The expectation was that this single reference map
of the 3 billion base pairs of DNA — the human genetic code — would quickly unlock the secrets of Alzheimer's, diabetes, cancer
and other scourges of human health.
As it turns out, Clinton's forecast was not unlike President George
Bush's "mission accomplished" speech in the early days of the Iraq
war, said Dr. Eric Topol of Scripps Translational Science Institute,
which is running a meeting On the Future of Genomic Medicine here
Thirteen years after Clinton's forecast, even Venter acknowledges
that mapping the human genome has had little clinical impact. "Yes,
there's been progress, but we all would have hoped it would have
been more rapid," he said in an interview in his offices this week.
But that is finally changing.
"We are at an inflection point," said Collins, who now directs the
National Institutes of Health. In a telephone interview, he said he
never expected an "overnight, dramatic impact" from sequencing the
human genome, in part because of cost.
Recently, a combination of lower-cost sequencing technology and a
growing list of wins in narrow corners of medicine are starting to
show that genomic medicine is on the verge of delivering on at least
some of those early claims.
Recent advances in sequencing have been "pretty stunning" and
genomics is "just on the threshold" of delivering results, Venter
Although much is left to be learned about the genome, scientists
believe knowing a person's genetic code will lead to highly
personalized treatments for cancer, better predictions for diseases
in babies and help unlock the puzzle of mysterious genetic diseases
that currently go undiagnosed and untreated.
Venter is staking his latest entrepreneurial venture on that
expectation. Earlier this week, he announced formation of a new
company, Human Longevity Inc., to undertake a massive project:
sequencing 40,000 human genomes a year in a search for new therapies
to preserve health and fight off diseases, including cancer, heart
disease and Alzheimer's.
To do that, Human Longevity will use two HiSeq X Ten machines and
has an option to buy three more. The sequencers, made by Illumina
Inc., can map a single genome for as little as $1,000.
Collins' government-funded Human Genome Project spent $3 billion and
took 13 years to sequence the human genome.
Breaching the $1,000 genome could prove to be a watershed. At that
cost, said Illumina Chief Executive Jay Flatley, ambitious projects
like Venter's are economically feasible and clinical results more
"We've still only scratched the surface of what the genome holds,"
he said. "What we need to do now is get hundreds of thousands to
millions of genomes in databases with clinical information," he
MAKING A DIFFERENCE
Advances in sequencing equipment and the advent of next-generation
sequencing has transformed the work Dr. Elizabeth McNally does as
director of the Cardiovascular Genetics Clinic at the University of
In seven short years, she said, her group has gone from testing just
one gene at a time to testing 60 to 70 genes and she is moving
quickly into whole genome sequencing.
McNally points to the case of Jeanne Sambrookes — a patient who is
alive today because of these advances.
As a child, Sambrookes often noticed the distinct, hunched posture
of her mother, her aunt and her grandmother as they struggled to
climb a flight of stairs.
Sambrookes had been very athletic as a young teen, but as she
matured, she noticed a heaviness in her legs. By age 20, running
left her tired. At 40, she needed a pacemaker, just like her mother
did at that age.
"I started thinking there is something to this," said Sambrookes,
now 56, who lives in Michigan City, Indiana.
After some dead ends, she found McNally, who cast a wide net,
testing for more than two dozen genes that could account for
Sambrookes' heart and muscle problems.
The culprit turned out to be a mutation in a gene called Lamin that
causes Limb-girdle muscular dystrophy. The disease can cause
weakness and wasting of the muscles between the shoulders and knees.
The mutation can also cause electrical disturbances of the heart.
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McNally recommended Sambrookes replace her pacemaker with an
implantable cardiac defibrillator that could protect against sudden
That proved to be the right call. Last August, Sambrookes' heart
stopped three times. Each time, the defibrillator shocked her back
"She literally tried to die three times," McNally recalls of her
patient. "It still takes my breath away."
Although McNally uses panels of 70 to 80 genes in her clinic, she
has started experimenting with whole genomes. With the reduced cost
of gene mapping, whole gene sequencing is a potentially cheaper,
more powerful tool.
The reduced cost of mapping is cutting the cost of research, too — another factor that could speed clinical outcomes. McNally's team
recently published a paper in the journal Bioinformatics in which
she used Beagle, a supercomputer housed at Argonne National
Laboratory, to analyze 240 full genomes in about two days. Such an
endeavor normally takes months.
"That dramatically decreases the cost associated with analysis
because we sped up the time," said McNally.
CORNERS OF MEDICINE
Dr. Jay Shendure, associate professor of Genome Sciences at the
University of Washington in Seattle, said the impact of gene
sequencing is beginning to emerge in specific areas — after a
startup period that was longer and narrower than expected.
"I do think there are these corners of medicine, which are important
ones, that may happen relatively quickly," he said.
A key example is the use of a pregnant woman's blood to see if
her fetus may have trisomies — chromosomal abnormalities associated
with Down syndrome and other disorders.
"Almost overnight, sequencing is in the process of taking over as
the primary means of screening for trisomies in at-risk populations,
and maybe eventually to everyone," Shendure said.
The clinical results are promising. A trial of Illumina's test
published last week in the New England Journal of Medicine found
about 3.6 percent of standard tests for trisomies had false positive
results, compared with 0.3 percent with Illumina's Verify test.
That means fewer women would need to go through invasive follow-up
diagnostic tests using amniocentesis or chorionic villus sampling,
both of which can cause miscarriages.
If the tests become routine practice, Goldman Sachs analyst Issac
Ro estimates the market could reach $6 billion a year.
Venter's new company, Human Longevity, has picked cancer as its
first sequencing target. Working with the University of California,
San Diego, the company plans to sequence the genomes, as well as the
tumors, of every cancer patient treated at UCSD's Moores Cancer
Collins calls cancer a "disease of the genome" and notes that
genomics has revealed cancer to be a collection of different
mutations, all of which contribute to its growth.
Drug companies have responded with treatments that block aberrant
pathways, an approach called precision medicine.
"That's happened pretty quickly because of this window that DNA
sequencing has provided," said Collins.
(Reporting by Julie Steenhuysen; editing
by David Greising and Dan Grebler)
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