August 6th, 2015:
TSRI Chemists Report Nicotine-Chomping Bacteria May Hold Key to Anti-Smoking Therapy
http://www.scripps.edu/news/press/2015/20150806janda.html
LA JOLLA, CA – August 6, 2015 – A new study from scientists at The Scripps Research Institute (TSRI) explores a bacterial enzyme that might be used as a drug candidate to help people quit smoking. The research shows that this enzyme can be recreated in lab settings and possesses a number of promising characteristics for drug development.
“Our research is in the early phase of drug development process, but the study tells us the enzyme has the right properties to eventually become a successful therapeutic,” said Kim Janda, the Ely R. Callaway Jr. Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at TSRI.
The new research, published online ahead of print on August 6 in the Journal of the American Chemical Society, offers a possible alternative to current smoking cessation aids, which are shown to fail in at least 80 to 90 percent of smokers. The idea behind an enzyme therapy would be to seek out and destroy nicotine before it reaches the brain—depriving a person of the “reward” of nicotine that can trigger relapse into smoking.
For more than 30 years, Janda and his colleagues have struggled to create such an enzyme in the lab, but they recently ran across a potential enzyme found in nature—NicA2 from the bacteria known as Pseudomonas putida. It turns out this bacterium—originally isolated from soil in a tobacco field—consumes nicotine as its sole source of carbon and nitrogen.
“The bacterium is like a little Pac-Man,” said Janda. “It goes along and eats nicotine.”
In the new study, the TSRI researchers characterized the bacterial enzyme responsible for nicotine degradation and tested its potential usefulness as a therapeutic.
The researchers first combined serum (a component of blood) from mice with a dose of nicotine equivalent to one cigarette. When they added the enzyme, the nicotine’s half-life dropped from two to three hours to just 9 to 15 minutes. Janda said a higher dose of the enzyme—with a few chemical modifications—could reduce the half-life of nicotine even further and keep it from ever reaching the brain.
Next, the researchers subjected the enzyme to a barrage of tests to determine its practicality as a drug candidate. “It was a long shot,” said Janda. “If it didn’t have the right metrics, it would be a bust.”
The results were encouraging. The enzyme stayed stable in the lab for more than three weeks at 98 degrees Fahrenheit—which Janda said was “pretty remarkable.” Importantly, the researchers detected no toxic metabolites produced when the enzyme degraded nicotine.
“The enzyme is also relatively stable in serum, which is important for a therapeutic candidate,” said Song Xue, a TSRI graduate student and first author of the new study.
Janda said the next step is to alter the enzyme’s bacterial makeup, which will help mitigate potential immune liabilities and maximize its therapeutic potential.
“Hopefully we can improve its serum stability with our future studies so that a single injection may last up to a month,” added Xue.
In addition to Janda and Xue, Joel E. Schlosburg of TSRI was an author of the study, “A new strategy for smoking cessation: Characterization of a bacterial enzyme for the degradation of nicotine.”
The research was supported by the Skaggs Institute for Chemical Biology at TSRI.
Tobacco Soil Bacterium is a Nicotine-Eating ‘Pacman’
http://patch.com/california/delmar-carmelvalley/tobacco-soil-bacterium-nicotine-eating-pacman
“The bacterium is like a little Pac-Man,” said Prof. Kim Janda. “It goes along and eats nicotine.
By Mirna Alfonso (Patch Staff) August 6, 2015
From The Scripps Research Institute
A new study from scientists at The Scripps Research Institute (TSRI) explores a bacterial enzyme — originally collected from soil in a tobacco field — that might be used as a drug candidate to help people quit smoking.
An enzyme from the bacterium can catch and keep the nicotine from ever reaching the brain, researchers said, depriving a person of the “reward” of nicotine that can trigger relapse into smoking.
The research shows that this enzyme can be recreated in lab settings and possesses a number of promising characteristics for drug development.
“Our research is in the early phase of drug development process, but the study tells us the enzyme has the right properties to eventually become a successful therapeutic,” said Kim Janda, the Ely R. Callaway Jr. Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at TSRI.
Janda has tried for 30 years to create a nicotine-eating enzyme in the lab but found it in nature recently — NicA2 from the bacteria known as Pseudomonas putida, originally isolated from soil in a tobacco field—consumes nicotine as its sole source of carbon and nitrogen.
“The bacterium is like a little Pac-Man,” said Janda. “It goes along and eats nicotine.”
In the new study, the TSRI researchers characterized the bacterial enzyme responsible for nicotine degradation and tested its potential usefulness as a therapeutic.
Janda said the next step is to alter the enzyme’s bacterial makeup, which will help mitigate potential immune liabilities and maximize its therapeutic potential.
“Hopefully we can improve its serum stability with our future studies so that a single injection may last up to a month,” added Xue.
In addition to Janda and Xue, Joel E. Schlosburg of TSRI was an author of the study, “A new strategy for smoking cessation: Characterization of a bacterial enzyme for the degradation of nicotine.”
The research was supported by the Skaggs Institute for Chemical Biology at TSRI.
The Business Behind Plain Packaging Tobacco
http://themarketmogul.com/business-behind-plain-packaging-tobacco/
On the 20th of May 2016, the increasingly progressive anti-tobacco efforts of the UK and Ireland will once again come into effect. This time it will be the introduction of plain packaging, involving the standardisation of all tobacco products. Products will appear homogenous with the removal of all marketing features, allowing for only the brand name and imagery promoting public heath warnings.
Understanding the implications of plain packaging tobacco is multiplex, which derives from the number of perspectives that need to be taken into consideration. A common, but somewhat naive outlook would be to simply suggest plain packaging results in a demand contraction, causing less people to smoke, thus lower profits for firms. In reality it important to consider that plain packaging is likely to have an array of effects beyond and even contrary to the theoretical predictions. This articles takes a forward looking analysis of the tobacco market, to uncover the likely effects and success of the plain packaging policy.
Market Analysis
In economic terms, the tobacco market can be classified as an oligopolistic structure, arising from the small number of companies with high individual market concentration, such as the well known Imperial Tobacco and Phillip Morris. The prominence of this market should not be understated, in 2012 the six largest tobacco companies outperformed; McDonalds, Microsoft and Coca-Cola’s earnings combined. In fact, the second largest US company Reynolds (RAI) share price has increased over 170% in the last five years, with others following similar growth.
However, the imposition of plain packaging policy is likely create permanent structural changes in the market, which will effect both the conduct and performance of incumbent firms. Firstly it’s important to recognise that firms currently compete on non-price factors, dominant firms have a high degree of brand loyalty, built up from years of marketing. Cigarette consumers often identify and associate branding with personal characteristics and have been found to value this superior to other factors such as taste and quality (Padilla). For example, one may associate a premium brand with higher social status – including characteristic such as wealth or attractiveness. This branding therefore acts as a significant barrier to entry for new firms aiming to successfully enter the market. Plain packaging is likely to reduce this barrier as product differentiation and this intrinsic value is removed, whilst the substitution ability between brands increases.
Plain packaging policy will force price competition, this is likely to encourage predatory pricing type behaviour, which has the potential to increase demand (opposite effect). Alternatively there could be a decrease in consumption, from the mandates on marketing and lower quality needed to retain profit margins whilst reducing prices. It would seem the desired effects of plain packaging on tobacco consumption is somewhat of a paradox. This may also be influenced by the ability of new firms to compete with incumbents and to combat other barriers such as economies of scale and market concentration.
Australia leading the way?
Although the UK, among many other advanced economies have previously remained hesitant over implementing plain packaging, Australia led the way. Australia is currently the only country to implement the policy, which they enforced in December 2012 and have since showed apparent signs of success. Recent figures released by the Australian Bureau of Statistics suggest an estimated $103 billion expenditure reduction on tobacco products between December 2012 (introduction of policy) and March 2014. Meanwhile daily smokers aged ’14 or older’ have significantly decreased from 15.1% to 12.8% between 2010 and 2013, with similar results in the ’18 or older’ group. Although causal relationships between plain packaging and consumption are difficult to make from these figures, they importantly show effectiveness in Australia’s anti-tobacco measures and they’re are on track to achieving smoking rates below 10% by 2018.
The future
In the short term, plain packaging policy may result in positive market performance, but it is important to recognise the new policy is likely to highly effective in deterring new smokers, especially if branding is such an influential factor. This will lead to a gradual reduction in the market size, which is the most important factor when considering the long-term health of the UK population. It would seem plain packaging may very much become a natural measure in efforts taken to reduce smoking rates in advanced economies, with many countries in the EU and beyond now considering it.
TTIP’s secret courts
https://fullfact.org/europe/ttip_secret_courts-46491#anchor
The impressively dry topic of investor-state dispute settlement (ISDS) is at the heart of the debate over a proposed treaty between the EU and US.
ISDS allows companies or individual investors to seek compensation from an independent arbitration panel if another signed-up country breaks an agreement to protect foreign investments. Almost all existing treaties involving guarantees to foreign investors use it.
Both sides want to include it in the Transatlantic Trade and Investment Partnership (TTIP, pronounced ‘T-tip’).
This is controversial. Campaigners complain about, among other things, a lack of transparency in ISDS proceedings.
Who decides cases, and where?
Using ISDS, a foreign investor that thinks it’s been treated in a way that an investment treaty doesn’t allow can ask an arbitration panel to decide the matter, rather than having to rely on the courts of the country they’re arguing with.
The arbitrators are usually commercial lawyers and academic experts in international law. Unlike a judge in a British court, they often double up: acting as an advocate for a government or company in one case, handing down decisions in another.
In general, each side will choose one arbitrator, with a third agreed upon or chosen by the organisation hosting the case.
The vast majority of cases are administered by the International Centre for Settlement of Investment Disputes (ICSID), part of the World Bank, or in line with rules published by the United Nations Commission on International Trade Law (UNCITRAL).
Are cases heard in secret?
Like other arbitration panels but unlike most courts, ICSID doesn’t make its hearings or decisions public unless the parties agree (although it does publish its legal reasoning and a list of cases).
UNCITRAL, the other major system, was so concerned at the lack of transparency that it changed its rules recently. They now say that decisions must be published, hearings should be public, and third parties (such as NGOs) can make arguments in the case. But this only applies to new investment treaties, and countries can agree to leave this part of the rules out.
Where the new rules don’t apply, “the very existence of a dispute can be kept secret if both parties so wish”. The EU has included the new UNCITRAL rules on transparency, with some modification, in a draft treaty with Canada that’s similar to TTIP.
How many are there?
While the rules on transparency make it hard to be exact about the volume of ISDS cases, campaigners often make claims about how many are taken by investors, and how frequently they succeed.
The most comprehensive breakdown of known cases is held by a United Nations agency, which tells us that they frequently revise and update their records.
At the time of writing, the database showed 608 cases launched between 1987 (when the first was recorded) and the end of 2014. The number has increased markedly in recent years, with 2013 seeing 59 new claims recorded—the highest number ever in a single year.
The increase in ISDS cases can, at least in part, be explained by the volumes of foreign direct investment over the same period, with the growth in ISDS cases and in outward investment following a similar trend.
Where do they come from?
ISDS claims typically come from companies based in relatively rich countries; the respondents are more likely to be poorer nations. Investors from the EU and US account for three-quarters of all claims.
Although no ISDS cases between the US and an EU-15 country have been identified, there have been a small number between the US and newer EU member states.
Overall, the UN records that EU member states have had 131 known claims lodged against them (around one fifth of the worldwide total). The most frequent respondents have historically been Argentina, Venezuela, the Czech Republic and Egypt.
It’s been argued that the most targeted countries are also those which score poorly in terms of legal quality. For instance, Argentina and Venezuela are currently ranked 143rd and 144th (out of 144) in the World Economic Forum’s index of “Efficiency of legal framework in challenging regulations”.
That situation seems to be changing, though. In 2014, 40% of all new claims were brought against rich countries, and a quarter were between an EU investor and another EU country (11 out of 42).
What are the outcomes?
At the end of 2014, 405 known ISDS cases had reached a resolution. The state won in 36% of these, while most of the rest were either decided in favour of the investor (27%) or settled (26%). Settled cases will typically involve the state paying an amount it is satisfied with, but the exact terms aren’t published.
To date there have been 16 cases against EU countries in which the tribunal awarded compensation to the investor, while another 13 were settled.
Only two ISDS challenges have ever been brought against the UK. The outcome of one is unknown; the other claim, against the UK and France over the Channel Tunnel, was partially successful. The companies involved were reportedly awarded compensation of around €24 million, although we don’t currently know how much, if any, of that the British government paid.
The debate about whether it should be included in TTIP is ongoing. The European Parliament has recommended that “the inclusion of any form of private arbitration courts in TTIP must be ruled out”.
The EU Trade Commissioner has expressed support for a permanent court to replace the ISDS procedure, and wants TTIP to allow for appeals and changes to how arbitrators are selected. This will have to be negotiated with the Americans over the next few months.
Update 07/08/2015
We originally said that the UK had lost neither of the ISDS cases taken against it, on the basis of a UN database. This was incorrect; in fact, a compensation award was made against the UK and France jointly in one case. We’ve updated our article, and our graph of results, to reflect this.
Mondelez and Kraft: A Storied History
http://blogs.wsj.com/moneybeat/2015/08/06/mondelez-and-kraft-a-storied-history/
While it’s far from a household name, few corporations in American history can claim a more storied history than Mondelez International Inc. Now, activist investor William Ackman is unveiling a $5.5 billion stake in the snack company and plans to push it to write a new chapter.
The latest twist has prompted MoneyBeat to revisit the company’s complicated family tree, which includes links with Philip Morris , General Foods, RJR Nabisco –and, most closely, Kraft Foods.
Here’s a timeline of the complicated relationship between Mondelez, Kraft and some other food giants, past and present.
1903: James L. Kraft begins selling cheese from a horse-drawn wagon in Chicago. By 1914, his company begins manufacturing cheese on its own.
1924: The company changes its name to Kraft Cheese Co. from J.L. Kraft & Bros. Co. and goes public on the Chicago Stock Exchange.
1928: Kraft merges with Phenix Cheese, which makes Philadelphia cream cheese.
1930: Kraft is acquired by National Dairy Products Corp.
1969: National Dairy Products Corp. changes name to Kraftco Corp.
1976: Kraftco Corp. changes names to Kraft Inc.
1980: Kraft Inc. merges with Dart Industries Inc., maker of Duracell batteries and Tupperware .
1985: Cigarette maker R.J. Reynolds merges with snack company Nabisco Brands, owner of brands such as Ritz and Oreo, in a $4.9 billion deal to form RJR Nabisco. (RJR Nabisco will soon become the target of the most legendary corporate raid of all time, but more on that later.)
1985: As part of a long diversification away from tobacco, cigarette company Philip Morris pays $5.6 billion to buy General Foods, owner of Oscar Mayer hot dogs, Entenmann’s pastries, Jell-O, Sanka coffee and Kool-Aid.
1986: Kraft spins off its non-food businesses. It also acquires Tombstone Pizza Corp.
1988: Kraft sells its Duracell battery business to buyout firm Kohlberg Kravis Roberts .
1988: Philip Morris buys Kraft for about $13 billion to combine the General Foods and Kraft brands under one roof.
1988: After a fierce bidding war engulfing some of the biggest Wall Street banks and investors in the world, KKR in 1988 wins a $25 billion takeover of RJR Nabisco, the deal chronicled in the business tome “Barbarians at the Gate.” (How this involves Kraft is coming up)
1995: Kraft General Foods is reorganized and a number of business lines are sold, including confections, bakery products and tablespreads. Brands included in these sales are Entenmann’s, Freihofer’s, Parkay and Touch of Butter
2000: Philip Morris adds Nabisco Holdings, which RJR Nabisco had just left as a separate company. The Nabisco purchase was eventually valued at around $19.2 billion. The cigarette giant then combines Nabisco with Kraft.
2001: Philip Morris spins off a small portion of its stake in Kraft Foods, which becomes publicly traded.
2007: Echoing the breakup of RJR Nabisco years earlier, Altria Group (the renamed Philip Morris), completes a spinoff of its majority stake in Kraft. Under pressure from investor Nelson Peltz, Kraft also agrees to sell its Post line of cereal – Grape-Nuts, Honey Bunches of Oats and more — to Ralcorp.
2010: Kraft closes a roughly $19 billion purchase of U.K. candy company Cadbury after a lengthy fight. Kraft also sells its Digiorno frozen pizza line to Nestle SA. Warren Buffett, whose Berkshire Hathaway Inc. was the largest shareholder of Kraft at the time, called both transactions “dumb.”
2011: Ralcorp decides to split its Post Foods cereal and private-label food businesses into two publicly traded companies. The deal throws a curveball into ConAgra Foods Inc.’s attempt to buy the entire company.
2012: Under pressure from Trian Fund Management LP, Kraft decides to split in two, spinning off its mature North American grocery business to highlight its global snack-food business. The larger global business–which includes Oreo, Cadbury, Wheat Thins, and other brands–is named Mondelez International Inc. The smaller company, dubbed Kraft Foods Group Inc., gets the Kraft cheese products, Maxwell House coffee, Jell-O, and Planters nuts, among other brands.
2012: After the Post cereal spinoff, ConAgra Foods Inc. agrees to acquire Ralcorp for $4.95 billion, making it the largest private-label food manufacturer in the U.S.
2013: Heinz sells itself for $23 billion to 3G Capital Partners and Warren Buffett’s Berkshire Hathaway Inc.
2013: Activist shareholder Nelson Peltz says in an interview on CNBC that his firm, Trian, is urging PepsiCo Inc. to acquire Mondelez International Inc. to create a global snack giant and spin off PepsiCo’s underperforming beverage business.
2014: Mr. Peltz wins a board seat at Mondelez but Trian ends its efforts to merge the food company with the snacks business of PepsiCo Inc.
March 2015: Kraft Foods Group and Heinz agree to merge, with Berkshire and 3G contributing $10 billion to pay a special dividend for Kraft shareholders. Berkshire and 3G end up owning just over half the combined Kraft Heinz Co., the fifth-largest food company in the world by sales, while the rest is publicly traded.
June 2015: Jana Partners takes a 7.2% stake in ConAgra and pressures the company to unwind the Ralcorp deal, which the company quickly agrees to do.
August 2015: Activist investor William Ackman unveils a $5.5 billion stake in Mondelez International Inc. The activist investor believes Mondelez has to grow revenues faster and cut costs significantly or sell itself to a rival. Mr. Ackman suggests that one potential buyer could be the newly formed Kraft Heinz.