Discovery of DNA Repair Methods Nails 2015 Chemistry Nobel Prize

Three scientists who found ways that cells fix damaged DNA—staving off cancer and other diseases—have won this year's prize

There are three reasons we are not constantly riddled with cancer, and today the scientists who discovered those reasons—three ways that cells repair damaged DNA that can ruin bodies--won the 2015 Nobel Prize for Chemistry.

This morning The Royal Swedish Academy of Sciences announced the coveted prize is going to Tomas Lindahl from the Francis Crick Institute and Clare Hall Laboratory in Hertfordshire, England; Paul Modrich from the Howard Hughes Medical Institute and Duke University School of Medicine in North Carolina in the United States; and Aziz Sancar from the University of North Carolina in Chapel Hill, also in the U.S. “I know, over the years, that I’d been mentioned for the prize,” Lindahl said in a telephone call to the academy. “But hundreds of people get considered every year so I feel very lucky.”

He and the other two researchers, working independently over the last 40 years, described three different mechanisms that create errors in DNA—the molecule that controls cell behavior—and the different ways that chemical and biological processes fix many of these problems.

“All forms of cancer start with DNA damage,” said biochemist Claes Gustafsson, one member of the Nobel chemistry committee. “If you do not have DNA repair, we would have a lot more cancer. That’s how important this is.” He added that the repair techniques let us understand how cigarette smoke, sunlight, and even mundane substances like water can damage DNA and point to ways that the damage can be rectified.

It is not just about cancer, Diane Grob Schmidt, president of the American Chemical Society, told Scientific American in an interview. “The understanding that we have of these mechanisms help us design drugs to repair all sorts of DNA errors,” she said. There are also several genetic diseases caused by the inability of cells to fix DNA properly, for instance, and work on the repair methods aids understanding of these ailments and how to treat them.

The discoveries illustrate the crucial and central role of chemistry, Schmidt added. “These mechanisms are fundamentally about the making and breaking of chemical bonds,” she said.

Scientists used to believe that DNA molecules were extremely stable. After all, they had to reliably transmit genetic information from generation down to generation. Then in the 1970s Lindahl demonstrated that the neat double helix and its components constantly decays. Every day, hundreds of those components, the DNA building block chemicals abbreviated as A, T, C, and G, get knocked out of their places. If the process continued unabated, the development of life on Earth would have been impossible. This insight led Lindahl to discover a series of enzymes and reactions, called base excision repair, which constantly works to fight this decay. The C building block, for instance, is repeatedly broken down into another molecule that should not be in DNA. The enzymes Lindahl found identify that broken molecule and rebuild it into a C.

Sancar found that cells use another technique to repair damage to DNA caused by ultraviolet light, the same thing that gives you a sunburn. This DNA fix is called nucleotide excision repair. People born with defects in this repair system will develop skin cancer if they are exposed to sunlight. Excision enzymes cut out the DNA lesions. The cell also uses this repair system to correct DNA damage people get after they are born, when they encounter mutagenic substances

Finally, Modrich found out how a cell corrects errors that occur during a vital biological process: Cell division, when DNA is replicated. This copying process is supposed to produce identical strands of DNA but often there are stretches of the new stand that do not match up. The set of cellular chemicals that Modrich found, a complex called mismatch repair, scans the strands and fixes them, reducing the error frequency during replication by about a thousand times during each replication cycle. (Modrich co-authored a Scientific American article on genetic engineering.)

“Without all of these repair mechanisms.” Lindahl said, “we would not be long-lived.” For finding them, he and the two other scientists will split $1 million dollars in three equal shares.
- By Josh Fischman | Scientific American







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TPPA a bad deal for Malaysia, can't isolate China, only trade growth defines merits of TPP

KUALA LUMPUR: United Nations assistant director-general and coordinator for economic and social development, food and agriculture organisation, Dr Jomo Kwame Sundaram (pix) has called on the government not to join the Trans Pacific Partnership Agreement (TPPA) as it provides little benefit for Malaysia.



“I am extremely disappointed. I think it is going to affect, not only the Malaysian business community, but also Malaysian consumers and citizens adversely,” he told reporters on the sidelines of the Khazanah Megatrend Forum 2015 .

On Monday, the Ministry of International Trade and Industry (Miti) said the recently concluded TPPA negotiations had agreed to take into consideration almost all of Malaysia’s concerns and sensitivities such as government procurement, state-owned enterprises and bumiputra issues.

The TPP is a trade agreement initiative involving 12 countries namely Australia, Brunei, Canada, Chile, Japan, Malaysia, Mexico, New Zealand, Peru, Singapore, the US and Vietnam.

Miti said the TPPA will be presented to parliament once the complete and official text of the agreement is prepared.

Bloomberg reported that Malaysia’s state-owned enterprises may suffer from the deal, which calls for equal access to government procurement even though electronics, chemical products, palm oil and rubber exporters benefit from it.

Jomo said that the TPPA is politically motivated, in that it is an attempt by the US to try and isolate China, with minimum trade advantages for Malaysia.

“For example, if Malaysia produces solar panels it can’t be sold in the US and elsewhere. These are all contravening the bilateral agreements. You cannot expect the TPPA to overcome that,” he explained.

On intellectual property rights, Jomo said that the most significant implication is the cost of medication.

“They have exclusive rights and have been depriving people from the benefits of this. This is scandalous and inhumane, it cannot explain why Malaysia agreed to this,” he said.

In a statement late on Monday however, Miti had reiterated that the TPPA should not hinder the public’s access to affordable drugs and healthcare, while ensuring the necessary incentives for pharmaceutical innovators to produce new drugs and medicines.

Even though there will be “small” benefits, Jomo said the government should look at it as a whole, especially from the cost perspective.

He also said foreign complainants will have more legal resources for dispute settlement through new arbitration panels compared with those from developing countries.

“Even in the negotiations, they (developing countries) are not very well prepared, and everyone knows most of the developing countries just accepted what was given to them. It was the developed countries such as Australia, New Zealand and Japan that were insisting on it and the US compromised to them,” he added.

Meanwhile, Miti secretary-general Tan Sri Rebecca Fatima Sta Maria stressed that the full text of the TPPA will be made available to the public soon.

“We’ve nothing to hide, at the end of the day, the important thing is we want to be sure this works for Malaysia,” she said.

She does not foresee the TPPA taking effect in the next two years considering it has to be approved by every participating country

“ It will be a long process, maybe two years or more, I don’t know,” she added.

A cost benefit analysis commissioned by Miti to determine the attractiveness of the deal is yet to be completed.

TPPA cost benefit analysis still pending

Should have been finalised earlier for the sake of public understanding



PETALING JAYA: The cost benefit analysis on the Trans-Pacific Partnership Agreement (TPPA) should have been finalised and released earlier for the sake of public understanding, Bantah TPPA group chairman Mohd Nizam Mahshar said in a statement yesterday.

Commenting on the conclusion of the TPPA negotiations, he said the cost benefit analysis should have been finalised and released earlier, to provide the public and interested parties with a greater understanding of the TPPA and its implications.

The release of the cost benefit analysis has been delayed for months.

“Until now, it has not been released and we only have three months from the official date of the negotiation’s conclusion to the date that it has to be signed,” he added.

International Trade and Industry Minister, Datuk Seri Mustapa Mohamed said in a Facebook posting yesterday that the contents of the TPPA deal will be made public next month and presented to parliament for debate within the next two months.

The minister said it would also include the completed cost benefit analysis.

“This does not mean a thing. Even though debated by parliamentarians, the agreement cannot be amended,” Mohd Nizam said. “From this day to the next 90 days Malaysia has only two choices, either to take the TPPA agreement as a whole or to reject it completely. We still have a say if we choose to speak up,” he added.

Nizam said despite the conclusion of the negotiations, the group is maintaining its position that the TPPA deal will not benefit the country’s trade or economic health.

He said the possible impact includes restrictions of policy space, intrusions on legal and political sovereignty, huge impact to small and medium enterprises and infant industry, access to affordable medicine, as well as intellectual property effects to knowledge and information institutions and industries.

Meanwhile, the recently formed coalition party Parti Amanah Negara said it hoped all comments from the public will be considered seriously.

“We also hope all necessary action will be taken and the debate will not merely be an exercise in ‘public relations’,” its communication director Khalid Abd Samad said in a statement.

He added that the minister previously had acknowledged that there were several concerns regarding the TPPA, saying among the concerns in the agreement is that it seeks to ensure free competition with minimal government control or intervention.

“This will only result in stronger companies overcoming all others and dominating the market,” Khalid said, explaining that local companies, which are much smaller than the United States multinational companies and other member countries will not be able to compete and therefore become sidelined.

Commenting on the intellectual property rights issue, Khalid said it would have a direct impact specifically on the price of medicine, and enforcement of intellectual property rights would cause higher prices of medicine.

“Even though this may be good for the pharmaceutical companies, it will certainly have a negative effect on the population as a whole,” Khalid added, saying that the party is worried that the deal will only bring short-term benefits, while increasing the country’s dependency on specific sources of revenue.

Meanwhile, Asian Strategy and Leadership Institute’s Centre for public policy studies chairman Tan Sri Ramon Navaratnam said the Ministry of International Trade and Industry should hold several town hall meetings to explain the TPPA deal to the public.

“We cannot afford to leave important national agreements and treaties only to politicians to decide, as they may have their own political deals to settle. We all have to actively participate in the debate outside parliament as well,” he added. - The Sunbiz

TPP cannot ‘isolate China’ - Chinese economy increasingly open, inclusive: economist

The US-led Trans-Pacific Partnership (TPP) trade agreement will not isolate China or seriously hurt the Chinese economy, experts said Wednesday, adding it could lead the world's second-largest economy to reach similar deals with other nations, after a deal was reached on the TPP earlier this week.

Amid widespread online pessimism over the trade pact among 12 Pacific Rim nations that some believe deliberately excluded China, Chinese economists said such anxieties have been overblown.

Huang Wei, director of the Institute of World Economics and Politics at the Chinese Academy of Social Sciences, said the TPP will affect China, but will have a "minimal negative impact" on the Chinese economy in the long run because of the economy's size and its irreplaceable role in regional and global markets.

Huang believes the TPP creates more of a "psychological effect" on China that the country has been left out by its neighbors and trading partners from such a significant trade agreement. "But don't turn pale just at the mention of a tiger," she told the Global Times on Wednesday.

She said, if anything, the trade accord will push China to further engage with regional and global economies and pursue more trade agreements with countries in Asia and around the world, which will help the Chinese economy grow and better compete globally.

Chen Fengying, an expert at the Institute of World Economics Studies under the China Institute of Contemporary International Relations, also believes that the TPP will not isolate China from the regional economy and could even be beneficial.

"Given the important role China plays in regional and global economics, a single agreement won't isolate China," Chen told the Global Times Wednesday. She added that if the TPP can help build a more open and prosperous Asia, it will be conducive for the Chinese economy.

Both Huang and Chen's comments come after trade ministers from the US, Canada, Mexico, Chile, Peru, Japan, Malaysia, Vietnam, Singapore, Brunei, Australia, and New Zealand reached a deal.

After days of negotiations on the details of the deal in Atlanta, US officials announced Monday that an agreement had been reached, ending years of talks, though the deal still needs to go through the legislative process of each country before it can be signed and implemented.

Prevailing issues

Some posts on popular social media platforms in China suggested Wednesday that China's own issues in areas such as intellectual property protection, environmental standards and currency policies prevented it from being included in the deal, while others said the US is trying to single out China and counter China because the US feels its economic and political dominance is being threatened.

Experts said understanding the TPP's impact should not only be based on the "US conspiracy theory" or the "China-deserves-it" angle.

Zhang Jianping, a foreign trade expert at the National Development and Reform Commission, told the Economic Daily that China lags behind in meeting the TPP's requirements, such as environmental, finance and labor standards. It will take a long time for China to reach those standards, and that is why China held back in joining the TPP, he said.

Chen also said that intellectual property protection, environmental standards and other factors might have been reasons why China did not sit at the negotiating table, but such a move has pushed China to improve in such areas, as it holds numerous trade talks with countries in Asia and beyond, including TPP member-nations.

China engages world

China has reached separate free trade agreements with Australia, New Zealand, Chile, Peru, and Singapore, who are also involved in the TPP, while continuing talks with the US, Japan and other countries on free-trade deals.

China is also engaged in regional multilateral trade talks, such as the Free-Trade Area of the Asia-Pacific (FTAAP) with Asia-Pacific Economic Cooperation (APEC) economies, and the Regional Comprehensive Economic Partnership (RCEP) with the Association of Southeast Asian Nations (ASEAN) and Japan, South Korea, Australia, New Zealand and Indonesia.

All these efforts and other projects such as the "Belt and Road" initiative and the Asia Infrastructure Investment Bank (AIIB) show the Chinese economy is moving toward being more open and inclusive, Chen said. It will help the country to maintain its increasing influence over regional and global trade, she added.

Chen also said she believes these trade deals are not mutually exclusive, saying they can complement each other by building a more open and fair regional economy in the Asia-Pacific.

China's Ministry of Commerce said Tuesday that China is open to any trade agreement "compatible" with rules established by the World Trade Organization, and that is conducive to the regional economic integration of the Asia-Pacific region.- Global Times

Only trade growth will define merits of TPP


Labourers work at a garment factory in Sai Dong, outside Hanoi, Vietnam. [Photo/Agencies]

At a critical moment when trade is set to grow less than the global economy for the first time in the last four decades, there is no reason not to welcome the ambitious pact that 12 Pacific Rim countries reached on Monday to create the largest free trade area of the world.

That is why China's Ministry of Commerce said on Tuesday that the Trans-Pacific Partnership is one of the key free trade agreements for the region and China is open to any mechanism that follows the rules of the World Trade Organization and can boost the economic integration of the Asia-Pacific.

As a top global trading power that has hugely contributed to and benefited from the global trade growth for the last two decades, China sincerely hopes the TPP pact and other free trade arrangements in the region can strengthen each other and boost trade, investment and economic growth in the Asia-Pacific, to benefit not just the region but also the rest of the world.

It is also the common wish of the international community that, as a long-term driving force, the current slow pace of global trade growth should be revived through deeper and wider reforms of the international trade system to fuel a sustainable global recovery from the 2008 financial crisis.

The appealing promise that the TPP may reshape industries and liberalize commerce in 40 percent of the world's economy has understandably given rise to praise such as the "most ambitious trade pact in a generation".

Yet the real implications of the TPP deal are far from clear since it has been largely negotiated under a blanket of secrecy to facilitate give-and-take among the signatories.

The power of a successful trade deal is to maximize as much as possible each participant's comparative advantages in global trade while minimizing predictable political opposition from various domestic vested interests.

Nevertheless, even before the five-year marathon talks have secured a really workable arrangement, US President Barack Obama hastened to paint the pact as a way of stopping China from writing the rules of the global economy in an illusion that he may easily win over the domestic political support he expects.

However, if the deal is based on the political priority of one partner, rather than the shared benefit of all partners, it would be hard to believe that it can ensure free market trade as it is being touted.

The world needs a trade-boosting deal. The United States has a huge onus to prove the merits of the TPP.  - China Daily

Economic woes a test for South East Asia

Speculative attacks will challenge reserves, defences built after 1997/98

A man is silhouetted as he fishes near Northport in Klang outside Kuala Lumpur June 6, 2014. REUTERS/SAMSUL SAID

Southeast Asia has spent the best past of two decades shoring defenses against a repeat of the Asian financial crisis, including building up record foreign exchange reserves, yet is now feeling vulnerable to speculative attacks again.

Officials are growing increasingly concerned as souring sentiment has made currencies slide and investors reassess risk profiles in an environment where China is slowing and U.S. interest rates will rise at some point.

And while economists have long dismissed comparisons with the 1997/98 currency crisis, pointing to freer exchange rates, current-account surpluses, lower external debt and stricter oversight by regulators, lately there has been a change.

Malaysia and Indonesia, which export oil and other commodities to fuel China's factories, are looking vulnerable as the world's second-largest economy heads for its slowest growth in 25 years and the prices of their commodity exports plunge.

"We are worried about the contagion effect," Indonesian Finance Minister Bambang Brodjonegoro said last week, using a word widely used in 1997/98.

In 1997, "the thing happened first in Thailand through the baht, not the rupiah. But the contagion effect became widespread," he added.

Taimur Baig, Deutsche Bank's chief Asia economist, said that unlike 1997, when pegged currencies were attacked as over-valued, today's floating ones are "weakening willingly" in response to outflows.

But there can still be contagion, as markets lump together economies reliant on China or on commodities. "If you see a sell-off in Brazil, that can easily spread to Indonesia, which can spread to Malaysia, and so on," he said.

Foreign funds have sold a net $9.7 billion of stocks in Malaysia, Thailand and Indonesia this year, with the bourses in those three countries seeing Asia's largest net outflows, Nomura said on Oct. 2.

Baig said that as in 1997/98, falling currencies will naturally pose balance-sheet problems for companies with dollar debts and local-currency earnings.

This year, Malaysia's ringgit MYR= has fallen nearly 20 percent against the dollar and its reserves dropped by about the same percentage, to below $100 billion.

"It's almost like a perfect storm for Malaysia," the country's economic planning minister, Abdul Wahid Omar, said.

Malaysian officials insist the economic fundamentals are stronger than two decades ago, but some economists aren't sure.

Chua Hak Bin of Bank of America Merrill Lynch said he draws "little comfort" from comparisons with 1997. While in many ways Malaysia's economy is stronger now, for example by having a current account surplus, its external debt is 70 percent of gross domestic product, compared with 44 percent in 1997, and there's "significant downside risk even after the sharp ringgit correction".

None of the three main credit-rating agencies has downgraded Malaysia's creditworthiness in response to market ructions, but Moody's said in September the currency's fall was a symptom of declining exports and other factors negatively impacting key credit buffers.

SOURING SENTIMENT

Indonesia, Southeast Asia's largest economy, has a lower external debt relative to GDP - 32 percent – but foreigners also own a large share its local-currency bonds.

This makes the rupiah, down 13 percent against the dollar this year after jumping on Tuesday, vulnerable to souring sentiment.

"We are trying to differentiate ourselves from Malaysia," Indonesia's Brodjonegoro said. "At least we can get the inflows, we can still create positive sentiment."

At end-February, Indonesia's reserves topped $115.5 billion. On Sept. 21, they were $103 billion.

On Wednesday, the central banks of Indonesia and Malaysia are due to announce fresh reserve figures.

By months of import cover, Southeast Asia's holdings of foreign reserves still seem sufficient. But looking at them relative to overall foreign financing needs, they are more stretched.

Malaysia's reserves barely cover its short-term external debt due this year, while Deutsche Bank says Indonesia's are about 1.5 times what's needed to finance its debts and current-account deficit.

The Philippines, by contrast, has reserves equal to 11 times its financing needs. The $2 billion monthly remittances from its overseas workers provides a solid buffer.

BY NICHOLAS OWEN Reuters

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