In search of the Holy Grail
The questions kept getting bigger once I was able to show that the synthetic material could do everything that normal nucleic acid could do.
Genetically modified organisms have been hailed as an important step to countering the common agricultural problems that lead to crop failure. But there have long been concerns about their safety due to possible cross contamination.
Vitor Pinheiro  has been researching this issue for years and now leads his own research group at University College London. But his ambitions don’t stop there. He is interested in the Holy Grail of biology - whether the very chemistry of life can be changed.
His rise up the scientific career ladder has been rapid due to his ground-breaking research on synthetic DNA or XNA, but Vitor’s story could have been very different.
He was born in São Paulo where his father was a lawyer and his mother a secretary. Having attended a private primary school followed by one of the top secondary schools in the country, he wanted to study science at university, but felt his options were limited in Brazil. His family, many of whom are in the legal profession, favoured him doing law.
His grandfather, however, had “run away” to the UK for a year when he was younger, telling his parents he was visiting his girlfriend when he was really planning to catch a boat to the UK. He said he had really appreciated the experience. He said he would pay for Vitor to go to Scotland for a year towards the end of his school studies so he could “learn about the world”. Other members of the family were also given the opportunity, but soon came home.
Vitor was interviewed in São Paulo by the headmaster of British School in São Paulo, a personal friend of the headmaster of Gordonstoun School in Scotland. The idea was for Vitor to go to Scotland for a year then finish his studies in Brazil, but he thrived and stayed for two years to do his A Levels. His end of year reports suggested he had the potential to get into Cambridge University. “Cambridge is very highly regarded in Brazil and my whole family is fairly anglophile so it was an easy sell,” says Vitor.
He applied successfully to Cambridge to do a degree in Natural Sciences, but had to take a gap year to try and raise the money to attend. Over that year friends and family convinced his grandfather to fund the degree. He also tried to get some laboratory experience and taught English in São Paulo for six months.
Vitor started his undergraduate degree in 1997 focusing on biochemistry. Over the course of his degree his plans for the future changed several times. Earlier in his degree he had a bad experience on a project and thought he might return to Brazil and become a consultant, but then he spent his fourth year doing his masters in “a fantastic laboratory” which played a big role in his decision to stay on to do a PhD in the Biochemistry Department. He did his masters on biopesticides, looking at ways to increase the target range and potency of insecticidal toxins used in organic farming. “It gave me the skills I needed. The people were fantastic. It changed my view and made me want to stay in the lab,” he says.
Vitor had few options funding-wise so when he heard about the Gates Cambridge Scholarship which had just started up he decided to apply. He says being in the first year of the scholarship was exciting. He began his PhD building on the organism he used in his masters, Bacillus thuringiensis, which is seen as safe for human consumption and produces insecticidal toxins that underpin many of the current GM crops. The goal was to compare B. thuringiensis with B. cereus, a closely related organism that can be a human pathogen.
In trying to establish a system where bacterial interaction with human and insect cells could be studied, he determined that another human pathogen, the bacterium Yersinia pseudotuberculosis could interact with insect cells. Y. pseudotuberculosis is closely related to the far more dangerous Y. pestis, which causes the bubonic plague in humans and requires interaction with insects. The race was then on to demonstrate that interaction and investigate a then recently reported set of genes in Y. pseudotuberculosis which could have insecticidal activity. It is an area that has been little studied. He finished his laboratory work on his PhD in 2005, but it was not until the final six months that everything came together.
He then he spent five and half months writing up his thesis, supported by his wife who had just finished her PhD at Oxford.
As he was writing up, the opportunity came up to work as a career development fellow at the Medical Research Council’s Laboratory of Molecular Biology. Three years later he was promoted to research investigator. He worked on two overlapping projects. One involved looking at whether genetic information can be stored in anything other than DNA and RNA. Within three years of starting he got proof that this was possible, hence developing the first synthetic genetic materials. The second project focused on trying to isolate synthetic molecules that could work as ligands or even enzymes, with potential biotechnological and therapeutic applications. “The questions kept getting bigger once I was able to show that the synthetic material could do everything that normal nucleic acid could do,” says Vitor. His supervisor wanted to look at how the findings could be applied to diagnostics and therapy, but Vitor was more interested in continuing to push the boundaries of molecular biology and to work on creating a stable biological system in vitro which was not dependent on RNA or DNA.
He says things started to move very fast as excitement around the discovery of XNA built. He published several papers.
In 2013 he set up his own research group, the Pinheiro Group, at University College London focused on developing novel platforms for protein directed evolution with a view to rewriting biology: creating life dependent on synthetic genetic materials, rewriting the genetic code, building new tools for molecular biology. Those aims can be adapted for containment of genetically modified organisms, creating a biological firewall: organisms that cannot exist outside the lab harbouring genetic information that cannot be used by nature. Vitor, who is a Lecturer in Synthetic Biology at UCL and at the Institute of Structural and Molecular Biology, is collaborating with nine other groups and says: “We are going for the Holy Grail of creating life from synthetic material.”
His group includes four postdoctorate researchers, two technicians and two PhD students. Vitor says there is a lot of resistance to genetically modified organisms in Europe despite the fact that genetic engineering has long been common in farming through hybridisation, selection and breeding . “It’s the visceral response they struggle with as they are worried about escapes, which makes our work highly relevant. In Brazil there is much more acceptance of GMOs,” he says.
He would like to return to Brazil at some point, but knows he can attract more funding for his work in the UK so he is keen to grow the synthetic biology community in Europe. He has been in touch with another Gates Cambridge Scholar, Christian Boehm, who set up the European Association of Students and Postdocs in Synthetic Biology, and says he hopes to mentor him.
Vitor credits a lot of his success to Gates Cambridge. “It was a life-changing experience,” he says. “If I had not got it I would not have done my PhD in Cambridge and I would have gone home. I would probably not be a scientist. Being at a world-leading research facility and university has enabled everything that has followed.”