In an essay on scientific discoveries, the former editor in chief
of Science magazine, Daniel E. Koshland Jr., noted that
most important breakthroughs don't come in a single "Eureka!"
moment. More often it's a matter of several discoveries coming
together in just the right combination. Koshland, who died in
2007, used Sir Isaac Newton as an example: to put his theory of
gravity on a firm footing, he also had to develop calculus and
the laws of physics he described in his Principia.
So it is with our 10 nominees for health and medical significance
in 2007, although we don't mean to invite any comparisons to
Newtonian genius. Several items on our list have come about
because of the slow, steady accretion of basic research findings
and trial results. Some involve politics, which is almost always
a grind — especially when it comes to health care. And with a
couple of others we're intentionally marking trends, not a single
event. Sometimes the Eureka moments come when you realize that
there isn't always a splashy breakthrough but many events on a
continuum — a lot that came before and even more to follow.
1. Did we learn a lesson from Avandia?
The FDA is supposed to allow drugs on the market only if they are
safe and effective. In 2007, rosiglitazone (Avandia), became the
latest medication found to have serious side effects that weren't
apparent when it was approved.
Like insulin and other diabetes drugs, rosiglitazone and a
similar drug, pioglitazone (Actos), lower blood sugar. Studies
published in 2007 confirmed some earlier evidence that both drugs
could, in rare instances, cause liver and heart failure. The
surprise came with study results showing that rosiglitazone — but
not pioglitazone — markedly increases the risk of heart attack,
as well as overall risk of dying from heart disease. The absolute
risk is small: about one additional heart attack or cardiac death
in 1,000 people taking the drug. The FDA put a "black box"
warning on it, but rosiglitazone stayed on the market, unlike
rofecoxib (Vioxx), the COX-2 painkiller that was pulled off in
2004 when it was found to cause heart problems.
No drug is entirely safe, and it would be impractical to require
studies large enough to identify all of a drug's problems as a
condition of approval. Instead, the FDA needs more money — and
clout — to make sure drugs are monitored for safety after they're
on the market and to take prompt action if necessary. Congress
passed legislation in 2007 that would give the agency that
funding and power, as well as make some other important reforms
(a requirement that all clinical trials be recorded in a central
registry, for example). Time will tell whether these changes make
a difference and restore lost confidence in medication safety.
2. Genome-wide association studies: Neighborhood searches
The human genome — all of our genes collectively, as well as
noncoding parts of our DNA — consists of three billion chemical
bases strung in a sequence, like letters forming the words in a
very long book. The first diseases linked to genetic
"misspellings" involved a single gene. But what happens when the
candidate gene is not obvious, or the disease is caused by
misspellings in multiple genes, as is so often the case? To find
all of the genes, scientists would have to read the entire three
billion letter genome. And to firmly establish a link to a
disease, they'd have to read the genomes of hundreds, if not
thousands, of people with and without the disease. Talk about
finding a needle in a haystack.
Genome-wide association research is a shortcut that takes
advantage of the discovery of unique "flags" flying in each
neighborhood of the genome. Researchers find the flags associated
with disease and then conduct an intensive search for genetic
miscues just in that neighborhood. That's a lot more efficient
than a dragnet through the entire genome.
There's been a flurry of genome-wide association studies in 2007.
The technique has identified genes important for everything from
type 2 diabetes to multiple sclerosis to natural resistance to
HIV infection. More discoveries are sure to come.
3. Genome sequencing in a jiffy — and getting cheap, too
Sequencing genomes — identifying all the chemical base pairs of
all genes — is expensive, but rapidly becoming cheaper. In 2003,
sequencing all three billion base pairs of the human genome cost
$10 million to $25 million. In 2007, the entire genome of James
Watson, co-discoverer of the DNA double helix, was sequenced for
$1 million. Some experts are predicting that the price will drop
to $1,000 per genome by 2017.
One of the new gene sequencing techniques that may make rapid and
inexpensive scanning possible involves shattering the DNA of the
genome into millions of pieces and sequencing the letters
simultaneously. After this "massively parallel" sequencing is
finished, computers knit the fragmented data into a single
sequence. This technology is already being used in genome-wide
association studies. Once the neighborhood where problem genes
lie has been identified, ultra-fast gene sequencing can rapidly
check all the genes just in that area of the genome.
In the future it may become routine for children to have their
genomes sequenced, enabling doctors to tailor health advice and
medical treatments to each individual's genes. Along with the
opportunities come moral and ethical pitfalls. One of the great
challenges of this century will be harnessing this explosion in
genomic information so it won't be used to discriminate,
persecute, or invade privacy.
4. Waking up to a new health habit: Sleep
None of us needs a study to tell us that we feel better after a
good night's sleep. But research is showing that getting enough
sleep — between seven and nine hours a night for most people — is
one of the pillars of good health, along with exercise, eating
plenty of fruit and vegetables, and staying slim.
No one study made a big splash in 2007, but the evidence has
reached a critical mass. Studies have linked short and poor sleep
to many modern maladies: diabetes, heart disease, high blood
pressure, inflammation, stroke. Short sleep may be a factor in
the obesity epidemic: sleep lab studies have shown that it alters
the activity of leptin, the "fullness" hormone, and ghrelin, the
Meanwhile, scientists are beginning to understand the sleeping
brain and the role it plays in our mental lives and health. One
popular theory is that we need sleep to store — and possibly
attach meaning to — our memories. So if you make sleep a
priority, you might improve your memory and your health.
5. Health is going global
Perhaps all politics are local, but American medicine and health
are going increasingly global. Students at American medical
schools and schools of public health are flocking to seminars,
courses, and programs devoted to global health. Hospitals have
established global health residencies that allow doctors to train
overseas. Medical journal editors are getting involved. In
October 2007, more than 200 journals throughout the world
simultaneously published articles devoted to the topic of poverty
and human development. Celebrities like Oprah Winfrey (AIDS in
Africa) and George Clooney (Darfur) have attached themselves to
global health causes, giving them glamour and media attention.
Others, like Drs. Paul Farmer and Jim Kim of the Harvard School
of Public Health, are well known because of their work in the
Money is pouring in, too. The Bill and Melinda Gates Foundation
has committed $8 billion to global health projects since its
founding in 1994. In 2007, governments pledged $9.7 billion to
the Global Fund to Fight AIDS, Tuberculosis and Malaria, less
than the original goal of $15 to $18 billion, but still a major
Some of the motivation for the concern is enlightened
self-interest. Severe acute respiratory syndrome (SARS), avian
flu, and, of course, AIDS have shown how disease can travel
easily from country to country, and around the globe, in an era
of almost frenetic trade and travel. There's also a basic
humanitarian concern for people so much less fortunate.
The resources, the training, the publicity — they're welcome and
badly needed. Experts worry, though. Charitable efforts can be
counterproductive, competing with each other or, worse, with
local governments. Too many disease-specific programs can
balkanize health care. Interest could fade and money dry up once
global health no longer seems quite so fashionable, but the
problems will remain.
6. Putting out the fire
When it's under control, inflammation is a normal part of our
immune response. But when it gets out of control, inflammation
causes disease and pain, and fanning the flames is a protein
called tumor necrosis factor-alpha (TNF-alpha).
In the 1990s, researchers genetically engineered a protein that
blocks TNF-alpha. The FDA approved the fruits of this labor,
etanercept (Enbrel), in 1998.
Now two others — infliximab (Remicade) and adalimumab (Humira) —
are on the market, and a third — certolizumab — is waiting in the
The medications have greatly improved the treatment of several
inflammatory conditions, including rheumatoid arthritis,
psoriatic arthritis, ankylosing spondylitis (a condition that
affects the spine and the sacroiliac joints), and Crohn's
disease, a bowel disorder. A combination of a TNF-alpha blocker
and methotrexate, a standard antirheumatic drug, is twice as
effective as methotrexate alone in the treatment of rheumatoid
arthritis. Sales of the TNF-alpha blockers have more than tripled
since 2002, according to IMS Health.
The TNF-alpha blockers have serious drawbacks: they're expensive
($10,000 to $25,000 annually per patient), can result in serious
infections, and have been linked to cancer, particularly
lymphoma. But by tackling inflammation at its roots, they may be
paving the way for a new approach to treating many diseases. In
2007, National Institutes of Health researchers proposed using
TNF-alpha inhibition to treat brain diseases with an inflammatory
component, such as Alzheimer's and Parkinson's disease.
7. Covering the uninsured
"Are we there yet?" children ask on car rides long before the
trip is over. Asking about progress toward universal health
insurance coverage in the United States can seem just as
premature — and headache-inducing.
Roughly 47 million people in the country — or about one in every
six — don't have health insurance. Fewer employers are offering
coverage to their employees (60% in 2006, down from 69% in 2000).
Cost is a major factor: since 2002, the price of health insurance
premiums has risen over 4� times faster than the inflation rate
(78% vs. 17%).
Are we there yet? Sometimes it seems like we're headed in the
But lawmakers are cobbling together solutions. Massachusetts
started implementing its groundbreaking plan in 2007 which
includes a requirement that all adults buy health insurance,
subsidies for those who can't afford premiums, and insurance
regulatory reforms. California and other states may follow suit
with similar schemes. The All Kids program in Illinois, paid for
entirely with state funds, offers coverage to all uninsured
children, with premiums priced on a sliding scale based on family
income. As of April 2007, 50,000 children were enrolled. Medicare
Part D has its problems, but it has been successful in extending
insurance coverage for prescription drugs. Now less than one in
every 10 seniors lacks drug coverage, compared with one in three
a few years ago.
The 2008 presidential election will undoubtedly politicize many
health care issues, including how to cover the uninsured (look
what happened to the vetoed State Children's Health Insurance
Program in 2007). But, as with long trips and many difficult
problems, progress is being made a step at a time.
8. Doing the right thing — and getting paid for it
2007 saw some progress toward rewarding doctors and hospitals for
the quality of the care they deliver, not just the quantity.
Medicare started paying doctors a bonus for reporting certain
quality measures, such as the percentage of their diabetic
patients with controlled blood pressure. The Geisinger Health
System in Pennsylvania grabbed headlines with its program, which
promises to meet 40 quality-of-care benchmarks in the care of
heart bypass patients — and by putting real money on the line by
agreeing not to charge for care related to complications that
occur within 90 days of surgery. Geisinger's math: Quality pays
for itself, and then some, by reducing complications. That's also
the calculation behind a new Medicare payment system scheduled to
go into effect in the fall of 2008 that won't pay hospitals for
treating several secondary conditions, such as bedsores,
considered to be preventable complications.
Drug companies are venturing into uncharted pay-for-performance
waters. When British health officials refused to cover the cost
of bortezomib (Velcade), an expensive cancer drug, the
manufacturer, Johnson & Johnson, offered not to charge for
the medication unless it produced a response. Devils lurk in the
details, most notably in defining what constitutes a response,
but performance-based payment could help rein in drug costs.
The Internet and consumer choice are major ingredients in this
push for quality. The hope is that the public will use
information posted on Web sites to seek out doctors and hospitals
that provide quality care — and avoid the ones that don't.
Private vendors got into this business some years ago, but the
federal government has a Web site, www.hospitalcompare.hhs.gov,
that makes it pretty easy to compare hospitals on 21 different
The worry: we'll get a superficial, "cookbook" version of
medicine, not real quality. In addition, some fear that doctors
and hospitals will have a new, perverse incentive to avoid
patients who are difficult to treat because they might drag down
marks on a quality-of-care report card.
9. A better mammogram?
For most women, mammograms do a good job of finding breast cancer
early. But no screening test is perfect, and the x-ray images of
the traditional mammogram miss some cancers.
Magnetic resonance imaging (MRI) scans provide extremely detailed
images of soft tissues. Two studies of high-risk women published
in 2007 compared breast MRIs with other screening tests —
including standard x-ray mammography, ultrasound, and clinical
breast exams — and found that MRI scans identified cancers the
other techniques missed. The MRIs were especially helpful in
women with dense breasts, which have more glandular and
connective tissue — and less fat — than normal.
The American Cancer Society revised its screening recommendations
to say that women at high risk for breast cancer should get a
breast MRI every year, in addition to a regular mammogram. This
high-risk group includes women who have a BRCA1 or BRCA2 breast
cancer gene mutation or whose first-degree relatives (parents,
siblings, children) do. The cancer society guidelines are part of
a long-term trend of increasingly complicated screening
protocols, tiered by risk group.
MRI scans won't replace conventional mammography any time soon.
Cost and access are major obstacles. In addition, the current
technology would generate too many false positives — finding
lumps that turn out not to be cancer and increasing the number of
unnecessary biopsies. The technology will probably improve,
though. Over the next few years, MRIs may become a major part of
breast screening programs, particularly for women with dense
10. Peeking into the brain
When doctors diagnose Alzheimer's disease, depression, and many
other conditions related to the brain, they have only symptoms to
go by. But with advances in imaging technology, researchers are
getting the brain to give up its secrets, and more direct tests
may soon be possible.
Functional magnetic resonance imaging (fMRI) scans are allowing
researchers to measure minute changes in brain activity.
Voltage-sensitive dyes can isolate specific brain circuits.
Positron emission tomography (PET) scans use radioactive tracers
and CT scanners to generate exquisitely detailed images of brain
University of Pittsburgh researchers have developed a PET tracer
— dubbed PIB, short for Pittsburgh Compound B — that labels beta
amyloid, the protein fragment that many Alzheimer's researchers
believe is the main cause of the disease.
Researchers are heralding PIB testing as a breakthrough. It could
— at last — provide a way to detect Alzheimer's disease before
symptoms appear. Treatments directed at reducing beta amyloid are
under development. If beta amyloid plaque could be found with PIB
testing, these medications might be given early in the disease,
before symptoms occur.
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