The Future (45 page)

The furor over embryonic stem cell research grows out of a related issue. Even if it is judged appropriate for women to have the option of terminating their pregnancies—under most circumstances—is it also acceptable for the parents to give permission for “experimentation” on the embryo to which they have given the beginning of a life? Although this controversy is far from resolved, the majority of people in most countries apparently feel that the scientific and medical benefits of withdrawing
stem cells from embryos are
so significant that they justify such experiments. In many countries, the justification is linked to a prior determination that the embryos in question are due to be discarded in any case.

The discovery of nonembryonic stem cells (induced pluripotent, or iPS cells) by
Shinya Yamanaka at Kyoto University (who
was awarded the 2012 Nobel Prize in Medicine) is creating tremendous excitement about a wide range of new therapies and dramatic improvements in drug discovery and screening. In spite of this exciting discovery, however, many scientists still argue that embryonic stem cells may yet prove to have
unique qualities and potential that justify their continued use. Researchers at University College London have already used stem cells to successfully
restore some vision to mice with an inherited retinal disease, and believe that some
forms of blindness in humans may soon be treatable with similar techniques. Other researchers at the University of Sheffield have used stem cells to
rebuild nerves in the ears of gerbils and restore their hearing.

In 2011, Japanese fertility scientists at Kyoto University caused a stir when they announced that they had successfully used embryonic mouse stem cells to produce
sperm when transplanted into the testicles of mice that were infertile. When the sperm was then extracted and put into mouse eggs, the fertilized eggs were transferred to the uteri of female mice, and resulted in normal offspring that could then reproduce naturally. Their work builds on an English science breakthrough in 2006 in which biologists at the University of Newcastle upon Tyne first produced functioning sperm cells that had been converted from stem cells and produced live offspring,
though the offspring had genetic defects.

One reason why these studies drew such attention was that the same basic technique, as it is developed and perfected, may soon make it possible
for infertile men to have biological children—and opens the possibility for gay and
lesbian couples to have children that are genetically and biologically their own. Some headline writers also savored the speculation that since there is no reason why women cannot, in theory, produce their own sperm cells using this technique: “Will Men Become Obsolete?” On the lengthening list of potentially disquieting outcomes from genetic research, this possibility appears destined to linger near the bottom, though I am certainly biased in making that prediction.

Just as scientists working on fertility have focused on the beginning of life, others have been focused on the end of life—and have been making dramatic progress in understanding the factors affecting longevity. They are developing new strategies, which they hope will achieve not only significant extensions in the average human lifespan, but also the extension of what many refer to as the “healthspan”—the number of years we live a healthy life without debilitating conditions or diseases.

Although a few scientific outliers have argued that genetic engineering could
increase human lifespans by multiple centuries, the consensus among many aging specialists is that an increase of up to
25 percent is more likely to be the range of what is possible.
According to most experts, evolutionary theory and
numerous studies in human
and animal genetics lead them to the conclusion that environmental and lifestyle factors contribute
roughly three quarters to the aging process and that genetics makes a more modest contribution—
somewhere between 20 and 30 percent.

One of the most famous studies of the relationship between lifestyle and longevity showed that
extreme caloric restriction extends the lives of rodents dramatically, although there is debate about whether this lifestyle
adjustment has the same effect on longevity in humans. More recent studies have shown that
rhesus monkeys do
not
live longer with severe caloric restrictions. There is a subtle but important distinction,
experts on all sides point out, between longevity and aging. Although they are obviously related, longevity measures the length of life, whereas aging is the process by which cell damage contributes over time to conditions that bring the end of life.

Some highly questionable therapies, such as the use of human growth hormone in an effort
to slow or reverse unwanted manifestations of the aging process, may well have side effects that shorten longevity, such as triggering the onset of diabetes and the growth of tumors. Other hormones that have been used to combat symptoms of aging—
most prominently, testosterone and estrogen—have also led to controversies about side effects that can shorten longevity for certain patients.

However, excitement was also stirred by a Harvard study in 2010 that showed that the aging process in mice could be halted and even
reversed
by the use of enzymes known as telomerases, which serve to
protect the telomeres—or protective caps—on the ends of chromosomes in order to prevent them from damage. Scientists have long known that these telomeres get shorter with the aging of cells and that this shortening process can ultimately halt the renewal of the cells through replication. As a result of the Harvard study, scientists are exploring strategies for protecting the telomeres in order to retard the aging process.

Some researchers are optimistic that extensive whole genome studies of humans with very long lifespans may yet lead to the discovery of
genetic factors that can be used to extend longevity in others. However, most of the dramatic extensions in the average human lifespan
over the last century have come from improvements in sanitation and nutrition, and from medical breakthroughs such as the discovery of antibiotics and the development of vaccines. Further improvements in these highly successful strategies are likely to further improve average lifespans—probably, scientists speculate, at the rate of improvement we have become used to—
about one extra year per decade.

In addition, the continued global efforts to fight infectious disease threats are also extending average lifespans by reducing the number of premature deaths.
Much of this work is now focused on malaria, tuberculosis,
HIV/AIDS, influenza,
viral pneumonia,
and multiple so-called “neglected tropical diseases” that are barely known in the industrialized world but afflict more than a billion people in developing tropical and subtropical countries.

There has been heartening progress in reducing the number of people who die of AIDS each year.
In 2012, the number fell to 1.7 million, significantly down from its 2005 peak of 2.3 million. The principal reason for this progress is greater access to pharmaceuticals—particularly antiretroviral drugs—that extend the lifespan and improve the health of people who have the disease. Efforts to
reduce the infection rate continue to be focused on preventive education,
the distribution of condoms in high-risk areas,
and accelerated efforts to develop a vaccine.

Malaria has also been reduced significantly over the past decade with a carefully chosen combination of strategies. Although the largest absolute declines were in Africa, according to the U.N., 90 percent of all malaria deaths still take place in Sub-Saharan Africa—most of them involving
children under five.
Although an ambitious effort in the 1950s to eradicate malaria did not succeed, a few of those working hard to eradicate malaria, including Bill Gates, now believe that their goal may actually be realistic within the next few decades.

The world
did succeed in eliminating the terrible scourge of smallpox in 1980. And in 2011 the U.N. Food and Agriculture Organization
succeeded in eliminating a second disease, rinderpest, a relative of measles that killed cattle and other animals with cloven hooves. Because it was an animal disease, rinderpest never garnered the global attention that smallpox commanded, but it was one of the deadliest and most feared threats to those whose families and communities depend on livestock.

For all of the appropriate attention being paid to infectious diseases, the leading causes of death in the world today, according to the World Health Organization, are
chronic diseases that are not communicable. In the last year for which statistics are available, 2008, approximately 57 million people died in the world, and almost 60 percent of those deaths were caused by chronic diseases, principally cardiovascular disease, diabetes, cancer, and chronic respiratory diseases.

Cancer is a special challenge, in part because it is not one disease, but many. The U.S. National Cancer Institute and the National Human Genome Research Institute have been spending $100 million per year on a
massive effort to create a “Cancer Genome Atlas,” and in 2012 one of the first fruits of this project was published in
Nature
by more than 200 scientists who detailed genetic peculiarities in colon cancer tumors. Their study of more than 224 tumors has been regarded as a potential turning point in the development of new drugs that will take advantage of vulnerabilities they found in the tumor cells.

In addition to focusing on genomic analyses 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 Institutes of Cardiovascular Disease has dramatically improved cardiac function in adult mice by
reprogramming cells to restore the health of heart muscles.

I
N 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 principal 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 analyzed 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 assistants 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 assist 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 analyses 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. Nanobots 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 analysis 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.