The instruction on medication to "take three times a day" is so familiar that few of us would question its origins. But a scientific revolution sweeping through the pharmaceutical industry may soon consign it to medical history.
It's known as systems biology, a bland name for an emerging science whose implications are anything but run of the mill. For decades, researchers have sought to unravel the mysteries of life by focusing on its most basic components: genes. Made up of long sequences of chemicals forming the famous double helix molecule DNA, genes form the instructions used by every living cell.
Yet despite the huge effort poured into this "reductionist" view of biology, the payoff in terms of new drugs for conditions like cancer and heart disease has been meagre. It's now clear that in the search for medical breakthroughs, understanding genes alone is not enough.
Attention is now focusing on the host of factors that affect the behaviour of genes, from interactions with other genes to their physical location in organs. Understanding this incredibly complex web of interactions is the aim of systems biologists.
Their principal tools are not test-tubes or laboratory animals but supercomputers, whose number-crunching power allows simulations of the behaviour of entire living cells and even organs - with results likely to transform medical research.
Last month, scientists gathered at the International Conference on Systems Biology in Gothenberg, Sweden, to hear the latest results emerging from such computer simulations. And among the highlights was a study by researchers in the UK into one of the most basic yet neglected factors affecting the behaviour of cells: the time of day.
From bacteria to blue whales, all life follows the same roughly 24 hour circadian cycle of activity and rest. Its driving force seems obvious: the daily rising and setting of the sun. Yet a simple experiment first performed more than 250 years ago reveals an unexpected twist. Intrigued by the way plants open and close their leaves each day, the French scientist Jean Jacques de Mairan put a heliotrope in a dark room, to see how the plant would respond to being robbed of its daily cue. To his astonishment, its leaves continued to open and close, apparently in response to the ticking of some internal clock of its own.
Following de Mairan's pioneering work, researchers found that when deprived of the cues provided by the sun, organisms settle down to so-called free-running cycles that are close to 24 hours. In the case of humans, experiments revealed the cycle to be around 24.5 hours long. Yet the location and nature of the internal "clock" responsible for this cycle remained unclear.
The first big clue emerged in the late 1960s, when scientists identified a collection of nerve cells in the brain known as the suprachiasmatic nucleus (SCN). Linked to photosensitive cells in the eye, the SCN senses daylight and triggers the release of hormones like melatonin, which keep body functions in synch with the time of day. Then in 1995 researchers at Massachusetts General Hospital isolated nerve cells from the SCN, and found they could maintain a circadian rhythm without help from daylight. Finally, in 1997, scientists at Northwestern University in Illinois, found a gene that regulates the daily rhythms of cellular activity in mammals, including humans.
Such connections between genes, cells and the time of day is a classic example of systems biology - and one with major implications for drug design. For despite the medical mantra of "three times a day", doctors have long suspected some drugs work better when given at a specific time of day.
In the mid-1980s, William Hrushesky of the University of South Carolina published a pioneering study of patients with advanced ovarian cancer who were given one of two standard drugs - cisplatin and adriamycin - either at 6am or 6pm, with the other being administered exactly 12 hours later. The results showed that those given cisplatin in the morning followed by adriamycin in the evening suffered a far higher rate of toxic reaction than those receiving the same drugs in reverse order. Similar findings have been discovered by other researchers. Yet despite their obvious relevance to patients, such findings have yet to be put into practice - not least because the benefits of correct timing aren't believed to be worth the added complexity they bring to treatment.
That could soon change, in the light of research presented at last month's systems biology conference. Dr David Orrell of the UK-based pharmaceutical consultancy Physiomics presented the results of simulations of how timing of medication affects how a drug interacts with cells.
Dr Orrell and his colleagues have created a computer model of a living cell, complete with the kind of internal "clock" known to regulate its behaviour over the course of a day.
They have also simulated a real-life drug code-named CYC202, which is currently undergoing trials for use against lung cancer. The drug works by interfering with cell division - the process which, when uncontrolled, turns healthy cells cancerous.
As so often with cancer treatment, the challenge for doctors is to target the cancer cells while doing minimal harm to healthy cells. The computer simulations revealed that if the drug is given at the wrong time of day, it affects the division of healthy cells as well as cancerous cells, producing toxic side effects. But if given 16 hours later, the healthy cells are no longer susceptible - while the cancerous cells, which are constantly dividing, still feel the full effect of the drug.
More research is needed to find ways of identifying the optimal treatment time for each patient - and to minimise the inconvenience of taking the drug. But these early insights from the emerging field of systems biology suggest that, in medicine as in so much else, timing is everything.
Robert Matthews is a Visiting Reader in Science at Aston University, Birmingham, England
www.robertmatthews.org
Test
Director: S Sashikanth
Cast: Nayanthara, Siddharth, Meera Jasmine, R Madhavan
Star rating: 2/5
NO OTHER LAND
Director: Basel Adra, Yuval Abraham, Rachel Szor, Hamdan Ballal
Stars: Basel Adra, Yuval Abraham
Rating: 3.5/5
THREE
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The%C2%A0specs%20
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The specs: Aston Martin DB11 V8 vs Ferrari GTC4Lusso T
Price, base: Dh840,000; Dh120,000
Engine: 4.0L V8 twin-turbo; 3.9L V8 turbo
Transmission: Eight-speed automatic; seven-speed automatic
Power: 509hp @ 6,000rpm; 601hp @ 7,500rpm
Torque: 695Nm @ 2,000rpm; 760Nm @ 3,000rpm
Fuel economy, combined: 9.9L / 100km; 11.6L / 100km
Real estate tokenisation project
Dubai launched the pilot phase of its real estate tokenisation project last month.
The initiative focuses on converting real estate assets into digital tokens recorded on blockchain technology and helps in streamlining the process of buying, selling and investing, the Dubai Land Department said.
Dubai’s real estate tokenisation market is projected to reach Dh60 billion ($16.33 billion) by 2033, representing 7 per cent of the emirate’s total property transactions, according to the DLD.
2025 Fifa Club World Cup groups
Group A: Palmeiras, Porto, Al Ahly, Inter Miami.
Group B: Paris Saint-Germain, Atletico Madrid, Botafogo, Seattle.
Group C: Bayern Munich, Auckland City, Boca Juniors, Benfica.
Group D: Flamengo, ES Tunis, Chelsea, (Leon banned).
Group E: River Plate, Urawa, Monterrey, Inter Milan.
Group F: Fluminense, Borussia Dortmund, Ulsan, Mamelodi Sundowns.
Group G: Manchester City, Wydad, Al Ain, Juventus.
Group H: Real Madrid, Al Hilal, Pachuca, Salzburg.
The Saga Continues
Wu-Tang Clan
(36 Chambers / Entertainment One)
ULTRA PROCESSED FOODS
- Carbonated drinks, sweet or savoury packaged snacks, confectionery, mass-produced packaged breads and buns
- margarines and spreads; cookies, biscuits, pastries, cakes, and cake mixes, breakfast cereals, cereal and energy bars;
- energy drinks, milk drinks, fruit yoghurts and fruit drinks, cocoa drinks, meat and chicken extracts and instant sauces
- infant formulas and follow-on milks, health and slimming products such as powdered or fortified meal and dish substitutes,
- many ready-to-heat products including pre-prepared pies and pasta and pizza dishes, poultry and fish nuggets and sticks, sausages, burgers, hot dogs, and other reconstituted meat products, powdered and packaged instant soups, noodles and desserts.
In numbers: China in Dubai
The number of Chinese people living in Dubai: An estimated 200,000
Number of Chinese people in International City: Almost 50,000
Daily visitors to Dragon Mart in 2018/19: 120,000
Daily visitors to Dragon Mart in 2010: 20,000
Percentage increase in visitors in eight years: 500 per cent
The%20specs
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more from Janine di Giovanni
Mercer, the investment consulting arm of US services company Marsh & McLennan, expects its wealth division to at least double its assets under management (AUM) in the Middle East as wealth in the region continues to grow despite economic headwinds, a company official said.
Mercer Wealth, which globally has $160 billion in AUM, plans to boost its AUM in the region to $2-$3bn in the next 2-3 years from the present $1bn, said Yasir AbuShaban, a Dubai-based principal with Mercer Wealth.
“Within the next two to three years, we are looking at reaching $2 to $3 billion as a conservative estimate and we do see an opportunity to do so,” said Mr AbuShaban.
Mercer does not directly make investments, but allocates clients’ money they have discretion to, to professional asset managers. They also provide advice to clients.
“We have buying power. We can negotiate on their (client’s) behalf with asset managers to provide them lower fees than they otherwise would have to get on their own,” he added.
Mercer Wealth’s clients include sovereign wealth funds, family offices, and insurance companies among others.
From its office in Dubai, Mercer also looks after Africa, India and Turkey, where they also see opportunity for growth.
Wealth creation in Middle East and Africa (MEA) grew 8.5 per cent to $8.1 trillion last year from $7.5tn in 2015, higher than last year’s global average of 6 per cent and the second-highest growth in a region after Asia-Pacific which grew 9.9 per cent, according to consultancy Boston Consulting Group (BCG). In the region, where wealth grew just 1.9 per cent in 2015 compared with 2014, a pickup in oil prices has helped in wealth generation.
BCG is forecasting MEA wealth will rise to $12tn by 2021, growing at an annual average of 8 per cent.
Drivers of wealth generation in the region will be split evenly between new wealth creation and growth of performance of existing assets, according to BCG.
Another general trend in the region is clients’ looking for a comprehensive approach to investing, according to Mr AbuShaban.
“Institutional investors or some of the families are seeing a slowdown in the available capital they have to invest and in that sense they are looking at optimizing the way they manage their portfolios and making sure they are not investing haphazardly and different parts of their investment are working together,” said Mr AbuShaban.
Some clients also have a higher appetite for risk, given the low interest-rate environment that does not provide enough yield for some institutional investors. These clients are keen to invest in illiquid assets, such as private equity and infrastructure.
“What we have seen is a desire for higher returns in what has been a low-return environment specifically in various fixed income or bonds,” he said.
“In this environment, we have seen a de facto increase in the risk that clients are taking in things like illiquid investments, private equity investments, infrastructure and private debt, those kind of investments were higher illiquidity results in incrementally higher returns.”
The Abu Dhabi Investment Authority, one of the largest sovereign wealth funds, said in its 2016 report that has gradually increased its exposure in direct private equity and private credit transactions, mainly in Asian markets and especially in China and India. The authority’s private equity department focused on structured equities owing to “their defensive characteristics.”
COMPANY%20PROFILE
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Common%20symptoms%20of%20MS
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Volvo ES90 Specs
Engine: Electric single motor (96kW), twin motor (106kW) and twin motor performance (106kW)
Power: 333hp, 449hp, 680hp
Torque: 480Nm, 670Nm, 870Nm
On sale: Later in 2025 or early 2026, depending on region
Price: Exact regional pricing TBA
