Dolly @ 20: My day at the symposium marking her legacy

The 5^th of July 1996 marked the birth of the world’s most famous sheep, Dolly. A scientific revelation, she was the first mammal to be cloned from an adult somatic cell through nuclear transfer. Earlier this month, scientists from far and wide gathered at the Roslin Institute in Edinburgh for a special one-day symposium dedicated to Dolly’s legacy.

The significance of the day was underlined by the opening of the symposium by the Principal of the University of Edinburgh, Prof Sir Tim O’Shea. The initial welcome was followed by a short speech on how scientific discoveries can change the world outside of the sphere of research.

The first session of the day was the keynote lecture from Professor Sir Ian Wilmut, who led the team that produced Dolly. His talk was a tour de force of the scientific thinking behind cloning and scientific work that preceded Dolly. It was surprising to hear that only a few years before the Dolly experiments, the prevailing thinking was that cells lose genes as they differentiate. Transcription factors were still a relatively new discovery, making the re-programming of a somatic cell even more revolutionary. It was a pleasure to hear Sir Ian’s anecdotes about the international reaction that followed Dolly’s birth. A short coffee break followed the talk, and after this pick-me-up, we were ready to hear how Dolly’s legacy is still creating breakthroughs.

The second session of the day was titled ‘From Dolly to Engineered Farm Animals’. This session was focussed on how cloning and genetic engineering are being used in farm animals for the benefit of human and animal health. Prof Goetz Laible opened the session with his talk on the production of transgenic cattle via siRNA insertion into the cow’s genome. The cows are engineered to alter their milk composition so it is more beneficial for human consumption. The first of the Roslin Institute’s own speakers to talk was Dr Chris Proudfoot, who also spoke about altering livestock animals, but for a different purpose. Dr Proudfoot described the use of CRISPR/Cas9 technology to produce livestock that are less prone to contracting disease, benefitting farmers.

The second of the Roslin-based speakers to talk was Dr Lissa Heron whose questionable pun title (Eggcellent therapeutics) was nonetheless followed by a discussion of great research. She spoke of genetically engeneered chickens that were made to produce high levels of pharmaceutical proteins in their eggs whites. This is a process that has commercial benefits over the way drug proteins are produced currently. The final speaker of the session, Prof Angelika Schnieke differed from the others and spoke about genetically engineered pigs as a model for human disease. After a brief tribute to Dolly, she quickly moved to the central tenet of her talk: the sheep got all the glory but now the pigs are doing the work. She spoke about how research using pigs is helping us to understand the genetic basis of cancer and how pigs should be more widely used in research, especially in pre-clinical drug testing.

The third session, titled ‘Alternatives to cloning for altering cell identity’, included talks that moved away from cloning to the area of science concerned with cell identity, cell development and how understanding these processes can be used to tackle human disease. The first speaker was Prof Shinya Yamanaka, Nobel Prize Laureate Physiology or Medicine 2012. Whilst Sir Ian’s was the highlight of my day, this talk was a close second. Prof Yamanaka spoke about his Nobel -prize-winning research in inducing pluripotency in differentiated cells – creating induced pluripotent stem cells (iPSCs). He also updated the audience on his current research, centered around creating a bank of iPSCs from ‘super donors’ that could be used in the clinic to treat disorders such as age-related macular degeneration and achondroplasia. Prof Shimoyama celebrated the 10^th anniversary of his groundbreaking work this year, and his talk provided the backbone for a number of talks that followed.

The next two speakers were Dr Abdenour Soufi and Dr Sally Lowell, who are based at the University of Edinburgh. They spoke about their work on cell fate decisions made by pluripotent cells. First up, Dr Soufi detailed his work on pioneer transcription factors that pave the way during reprogramming of iPSCs. He went on to speak about how chromatin structure may hold the key to cellular identity. Following his talk, Dr Lowell spoke about her findings into how transcription factors can control the first steps towards differentiation. A new angle was presented on how cell morphology and adhesion may be responsible for the developmental cues cells receive, providing insight into why cells often differentiate in an unpredictable fashion. Prof Marius Wernig was the final speaker of the session, and he presented his work on the direct reprogramming of somatic lineages. Building on the work of Prof Yamanaka, Prof Wenig showed that mouse fibroblasts could be reprogrammed to produce functional neural cells. He spoke of his aim to improve gene targeting in iPSCs in order to correct disease-causing mutations.

Another chance to grab a coffee preceded the final session: ‘Taking stem cell science towards the clinic’. The first to talk was Prof Paul Tesar who spoke about his work studying iPSCs to analyse the molecular mechanisms of myelin disorders. He spoke about his experiments with oligodendrocyte precursor cells and how they contribute to multiple sclerosis. Using high-throughput techniques, he is using these cells to test a variety of compounds as a platform for discovering new therapeutics. Prof Stuart Forbes (also the session chair) stepped in to talk about his work on hepatocyte regenerator cells and how these could be used in cirrhosis to regenerate the liver.

The next speaker was Prof Andrew Jackson, who spoke of how microcephaly could represent a disorder of the neural stem cells. Prof Jackson explained how altered cell machinery could disrupt their normal turnover depriving the brain of neural stem cells. He described how patient skin cells can be reprogrammed to pluripotent stem cells and used to produce a 3D cortical organoid – reported by the media as ‘mini-brains’. This technique allows the cell machinery to be studied in a representative 3D environment. The next speaker Prof Mar van de Wetering gave the final talk of the day, speaking about his use of patient-derived organoids to study the crypts of the small intestine and how these may give rise to cancer.

Prof David Hume, director of the Roslin institute whose short speech was followed by a wine reception, closed the day. The symposium excellently highlighted and celebrated the legacy that Dolly left, not only on the world of research but on society in general. Rather than being a significant part of any one particular strand of science, the team behind Dolly the sheep birthed a new area of science altogether.

I would like to thank the sponsors of the symposium Disease Models & Mechanisms (DMM) for enabling me to attend by funding my registration fee.  For more information about the journal, visit: http://dmm.biologists.org/

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