Regenerative Medicine Rising in the East

Asian markets at the forefront of regenerative medicine advancements.

Across the pharmaceutical industry, the Asia-Pacific has grown in importance, attracting big pharma to the region with its easy access to patient populations and low manufacturing costs.  In addition, generic drug manufacturing has massively boosted the market. However, one area in which the Asia-Pacific has really been forging its own path is in regenerative medicine. Encompassing stem cell therapy, gene therapy and tissue engineering, this innovative area of science offers the chance to repair damaged tissue and restore proper functioning to cells. It is an area of increasing interest globally, with massive potential, as demand for novel curative and reparative therapies soars as a result of the growing aged populations and rising incidence of cancers and chronic diseases. However, to date, regulatory bodies have been unwilling to approve gene therapies and stem cell therapies in the west, because of the unproven nature of the science. Instead, Asia-Pacific countries have emerged at the forefront of the commercial clinical use of these pioneering approaches.

China has led the way in gene therapy approvals to date, with Gendicine and Oncorine hitting the market in 2003 and 2005 respectively. These approvals demonstrated an important fact – that China was serious about developing regenerative medicine, sensing an opportunity to enter a young, growing market at an early stage and attract industry attention with favourable approval mechanisms. This has been replicated across other Asia-Pacific countries. In South Korea, the world’s first approved clinical stem cell treatment is Hearticellgram-AMI from FCB-Pharmicell, which uses a stem cell transplant from the patient to improve heart function. This was approved in 2011 and was followed by two other stem cell therapies in 2012. Their long-term success in the market has yet to be determined, but they represent important milestones in regenerative medicine commercialisation. Singapore, meanwhile, has made a deliberate effort to set itself up as a hub of regenerative medicine research.

It isn’t just local companies that are getting in on the action in the Asia-Pacific – US company Epieus Biotechnologies commercialised its cancer gene therapy Rexin-G in the Phillippines, and US companies such as Vical and Genzyme have entered into collaborations with Asian companies.

Some of the same advantages that make approval easier in countries such as China also damage the country’s chances of leading the industry, however. Regulations governing approval are less strict, which has led to the early approvals of therapies such as Gendicine and Oncorine. This lack of stringency in the requirements for approval has meant that without extensive further testing, the therapies cannot enter other markets such as the US and EU. In addition, there is general scepticism as to the actual benefit of therapies approved without detailed clinical trial data. In addition, despite China having a high number of patients with head and neck cancer who could benefit from the approved therapies, reimbursement and insurance coverage limitations for Chinese citizens mean that access is severely restricted. Consequently, the revenues of therapies such as Gendicine, previously predicted as having blockbuster potential, have remained stubbornly disappointing. Benda Pharmaceuticals, who own the rights to the product, was worth only $4.1m in 2010.

The unproven and unfamiliar nature of the science has led to caution from regulatory bodies and has been a frustrating deterrent to R&D by industry in the US and EU, but high patient populations, more permissive approval processes and a desire to gain a competitive advantage in a developing area with high growth potential have given the Asia-Pacific a head start in regenerative medicine. Western governments and industry are paying increasing attention to the region, attempting to ensure that they are not losing ground in the regenerative medicine market but also keen to leverage the opportunities offered in the Asia-Pacific as acceptance, demand and expertise flourish there. 

Amy Baker is a Life Science Analyst at GBI Research

Photograph: Getty Images

Amy Baker is a Life Science Analyst at GBI Research.

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Inside Big Ben: why the world’s most famous clock will soon lose its bong

Every now and then, even the most famous of clocks need a bit of care.

London is soon going to lose one of its most familiar sounds when the world-famous Big Ben falls silent for repairs. The “bonging” chimes that have marked the passing of time for Londoners since 1859 will fall silent for months beginning in 2017 as part of a three-year £29m conservation project.

Of course, “Big Ben” is the nickname of the Great Bell and the bell itself is not in bad shape – even though it does have a huge crack in it.

The bell weighs nearly 14 tonnes and it cracked in 1859 when it was first bonged with a hammer that was way too heavy.

The crack was never repaired. Instead the bell was rotated one eighth of a turn and a lighter (200kg) hammer was installed. The cracked bell has a characteristic sound which we have all grown to love.

Big Ben strikes. UK Parliament.

Instead, it is the Elizabeth Tower (1859) and the clock mechanism (1854), designed by Denison and Airy, that need attention.

Any building or machine needs regular maintenance – we paint our doors and windows when they need it and we repair or replace our cars quite routinely. It is convenient to choose a day when we’re out of the house to paint the doors, or when we don’t need the car to repair the brakes. But a clock just doesn’t stop – especially not a clock as iconic as the Great Clock at the Palace of Westminster.

Repairs to the tower are long overdue. There is corrosion damage to the cast iron roof and to the belfry structure which keeps the bells in place. There is water damage to the masonry and condensation problems will be addressed, too. There are plumbing and electrical works to be done for a lift to be installed in one of the ventilation shafts, toilet facilities and the fitting of low-energy lighting.

Marvel of engineering

The clock mechanism itself is remarkable. In its 162-year history it has only had one major breakdown. In 1976 the speed regulator for the chimes broke and the mechanism sped up to destruction. The resulting damage took months to repair.

The weights that drive the clock are, like the bells and hammers, unimaginably huge. The “drive train” that keeps the pendulum swinging and that turns the hands is driven by a weight of about 100kg. Two other weights that ring the bells are each over a tonne. If any of these weights falls out of control (as in the 1976 incident), they could do a lot of damage.

The pendulum suspension spring is especially critical because it holds up the huge pendulum bob which weighs 321kg. The swinging pendulum releases the “escapement” every two seconds which then turns the hands on the clock’s four faces. If you look very closely, you will see that the minute hand doesn’t move smoothly but it sits still most of the time, only moving on each tick by 1.5cm.

The pendulum swings back and forth 21,600 times a day. That’s nearly 8m times a year, bending the pendulum spring. Like any metal, it has the potential to suffer from fatigue. The pendulum needs to be lifted out of the clock so that the spring can be closely inspected.

The clock derives its remarkable accuracy in part from the temperature compensation which is built into the construction of the pendulum. This was yet another of John Harrison’s genius ideas (you probably know him from longitude fame). He came up with the solution of using metals of differing temperature expansion coefficient so that the pendulum doesn’t change in length as the temperature changes with the seasons.

In the Westminster clock, the pendulum shaft is made of concentric tubes of steel and zinc. A similar construction is described for the clock in Trinity College Cambridge and near perfect temperature compensation can be achieved. But zinc is a ductile metal and the tube deforms with time under the heavy load of the 321kg pendulum bob. This “creeping” will cause the temperature compensation to jam up and become less effective.

So stopping the clock will also be a good opportunity to dismantle the pendulum completely and to check that the zinc tube is sliding freely. This in itself is a few days' work.

What makes it tick

But the truly clever bit of this clock is the escapement. All clocks have one - it’s what makes the clock tick, quite literally. Denison developed his new gravity escapement especially for the Westminster clock. It decouples the driving force of the falling weight from the periodic force that maintains the motion of the pendulum. To this day, the best tower clocks in England use the gravity escapement leading to remarkable accuracy – better even than that of your quartz crystal wrist watch.

In Denison’s gravity escapement, the “tick” is the impact of the “legs” of the escapement colliding with hardened steel seats. Each collision causes microscopic damage which, accumulated over millions of collisions per year, causes wear and tear affecting the accuracy of the clock. It is impossible to inspect the escapement without stopping the clock. Part of the maintenance proposed during this stoppage is a thorough overhaul of the escapement and the other workings of the clock.

The Westminster clock is a remarkable icon for London and for England. For more than 150 years it has reminded us of each hour, tirelessly. That’s what I love about clocks – they seem to carry on without a fuss. But every now and then even the most famous of clocks need a bit of care. After this period of pampering, “Big Ben” ought to be set for another 100 or so years of trouble-free running.

The Conversation

Hugh Hunt is a Reader in Engineering Dynamics and Vibration at the University of Cambridge.

This article was originally published on The Conversation. Read the original article.