In our era of
instant gratification, the world of medicine seems like an outlier. The
path from a promising discovery to an effective treatment often takes a
decade or more.
But from that process—of fits and
starts, progress and setbacks and finally more progress—grow the
insights and advances that change the course of medicine.
A decade ago, the completion of the
Human Genome Project sparked optimism that cures for debilitating
diseases were just around the corner. Cures still generally elude us,
but now the ability to map human DNA cheaply and quickly is yielding a
torrent of data about the genetic drivers of disease—and a steady stream
of patients who are benefiting from the knowledge. On other fronts,
technology is putting more power in the hands of patients, and
researchers are learning to combat disorders by harnessing the body's
own ability to heal and grow.
bring other challenges, including how to pay for them. Meanwhile, the
complex biology that stymies gains for some patients sets goals for new
Here are six of today's potentially transformative trends.
Growing a Heart
Boston Children's Hospital have developed a way to help children born
with half a heart to essentially grow a whole one—by marshaling the
body's natural capacity to heal and develop.
About 1,000 babies are born in the U.S.
each year with a condition called hypoplastic left-heart syndrome, the
result of a genetic anomaly that leaves them without a functioning left
ventricle, the heart's main pumping chamber. Without a surgical repair,
the defect is almost always fatal.
standard treatment is a series of three open-heart operations to reroute
circulation so that the right ventricle can take over pumping blood to
the body's organs and extremities. But the right ventricle "is meant to
handle low-pressure blood flow to the lungs," says Sitaram Emani, the
surgeon heading the effort on the new approach. "Now you're asking it to
do the work of a high-pressure system and to do that work for many
years. Eventually it fails." That's one reason why 30% of patients or
more don't survive to adulthood.
Dr. Emani and his colleagues devised a
complex strategy to open obstructed valves and repair other
malformations to direct blood flow to the left ventricle instead of away
from it. That triggers biological processes that promote the heart's
Last month, after using the approach on
34 carefully selected patients over the past decade, the doctors
reported in the Journal of the American College of Cardiology that 12
now have two working ventricles. One of them, 9-year-old Alexa Rand of
Kings Park, N.Y., whose treatments began in utero, is thriving. She
sings, dances and surprises doctors with how long she can walk on a
treadmill, says her mother, Rosamaria Rand.
The main drawback: The strategy
requires one more surgical procedure, on average, and significantly more
days in the hospital than the conventional surgery. The hope is, Dr.
Emani says, that the long-term benefits will outweigh the extra hospital
DNA Sequencing for Routine Checkups
a genetics conference in November, Oxford Nanopore Technologies
unveiled the first of a generation of tiny DNA sequencing devices that
many predict will eventually be as ubiquitous as cellphones—it's already
the size of one.
Since the first sequencing of the human
genome was completed in 2003 at a price tag of over $2 billion, the
speed, price and accuracy of the technology have all improved. Illumina
has dropped its price for individual readouts to $5,000; earlier this
year, Life Technologies introduced a sequencer it says can map the human
genome for $1,000. The smallest machine is now desktop-size.
nanopore sequencing devices, which are designed to be even smaller and
more affordable, could speed efforts to make gene sequencing a routine
part of a visit to the doctor's office. DNA molecules are exceedingly
long and complicated; that makes them hard to read. Nanopore technology
measures changes in the molecules' electrical current as the DNA is
threaded in a single strand through tiny holes called "nanopores"
created in a membrane.
So far, U.K.-based Oxford has released
the results of sequencing a virus genome with this technique. The
company hasn't provided data, however, showing that the sequencers can
analyze the much larger human genome. A spokeswoman for Oxford says the
company is working hard toward being able to sell devices, including one
that is expected to cost under $1,000, though it doesn't yet have a
Amit Meller—an associate professor at Boston University,
a scientific adviser at Oxford and the co-founder of Noblegen
Biosciences—is at work on another nanopore device that he says would use
fluorescent signals to read the DNA information. His company is still a
number of years away from a prototype, but Dr. Meller says the goal is
to speed up sequencing even more—with results in a few hours, not the
current weeks or days, at a cost of less than $100.
—Amy Dockser Marcus
Matching a Tumor to a Drug
growing understanding of the workings of the human genome is posing a
new challenge: How to use that data to change the course of disease.
Consider cancer. As seen through a gene-sequencing machine, some cancers
can appear as at least a dozen different genetic diseases, some of
which have been shown to respond uniquely to a specific drug. But how do
cancer doctors quickly match a patient's tumor with a drug that targets
One answer is a
test developed by Foundation Medicine Inc., a Cambridge, Mass., startup
whose scientific founders include one of the leaders of the Human
Genome Project. The test, officially launched last June, enables doctors
to test a tumor sample for 280 different genetic mutations suspected of
driving tumor growth.
This changes "everything in terms of
how we approach patients with cancer," says David Spigel, director of
lung-cancer research at the Sarah Cannon Research Institute in
Nashville, Tenn. He used the test in one patient with advanced disease
and few apparent options. She turned out positive for an alteration in a
gene targeted by several drugs currently in development. She was signed
up for one of the studies. A short time later, "she's like a new
person," he says. "She's off pain medicines. She gained her weight
Michael Pellini, Foundation's chief executive officer,
says that more than 600 oncologists have requested the test, which lists
for $5,800. So far, he says, about 70% of cases have turned up a
mutation that is potentially targeted by a drug on the market or in a
In one recent case, Dr. Pellini says, a
sample from a woman with advanced pancreatic cancer yielded a response
for "her2," an alteration associated with a certain form of breast
cancer. She was treated and her cancer responded to the breast-cancer
drug Herceptin. Few oncologists would think to look for her2 in a
patient with pancreatic cancer, he says.
Letting Your Body Fight Cancer
Few advances in cancer care are generating more enthusiasm than harnessing the power of the immune system to fight the disease.
Tom Stutz is one reason why. Last April, the 72-year-old
retired lawyer was confined to a wheelchair, struggling for every
breath, and required help with simple tasks such as eating, all because
of a previously diagnosed skin cancer that had spread to his lungs and
liver. "I was ready to check out, to be honest," he says.
That month, he began taking an
experimental drug known as MK3475. Six weeks later, he started feeling
better. Today, Mr. Stutz has jettisoned the wheelchair and regularly
walks a 3.5-mile loop near his home in Los Angeles. "I feel terrific,"
says Mr. Stutz, who learned after a checkup in the fall that his tumors
had shrunk by about 65% so far.
For decades, cancer researchers have
wondered why the immune system typically doesn't treat tumor cells as
invaders and target them. Part of the mystery was recently solved:
Tumors protect themselves by hijacking the body's natural brake for the
MK3475, being developed by Merck &
Co., is among a new category of drugs that release the brake, unleashing
an army of immune cells to hunt down the cancer. A recent report from a
trial in which Mr. Stutz participated said that of 85 patients who took
the drug, 51% saw their tumors significantly shrink; in eight cases,
the tumors couldn't be detected on imaging tests.
Still, not everyone was helped. And
unleashing the immune system can put normal cells in harm's way: In
studies of MK3745 and similar drugs, some patients developed serious
side effects related to immune-system response, including a small number
But interest in the approach is strong. Bristol-Myers Squibb
drug Yervoy, approved by the Food and Drug Administration in 2011, is
the first of its kind to reach the market. The company has others in
PLC and AstraZeneca
MedImmune are among others exploring ways to activate the immune system against cancer.
reason for the excitement is that most "solid" tumors—colon, lung,
breast, prostate—use the same or a similar mechanism to hide from the
immune system. Obstructing that mechanism may have a broad impact across
a variety of malignancies.
Health in the Palm of Your Hand
a good chance that you already own one of the most ubiquitous
health-care innovations: a smartphone. Last month, the FDA cleared a new
iPhone add-on that lets doctors take an electrocardiogram just about
anywhere. Other smartphone apps help radiologists read medical images
and allow patients to track moles for signs of skin cancer.
"I see the smartphone as one piece of
how we're going to try to get health costs under control," says David
Albert, the Oklahoma City-based inventor of the just-approved AliveCor
At $199, AliveCor consists of a case
that snaps onto the iPhone, with electrodes on the back. It reads heart
rhythms and relays the recording to an iPhone app, allowing physicians
to read the data. Dr. Albert says a $99 version should be available soon
that will let patients capture their own heart data, documenting
sometimes-fleeting arrhythmias when they feel symptoms or tracking the
success of lifestyle changes at curbing heart troubles.
Doctors say that mainstream EKG
machines provide more information but the iPhone version is sufficient
for many diagnostic needs. "When I go to [the] clinic, I use it in place
of an EKG all the time," says Leslie Saxon, chief of the University of
Southern California's heart-rhythm department, which has conducted
research using AliveCor's device.
The FDA has cleared a handful of apps,
beginning with an iPad and iPhone-based medical imaging reader in 2011.
The smartphone lets us "bring health care into the home," says Erik
Douglas, CEO of CellScope. His company is developing an iPhone-based
otoscope that would allow parents to upload images of their children's
inner ears when they show signs of infections, with the aim of avoiding
unnecessary doctors visits.
Rejigging Your Genes
years of controversy, gene therapy is poised to become a viable option
for a variety of often life-threatening medical conditions, especially
those resulting from a single defective gene. Last month, the European
Union approved Glybera for treatment of a rare genetic disease, making
it the first gene-therapy medicine approved in the Western world. The
approval comes amid a flurry of research showing broader promise for the
approach in a range of disorders, from a rare form of blindness to
hemophilia to heart failure.
Though outright cures are still
elusive, gene therapy "is beginning to emerge as a meaningful clinical"
strategy, says Stephen J. Russell, director of molecular medicine at the
Mayo Clinic in Rochester, Minn.
Gene therapy's tantalizing attraction
is that a single treatment has the potential to cure lethal diseases by
enabling normal genes to take over for defective ones. The treatment
involves loading a functional gene onto a fragment of a deactivated
virus that transports the gene to a cell's nucleus, where it is intended
to take over.
The idea suffered major setbacks in
1999 when a U.S. teenager died in a gene-therapy trial and again soon
after when several children in Europe developed leukemia after receiving
The episodes prompted criticism that
researchers had moved too quickly. Scientists returned to the
laboratory, hoping to develop better delivery vehicles and to improve
both the safety and efficacy of the treatments.
Bluebird Bio, a Cambridge, Mass.,
gene-therapy startup, expects to launch studies next year for two rare
genetic diseases: childhood adrenoleukodystrophy, or ALD, an inherited
and lethal neurological disorder; and beta thallasemia, which causes the
destruction of red blood cells and leads to life-threatening anemia.
Its technique involves extracting a patient's own bone-marrow cells,
isolating certain stem cells, and delivering the gene therapy before
returning the cells to the body.
Four boys in Paris with ALD have been
successfully treated, says Nick Leschly, Bluebird's president and chief
executive officer, including two treated nearly six years ago. They are
now in their teens and would otherwise likely have died before age 10,
Other gene-therapy efforts include Novartis
partnership with the University of Pennsylvania on a treatment for
cancer, GlaxoSmithKline's alliance with Italian scientists for a range
of disorders, and Celedon Corp.'s clinical trial of a gene therapy in
patients with advanced heart failure.
A version of this article appeared December
29, 2012, on page C2 in the U.S. edition of The Wall Street Journal,
with the headline: No Headline Available.