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 "appetite" hormone.
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 field.
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 commitment.
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 wings.
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 opposite direction.
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 quality measures.
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 breast tissue.
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 metabolism.
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.
As a service to our readers, Harvard Health Publishing provides access to our library of archived content. Please note the date of last review or update on all articles. No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician.