Monday, June 10, 2013 C7
WING AND A PEAR
Humans have fruit flies to thank for breakthroughs in life-saving drugs and treatments for mental illness, writes David Tan
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hen you look at the humble fruit fly, it is difficult to imagine how you could be in any way similar to it. With its large, red compound eyes, silvery wings and yellowand-black-striped body, the fruit fly appears to be a world apart from human beings. However, appearances can be deceiving and scientists are discovering just how alike these little critters are to us. The fruit fly, or Drosophila melanogaster in scientific speak, is widely used in research because it shares about 60 per cent of human genes. About 75 per cent of disease-related genes in humans have a counterpart in these flies. For more than 100 years, fruit flies have been used for scientific research, allowing breakthroughs in genetics, body structure and function. The first gene for jet lag and the first learning gene were identified in flies. In April, researchers from Britain published the first ever basic training package on the best ways to use the fruit fly for research. It is hoped the guide will encourage more researchers working on a range of conditions, from cancer to Alzheimer’s disease, to use the humble fly. “Flies need very little space so are ideal for breeding. They develop in just two weeks and it is a simple process to follow a genetic mutation through the generations by analysing the patterns on their bristles, wings or eyes which provide easy visible markers,” says Dr Andreas Prokop of the University of Manchester, who co-developed the training package. Our brains control behaviour in a “strikingly similar” way, according to a recent study. Comparing the central brain regions in fruit flies (called the central complex) and humans (the basal ganglia), scientists found that these structures were organised similarly. Dr Frank Hirth, a senior lecturer at the King’s College London Institute of Psychiatry who conducted the research, says the way flies and humans respond to basic survival situations are controlled by common systems in the brain. “Flies, crabs, mice and humans all experience hunger, need sleep and have a preference for a comfortable temperature, so we speculated there must be a similar mechanism regulating these behaviours,” Hirth says. “We were amazed to find just how deep the similarities go, despite the differences in size and appearance of these species and their brains.” Glial cells make up about half of the human brain, providing
The central complex (green) in an adult fruit fly’s brain works similarly to the human basal ganglia. Photo: King’s College London support for neurons, forming connections between brain cells and controlling the flow of blood. They are also important in diseases; for example, they are the main component of glioblastomas, a type of brain tumour. But scientists still don’t fully understand how they function, says Dr Lynette Foo, a postdoctoral fellow with the Institute of Molecular and Cell Biology in Singapore. Foo is using fruit flies to find the answers, zooming in on a particular group of molecules known as microRNAs which control various aspects of glial cells. “The simplicity of the fruit fly nervous system coupled with the genetic tools that enable us to genetically manipulate cells in vivo [in living flies] make fruit flies a very useful and powerful system,” says Foo. “We can attempt to understand how specific genes work in a simplified context and apply the knowledge gained to the more complex mammalian system.” Fruit flies are also helping scientists develop new treatments for neurological disorders, by revealing disease pathways of conditions ranging from sleep disturbances and attention deficits, to autism and schizophrenia. Hirth describes the recent discovery of a signalling pathway in Parkinson’s disease, which was first found in flies and later validated in human patients. The malfunctioning pathway causes mitochondria, the energy engines of cells, to fail. Cells become depleted of energy and degenerate, leading to movement problems and brain defects. “Diseased fruit flies show several characteristic features of human neurological disorders, including problems with movement, sleep disturbances and memory deficits, as well as age-related degeneration of nerve cells. Therefore, identifying
disease pathways in fruit flies is a reasonable means to begin to find treatments,” says Hirth. In one such study, researchers from the Tel Aviv University in Israel, led by Dr Daniel Segal,
We were amazed to find just how deep the similarities go, despite the differences in size and appearance of these species DR FRANK HIRTH, LECTURER
tested the common sweetener, mannitol, on fruit flies with a form of Parkinson’s. Mannitol can enable drugs to enter the brain from blood, breaching a barrier that normally exists between the blood and brain to prevent infection. Of key interest is the sweetener’s ability to prevent the build-up of a sticky protein that gums up a part of the brain among Parkinson’s patients. Fruit flies with a form of Parkinson’s caused by this gummy protein are unable to climb the walls of a test tube, indicative of “severe motor dysfunction”. When such flies were fed mannitol, the scientists found that the gummy protein in their brains decreased by 70 per cent and they could eventually climb up the test tube walls. To test treatments, diseased flies are given drugs to find those that can stop the disease, or at least slow its progression. Successful findings in flies must always be retested in human cells and in larger animal models such as mice. Because of the differences in size between humans, mice and flies, drugs are metabolised at different rates. The few candidates that pass many rounds of rigorous testing are then allowed to enter clinical trials. Hirth recounts a successful case where vitamins were used to stop the degeneration of nerve cells in fly models of Parkinson’s. “After several successful tests in other models, these findings are
Disease pathways in the insect’s brain offer clues to treating Parkinson’s. Photo: Masek Pavel
75% Percentage of disease-related genes shared by humans and fruit flies
Ask the doctors ................................................ Dr Durai Raj Subramaniam life@scmp.com Q: Does eating certain foods give you body odour? My friend tells me that eating garlic makes you smell the next day. A: You really don’t need a doctor to answer this. If you know people who have eaten garlic regularly for health purposes, you might notice that they suddenly lose all their friends. I have been told that monks refrain from garlic due to its aphrodisiac properties – but if anyone takes it to improve their sexual prowess, they better make sure their partner is either on garlic too or has a damaged sense of smell! The rancid, pungent and musty odour will more likely kill the mood. OK, joking aside, it is true that certain foods can cause one to suffer from body odour, known as bromhidrosis. So what are the usual suspects? The journal Medscape states that the “omission of certain foods may be of value if these factors can be isolated or identified as contributory factors to the bromhidrosis. Common culprits include curry spices, onions, garlic and alcohol.” But not all of us are affected in the same way and some of
us have a greater predisposition to suffer from this condition than others. Some of these factors are not modifiable, such as being born with a genetic predisposition. Other factors, however, are modifiable. We can do something about poor hygiene, obesity and even diabetes, such as using antiperspirants and soap, losing weight and taking diabetes medications. There also are certain genetic conditions that can make some people smellier than others. One such condition is trimethylaminuria (TMAU). People with this condition suffer from a relative deficiency of a certain enzyme that breaks down trimethylamine (which has a fishy odour) from food. So when there is an increased production of trimethylamine in the body for whatever reason (such as consuming the usual suspects above, hormonal changes around menstruation or emotional-stress-induced sweating), the compound leaches out through urine, sweat and, yes, even reproductive fluids. Think of it like a toilet that does not flush properly and overflows when it is blocked.
currently being tested in clinical trials [in human patients].” The similarities between humans and fruit flies aren’t just internal. Externally, while human skin and a fruit fly’s hard casing may appear completely different, both serve the same purpose of protecting against injury, infection and dehydration. Because of this, the outermost cells of both humans and flies respond to some of the same signals. In the laboratory of Professor William McGinnis of the University of California San Diego, researchers established that the immune system kicks in as soon as the fly’s casing is breached. This first response prepares the fly to fight against bacterial or fungal infection. The next wave of response involves proteins that repair the wound, followed by activation of processes that colour the healed outer casing. McGinnis’ team found eight molecules that previously had not been known to participate in wound healing. These components are usually not present or present at low levels, and are only called into action once injury occurs. Scientists are now exploring if the same molecules in humans play comparable roles. “One amazing application of our studies may be to build a better bandage containing compounds to promote wound healing,” says Dr Michelle Juarez, a member of McGinnis’ team. life@scmp.com
My opinion is that all of us have a predisposition for body odour, [linked] with our diet Some toilets are high-quality systems that can cope with practically anything, while others are more delicate – such that if you throw in something that causes it to jam up, it creates a stink. My opinion is that all of us have a certain predisposition for body odour, associated with our diet. Some of us are fatter than
others, some of us like certain foods more than others, some of us live in more humid climates and some of us are more likely to sweat more under stress. By balancing our lifestyles which include our food choices we may be able to control our body odour. For those of us who still suffer from bromhidrosis despite using every effort to ease it, there are certain medical interventions that include using medicated soaps and oral antibiotics as well as more drastic measures such as botox injections and laser treatment of the sweaty areas in order to reduce sweating. Dr Durai Raj Subramaniam is a resident physician at Gleneagles Hospital in Singapore
HEALTH Best practitioners now within reach ................................................ Jeanette Wang jeanette.wang@scmp.com The super rich often have their personal fortunes managed by single family offices, which offer exclusivity and privacy over commercial banks or investment companies. Taking a leaf from their books, a local businessman has launched Hong Kong’s first dedicated family health office. Qineticare offers 24/7 services, with a personal care team managing all aspects of its members’ health care, including priority access to “the finest medical and wellness professionals in Hong Kong”. “Our aim is to transform the focus from reactive sickness management to proactive health care,” says the company’s founder and CEO, Feisal Alibhai. Its target audience is the time-poor, stressed professional who tends to overlook health – no doubt a common crowd in Hong Kong. Feisal, 44, who was born in the Democratic Republic of Congo and who has lived all over the world, says most people he meets are not prepared for illness. “It’s quite shocking,” he says. Feisal moved from New York to Hong Kong in 1992 to set up a buying office for his garment and textile company. Back then, with frequent work trips to Eastern Europe and Africa, he surrounded himself with the best doctors, just in case he picked up any infectious or tropical diseases. So, when diagnosed with stage three lung cancer in 2004, he was taken by surprise – but he was prepared. “I was able to handle the situation with a minimal amount of stress because I had access to the top doctors, a comprehensive worldwide medical plan and a family that supported me throughout,” says Feisal. Doctors found 10 tumours – the largest, the size of a Rubik’s Cube, in his chest; another tennis-ball-sized one in his neck; and the rest, between 1cm and 2cm each, in his lungs. He was treated in Hong Kong. Twenty rounds of chemotherapy and three operations later, he has fully recovered. He realised his calling was assisting others with their health care. He started helping family and friends access Hong Kong’s best doctors, whom he knew after repeated hospital visits. Between 2007 and 2010, Feisal lived in Dubai and did the same there. Qineticare was formed to help people beyond his circle of influence. Membership costs US$2,000 for adults and US$1,000 for children per year. New members go through an “onboarding” process that includes collecting the medical history of the individual and his or her family, and a wellness assessment and coaching for lifestyle changes, says general manager Zeynep Incekara. A nurse is assigned to each
Qineticare CEO Feisal Alibhai. Photo: Qineticare
Our aim is to transform the focus from reactive … to proactive health care member. “If you wake up in the morning with severe neck pain, for example, you call your dedicated nurse and she will give you the names of three orthopaedic surgeons,” explains Feisal. “Once you pick one, she will arrange an appointment as soon as possible.” Qineticare has a panel of about 150 doctors covering 25 key categories of medicine. They are the “crème de la crème of Hong Kong”, he says. He assembled the panel after conducting a peer survey among a group of doctors. “I had them pick five or six specialists they would [seek treatment from] themselves for each category.” Feisal says 95 per cent of his panel match those on the International SOS list. Qineticare also has over 100 wellness practitioners of Eastern and Western philosophies. The company has partnerships with International SOS, for emergency aid worldwide, and Patients Know Best, an online medical records company based in Britain. It also works with insurance brokers. Members will have 50 per cent of their medical insurance commissions returned to them. Feisal says the membership fees are Qineticare’s only earnings. “There are no commissions, kickbacks, service fees – nothing – from insurance brokers, clinics, doctors, wellness providers and so on,” he says. Why, then, would this panel of doctors give his members priority access? “It’s a matter of building relationships,” says Feisal, who claims to have the numbers of Hong Kong’s top doctors in his wallet. He adds that priority access is based on “a level of common sense”. “Priority doesn’t mean immediate, it’s based on [the severity of] the situation,” he says.