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The dawning of the age of genomic medicine, finally
By Julie Steenhuysen
16 hours ago
Craig Venter (R) speaks with Eric Topol, Scripps Health chief academic officer and director of the Scripps …
By Julie Steenhuysen
LA JOLLA,
California (Reuters) - When President Bill Clinton announced in 2000
that Craig Venter and Dr. Francis Collins of the National Human Genome
Research Institute had succeeded in mapping the human genome, he
solemnly declared that the discovery would "revolutionize" the treatment
of virtually all human disease.
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 March 6-7.
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.
"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 told Reuters.
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.
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 achievable.
"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 added.
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 Chicago.
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.
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.
McNally recommended Sambrookes replace her pacemaker with an
implantable cardiac defibrillator that could protect against sudden
cardiac death.
That proved to be the right call. Last August, Sambrookes'
heart stopped three times. Each time, the defibrillator shocked her back
to life.
"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 Center.
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)
