GeneticsWatch

Creating Life and Curing Blindness

May 21, 2010

Tags: Venter, DNA, creating life, genome, American Society of Gene and Cell Therapy, gene therapy, blindness

I’ve been at the American Society of Gene and Cell Therapy annual meeting this week, garnering tales for my book, tentatively entitled “The Forever Fix.” It is largely the story of 9-year-old Corey Haas, who was on his way to certain blindness when gene therapy performed at the University of Pennsylvania in September 2008

Poor justice for the innocent

Living a Life Sentence
Kelly Cobiella
CBS Sunday Morning
April 19, 2009

Anything can happen to anyone at anytime and good things do not always happen to good people. One of the worst nightmares that can happen in a person’s life is to be falsely imprisoned and, even worse, executed. But this recurring nightmare has been experienced by thousands of people through the years. Some spend the remainder of their lives in prison, never returning to the life they once knew. Thanks to the breakthrough of DNA evidence, many have been fortunate to be exonerated of rape and murder charges after years and even decades behind bars. Others are freed as a result of determined sleuth work on the part of supporters or loved ones, people recanting original testimonies, suppressed evidence being revealed, or the surfacing of new evidence. Whatever the circumstances of their release, all of the newly freed face the same challenges of reintegrating into society.

After the initial elation of finally achieving the dream of freedom, reality is a real slap in the face for the newly exonerated. While decades passed, society moved on, technology advanced, and life slipped away. Homes were lost, careers destroyed, families broken up, insurance coverage stripped away, and children grew up. Release brings a new beginning for the wrongfully accused, with a prison record on their resumes. Many were imprisoned based on little or no evidence. In some cases, evidence was suppressed by police or prosecutors, physical evidence planted by police, other evidence manufactured by forensic scientists, and lying witnesses knowingly placed on the stand by prosecutors, all for the purpose of getting a conviction, whether to advance a career or for political or other reasons.

Beverly Monroe was 55, with a successful career as a chemist, when she was convicted of murdering her companion, Roger de la Burde, in 1992, even though police thought it was a likely suicide. There was no other evidence against Beverly but the prosecutor withheld this crucial information during her trial. Beverly’s daughter, Kate, was just starting her career as a lawyer and she quit her job to devote the next six years to freeing her mother, which she was able to do in 1999 based on the suppressed evidence. Beverly is now 62 and trying to piece her life together. Although potential employers have been sympathetic to her story, her prison record remains, and she has only been able to find a job as an administrative assistant with no benefits, a stark contrast to the success she had enjoyed before her conviction.

Following her mother’s release from prison, Kate Monroe moved to Utah to work as executive director of the Rocky Mountain Innocence Project, which has worked to pass a compensation law to aid the wrongfully convicted upon their release from prison. The law, which was passed in 2008, awards about $35,000 for each year of false imprisonment up to 15 years, and expunges the person’s criminal record. Only 25 states have such a program. Virginia, where Beverly Monroe lives, is not one of them. Another group called the Innocence Project has helped free 235 people with DNA evidence; 17 of them were on death row. The Innocence Project also works to reform the criminal justice system in order to prevent recurrences of such stories, many of which are far worse than Beverly Monroe's.

It’s true that mistakes can happen. But it’s hard to imagine the sheer powerlessness and devastating bitterness one must feel at the hands of someone who deliberately steals your life from you for personal gain. We never hear the names of the prosecutors or police officers who tamper with evidence or suppress information. There must be a law that is protecting them. We need laws that provide accountability for such misconduct. Or maybe we have them but the victims simply don’t have the fight left in them or the resources to engage in another battle. Or maybe they’re just grateful to be free. It seems that there is a conspiracy of silence regarding this issue. It is fair that victims of the justice system should be compensated and their records expunged in the case of wrongful incarceration. State governments should all adopt laws similar to the one passed in Utah and I further propose that resources should be allocated to psychological counseling and job counseling, as well as job placement and other services to ease the transition from prison to society. It wouldn’t give back the lost years but it would help to make the remaining ones better.

Biobanking Throwdown: 2nd Round

We had posted earlier about the ongoing debate on the ethics of DNA databasing -- here is round two in the debate. Our poll is still open, let us know where you stand!

First Female DNA Decoded

[Cross-posted from the Blazing Indiscretions blog, hat tip to blogger Jay Vos]

The first decoding of DNA in a female was done in The Netherlands, reports DutchNews.nl. A red-haired, 34-year-old Dutch woman has become the first woman in the world to have her compete DNA unraveled, genetic scientists at Leiden University Medical Centre announced on Monday.
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[T]he sequencing data of a female provides more insight into the X chromosome. 'Because the X chromosome has to do all the work in one half of the population - the males - selection has been tougher during human evolution,' according to Van Ommen. 'This means the X chromosome is less variable.'

Male sequencing data has already been unraveled from Jim Watson, co-discoverer of the double helix structure of DNA, from researcher Craig Venter and from two Yoruba Africans. 'It was time to balance the genders a bit,' news agency AP reported Van Ommen as saying.

Decoding the DNA took six months, but the scientists point out they could only use the sequencing equipment when it was not being used for other projects.

Feds to cast a wider DNA dragnet

Following up on Sue's post last week about surreptitious sampling of DNA by law enforcement officials comes this disturbing report about Federal plans to widen their DNA database, CODIS, to include samples taken from anyone arrested by a federal law enforcement agency. This represents a major change from the Federal government's current policy of collecting genetic samples only from those convicted of felonies. 

For all of us, but particularly for those of us who have been detained by the Feds in the past for being in the wrong place at the wrong time (okay, well maybe because of being at a protest ... but the charges were dropped), this new policy raises serious privacy and civil liberty issues. The newly proposed regulations will be published in the Federal Register shortly, followed by a 30-day public comment period. 

The implications of "surreptitious sampling" of DNA

A recent NYT piece by Amy Harmon highlights a law-enforcement practice called "surreptitious sampling," which refers to the collection of an individual's DNA without their permission or knowledge. All of us are leaving traces of our DNA all over the place, all the time: on drinking glasses, kleenex, soup spoons, cigarette butts, etc. If the police wanted a blood sample, they'd have to get a court order; but these discarded or overlooked materials may be gathered by US law enforcement agencies--without probable cause or any oversight from the courts--and used to match samples collected in criminal investigations. If the DNA from the murder scene matches the DNA on your soda straw, you're in big trouble.

At the moment, there's no legal barrier against the Feds' deciding to build a national database of our genetic information to be used for law enforcement purposes. The FBI already has a database of genetic information from convicted criminals, and it has lobbied to make the database more inclusive (eg, to retain samples/data from people who have been arrested but not convicted).

In the UK, a national DNA database has been built that contains genetic information on more than 5% of the population (compared with the FBI's collection on 0.5% of Americans). There's been substantial debate in the UK about the legality and propriety of the resource: you can read more here, here, and here, for example.

Lots of people--including health researchers, pharma companies, insurers, employers, and law-enforcement agencies--would like access to huge datasets of individuals' genetic information. Once such repositories are built (and they are already being built), arguments in favor of a centralized resource are sure to follow, citing efficiency and cost-savings benefits. There are (imo) important privacy and civil liberties reasons to resist such developments.

the democratization of DNA?

Some people say it's the democratization of DNA. Others are seeing dollar signs in the double helix. And some states, like New York, the option isn't even there. But in most states, you can now pick up a DNA test for a few bucks that will answer the question: are you my daddy? The paternity test by Identigene cost around $30 in store - with another $120 in lab processing fees. But it guarantees to answer, with a 99% accuracy, whether or not someone is the father of the child in question.

It's not a legal kit, it won't hold up in court - those are also available over the counter (or at least, over the internet), and cost quite a bit more money. But people are suggesting that the use here is not necessarily to prove paternity in a court case, but to try to prevent a case from going that far to begin with. A sort of pre-court negotiation tactic, I suppose. But I wonder how effective that's really going to be? I know more than one couple with an acrimonious split where, if this kit were used to prove paternity, the retort would just be that the woman was using the DNA of the "real" father, and not the man in question; it would just feed fires rather than calm them. Perhaps calmer heads to prevail...

I just don't see this offering the peace of mind it's being advertised to offer. If there's that level of suspicion and mistrust already, is a test going to help? I suppose it might, so long as it answers the affirmative - that the child is his son. But what does it do to trust in a relationship? What are the social implications? And what does it say that Identigene is offering the kits so inexpensively because of the anticipated volume of sales?

Maybe most importantly, what happens when a test result comes in, and it's not the result you want (either way)? There's no one around to talk to, or help you work through possible conflicting emotions (or anger). There's not necessarily a cooler head to prevail, and to get one, you're probably going to have to spend the money over again, to have an actual legal and verifiably untampered sample taken and tested. Which just means spending more money in the long run.

The more I think about it, the more this seems like it's taking advantage of people's fears without any sort of positive payoff for the person involved - but it's also early Monday morning, I haven't had coffee, and I am admittedly cranky. Does anyone else have another/different take on this? Can you see a positive here that I am missing?
-Kelly

New Gene Research Exciting...and Risky

While news of the research has yet to be published, British scientists announced the creation of human embryos containing DNA from two women and a man. The scientists say the goal of the research is to one day obtain the ability to produce embryos free of genetic disease.

Presented at a recent scientific conference, and funded by the British Muscular Dystrophy Campaign, the researchers employed a process that basically took normal embryos with defective mitochondria in the woman's egg, and replacing it with an egg donated from a second woman with healthy mitochondria. Errors in the mitochondria's genetic code is what results in diseases such as muscular dystrophy, strokes and epilepsy, for example.

Supporters of the research say the procedure offers hope for families facing the heartache of unavoidable inherited disease. Opponents fear genetically modified babies.
Read the details of the research here:

Biobanking, part 3: returning research results to participants

So: you've agreed to participate in a genetic study for health purposes, and (with or without your consent--see post #2 on biobanking) the data you've provided has been made available to the broader research community. A sample of your DNA is stored in a biobank, and researchers who have been vetted by the biobank owners are allowed to use that DNA in future studies.

The consent form you were required to sign at the time you agreed to participate in the original study stated that you would not be contacted by the research team with information about the results of the research, or of any testing or other processes they might perform as part of their study. "Ok," you thought--having been informed that most genetic research being done today isn't informative at an individual level and wouldn't be clinically useful anyway--"fair enough. I don't need the researchers to contact me with information I can't act on anyway."

Fast forward 20 years. The promise of genetic research is beginning to deliver. As research uncovers more information about how genetics interacts with environment and behavior, the DNA sitting in biobanks around the world is telling more tales than it used to. The DNA that was formerly mere data is increasingly yielding meaningful information about the health risks of individuals. So, in our imaginary scenario, let's say that--20 years after you consented to participate in a breast cancer study--researchers working on a different project discover that you carry a genetic mutation that has been definitively linked to Serious Medical Problem X.

Here are some of the questions this (not terribly far-fetched) scenario brings up for me. Do the researchers have a professional and/or moral obligation to share this information with you? Does it matter that the original consent form, which was written for a single study that the researchers truly didn't expect to provide individually meaningful information, said they would not contact you? What if the researcher contacts you with information that you didn't want? Might the researchers' obligation to re-contact participants depend on whether or not there are good risk-reduction or treatment options for Serious Medical Problem X?

Here's some additional reading for those who want to read more on return of results from genetic studies: here's a paper from the Social Science Research Network; recommendations of a working group at the National Heart, Lung, and Blood Institute; a nice list of refs from Stanford's Center for Clinical Bioethics; and the issue of the American Journal of Bioethics that features a target article and open peer commentaries on this topic.

Wanna read the first 2 posts on this topic? Here they are: 1 2

Genetic tests and clinical utility

There was a story on NPR's Talk of the Nation earlier this week (listen here) about the array of genetic tests that are now available to you, the consumer. The news hook was a new blood test that researchers claim can define individuals' likelihood to develop Alzheimer disease. Like many other such tests, this one doesn't yield a yes/no answer: it identifies an increased propensity to develop the condition. It can't say for sure whether a person will in fact get Alzheimer disease, or, if she does, what the course of the illness is likely to be. But, for many people, the trouble is not just the certainty of the diagnosis or the accuracy of the prediction.

For some conditions, like Alzheimer's and Huntington's, treatment is limited and cures have not yet been found ... so there isn't anything that a person might do differently to reduce the risk of getting sick. The clinical utility of testing in these situations is limited: the results of the test will not change the medical management of the patient. Some people want such information to help them plan for their own futures and those of their families; others don't want to know and might see such unwanted information as burdensome.

Lots of questions here. Would you want to know? What is the value of information in this situation, and are all reasons for testing equally deserving of respect? Should such tests be available in direct-to-consumer form, without medical direction or involvement--and does it matter if the reason people pursue testing "off the books" is to prevent their insurance company from finding out that they're at increased risk? Should counseling be mandatory, or is that too much paternalism?

New Vistas in Mapping the Genome of Life

In the continuing quest to get one step closer to making man-made life a reality, genetic engineering researcher Dr. J. Craig Venter has announced that he and his team have manufactured the entire genome of a bacterium, through a clever "stitching together" of its chemical components, a feat being heralded as "watershed" for the emerging field called synthetic biology.
This genome is more than 10 times as long as the longest piece of DNA ever previously synthesized. What it means is the possibility of scientists to be able to one day design an organism on a computer, press the “print” button to have the necessary DNA made, and then put that DNA into a cell to produce a custom-made creature, a possibility certain to raise many ethics questions in the minds of scholars and laymen alike.

See details of this emerging technology in this from the NY Times.

Should genetic researchers be able to share your DNA?

As promised (or warned--I guess it depends on whether you think this is an interesting issue), here is another thing to think about with regard to genetic biobanking studies.

So: say you've agreed to participate in a research study that is trying to identify whether there is a genetic contribution to breast cancer. In this particular study, the researchers will follow a cohort of women who have not developed breast cancer at the time of enrollment. The researchers will take blood samples and do physical exams periodically. They will also sequence your DNA. As time goes on, some number of women in the study cohort will develop breast cancer, and some won't. The researchers will look at the DNA sequences to see whether there are different patterns in the genetics of the women who develop cancer as compared with those who don't. If they find such patterns, they'll go on to investigate what those specific mutations do.

This kind of research, which is called a genome-wide association study, GWAS for short--because it's looking for associations between genetic patterns and disease--is a lot like a fishing expedition. (You can learn more about these studies in this archived Science Friday audio panel with Ira Flatow.) How GWAS's work has a couple of important implications. One is that, for such studies to work at all, researchers need really big datasets to sift through. Another is that the same dataset could be used for lots of different purposes.

For these reasons, and for efficiency and cost-effectiveness reasons as well, the National Human Genome Research Institute (NHGRI) is trying to develop plans to pool or share such datasets across different projects.

Think back to our breast cancer study example. If you'd consented to participate in that study at your local research university, how would you feel about your (de-identified) information being used by researchers somewhere else? Would you feel that you needed to be offered the chance to opt out of this "wide data sharing?" Or would you feel that your original consent covered such subsequent uses?

Here's another permutation to think about. Say the researchers did the breast cancer study, and in the course of that work they noticed that there seemed to be a correlation between certain genetic patterns and alcoholism or schizophrenia. Would it be ok with you for them to pursue this line of inquiry using your genetic information? Would you feel that you needed to be offered the chance to opt out?

You can read about the NHGRI policy, and the scientific community's reaction, in The Scientist, here. Salon.com ran an article a few years ago about a much smaller open-source approach to genetics, here (which is where the nifty kitty photo came from).

Embryonic Stem Cells for Therapeutic Cloning in Humans

A California research team has become the first to report, and document, the cloning of a human embryo using donated oocytes (egg cells) and DNA from the cells of an adult donor.

The study has been published online by the journal "Stem Cells."

The experiments, using a technique called somatic cell nuclear transfer (SCNT), provide key steps toward the development of patient-specific embryonic stem cells for use in developing new treatments for conditions such as Alzheimer's disease, Parkinson's disease, and spinal cord injury, among others. The lead author was Andrew J. French, Ph.D., of Stemagen Corp., a private company headquartered in La Jolla, Calif.

In the experiments, the researchers removed the nuclei of mature oocytes from healthy young women who had previously donated eggs for successful infertility treatments. The SCNT technique was then used to insert DNA from an adult male donor into the oocytes. The DNA was derived from a type of cell called fibroblasts, obtained from skin biopsies.

Subsequently, several of the reconstructed oocytes continued to develop as normal embryos, to the blastocyst stage. Extensive and carefully documented genetic tests were performed to confirm the genetic identity of the cloned embryos. In three embryos, tests showed the same DNA as the male fibroblast donor.

In one of the three cases, additional tests showed that the embryo had another type of DNA, called mitochondrial DNA, from both the female oocyte donor and the male DNA donor.

Mitochondrial DNA testing is viewed as an essential proof of successful human cloning -- particularly after previous fabricated reports from a South Korean research group.

The ability to generate stem cells using the patient's own DNA is significant in the treatment of currently incurable degenerative diseases, as well as for cell-based drug discovery. Previous studies reporting the development of cloned human embryos have used embryonic stem cells as the DNA donors.

While the study is an important step toward the development of stem cells for therapeutic cloning, much more research will be needed to confirm and extend the results.

UK will allow human-animal hybrids for stem cell research

On January 17, the UK's Human Fertilisation and Embryology Authority (HFEA) granted two universities 1-year licenses to pursue the development of human-animal embryos for research purposes. This is a reversal of prior policy, which banned such transgenic experimentation.

The ultimate aim of this work will be to develop personalized stem cells that can be used to cure disease. The researchers will clone individuals with serious illnesses by inserting their DNA into enucleated cow and rabbit eggs, resulting in hybrid embryos from which stem cells can be extracted. The hybrid embryos are to be destroyed no later than 14 days after they are created. It is hoped that using patients' own DNA in this process will reduce (or, better still, eliminate) the risk of transplant rejection (graft vs. host disease) when the stem cells, or organs grown from them, are implanted in the patient's body.

The UK's approach sidesteps at least two issues that have been problematic for scientists in the US: (1) the destruction of human embryos question (because they're hybrids, not solely human), and (2) the problem of gathering a sufficient number of donated human ova for research purposes. It's at least a little bit interesting to note that public opinion in the UK generally favors this approach, even as the rejection of genetically modified "Frankenfoods" continues to be reported in the news there.

However, US opinion has been quite strongly against such transgenic experimentation, generally because of concerns of developing chimeras with human (or human-like) consciousness. Additionally, the requirement that the chimera embryos be destroyed within 14 days of creation is probably pretty close to unenforceable-which gives rise to the kinds of nightmare scenarios Margaret Atwood contemplated in Oryx & Crake ("baby orchards" for organ transplants).*

So: Does the HFEA's approach create more problems than it solves? Talk amongst yourselves.

News here: The Guardian, Financial Times


*And yes, that's another WBP Book Club selection! Go here for more info.

Biobanking and you

Imagine this scenario: you're a healthy person, no major complaints. You go for your annual physical exam, and you have a couple of blood tests--standard stuff, checking to make sure your cholesterol's ok, you're not anemic, etc. A couple of weeks go by, you get a card in the mail that says everything's fine. End of story, right?

Maybe not.

Now imagine that the hospital or clinic has retained the blood left over from the tests your dcotor ordered. And further imagine that the hospital or clinic has what's called a biobank or biorepository--that is, a collection of stored tissue for use in research. Your DNA is extracted from the blood sample and sequenced--which means that some piece of your genotype is now known to some researcher (but not to you). In some institutions, this couldn't happen without your explicit (written) informed consent; but in others, it's standard practice that "waste tissue" from blood tests, pathology samples, etc. becomes the property of the hospital or clinic. Should informed consent be required, or is an opt-out model more appropriate?

Generally speaking, biobank participants' DNA samples aren't associated with their name, Social Security Number, street address, or other information traditionally considered "identifying"--but the reality is, nothing is a more precise identifier of who you are than your so-called genetic fingerprint. Is this worrisome?

I'd be interested to hear what others think about this--and, fair warning, I am likely to be asking more questions along these lines, as the DNA biobanking issue is on my mind a lot these days!

While I'm at it, here are two references for further reading, if you are so inclined. The Stored Tissue Issue, from Robert Weir, Robert Olick, and Jeffrey Murray, is an academic treatment of the issues. Michael Crichton's Next is an entertaining look at some of these questions--and it just happens to be a WBP Book Club selection.

Creation of New Life Forms: the next step for DNA?

This article fascinated me. Scientific breakthroughs, especially revolving around the use of DNA science--and the ethics of it--always gets my attention. But this article was a mixture of fascination, awe--and fear. There also remained the lingering question in my mind of whether this could really be true--that researchers are indeed considering taking this next step--or if just simply a rumor spawned by someone's overactive imagination.

You can read the Washington Post article, and decide for yourself: whether the prospect of creating new life forms--synthetic life forms--from artificial DNA should be considered a scientific breakthrough--or a major mistake, and what questions it raises about science, religion, ethics and the very essence of genetics.