Human Genome Sequencing Affordable, but Practical?

SAN FRANCISCO – The cost of sequencing one person’s genome has shrunk from nearly $3 billion 14 years ago to an anticipated $1,000 within the next year or two, a development that positions human genome sequencing to explode into widespread use by researchers and clinicians.

Or maybe not, depending in part on recommendations to President Obama from the Presidential Commission for the Study of Bioethical Issues, which will submit a report on the topic later this year. In preparation, the Commission conducted a day-long public discussion with multiple experts about the potential for medical discoveries from genome research, and the difficulties of protecting patient privacy.

Photos: Sherry Boschert/Elsevier Global Medical News

Excitement in some quarters about the already proven ability to diagnose rare disorders via genome sequencing has been tempered by concerns that the field may be moving too fast for the general good. The ability to collect genome data far exceeds the ability to interpret the data. And the growing use of such tests threatens to bankrupt the medical system if it leads to an avalanche of tests for the worried well and untreatable disorders.

Currently, physicians can order sequencing of an individual’s whole exome (all the expressed genes) or whole genome from a few centers on a very limited basis. Approximately 10,000 people had their genomes sequenced in 2011. Perhaps 100,000 will do the same in 2012, estimated Dr. Richard A. Gibbs, director of the Human Genome Sequencing Center at Baylor College of Medicine, Houston.

While many stakeholders emphasize the importance of free and unrestricted release of human genome data to all researchers, others argue that such open access would also allow third parties to manipulate data to deny individuals insurance or employment, he said. The race is on to try to understand genome data better before uninformed interpreters can do their damage. But clearly, having access to lots of genome data is key to advancing the science, he said.

"Less than 1% of the American public understands" genetics, opening the door to manipulation, said Commission Chair Amy Gutmann, Ph.D., president of the University of Pennsylvania, Philadelphia. "There’s a snake oil salesman out there for everything."

Benefits of Unrestricted Access

Among those arguing in favor of the unrestricted access to human genome data to all researchers is Retta Beery. The Baylor center helped diagnose a rare but treatable disorder in her twins, Alexis and Noah. After years of extremely limited mobility, severe breathing problems, costly emergency department visits, imaging tests, and visits to specialists, genome sequencing identified mutations in a gene called SPR that encodes the enzyme sepiapterin reductase. With proper drug treatment, the twins are healthy and high-functioning teenagers today.

"We believe this saved Alexis’s life," Ms. Beery told the Commission. "Weighing privacy versus life-saving treatment – it didn’t balance out at all." The family started a website to support others with similar challenges dealing with dystonia.

Another proponent of unrestricted access, Dr. Daniel Masys described the PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) project that he helped launch at Vanderbilt University, Nashville, Tenn., in 2010. The system prospectively gathers genome data from patients’ blood samples and makes clinically useful pharmacogenomic information available to physicians and patients through electronic medical records so that the right drug and dose get chosen for a specific patient.

Researchers there also are starting to analyze genomic data in a way that turns the traditional model on its head. Instead of picking a phenotype and looking for associations among all genetic polymorphisms, they pick a genotype and interrogate the set of all phenotypes (diseases) as recorded in the electronic medical records, Dr. Masys explained. Data from DNA "biorepositories" at seven U.S. centers get shared within the eMERGE (Electronic Medical Records & Genomics) Network for conducting genomic studies.

A Long Way to Go

The good news is we have the human genome. The bad news is it’s largely just a parts list," said Dr. Masys, currently an affiliated professor of biomedical and health informatics at the University of Washington, Seattle. "Our ability to acquire person-specific DNA data far exceeds our understanding of its meaning."

To advance the science quickly, genome data from hundreds of thousands or millions of people will be needed to draw clinical correlations. "The principle impediment is that this is a scale of science that we’ve never seen before," Dr. Masys said. He urged the Commission to not let privacy concerns slow the rapidity of this research.

Computerized clinical decision support is the only effective way to apply genomic variation–based guidance into clinical care because of the complexity of interpreting an individual’s data. And because an individual’s genomic data may evolve with age and other factors, electronic medical records will need to store multiple genomes. This is possible with today’s technology, but less than 2% of U.S. hospitals have fully adopted comprehensive electronic medical records, he said.

"Clearly, adoption of fully functional electronic medical records, including those that have patient-specific clinical decision support that can reason with data such as DNA variation, will be an essential feature of 21st-century health care," Dr. Masys said in an interview. "The sooner we get there, the sooner it will be easier for doctors to deal with what otherwise is an impossible task of trying to read and understand and keep up with this rapidly expanding science."

There is a risk, however, that delving into genomic data will identify numerous "incidentalomas," which will unnecessarily trigger expensive follow-up tests or misguided treatments, he said.

George Annas, J.D., chair of Health Law, Bioethics and Human Rights at Boston University, agreed and questioned whether "personalized medicine" is realistic. "At a time when the cost of health care is the No. 1 issue on the political agenda, it’s kind of bizarre that we would do something that’s the most expensive [thing to do] in medicine," he said.

Patient consent is another important issue, said Mr. Annas, citing the example of Henrietta Lacks, whose cells fueled decades of medical research without her knowledge or consent. "If people want to make their genetic information public, that’s fine with me. But to say everyone must is not the kind of country most people want to live in," he said.

Protections especially are needed for people who are unable to give informed consent, said Mark A. Rothstein, J.D., chair of law and medicine at the University of Louisville, Ky. "Those who are advocating newborn genome sequencing are throwing out long-standing policy in genetics not to test for late-onset disease," he said.

At least 25 million U.S. residents each year must sign authorizations for release of medical records to get a job or insurance or for other reasons, and adding genome data to those records could put them at greater risk. "I don’t think we’re ready for this huge onslaught of additional information, because there’s too much opportunity for misuse," he said.

Developments, such as the phenome-wide association studies at Vanderbilt, are exciting, Commissioner Nelson L. Michael noted in an interview. The human genome "is a new ‘book’ that many of us don’t know how to read very well," but this new approach to research should help translate that book, said the director of retrovirology at the Walter Reed Army Institute of Research, Bethesda, Md. "The better we are able to understand how the book is read and what it means, I think we are going to be able to translate that into clinical benefits" for a reasonable risk/benefit ratio, said Dr. Michael.

Dr. Gibbs reported being an investor in Life Technology and cofounder of the company Seq-Wright. The other speakers and commissioners did not report financial disclosures.

SAN FRANCISCO – The cost of sequencing one person’s genome has shrunk from nearly $3 billion 14 years ago to an anticipated $1,000 within the next year or two, a development that positions human genome sequencing to explode into widespread use by researchers and clinicians.

Or maybe not, depending in part on recommendations to President Obama from the Presidential Commission for the Study of Bioethical Issues, which will submit a report on the topic later this year. In preparation, the Commission conducted a day-long public discussion with multiple experts about the potential for medical discoveries from genome research, and the difficulties of protecting patient privacy.

Photos: Sherry Boschert/Elsevier Global Medical News

Excitement in some quarters about the already proven ability to diagnose rare disorders via genome sequencing has been tempered by concerns that the field may be moving too fast for the general good. The ability to collect genome data far exceeds the ability to interpret the data. And the growing use of such tests threatens to bankrupt the medical system if it leads to an avalanche of tests for the worried well and untreatable disorders.

Currently, physicians can order sequencing of an individual’s whole exome (all the expressed genes) or whole genome from a few centers on a very limited basis. Approximately 10,000 people had their genomes sequenced in 2011. Perhaps 100,000 will do the same in 2012, estimated Dr. Richard A. Gibbs, director of the Human Genome Sequencing Center at Baylor College of Medicine, Houston.

While many stakeholders emphasize the importance of free and unrestricted release of human genome data to all researchers, others argue that such open access would also allow third parties to manipulate data to deny individuals insurance or employment, he said. The race is on to try to understand genome data better before uninformed interpreters can do their damage. But clearly, having access to lots of genome data is key to advancing the science, he said.

"Less than 1% of the American public understands" genetics, opening the door to manipulation, said Commission Chair Amy Gutmann, Ph.D., president of the University of Pennsylvania, Philadelphia. "There’s a snake oil salesman out there for everything."

Benefits of Unrestricted Access

Among those arguing in favor of the unrestricted access to human genome data to all researchers is Retta Beery. The Baylor center helped diagnose a rare but treatable disorder in her twins, Alexis and Noah. After years of extremely limited mobility, severe breathing problems, costly emergency department visits, imaging tests, and visits to specialists, genome sequencing identified mutations in a gene called SPR that encodes the enzyme sepiapterin reductase. With proper drug treatment, the twins are healthy and high-functioning teenagers today.

"We believe this saved Alexis’s life," Ms. Beery told the Commission. "Weighing privacy versus life-saving treatment – it didn’t balance out at all." The family started a website to support others with similar challenges dealing with dystonia.

Another proponent of unrestricted access, Dr. Daniel Masys described the PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) project that he helped launch at Vanderbilt University, Nashville, Tenn., in 2010. The system prospectively gathers genome data from patients’ blood samples and makes clinically useful pharmacogenomic information available to physicians and patients through electronic medical records so that the right drug and dose get chosen for a specific patient.

Researchers there also are starting to analyze genomic data in a way that turns the traditional model on its head. Instead of picking a phenotype and looking for associations among all genetic polymorphisms, they pick a genotype and interrogate the set of all phenotypes (diseases) as recorded in the electronic medical records, Dr. Masys explained. Data from DNA "biorepositories" at seven U.S. centers get shared within the eMERGE (Electronic Medical Records & Genomics) Network for conducting genomic studies.

A Long Way to Go

The good news is we have the human genome. The bad news is it’s largely just a parts list," said Dr. Masys, currently an affiliated professor of biomedical and health informatics at the University of Washington, Seattle. "Our ability to acquire person-specific DNA data far exceeds our understanding of its meaning."

To advance the science quickly, genome data from hundreds of thousands or millions of people will be needed to draw clinical correlations. "The principle impediment is that this is a scale of science that we’ve never seen before," Dr. Masys said. He urged the Commission to not let privacy concerns slow the rapidity of this research.

Computerized clinical decision support is the only effective way to apply genomic variation–based guidance into clinical care because of the complexity of interpreting an individual’s data. And because an individual’s genomic data may evolve with age and other factors, electronic medical records will need to store multiple genomes. This is possible with today’s technology, but less than 2% of U.S. hospitals have fully adopted comprehensive electronic medical records, he said.

"Clearly, adoption of fully functional electronic medical records, including those that have patient-specific clinical decision support that can reason with data such as DNA variation, will be an essential feature of 21st-century health care," Dr. Masys said in an interview. "The sooner we get there, the sooner it will be easier for doctors to deal with what otherwise is an impossible task of trying to read and understand and keep up with this rapidly expanding science."

There is a risk, however, that delving into genomic data will identify numerous "incidentalomas," which will unnecessarily trigger expensive follow-up tests or misguided treatments, he said.

George Annas, J.D., chair of Health Law, Bioethics and Human Rights at Boston University, agreed and questioned whether "personalized medicine" is realistic. "At a time when the cost of health care is the No. 1 issue on the political agenda, it’s kind of bizarre that we would do something that’s the most expensive [thing to do] in medicine," he said.

Patient consent is another important issue, said Mr. Annas, citing the example of Henrietta Lacks, whose cells fueled decades of medical research without her knowledge or consent. "If people want to make their genetic information public, that’s fine with me. But to say everyone must is not the kind of country most people want to live in," he said.

Protections especially are needed for people who are unable to give informed consent, said Mark A. Rothstein, J.D., chair of law and medicine at the University of Louisville, Ky. "Those who are advocating newborn genome sequencing are throwing out long-standing policy in genetics not to test for late-onset disease," he said.

At least 25 million U.S. residents each year must sign authorizations for release of medical records to get a job or insurance or for other reasons, and adding genome data to those records could put them at greater risk. "I don’t think we’re ready for this huge onslaught of additional information, because there’s too much opportunity for misuse," he said.

Developments, such as the phenome-wide association studies at Vanderbilt, are exciting, Commissioner Nelson L. Michael noted in an interview. The human genome "is a new ‘book’ that many of us don’t know how to read very well," but this new approach to research should help translate that book, said the director of retrovirology at the Walter Reed Army Institute of Research, Bethesda, Md. "The better we are able to understand how the book is read and what it means, I think we are going to be able to translate that into clinical benefits" for a reasonable risk/benefit ratio, said Dr. Michael.

Dr. Gibbs reported being an investor in Life Technology and cofounder of the company Seq-Wright. The other speakers and commissioners did not report financial disclosures.

SAN FRANCISCO – The cost of sequencing one person’s genome has shrunk from nearly $3 billion 14 years ago to an anticipated $1,000 within the next year or two, a development that positions human genome sequencing to explode into widespread use by researchers and clinicians.

Or maybe not, depending in part on recommendations to President Obama from the Presidential Commission for the Study of Bioethical Issues, which will submit a report on the topic later this year. In preparation, the Commission conducted a day-long public discussion with multiple experts about the potential for medical discoveries from genome research, and the difficulties of protecting patient privacy.

Photos: Sherry Boschert/Elsevier Global Medical News

Excitement in some quarters about the already proven ability to diagnose rare disorders via genome sequencing has been tempered by concerns that the field may be moving too fast for the general good. The ability to collect genome data far exceeds the ability to interpret the data. And the growing use of such tests threatens to bankrupt the medical system if it leads to an avalanche of tests for the worried well and untreatable disorders.

Currently, physicians can order sequencing of an individual’s whole exome (all the expressed genes) or whole genome from a few centers on a very limited basis. Approximately 10,000 people had their genomes sequenced in 2011. Perhaps 100,000 will do the same in 2012, estimated Dr. Richard A. Gibbs, director of the Human Genome Sequencing Center at Baylor College of Medicine, Houston.

While many stakeholders emphasize the importance of free and unrestricted release of human genome data to all researchers, others argue that such open access would also allow third parties to manipulate data to deny individuals insurance or employment, he said. The race is on to try to understand genome data better before uninformed interpreters can do their damage. But clearly, having access to lots of genome data is key to advancing the science, he said.

"Less than 1% of the American public understands" genetics, opening the door to manipulation, said Commission Chair Amy Gutmann, Ph.D., president of the University of Pennsylvania, Philadelphia. "There’s a snake oil salesman out there for everything."

Benefits of Unrestricted Access

Among those arguing in favor of the unrestricted access to human genome data to all researchers is Retta Beery. The Baylor center helped diagnose a rare but treatable disorder in her twins, Alexis and Noah. After years of extremely limited mobility, severe breathing problems, costly emergency department visits, imaging tests, and visits to specialists, genome sequencing identified mutations in a gene called SPR that encodes the enzyme sepiapterin reductase. With proper drug treatment, the twins are healthy and high-functioning teenagers today.

"We believe this saved Alexis’s life," Ms. Beery told the Commission. "Weighing privacy versus life-saving treatment – it didn’t balance out at all." The family started a website to support others with similar challenges dealing with dystonia.

Another proponent of unrestricted access, Dr. Daniel Masys described the PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) project that he helped launch at Vanderbilt University, Nashville, Tenn., in 2010. The system prospectively gathers genome data from patients’ blood samples and makes clinically useful pharmacogenomic information available to physicians and patients through electronic medical records so that the right drug and dose get chosen for a specific patient.

Researchers there also are starting to analyze genomic data in a way that turns the traditional model on its head. Instead of picking a phenotype and looking for associations among all genetic polymorphisms, they pick a genotype and interrogate the set of all phenotypes (diseases) as recorded in the electronic medical records, Dr. Masys explained. Data from DNA "biorepositories" at seven U.S. centers get shared within the eMERGE (Electronic Medical Records & Genomics) Network for conducting genomic studies.

A Long Way to Go

The good news is we have the human genome. The bad news is it’s largely just a parts list," said Dr. Masys, currently an affiliated professor of biomedical and health informatics at the University of Washington, Seattle. "Our ability to acquire person-specific DNA data far exceeds our understanding of its meaning."

To advance the science quickly, genome data from hundreds of thousands or millions of people will be needed to draw clinical correlations. "The principle impediment is that this is a scale of science that we’ve never seen before," Dr. Masys said. He urged the Commission to not let privacy concerns slow the rapidity of this research.

Computerized clinical decision support is the only effective way to apply genomic variation–based guidance into clinical care because of the complexity of interpreting an individual’s data. And because an individual’s genomic data may evolve with age and other factors, electronic medical records will need to store multiple genomes. This is possible with today’s technology, but less than 2% of U.S. hospitals have fully adopted comprehensive electronic medical records, he said.

"Clearly, adoption of fully functional electronic medical records, including those that have patient-specific clinical decision support that can reason with data such as DNA variation, will be an essential feature of 21st-century health care," Dr. Masys said in an interview. "The sooner we get there, the sooner it will be easier for doctors to deal with what otherwise is an impossible task of trying to read and understand and keep up with this rapidly expanding science."

There is a risk, however, that delving into genomic data will identify numerous "incidentalomas," which will unnecessarily trigger expensive follow-up tests or misguided treatments, he said.

George Annas, J.D., chair of Health Law, Bioethics and Human Rights at Boston University, agreed and questioned whether "personalized medicine" is realistic. "At a time when the cost of health care is the No. 1 issue on the political agenda, it’s kind of bizarre that we would do something that’s the most expensive [thing to do] in medicine," he said.

Patient consent is another important issue, said Mr. Annas, citing the example of Henrietta Lacks, whose cells fueled decades of medical research without her knowledge or consent. "If people want to make their genetic information public, that’s fine with me. But to say everyone must is not the kind of country most people want to live in," he said.

Protections especially are needed for people who are unable to give informed consent, said Mark A. Rothstein, J.D., chair of law and medicine at the University of Louisville, Ky. "Those who are advocating newborn genome sequencing are throwing out long-standing policy in genetics not to test for late-onset disease," he said.

At least 25 million U.S. residents each year must sign authorizations for release of medical records to get a job or insurance or for other reasons, and adding genome data to those records could put them at greater risk. "I don’t think we’re ready for this huge onslaught of additional information, because there’s too much opportunity for misuse," he said.

Developments, such as the phenome-wide association studies at Vanderbilt, are exciting, Commissioner Nelson L. Michael noted in an interview. The human genome "is a new ‘book’ that many of us don’t know how to read very well," but this new approach to research should help translate that book, said the director of retrovirology at the Walter Reed Army Institute of Research, Bethesda, Md. "The better we are able to understand how the book is read and what it means, I think we are going to be able to translate that into clinical benefits" for a reasonable risk/benefit ratio, said Dr. Michael.

Dr. Gibbs reported being an investor in Life Technology and cofounder of the company Seq-Wright. The other speakers and commissioners did not report financial disclosures.