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Human Mini-Brains Replacing Animals In Zika Virus Research

03/10/2016 14:48

Brazil has been in the news a lot lately, and for good reason: weeks of top-class Olympic and Paralympic sporting events have inspired and motivated us, and although less celebrated, arguably even more critical for human health, top-class Brazilian science has been applied to address the Zika virus outbreak.

Before we can develop a treatment for a viral infection, we need to identify the specific virus that is the actual cause, and that's precisely what the innovative scientists from the Northwest region of Brazil did for Zika.

Babies with microcephaly are born with abnormally small heads, as a result of reduced brain growth and developmental defects. Microcephaly can be caused by infection, injury or genetic mutations, so the first challenge for Brazil and the world at large was determining whether infection with the Zika virus could be specifically responsible for the high numbers of babies born with microcephaly. Prof Rehen and his team at the D'Or Institute of Research and Education and the Federal University of Rio de Janeiro used a cutting-edge new technology -- human mini-brains -- to demonstrate that infection with the Zika virus was causing this high incidence of microcephaly.

Mini-brains are miniature human brain-like "organoids," grown in the laboratory using donated, ethically-sourced human cells. Like many scientific breakthroughs, such as the discovery of penicillin, chance played a role in the development of the mini-brain. In 2011, Dr Madeleine Lancaster used specially modified human skin cells, which had been altered so they were no longer skin cells and had the ability to become any cell type in any organ. These modified skin cells are induced pluripotent stem cells, or iPSC, which frequently make the headlines. However, Dr Lancaster was first to discover that these human skin-derived stem cells could be turned into a mini-brain.

Mini-brains are a very important research tool as they mimic many aspects of the human brain and represent a huge advance for science. Now we can use human mini-brains to investigate human brain development and diseases, and we no longer need to rely on artificial animal models using mice or other species. There are huge, obvious differences between animals and humans, and criticism of science's reliance on animal models is on the increase. The differences between animals and people make it difficult to apply the results obtained from animal models to human disease. In research on viral infections, for example, animal species may be used that are not normally infected by the virus. This means that researchers have to artificially infect the animals with huge amounts of virus or artificially alter the animal cells in order to get a response. As a result, drugs that show promise in treating artificially-induced infection in animals do not work in people.

There is also a lot of variation in how each animal responds to different compounds and stimuli. Thus, most animal studies have generated results that are not reliable as they cannot be repeated by other research groups. With such studies, millions of scarce health care funds are wasted, time, energy and lives are lost, and we are left with no solutions or treatments. We must give preference to research using alternatives to animal models, and the good news is that many alternatives, such as the mini-brains, already exist, and the choice of alternative methods is increasing.

Prof Rehen's team in Brazil used their mini-brains to demonstrate that damage to the brain cells was specific to infection with Zika virus. Their results also showed that infection with other infectious agents commonly found in Brazil (such as the Dengue virus) could not produce the brain-damaging effect. The study results were so significant that shortly after they were published, the World Health Organization released a report confirming the causal link between Zika virus and the occurrence of microcephaly in Brazil. This month, Prof Rehen's results were confirmed in a study, carried out by another team of Brazilian scientists, led by Dr de Araújo. This clinical study looked at babies born at eight public hospitals throughout Brazil, in a region known to be a Zika infection hotspot. They compared babies with and without microcephaly to show that there was a strong association between maternal Zika virus infection and brain abnormalities in babies. Finally knowing that the Zika virus causes microcephaly means that we can be prepared and target this disease properly.

We are often told that the use of animals is essential for medical research and advances in science. This research shows that this is not necessarily the case. Here, we have the crucial piece of one the biggest medical puzzles this decade falling into place without the use of animals. The success story from this is that those scientists in Brazil, in the face of so many difficulties, have used a state-of-the-art approach to provide the answers that everyone sought.

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