GENETIC RESEARCH - Unlocking Mutations

"How genetic sequencing can unlock secret DNA mutations — and save lives" PBS NewsHour 5/13/2016

Excerpt

SUMMARY:  Every year, thousands of young people who seemed otherwise healthy die suddenly.  The reason sometimes is long-rooted, secret gene mutations passed down through the generations.  Doctors at the Scripps Translational Science Institute are using gene sequencing and “molecular autopsies” to uncover these hidden mutations and allow patients to take preventative action.  David Wagner of KPBS reports.

DAVID WAGNER (KBPS San Diego):  Dardie Robinson leads a typical life in Portland, Oregon.  She spends her days working as a paralegal and catching up with all the kids she has raised.

But unknown to her, she was carrying a genetic mutation that left her and family members vulnerable to sudden heart failure.  A year-and-a-half ago, she received an unexpected call.  t was about her son, Daniel.

DARDIE ROBINSON, Mother:  I got a call out of the blue from his girlfriend.  And — sorry — she said that paramedics were there working on Daniel, that she had found him, that he was blue and unresponsive.

And I told her, I said, “Tell him his momma loves him.”

And she said, “Well, I'm sure he can't hear you.”

I said, “Tell him anyway.”

And so she did.

DAVID WAGNER:  In tears, she left the office and got in her car.

DARDIE ROBINSON:  And on the way home, I got the call that there was nothing they could do, and that he was gone.

DAVID WAGNER:  Daniel was 29 and otherwise healthy.  No one knew why he had died so suddenly.

DARDIE ROBINSON:  That was, to me, part of the — really the worst part, is because the word to us initially was, they thought that he must have committed suicide, he must have taken something.  And I kept saying, that doesn't make sense.

DAVID WAGNER:  An autopsy pointed to problems with his heart.  And while she was relieved suicide was ruled out, the autopsy left her unsettled.

If this could kill Daniel at 29, could it strike her other biological children?

ALL IN THE FAMILY - 3 'Parent' Babies

"Three-parent DNA treatment for rare defect raises debate" PBS NewsHour 2/3/2016

Excerpt

SUMMARY:  When women have defective mitochondria, their children can inherit terrible, sometimes fatal problems.  A new technology, pioneered in England, adds healthy cellular structure from a third person, meaning that children are born with DNA from three people.  William Brangham learns more from Jeffrey Kahn of Johns Hopkins University and Marcy Darnovsky of the Center for Genetics and Society.

GWEN IFILL (NewsHour):  Now to questions surrounding a significant advance in reproductive technology with DNA and embryos.

The change on the horizon was pioneered and approved in England and it is now being considered for use in the U.S.  Proponents believe it may eliminate dangerous disease in children, but others have raised ethical concerns.

Today, the National Academy of Sciences recommended that clinical trials go forward in the U.S.

William Brangham has our look.

WILLIAM BRANGHAM (NewsHour):  This new technology is called mitochondrial replacement technique, or MRT for shot.

Mitochondria are tiny structures that exist in nearly all the cells in our bodies, and have their own unique DNA.  The problem is, a very small number of women have defective mitochondria, and if they have children, those kids inherit their mom’s mitochondria and can suffer terrible, sometimes fatal, problems, including brain damage and heart failure.

This new technology would, in essence, replace that original mitochondria in either the mother’s egg or in the parents’ embryo with healthy mitochondria from a third person.  A child born this way would then be carrying the DNA of three different people.

Earlier today, patient advocate Laurie Strongin told us why the advance was so important for a small group of parents.

LAURIE STRONGIN, Patient Advocate:  One of the things that we have found is that parents’ desire to have genetically related offspring is a widely held desire.  It’s not universal, but it’s widely held.

And the potential to use MRT to have offspring who are genetically related to both parents is something that families who carry mtDNA disease really want.  And not everyone is going to pursue it, but for the family for whom having children who are — who have a nuclear genetic connection to them, this is something that will just be one of numerous options available to them.

BREAKTHROUGHS - 2015 Biggest, Designer Babies

"2015’s biggest breakthrough could deliver designer babies" PBS NewsHour 12/30/2015

Excerpt

SUMMARY:  CRISPR, a new method for editing genes, has been called a development that could revolutionize medicine.  Cheaper and more precise than past gene editing, this promising tool has also raised concerns.  Gwen Ifill talks to Jennifer Doudna of University of California, Berkeley and Paul Knoepfler of University of California, Davis.

GWEN IFILL (NewsHour):  It’s been called the scientific breakthrough of the year, and a development that could revolutionize medicine.  It’s all about a way of editing genes, known as CRISPR.

The new method allows scientists to snip out a faulty section of DNA and replace specific genes in living cells.  Researchers have long edited genes in the lab, but CRISPR is cheaper, far more precise, and could even be used in DNA found in eggs and sperm.

It has lots of promise, but it has raised many concerns too.

We explore those questions with Jennifer Doudna, a professor at the University of California, Berkeley, who helped develop this breakthrough, and Paul Knoepfler, a biologist and writer from at University of California, Davis.

Welcome to you both.

Jennifer Doudna, I’m going to start by just asking you to define in laywoman’s language gene editing and CRISPR.

JENNIFER DOUDNA, University of California, Berkeley:  Well, I would say gene editing is a method of making very precise changes to the DNA in a cell, and the CRISPR methodology allows scientists to do that with just really unprecedented precision.

GWEN IFILL:  So, there is a targeted, practical use for this?

JENNIFER DOUDNA:  Indeed, actually many.

It’s a technology that operates in basically all types of cells and allows very precise changes to be made to the genetic code that allows scientists to do things like explore the function of genes and also, in principle, correct mutations that cause disease.

WARNING - The big "IF" is if 'they' get it scientifically right AND ethically right.  If 'they' get it ethically wrong, we could end up with only the rich-and-powerful engineering the 'super race.'

Also, here's a scary book title:  "GMO Sapiens" (as mentioned in video)

TEXAS - Law to Increase Criminal DNA Testing

"Some Worry Over a Law to Increase DNA Testing" by BRANDI GRISSOM, New York Times 8/17/2013

In some Texas counties, it takes six months or longer to get DNA test results from the Department of Public Safety, says William Lee Hon, the Polk County criminal district attorney.

Now, Mr. Hon and other prosecutors fear that come Sept. 1, when a new law takes effect requiring DNA analysis of all biological evidence in death penalty cases, the wait could grow longer.  “We’re not sure that D.P.S. has the resources currently to adequately comply with that legislation,” he said.

In Texas, there have been 54 exonerations based on DNA test results, including those of two inmates on death row, according to the National Registry of Exonerations.  Lawmakers this year approved Senate Bill 1292, written by Senator Rodney Ellis, Democrat of Houston, which aims to prevent wrongful convictions.  Many prosecutors say that the bill may go too far, and that the pursuit of testing in some cases could be used to delay a conviction.

Tom Vinger, a safety department spokesman, said it was too early to predict the law’s impact.  Mr. Ellis, who is the board chairman of the Innocence Project, which is dedicated to using DNA evidence to exonerate the wrongfully convicted, said that if the state sought the death penalty, expedience should not take priority over certainty.

“If you’re going to ask for the death penalty,” he said, “you ought to be confident that you have the right person.”

The bill’s champions include Attorney General Greg Abbott, the leading Republican candidate for governor, who said the measure would save Texas years of appeals.

“There’s no reason to test these items more than a decade after the crime was committed,” Mr. Abbott said in March.  “The family of the victim shouldn’t have to go through this time after time.”

Mr. Abbott cited the case of Hank Skinner, a death row inmate who was convicted in 1995 of killing his girlfriend and her two adult sons.  Mr. Skinner said he was unconscious at the time of the crime.

He started asking for DNA testing in 2000.  Less than an hour before he was to be executed, in 2010, the United States Supreme Court delayed his punishment.  Mr. Abbott’s office agreed in 2012 to the testing, which is still not complete.

Kathryn Kass, the executive director of the Texas Defender Service, which represents death row inmates, said the law would help prevent investigators from homing in on one suspect and inadvertently ignoring evidence that could implicate others.

“When a crime is being investigated, the most important search is the search for objective evidence,” Ms. Kase said.

While additional testing may require more time, Bobby D. Mims, the president of the Texas Criminal Defense Lawyers Association, said certainty would improve the system.

“A rush to judgment is never good and beneficial to the justice system,” Mr. Mims said.

Mr. Hon said prosecutors agree that testing to verify the identity of a killer is worth the time and expense.  But, he said, prosecutors worry that defense lawyers will ask for testing in cases where the killer’s identity is not in question.

He said that for rural communities like his that rely on the safety department’s labs, additional testing could delay trials.

COMMENT:  From the tone of this article, it sounds like the law increased DNA testing but did not require or fund bigger labs to handle the increased load.

LAW - Misinterpreted or Mishandled Forensic Evidence

Note that IMHO the story title is misleading.  The science of "forensics" is not the issue, but on how it's handled and interpreted.

"High-Tech, High-Risk Forensics" by OSAGIE K. OBASOGIE, New York Times 7/24/2013

Excerpt

WHEN the police arrived last November at the ransacked mansion of the millionaire investor Raveesh Kumra, outside of San Jose, Calif., they found Mr. Kumra had been blindfolded, tied and gagged.  The robbers took cash, rare coins and ultimately Mr. Kumra’s life; he died at the scene, suffocated by the packaging tape used to stifle his screams.  A forensics team found DNA on his fingernails that belonged to an unknown person, presumably one of the assailants.  The sample was put into a DNA database and turned up a “hit” — a local man by the name of Lukis Anderson.

Bingo.  Mr. Anderson was arrested and charged with murder.

There was one small problem, the 26-year-old Mr. Anderson couldn’t have been the culprit.  During the night in question, he was at the Santa Clara Valley Medical Center, suffering from severe intoxication.

Yet he spent more than five months in jail with a possible death sentence hanging over his head.  Once presented with Mr. Anderson’s hospital records, prosecutors struggled to figure out how an innocent man’s DNA could have ended up on a murder victim.

Late last month, prosecutors announced what they believe to be the answer, the paramedics who transported Mr. Anderson to the hospital were the very same individuals who responded to the crime scene at the mansion a few hours later.  Prosecutors now conclude that at some point, Mr. Anderson’s DNA must have been accidentally transferred to Mr. Kumra’s body — likely by way of the paramedics’ clothing or equipment.

This theory of transference is still under investigation.  Nevertheless, the certainty with which prosecutors charged Mr. Anderson with murder highlights the very real injustices that can occur when we place too much faith in DNA forensic technologies.

In the end, Mr. Anderson was lucky.  His alibi was rock solid; prosecutors were forced to concede that there must have been some other explanation.  It’s hard to believe that, out of the growing number of convictions based largely or exclusively on DNA evidence, there haven’t been any similar mistakes.

In one famous case of crime scene contamination, German police searched for around 15 years for a serial killer they called the “Phantom of Heilbronn” — an unknown female linked by traces of DNA to six murders across Germany and Austria.  In 2009, the police found their “suspect,” a worker at a factory that produced the cotton swabs police used in their investigations had been accidentally contaminating them with her own DNA.

Contamination is not the only way DNA forensics can lead to injustice.  Consider the frequent claim that it is highly unlikely, if not impossible, for two DNA profiles to match by coincidence.  A 2005 audit of Arizona’s DNA database showed that, out of some 65,000 profiles, nearly 150 pairs matched at a level typically considered high enough to identify and prosecute suspects.  Yet these profiles were clearly from different people.

There are also problems with the way DNA evidence is interpreted and presented to juries.  In 2008, John Puckett — a California man in his 70s with a sexual assault record — was accused of a 1972 killing, after a trawl of the state database partially linked his DNA to crime scene evidence.  As in the Anderson case, Mr. Puckett was identified and implicated primarily by this evidence.  Jurors — told that there was only a one-in-1.1 million chance that this DNA match was pure coincidence — convicted him.  He is now serving a life sentence.

But that one-in-1.1 million figure is misleading, according to two different expert committees, one convened by the F.B.I., the other by the National Research Council.  It reflects the chance of a coincidental match in relation to the size of the general population (assuming that the suspect is the only one examined and is not related to the real culprit).  Instead of the general population, we should be looking at only the number of profiles in the DNA database.  Taking the size of the database into account in Mr. Puckett’s case (and, again, assuming the real culprit’s profile is not in the database) would have led to a dramatic change in the estimate, to one in three.

One juror was asked whether this figure would have affected the jury’s deliberations.  “Of course it would have changed things,” he told reporters.  “It would have changed a lot of things.”

DNA forensics is an invaluable tool for law enforcement.  But it is most useful when it corroborates other evidence pointing to a suspect, or when used to determine whether any two individual samples match, like in the exonerations pursued by the Innocence Project.

But when the government gets into the business of warehousing millions of DNA profiles to seek “cold hits” as the primary basis for prosecutions, much more oversight by and accountability to the public is warranted.  For far too long, we have allowed the myth of DNA infallibility to chip away at our skepticism of government’s prosecutorial power, undoubtedly leading to untold injustices.

In the Anderson case, thankfully, prosecutors acknowledged the obvious, their suspect could not have been in two places at once.  But he was dangerously close to being on his way to death row because of that speck of DNA.  That one piece of evidence — obtained from a technology with known limitations, and susceptible to human error and prosecutorial misuse — might mistakenly lead to execution at the hands of the state should send chills down every one of our spines.  The next Lukis Anderson could be you.  Better hope your alibi is as well documented as his.

AMERICA - Local Law Enforcement Collecting DNA

"Police Agencies Are Assembling Records of DNA" by JOSEPH GOLDSTEIN, New York Times 6/12/2013

Excerpt

Slowly, and largely under the radar, a growing number of local law enforcement agencies across the country have moved into what had previously been the domain of the F.B.I. and state crime labs — amassing their own DNA databases of potential suspects, some collected with the donors’ knowledge, and some without it.

And that trend — coming at a time of heightened privacy concerns after recent revelations of secret federal surveillance of telephone calls and Internet traffic — is expected only to accelerate after the Supreme Court’s recent decision upholding a Maryland statute allowing the authorities to collect DNA samples from those arrested for serious crimes.

These local databases operate under their own rules, providing the police much more leeway than state and federal regulations.  And the police sometimes collect samples from far more than those convicted of or arrested for serious offenses — in some cases, innocent victims of crimes who do not necessarily realize their DNA will be saved for future searches.

New York City has amassed a database with the profiles of 11,000 crime suspects.  In Orange County, Calif., the district attorney’s office has 90,000 profiles, many obtained from low-level defendants who give DNA as part of a plea bargain or in return for having the charges against them dropped.  In Central Florida, several law enforcement agencies have pooled their DNA databases.  A Baltimore database contains DNA from more than 3,000 homicide victims.

These law enforcement agencies are no longer content to rely solely on the highly regulated network of state and federal DNA databases, which have been more than two decades in the making and represent one of the most significant developments in the history of law enforcement in this country.

The reasons vary.  Some police chiefs are frustrated with the time it can take for state crime labs to test evidence and enter DNA profiles into the existing databases.  Others want to compile DNA profiles from suspects or low-level offenders long before their DNA might be captured by the state or national databases, which typically require conviction or arrest.

“Unfortunately, what goes into the national database are mostly reference swabs of people who are going to prison,” said Jay Whitt of the company DNA:SI Labs, which sells DNA testing and database services to police departments.  “They’re not the ones we’re dealing with day in day out, the ones still on the street just slipping under the radar.”

The rise in these local databases has aroused concerns among some critics, worried about both the lax rules governing them and the privacy issues they raise.

“We have been warning law enforcement that when public attention began to focus on these rogue, unregulated databases, people would be disturbed,” said Barry Scheck, a co-director of the Innocence Project, which seeks to exonerate wrongfully convicted prisoners.  “Law enforcement has just gone ahead and started collecting DNA samples from suspects in an unregulated fashion.”

For their part, law enforcement officials say that the crime-solving benefits of local databases are dramatic.

“Our take is that it’s good for law enforcement and good for the community,” said Doug Muldoon, police chief of Palm Bay, a city of about 100,000 in Central Florida, about its database, which has produced 1,000 matches.  He said his officers could now use DNA to address the crime conditions “in our community — property crimes and burglaries.”  State crime labs can take months to analyze evidence from low-level felonies like that, he said.

SUPREME COURT - Rules on DNA Collected on Arrest

"High Court Says Police Can Collect DNA From People Arrested for Serious Crimes" PBS Newshour 6/3/2013

Excerpt

SUMMARY:  In a 5-4 vote, the Supreme Court ruled that police officers can take DNA samples without a warrant from people they arrest for serious crimes without violating the Fourth Amendment.  Marcia Coyle of The National Law Journal joins Gwen Ifill to help clarify the details of the ruling and how the justices were split on the decision.

BIOLOGY - Unfertilized Human Egg, to Early-Stage Blastocyst, to Heart Cells

"Major Embryonic Stem Cell Advance Raises Ethical Quandaries" PBS Newshour 5/16/2013

Excerpt

JEFFREY BROWN (Newshour):  And finally tonight, a major advance in stem cell work, but one that again raises ethical questions.

Researchers at Oregon Health and Science University were able to create embryonic stem cells through a cloned human embryo, a longtime goal, since such cells are capable of transforming into tissues and organs genetically identical to a patient who needs them.

Researchers took the DNA from a donor's unfertilized egg, then inserted mature skin cells containing the DNA of a patient.  That led to the creation of an early-stage embryo called a blastocyst, a group of 50 to 100 cells.  From that, scientists derived stem cells and then transformed them into heart cells.

The blastocyst was destroyed in the process and was never implanted in a human womb.

Rob Stein has been covering this story for NPR and joins us now.

HOME TOWN - San Diego's Innovation DNA

"What is San Diego’s innovation DNA?" by Roxana Popescu, San Diego Union-Tribune 4/12/2013

Excerpt

San Diego is known for being on the cutting edge of life science, wireless technology and, increasingly, wireless health — and that’s not an accident.

Imagine if French software companies started dominating the Internet and fashion designers from Silicon Valley started dictating next year’s trends. Impossible?  No, but it’s certainly unlikely.  Some very specific elements came together in Silicon Valley to enable that region to nurture Facebook, Intel and Apple, just like Paris evolved over the last century to become the world’s fashion capital.

The same goes for San Diego.  What fuels this region’s unique innovation personality — what people focus on and how they do it?  The region’s size, its many research and educational institutions, the infrastructure and urban planning decisions, a critical mass of talent and capital, the booms and busts of certain industries and even the sunshine helped transform this region into a vortex of creative energy and action, says Mary Walshok, an innovation expert at UC San Diego and co-founder of CONNECT, a nonprofit that fosters local entrepreneurship.  Her new book, out later this year, is called “Invention and Reinvention:  The Evolution of San Diego’s Entrepreneurial Economy.”

People involved in the region’s “entrepreneurial economy” — from experienced CEOs to aspiring startup founders to venture capitalists to academics — say three features characterize San Diego’s unique innovation DNA; it is collaborative between individuals and organizations, it does not scare away newcomers, and it embraces risk and perseverance with that beach-meets-frontier West Coast swagger.

A culture of collaboration

Collaborative, open to dialogue: that’s how people describe the local life science and technology innovation landscape in San Diego.

“What’s interesting about San Diego is how open it is, how permeable it is,” Walshok said.  Countless others seconded her, as if they’d all received the same “we play nice together” memo.

One reason is that many startups are spin offs from larger employers that shed workers during economic downturns.  It feels like everyone knows everyone else, many said.  A second reason are the trade and nonprofit groups that were created to bring together entrepreneurs, researchers, investors and anyone who can support their goals.  These include BIOCOM, the local chapter of the MIT Enterprise Forum, CommNexus, the San Diego Venture Group, StartupCircle and CONNECT.

Other cities where science and technology are thriving have networking groups.  Boston is a smorgasbord of schmoozing opportunities for the entrepreneurially inclined.  But people in Boston may be somewhat less inclined to team up, share resources or help each other out, various people who’ve experienced the startup scene in both cities said.

“Nobody is under any false impressions about the degree to which companies are in competition with each other.  But at the same time, we found a very collaborative environment,” said Eric David, co-founder and chief strategy officer of Organovo, a 3D tissue bioprinting company.  David moved to San Diego about a year ago from San Francisco.  He is also familiar with the biotech scenes in New York and Cambridge, Mass. Companies, academics and investors come together “in a much more open dialogue here than occurs in either San Francisco or Boston,” and that makes a difference, especially for startups, he said.

'My kind of town, San Diego is'....

SCIENCE - So Called 'Junk' DNA Isn't

"Bits of Mystery DNA, Far From ‘Junk,’ Play Crucial Role" by GINA KOLATA, New York Times 9/5/2012

Excerpt

Among the many mysteries of human biology is why complex diseases like diabetes, high blood pressure and psychiatric disorders are so difficult to predict and, often, to treat. An equally perplexing puzzle is why one individual gets a disease like cancer or depression, while an identical twin remains perfectly healthy.

Now scientists have discovered a vital clue to unraveling these riddles. The human genome is packed with at least four million gene switches that reside in bits of DNA that once were dismissed as “junk” but that turn out to play critical roles in controlling how cells, organs and other tissues behave. The discovery, considered a major medical and scientific breakthrough, has enormous implications for human health because many complex diseases appear to be caused by tiny changes in hundreds of gene switches.

The findings, which are the fruit of an immense federal project involving 440 scientists from 32 laboratories around the world, will have immediate applications for understanding how alterations in the non-gene parts of DNA contribute to human diseases, which may in turn lead to new drugs. They can also help explain how the environment can affect disease risk. In the case of identical twins, small changes in environmental exposure can slightly alter gene switches, with the result that one twin gets a disease and the other does not.

As scientists delved into the “junk” — parts of the DNA that are not actual genes containing instructions for proteins — they discovered a complex system that controls genes. At least 80 percent of this DNA is active and needed. The result of the work is an annotated road map of much of this DNA, noting what it is doing and how. It includes the system of switches that, acting like dimmer switches for lights, control which genes are used in a cell and when they are used, and determine, for instance, whether a cell becomes a liver cell or a neuron.

“It’s Google Maps,” said Eric Lander, president of the Broad Institute, a joint research endeavor of Harvard and the Massachusetts Institute of Technology. In contrast, the project’s predecessor, the Human Genome Project, which determined the entire sequence of human DNA, “was like getting a picture of Earth from space,” he said. “It doesn’t tell you where the roads are, it doesn’t tell you what traffic is like at what time of the day, it doesn’t tell you where the good restaurants are, or the hospitals or the cities or the rivers.”

The new result “is a stunning resource,” said Dr. Lander, who was not involved in the research that produced it but was a leader in the Human Genome Project. “My head explodes at the amount of data.”

The discoveries were published on Wednesday in six papers in the journal Nature and in 24 papers in Genome Research and Genome Biology. In addition, The Journal of Biological Chemistry is publishing six review articles, and Science is publishing yet another article.

Human DNA is “a lot more active than we expected, and there are a lot more things happening than we expected,” said Ewan Birney of the European Molecular Biology Laboratory-European Bioinformatics Institute, a lead researcher on the project.

HEALTH - Less Evasive DNA Test for Fetuses

"DNA Blueprint for Fetus Built Using Tests of Parents" by ANDREW POLLACK, New York Times 6/6/2012

Excerpt

For the first time, researchers have determined virtually the entire genome of a fetus using only a blood sample from the pregnant woman and a saliva specimen from the father.

The accomplishment heralds an era in which parents might find it easier to know the complete DNA blueprint of a child months before it is born.

That would allow thousands of genetic diseases to be detected prenatally. But the ability to know so much about an unborn child is likely to raise serious ethical considerations as well. It could increase abortions for reasons that have little to do with medical issues and more to do with parental preferences for traits in children.

“It’s an extraordinary piece of technology, really quite remarkable,” said Peter Benn, professor of genetics and developmental biology at the University of Connecticut, who was not involved in the work. “What I see in this paper is a glance into the future.”

The paper, published Wednesday in the journal Science Translational Medicine, was written by genome scientists at the University of Washington. They took advantage of new high-speed DNA sequencing and some statistical and computational acrobatics to deduce the DNA sequence of the fetus with about 98 percent accuracy.

The process is not practical, affordable or accurate enough for use now, experts said. The University of Washington researchers estimated that it would cost $20,000 to $50,000 to do one fetal genome today.

But the cost of DNA sequencing is falling at a blistering pace, and accuracy is improving as well. The researchers estimated that the procedure could be widely available in three to five years. Others said it would take somewhat longer.

It is already possible to determine the DNA sequence of a fetus by acquiring fetal cells through amniocentesis or chorionic villus sampling, which involves testing the placental tissue. But these procedures are invasive and carry a slight risk of inducing a miscarriage.

For couples worried about passing on a genetic disease, it is also possible to use in vitro fertilization and have an embryo genetically tested before implantation into the womb.

But the technique described in the paper would not require complete cells from the fetus and would make such DNA testing easier and less risky.

SCIENCE - New, Faster DNA Decoding

"Decoding DNA With Semiconductors" by NICHOLAS WADE, New York Times 7/20/2011

Excerpt

The inventor of a new machine that decodes DNA with semiconductors has used it to sequence the genome of Gordon Moore, co-founder of Intel, a leading chip maker.

The inventor, Jonathan Rothberg of Ion Torrent Systems (opens in new page, site includes videos via Technology tab) in Guilford, Conn., is one of several pursuing the goal of a $1,000 human genome, which he said he could reach by 2013 because his machine is rapidly being improved.

“Gordon Moore worked out all the tricks that gave us modern semiconductors, so he should be the first person to be sequenced on a semiconductor,” Dr. Rothberg said.

At $49,000, the new DNA decoding device is cheaper than its several rivals. Its promise rests on the potential of its novel technology to be improved faster than those of machines based on existing techniques.

Manufacturers are racing to bring DNA sequencing costs down to the point where a human genome can be decoded for $1,000, the sum at which enthusiasts say genome sequencing could become a routine part of medical practice.

But the sequencing of Dr. Moore’s genome also emphasizes how far technology has run ahead of the ability to interpret the information it generates.

Dr. Moore’s genome has a genetic variant that denotes a “56 percent chance of brown eyes,” one that indicates a “typical amount of freckling” and another that confers “moderately higher odds of smelling asparagus in one’s urine,” Dr. Rothberg and his colleagues reported Wednesday in the journal Nature. There are also two genetic variants in Dr. Moore’s genome said to be associated with “increased risk of mental retardation” — a risk evidently never realized. The clinical value of this genomic information would seem to be close to nil.

Dr. Rothberg said he agreed that few genes right now yield useful genetic information and that it will be a 10- to 15-year quest to really understand the human genome. For the moment his machine is specialized for analyzing much smaller amounts of information, like the handful of genes highly active in cancer.

The Ion Torrent machine requires only two hours to sequence DNA, although sample preparation takes longer. The first two genomes of the deadly E. coli bacteria that swept Europe in the spring were decoded on the company’s machines.

The earliest DNA sequencing method depended on radioactivity to mark the four different units that make up genetic material, but as the system was mechanized, engineers switched to fluorescent chemicals. The new device is the first commercial system to decode DNA directly on a semiconductor chip and to work by detecting a voltage change, rather than light.