Pioneering Rare Disease Diagnostics in China—An Interview with Fudan Children’s Hospital Clinicians at ASHG17

wuxi-nextcode-fudan-university

The first year of WuXi NextCODE’s partnership with Fudan Children’s Hospital has delivered 11,000 clinical reports and a diagnosis rate of 33%, matching the throughput and success rate of the world’s leading laboratories.

One year ago, WuXi NextCODE (WXNC) and the Children’s Hospital of Fudan University (CHFU) launched a joint laboratory to put the global gold standard in sequence-based rare disease diagnostics at the service of patients in China. In the first year of that joint effort, the partnership delivered some 11,000 clinical reports—with more than 1,000 new reports now being generated each month—and a diagnosis rate of 33%. This matches the throughput and success rate of the leading laboratories in the world.

Dr Lin Yang of CHFU presented a summary of this remarkable progress at WXNC’s breakfast session on rare disease at the ASHG17 meeting held recently in Orlando. Afterwards, WXNC’s global communications lead, Edward Farmer, sat down to talk about this collaboration and what it means for patients, with Associate Professor and Laboratory Director Dr. Huijin Wang from the clinical team; Dr. Bing Bing Wu, director of the medical diagnostics laboratory; and Assistant Professor Dr Xinran Dong, who leads the bioinformatics team, as well as WXNC Chief Scientific Officer, Jeff Gulcher.

Edward Farmer: It’s a real pleasure to have with us our colleagues from Fudan and to be able to hear about this collaboration in rare disease diagnostics and genome-based testing in the neonatal unit. To start us off, Jeff, can you tell us how this partnership came about and how you see its importance to rare disease diagnostics in China and worldwide?

Jeff Gulcher: It’s been a fantastic partnership that started about two-and-a-half years ago, when we began discussing the possibility of creating a joint laboratory. The aim was to take advantage of WXNC’s technology and sequencing expertise together with Fudan’s expertise, both on the medical side and the interpretation side. The goal was to enable whole exome or medical exome sequencing of very sick children. In parallel, we decided to see if sequencing is useful in the neonatal ICU setting.

Through this partnership, we’ve now sequenced a large number of children and worked together to make diagnoses. Our medical genetics teams have worked closely together to interpret these cases, and in about one-third of the cases, we’ve been able to deliver diagnoses that were not suspected by the treating physician. In many cases, that has led to different treatments, with better outcomes for the children.

Together, we have now sequenced over 11,000 pediatric cases, including some 2,500 neonatal ICU cases, and we are very pleased with this partnership.

Edward Farmer: We have with us several senior people from Fudan. Huijin, let’s begin with you, as director of our joint laboratory. Can you share with us your impressions of this partnership so far and some of your results?

Huijin Wang: We have had a very good experience with this collaboration. We have many cases and, each week, we have a case meeting with the Cambridge WXNC team and we discuss the data and variant curation for the more difficult ones. The results have been impactful for the patients. In many cases, we can deliver a clinical diagnosis, and some of these offer real treatment options.

I remember one case that first came to the neurological clinic with seizures and hypoglycemia. This child had presented with recurrent hypoglycemia at a very early age and was in the NICU. We sequenced the family and found a recessive variant in the FBP1 gene, which the patient had inherited from both parents.

After this diagnosis, the doctor was able to discuss the problem with the family and advise them on how to limit the child’s diet to avoid hypoglycemia. The child is now doing well and no longer experiencing hypoglycemic episodes. And his family came back later and planned to have another child, and we referred them for prenatal diagnosis, and they were able to have another child who is healthy. This was a very successful case and is the sort of story that encourages us and shows us the value of the work we are doing.

Edward Farmer: That is an encouraging result. Lin, as an attending physician, how do you see the impact of introducing this technology into China at scale?

Lin Yang: We have more and more children at our hospital with birth defects or congenital malformations, so we really want to get a diagnosis and whatever possible treatment for them, including new treatments when available.

The collaboration between our hospital and WXNC starts with us deciding whether the case is likely to be the result of a genetic disorder. If it is, we do pre-testing counseling for the whole family before taking DNA samples. We then use WXNC’s capabilities for the sequencing and analysis of the results. Finally, we need to interpret the sequencing results and report them to the parents. It is often very difficult for parents to understand “what is a gene,” “what is a mutation,” “what is the disorder,” and “how can your child benefit from a molecular diagnosis?” So that is a critical part of our work.

But more and more patients are choosing molecular diagnosis and, if they get a correct diagnosis early, they may find a useful and more targeted treatment earlier.

In the NICU, we have some patients that have immune deficiency disorders. These can be very serious conditions, as the children suffer from repeated infections. It is very hard on the whole family. For such cases, if you have a specific diagnosis, there is often a cure. This is very good news for these families in the NICU, as they now have the possibility of getting a molecular diagnosis and then a treatment.

Edward Farmer: Are there any specific examples or cases that you can share with us?

Lin Yang: I had a newborn patient who had very low platelet counts and petachiae (red spots from small bleeds) on his face and body. We found that he has a mutation in the WAS gene, inherited from his mother’s side of the family, which means that his bone marrow is not producing enough platelets. But with a hematopoietic cell transplantation [HCT, which can include bone marrow] from a relative or closely matched donor, he has every chance of being cured of the disease and becoming a healthy boy. He is now waiting for a matched donor.

Edward Farmer: Huijin, you’ve done amazing work so far, and I know you are only getting started, but I wonder what proportion of the patients you see are able to benefit from the work of your lab and the collaboration with WXNC?

Huijin Wang: Currently, we are delivering a diagnosis to about 30% of patients, and we are able to recommend specific clinical treatment for about 20% of our patients.

And very often, we can give some guidance, if not a cure. Sometimes just knowing exactly what the diagnosis is gives patients peace of mind and new options. For example, many can go to a specialty clinic. But just knowing the diagnosis is often a comfort.

There is also a big need, and as a national center of excellence our diagnostics can help people across the country. About 80% of our patients come from outside of Shanghai, so with a diagnosis, they can go back to where they live and take some action there.

Lin Yang: There is also a difference among different diseases. I think we are now able to provide actionable results to about 50% of patients with neuromuscular disorders, and for respiratory maybe something less than that. For NICU, it’s maybe 15% that get a diagnosis, but we want to boost all of these.

We can benefit many more patients with this technology. In our hospital and with the WXNC collaboration, we can see an increasing number of patients. But there are a lot of undiagnosed patients, and in many places, there is not yet access to molecular diagnostics, so we hope this capability spreads to other parts of the country as well.

Edward Farmer: And Xinran, as we’re talking about building the scale and reach of molecular diagnostics, perhaps you can tell us a bit about how you are dealing with all of this data.

Xinran Dong: We have collected a lot of data. And from my bioinformatics perspective, one of the things that the WXNC collaboration is helping us to do is to make good use of the data, both for our clinical cases and for research.

I see part of my job as helping to build this into one of the biggest databases on rare disease in China and maybe the world. This is going to help patients today and advance the discovery of new genes.

Edward Farmer: Clearly there is no lack of ambition here. I want to thank you all for your time, and we look forward to sharing more stories of our work together.

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New Breast Cancer Study Underscores the Need for More Sequencing

Gene sequencing for breast cancer. More than the usual suspects at play.

Ever since actress Angelina Jolie’s highly publicized preventive mastectomy ignited discussion about BRCA 1 and BRCA2, almost everyone has heard about these genes and how they can increase risk of breast cancer.  Some people even refer to them as “the breast cancer genes.” But how genes cause this disease is much more complicated than just through the most well known BRCA mutations, as a recent study in JAMA of Ashkenazi Jewish women has demonstrated. http://jamanetwork.com/journals/jamaoncology/fullarticle/2644652

This intriguing study raises a crucial question: How much sequencing is enough when diagnosing breast cancer in the age of targeted therapies? The number of these therapies keeps growing, as does our knowledge of the links between what drugs work for women with particular mutations. But at what point should we say we have uncovered enough mutations to make a proper diagnosis? And in a field in which we know there’s a lot we don’t know, is there such a thing as enough?

The good thing is that sequencing costs are going down. “It used to be that just testing for a single gene cost several thousand dollars,” says Jim Lund, Director of Tumor Product Development at WuXi NextCODE.  “Now a panel of genes costs that and whole exome sequencing is slightly more.” At the same time, the number of mutations that are discovered and studied is increasing – in the genomes of patients and the genomes of their tumors.

The data here has a message about data itself: in principle, we should be generating as much sequencing data as possible. By generating it, storing it for vast numbers of patients and their healthy relatives, creating more comprehensive databases of all disease-linked variants, and then reanalyzing patient and tumor samples as more is learned, we can improve the risk assessment and the speed and accuracy of diagnosis for patients everywhere. Since we can do this, the question isn’t whether we can afford to do more sequencing, but why anyone would argue that we can afford not to.

The researchers who led the recent JAMA study used multiplex genomic sequencing on breast tumor samples from 1007 patients. They tested for a total of 23 known and candidate genes.  It has been well documented that women of Ashkenazi descent have a higher risk of breast and ovarian cancer, and that is at least in part because of three particular BRCA1 and BRCA2 mutations. These are called founder mutations, because they probably originated among some of the earliest members of this ethnic group, and have been propagated because of a strong history of marriage within the same community.

But the researchers working on this study wanted to know if there were mutations in other genes besides BRCA that made it more likely these particular women would develop breast cancer. The patients were from 12 major cancer centers; had a first diagnosis of invasive breast cancer; self-identified as having Ashkenazi Jewish ancestry; and had all participated in the New York Breast Cancer Study (NYBCS).

Surprisingly, only 104 of the patients were carrying one of the infamous founder alleles. Seven patients had non-founder mutations in BRCA1 or BRCA2, and 31 had mutations in other genes linked to increased risk of breast cancer, including CHEK2. The vast majority of these women carried none of the mutations that are “obvious suspects” for breast cancer. “We do not know why those women got breast cancer,” says Shannon T. Bailey, Associate Director of Cancer Genetics at WuXi NextCODE.

It’s important to note that thousands of different cancer-predisposing mutations have been found in BRCA1 and BRCA2 alone. Every population studied to date includes people with such mutations.  The three founder mutations that have been established as being common among Ashkenazis are estimated to account for about 10% of breast cancers in this group. The rest of BRCA1 and BRCA2 mutations are considered extremely rare under any circumstances.

“If you look at the genes on the panel used in this study, it looks as if they are mostly associated with DNA damage and there are no cell cycle regulating genes included,” says Bailey. “But there are all kinds of mutations that cause breast cancer, even in noncoding regulatory zones.” As a result, even the best designed panel may fall short.

That’s why this study is so important. It tells us that even with founder mutations, family history matters but it doesn’t yet always tell you everything you’d like to know. Of the women with the founder BRCA mutations, only about half had a mother or sister with breast or ovarian cancer.  It’s also already well known that just carrying a BRCA1 or BRCA2 mutation is no guarantee the patient will get cancer. For reasons we don’t yet understand, these mutations raise overall risk, but not everyone who carries one will develop the disease. So while BRCA mutations are important, we need lots more information about other genes too.

The authors of this JAMA report suggest that Ashkenazi patients with breast cancers should have “comprehensive sequencing,” including, perhaps, complete sequencing of BRCA1 and BRCA2 and possibly testing for other breast cancer genes as well.

And what about other patients?  WuXi NextCODE’s Lund points out that even the most highly regarded recommendations for breast cancer testing do not cite specific panels. Those recommendations come from the U.S. Government Task Force [https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/brca-related-cancer-risk-assessment-genetic-counseling-and-genetic-testing] and the NCCN Clinical Practice Guidelines. Women with a family history will likely get more comprehensive testing, but beyond that it is not clear exactly how to proceed in every case.

At WuXi NextCODE we believe that this is clear evidence pointing to the value of doing more sequencing across all ethnic groups – for healthy individuals, patients, and their tumors, and pushing towards sequencing as standard of care. This would expand our knowledge of the genetic risk factors for breast and other cancers; provide vast new cohorts for research; and deliver the most actionable insights to patients, from risk assessment through diagnosis and then ongoing as new discoveries are made.

All of the participants in this JAMA study consented to have their sequence data used to advance research. They are already helping to do that, and this is just one study of thousands that are now underway and that are helping us to expand our data- and knowledgebases with the ultimate aim of delivering even better outcomes for all people and patients everywhere.

FDA Approval Moves DTC Genetic Testing Forward

DTC genetic testing, Hannes Smarason

23andMe is relaunching its direct-to-consumer genetic tests in the U.S. with the approval of the FDA to provide consumers “carrier status” information on 36 genes that can cause rare diseases. I am optimistic that DTC genetic testing will expand its impact over time, ultimately having a tremendous impact on human health globally.

Today, genomics industry maverick, 23andMe, is relaunching its direct-to-consumer (DTC) genetic testing in the U.S., with the approval of the FDA to inform consumers whether they carry a genetic variant for one of 36 rare diseases that could potentially be passed on to their children. In addition to this carrier status information that now meets FDA standards, reports from the newly launched 23andMe test will include information on wellness, traits, and ancestry.

A big positive step forward

For the genomics industry as a whole, this is a significant step forward as the FDA’s decisions have global influence. Indeed, this is a landmark FDA decision, as it is the first time ever that the FDA has allowed such a broad spectrum of medically relevant genetic information to be provided directly to consumers. Both the FDA and 23andMe deserve credit for working through the challenges that, less than two years ago, resulted in the FDA ordering 23andMe to stop marketing its genetic testing kits in the U.S. That the FDA—one of the world’s most thoughtful medical regulatory agencies—has come so far so fast is indicative of the potential it likely sees in DTC genetic testing improving the health of U.S citizens.

A larger journey ahead for direct-to-consumer genetic testing

Moving forward, there are at least two important directions that—in collaboration with the appropriate regulatory agencies, such as the FDA—I think DTC genetic testing will advance:

• DTC genetic testing will expand its reach globally; and
• DTC genetic testing will likely expand the medical impact of its reported results.

DTC genetic testing will expand its reach globally.

Catalyzed by demand for improved health, DTC genetic testing services will inevitably become accessible to much of the world’s population over the decades to come. To be successful, these services will need to be customized by geography and culture and approved by the appropriate local governmental agencies. While the genome is shared by all humans, it is naïve to think that DTC genetic testing services will be the same across all people living anywhere. It is incumbent on industry participants to align their DTC reports and services to best meet the needs of the specific customers in specific countries and geographies—and to do so in a spirit of cooperation with the appropriate governmental health regulators.

DTC genetic testing will likely expand the medical impact of its reported results.

As noted, today’s FDA approval for 23andMe to be able report on carrier status is a significant step forward, but more health data remains to be gleaned—and reported—from an individual’s genomic data. From 23andMe’s announcement, you can see the foreshadowing of what may ultimately be possible:

About [23andMe’s] Carrier Status Tests
[23andMe’s tests] can be used to determine carrier status in adults from saliva collected using an FDA-cleared collection device (Oragene DX model OGD.500.001), but cannot determine if you have two copies of the genetic variant. Each test is most relevant for people of certain ethnicities. The tests are not intended to diagnose a disease, or tell you anything about your risk for developing a disease in the future. On their own, carrier status tests are not intended to tell you anything about the health of your fetus, or your newborn child’s risk of developing a particular disease later in life.

Clearly, working with regulators such as the FDA, and others, such as thoughtful genetic counselors, there is a future potential for the right service to be able to report on people’s risk for developing specific diseases. Informed, health-conscious consumers are very likely to demand access to this information—and millions of individuals have already paid significant sums out of their own pockets to have their genomes sequenced and analyzed. Indeed, from news reports covering 23andMe, we know that when ordered by the FDA to stop providing health information such as the disease risk, their rate of new customer sign-ups dropped by more than half.

I am very optimistic that DTC genetic testing will expand its impact over time, overcoming skepticism and ultimately having a tremendous impact on human health globally. I am proud that our team at WuXi NextCODE will be a part of making this exciting future happen, and today I am especially proud that WuXi Ventures recently invested in 23andMe, making us active supporters of its current and noteworthy success.

Genomics in Cancer: Continuing to Push the Leading Edge

genomics in cancer - hannes smarason

Genomics is helping to prevent and treat cancer at an accelerating rate, supporting the goal of oncologists to dramatically improve cancer patient outcomes.

The progress in the use of genomics to help prevent and treat cancer continues to grow at a pace that is impressive. Indeed, there is expanded use of genomics to drive patient care and improve outcomes across an ever-expanding number of cancers by a growing number of oncologists.

Genomic Knowledge Can Clearly Drive Better Care

Applying genomics to cancer treatment is a powerful clinical application, as genomics can provide a window into how to best treat a patient’s particular cancer as it:

  1. may help better understand the genetics of the tumor itself, and
  2. can provide insight into how cancerous tumors may grow and spread over time.

With a genomic-based approach to cancer care, oncologists can more personally tailor anti-cancer treatments to an individual tumor’s mutations, thus molecularly targeting the specific cancer’s Achilles heel. Already, there are well-documented successes of molecularly targeted anti-cancer agents, such as cancer drugs that target certain genes—HER2, EFGR, ALK, and others.

In 2015, the pace of adoption of genomics in clinical oncology has advanced significantly. Recent evidence of the accelerating use of genomics to help fight cancer includes:

  • Evolving from ‘why’ to ‘how’ to use genomics at leading cancer centers. At the top cancer care facilities, genomics has become part of the programmatic approach to provide certain cancer patients with optimal care—care that is fundamentally designed to lead to the best outcomes. The question for leading medical centers globally has evolved over the last few years from “do we need genomics?” to “for which cancer types and at what stages of cancer treatment and diagnosis can we best use genomic sequencing and analysis?”—an evolution from “why?” to “how?” at a very fundamental level. The accelerating use and deployment of genomics by leading medical facilities validates that they are deriving significant value from genomics, and that value is resulting ultimately in meaningfully advancing better care for cancer patients.
  • Expanding potential applications of genomics within different types of cancers, broadening the types of cancers and tumors that can potentially benefit from genomics. Researchers and clinicians continue to publish a wealth of information validating the potential of genomics to improve outcomes in certain types of cancer patients. In 2015 alone, highlights of these advancements include certain prostate cancers, brain cancers, rare types of pediatric kidney cancers, and even potential targets in certain non-small cell lung cancers.
  • Broadening acceptance in cancer prevention. Driven in part by the education of oncologists and physicians generally and in part by the empowerment of knowledgeable patients, people are seeking and benefiting from genetic tests that reveal their personal risk for certain tumors (such as BRCA for breast or ovarian cancers). 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 is—for certain individuals with specific family histories and genetics—driving appropriate medical decisions for patients who may be at high risk for certain cancers.
  • Powering clinical trials with genomics. The use of genomics in cancer clinical trials – whether for inclusion in data-gathering or even screening of patients—has gone from rare to commonplace over recent years, and is improving knowledge around the safety and efficacy of drugs in cancer and beyond. Two large-scale cancer trials have been initiated in 2015 with the bold goal of substantially advancing the understanding and use of genomics in cancer care. The anti-cancer treatments being tested in both trials were selected for their activity on a specific molecular target, independent of tumor location and histology. The two trials are actively enrolling and are (1) an American Society of Clinical Oncology (ASCO)-sponsored study, called TAPUR (Targeted Agent and Profiling Utilization Registry) and National Cancer Institute (NCI) and is called NCI-MATCH (Molecular Analysis for Therapy Choice). These trials and any subsequent follow-on trials will doubtless provide insightful information to drive the growing use of genomics in improving cancer care.

In summary, genomics is helping to prevent and treat cancer at an accelerating rate, supporting the goal of oncologists to dramatically improve cancer patient outcomes. There are at least four frontiers where we can see substantial progress in the use of genomics in cancer care, including expanded use in leading medical centers, increased potential applications within cancer, widespread acceptance in cancer prevention, and an increase in the use of genomics within clinical trials. I am personally committed to continue to drive and accelerate this genomic revolution to continue to bring true progress in improving cancer care to patients in need globally.

Trends in Sequencing and Analysis Today Leading to Tomorrow’s Clinical Advances

The insights we’re gaining from sequencing and analysis techniques are delivering new advances in healthcare with ever greater speed and precision.

The challenge for programs seeking to accelerate their research discoveries with genomic data is how to analyze the wealth of information—to make it clinically relevant and rapidly deliver reliable insights to better inform patient care.

The insights we’re gaining from sequencing and analysis techniques are delivering new advances in healthcare with ever greater speed and precision. It’s a particularly exciting time to be a part of this evolving industry, with continual opportunities for new clinical applications of these technologies and platforms.

Companies like Illumina and others who are delivering next-generation sequencing technologies are gaining global exposure. New partnerships and programs are placing these advanced techniques into the hands of the world’s leading clinicians and researchers, who are then applying them to some of today’s greatest medical challenges.  Recently, plans to integrate sequencing technologies have been announced by world renowned organizations like the Baylor College of Medicine in the U.S., Genomics England, and Sidra Medical and Research Center in Qatar.

The challenge for these and other programs seeking to accelerate their research discoveries with genomic data is how to analyze this wealth of information – to make it clinically relevant and rapidly deliver reliable insights to better inform patient care.

NextCODE Health is working to advance this piece of the puzzle with its Genomically Ordered Relational (GOR) database and its clinical and discovery interfaces (the Clinical Sequence Analyzer​™ and Sequence Miner™).  Combining next-generation sequencing techniques with increasingly robust analysis tools, NextCODE Health is helping to accelerate global research progress today to deliver unprecedented advances in patient care in the years just ahead.

Prime Targets for Whole Genome Sequencing: Cancer and Rare Diseases

genome sequencing cancer and rare genetic diseases

There’s a huge opportunity ahead for genome sequencing to impact human health, beginning with cancer and rare genetic diseases.

There 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

Lower-cost genome sequencing, genomic analysis tools support personalized medicine

Lower-cost genome sequencing, genomic analysis tools, and reference databases for human genomes are the “3-legged stool” that will help the world reach personalized medicine.

Genome 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.

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

Supreme Court BRCA gene patent

The unanimous decision by the Supreme Court Justices to strike down patent claims by Myriad Genetics on the BRCA gene 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.

Recently 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 decision

Angelina 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.

The 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.