Relevant and even prescient commentary on news, politics and the economy.

Innovation, statistics, and truth

The New England Journal of Medicine had a statement that caught my attention that bore on the topic started on this post and this post about safety in big pharma and food.

…For example, we know that in type 1 diabetes, metabolic control can reduce the risk of microvascular complications. On the other hand, the two largest randomized, placebo-controlled trials in patients with type 2 diabetes, the United Kingdom Prospective Diabetes Study and the University Group Diabetes Program, failed to find a significant reduction in cardiovascular events even with excellent glucose control.2 Moreover, we are facing a troubling paradox: preliminary data that were presented at the meeting and published by Gerrits et al.3 suggest that among the thiazolidinediones — a class of drugs that has been shown to improve metabolic control — rosiglitazone may increase cardiovascular risk whereas pioglitazone may reduce it. Until we have a better grasp of the pathogenesis of atherosclerosis in type 2 diabetes, it will be difficult to design therapies to prevent this complication or even to determine how the currently available agents that act at multiple sites may affect clinical outcomes in very different ways.

Not surprisingly, glycemic control has been the centerpiece of therapeutic interventions in type 2 diabetes for many years. Within the past decade, several new drugs that result in “glycemic durability” — a reduction in the glycated hemoglobin level — have been approved by the FDA. However, change in the glycated hemoglobin level is a relatively poor surrogate for cardiovascular outcomes in type 2 diabetes, accounting for only 5 to 15% of the variation in ischemic risk.2 This finding represents a major dilemma for practitioners, regulatory agencies, and patients who seek the newest and best treatments for this disease.

The controversy surrounding biochemical surrogates versus clinical outcomes was also highlighted at the FDA meeting when the advisory committee reviewed one of the largest randomized trials of rosiglitazone, A Diabetes Outcome Prevention Trial, or ADOPT. In that study, the percentage decrease in glycated hemoglobin was greater with rosiglitazone than with metformin or sulfonylureas, yet the risks of congestive heart failure and cardiovascular ischemia were higher.4 These data suggest that we urgently need to change the regulatory pathway for drugs for the treatment of type 2 diabetes to make clinical outcomes, not surrogates, the primary end points. This is not a radical proposal: 20 years ago, the FDA shifted its primary efficacy end point for osteoporosis drugs from bone mineral density (a reasonable surrogate for the risk of fracture) to fractures themselves. Without a regulatory sea change with regard to diabetes drugs, we are certain to be in the same position 5 years from now that we are in now: we will again find ourselves in possession of a new wonder drug that is designed to treat a devastating chronic disease but that may do more harm than good.

Drugs are approved or removed from the market on the basis of evidence from randomized, controlled trials. In the FDA hearing on rosiglitazone, several meta-analyses (see Table 1) revealed a significant increase in the risk of myocardial ischemic events among patients taking rosiglitazone. However, an interim analysis of the ongoing Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) trial, which was designed specifically to assess cardiovascular risk among patients receiving rosiglitazone, failed to demonstrate a similar risk.5 In addition, two large observational studies, one conducted by Tricare for the Department of Defense and one conducted by WellPoint (the largest health insurer in the United States), noted no appreciable signal of increased cardiovascular risk with either of the available thiazolidinediones (see Table 2). The contrasts among the levels of evidence and the results regarding the safety of rosiglitazone raised new questions about relative and absolute risks but also highlighted the weaknesses of observational studies examining events that are common and whose rates are likely to be increased only slightly by a given drug, even in a large cohort (such as that used by WellPoint, which comprised 160,000 patient records).

This issue led to an interesting sidelight at the meeting. Recently, there have been calls for the FDA to fund and oversee phase 4 postmarketing studies as a means of determining the safety of newly approved drugs. The two observational studies on thiazolidinediones whose results were presented at our meeting had been performed independently of the manufacturers and the FDA. The indeterminacy of their results, due to the inevitable effects of the many confounding variables inherent in such studies, illustrates why this approach alone will neither solve the overriding problems of drug safety nor ultimately help a chronically underfunded federal agency. There is no doubt that it will be costly to undertake true safety and efficacy studies of new drugs using clinical outcomes as primary measures, but in the long run, these efforts will save time, energy, and money.

Such reading is difficult for non-medical, but the thought is clear. The same theme is presented that proper testing is severely deficient and apt to get false negatives for safety as part of the design. It is unlikely that companies would furnish or finish appropriate testing for followup safety concerns that have NO longitudinal studies done. There is a growing share of the market that is tweaking current medications for the sake of patent production and sales but reveal little improvement in efficacy and actual concern of harm.

The gardasil vaccine is innovative and has been approved of course, but the immense pressure to get to market before a rival company predisposes companies to push increasingly more quickly and with greater ‘advertising’ (a governor advocating mandatory vaccination!) that turns the market into a medical experiment of large proportion.

(Next stop is in India where generic antibiotics are made to lower our costs for drugs)

Where is Gwadar? In Balochistan, where else?

The BBC News reports:

Gwadar port is on the Arabian Sea at the mouth of the Gulf through which 30% of the world’s daily oil supply passes.
Officials say the port will benefit Balochistan. That is disputed by Baloch militants fighting the government.
The current estimated cost of the port project is nearly $1bn. Much of the funding has come from China.

While inaugurating the port, President Musharraf described the occasion as “a historic moment” for Pakistan.
A high-level Chinese delegation, led by Minister for Communications Li Shenglin, was in attendance.
Gen Musharraf also announced that a modern airport would be built near the port with Chinese assistance.

“The same Chinese friends will build an airport here for us, where the best aircraft will come,” Musharraf said according to AFP news agency.
Gwadar is expected to provide strategic storage and transport facilities, as well as road and rail links to China.
The port is seen by observers as China’s first foothold in the Middle East.

China’s involvement has been viewed with hostility and suspicion not just in Pakistan, but also internationally.
The port is said to be part of Chinese naval expansion along the Asian and African coasts called the ‘string of pearls’ initiative, according to a US Department of Defense report.
It entails the maintenance of ports and bases at strategic places in the region.
Observers say that United States as well as the Gulf countries have major reservations at the ‘overwhelming’ Chinese involvement in the project.
The Gwadar port is situated right next to the strategic Straits of Hormuz and its busy oil shipping lanes.
The surrounding region is home to around two-thirds of the world’s oil reserves.
It is also on the shortest route to the oil rich Central Asian states through land-locked Afghanistan.

The Association for Asian Research elaborates on the issue of the port and how military presence of some kind is a part of expansion.

Who else is moving into the area? With some form of military? And with defense against Islamic terrorism as part of the discussion?

(Read India and Tajikistan, with ties to Russia, as part of a pact on energy and militant Islam. Discussed in Part III.)

Where is Balochistan? Part I

Antigua update Part I WTO GATS

Reader JohnA forwarded this article as an update to the toe in the water scenario for implementing WTO GATS policy. The New York Times article suggests possibilities.

Antigua is best known to Americans for its pristine beaches and tourist attractions like historic English Harbor. But the dozens of online casinos based there are vital to the island’s economy, serving as its second-largest employer.
More than a few people in Washington initially dismissed as absurd the idea that the trade organization could claim jurisdiction over something as basic as a country’s own policies toward gambling. Various states and the federal government, after all, have been deeply engaged for decades in where and when to allow the operation of casinos, Indian gambling halls, racetracks, lotteries and the like.
But a W.T.O. panel ruled against the United States in 2004, and its appellate body upheld that decision one year later. In March, the organization upheld that ruling for a second time and declared Washington out of compliance with its rules.
That has placed the United States in a quandary, said John H. Jackson, a professor at Georgetown University Law Center who specializes in international trade law.
Complying with the W.T.O. ruling, Professor Jackson said, would require Congress and the Bush administration either to reverse course and permit Americans to place bets online legally with offshore casinos or, equally unlikely, impose an across-the-board ban on all forms of Internet gambling — including the online purchase of lottery tickets, participation in Web-based pro sports fantasy leagues and off-track wagering on horse racing.
But not complying with the decision presents big problems of its own for Washington. That’s because Mr. Mendel, who is claiming $3.4 billion in damages on behalf of Antigua, has asked the trade organization to grant a rare form of compensation if the American government refuses to accept the ruling: permission for Antiguans to violate intellectual property laws by allowing them to distribute copies of American music, movie and software products, among others.
For the W.T.O. itself, the decision is equally fraught with peril. It cannot back down because that would undermine its credibility with the rest of the world. But if it actually carries out the penalties, it risks a political backlash in the United States, the most powerful force for free-flowing global trade and the W.T.O.’s biggest backer.

There are several thought that come to mind:

1) The Doha Rounds of talks have pretty much stalled completely on the agricultural subsidy problem between two big players, the US and the EU. China has resisted US pressure to respect intellectual property rights, so the ‘moral high ground’ is in danger for the US on the symbolic level at least.

2) The testing of rules and jurisdictions would be easier if the short term stakes look small, as in this David/Goliath case.

Antigua is a small country (70,000 people) so the penalty imposed on intellectual property would be tiny for the US in relation to the economy. But the issue of jurisdictions is huge. The US federal government has restricted use of credit cards and such for internet gambling offshore, and there is a long history of regulation at the state and local levels of government.

3) I do not think that the gambling industry has as powerful a lobby and financial backers as agricultural, and is less centralized. Americans are also ambivalent about the industry, but it has become a money maker for states as sole providers of tickets.

4) Alternative routes to globalization are being explored in various multi-lateral agreements based on regional interests with similar political goals or more familiar cultural values as more local businesses become involved in regional trade.

Psychologists and torture

The Houston Chronicle comments on the American Psychological Association and the recent national meeting regarding psychologists’ role in interrogation.

One of the mental health profession’s strengths is its grasp of ambiguity. Love and hate, rage and attraction, altruism and greed can coexist in the same person, and practitioners help clients accept that.
The Hippocratic oath, on the other hand, is simple. Do no harm. Based on this mandate, American psychologists should have nothing to do with the interrogation of terrorist suspects in prisons such as Guantanamo Bay.
Even when legal, the harsh techniques used in these centers include inflicting mental anguish; the very basis on which these prisoners are held — depriving them of both the protections afforded prisoners of war and the legal rights of criminal suspects — comprises a human rights violation. By helping interrogators in such prisons, psychologists are promoting, not healing, mental distress.
Unfortunately, the American Psychological Association last week concluded otherwise. To its credit, in a closely watched decision at their annual meeting, the group forbade members from “direct or indirect participation” in about 20 extreme interrogation techniques that have been used recently by U.S. military forces and intelligence agencies.
The association singled out waterboarding, exploiting detainees’ phobias and exposure to extreme temperatures.
But the resolution didn’t go far enough. Because psychologists are heavily involved in intelligence work — from giving advice to conducting studies — any ambiguity about their role in inflicting harm has special consequence.
The American Medical Association and American Psychiatric Association ban their members from taking any part in prisoner interrogations. According to Leonard Rubenstein of the nonprofit Physicians for Human Rights, medical professionals’ ethics plainly ban them from using their expertise in any situation in which distress is purposely inflicted.
Though the American Psychological Association “unequivocally condemns torture,” its members may still help interrogators at Guantanamo and similar facilities.
Still worse, a number of exposés show that in recent years psychologists have been pivotal in creating some of the most abusive tactics in use since 9/11.
These extreme measures don’t even produce reliable evidence, many mental health and intelligence experts agree. Under duress, prisoners just say what they think interrogators want to hear. Experienced interrogators, on the other hand, build rapport and incentives, which do produce useful information. Psychologists are neither trained, nor necessary, for this non-therapeutic questioning process.
The worst argument for psychologists’ presence at interrogations comes from U.S. Army Col. Larry James, director of the psychology department of a military medical center.
“If we lose psychologists from these facilities, people are going to die,” he said at the APA meeting. Psychologists, James suggested, can rein or report overzealous violators.
Any interrogation system that teeters so close to atrocities needs more than a psychologist. It requires thorough overhaul and specific bans of the most extreme methods. The Department of Defense has listed such prohibitions. The CIA has not.
Torturing prisoners doesn’t produce reliable data. It does, however, violate human rights and strip Americans of the right to protest torture of its own men and women. Above all, it blurs our credibility as a democracy worth defending.
No American psychologist should have a part in an interrogation system with the potential to devolve into murder. No American should.

The failure of the APA is a serious one in my view. I believe the carrot to be the authorization of writing script for medication for the DOD, currently not allowed by any state medical board.

Both the American Medical Association and the American Psychiatric Association have resolutions restricting members participation as a policy. As an institution I believe the American Psychological Association is on the way to crossing a very dangerous line for the profession.

The comments made by readers of the Houston Chronicle were generally opposed to the editorial point of view. Comments?

A counter-insurgency story

The Washington Post published an article by Nathaniel Frick, former Marine captain in counter-insurgeny training in Afghanistan, that makes compelling points.

On a highway north of Kabul last month, an American soldier aimed a machine gun at my car from the turret of his armored Humvee. In the split second for which our eyes locked, I had a revelation: To a man with a weapon, everything looks like a threat.

I had served as an infantry officer in Afghanistan in 2001-02 and in Iraq in 2003, but this was my first time on the other end of an American machine gun. It’s not something I’ll forget. It’s not the sort of thing ordinary Afghans forget, either, and it reminded me that heavy-handed military tactics can alienate the people we’re trying to help while playing into the hands of the people we’re trying to defeat.

Welcome to the paradoxical world of counterinsurgency warfare — the kind of war you win by not shooting.

The objective in fighting insurgents isn’t to kill every enemy fighter — you simply can’t — but to persuade the population to abandon the insurgents’ cause. The laws of these campaigns seem topsy-turvy by conventional military standards: Money is more decisive than bullets; protecting our own forces undermines the U.S. mission; heavy firepower is counterproductive; and winning battles guarantees nothing.

My unnerving encounter on the highway was particularly ironic since I was there at the invitation of the U.S. Army to help teach these very principles at the Afghanistan Counterinsurgency Academy. The grandly misnamed “academy” is a tiny collection of huts and tents on Kabul’s dusty southern outskirts. Since May, motley classes of several dozen Afghan army officers, Afghan policemen, NATO officers, American officers and civilians have been learning and living side by side there for a week at a time.

The academy does much more than teach the theory and tactics of fighting the Taliban insurgents who are trying to unseat President Hamid Karzai and claw their way back to power. It is also a rare forum for military officers, civilian aid workers, academics and diplomats — from Afghanistan and all 37 countries in NATO’s International Security Assistance Force — to unite in trying to bring good governance, prosperity and security to Afghanistan. The curriculum is based on the Army and Marine Corps’ new counterinsurgency doctrine, released in December. Classes revolve around four so-called paradoxes of counterinsurgency. Unless we learn all four well, we’ll continue to win battles in Afghanistan while losing the war.

The first tenet is that the best weapons don’t shoot. Counterinsurgents must excel at finding creative, nonmilitary solutions to military problems.

Said another way: Reconstruction funds can shape the battlefield as surely as bombs. But such methods are still not used widely enough in Afghanistan. After spending more than $14 billion in aid to the country since 2001, the United States’ latest disbursement, of more than $10 billion, will start this month. Some 80 percent of it is earmarked for security spending, leaving only about 20 percent for reconstruction projects and initiatives to foster good governance.

Afghanistan, however, isn’t Iraq. Tourists travel through much of the country in relative safety, glass office towers are sprouting up in Kabul, and Coca-Cola recently opened a bottling plant. I drove through the capital in a dirty green Toyota, wearing civilian clothes and stopping to shop in bazaars, eat in restaurants and visit businesses. In two weeks, I saw more of Kabul than most military officers do in a year.

This isolation also infects our diplomatic community. After a State Department official gave a presentation at the academy, he and I climbed a nearby hill to explore the ruins of an old palace. He was only nine days from the end of his 12-month tour, and our walk was the first time he’d ever been allowed to get out and explore the city.

Of course, mingling with the population means exposing ourselves to attacks, and commanders have an obligation to safeguard their troops. But they have an even greater responsibility to accomplish their mission. When we retreat behind body armor and concrete barriers, it becomes impossible to understand the society we claim to defend. If we emphasize “force protection” above all else, we will never develop the cultural understanding, relationships and intelligence we need to win.

The third paradox hammered home at the academy is that the more force you use, the less effective you may be. Civilian casualties in Afghanistan are notoriously difficult to tally, but 300-500 noncombatants have probably been killed already this year, mostly in U.S. and coalition air strikes. Killing civilians, even in error, is not only a serious moral transgression but also a lethal strategic misstep. Wayward U.S. strikes have seriously undermined the very legitimacy of the Karzai government and made all too many Afghans resent coalition forces. If Afghans lose patience with the coalition presence, those forces will be run out of the country, in the footsteps of the British and the Soviets before them.

I stress this point because one of my many gratifying moments at the academy came at the start of a class on targeting. I told the students to list the top three targets they would aim for if they were leading forces in Zabul province, a Taliban stronghold. When I asked a U.S. officer to share his list, he rattled off the names of three senior Taliban leaders to be captured or killed. Then I turned and asked an Afghan officer the same question. “First we must target the local councils to see how we can best help them,” he replied. “Then we must target the local mullahs to find out their needs and let them know we respect their authority.” Exactly. In counterinsurgency warfare, targeting is more about whom you bring in than whom you take out.

Another voice heard from a retired member of our military.

Opting in, opting out – What is a person to do?

Some readers want to opt out of certain programs. Some readers want to opt in certain programs. Pictures are worth a thousand words, especially on a blog with limited bandwidth.

Note: Totals may not add up to 100% due to rounding.
$ 10,000

Tax pie chart

Of the $10000.00 you paid in taxes:
$2720.00 goes to the military
$1870.00 goes to pay the interest on the debt
$2090.00 goes to health care
$600.00 goes to income security
$450.00 goes to education
$340.00 goes to benefits for veterans
$260.00 goes to nutrition spending
$190.00 goes to housing
$150.00 goes to environmental protection
$30.00 goes to job training
$1240.00 goes to all other expenses
Source: Breakdown of income taxes is based on Budget of the United States Government
View sources and methodology

Income security costs are about 6% of outlays, and the other three highest are about 61% of outlays. Since as far as I know all are still mandatory, which to opt ? I vote this way. 🙂
1)Maybe the Fed to limit bailouts for the top oner’s
2) Or the NIH to get rid of unnecessary funding for subtle toxins?
3) My Social Security?

4)Or abandon infrastructure before it goes kaput?
5)Or the secret funds for foreign intrigue?

We could vote in a buffet style tax opt in system, or an opt out system which would probably have a different result.
If we opt out of social security, who is gonna pay for the goodies? We already know who pays this year:

Part ll on roles of government/private sector public health

Hat tip to Laura Wright at On Earth magazine and NRDC (National Resources Defense Council) for the following link:

CuraGen offers toxigenomic screens.

CuraGen’s industrialized Predictive Toxicogenomics Screen enables inexpensive cellular screening of thousands of compounds annually, and provides results on nine different modes of liver toxicity. Evidence of liver toxicity is one of the primary reasons that drug compounds fail during preclinical development. Nearly 75% of pharmaceutical research and development expenditures are devoted to developing drugs that never reach the market. Detailed information generated by this screen can be used by scientists to prioritize compounds based upon their potential for toxicity, in order to avoid work on compounds that are likely to fail in safety tests later in development.

CuraGen and Bayer scientists developed this unique assay by analyzing more than 100 known toxic compounds and identifying marker genes whose activity correlates with specific modes of liver toxicity. These genes have been subcategorized into
marker sets predictive of nine specific liver histopathologies, including cholestasis, necrosis, or hypertrophy, and have been affixed to gene expression microarrays for use in high-throughput comparative analysis. Drug compounds under review are applied in extremely small quantities to primary hepatocyte cells in vitro. The cellular activity of these dosed compounds is then evaluated against the proprietary toxicity markers. The results of this comparison provide scientists with a rank-ordered list of compounds based upon their potential for toxicity, which can be used in determining which compounds have the highest likelihood for successful clinical development.

CuraGen Corporation has been a pioneer in the field of pharmacogenomics, which includes the study of how drugs work, why drugs fail, and which characteristics are indicative of drug toxicity. CuraGen’s expertise stems from pharmacogenomic research conducted with many of the world’s leading pharmaceutical companies in prioritizing portions of their drug pipelines.

CuraGen Corporation (NASDAQ: CRGN) is a genomics-based pharmaceutical company.

More thoughts:

1) Is there a moral obligation of private companies to invest in public health as part of their own product development? If the current regulatory structure is not even knowledgeable about the issue as part of the public forum, is this wise?

2) In light of the US experience with Chinese products and safety, is it useful to wait for the EU regulations on cosmetics to take effect in the US instead of being more pro-active? Revlon and L’Oreal have volunteered to comply with EU rules and also sell the same to the US, but other companies have not, so known toxins remain in the market.

3) How do you see the balances of interests happening in the future?

More thoughts?

Where is Balochistan?

Pakistani ISI and Iranian intelligence working together? And when you thought you knew the players.

Pakistani Intelligence ISI in collaboration with Iranian intelligence crafted a unique strategy to fight Baloch nationalists who are waging a deadly guerilla warfare against Pakistani Army in the Balochistan province – Islamize youth and kill Nationalists – according to sources in Balochistan . Baloch Nationalists have alerted Western Governments and think tanks abroad about this new development; witnessed by locals, widely circulated in baloch forums, that a promotional gathering of Tabligi was orchestrated under the watchful eyes of ISI on July 31 in Gawadar, the costal city Balochistan. One Mr.Archen Baloch said “Fanatic mullahism is been promoted proactively in collaboration with insignificant, discarded local mullahs against the Baloch nationalism which seeks the restoration of its national sovereignty over Balochistan. “. This phenomenon suggests that Pakistani intelligence is adding a new dimension to its Counter insurgence strategy to contain Baloch nationalists- who are regarded as secular, unlike other groups. IntelliBriefs sources in Pakistan say such events are “taking place in all over Balochistan, and this phenomenon suggest a new conspiracy against Baloch nationalist” and is also considered as “second force of Pakistani government after its armed force”.

While one need not be surprised about strong alliance between ISI and Islamic groups ,it is believed that ISI has activated its network of Mullahs to counter Baloch Nationalists after the failure of Pakistani army to crush the Baloch Resistance . Now Pakistan ” wants dilute the intensity of Baloch nationalism by mobilizing the religious elements in our society” said Archen Baloch . All these activities are funded by ISI and spearheaded by Mr.Mulana Sherani ,member of Pakistan national assembly and he heads JUI in Balochistan .

On Iranian side of Balochistan ,Abdolmalik Rigi’s open revolt against Iran has forced Iranians to use Mullahs as weapons against Baloch Nationalists . Iranian officials are spending sleepless nights over the unrest in its Sistan Balochistan Province which shares border with Pakistani side of Balochistan . Sources say Baloch are facing harassment by Iranian officials at the border who visit their relatives on the other side of the border in the Iran . They say “we have to go through harsh security by Pasdarane Inqalab, the Revolutionary Guard.” . IntelliBriefs learned that those who want to participate in religious gathering in Pakistani held Balochistan face no restrictions, they can pass the boarder without any document or “Rahdari” permit.

Map of tribal areas: The map did not translate, but is worth a look to see how porous all the borders are between political and tribal boundaries.

The other side of the coin in Iraq

Reporters at the Institute for War and Peace Reporting offer insight into local political and military conditions in Basra. Reporting appears to dovetail with Cactus’s post.

The concrete walls that surround the Fadhila party’s compound in Sharish, north of Basra city centre, resemble the barricades around the fortified Green Zone in Baghdad. Last spring, fierce clashes erupted between Fadhila and the Mahdi Army, a paramilitary group loyal to radical Shia cleric Muqtada al-Sadr. Several people were killed on both sides and offices and buildings belonging to the two parties were destroyed. Mediators from tribes and other political parties managed to end the fighting but as Abu Ali al-Baaj, a mid-level Mahdi Army commander, put it, “The tensions were not buried for good.”

The reason for the battle was simple – as the governing party in Basra, Fadhila had replaced the head of the local electricity department, who happened to be a Sadr supporter. Behind the façade of democratic institutions such as councils and the police force, Iraq’s second-largest city with about 2.6 million inhabitants, has fallen into the grip of competing militias who are as suspicious of one another as rival mafia families. When the two militias began fighting over the post of electricity chief, the police force divided into factions which turned their weapons on one another. Police cars were used to transport militia members. The Fadhila party runs the provincial council of Basra and controls most of the government institutions there. It was founded after Saddam Hussein’s regime was toppled in April 2003, and holds 15 seats in the Iraqi parliament.

With leading Shia cleric Sheikh Mohammed al-Yaqubi as its spiritual leader, the party also features Basra’s governor Mohammed al-Waili among its leading members. Basra had so little to lose and so much to gain from the demise of Saddam Hussein’s regime that, initially at least, it had all of the makings of a post-liberation success story. The city had been neglected for at least a decade as punishment for its largely Shia population’s support for the 1991 rebellion against Ba’ath party rule.

Whichever party wins, residents fear they will be the losers. Many say all they want is decent public services and accountable officials.”The religious parties and coalitions plant fear and terror among people to make sure they keep their mouths shut,” said Ahmed al-Hassawi, a traffic policeman. “This creates a terrorised community that can’t hold officials accountable even when they make mistakes. “I don’t care about the name or approach of the party that runs the province – my concern is what they will provide for my children and me.”However, Basra could be set for another bout of turbulence well ahead of any election. After Maliki dismissed Governor Waili, the Fadhila party threatened to mount protests on July 30. The protests were called off at the last minute, apparently after the party received assurances that Waili’s replacement would again be drawn from its ranks rather than from some rival group.

Absolute proof or preponderance of evidence?

This article in On Earth marks the beginning of research that might have far reaching consequences in how we view disease and how our consumption is currently involved in creating health problems:

Although some diseases are inherited through a single genetic mutation — cystic fibrosis and sickle cell anemia are examples — the classic “one gene, one disease” model doesn’t adequately explain the complex interplay between an individual’s unique genetic code and his or her personal history of environmental exposures. That fragile web of interactions, when pulled out of alignment, is probably what causes many chronic diseases: cancer, obesity, asthma, heart disease, autism, and Alzheimer’s, to name just a few. To unravel the underlying biological mechanisms of these seemingly intractable ailments requires that scientists understand the precise molecular dialogue that occurs between our genes and the environment — where we live and work, what we eat, drink, breathe, and put on our skin. Herbert’s literature scan was a nod in this direction, but actually teasing out the answers in a laboratory has been well beyond her or anyone else’s reach — until now.

The earliest prototype was devised about a decade ago; since then these tiny devices, as well as other molecular investigative tools, have grown exponentially in their sophistication, pushing medical science toward a new frontier.
Gene chips are small, often no larger than your typical domino or glass laboratory slide, yet they can hold many thousands of genes at a time. Human genes are synthesized and bound to the surface of the chip such that a single copy of each gene — up to every gene in an organism’s entire genome — is affixed in a grid pattern. The DNA microarray allows scientists to take a molecular snapshot of the activity of every gene in a cell at a given moment in time.

The process works this way: Every cell in your body contains the same DNA, but DNA activity — or expression — is different in a liver cell, say, than it is in a lung, brain, or immune cell. Suppose a scientist wishes to analyze the effect of a particular pesticide on gene activity in liver cells. (This makes sense, since it is the liver that processes and purges many toxins from the body.) A researcher would first expose a liver cell culture in a test tube to a precise dose of the chemical. A gene’s activity is observed through the action of its RNA, molecules that convey the chemical messages issued by DNA. RNA is extracted from the test tube, suspended in a solution, then poured over the gene chip. Any given RNA molecule will latch on only to the specific gene that generated it. The genes on the chip with the most RNA stuck to them are the ones that were most active in the liver cells, or most “highly expressed.” The genes that don’t have any RNA stuck to them are said to be “turned off” in those cells. Scientists use the micro array to compare the exposed cells to non-exposed, control cells (see sidebar). Those genes that show activity in the exposed cells but not in the control cells, or vice versa, are the ones that may have been most affected by the pesticide exposure.

…a scientist at the Natural Resources Defense Council (NRDC), who was then a postdoctoral researcher at the University of Maryland, designed an experiment that included the use of microarrays and other molecular tools to figure out how, exactly, mercury was interfering with both our nervous and immune systems. She grew cells in test tubes — one set for mouse brain cells, another for mouse liver cells — and exposed them to various doses of mercury so that she could see which genes were being switched on and off in the presence of the toxic metal. In the brain and the liver cells, she noticed unusual activity in the gene interleukin-6, which both responds to infection and directs the development of neurons.
“We thought we had mercury figured out,” says Ellen Silbergeld, a professor of environmental health sciences at Johns Hopkins University, who collaborated with Sass on the study. Genomic tools may identify effects of other chemicals by allowing scientists to “go fishing,” as Silbergeld puts it, for things they did not know to look for.

But first, a more fundamental question: Do we even understand what today’s chronic diseases are? It is beginning to appear that what we call autism may in fact be many illnesses that we’ve lumped together because those who are afflicted seem to behave similarly. Doctors base their diagnosis on behavioral symptoms, not on what caused those symptoms. Some scientists now refer to the condition as “autisms,” acknowledging that we’ve yet to find a single, unifying biological mechanism, despite the identification, in some studies, of a handful of genes that may confer increased vulnerability. But then, genes or environmental exposures that appear to be important causal factors in one study may not show up at all in another. This leaves scientists to wonder whether the problem isn’t that the disease is so diverse in its biological origins that only a truly massive study — involving many thousands of patients — would have the statistical power to tease apart the various factors involved.

Norway has a study going with 100,000 people on the impact of environment on disease symptoms and causes using this genetic array testing. Clinton started a program in 2000 looking at large numbers of Americans and possible causes of disease symptoms, and includes a number of data sets that could be used for more general purposes. Recruiting has not started to date due to funding problems. The UK is also beginning another large, long term study.

I have included mercury levels in unborns as an example of how innovation in diagnostic procedures will allow us to measure what I have called ‘subtle toxins’ in the environment not because effects are subtle, but measurement is. Our water contains lots of medications and soluble chemicals, and there are no procedures in place to determine safety to unborns and newborns, small children (under 5).

Our ignorance is not limited to dramatic breakthroughs in technological diagnostics, however. Some procedures are simply more commonsense. The American Academy of Pediatricians found that safety levels for mercury blood levels in pregnant women was determined by drawing blood from the mother. Later, it dawned on people to test blood levels from the cortical blood of the fetus, which turned out to average 70% higher levels of mercury than the mothers, and put the fetus way over limits of safety published by EPA. Mercury is fairly common in the environment.

This sort of research costs money, and if it goes where I think it will go over the next ten years, will create concern. Does this sort of research deserve funding by government? Is the initial funding something the current private sector would ever consider? Beginning results are not expected to be ready until 2011 or later, and final results from these particular studies could carry on for several decades.