March 2008, HHMI – In an undertaking so computationally demanding it required donated computer time from thousands of people around the world, Howard Hughes Medical Institute (HHMI) researchers have designed and built two functional enzymes never seen in nature.

Enzymes are nature’s catalysts, and without them, vital biological tasks like converting sugar to energy or replicating DNA would take cells billions or even trillions of times longer than they do. Researchers have long sought to mimic nature’s efficiency by creating custom enzymes that speed up sluggish industrial processes in the production of pharmaceuticals and fuels. The molecules’ complexity, however, has hampered their efforts.

“Enzymes are some of nature’s most miraculous creations, but we still don’t really know how they work. Trying to create new ones from scratch will really tell us what is critical for something to be a good catalyst.”
David Baker

The HHMI-led team leveraged its understanding of the basic rules that govern protein function to overcome the problems and create two un-natural functional enzymes from scratch.

According to senior author David Baker, an HHMI investigator at the University of Washington, “the methods can, in principle, be applied to any chemical reaction,” and may lead to advances in pharmaceutical manufacturing, toxic waste cleanup, and many other fields.

The research team published its findings in two papers, one in the March 7, 2008, issue of Science, and the second March 19, 2008, in an advanced online publication of the journal Nature.

Like other proteins, enzymes are constructed from long chains of amino acids. Twenty amino acids are the basic structural building units of proteins and each has different properties. As a protein is synthesized, it folds spontaneously into a precise three-dimensional shape that represents a balance between the repulsive and attractive interactions of the atoms in its amino acids and the water molecules that surround them.

An enzyme’s shape is critical to its function because it creates a crevice called an active site specifically shaped to bind the enzyme’s target molecule. Once the target molecule binds, atoms lining the active site interact with it – snipping starch into individual glucose molecules, for example. Without a precise fit, the enzyme doesn’t work.

For their enzyme design project, the team chose two model reactions from the world of chemistry,. “Chemists had studied these for a while,” said Baker, “so there was a pretty good idea of what would be needed [in an active site] to catalyze them.” According to Baker, the key to creating their novel enzymes was designing an amino acid sequence that would fold up to create that active site.

Predicting the form a given amino acid chain will take is a specialty of Baker’s. In October 2007, his team reported significant progress in the prediction of the structure of natural proteins based solely on their amino acid sequences. To make the predictions, Baker’s team used Rosetta, a computer program they developed to model the atomic interactions that govern protein shape. However, said Baker, “the calculations involved require very large amounts of computer time.” So much time is needed that Baker needs access to thousands of computers.

When he first started predicting protein structures, Baker used computer clusters in his laboratory. Several years ago, he realized that the amount of computing required to make significant advances was far beyond what his laboratory could afford. But the computing capacity Baker needed was all around him, in the homes and businesses of ordinary people.

So Baker created Rosetta@home, an online community that pairs Rosetta to the Berkeley Open Infrastructure for Network Computing (BOINC). BOINC divvies up the calculations into manageable chunks and sends the chunks off to an army of volunteers around the world who donate their computer downtime to folding proteins. Today, Rosetta@home has nearly 190,000 members.

For the enzyme design project, Baker’s team, led by senior fellows Daniela Rothlesberger and Eric Althoff and graduate students Lin Jiang and Alex Zanghellini, designed active sites they thought would speed up the chemical reactions. They then used the Rosetta@home network to find amino acid sequences that would fold to produce those active sites. After that step, they created actual genes encoding those amino acid sequences and inserted them into bacteria to see if the proteins they produced speeded up their reactions.

According to Baker, the enzymes worked, though not as well as those found in nature. “Rather than speeding up the rates of reaction a trillion-fold, we’re only getting on the order of 100,000-fold rate enhancements,” he said. “There is clearly something we’re missing, and very important to [our research] is trying to figure out what that is.”

To help, Baker’s Israeli collaborators, Dan Tawfik and Olga Khersonsky (co-authors of the paper that appears in Nature), took one of the enzymes and forced it to evolve. Working in a test tube, the pair created thousands of versions of the enzyme with random mutations. By chance, some of these mutations sped their enzyme up. According to Baker, several rounds of “directed evolution” improved the enzyme’s speed 200-fold, and analyzing the changes will help the team fine tune their computer models for future projects.

According to Baker, the studies’ findings are important for two reasons. First, he says, “enzymes are some of nature’s most miraculous creations… but we still don’t really know how they work. This project of trying to create new ones from scratch will really tell us what is critical for something to be a good catalyst.” The second, says Baker, is that “there are huge numbers of important practical applications for enzymes.” For example, he says, in speeding up the production of pharmaceuticals, creating new fuels, or cleaning up pollutants. “One could imagine new enzymes that will help all of us,” he said.

By Christopher J. Volgraf CSCS, Princeton Longevity Center – With almost 40% of the population having high cholesterol, exercise has become extremely important in treating patients across the country. There are many of environmental and personal factors that may influence a person’s cholesterol composition including genetics, age, gender, level of body fat, dietary intake of fat, cholesterol and carbohydrates, alcohol consumption, cigarette smoking, medication, menopausal status, and exercise. Exercise can be used by itself or in tandem with proper diet and medication to bring about positive changes in lipid profiles.

A study out of Duke University found that the extent of the body’s positive adaptations to exercise appear to depend on the amount and intensity of the exercise. The more frequent and intense the exercise, the more changes were seen in lipid profiles.

Patients were grouped into jogging 20 miles a week, jogging 12 miles a week and walking briskly 12 miles a week for the eight month study. After the study was completed, patients stopped their exercise program for 14 days. Significant improvements were observed in the lipid profiles of all three groups only one day removed from exercise, but the walking group did not show remaining signs of improvement 14 days after cessation of exercise. This study shows the importance of sticking with a consistent exercise program, as most Americans exercise at a low to moderate intensity. Even after a brief break from exercise after 8 months, improvements were lost in the moderate intensity or walking group.

Both men and women in the 20 mile/week jogger’s group experienced improvements in HDL cholesterol (or good cholesterol), HDL size and large HDL particles for the entire 14 days. Men and women in the walking group saw lower levels of triglycerides one day after cessation of exercise, but only the men sustained this benefit over 14 days. The precise mechanisms are unclear, but evidence indicates that other factors including diet, body fat, weight loss, and hormone and enzyme activity interact with exercise to alter the rates of synthesis, transport and clearance of cholesterol from the blood.

So the question is how much exercise is necessary to bring about positive changes in their lipid profile?

  • Moderate to intense exercise (4-8 on a scale of 1-10 Rating of Perceived Exertion) for 20-30 min on most days of the week.
  • Since high volume/intensity exercise has the highest impact on cholesterol, set a goal of 1,500 calories (burned through exercise), which is the equivalent of 3-4 hours of walking, jogging, or cycling at a moderate to intense pace in a week.
  • Resistance Training should be performed 2-3 sets of 8-12 reps, at least twice a week for beginners. Exercises should target all major muscle groups.
  • In general, the exercise prescription is very similar to that of a weight loss prescription since reduction in weight, body fat and abdominal fat have shown to coincide with lipid profile improvement.

March 20, 2008, IBM and Forterra Systems are working to solve an age-old problem that challenges U.S. security and costs taxpayers millions. Forterra plans to develop a futuristic unified communications solution code-named “Babel Bridge” that could allow U.S. intelligence agencies to use a common graphical collaboration system to instantly communicate within a virtual world.

To meet this challenge, IBM and Forterra have entered into a teaming agreement under which Forterra will integrate its On-Line Interactive Virtual Environment (OLIVE(TM)) 3D platform with the IBM Lotus® Sametime® software and the IBM Unified Communications and Collaboration (UC2(TM)) platform. The new system would give online collaborators instant insight through the display and discussion of multiple data forms in parallel including documents, graphic displays, and human expertise via anytime, anywhere connectivity through the Internet or a mobile phone.

It is frequently noted by leaders of U.S. government agencies — even those charged with protecting the nation in military and intelligence roles — that their agencies often are hampered in their efforts to work together by the use of different communications systems and procedures, evocative of the language barriers erected by the biblical “Tower of Babel.” The ability to instantly share information for planning and real-time action in support of U.S. interests, including the War on Terror, has become a leading objective of many government agencies.

This Forterra solution, including IBM technology, is being designed to build greater collaboration and real-time information sharing between analysts and operators within and between government agencies. The integration between Forterra’s virtual collaboration application with IBM Lotus Sametime software carries the potential to become the primary collaboration platform used throughout the intelligence community, and with other branches of the government.

Imagine an example in which intelligence agents are training to take down a terrorist cell. The mission requires cooperation from MI5, the FBI and local operatives on the ground. Through OLIVE’s virtual reality capabilities, the agencies are able to recreate the location of the terrorists and rehearse the mission. By integrating UC2 capabilities into the virtual reality model, the team instantly knows which experts are available and their location to harness the necessary resources in real-time to gain the necessary approvals for any changes as the rehearsal is taking place. They can also share and integrate into the training new information from operatives in the field such as streaming video, images from drone planes and audio files.

“The value of Unified Communications and Collaboration does not come from singular features like click-to-call,” said Bruce Morse, Vice President, IBM Unified Communications and Collaboration. “The true value of UC2 is realized when multiple collaboration capabilities are well integrated within a business task or process — like bringing several organizations together to share, review, approve and take immediate actions for national security. Managing communication and collaboration effectively within business processes can make all the difference between the success and failure of critical projects.”

Under the terms of the integration agreement, Forterra will deliver plug-ins to the Lotus Sametime platform and integration to the IBM Lotus Notes® calendar that allow easy access, scheduling and launching of meetings in the virtual world. Forterra will also embed key services, such as presence and location information, document, whiteboard, and application sharing, from the Lotus Sametime platform into the virtual world to enable faster, more effective communication and collaboration within the context of a situation or a meeting.

With integrated location information, any meeting that requires the most appropriate experts can be instantly initiated at the click of a button, pulling all the relevant resources into the virtual world meeting. Integration with the IBM Lotus Sametime Unified Telephony offering will allow any landline PBX, VoIP, or mobile phone caller to join a virtual meeting. In addition, IBM and Forterra have entered into negotiations for Frontera to resell Lotus Sametime software through an OEM (original equipment manufacturer) model with its virtual world solutions focused on its top business processes which include collaboration, training, product lifecycle management, and operations management.

Forterra announced in September 2007 a strategic investment and technology advancement agreement with Washington, DC-based In-Q-Tel (IQT), the strategic investment firm that works to identify, adapt, and deliver innovative technology solutions to support the mission of the U.S. Intelligence Community (IC). IQT historically makes investments in new technologies that meet current and future Intelligence Community needs and also exhibit the potential for broader commercial appeal.

“Member agencies within the U.S. Intelligence Community and private sector organizations have distinct but also overlapping challenges in monitoring global or regional situations and then pursuing real-time analysis and problem-solving,” said Steve Bowsher, Executive Vice President of Investments at Washington-based investment firm In-Q-Tel. “We believe secure virtual worlds integrated with unified communications and collaboration will enable users to engage the right subject matter experts within and between organizations to analyze complex situations. The goal of unified communications products that provide a crucial, distributed collaboration platform for both the public and private sectors offers the potential to help the agencies of the U.S. Intelligence Community collaborate more effectively with one another, with other federal groups, with state and local law enforcement, and with international partners.”

“Forterra is thrilled with the work program and relationship that In-Q-Tel awarded our company last year,” indicated Dave Rolston, CEO of Forterra Systems. “Our relationship with IBM and forthcoming integration to Lotus’ leading UC2 technologies enable us to deliver critical functionality that builds on that strategic investment. We are committed to meeting the requirements of both public and private sector organizations for an easy-to-use, trusted, secure collaboration platform, and we are confident that this announcement allows us to take the lead in meeting the demands of a new market trend. We feel this program will develop the advanced collaboration capabilities that are just starting to be in high demand with our commercial customers, which is an important end goal for In-Q-Tel as well.”

The integrated Forterra solution will deploy behind and through firewalls so enterprise IT departments can achieve the security needed to conduct private, by invitation only, or public discussions and document sharing.

Forterra Systems is a venture backed software company providing online distributed virtual world technology for the corporate, healthcare, government, and entertainment industries. The company’s investors include Jerusalem Venture Partners (JVP), Sutter Hill and private investors. “IBM’s Venture Capital Group facilitated Forterra’s introduction into IBM’s ecosystem,” said Erel N. Margalit, founder and managing partner of JVP. “The result is that we were able to quickly integrate Forterra’s breakthrough platform with IBM’s deep technical and business prowess to bring to market an unprecedented and innovative set of new workplace collaboration tools.”

“Babel Bridge” is part of Forterra’s ongoing efforts to build enterprise ready 3D Internet solutions. The solution is planned for development beginning in the second quarter of 2008.

About Forterra Systems

Forterra’s software and services enable organizations to build their own virtual worlds to train, plan, rehearse, and collaborate in ways previously considered impossible or impractical. Using the OLIVE (On-Line Interactive Virtual Environment) platform and industry standard PC hardware, customers can rapidly generate realistic, collaborative, 3D Internet solutions.

For more information on IBM’s unified communications platform:

Species of Frogs Decimated By Fungus:
Honey Bees Disappearing World-Wide:
Bats Are Dying – Possibly Fungus:
Tuna Is Contaminated:
Salmon Is Infected:
When Do Humans Respond?

Virus Is Killing Chile’s Salmon


By Alexei Barrionuevo, March 27, 2008, New York Times – PUERTO MONTT, Chile — Looking out over the low green mountains jutting through miles of placid waterways here in southern Chile, it is hard to imagine that anything could be amiss. But beneath the rows of neatly laid netting around the fish farms just off the shore, the salmon are dying.
A virus called infectious salmon anemia, or I.S.A., is killing millions of salmon destined for export to Japan, Europe and the United States. The spreading plague has sent shivers through Chile’s third-largest export industry, which has left local people embittered by laying off more than 1,000 workers.

It has also opened the companies to fresh charges from biologists and environmentalists who say that the breeding of salmon in crowded underwater pens is contaminating once-pristine waters and producing potentially unhealthy fish.

Some say the industry is raising its fish in ways that court disaster, and producers are coming under new pressure to change their methods to preserve southern Chile’s cobalt blue waters for tourists and other marine life.

“All these problems are related to an underlying lack of sanitary controls,” said Dr. Felipe C. Cabello, a professor in the Department of Microbiology and Immunology at New York Medical College in Valhalla that has studied Chile’s fishing industry. “Parasitic infections, viral infections, fungal infections are all disseminated when the fish are stressed and the centers are too close together.”

Industry executives acknowledge some of the problems, but they reject the notion that their practices are unsafe for consumers. American officials also say the new virus is not harmful to humans.

But the latest outbreak has occurred after a rash of nonviral illnesses in recent years that the companies acknowledge have led them to use high levels of antibiotics. Researchers say the practice is widespread in the Chilean industry, which is a mix of international and Chilean producers. Some of those antibiotics, they say, are prohibited for use on animals in the United States.

Many of those salmon still end up in American grocery stores, where about 29 percent of Chilean exports are destined. While fish from China have come under special scrutiny in recent months, here in Chile regulators have yet to form a registry that even tracks the use of the drugs, researchers said.

The new virus is spreading, but it has primarily affected the fish of Marine Harvest, a Norwegian company that is the world’s biggest producer of farm-raised salmon and exports about 20 percent of the salmon that come from Chile.

Salmon produced in Chile by Marine Harvest are sold in Costco and Safeway stores, among other major grocery retailers, said Torben Petersen, the managing director of Marine Harvest here.

Arne Hjeltnes, the main spokesman in Oslo for Marine Harvest, said that his company recognized that antibiotic use was too high in Chile and that fish pens too close together had contributed to the problems. He said Marine Harvest welcomed tougher environmental regulations.

“Some people have advocated that this industry is too good to be true,” Mr. Hjeltnes said. “But as long as everybody has been making lots of money and it has been going very well, there has been no reason to take tough measures.”

He called the current crisis “eye-opening” to the different measures that are needed.

On a recent visit to the port of Castro, about 105 miles south of Puerto Montt, a warehouse contained hundreds of bags, some weighing as much as 2,750 pounds, filled with salmon food and medication.

The bags — many of which were labeled “Marine Harvest” and “medicated food” for the fish — contained antibiotics and pigment as well as hormones to make the fish grow faster, said Adolfo Flores, the port director.

Environmentalists say the salmon are being farmed for export at the expense of almost everything else around. The equivalent of 7 to 11 pounds of fresh fish are required to produce 2 pounds of farmed salmon, according to estimates.

Salmon feces and food pellets are stripping the water of oxygen, killing other marine life and spreading disease, biologists and environmentalists say. Escaped salmon are eating other fish species and have begun invading rivers and lakes as far away as neighboring Argentina, researchers say.

“It is simply not possible to produce fish on an industrial scale in a sustainable way,” said Wolfram Heise, director of the marine conservation program at the Pumalin Project, a private conservation initiative in Chile. “You will never get it into ecological balance.”

When companies began breeding non-native Atlantic salmon here some two decades ago, salmon farming was seen as a godsend for this sparsely populated area of sleepy fishing towns and campgrounds.

The industry has grown eightfold since 1990. Today it employs 53,000 people either directly or indirectly. Marine Harvest runs the world’s largest “closed system” fish-farming operation at Rio Blanco, near Puerto Montt, where 35 million fish a year are raised until they weigh about a third of an ounce.

As the industry abandons the Lakes region in search of uncontaminated waters elsewhere, local residents are angry and worried about their future.

The salmon companies “are robbing us of our wealth,” said Victor Guttierrez, a fisherman from Cochamó, a town ringing the Gulf of Reloncavi, which is dotted with salmon farms. “They bring illnesses and then leave us with the problems.”

Since discovering the virus in Chile last July, Marine Harvest has closed 14 of its 60 centers and announced it would lay off 1,200 workers, or one-quarter of its Chilean operation. Since the company announced last month that it would move south, to Aysén, the government has said the virus has spread there as well, in two outbreaks not involving Marine Harvest.

Industry officials say Chile is suffering growing pains similar to salmon farming operations in Norway, Scotland and the Faroe Islands, where a different form of the I.S.A. virus struck previously.

Norway, the world’s leading salmon producer, eventually decided to spread salmon farms farther apart, reducing stress on the fish, and responded to criticism of high antibiotic use with stronger regulations and the development of vaccines.

Researchers in Chile say the problems of salmon farming go well beyond the latest virus. Their concerns mirror those of the Organization for Economic Cooperation and Development in Paris, which heavily criticized Chile’s farm-fishing industry in a 2005 report.

The O.E.C.D. said the industry needed to limit the escapes of about one million salmon a year; control the use of fungicides like green malachite, a carcinogen that was prohibited in 2002; and better regulate the colorant used to make salmon more rosy, which has been associated with retina problems in humans. It also said Chile’s use of antibiotics was “excessive.”

Officials at Sernapesca, Chile’s national fish agency, declined repeated requests for interviews for this article and did not respond to written questions submitted more than a week ago.

But Cesar Barros, the president of SalmonChile, an industry association, said, “We are working with the government to improve the situation.”

He dismissed the broader criticism of sanitary conditions, saying there was no scientific evidence to support the claims. But researchers charge that the industry has been reluctant to pay for scientific studies, which Chile sorely needs.

Residual antibiotics have been detected in Chilean salmon that have been exported to the United States, Canada and Europe, Dr. Cabello said.

He estimated that 70 to 300 times more antibiotics are used by salmon producers in Chile to produce a ton of salmon than in Norway. But no hard data exist to corroborate the estimates, he said, “because there is almost an underground market of antibiotics in Chile for salmon aquaculture.”

Researchers say that some antibiotics that are not allowed in American aquaculture, like flumequine and oxolinic acid, are legal in Chile and may increase antibiotic resistance for people. Last June the United States Food and Drug Administration blocked the sale of five types of Chinese seafood because of the use of fluoroquinolones and other additives.

But huge numbers of fish go uninspected. The F.D.A. inspected only 1.93 percent of all imported seafood in 2006, Food and Water Watch said, citing F.D.A. data.

Stephanie Kwisnek, a spokeswoman for the F.D.A., said that she did not know the percentage inspected. But she said the F.D.A. tested 40 samples of the 114,320 net tons of salmon imported from Chile in 2007. None of them tested positive for malachite green, oxolinic acid, flumequine, Ivermectin, fluoroquinolones or drug residues, she said.

The F.D.A. is planning an inspection trip to assess Chile’s overall controls on its farmed salmon, she added.

Mr. Petersen, the managing director of Marine Harvest in Chile, said the company planned to return to the Lakes region in a few years, once the area had become free of contamination. In the longer term, he said, Marine Harvest will leave Chile’s fresh-water lakes and produce more older salmon in closed systems where it can maintain “biological control.”

Meanwhile, neighboring fishermen who have been affected by the fish-farming industry can only hope for better days. Mr. Guttierrez, 33, said that just six years ago he and his fishing partner would haul in 1,100 pounds of robalo on a typical day. On a recent day he pointed to that morning’s catch of only 88 pounds in a cooler in the bed of a pickup truck.

He lamented the changes he had observed in the fish: they are rosier than before, and their skin is flabbier. He said he suspected that the wild fish were eating the same food pellets that the salmon were being fed, which he said were falling to the sea floor.

“If the water continues to be contaminated, we will simply have to go to another area to find our fish,” he said. “But it is getting harder and harder.”

Joao Pina for The New York Times
A fisherman and his catch at Puerto Montt, Chile, where infectious salmon anemia is killing millions of fish destined for export to Japan, Europe and America.

Chinook Salmon Vanish Without a Trace
The Chinook salmon that swim upstream in the Sacramento River to spawn in the fall have disappeared, threatening the regional fishing industry.

Collapse of Salmon Stocks Endangers Pacific Fishery
March 17, 2008
Federal officials are contemplating closing the Pacific salmon fishery from northern Oregon to the Mexican border because of an enormous collapse in crucial stocks.

US and World Situation: Salmon
USDA Foreign Agricultural Service

1998:The drug Viagra from the pharmaceutical company Pfizer was approved by the U.S. Food and Drug Administration for use in treating erectile dysfunction.

March 25, 2008, – Even the most decent, charismatic or bold politicians tend to adhere to conventional wisdom and conventional prescriptions in addressing America’s economic future. In doing so, they miss the point that it is the unconventional that has driven America’s recent success, and the unconventional that must drive our future success.

A quarter of a century ago, most leading economists–whether liberal or conservative–predicted that American economic growth would fall behind Japan and Germany by 2007. They typically estimated that Japan’s annual gross domestic product would be roughly $5 trillion by now, with Germany at around $4 trillion, and the U.S. lagging behind at roughly $3.5 trillion.

The predictions for Japan and Germany were reasonably accurate. But America grew to $13 trillion.

How did the U.S. nearly quadruple the estimates of the world’s best economists? One key is that these economists had based their guesses on a nation’s quantity of natural resources, not on the quality of its intellectual capital or its ability to put that intellectual capital to use.

America’s surprising economic growth has been traced back to some 1,000 key innovators, entrepreneurs, rainmakers, mentors and creative geniuses–some 60% of whom were foreign-born persons who were educated at American universities.

This meant that the U.S. had a unique edge in terms of the talent and the environment that was necessary for growth. The revolutions of technology–in electronics, in space technology and satellite communications, in personal computing, in the Internet and in information technology–were all American revolutions. The U.S. innovated while others imitated.

America’s outrageous success in the past quarter-century, owing to the 1,000 unconventional superstars and rainmakers and the tens of thousands of stars who surrounded them, was mainly serendipitous. But a repeat of this success will require forward-thinking strategy and investment, in the face of an emerging Asia, a resurgent Europe and stiffer competition around the globe.

We would recommend a few cornerstone strategies, which would preserve and enhance the environment in which America can cultivate its next generation of stars of unconvention.

First, we must set our faces toward the medical and biological science frontiers, as those are the likely settings for the planet’s next technological and humanistic revolutions.

The federal government also must strengthen its support for the American research enterprise–which since World War II has been carried out chiefly at some 50 leading U.S. research universities. Those universities produce some 80% of our Ph.D.s, and these Ph.D.s are the manpower and womanpower for this country’s work in basic science.

Basic science and technology is the creator and destroyer of global industries and eras. Its discoveries can lead to marketplace innovations that create vast new economic sectors, businesses, jobs and products to drive the global economy. The Internet is the most recent example. Nanoscience may be the next one.

Yet given recent actions by Congress to skimp on research funding for university-based research for the Department of Defense, such a level of commitment no longer exists. Industry, given its constraints and pressures, is not in a position to perform science research on its own. America’s best bet is for government, research universities and industry to work together in generating new discoveries and facilitating their way to the marketplace.

Our younger citizens must be prepared for a lifelong process of learning and unlearning. We must not merely train them in conventional skills–we must equip them to develop for themselves the sets of skills that would be appropriate for unexpected professional and technological developments. This requires every citizen to be as fluent in timeless arts and humanities as in timely technologies.

Finally, given that three in five of America’s 1,000 key superstars and rainmakers were born in other nations, we must incentivize the continued migration of the world’s best minds to America. Here we face escalating competition from Australia, England and other countries for “brain gain,” the new Holy Grail of global leadership.

Just as yesterday’s conventional wisdom held that Japan and Germany would pass us by, today’s conventional wisdom holds that other nations soon will exceed us in skills and productivity. Yet by maintaining our edge in the unconventional things–especially in our ability to innovate while others continue to imitate–America will remain the pacesetter in this still-young century.

Jim Clifton is the CEO of the Gallup Organization and C. L. Max Nikias is the Provost of the University of Southern California.
Mark Gottfredson and Steve Schaubert 03.25.08, 6:00 AM ET

Even though employment, manufacturing and consumer confidence are all trending downward in the U.S., many economists are still reluctant to use the R-word. But however you define today’s business environment, CEOs are in the hot seat. Their challenge is to anticipate where slowing momentum will hurt the business most–and then take actions to blunt those effects and position the business for a quick turnaround.

While many companies batten down the hatches and try to survive, our experience is that, for prepared companies, economic slowdowns can provide significant opportunities to improve their positions and accelerate into the next up cycle.

Where should managers focus their attention? In a downturn, you don’t have to wait for a lot of data to decide. Most companies encounter four critical pressure points.

The most obvious and most important is costs. In good times, companies often focus on increasing sales and opening up new markets rather than on managing their costs down the time-honored experience curve–that practice may come back to bite them in a downturn.

As sales slow, cost leaders find that they have even more built-in advantages than usual; cost laggards find that they are even farther behind than they thought. Toyota, for example, has just unveiled the first car produced under its latest cost-cutting program. The company expects the program to generate $2.8 billion in savings. A downturn is a great time to create the “burning platform” necessary to accomplish cost savings and get back onto the experience curve.

At the same time, managers must be very thoughtful about where to cut and where to invest. Investing in the areas customers care the most about while everyone else is cutting back–though counterintuitive–can help a company leapfrog the competition.

A second pressure point is market position. In ordinary times, well-managed market leaders generally outperform followers–leaders’ profits and revenues grow faster, their returns on equity are higher and their customers are more loyal, to mention just a few measures.

In a downturn, the competition for position grows more intense, and existing positions may be vulnerable. Leaders may use their deeper pockets to dial up the pressure on followers, or to snap them up at bargain prices. Followers can sometimes turn the pressure exerted by a downturn to their advantage and leapfrog into the No. 1 position.

The merger talks now taking place among U.S. airlines reflect the imperative for every carrier to be top dog in as many markets as possible–and show how urgently CEOs facing a downturn feel that pressure. If consummated, the deals may re-order many airlines’ market positions, creating great opportunities for some and dire threats for others.

A third pressure point: customer behavior. Customers never sit still, of course. But in a downturn, both businesses and consumers are likely to shift their buying patterns faster than ever. They seek out bargains. They do without some things altogether. These changes in behavior can significantly rearrange the pools of profits that companies compete for.

The “mass luxury” market is already feeling the pain. McDonald’s recently announced it would begin serving souped-up coffee beverages at lower prices than the competition, a move widely interpreted as a direct challenge to Starbucks. In ordinary times, the move would be as risky as any attack on an entrenched market leader. In a downturn–who knows?–McDonald’s’ challenge might pay off.

A fourth pressure point–and perhaps the least recognized–is complexity. Companies in good times tend to add features, variations and line extensions, thereby complicating both their production processes and their organization. Even in good times, this can raise costs and interfere with a company’s agility.

But the drawbacks of complexity are particularly noticeable in a downturn. Japanese carmakers don’t just enjoy a cost advantage over Detroit, they also have a complexity advantage–with fewer models, fewer options and fewer different parts.

Honda requires half a day to build all possible variations on the Accord, while Detroit automakers need more than 90 days to build all possible variations of some American compacts. In a downturn, can Detroit sell enough of all those variations to cover the costs of the complexity?

These four pressure points are where any company facing a slowdown should focus. They are the parts of the business where trouble can quickly spin out of control; they also provide four useful gauges of a company’s vulnerability. A company knows it is taking the right steps if its costs are trending downward at least as fast as the competition’s, and if its competitors’ market positions are more vulnerable to a sales slowdown than its own.

Managers can also tell if they are on track when their customers’ loyalty increases (or at least holds steady), and when they can point to signs of greater simplicity in their products, businesses processes and organizations.

Downturns aren’t all bad news for companies. Our research has shown that changes in economic and strategic position are twice as likely in a downturn as during other economic periods. Firms that paid attention to these pressure points–like the drugstore chain Walgreen, for example–gained share over their competitors in the last downturn and substantially improved their positions in earnings and sales.

For companies that are prepared, managing in a downturn can open more doors than it closes.

Mark Gottfredson, based in Dallas, leads Bain & Company’s Global Performance Improvement Practice. Steve Schaubert is a Bain partner in Boston. They are co-authors of “The Breakthrough Imperative: How the Best Managers Get Outstanding Results.”

By Steve Conner Science Editor, March 24, 2008, The Independent UK – A potential cure for Parkinson’s disease has come a significant step closer today with a study showing that it is possible to treat the degenerative brain disorder with cells derived from cloned embryos – a development condemned by the Roman Catholic Church.

The research was carried out on laboratory mice but scientists believe the findings are proof that the techniques could be applied to humans suffering not just from Parkinson’s, but a range of other incurable diseases.

Researchers have demonstrated the possibility of treating Parkinson’s disease by transplanting laboratory-matured brain cells back into the individual who supplied the skin cells that were turned into cloned embryos – a process known as therapeutic cloning.

“This is an exciting development, as for the first time it may be possible to create a person’s own embryonic stem cells to potentially treat Parkinson’s disease,” said Kieran Breen, director of research at the Parkinson’s Disease Society – a charity representing the 120,000 people in Britain affected by the illness.

Dr Breen said: “Stem cell therapy offers great hope for repairing the brain. It may ultimately offer a cure, allowing people to lead a life that is free from the symptoms of Parkinson’s disease.”

Proof that therapeutic cloning is more than a pipedream will be used by British scientists as justification for their push to expand the boundaries of their research to include the use of animal-human “hybrid” embryos for medical experiments, a process that is bitterly opposed by the Catholic Church.

Scientists say that, because of the shortage of human eggs for research purposes, they need to use cow or rabbit eggs for cloning experiments, and have lobbied hard for it to be allowed under the Human Fertilisation and Embryology Bill currently going through Parliament. Even though the stem cells derived from cloned hybrid embryos will never be used on patients, the practice is condemned by the Church, which wants all MPs to be given a free vote in the Commons.

The latest development, published in the journal Nature Medicine, is further proof-of-principle that therapeutic cloning can effectively treat – and possibly cure – a degenerative brain disorder.

For the first time scientists have been able to create healthy, working brain cells from immature stem cells, derived from embryos cloned from skin cells, and transplant them back into the diseased brain.

The laboratory mice in the study suffered from a type of Parkinson’s disease, which is marked by the death of certain nerve cells or neurons in the brain that produce the neurotransmitter dopamine. Skin cells were scraped from the tails of the animals and cloned using mouse eggs, which had their own cell nuclei removed. Stem cells taken from the resulting cloned embryos were grown in the laboratory into mature dopamine-producing brain cells. After transplanting the cells back into the brain, the mice showed significant improvements in a range of experiments designed to test skills that become notably worse in those with Parkinson’s disease.

The team of American and Japanese scientists, led by Lorenz Studer of the Sloan-Kettering Institute in New York, were able to produce 187 different strains of embryonic stem cells from 24 Parkinsonian mice. A key finding of the experiment was that there were no signs of tissue rejection because the transplanted brain cells were derived from the same mouse that supplied the skin cell for the cloned embryo.

Professor Robin Lovell-Badge of the Medical Research Council said the study provided further proof-of-principle that therapeutic cloning was a potential treatment for severe disorders of the brain. He said: “The authors were also able to test several independent embryonic stem cell lines corresponding to individual mice, and could show that most seemed to work well. This is very encouraging as it indicates that the cloning process is a sufficiently robust method of reprogramming cells back to an early embryonic state, at least when the early embryos are used to derive embryonic stem cell lines.

“Ideally one of the next steps will be to repeat the whole procedure with a monkey model. This will allow much better tests of functional recovery and safety.”

Life with the disease

“I wish one of these pontificators could get inside my body and see what it feels like. Parkinson’s is like being locked in your own body when your mind is still there. I can become as rigid as a plank and my legs won’t bend. It’s as though there is a ton of cement on my chest and an army of ants crawling up and down my body with spears. It’s like being buried alive.

“By the age of 70, three-quarters of those in this country will have Parkinson’s disease to some degree as it is a degenerative illness. Once you have it, it never goes into remission. But no one tells you how difficult it is to live with.

“It makes me so angry when I hear academics, theologians or medics arguing about cloning. For me, it is like hearing any hopes we may have of returning to normality being taken away. By mixing ethics with religion and politics, which is a lethal concoction, they are not thinking about the people who have the disease. I feel like saying, ‘Get off your high horse.’

“I would not want to stop any process unless it I knew it was categorically not going to work for those who are suffering. I don’t believe cloning embryos is like taking life. Parkinson’s is such a desperately painful disease. You would have thought that everyone would support anything reasonable to find a cure, and I believe what is being suggested is reasonable.”

Dr. Jill Bolte Taylor’s website:

Transcript of Jill Taylor’s talk at TED:

Chris Anderson introduces Jill Bolte Taylor by telling us that his mother recently had a stroke. In 30 seconds, he tells us, she was “turned into someone entirely different – a mystery.” Bolte Taylor is in a unique place to decipher this mystery for us. She’s a research psychiatrist at Harvard, with a specialty in brain chemistry. And she’s recovered from a massive stroke, which taught her amazing lessons about how the brain works.

She decided to study the brain because she grew up with a brother who suffered from schizophrenia. Why, she wondered, could she take her dreams and connect them to her reality and make them come true, and why can’t her brother connect his dreams to a common and shared reality? Why instead do they become delusions? At Harvard, she was studying the biological and chemical differences between the brains of people who were normal, schizophrenia, schizoaffective and who had bipolar disorder. On the weekends, she travelled as an advoate for NAMI – National Advocates for Mental Illness.

On December 10, 1996, “I woke up with a brain disorder of my own.” She suffered a massive hemmorhage in her left cerebral cortex. By the end of the day, she couldn’t walk, talk, read, write, or recall any of her life. She’s brought in a human brain to show us. “It’s obvious that the two hemispheres are completely separate from one another…The right hemisphere functions as parallel processor, the left functions as a serial processor.” While they’re connected by the corpus callosum, they operate to a great deal independently from one another.


To the right hemisphere, the world is a wash of sensations. “We are energy beings connected to energy of each other through the consciousness of the right hemispheres. In this moment, we are perfect, we are whole, and we are beautiful.”

The left hemisphere is a different place, all about the past and the future. Its job is to pick out the details from those waves of sensation and to categorize and organize all that information. It thinks in language, “ongoing brain chatter that connects internal and external world.”

Bolte Taylor woke up that morning with acute pain, like eating ice cream. She tried to start her daily ritual, exercising on a cario machine. But she percieved her hands as claws, and felt a weird feeling of externalization. She began slowing down, sensing constriction in her area of perception. As she tried to get into the shower, she could hear the dialog inside her body: “Okay, you muscles contract, you muscles relax.” As the water turned on, she discovered she could no longer define the boundaries of her body. “The atoms and molecules of my arm blended with the atoms of the wall. All I can detect is this energy.” And for a moment, that left hemisphere brain chatter went totally silent/

“I was totally shocked inside a silent mind, captivated by the energy around me.” It was a liberating experience, leaving all the cares of daily life behind. “I felt enormous, expansive, at one with all the energy. It was beautiful there.” And then her left hemisphere came back online, yelling, “We got a problem here!”

As she realized she was having a stroke, one of her first thoughts was, “This is so cool! How many brain scientists have a stroke?” That thought was rapidly followed by, “But I’m a busy woman. I can’t afford to deal with this than longer than a couple of weeks.” She realized how serious things were when she discovered she no longer knew her workplace number. She shuffled through a huge stack of business cards, hoping to find her own card. But the letters were no more than squiggles, and she wasted 45 minutes, during which her brain was bleeding, trying to find the right squiggle to dial. When she finally connected, she couldn’t understand human speech – “My colleague sounded like a golden retriever.” She hadn’t realized she couldn’t understand until she’d attempted to speak. As the ambulance took her to the hospital, she remembers realizing, “I am no longer the choreographer of my actions,” and surrendering, perhaps to life post-stroke, perhaps to death.

After she emerged from coma, “light burned my brain like wildfire.” Noise was painful, and she couldn’t pick sounds from the noise. But she found the expansive feeling again, that moment of connection to the rest of the world, a feeling that felt like nirvana. “If I am alive and could find nirvana, then anyone could find nirvana. People could purposely choose to step to the right of their left hemispheres. What a gift this experience could be!”

It was a gift with a huge cost. Two and a half weeks after the stroke, a surgeon removed a blood clot the size of a golf ball from her brain. It took her eight years to recover completely. She asks, “Who are we? We are the life force power of the universe, with manual dexterity and two cognitive minds… We have the power moment to moment to choose how we want to be in the world,” whether we want to be purely rational or live within our right brains. “The more time we spend on the right brain, the peace circutry of our brains, the more peace we will see in the world.” Tears in her eyes, she concludes, “I thought that was an idea worht spreading.”

Next Page →