Early Adopters of Sequencing in the Clinic

Hannes Smarason Early AdoptersIt is increasingly evident that sequencing and analyzing genomic information can contribute to more informed healthcare decisions, and major research institutions and medical centers around the world seem to agree.

Leaders in the medical community are actively enhancing their facilities with DNA sequencers and supercomputers, recognizing the efficiencies of having this advanced technology at their disposal for innovative research programs. And as they look to the future, they are taking steps toward the routine sequencing of patient genomes that will inform the full spectrum of care decisions, from defining risk, to diagnosing disease, to defining the ideal course of treatment for the best possible outcome.

Just a few examples of the major advances in the use of sequencing technologies that have been announced recently…

From medical centers:

  • Mount Sinai Medical Center in New York initiated a program in which 24,000 patients participate in a biobank to include their DNA sequence and research over their lifetimes. The program, called BioMe™, is among the largest in the United States.
  • Memorial Sloan-Kettering Cancer Center researchers are active in a range of collaborations that seek to understand the molecular changes that characterize cancer, the largest of which is The Cancer Genome Atlas (TCGA), a project jointly funded by the NCI and the National Human Genome Research Institute. MSK currently houses one of TCGA’s Genome Data Analysis Centers.
  • Phoenix Children’s Hospital launched a new molecular and personalized medicine research institute that will “bring genomics research to the forefront of pediatrics.” The infrastructure will include a range of capabilities, such as a biospecimen repository, DNA sequencing and analysis, and a CLIA lab for genomic profiling.

And research institutions:

  • The Wellcome Trust Sanger Institute is dramatically upgrading its storage and data management capacity.  The Institute already operates 30 DNA sequencers, each of which generates roughly a terabyte of data every day. New upgrades will double their capacity and improve data management and organization software.
  • Harvard Medical School’s Center for Biomedical Informatics, conducts informatics research with a strong emphasis on translational science informed by innovative computational strategies; the research staff use mathematical modeling to predict when genetic information could lead to more effective treatment.

By members of industry:

  • Google is jumping into the genomics industry with the launch of “Calico,” a new company that will focus on genomic sequencing and advanced analytics to identify solutions for some of the most challenging diseases today.
  • “N-of-One” is a company offering personalized cancer treatment strategies as a new employee benefit tool for innovative, health-minded employers. Through the service, the company provides interpretation of molecular profiling to employees, their family members fighting cancer and their physicians to help inform treatment decisions.

And even the U.S. government:

  • The National Institutes of Health is one of the greatest proponents of genomic sequencing for research purposes. In fact, a recently initiated program is funding research teams to examine whether sequencing newborn genomes or exomes may provide useful information beyond what is currently captured in newborn screening programs.
  • Further, in the fight against infectious diseases and “super-bugs,” the National Institute of Allergy and Infectious Diseases established the Genomic Sequencing Centers for Infectious Diseases (GSCID) to sequencing priority pathogens, microorganisms responsible for emerging and re-emerging infectious diseases and related organisms.

With such a broad array of innovative research underway within the halls of the world’s leading institutions, there is no doubt sequencing is on the verge of delivering exciting breakthroughs in medicine. In fact, we’re seeing evidence of this with NextCODE, which has engaged with several “early adopter” organizations around the globe.  Check it out here.

Prime Targets for Whole Genome Sequencing: Cancer and Rare Diseases

200296817-001There is a documented history of conditions classified as “diseases of unknown origin”—in these cases, the biological mechanisms that led to the disease are simply unknown or have not yet been discovered. Yet as we learn more every day, certain diseases have clear links to underlying genetic mutations. As such, analyzing the genome sequence of a patient diagnosed with one of these diseases might help lead to a better understanding of the disease etiology and potential treatment strategies, particularly in the areas of cancer and rare genetic disorders.

Preventing cancer

While cancers have a range of causes and correlations, many have a set of genetic mutations that drive malignant growth. Recent advances have already introduced sequencing to the cancer category, as cancer patients are benefiting from genetic tests that reveal their personal risk for certain tumors (such as BRCA for breast cancer).  Recently, evidence has suggested that certain genetic mutations could be responsible for the development of a wide range of tumor types (see the recent study in Nature, for example). These findings support the idea of using genomic analysis to predict an individual’s cancer risk, by comparing their genome with databases of confirmed genetic mutations linked to disease.

Treating Cancer

In addition, genomic sequencing and analysis may help better understand the genetics of the tumor itself, and can provide explanations for how tumors evolve over time. Tests are increasingly available today that can help predict a tumor’s response to a specific type of treatment. With a genomic-based approach to cancer care, researchers expect that treatment will evolve to be more tailored to an individual tumor’s mutations and, eventually, through drugs that can attack several targeted gene mutations at once. Already we’ve seen evidence of this in certain areas, such as breast cancer drugs intended for use only in patients who test positive for the HER2 gene.

 Identifying Rare Diseases

Rare diseases are another area of significant opportunity for improved diagnosis and treatment through the use of genomics.  Every year there are new cases of children with “unknown” diseases, many of which are likely related to a hereditary genetic disorder. These children and their families often spend years undergoing testing and experimental treatments for a wide range of diseases to attempt to properly diagnose and treat them, usually accompanied by a very high financial and emotional burden.

There is a hope that by offering whole genome sequencing to patients with a suspected rare genetic disease, mutations that might be causing the disease may be identified, and thus correct treatment can be employed much earlier to eliminate the burden of a long-term diagnostic and treatment odyssey.

Cancer and rare genetic diseases are just the start.  There’s a huge opportunity ahead for genome sequencing to impact human health, and personalized medicine may be just on the horizon.  In fact, we are focusing on just these areas with NextCODE, the newly launched company I’ve founded. The improvements brought about by the genomics industry, with the help of the technologies and services offered at NextCODE, will provide enormous value to patients, doctors, and the health care system as a whole.

The Technologies That are Key to Unlocking Genome Analysis

The technologies that are key to enabling personalized medicineGenome sequencing technology available today can accurately sequence a whole genome from an individual’s test sample for a surprisingly low cost—a few thousand dollars (and dropping fast). As a result, the adoption of this technology is rapidly expanding as medical centers around the world embrace its utility in informing healthcare decisions—an emerging reality of personalized medicine.

Three important areas of technology progress have enabled the medical community to reach this point:

  1. Lower-Cost Genome Sequencing: Major technological advances have reduced the cost of sequencing to nearly $1,000 or less, a critical milestone to enable the use of sequencing as a mass-market product for medical care.
  2. Genomic Analysis Tools: Since the human genome was first sequenced more than a decade ago, an increasingly robust body of research has showcased the links between mutations identified in the genome and disease risk. Informatics tools have been developed by medical centers and genomics companies to apply to whole-genome samples. Increasingly, these genome analysis tools will need to adapt to the steady pace of new genomic linkages to disease and to operate at a level approaching “big data.”
  3. Reference Databases for Human Genomes: There are a growing number of robust databases of human genomes, including data for healthy people or those with certain diseases.  When properly analyzed, these databases offer the potential to provide the medical community with a reference library against which to compare genetic data. Large-scale, high-quality databases are an essential element to cross-reference a patient genome to guide more informed medical decisions.

These three technology domains represent the “3-legged stool” that will help the world reach personalized medicine. The technology is in place, and the corresponding insights and uses are expanding every day. Yet there are challenges to be resolved before implementing these tools on a universal basis.

For example, logistically, how will new DNA and supercomputing equipment be accessed by medical centers, and how will the data be stored? And more importantly, what is the most efficient way to compare an individual’s genome to the massive body of genomic information available to help inform medical decisions for that patient?

One important part of the solution: we must turn to “big data” solutions to manage and make use of the enormous amounts of data produced through sequencing. The whole-genome sequence of a single human is roughly 100GB—that’s the entire storage capacity of a single Macbook Air®.

The progress to date has been amazing. Yet the opportunities ahead are even more extraordinary to improve the speed, accuracy, and accessibility of genomic information to improve human health.

Personalized Medicine: The Future is Almost Here

genome-sequencing-interpretation-databasesIt’s been more than a decade since the human genome was first sequenced. Since then, we have been on the journey of applying this profound new discovery to create personalized medicine and advance human health.

Two significant triumphs along this human genome journey:

  • Using genomic data to better understand diseases; and
  • Achieving low-cost genome sequencing.

Each of these accomplishments has been a stepping stone into the exciting new era that is dawning now: where genomic information is becoming integrated into medical care.

Using Genomic Data to Better Understand Diseases

Let’s take a look back at the early days of using genomic data to connect the dots between genetic mutations and disease. From 1997-2004, I was part of the leadership team at deCODE, the Icelandic genomic company. This was the period when deCODE was building the world’s most productive human genomics platform, with a database of  tens of thousands of individuals who participated in genetic studies and including the largest database of genomes to this day. deCODE’s genomic engine was able to successfully identify the genetic variations associated with human disease. This resulted in dozens of groundbreaking discoveries that were published in major, peer-reviewed journals.

The legacy of deCODE was the creation of an industrialized platform capable of massive storage and analysis capabilities. This enabled researchers to crunch genomic data to gain insights about genetic variants, or risk factors, associated with many common diseases. deCODE’s premise was that once the genetics of disease was better understood that information could be used to create new ways to diagnose, treat and prevent disease. However, when I left deCODE in 2004, there were still barriers to overcome before this genomic information could be widely applied to the level of an individual patient. Chief among them was that the cost of genome sequencing was still prohibitively high. (deCODE was subsequently acquired by Amgen).

Achieving Low-Cost Genome Sequencing

Back in 2004, the cost to sequence a single human genome was hundreds of thousands of dollars. Today that cost is a few thousand dollars (and, in fact, fast approaching $1,000) for a whole genome sequence. DNA sequencing costs continue to fall, as speed and accuracy increase.

This means we are rapidly approaching a tipping point where, as the sequencing of human genomes becomes more economical, its adoption in the medical community becomes more widespread and genomic data can become more routine in medical care. This is why personalized medicine is becoming a reality.

The Era of Genome Sequencing in Medical Care

The steep drop in the costs of sequencing, combined with the explosion of research on gene variants and disease, mean the time is fast approaching when genome sequencing will become routine in medical care. Today, pathologists perform blood cultures to decide which antibiotics will stop a patient’s bacterial infection. Soon a patient sample can be taken to perform a genome sequencing to analyze the genetic characteristics of a patient to determine ways a disease can be prevented or, if they are sick, which treatments might work best for their disease.

The body of genomic knowledge and the large databank of human genomes built by pioneers like deCODE established the key building blocks that enable genome sequencing to have predictive power for individual patients. As more human genomes are sequenced and more genetic variants are associated with disease, the predictive power of knowing about risk genes and effective treatments for each patient – a.k.a. personalized medicine – will become an essential part of medical care.

Genome Sequencing Being Implemented by Medical Centers

In preparation for the future of personalized medicine, major medical centers in the U.S., Europe and Asia are actively beginning to install DNA sequencers and supercomputers as important tools for integrating genome sequencing into medical care. These medical centers are taking initial steps toward the routine sequencing of every patient’s genome to define the ideal course of prevention and treatment based on variants found in a patient’s genes.

Evidence of this adoption of genome sequencing by medical centers appeared in an article in The New York Times in April 2013 citing that:

  • Medical centers in New York City are spending more than $1 billion on new genomic research centers;
  • Several hospitals around the U.S. are undertaking systematic genome sequencing in patients;
  • Mount Sinai Medical Center has a program in which 24,000 patients participate in a biobank to include their DNA sequence and research over their lifetimes;
  • Memorial Sloan-Kettering Cancer Center sequenced 16,000 tumors from cancer patients in 2012; and
  • Phoenix Children’s Hospital opened a new institute in December 2012 to sequence the genomes of 30 percent of their childhood cancer patients.

For now, the use of whole genome sequencing in medical practice is still in its infancy, but the pace of progress continues to accelerate. Clearly, genome sequencing will soon become part of the nucleus of medical care. This will herald a new era in personalized medicine revolutionizing healthcare as we know it and transforming our lives. When do you think genome sequencing will become a part of the medical decisions in your life?

Myriad and the Supreme Court: A Battle of Ownership in the Field of Genetic Testing

Supreme Court Myriad DecisionRecently the Supreme Court struck down patent claims by Myriad Genetics on the BRCA gene. The Court ruled that while synthetically produced DNA may be patentable, isolated genomic DNA (gDNA), discovered in nature and separated from its environment in the cell, is not patent-eligible.

The unanimous decision by the Supreme Court Justices has significant implications for patients, physicians, and the health care and life sciences industries. In many ways, this is a milestone that will greatly shape the future of the genetic testing industry and, in fact, accelerate progress toward the use of whole-genome sequencing for patients well beyond breast cancer.

Within a day of the Court’s verdict, 10 companies announced their intention to compete with Myriad—and more are sure to follow, as BRCA has proven to be a very relevant gene for assessing risk levels, disease targets, and potential treatments.

While this industry flurry illustrates the potentially significant commercial opportunity here, the greater implication is that the landscape is beginning to shift toward sequence analysis on a genome-wide basis rather than on individual gene testing.

Because fundamentally, the gene-by-gene approach to genetic testing that would be necessary if individual companies had patents on certain genetic tests is un-economical and wasteful, compared with the scope of knowledge and insights to be gained from a whole-genome sequencing analysis. As evidenced by Myriad’s recent announcements to abandon individual BRCA testing by 2014, it seems they also acknowledge this trend.

Ultimately, then, the future of competition in genetic testing will be driven by the ever-improving tools for sequencing, managing genomic data, and manipulating large data sets—and not simply by patents on DNA sequences discovered in nature.

Angelina Jolie: Genetic Testing in the Mainstream Spotlight

Angelina Jolie Genetic Testing Hannes SmarasonThe May 14 New York Times featured an op-ed from recognized actress Angelina Jolie, entitled “My Medical Choice.” The piece recapped why she had her genes sequenced, and why she made the decision to undergo prophylactic bilateral mastectomy upon finding that she carried a very high-risk mutation in her BRCA gene. That mutation gave her a high likelihood of getting the same type of cancer that killed her mother.

Ms. Jolie is perhaps the first highly visible public figure to “endorse” the idea of gene screening and make a very personal, radical medical decision as a result. Her decision is a poignant example of the recent trend toward consumer-driven healthcare, wherein consumers take on a partnership role with their doctor in making major decisions, informed by science, which will greatly impact their future.

This trend will only accelerate as more technologies like whole genome sequencing are developed to aid in the decision-making process. As consumers gain increased access to medical information, they are more proactively seeking solutions that work for their personal circumstances.

The challenge for all of us in the health care industry is to embrace this empowered patient—and to work with them to ensure that they are part of making the best decision for their individual situation.  Embracing patient empowerment implies new attitudes for physicians and health care providers, as well as new economic considerations for hospitals, insurance companies, and service providers.

It should be noted that Jolie was among the minority of the population who can currently afford to seek the data, information, and counsel she needed to help her make her medical choices based on her established family risks.

However, as technology evolves and expanded uses for genetic testing helps to drive industry-wide economies of scale, these types of tests will become more broadly available to everyone. Ultimately, these tests and the medical care that they enable will become a routine part of mainstream care for all.