make up DNA is look it up in a database. Bird has made a huge contribution to this watershed in biomedical science. His first major finding, in the 1980s, enabled researchers to locate genes in the genome long before the human genome was sequenced.
The achievement came about in phases. First Bird, who at the time was studying frog oocytes to determine whether all an organism’s cells have the same genes, managed to identify the methylated regions of the genome; methylation being the attachment to the genome of a type of molecule known as a methyl group. “I still remember doing the experiment and looking at the result in the darkroom,” he says. “These moments are what makes scientific research addictive.” This insight lit up the field because, as Bird would later observe, DNA methylation was almost everywhere in the genome, except at short regions near genes. The methylation map, in other words, was also a negative map of the genes.
“Genes make up only a small fraction of our DNA, less than 3 percent, so finding them was initially a massive problem,” Bird explains. “Once whole genomes could be sequenced, this methodology became obsolete, but by then it had helped discover many genes.” The discovery was also a major step towards the new laureate’s goal of finding simplifications or general rules in the code of life. The paper describing the work was published in Nature in 1985, and remains one of his most highly cited.
The next milestone in Bird’s career also marked his entry to epigenetics. Methylation is one of the main elements of the epigenetic language: genes in each cell are activated or not depending on whether they are methylated. In other words, all cells have the same genome but not the same epigenome. Bird’s interest in the process led him to the first protein sensitive to DNA methylation. Named MeCP2, it only binds chemically to methylated DNA, making it what we might call the first letter in the epigenetic code.
But the story of MeCP2 does not end there. In the late 1990s, another group found that mutations in this protein are behind Rett syndrome, and this chance connection set Bird’s career on an entirely different course. In 2001, his team created a mouse presenting symptoms similar to the disease in humans, and in 2007, came up with a way to restore the altered gene. Their success took them all by surprise. “It was spectacular, a real Eureka moment,” says Bird, looking back. “It was assumed that once you have a neurological disorder, you have it forever, so we thought we might, with luck, delay the animals’ death or alleviate some of the symptoms. But what we got was a cure.”
The technique used in mice is not replicable in humans, and Bird warns that we are still far from finding a cure. But his work “provides a proof of concept that has got many other research groups involved in the search for therapies.” On a more personal note, he adds that “I have met the affected girls and their parents. I feel involved and appreciate what it would mean to be able to do something positive for this condition. I would love to think that we can achieve this within my working lifetime.”
Meantime, epigenetics has become a fast growing research field. Work is being done on the role of the environment in epigenetics, and even on the heritability of epigenetic traits. And it seems safe to say that the challenge of deciphering life’s rules will remain at the forefront of science.
