The OpenHelix Blog

Please indulge a long post from a personal perspective, what genomics is about to do for _me_. This is information that many, if not all, of our readers already know. I’ve been researching and working in either experimental biology or genomics for over 20 years. Ever since the beginning of the Human Genome Project , which coincidently started the same year I started my Ph.D. program, into my postdoctoral research at EMBL and now my work at OpenHelix, I’ve known that someday personal genomics was going to impact me, and millions of others, in a big way. Yet, it has always felt that it was one of those things that would be a decision I and we as a society didn’t have to make until we turned that corner that seemed always “just ahead.”

But now I think we’ve turned a corner. It feels, to mix metaphors, that we’ve hit a tipping point. The Human genome project, the mapping and sequencing of the/a human genome from 1990 to 2003, cost approximately 2,700,000,000 dollars (that’s 2.7 billion, I wanted to get all the zeros in). Celera did the genome for 300,000,000. The cost of sequencing an entire human genome has been plummeting ever since. In 2007, the cost of sequencing the genome of James Watson (co-discoverer of DNA) was about 2,000,000. The today cost is about 10,000. Complete Genomics and other companies are on the march to quickly reducing the cost of sequencing a genome under 1,000.

Let me graph the last 8 years for you, mind you, this is starting from the 300,000,000 number, not the 2.7billion, because that graph would be a straight line down.

So, within a year, the cost of sequencing your, my, genome will reach 1,000. If not less. We’ve seen this coming for years now, and it’s upon us. But what does it mean?  A lot of data. But data means nothing without context and analysis. Sequencing my genome would be a waste of 1,000 dollars if I gleaned nothing from it.

Yet, even that seems to have turned the corner from a few tidbits of genetic information to a steady steam and the beginning of a flood.

You know you’ve turned a corner when a genomics testing company begins to offer genetic tests to the mass market through Walgreens. There’s enough context in that data to make money from it, or so they hope. You can be sure the corner is safely behind you when the FDA tells Pathway Genomics and Walgreens that they will need to hold off while they make sense of the regulatory implications. Genomic ancestry test are are also gaining is usability… and scrutiny.

It was the recent Lancet paper on the clinical analysis that seemed to be a tipping point, not for me or those in the field. Genomics has been on my radar since 1988, but for society. I blogged about the paper and it’s use of genomics resources such as GVS, dbSNP and others. In the paper, the researchers did a thorough clinical assessment of an individual’s genome. We’ve brought down the cost of sequencing, now we are learning how much it’s going to take to assess that data from a medical point of view, and importantly, what we can learn from it.

What can we learn from it? I read this paper again from a personal perspective now. Could I learn something from sequencing and analyzing my genome, and if so what. My answer came to this: yes, I could learn something and in fact enough that I’m not convinced that as soon as that sequencing gets down to a 1,000 or lower (and is a high quality sequence , I’m going to do it.

There are three things I see from this paper that one could learn from assessing their genome: prevention, early detection and therapy. I believe the former will be, for most people, something they already know and their genome sequence will tell them nothing new. The other two could be a wealth of information they will want, even need, to know. You’ll notice I left off ‘cure.’ I saw nothing in this paper, and nothing on the near horizon, that suggests to me that our genome sequence data will help with curing anything. Perhaps, just not much. Yet, the possibilities of early detection of disease and personalized drug treatment are tantalizing.

So last week I treated myself to my first vacation in a long time.  It was my birthday, and I wanted to disconnect a bit and recharge.  Mostly it worked, although the hundreds of emails I’m facing this morning are a bit daunting.  But just before I left I got an email from a colleague who asked me a really great question:

….I would love to know where you would start when you get back a personal genome sequence….

And I couldn’t shake this out of my head.  I was sitting on a bridge outside Windsor Castle thinking about it as the sun set on my first day.  (On subsequent days I found that the far superior ciders in the UK were able to push this question out of my head for some periods of time. And also pie.)

I’ve spent some significant time thinking about the onslaught of personal genomics, of course.  It’s all been very theoretical, because I would have refused to even begin the process of obtaining my personal genome sequence until the GINA legislation fully kicked in.  But now that barrier is down.  I’m still not ready to get mine done for a variety of reasons (cost, quality, informative value).  But it’s still worth thinking about what I would do with it if it was handed to me–in specific terms, with concrete actions.  So here’s what I decided I would do.  Your mileage may vary.  And I’d love to hear what others might do with theirs.  Follow the link for the specific actions I’d take.

I’m very interested in public policy and genetics. There are a number of threads that I was following along those lines. On the actual legislation I was watching the GINA efforts, and participating where I could. I was reading an article on the downstream effects of that today (Two Cheers for GINA, by McGuire and Majumder, Genome Med 2009, 1:6 doi:10.1186/gm6).  One sentence sums up my feeling on GINA–we absolutely needed some protection, but other problems in our health care and insurance systems will persist…

If significant sections of the public focus on these gaps in US policy, reluctant to enter the genomic era without a blanket guarantee against harm, GINA may fail to live up to the hopes of its supporters.

There was also a series of public meetings about biobanking and genetics research that I was following (Town hall meetings on genes + environment studies).  I wish I could have participated in these town halls to get a sense of the room full of people interested in this topic–but none of them were near me.  However, the report on these was just released and you can get the summary of the outcomes from the sessions:

Center releases report on genetic town hall series

….Most participants felt that the biobank should go forward, and more than half indicated they were likely to participate in it if asked. Among the issues participants weighed in on were privacy protections for participants and concerns about possible misuse of information collected, the nature of the proposed study’s consent agreement, and the ability to get individual research results back from the study….

If you go to the DNApolicy.org site you can download the report in PDF form.  It is clear that the participants were concerned about discrimination based on the information–especially by insurers, but also law enforcement.  And this is despite the passage of GINA during this timeframe.  There are privacy concerns in general, too.  And the potential for misuse for “nefarious” purposes.  They also saw the benefits–research and new knowledge, new medications, increased precision for treatments.

Thanks to the Genetics & Public Policy Center folks for the report.  Thanks to the Genetic Alliance Policy Bulletin mailing list for the heads-up.

This week’s Genetic Alliance Weekly Bulletin led me to a paper that investigated public opinions on genetic research that I wanted to examine. The GA link brought me to this press release about the paper:

Survey finds wide public support for nationwide study of genes, environment, and lifestyle

Four in five Americans support the idea of a nationwide study to investigate the interactions of genes, environment, and lifestyle, and three in five say they would be willing to take part in such a study….

This paper by Kaufman et al (Genetics in Medicine. 10(11):831-839, November 2008) kept me busy while waiting for a doctor’s appointment this week.

I think this is good news for the progress of research. And after we have GINA in place I might even take part in some. I would not have done so before, and I would have advised family members not to participate.

But there were a few things that struck me as interesting. First, in the study description that survey participants were to see there was no mention of possible implications of legal protection (or lack of). That’s something I would want to see in any kind of agreement and I would like to see how the public would respond with or without legal protection. {You can access the study descriptions that participants saw from the supplement page, the second PDF = Article Plus #2}

But maybe that’s just me. I’m a suspicious Yankee. In fact, in the paper it turns out that we were less likely to support the work than other regional groups.

% who would probably or definitely participate {snipped from Table 2}

Northeast: 57

Midwest: 59

South: 59

West: 64

Hmm.

Interestingly–91% of survey participants ‘wanted their individual research results about health risks “even if there was nothing [they] could do about them.”‘ It even went up from there when they were asked if they wanted to know if a genetic risk factor was found or if they were higher risk for a treatable or untreatable condition. This is going to require serious education of the general public to understand the data properly.

However–despite agreeing to this in the form of this survey, I wonder how many would actually go and participate. At one point the authors refer to their outcome of willingness to participate as in range with similar types of studies about donating blood or DNA for other purposes. I know it isn’t directly comparable, but the actual rate of blood donation for medical purposes is only 5%. I was shocked to hear that statistic one time. The authors do acknowledge in the discussion that support for participation is not the same as actually doing it.

An odd tidbit for people who are curious about the effectiveness of conveying information with a video format:

Viewing the video was a significant predictor of overall support for the study but not of people’s willingness to participate. Inflection, tone, and images in the audio and video may have given more concrete meaning to the words and increased understanding, may have lent a measure of credibility to the study description, or may have created a persuasive bias. However, though the difference in support for the study was statistically significant, it was not large.

For someone who spends a lot of time making movies that convey information this was a nice observation . But I can’t find the numbers on that.

The authors do muse about the passage of GINA and whether that would affect subsequent surveys. I wonder too. And they also conclude:

This suggests that more detailed research to explore what the public understands and believes about individual research results may be warranted.

I definitely agree with that.

The paper:

Subjects matter: a survey of public opinions about a large genetic cohort study.
Genetics in Medicine. 10(11):831-839, November 2008.
Kaufman, David PhD; Murphy, Juli MS; Scott, Joan MS, CGC; Hudson, Kathy PhD

DOI: 10:1097/GIM.0b013e31818bb3ab

In the current deadlocked state of affairs in Congress, I am still shocked that the GINA legislation was able to make it through. And although some people didn’t understand why we needed it, it only becomes more clear that the information from even beneficial research could be misused.

The legislation still doesn’t take effect for a while (it begins to protect us only after May and November 2009), but one of the major groups lobbying for this bill has produced a user-friendly interpretation of what we should be able to expect from GINA. Things like what it does prohibit and what it doesn’t prohibit.

Here’s a piece of the press release:

The Coalition for Genetic Fairness today announced the launch of an interactive, online guide to the landmark Genetic Information Nondiscrimination Act (GINA). The resource, “What Does GINA Mean? A Guide to the Genetic Information Nondiscrimination Act” , summarizes the protections of the first civil rights legislation passed in the new millennium and outlines its impact on the future of health in America.

Check it out if you are curious about what GINA will do. You can find the whole thing on the Coalition for Genetic Fairness site and on the Genetic Alliance site as well.

This was just NOT a headline I was expecting to see as I read my latest GenomeWeb email:

“Forensic Breakthrough Stirs NIH to Close GWAS Data from Public View”

I mean, so much of what I have been reading and seeing in resources lately is a push to make GWAS data available and possible to analyze. And all the enthusiasm we all felt after GINA finally passed. The headline took me by surprise. But now that I’ve gotten past my initial response, I’ve had some time to look into this a bit more & it isn’t an early April Fool’s joke. Researchers at the Translational Genomics Institute (TGen) and at UCLA used high-density SNP genotyping microarrays to accurately determine if an individuals DNA was included in a mixture of DNA from 200 people or more, even when the individual’s DNA accounted for less than 1% of the total DNA. Before this study, it has largely been assumed that pooled allele frequency data was too complex for any one individual to be identified as a member of the group contributing the DNA. The research and results are beautifully presented in the PLoS Genetics paper that I’ve reference below.

But the privacy implications of this research are huge & already causing major changes in the way that GWAS data is being presented – as indicated by the title of the GenomeWeb article. NIH has altered their GWAS data access policies, and today it was announced that the data from two such studies have been removed from the the UCSC Genome Browser. I am glad that the authors of the research raised their concerns with NIH well in advance of publication, and I’m glad that NIH and other resources are taking the privacy concerns so seriously – I just hope everyone (read popular media) reacts as calmly and intelligently and that this doesn’t cause an unwarranted back-pedaling on all GWAS efforts. I am very anxious to see the public reaction (if any) to this, and how this all turns out. Where do you think this will take us? Do comment with your thoughts!

Here’s where I got my information:
Jiali Han, Peter Kraft, Hongmei Nan, Qun Guo, Constance Chen, Abrar Qureshi, Susan E. Hankinson, Frank B. Hu, David L. Duffy, Zhen Zhen Zhao, Nicholas G. Martin, Grant W. Montgomery, Nicholas K. Hayward, Gilles Thomas, Robert N. Hoover, Stephen Chanock, David J. Hunter, Gonçalo Abecasis (2008). A Genome-Wide Association Study Identifies Novel Alleles Associated with Hair Color and Skin Pigmentation PLoS Genetics, 4 (5) DOI: 10.1371/journal.pgen.1000074

2. National Institutes of Health: Modifications to Genome-Wide Association Studies (GWAS) Data Access (August 28, 2008) http://grants.nih.gov/grants/gwas/data_sharing_policy_modifications_20080828.pdf

3. Forensic Breakthrough Stirs NIH to Close GWAS Data from Public View

(August 29, 2008 By Matt Jones, a GenomeWeb staff reporter) http://www.genomeweb.com/issues/news/149097-1.html?type=pf

4. TGen, UCLA Scientists Reveal Approach for Finding Needle in Genetic Haystack (August 29, 2008 By Andrea Anderson, a GenomeWeb staff reporter) http://www.genomeweb.com/issues/news/149084-1.html

5. TGen scientists uncover new field of research that could help police in crime scene forensics (PHOENIX, Arizona – August 29, 2008) http://www.tgen.org/news/index.cfm?newsid=1204#

6. [Genome-announce] GWAS data access removed from UCSC website (Donna Karolchik, Tue Sep 2 09:06:57 PDT 2008) https://www.soe.ucsc.edu/pipermail/genome-announce/2008-September/000138.html

The successful passage of the GINA legislation (Genetic Information Nondiscrimination Act) was long in coming, and the celebrations are still going on. The Genetic Alliance newsletter just offered a link to a video from the celebration, which includes Francis Collins for the soundtrack and celebrants showing us how to dance to G-I-N-A. I don’t see this moving to MTV any time soon, but some of you will enjoy this.

There are more videos from the GINA celebration linked from the Collins video page–our huge thanks to all those people who worked so hard and so long to pass this important legislation.

Just got this notice from the Genetic Alliance newsletter:

You can learn more at the NHGRI site: http://www.genome.gov/27527023 This first one appears to be:

All About the Genetic Information Non-Discrimination Act of 2008 (GINA)

What is GINA? How will it affect me? How will I – and my family – be protected? Join NHGRI Deputy Director Alan Guttmacher, NHGRI Health Policy Analyst M.K. Holohan, and President and CEO of the Genetic Alliance Sharon Terry on July 17, 2008 at 1 p.m. Eastern to learn about this ground-breaking act that was passed into law in May 2008.

It does look like you have to register, so be sure to check out the NHGRI site and reply to that email for details.

I can’t attend–someone let me know how it goes! I wish I could hear it, I’ve been following this legislation for a long time….Maybe it will be available as a recording later, I can’t tell.

Whoa. Usually I don’t get my genetics news from Forbes, but I thought this was interesting for this field. My Bio SmartBrief email today had a link to this tidbit:

California Orders Stop To Gene Testing

California becomes the second big state to crack down on companies that offer gene tests to consumers via the Web. This week, the state health department sent cease-and-desist letters to 13 such firms, ordering them to immediately stop offering genetic tests to state residents….

23andme did not immediately return calls Friday afternoon. Navigenics confirmed it had received a letter. Navigenics Chief Executive Mari Baker said her company continues to process orders from California residents because “to the best of our knowledge, we are in compliance” with state law….

This area seems so wild-west to me at this point, I’m interested to see how this turns out. For specific information on clinical gene tests at this point I use GeneTests. They have a whole section of laboratory listings and the tests they perform. When we developed our tutorial on GeneTests they made us aware of this great graphic about tests available today. The growth in available tests is remarkable–and it is just the beginning. Thanks to Congress for GINA, but man…I’m daunted by the possibilities, and I know what the testing can and can’t tell you.

Wow, this is a big deal. I was surprised to learn this from a few sources, including Salon and an email I just found in my inbox. It is from the Genetic Alliance announcements list. I can’t find it on their website yet…but here is a copy of the announcement from NHGRI.

I was just enjoying the photo of a smiling Ted Kennedy and Francis Collins with the inimitable Louise Slaughter this week, too. What a team. This photo is my favorite, but there are more over at the Genetic Alliance photo page.

He is an impressive guy, and has done great things for this field. And I’m so glad that he was involved in getting the GINA legislation passed. Many thanks for Francis Collins for getting us to where we are today.

EDIT: I just found some videos of him actually singing…but is messes with the blog so you’ll have to search YouTube yourself. Here was one that was all DNA: http://youtube.com/watch?v=YXERB6me9ZE