Part 11 (2/2)

In addition to focusing on genomic a.n.a.lyses of cancer, scientists are exploring virtually every conceivable strategy for curing cancers. They are investigating new possibilities for shutting off the blood supply to cancerous cells, dismantling their defense mechanisms, and boosting the ability of natural immune cells to identify and attack the cancer cells. Many are particularly excited about new strategies that involve proteomics-the decoding of all of the proteins translated by cancer genes in the various forms of cancer and targeting epigenetic abnormalities.

Scientists explain that while the human genome is often characterized as a blueprint, it is actually more akin to a list of parts or ingredients. The actual work of controlling cellular functions is done by proteins that carry out a ”conversation” within and between cells. These conversations are crucial in understanding ”systems diseases” like cancer.

One of the promising strategies for dealing with systemic disorders like cancer and chronic heart diseases is to strengthen the effectiveness of the body's natural defenses. And in some cases, new genetic therapies are showing promise in doing so. A team of scientists at the University of California San Francisco Gladstone Inst.i.tutes of Cardiovascular Disease has dramatically improved cardiac function in adult mice by reprogramming cells to restore the health of heart muscles.

IN MANY IF not most cases, though, the most effective strategy for combating chronic diseases is to make changes in lifestyles: reduce tobacco use, reduce exposure to carcinogens and other harmful chemicals in the environment, reduce obesity through better diet and more exercise, and-at least for salt-sensitive individuals-reduce sodium consumption in order to reduce hypertension (or high blood pressure).

Obesity-which is a major causal factor in multiple chronic diseases-was the subject of discouraging news in 2012 when the British medical journal The Lancet published a series of studies indicating that one of the princ.i.p.al factors leading to obesity, physical inactivity and sedentary lifestyles, is now spreading from North America and Western Europe to the rest of the world. Researchers a.n.a.lyzed statistics from the World Health Organization to demonstrate that more people now die every year from conditions linked with physical inactivity than die from smoking. The statistics indicate that one in ten deaths worldwide is now due to diseases caused by persistent inactivity.

Nevertheless, there are good reasons to hope that new strategies combining knowledge from the Life Sciences Revolution with new digital tools for monitoring disease states, health, and wellness may spread from advanced countries as cheaper smartphones are sold more widely throughout the globe. The use of intelligent digital a.s.sistants for the management of chronic diseases (and as wellness coaches) may have an extremely positive impact.

In developed nations, there are already numerous smartphone apps that a.s.sist those who wish to keep track of how many calories they consume, what kinds of food they are eating, how much exercise they are getting, how much sleep they are getting (some new headbands also keep track of how much deep sleep, or REM sleep, they are getting), and even how much progress they are making in dealing with addictions to substances such as alcohol, tobacco, and prescription drugs. Mood disorders and other psychological maladies are also addressed by self-tracking programs. During the 2012 summer Olympic Games in London, a number of athletes were persuaded by biotech companies attempting to improve their health-tracking devices to use glucose monitors and sleep monitors, and to receive genetic a.n.a.lyses designed to improve their individual nutritional needs.

Such monitoring is not limited to Olympians. Personal digital monitors of patients' heart rates, blood glucose, blood oxygenation, blood pressure, body temperature, respiratory rate, body fat levels, sleep patterns, medication use, exercise, and more are growing more common. Emerging developments in nanotechnology and synthetic biology also hold out the prospect of more sophisticated continuous monitoring from sensors inside the body. Nan.o.bots are being designed to monitor changes in the bloodstream and vital organs, reporting information on a constant basis.

Some experts, including Dr. H. Gilbert Welch of Dartmouth, the author of Overdiagnosed: Making People Sick in the Pursuit of Health, believe that we are in danger of going too far in monitoring and data a.n.a.lysis of individuals who track their vital signs and more: ”Constant monitoring is a recipe for all of us to be judged 'sick.' Judging ourselves sick, we seek intervention.” Welch and some others believe that many of these interventions turn out to be costly and unnecessary. In 2011, for example, medical experts advised doctors to stop routinely using a new and sophisticated antigen test for prostate cancer precisely because the resulting interventions were apparently doing more harm than good.

The digitizing of human beings, with the creation of large files containing detailed information about their genetic and biochemical makeup and their behavior, will also require attention to the same privacy and information security issues discussed in Chapter 2. For the same reasons that this rich data is potentially so useful in improving the efficacy of health care and reducing medical costs, it is also seen as highly valuable to insurance companies and employers who are often eager to sever their relations.h.i.+ps with customers and employees who represent high risks for big medical bills. Already, a high percentage of those who could benefit from genetic testing are refusing to have the information gathered for fear that they will lose their jobs and/or their health insurance.

A few years ago, the United States pa.s.sed a federal law known as the Genetic Information Nondiscrimination Act, which prohibits the disclosure or improper use of genetic information. But enforcement is difficult and trust in the law's protection is low. The fact that insurance companies and employers usually pay for the majority of health care expenditures-including genetic testing-further reinforces the fear by patients and employees that their genetic information will not remain confidential. Many believe that flows of information on the Internet are vulnerable to disclosure in any case. The U.S. law governing health records, the Health Insurance Portability and Accountability Act, fails to guarantee patient access to records gathered from their own medical implants while companies seek to profit from personalized medical information.

Nevertheless, these self-tracking techniques-part of the so-called self-quantification movement-offer the possibility that behavior modification strategies that have traditionally been a.s.sociated with clinics can be individualized and executed outside of an inst.i.tutional setting. Expenditures for genetic testing are rising rapidly as prices for these tests continue to fall rapidly and as the wave of personalized medicine continues to move forward with increasing speed.

The United States may have the most difficulty in making the transition to precision medicine because of the imbalance of power and unhealthy corporate control of the public policy decision-making process, as described in Chapter 3. This chapter is not about the U.S. health care system, but it is interesting to note that the glaring inefficiencies, inequalities, and absurd expense of the U.S. system are illuminated by the developing trends in the life sciences. For example, many health care systems do not cover disease prevention and wellness promotion expenditures, because they are princ.i.p.ally compensated for expensive interventions after a patient's health is already in jeopardy. The new health care reform bill enacted by President Obama required coverage of preventive care under U.S. health care plans for the first time.

As everyone knows, the U.S. spends far more per person on health care than any other country while achieving worse outcomes than many other countries that pay far less, and still, tens of millions do not have reasonable access to health care. Lacking any other option, they wait, often until their condition is so dire that they have to go to the emergency room, where the cost of intervention is highest and the chance of success is lowest. The recently enacted reforms will significantly improve some of these defects, but the underlying problems are likely to grow worse-primarily because insurance companies, pharmaceutical companies, and other health care providers retain almost complete control over the design of health care policy.

THE STORY OF INSURANCE.

The business of insurance began as far back as ancient Rome and Greece, where life insurance policies were similar to what we now know as burial insurance. The first modern life insurance policies were not offered until the seventeenth century in England. The development of extensive railroad networks in the United States in the 1860s led to limited policies protecting against accidents on railroads and steamboats, and that led, in turn, to the first insurance policies protecting against sickness in the 1890s.

Then, in the early 1930s, when advances in medical care began to drive costs above what many patients could pay on their own, the first significant group health insurance policies were offered by nonprofits: Blue Cross for hospital charges and Blue s.h.i.+eld for doctors' fees. All patients paid the same premiums regardless of age or preexisting conditions. The success of the Blues led to the entry into the marketplace of private, for-profit health insurance companies, who began to charge different premiums to people based on their calculation of the risk involved-and refused to offer policies at all to those who represented an unacceptably high risk. Soon, Blue Cross and Blue s.h.i.+eld were forced by the new for-profit compet.i.tion to also link premiums to risk.

When President Franklin Roosevelt was preparing his package of reforms in the New Deal, he twice took preliminary steps-in 1935 and again in 1938-to include a national health insurance plan as part of his legislative agenda. On both occasions, however, he feared the political opposition of the American Medical a.s.sociation and removed the proposal from his plans lest it interfere with what he regarded as more pressing priorities in the depths of the Great Depression: unemployment compensation and Social Security. The introduction of legislation in 1939 by New York Democratic senator Robert Wagner offered a quixotic third opportunity to proceed but Roosevelt chose not to support the legislation.

During World War II, with wages (and prices) controlled by the government, private employers began to compete for employees, who were scarce due to the war, by offering health insurance coverage. Then after the war, unions began to include demands for more extensive health insurance as part of their negotiated contracts with employers.

Roosevelt's successor, Harry Truman, sought to revive the idea for national health insurance, but the opposition in Congress-once again fueled by the AMA-ensured that it died with a whimper. As a result, the hybrid system of employer-based health insurance became the primary model in the United States. Because older Americans and those with disabilities had a difficult time obtaining affordable health insurance within this system, new government programs were implemented to help both groups.

For the rest of the country, those who needed health insurance the most had a difficult time obtaining it, or paying for it when they could find it. By the time the inherent flaws and contradictions of this model were obvious, the American political system had degraded to the point that the companies with an interest in seeing this system continued had so much power that nothing could be done to change its basic structure.

With rare exceptions, the majority of legislators are no longer capable of serving the public interest because they are so dependent on campaign contributions from these corporate interests and so vulnerable to their nonstop lobbying. The general public is effectively disengaged from the debate, except to the extent that they absorb constant messaging from the same corporate interests-messages designed to condition their audience to support what the business lobbies want done.

GENETICALLY ENGINEERED FOOD.

The same sclerosis of democracy is now hampering sensible adaptations to the wave of changes flowing out of the Life Sciences Revolution. For example, even though polls consistently show that approximately 90 percent of American citizens believe that genetically engineered food should be labeled, the U.S. Congress has adopted the point of view advocated by large agribusiness companies-that labeling is unnecessary and would be harmful to ”confidence in the food supply.”

However, most European countries already require such labeling. The recent approval of genetically engineered alfalfa in the U.S. provoked a larger outcry than many expected and the ”Just Label It” campaign has become the centerpiece of a new gra.s.sroots push for labeling genetically modified (GM) food products in the United States, which plants twice as many acres in GM crops as any other country. Voters in California defeated a referendum in 2012 to require such labeling, after corporate interests spent $46 million on negative commercials, five times as much as proponents. Nevertheless, since approximately 70 percent of the processed foods in the U.S. contain at least some GM crops, this controversy will not go away.

By way of background, the genetic modification of plants and animals is, as enthusiastic advocates often emphasize, hardly new. Most of the food crops that humanity has depended upon since before the dawn of the Agricultural Revolution were genetically modified during the Stone Age by careful selective breeding-which, over many generations, modified the genetic structure of the plants and animals in question to manifest traits of value to humans. As Norman Borlaug put it, ”Neolithic women accelerated genetic modifications in plants in the process of domesticating our food crop species.”

By using the new technologies of gene splicing and other forms of genetic engineering, we are-according to this view-merely accelerating and making more efficient a long-established practice that has proven benefits and few if any detrimental side effects. And outside of Europe (and India) there is a consensus among most farmers, agribusinesses, and policymakers that GM crops are safe and must be an essential part of the world's strategy for coping with antic.i.p.ated food shortages.

However, as the debate over genetically modified organisms (GMOs) has evolved, opponents of the practice point out that none of the genetic engineering has ever produced any increase in the intrinsic yields of the crops, and they have raised at least some ecosystem concerns that are not so easily dismissed. The opponents argue that the insertion of foreign genes into another genome is, in fact, different from selective breeding because it disrupts the normal pattern of the organism's genetic code and can cause unpredictable mutations.

The first genetically engineered crop to be commercialized was a new form of tomato known as the FLAVR SAVR, which was modified to remain firm for a longer period of time after it ripened. However, the tomato did not succeed due to high costs. And consumer resistance to tomato paste made from these tomatoes (it was clearly labeled as a GM product) caused the paste to be a failure.

Selective breeding was used to make an earlier change in the traits of commercial tomatoes in order to produce a flatter, less rounded bottom to accommodate the introduction of automation in the harvesting process. The new variety stayed on the conveyor belts without rolling off, was easier to pack into crates, and its tougher skin prevented the machines from crus.h.i.+ng the tomatoes. They are sometimes called ”square tomatoes,” though they are not really square.

An even earlier modification of tomatoes, in 1930, also using selective breeding, was the one that resulted in what most tomato lovers regard as a catastrophic loss of flavor in modern tomatoes. The change was intended to enhance the ma.s.s marketing and distribution of tomatoes by ensuring that they were ”all red” and ripened uniformly, without the green ”shoulders” that consumers sometimes viewed as a sign that they were not yet ripe. Researchers working with the newly sequenced tomato genome discovered in 2012 that the elimination of the gene a.s.sociated with green shoulders also eliminated the plant's ability to produce most of the sugars that used to give most tomatoes a delicious taste.

In spite of experiences such as these, which ill.u.s.trate how changes made for the convenience and profitability of large corporations sometimes end up triggering other genetic changes that most people hate, farmers around the world-other than in the European Union-have adopted GM crops at an accelerating rate. Almost 11 percent of all the world's farmland was planted in GM crops in 2011, according to an international organization that promotes GMOs, the International Service for the Acquisition of Agri-biotech Applications. Over the last seven years, the number of acres planted in GM crops has increased almost 100-fold, and the almost 400 million acres planted in 2011 represented an increase of 8 percent from one year earlier.

Although the United States is by far the largest grower of GM crops, Brazil and Argentina are also heavily committed to the technology. Brazil, in particular, has adopted a fast-track approval system for GMOs and is pursuing a highly focused strategy for maximizing the use of biotechnology in agriculture. In developing countries overall, the adoption of modified crops is growing twice as fast as in mature economies. An estimated 90 percent of the 16.7 million farmers growing genetically engineered crops in almost thirty countries were small farmers in developing markets.

Genetically modified soybeans, engineered to tolerate Monsanto's Roundup herbicide, are the largest GM crop globally. Corn is the second most widely planted GM crop, although it is the most planted in the U.S. (”Maize” is the term used for what is called corn in the U.S.; the word ”corn” is often used outside the U.S. to refer to any cereal crop.) In the U.S., 95 percent of soybeans planted and 80 percent of corn are grown from patented seeds that farmers must purchase from Monsanto or one of their licensees. Cotton is the third most planted GM crop globally, and canola (known as ”rapeseed” outside the United States) is the other large GM crop in the world.

Although the science of genetically engineered plants is advancing quickly, the vast majority of GM crops grown today are still from the first of three generations, or waves, of the technology. This first wave, in turn, includes GM crops that fall into three different categories: * The introduction of genes that give corn and cotton the ability to produce their own insecticide inside the plants; * Genes introduced into corn, cotton, canola, and soybeans that make the plants tolerant of two chemicals contained in widely used weed killers that are produced by the same company-Monsanto-that controls the GM seeds; and * The introduction of genes designed to enhance the survivability of crops during droughts.

In general, farmers using the first wave of GM crops report initial reductions in their cost of production-partly due to temporarily lower use of insecticide-and temporarily lower losses to insects or weeds. The bulk of the economic benefits thus far have gone to cotton farmers using a strain that is engineered to produce its own insecticide (Bacillus thuringiensis, better known as Bt). In India the new Bt cotton made the nation a net exporter, rather than importer, of cotton and was a factor in the initial doubling of cotton yields because of temporarily lower losses to insects and weeds. However, many Indian cotton farmers have begun to protest the high cost of the GM seeds they must purchase anew each year and the high cost of the herbicides they must use in greater volumes as more weeds develop resistance. A parliamentary panel in India issued a controversial 2012 report a.s.serting that ”there is a connection between Bt cotton and farmers' suicides” and recommending that field trials of GM crops ”under any garb should be discontinued forthwith.”

New scientific studies-including a comprehensive report by the U.S. National Research Council in 2009-support the criticism by opponents of GM crops that the intrinsic yields of the crops themselves are not increased at all. To the contrary, some farmers have experienced slightly lower intrinsic yields because of unexpected collateral changes in the plants' genetic code. Selective breeding, on the other hand, was responsible for the impressive and life-saving yield increases of the Green Revolution. New research by an Israeli company, Kaiima, into a non-GMO technology known as ”enhanced ploidy” (the inducement, selective breeding, and natural enhancement of a trait that confers more than two sets of chromosomes in each cell nucleus) is producing both greater yields and greater resistance to the effects of drought in a variety of food and other crops. Recent field trials run by Kaiima show more than 20 percent yield enhancement in corn and more than 40 percent enhancement in wheat.

The genetic modification of crops, by contrast, has not yet produced meaningful enhancements of survivability during drought. While some GM experimental strains do, in theory, offer the promise of increased yields during dry periods, these strains have not yet been introduced on a commercial scale, and test plots have demonstrated only slight yield improvements thus far, and only during mild drought conditions. Because of the growing prevalence of drought due to global warming, there is tremendous interest in drought-resistant strains, especially for maize, wheat, and other crops in developing countries. Unfortunately, however, drought resistance is turning out to be an extremely complex challenge for plant geneticists, involving a combination of many genes working together in complicated ways that are not yet well understood.

After an extensive a.n.a.lysis of the progress in genetically engineering drought-resistant crops, the Union of Concerned Scientists found ”little evidence of progress in making crops more water efficient. We also found that the overall prospects for genetic engineering to significantly address agriculture's drought and water-use challenges are limited at best.”

The second wave of GM crops involves the introduction of genes that enhance the nutrient value of the plants. It includes the engineering of higher protein content in corn (maize) that is used primarily for livestock feed, and the engineering of a new strain of rice that produces extra vitamin A as part of a strategy to combat the deficiency in vitamin A that now affects approximately 250 million children around the world. This second wave also involves the introduction of genes that are designed to enhance the resistance of plants to particular fungi and viruses.

The third wave of GM crops, which is just beginning to be commercialized, involves the modification of plants through the introduction of genes that program the production of substances within the plants that have commercial value as inputs in other processes, including pharmaceutical inputs and biopolymers for the production of bioplastics that are biodegradable and easily recyclable. This third wave also involves an effort to introduce genes that modify plants with high cellulose and lignin in order to make them easier to process for the production of cellulosic ethanol. The so-called green plastics have exciting promise, but as with crops devoted to the production of biofuels, they raise questions about how much arable land can safely or wisely be diverted from the production of food in a world with growing population and food consumption, and shrinking a.s.sets of topsoil and water for agriculture.

Over the next two decades, seed scientists believe that they may be able to launch a fourth wave of GM crops by inserting the photosynthesizing genes of corn (and other so-called C4 plants) that are more efficient in photosynthesizing light into energy in plants like wheat and rice (and other C3 plants). If they succeed-which is far from certain because of the unprecedented complexity of the challenge-this technique could indeed bring about significant intrinsic yield increases. For the time being however, the overall net benefits from genetically engineered crops have been limited to a temporary reduction in losses to pests and a temporary decrease in expenditures for insecticides.

In 2012, the Obama administration in the U.S. launched its National Bioeconomy Blueprint, specifically designed to stimulate the production-and procurement by the government-of such products. The European Commission adopted a similar strategy two months earlier. Some environmental groups have criticized both plans because of the growing concern about diverting cropland away from food production and the destruction of tropical forests to make way for more cropland.

The opponents of genetically modified crops argue that not only have these genetic technologies failed thus far to increase intrinsic yields, but also that the weeds and insects the GM crops are designed to control are quickly mutating to make themselves impervious to the herbicides and insecticides in question. In particular, the crops that are engineered to produce their own insecticide (Bacillus thuringiensis) are now so common that the constant diet of Bt being served to pests in large monocultured fields is doing the same thing to insects that the ma.s.sive and constant use of antibiotics is doing to germs in the guts of livestock: it is forcing the mutation of new strains of pests that are highly resistant to the insecticide.

The same thing also appears to be happening to weeds that are constantly sprayed with herbicides to protect crops that have been genetically engineered to survive application of the herbicide (including princ.i.p.ally Monsanto's Roundup, which is based on glyphosate, which used to kill virtually any green plant). Already, ten species of harmful weeds have evolved a resistance to these herbicides, requiring farmers to use other more toxic herbicides. Some opponents of GM crops have marshaled evidence tending to show that over time, as resistance increases among weeds and insects, the overall use of both herbicides and pesticides actually increases, though advocates of GM crops dispute their a.n.a.lysis.

Because so many weeds have now developed resistance to glyphosate (most commonly used in Roundup), there is a renewed market demand for more powerful-and more dangerous-herbicides. There are certainly plenty to choose from. The overall market for pesticides in the world represents approximately $40 billion in sales annually, with herbicides aimed at weeds representing $17.5 billion and both insecticides and fungicides representing about $10.5 billion each.

Dow AgroSciences has applied for regulatory approval to launch a new genetically engineered form of corn that tolerates the application of a pesticide known as 2,4-D, which was a key ingredient in Agent Orange-the deadly herbicide used by the U.S. Air Force to clear jungles and forest cover during the Vietnam War-which has been implicated in numerous health problems suffered by both Americans and Vietnamese who were exposed to it. Health experts from more than 140 NGOs have opposed the approval of what they call ”Agent Orange corn,” citing links between exposure to 2,4-D and ”major health problems such as cancer, lowered sperm counts, liver toxicity and Parkinson's disease. Lab studies show that 2,4-D causes endocrine disruption, reproductive problems, neurotoxicity, and immunosuppression.”

Insecticides that are sprayed on crops have also been implicated in damage to beneficial insects and other animals. The milkweed plants on which monarch b.u.t.terflies almost exclusively depend have declined in the U.S. farm belt by almost 60 percent over the last decade, princ.i.p.ally because of the expansion of cropland dedicated to crop varieties engineered to be tolerant of Roundup. There have been studies showing that Bt crops (the ones that produce insecticide) have had a direct harmful impact on at least one subspecies of monarchs, and on lacewings (considered highly beneficial insects), ladybird beetles, and beneficial biota in the soil. Although proponents of GM crops have minimized the importance of these effects, they deserve close scrutiny as GM crops continue to expand their role in the world's food production.

Most recently, scientists have attributed the disturbing and previously mysterious sudden collapses of bee colonies to a new group of pesticides known as neonicotinoids. Colony collapse disorder (CCD) has caused deep concern among beekeepers and others since the affliction first appeared in 2006. Although numerous theories about the cause of CCD were put forward, it was not until the spring of 2012 that several studies pinpointed the cause.

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