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Corinne Chin and Matt Rhodes/MEDILL

Jim Lund, senior scientist at Wheeling-based sequencing lab ACGT Inc., compares DNA sequencing technolgoies. Sanger DNA sequencing has been the gold standard since the late 1970s while Next Generation sequencing joined the field about five years ago. Lund also reflects on the history of the field and discusses his hopes and worries for the future.

DNA sequencing: Magic mirror or Pandora's Box

by Corinne Chin and Matt Rhodes
Dec 06, 2012


Corinne Chin/MEDILL

Next Generation DNA sequencing can churn out several whole human genomes in the span of a few days.


Corinne Chin/MEDILL

ACGT Inc. in Wheeling offers DNA sequencing and molecular biology services for academic institutions, government, pharmaceutical companies and consumer-oriented clients.


Corinne Chin/MEDILL

Data from NHGRI


Corinne Chin/MEDILL

Chicagoan Adam Hecktman dribbled saliva into two empty vials. Then, he packed it up and sent it away.

“It was kind of gross,” he says.

Hecktman, a science aficionado who directs Chicago’s Microsoft Technology Center, purchased the “spit kit” from 23andMe, a biotechnology company that provides direct-to-consumer DNA genotyping. Scientists at 23andMe would analyze his sample and send him the results.

“I just want all the information possible,” Hecktman says. He found out he’s at an increased risk for psoriasis, among other things, he said.

His curiosity is not uncommon. DNA is the script of life. It determines eye color, influences athletic prowess and can even predict an aversion to cilantro. In a new project that will sequence 100,000 patients with cancers and rare diseases, the U.K. announced Dec. 10 that it’s on track to mainstream DNA sequencing in medicine. The $160 million program and resulting database is expected to be a catalyst for new drug development.

And direct-to-consumer DNA genotyping, a limited genetic test, now costs around $300.

The first human genome cost nearly $3 billion to sequence in 2000. Today, the price of sequencing a person’s entire genome has plummeted to around $7,500 – the highly anticipated “thousand-dollar genome” is in reach. Instead of taking several years to decipher the data, analysis can take two weeks or less.

Not all the kinks have been worked out, though. Scientists have been on a sequencing field day, but they still don’t know the significance of abnormalities in most of those 3 billion DNA bases. They won’t until more genomes are sequenced and more research is done.

Genome sequencing and genetic analysis can already answer significant medical questions. You might discover an unknown allergy. Perhaps you carry a gene that increases your likelihood of developing type-2 diabetes; you could take preventative measures with diet and exercise. You may even learn that you carry a BRCA gene mutation that dramatically increases your risk of breast cancer.

“For some people, (genetic) testing will change their life,” says Nick Eriksson, a principal scientist at 23andMe.

But having that information could also be life changing in a completely different way. The script may not play out as expected: Would you want to know whether your future holds an incurable disease, like Alzheimer’s?

Whole genomic sequencing has the potential to unlock the most intimate secrets of what makes us unique as individuals and as a species. It could also radically advance clinical care by enabling personalized genetic medicine. But this potential hinges on the collection of vast amounts of data of the most personal nature. Genome sequencing is laden with enough ethical issues to make your head spin faster than a vial of DNA in a centrifuge.

WGS defined

Whole genome sequencing determines the complete genetic code of an organism, or the order of the 3 billion building blocks (A, C, G and T) that make up an individual’s DNA.

“DNA sequencing has gotten cheap, but understanding the results of DNA sequencing is still very young,” says Jim Lund, senior scientist at ACGT Inc., an Illinois-based DNA sequencing company. “We can sequence your genome now, but we can’t tell you a lot about yourself from that.”

Whole genome sequencing is not yet available to most patients – it’s most often conducted in research settings, and it’s not yet a routine clinical test. In other words, you can’t just request a sequence of your genome; your doctor needs to order it as a diagnostic test. But hospitals are progressing closer to that model.

Issues in clinical DNA testing

Karyotyping, or routine chromosome analysis, was one of the first standard prenatal genetic tests. The test can detect extra or missing chromosomes in a developing fetus, says Blair Stevens, a genetic counselor at Baylor College of Medicine and Texas Children’s Hospital.

One of the most common chromosomal abnormalities is Down syndrome – trisomy 21 – where the 21st chromosome is tripled instead of doubled.

Now, doctors are moving toward more nuanced testing, such as chromosome microarray. If routine chromosome analysis is similar to looking at a bookshelf of encyclopedias (a missing or duplicated book would be obvious), the detailed microarray test opens those encyclopedias, looking closely at the individual pages for genetic mutations, Stevens says. One of the most common micro-deletion syndromes is Monosomy 1p36, which causes developmental delays and intellectual disability, said Justine Coppinger, a clinical lab counselor.

However, scientists are still unable to interpret many of the results, since it’s not yet known what every gene codes for.

“Sometimes the genetic abnormality just causes normal variation,” Stevens says.

“There’s so much we have not yet discovered about genetics. The harder you look, the more likely you will find things you don’t know how to explain.”

Microarray testing has raised several concerns among patients who receive unexpected information.

In a study published in Genetics in Medicine in September, researchers spoke with pregnant women who received ambiguous test results. The test revealed genetic mutations of unknown significance, and women say they felt “blindsided.” Some even called the knowledge “toxic information.” Some decided to terminate their pregnancies.

Cathy Wicklund, a prenatal genetic counselor at Northwestern University’s Center for Genetic Medicine, says any DNA testing must be carefully considered.

“No matter what type of test you decide to run, you could be getting results back that we don’t understand. Is that a position you want to be in?” Wicklund says. “The more we test for, the greater chance we find something wrong.”

As a counselor, Wicklund must regularly walk the fine line between preparing patients for the possibility of abnormal results and outright scaring them. As genetic testing becomes more advanced and genome sequencing increasingly accessible, results are becoming more complicated and difficult to interpret.

Wicklund says there is a growing need for genetic counseling.

“The technology is moving forward,” Wicklund says. “We’re getting a lot more genetic information. Some we understand – a lot we don’t.”

DNA goes DTC

As technology advances, many are bypassing the hospital by pursuing direct-to-consumer (DTC) testing.

Hecktman, who sent his saliva samples to 23andMe, was one of those curious consumers. He became fascinated with 23andMe’s $299 genotyping service after hearing about it from a friend in Paris. Hecktman can’t remember how long ago it was when he sent for the test. In return, he received an analysis of 1 million of his 3 billion DNA bases.

“The results have categories: disease risk, carrier status, drug response and traits,” Hecktman says. “What I thought was interesting were some of the risks that rose to the top. Age-related macular degeneration – and then some things that were just strange, like psoriasis. The estimated lifetime incidence (of psoriasis) is 11 percent, and mine is 22 percent.”

Hecktman says he wasn’t disappointed by the wealth of information he received; in fact, he was excited. Still, he was confused by the sheer amount of data.

“I felt overwhelmed. In fact, I wanted to bring it to my doctor and say, ‘What does all this mean?’” Hecktman says. “I wouldn’t recommend a hypochondriac to do anything like this.”

Hecktman’s physician told him the findings were interesting, but the disease risks were simply markers, not guarantees.

Katherine Wasson, assistant professor at Loyola University Chicago’s Neiswanger Institute for Bioethics, works primarily on direct-to-consumer genetic testing. She says she’s worried about people’s reactions to their genetic information when it is still largely unreliable.

“Would they then take action based on a false positive or a false negative or a misunderstanding of this perhaps inaccurate genetic information?” Wasson asks.

Wasson is currently working with colleagues on the second stage of a study on DTC testing. Researchers offered the 23andMe test to 20 people. After the test, researchers followed the participants for a year to see how they reacted to the results. The study is currently undergoing the peer review process.

“With direct-to-consumer genetic testing, there’s a lot of discussion around,” says Wasson. “Will they run to their doctors; will they flood the health care system because there may be no health care person involved to help them understand it?”

Plus, 23andMe results don’t stop when the analysis is run. Eriksson, one of the principal scientists, says that as new research and papers are released, 23andMe updates customers with new discoveries.

“We send out an email and say ‘Hey, there's four new reports based on your DNA (findings). There's new results on prostate cancer,’ or something like that,” Eriksson explains. “The science is moving fast, and it's not a static product.”

Though the science is progressing, many essential questions remain unanswered.

“What is innate in us, and what are the things that I can change?” Eriksson says. “A lot of what I'm doing is trying to get at that question. With these traits and predispositions, what part of that is due to genetics? What part of that is due to environment? What can we tell you about your future based on who you are?”

Incidental findings

One issue bioethicists are struggling with is how to handle the disclosure of this information, particularly when the information isn’t expected.

“Let’s say you go into the hospital and you have cancer,” Lund suggests. “One way of analyzing cancer to try to come up with a treatment is to sequence your genome, but that sequence also has all sorts of other information.”

Some of that other information might reveal a predisposition for type-2 diabetes, or a high probability that your child will have a genetic mutation in the HEXA gene on their 15th chromosome – likely resulting in Tay-Sachs, a disease that causes fatal nerve damage in just a few years.

In the same sentence, you may hear your doctor say, “Well, we have found a way to cure your cancer, but by the way, you’ll most likely experience early-onset dementia right around your 40th birthday – and there’s nothing we can do about that.”

Bioethicists such as Wasson are working on how to handle such cases. Unless the patient specifically requests a report of incidental findings, it is standard practice to withhold information that’s unrelated to the diagnosis if nothing can be done. However, just because there’s no treatment available today doesn’t mean that there won’t be one five years from now.

Wasson says one emerging model gives the participants a choice of what kind of information they want to receive and when. “Rather than having a one-size-fits-all approach,” some places are trying to customize how information is disclosed on an individual case basis, she explains.

The website is one such example. The platform, a University of Washington research project, explains different types of mutations and lets users choose whether they want to get certain results depending on their risk of disease, heredity and drug response. It also allows users to change their mind regarding what kind of information they receive and when.

The information helps people manage their results when they have their whole genome sequenced by the National Human Genome Research Institute, a research platform that is part of the National Institutes of Health. is also studying the preferences for and impact of receiving genetic information.  


Customized disclosure may help, but that’s not the only complication when it comes to incidental findings.

“Your genome is one of the most personal things about you,” says Wasson.

It’s also one of the most personal things about your closest relatives. Sequencing your own genome also reveals predictive information about the health risks of your family members.

If you find a single gene disorder that is undoubtedly shared with your sibling, does your doctor have an obligation to warn your brothers and sisters as well?

In October, the Presidential Commission for the Study of Bioethical Issues released Privacy and Progress in Whole Genome Sequencing, the fourth report since the commission’s inception in 2009.

“Large-scale collections of genomic data raise serious concerns for the individuals participating,” the commission reports. “One of the greatest of these concerns centers around privacy: whether and how personal, sensitive, or intimate knowledge and use of that knowledge about an individual can be limited or restricted by means that include guarantees of confidentiality, anonymity or secure data protection.”

Eriksson, the scientist from 23andMe, dismissed the threat of outsiders hacking into their databases, reassuring clients that their data is tightly secured. He says many of 23andMe’s data security employees come from PayPal, the online payment clearinghouse lauded for its security.

By the time Eriksson sees the data, it’s been stripped of any identifiers, so he has no idea whose DNA he’s examining.

But technological advancement has unchained genome sequencing from state-of-the-art scientific laboratories. It’s possible to sequence genomes on an office desk.

The Ion Proton Sequencer from Life Technologies costs only $149,000 and is roughly the size of an inkjet printer. Conceivably, someone could snag your discarded coffee cup, grab the remnants of your saliva and churn out your sequenced genome, all within a few hours.

The future

Under the federal Genetic Information Nondiscrimination Act (GINA) enacted in 2008, it’s illegal for an employer or insurance company to discriminate against people because of the composition of their genome.

Wasson also says the Affordable Care Act, better known by the nickname Obamacare, will offer some protection when it kicks in by 2014 (about the same time 1 million whole genomes will have been sequenced worldwide).

“If you can’t be denied insurance or coverage on the basis of preexisting conditions, some of those will be genetic,” says Wasson.

Still, the Presidential Bioethics Commission and scientists alike say that GINA is hardly exhaustive.

“GINA does not regulate access, security and disclosure of genetic or whole genome sequence information across all potential users, nor does it protect against discrimination in other contexts,” the commission reports.

Lund, the ACGT scientist, is also skeptical about how the current law will be able to protect against future abuses.

“It’s a first pass,” says Lund. “The information now has some use for an insurance company, but it isn’t a huge temptation for them at the moment. Until it becomes tempting for people to abuse, we won’t know how well the law is working.”