Typically $199, the ‘free’ DNA test is cheap, but not exactly $0. The offer requires you to sign up for 23andMe’s Personal Genome Service at $9/month for a year. Still, $108 is definitely less than you’d expect to pay. If you’ve ever wanted to check out the secrets of your genetic code, 23andMe’s ‘DNA Day’ discount might be exactly what you need to get you started. Hurry, though, the offer is only good while supplies last, and it will end tonight (April 11th) at midnight PDT.

23andMe is a smart company for many reasons. They were among the first to offer retail DNA analysis to a wide consumer market. In the case of a few big-named illnesses, like Parkinson’s, they have spear-headed drives to collect large numbers of DNA samples that might give scientists insights. They have organized user-driven research initiatives, allowing those who purchase their tests to help determine which diseases the company would try to link to genetic markers in the future. Needless to say, any discoveries about how these illnesses were linked to genes would inevitably make their DNA analysis services more valuable as well. Yet it’s not all so Machiavellian. When these tests end up showing important information about a patient they can be very helpful, and even save lives, as the following video from 23andMe will attest:

As smart as 23andMe has been in developing their business, I’m worried that the underlying technology of their company has an upcoming expiration date. They rely upon a very particular kind of DNA analysis – mapping important gene variations known as single nucleotide polymorphisms (SNPs). While SNPs can provide some meaningful insights on occasion, they are not nearly as comprehensive as sequencing your whole genome. Whole genome sequencing has a price tag of around $5000 or more, so the $108 SNP test seems like a much better bargain. In five years, however, I’m pretty sure that a retail whole genome service could be available for $100 or so as well. Why settle for just looking at pieces of your DNA when you can see the whole thing for about the same price?

Actually, you may not find either option very useful. While some patient will discover meaningful facts about their genes, most of us may not. I certainly didn’t when I took a SNP based test (from a different retailer). Personal genomics are still at such an early level that we don’t know how to weight much of the genetic information we learn from SNP or whole genome analyses. There need to be several more years of genetic research, and dozens of groundbreaking discoveries before DNA testing becomes the universally helpful medical boon we already expect it to be.

If I were to make a recommendation, it would be this: think of these tests as exercises in scientific curiosity. If you want a serious medical analysis, spend more time with your doctor and health professional. If however, you are interested in looking at pieces of DNA just to see what you can learn, then this kind of personal genomics may be exactly what you want. There’s really no better time to satisfy that intellectual itch, so shell up the $108 and order from 23andMe today. Let us know if you find out something interesting about your DNA. Hmm…I wonder if there is a SNP that corresponds to enjoying Singularity Hub.

[image and video credits: 23andMe]
[source: 23andMe]

Old friends and new allies poured $22 million into 23andMe. New research may be the key to keeping the company secure.

23andMe, one of the pioneering companies of personal genetics, is ramping up for another round of growth. According to a recent press release, the Mountain View based DNA analysis business raised more than $22 million in Series C funding. While it’s no surprise that early investors Google Ventures and New Enterprise Associates continued to back 23andMe (Google founder Sergey Brin is married to 23andMe founder Anne Wojicicki), the arrival of newcomer Johnson & Johnson Development Corporation shows that the startup is still attractive to outsiders. Wojicicki commented that the $22 million would go a long way towards expanding their research efforts. While 23andMe has had its issues in the past, this new round of funding could be a sign that the company is ready to bounce back stronger than ever.

Companies like 23andMe test the DNA of customers and analyze it for important single nucleotide polymorphisms (SNPs) – a process that has drawn fire in the past year for its over simplifications. 10 years after the first human genome was sequenced, genetic analysis has yet to provide clinically proven benefits to the majority of customers who use the services of companies such as 23andMe. The FDA, US Congress, and other government regulatory bodies are actively investigating how best to control mail order DNA testing. Experts, like Craig Venter, have dismissed the current state of personal genetics almost entirely. How much can we really predict about your health from just a few random variations in your DNA? Analyzing SNPs may be too simple of an approach to understanding the importance of your genes.

Yet clearly 23andMe’s investors are making a $22 million gamble that SNPs will prove to be a valuable commodity in the years ahead. It could pay off. At the recent annual meeting for the American Society of Human Genetics, 23andMe presented some of its ongoing research in linking SNPs to important medical conditions. Last year, they set out to gather data on 10,000 Parkinson’s patients, and have managed to collect samples from 3500 so far (with an additional 20,000 controls). 23andMe has also replicated 100 known associations for genetic conditions and found genetic links for the Mumps. All of this is part of their more general project of democratizing genetic research through customer data collection and feedback.

I don’t know how personal genetics will evolve in the next few years. If I had to take a guess it would be that whole genome sequencing, which is steadily dropping its price towards the $1000 level, will become the new gold standard. Where this will leave SNP analysis and personal DNA testing companies no one can say. It’s an uncertain time, but I think that 23andMe is making the right call. The only way they’re going to survive is by increasing our understanding of genetics. Research is the key to validating the personal genetics industry. We’ll see if $22 million is enough to make that happen.

[image credit:23andMe (modified)]
[source: 23andMe blog and press release]

Watch out HIV virus, we know your secrets.

If you’ve ever taken a class on sexually transmitted diseases, you were probably taught this fact: once you contract HIV, you will eventually get AIDS. Yet for about 1 in every 300 people this simply isn’t true. These ‘HIV controllers‘ have bodies which are somehow able to fight off the development of AIDS for years, sometimes for decades. Scientists may have finally pinpointed the reason why. Researchers lead by a team at Massachusetts General Hospital, have found the region of the genome that seems to be responsible for determining who will be a controller and who will not. Just five amino acids associated with the HLA-B gene/protein seem to be the key. This discovery, recently published in Science, is unlikely to lead to immediately available therapies or treatments in the short term. Eventually, however, knowing how controllers ‘naturally’ fight off AIDS could help us provide that same resistance to everyone who has contracted HIV.

The presence of HIV controllers has been acknowledged for a long time, but scientists have lacked the genetic tools needed to probe their resistance until recently. In 2006 Florencia Pereyra started the Controllers Consortium, gathering information and genetic samples from HIV controllers from all over the world. Since then, 300 collaborators at over 200 facilities on 6 continents have been gathering data on controllers. For the publication in Science, Pereyra along with lead co-authors Bruce Walker and Paul de Bakker, performed a genetic study using 974 HIV controllers and 2648 normal HIV patients. This genome wide association study (GWAS) looked at single nucleotide polymorphisms (SNPs) that differed between groups. After exhaustive examination, the global team of experts settled on the HLA-B gene as the crucial difference that allowed HIV controllers to outlive their peers.

This HLA-B protein has a section that identifies it with the immune system (red), and a stabilizing structure (pink).

HLA, or human leukocyte antigen, is part of the area of your genome that dictates immune system function. It’s a natural place to look for resistance to HIV. HLA-B gene helps your cells create proteins that rest on the cell’s surface. Those proteins use peptides to communicate with your immune system. If the peptide gives the wrong signal (say, because it’s been infected with a virus) your body will destroy the cell. Hundreds of different variations for the HLA-B gene are known, and it’s among one of these variations that five key peptides are developed that help an HIV controller’s body fight off HIV more efficiently.

This is some amazing information, but it’s going to take years before it really does us any good. First, these findings have to be confirmed and re-examined before we can even trust them. Luckily, the Controllers Consortium is continuing to gather genetic samples (1500+ and counting). Also, I don’t want to detract from SNP based GWAS because these studies can reveal some interesting insights into diseases. However, time and again we’ve been faced with reactions in the body that are the result of complex genetic interactions that SNPs simply cannot adequately track. HLA-B may be a crucial part of HIV controlling, it could even be the whole basis of HIV controlling, but there could also be a larger system of gene variations that work with it. Eventually, I suspect that whole genome sequencing may be needed to completely understand these interactions (and not just for this experiment, but many other genetic studies as well).

Even once we completely understand the genetic basis for HIV controlling, it will take time to develop therapies using that knowledge. Do we create a vaccine-like treatment that somehow spurs the body to produce more of the right kind of HLA-B amino acids? Do we pump patients with HIV full of these amino acids, or try to give them gene therapy? Whatever solution we adopt will need several years to test before we can apply it to large populations with HIV/AIDS.

Knowing how long it will take to apply this new understanding of the body’s response to HIV doesn’t keep me from being very hopeful about its eventual use. This is a good time in HIV/AIDS research. Mimicking the genes of an HIV controller is going to be a great tool in fighting the AIDS epidemic. Not only do controllers live longer without developing AIDS, they also have a reduced risk of transmitting HIV. Even if we can’t develop a vaccine, we could still get vaccine-like benefits and slow the spread of the disease. I have this growing hope that one day HIV/AIDS will follow the same path to destruction that we’ve managed for Small Pox, and are looking to find for Polio. As devastating as AIDS has been there’s always a chance that we’ll one day be able to eradicate it from the Earth completely. That day seems closer now than it has in a long time. I’m very, very happy about that.

*I’d like to mention some of the various organizations whose funding directly made this research possible:
Phillip T and Susan M Ragon Institute
Mark and Lisa Schwartz Foundation
Harvard Center for AIDS Research
Bill and Melinda Gates Foundation
Broad Institute

…If you know any more, please mention them in the comments section and I’ll add them up here.

[image credits: Ragon Institute, Broad Institute ]
[sources: The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation. Science, November 02, 2010, Ragon Institute, MGH/Ragon Press Release, ]

Newly found genes could be the key to living long and feeling young.

Researchers in Massachusetts have discovered a host of genetic variations that may be responsible for living past 100. Thomas Perls, director of the New England Centenarian Study, and colleagues examined the genes of 1055 people over the age of 100 and compared them to 1267 controls. As discussed recently in Science, the scientists found 150 single nucleotide polymorphisms (SNPs) that were linked to longevity. Using these genetic markers, they could predict whether a random genome belonged to a centenarian with 77% accuracy. We are now one step closer to understanding which genes code for long life and leveraging these findings to provide longevity for everyone.

As we discussed in our earlier conversation about living past 100, below the age of about 80, lifestyle choices seem to play a dominant role in determining who lives and dies. Yet if you want to live past 90, 100, or 110, having the right genes seems to be a huge requirement. Right now, scientists are merely trying to determine which genes are relevant. Once that list is established, scientists could study the associated proteins for each gene and possibly develop some means to extend their benefits of long life to the general population.

Interestingly, many centenarians have the same genetic disposition to geriatric diseases as non-centenarians. Yet many of those who live past 100 don’t develop age-related illnesses (with the exception of poor eyesight and arthritis) until their very last years. There is something, then, in their other genes that act as a kind of shield against poor health.

Using the 150 SNPs, Perls and his associates were able to build genetic profiles for a typical centenarian. 90% of those examined who lived past 100 would fit one of these 19 profiles. 45% of those that lived past 110 had even higher proportions of the SNPs associated with longevity. Looking at their control cases, Perls and company think that about 15% of people have a profile for becoming a centenarian. These are extraordinary finds. With that information we could study your genome and make a fairly accurate prediction about whether or not you’ll have a natural tendency towards longevity or even super longevity (110+ years).

Or we could…if you’re Caucasian in the Northeast US. Like many such projects, the New England Centenarian Study is focused on a demographic that is relatively narrow in terms of geography and ethnicity. It is likely that there are other sets of SNPs, and other genetic profiles that could be derived for other regions and ethnic groups. We’ve actually seen other research, like the Okinawa Centenarian Study, which has shed light on longevity factors in other regions. In general it will take the effort of many more researchers like Perls working all over the globe before we could build a definitive understanding of which genes are linked to longevity in the general population. But that work is coming.

As we wait for genetics to reveal more about the path to longevity, there are many things that you can do to extend your own expected lifespan. A study of regions where people routinely live past 100, the Blue Zones of the world, reveal common lifestyle choices: eating right, getting exercise, and avoiding stress through loving relationships. Perls has built a website, LivingTo100, that will give you a questionaire to judge how your lifestyle choices may be affecting your longevity. Try it out to get a sense of what simple things (quitting smoking, eating less processed meats, etc) could help you live longer.

Research about longevity is still in its early stages and for now most of the responsibility for living a long life is still on you. Eventually, however, we’ll find ways to extend life no matter how you live or what genes you were born with. Along with regenerative medicines aimed at repairing or replacing body parts injured in accidents, longevity research is helping us move towards the possibility of effective immortality. Those with centenarian genes who are born today may live well beyond 100, 200, or even 1000 years. And they won’t be alone.

[image credit: The Sun]
[source: Sebastiana et al, Science 2010]

Venter, Collins grace the Time cover, July 3, 2000

“It is fair to say that the Human Genome Project has not yet directly affected the health care of most individuals.” – Francis Collins, April 2010, Nature.

What’s in a genome?  Ten years ago, the completion of the Human Genome Project promised to usher in a whole new era of heath care.  Revolutionary gene therapies would soon conquer everything from cancer and heart disease to diabetes and autoimmunity.  A roll-call of our genes would unlock the causes (and the solutions) to death and disease.  But a decade on, most of these hopes have failed to materialize, and most of our lives haven’t changed.  So where’s the revolution?

A recent retrospective in Nature includes some sobering reviews by such genetic gurus as Craig Venter and Francis Collins.  Sure, there have been some significant gains.  In vitro genetic screening has greatly reduced the risk of many common genetic diseases at the pre-birth stage.  Risk factors for a range of adult diseases (including cancer) are coming into focus, and a host of new drugs have been developed.  But as scientists expected to find common genetic determinants underlying common diseases, they quickly discovered that the genome was anything but straightforward.  Instead, the genes behind disease have been shown to be highly complex and individually variable, even for widespread disorders.  There isn’t a SNP for cancer.

The problem is that currently, the field of genomics is data-rich and application-poor.  Thanks to companies like Complete Genomics, there is a flood of new genetic data and even more on the way – but we still don’t know how it works.  So far, the primary focus of interest (and funding) has been the most easily quantifiable advances, such as sequencing speed and costs.  Accomplishments in this arena have been impressive, but a complementary push for clinical applications is needed to sort through all of this genomic data that we still don’t understand.

The fate of commercial genetics hangs in the balance.  Companies like deCODE and 23andMe were born on the hope that laypeople might be willing to pay for a glimpse at their own DNA.  The bankruptcy of deCODE and troubling rumors about 23andMe raise the question of whether personal genomics is an industry born premature.  So far, their products feed a curiosity niche, not a utilitarian one.  When a genome points to little more than SNP-based correlations, few people can justify spending their recession-hit income on what remains a biotech novelty.

As Collins, Venter and others have suggested, a health care revolution requires bridging the gap between genomic data and its clinical utility.  Any disappointments of the past decade point to the directions of the next.  We’re learning that so-called “junk DNA” isn’t really junk, but can regulate the expression of other, coding sequences of the genome.  Untangling the various networks of gene regulation will illuminate the pathways which result in a given phenotype, pathological or not.  The roles of epigenetic processes are also undoubtedly complicating factors which will need to be better understood.

Most approaches over the past decade have used SNP chip analysis to identify mutations associated with particular phenotypes.  This type of analysis only looks at small parts of the genome, and has largely failed to identify the genetic determinants of most diseases.  The SNP chip approach will be phased out as whole-genome scans become faster and more affordable (costs should drop below $1000 within the next three years).  Complete Genomics aims to sequence 1 million human genomes within the next five years, and that’s a lot of data to crunch. Venter is calling for two ways of making better sense of this flood of whole-genome scans: more detailed phenotype analyses, and the development of computational tools that can link them to their genetic counterparts.

It’s interesting to note the parallel between difficulties encountered in genomics and neuroscience. Recent years have seen an increasing shift in brain science from localization (areas of the brain that “do” things) towards neural-network approaches.  Just as we’ll unlikely find a single gene that causes cancer, we’re not going to find the “irony zone” of the brain anytime soon.  Reconceptualizing both genomics and the brain as complex, interactive networks remains a necessary step to significant advances in either field (e.g. a health care revolution or AI, respectively). And despite these setbacks, we can expect big things on the way.

Genetics has already revolutionized our health care in certain respects. Preimplantation genetic diagnosis (PGD) has already made huge progress towards eradicating genetic disease before birth, a significant but often overlooked accomplishment. But more lies ahead. Coming decades will see the creation of genetic therapies based around the specific molecular details of a given disorder. Diseases such as pediatric cancer are already the target of multi-year genomic research, and more diseases will benefit from genomic research as costs come down. And as the genetic underpinnings of disease come into focus, personal genetics will also undoubtedly enjoy a second life – regardless of whether today’s companies survive to see it.

We’ve scanned the genome; what remains to be seen is what we can do with it.

Here is a short summary video from Reuters that may be of interest:

On Friday, Pathway Genomics personal DNA test kit (inset) will be offered at Walgreens across the US.

This Friday will see the launch of a new phenomenon: a genetic test you can buy at your local pharmacy. Walgreens will be selling the kits for Pathway Genomics personal DNA Test for around $20, and CVS is scheduled to carry them as early as August. While the kit is little more than a tube you fill with saliva, you can send it in (via FedEx) to have Pathway Genomics analyze your DNA and give you valuable information about your susceptibility to certain diseases, negative reactions you may have to certain drugs, and your genetic ancestry. You select which kinds of analysis you want performed with additional costs ranging from $80 to $250. I recently took a version of PG’s personal DNA test that’s identical to the one you’ll find in stores on Friday. I also spoke extensively with Ed MacBean VP of product management. Keep reading for a preview of what your own experience may be like, from spitting in the tube to speaking with a genetic counselor about your results. With almost 7000 Walgreens across the US set to offer the kits, Pathway is about to make widespread retail DNA testing a reality.

Pathway Genomics performs analysis on select portions of your DNA: mostly single nucleotide polymorphisms or SNPs (pronounced ‘snips’). They aren’t the only company providing these tests, there’s also 23andMe, Navigenics, and others in the US and around the World. SNPs are sort of like the cliff notes to your genome. They can give some important insights into certain areas, but they aren’t a complete scan of your DNA. If you want the entirety of your genes analyzed you’d need whole genome sequencing which is now available commercially through both Complete Genomics and Illumina but at a considerably higher price ($10k+ or more). For most people, SNP testing provides a good access point to their DNA, especially now that it will be available at your local pharmacy.

The Test

When you purchase the personal DNA test kit (either online at PG’s website or at Walgreens) you’ll receive a small box with the necessary equipment to collect your DNA. It’s actually very simple. This is a ‘spit test’, you fill a tube with your saliva and the DNA within that fluid is analyzed at PG’s lab in San Diego. The following video shows my adventures with the kit:

As it mentions in the video, spitting in the tube is really the second step in the personal DNA test journey. First you have to log on to the Pathway Genomics website, register, and fill out a survey. With around 20 questions, this online survey covers your family history, personal health, and habits. This information will be used later in conjunction with your DNA to provide an assessment of your risk for diseases.

*To avoid the controversy of giving genetic tests to children – Pathway will not be offering its kits to those under 18.

The Results

For some inheritable diseases, it's clear how risk it passed on to children.

A few weeks after sending in your saliva, you’ll receive an email from Pathway Genomics indicating that your results are ready. By logging into the PG website you’ll be able to download any and all analysis that you have purchased as a PDF. That analysis comes in two major flavors: health and ancestry. The former includes things like carrier status for diseases, genetic risks for various conditions, and likely drug reactions. You’ll be able to buy each of these analysis packages separately or together. The ancestry is not going to be initially offered through the Walgreens kit, but you can always purchase it later. Let’s take a look at each of these.

The easiest analysis to understand is the carrier status. Pathway looks for more than 35 diseases which have recessive inheritance. If you get two copies of the disease gene, you get the disease (more or less). But if you only have one copy of the disease gene you’re just a carrier and you’d never know it…until you have kids. If your mate was also a recessive carrier then there’s a chance your children will have the disease. As such, the carrier status is sort of like sifting for land mines in your DNA. Pathway gives you a brief description of each disease for which you possess the gene. Not pleasant, but something that can be very helpful when you start to plan your family. It’s a fairly common use of genetic testing, and one we’ve seen in various forms before.

Pathway can let you know if you are a carrier for various inheritable diseases. This is the top of an excerpt from that report.

Next comes the analysis of genetic predisposition to 24 different health conditions from asthma to ulcerative colitis. What I like about Pathway Genomics’ analysis is that they are very upfront with the limitations of their product. They don’t try to give you some ludicrously precise number to describe your associated risk for an illness (such as “you’re 75% more likely to have type I diabetes”) instead, Pathway lumps results into four ‘buckets’. Each bucket represents a general level of risk. If you have no genetic markers that have been shown to code for a condition, you are told to “live a healthy lifestyle.” If your risk is slightly higher (a few markers) you are told to “learn more.” More markers for a condition prompts a “be proactive.” If your genes show a strong disposition then you should “take action.”

Pathway gives you a broad idea of your risk for diseases based on your genes and lifestyle. It may seem vague, but trust me, this approach is better than hard numbers that don't really mean anything.

This is a vague way of approaching genetic risk, but right now genetic risk is itself a vague concept. Every year more genes are added to watch lists, and our understanding improves. In fact, Pathway outright labels which of its calculations are considered preliminary and which have been confirmed through multiple scientific publications. But we can’t simply say that because you have one gene you are certain to contract a related condition – it’s too early for that. Many different companies have used SNPs to analyze a person’s risk for a disease or health condition, and faced criticism for drawing too strong of conclusions. Pathway has decided to provide you with a wealth of information, in the hopes that you and your doctor can use it to round out your healthcare. It’s a little less precise, but I think it’s a better approach.

Along with your genetic ‘buckets’, Pathway also provides you a lifestyle bucket with the same four categories that it bases on your answers to the initial online survey. This lifestyle bucket is often different than the genetic one, includes consideration for your race/ethnicity, and is meant to round out your understanding of your risk for a health condition. There’s an additional fifth bucket here, “immediate attention” if you’ve really been living on the edge. Personally, I found these lifestyle buckets to be unhelpful. Pathway doesn’t specify which answers on the questionnaire affected your lifestyle bucket so there’s no clear idea of what you’d need to change to lower your risk. Also, according to Pathway, much of that risk is determined by age, gender, and race…all things you can’t really affect.

Pathway can let you know which of nine drugs you may have an atypical reaction to. Turns out I shouldn't be drinking so much caffeine.

The personal DNA test can also tell you about negative responses to drugs. At the moment there are nine such drugs which have clear enough DNA links for Pathway to believe in. That’s really very few, but representatives at the company said they were looking to double that number in the months ahead. In the grand scheme of things, we’ll probably see handheld DNA testing devices used in many hospitals and doctors offices to screen for these responses. For now Pathway gives a brief overview of each drug, your gene variation, and what associated risks (if any) you possess. Fairly straight forward. Most of these drugs have alternatives if you are at risk for a negative response, so this test probably doesn’t carry a lot of anxiety with it. Still, better to know of these risks before you are prescribed a medication than after.

SNP derived ancestry is…nebulous. I’m not sure what else to say. This is NOT a paternity test. Using genetic markers that have come to be associated with various ethnographic information, Pathway can give you some idea of where in the world (some of) your ancestors are from. There’s a nifty map of where in the history of human migration your particular markers seemed to have originated. Other than that, I didn’t find much to interest me here. If you were a real ancestry aficianado then you’d probably have more to enjoy. Of course, if that were the case, you’d probably have already done a lot of historical analysis which may be more meaningful than the genetic kind.

The ancestry migration map was sort of neat. Some ancient ancestor of mine in Eurasia. Meh, not the most enlightening of results.

I should mention that Pathway is continually improving its understanding of genetics. Every six months or so they’ll update their analysis. You can view these updates for free from your account on their website, and use your SNPs (as listed in each report) to get the most out of the new knowledge.

Genetic Counseling

Along with your results from Pathway Genomics, you are entitled to free genetic counseling from the company. In fact, you are encouraged to contact these counselors as soon as you receive your results. While you can do this through email, I went ahead and called San Diego. My counselor, Emily Enns was top notch. Not only did she have the right credentials (advanced degree in genetic counseling) she had a knack for explaining the test. She helps customers face bad news, like positive results for Alzheimer’s markers in your DNA. She helped me understand how I could have the gene for poor caffeine metabolism (in the drug response analysis) but still down energy drinks like candy and sleep like a baby (body weight, blood sugar, fatigue, etc). When I wanted even more information, she pointed me to the Harvard Medical School database, which is accessible to PG customers and which provides much of the reference information listed in the test results.

Pathway’s genetic counseling isn’t unique (other companies provide the same) but it is a crucial ingredient of their “inform the customer of everything” approach to the personal DNA test. Enns was clear to point out where associated genetic risk was vague or trumped by lifestyle risk (which is fairly often). In general, SNP testing doesn’t let you draw many hard conclusions, having a genetic counselor there to explain that, and to guide you to what conclusions you can reasonably draw, is a big plus.

I should point out that at the time of my test, there were only three full time counselors at Pathway Genetics. Two had masters in genetic counseling, one a MD in genetics. That’s a talented bunch, but with the launch of the Walgreens test kit they’ll need more manpower. VP MacBean did say that they would eventually expand as needed.

The Company and The Controversy

Overall I would rate my experience with Pathway Genomics as very positive. Part of that could be because I didn’t have to pay for it, but I’d like to think it was also because they sell a good product. Many, however, have questioned what customers are really buying for themselves when they get a SNP test. Whether it’s 23andMe, Navigenics, PG, or whoever, giving someone a DNA test at this point in genetic research is probably a little premature. Yes there are a few SNPs which have clear effects when found and which a customer would probably be better off for knowing, such as carrier status or drug response. Many patients, however, won’t test positive for these SNPs, or will only have one or two. You’d end up paying hundreds of dollars and not learn a great deal.

Unfortunately, you might think you had learned a great deal. That’s another critique of these tests, that they can promote the idea that you have increased your understanding of your own health by leaps and bounds. SNP testing, or even whole genome sequencing, is not developed enough to serve as a clear metric of your health. It’s just not there yet. We can learn bits and pieces (sometimes very helpful bits and pieces) but the majority of the population is still more likely to benefit from a regular trip to the doctor than from a DNA test of any kind.

Nowhere is this better seen than in the ‘health conditions’ analysis which gives you risk for things like obesity and osteoarthritis. Pathway has done everything it can to approach genetic predispositions realistically. They paint broad strokes, they admit when results are preliminary, and they update their databases often. You can check in every six months and see how scientific understanding of your SNPs has changed. Pathway has even partnered with Harvard Health to keep it at the forefront of genetic understanding. However, none of this can really change the underlying fact that DNA testing is still in its infancy. We’re still far from really knowing what a small increase in genetic risk for a condition actually means to a patient. Most people (those without severe genetic risk) should probably just focus on living a healthy lifestyle.

Considering these limitations it may seem surprising that Pathway is expanding to offer their services through kits sold at Walgreens and (soon) other pharmacies. Actually, it’s a very savvy move. This first wave of customers will include those who are willing to pay for a little peace of mind, and a lot of satisfied curiosity. As our understanding of genetics improves, Pathway will be able to provide clearer and more precise analysis. That will attract another round of customers to the established PG brand. Very smart.

And Pathway seems agile as well. They have their own (CLIA approved) genetic testing lab, so they could conceivably provide whole genome sequencing if they chose to go that route, or they could stick with looking at individual markers. Either way they have a good deal of private funding from the Founders Fund, the Edelson Fund, WPI and private investors. Most importantly, they have a commitment to keeping themselves current.

If you had asked me a few months ago what I thought of SNP testing, I would have told you that it was likely on its way out. Whole genome sequencing is going to drop in price in the next few years and it provides a better picture of your DNA. Why get the cliff notes when the novel is almost as cheap and much more informative? Well, with Pathway’s expansion into neighborhood pharmacies I have to adjust that opinion. With variable prices for customers with different interests, the retail test could attract quite a market. For now it’s likely that SNP testing will continue to serve as an entry point into genetic testing for the masses. It may continue to thrive in that position, and evolve into new ones, for years to come.

That role is being examined by the FDA. Various news outlets have reported that the agency could view the test as medical procedure rather than as an informational science. MacBean was quick to point out to me, however, that the kit itself is class I exempt, and companies have been providing DNA testing for years without problems from the FDA .

Whether it proves successful or problematic, Pathway’s expansion into the local retail market is a sign that the future is sure to be filled with more genetic testing. Every day sees the publication of more research which expands our understanding of how our DNA guides our risks for illness, our possibilities for achievement, and our hopes for longevity. With that increased understanding will come better personalized health opportunities, as well as new moral and political debates. The advent of genetics arrived many years ago, but this Friday may mark the first time that the average citizen may come face to face with it. Will they embrace personal DNA testing, or are we in for a long slow adoption of this powerful technology?

[image credits: Pathway Genomics]

[video credit: Aaron Saenz and Singularity Hub]
[source: Pathway Genomics]

A common gene variant is found in many centenarians. It could explain how some live past 100 despite their lifestyle.

German researchers at the Christian Albrechts University in Kiel recently confirmed that variants of the FOXO3A gene are a common characteristic for many people who live past 100. The CAU team studied 380+ centenarians, more than 600 people in their 90s, and more than 700 60-75 year olds to determine how prevalent these gene variations were. They found that not only were certain FOXO3A variants very common in 90 year olds, they were even more common in 100 year olds, emphasizing the importance of genetics for aging well. The CAU work confirms earlier research performed by J. Wilcox that found FOXO3A variants among Japanese American centenarians. Both papers were published in the Proceedings of the National Academy of Sciences (PNAS). CAU has a partner group in France that showed similar results there. Taken together, these studies suggest that FOXO3A may be a global factor for longevity. While none of these teams have worked to extend human life per se, understanding FOXO3A variations may eventually lead to genetic treatments to help us all live past the century mark.

The past few decades have seen a growing interest in longevity as medicine continues to advance life expectancy. Groups like the Methuselah Foundation (sponsors of the MPrize) are actively seeking technology to extend lifespans. Yet, understanding aging is not an exact science. We do know that genetics, environmental risks/lifestyle, and strong social bonds are all part of what helps someone live longer. Studies of centenarians, however, have suggested that while genetics don’t seem to make a big difference in the early decades of old age, they have a profound effect determining who makes it into extreme old age. Variants in FOXO3A may be one of the key ingredients that help take a healthy 80 year old, and turn her into a healthy 110 year old. Unfortunately, we can’t know which genes are important without actually understanding how they work to preserve us as we age.

It’s important that we make it clear that everyone has a FOXO3A gene. It is the variation in single sections of that gene (single nucleotide polymorphisms) which are important. CAU looked at 16 of these SNPs, while Wilcox studied 3. As we better understand which of these SNPs are key for longevity, you’ll be able to test for them with personal DNA tests or whole genome sequencing.

Of course, you probably don’t just want to know if you have great gene variants, you probably also want to be able to exchange your genes for better ones. There have been some promising results from scientists studying how limited genetic manipulation can extend the life of mice. In humans, however, we are likely to seek ways of producing the effects of genetic manipulation without actually splicing our genes. The FOXO3A gene codes for the FOXO3A protein. If we figure out how longevity variants of FOXO3A change the protein (in its form, frequency, etc) we could then produce drugs that replicate that change and give our bodies long life.

CAU was able to perform such a (relatively) large study so quickly thanks to the Schleswig Holstein biobank known as Popgen. It has more than 650 samples of centenarian DNA on file. Biobanks store genetic samples for use in scientific studies and are a resource of growing importance. I wonder what other insights we’ll develop in the next few years as biobank data becomes available to more researchers in a variety of fields. Getting older is wonderful if you are still healthy. Genetic research may not only tell us how to increase lifespans, but also how to extend our youth.

I’ll be taking a personal DNA test very soon (an article on that is forthcoming) and the CAU research has me excited about what I could learn. Admittedly, I doubt that any SNP detection company is ready to test for these FOXO3A variants yet, but there’s still a ton more to know. Genetics don’t dominate every part of your life but, as this research shows, there are times when they become very important. Learning more about your genes is the first step to taking advantage of (and compensating for) your body’s natural inclinations. I can’t wait.

New studies in the US and Japan highlight important genetic links to Parkinson's disease. Good news for those suffering from the debilitating illness.

Affordable genetic testing continues to enable scientists to find exciting new discoveries that may help doctors predict, prevent, and treat disease. Two teams of researchers recently published in Nature Genetics (a Japanese team from Kobe University, and a US team from NIH) have collaborated to find that five important genetic variants are linked to Parkinson’s. This debilitating brain disease degrades muscle control through a reduction in brain chemicals and affects 1-2% of those over 65. This research was the largest case of genetic testing for Parkinson’s, ever. With the amount of genetic data that can now be processed quickly and cheaply, studies like these are just the beginning.

These two Genome Wide Association Studies (GWAS) rely on finding important comparisons of single nucleotide polymorphisms (SNPs). 23andMe declared war on Parkinson’s by analyzing SNPs one individual at a time and hope to gather 10,000+ samples total. These two GWAS, however,  have already examined the genetics of many thousands of volunteers. By sifting through this massive amount of data, scientists can glean which genetic markers may indicate increased risks of the disease. It’s only been in the last few years that genetic testing has been cheap enough to facilitate such studies. As whole genome sequencing becomes cheaper, researchers will be able to study more DNA than just SNPs. This may lead to an even better understanding of the links between genes and illness. We live in a very exciting time – there is an ocean of data in our DNA that is going to be explored in the next few years.

The Japanese team, led by Dr. Tasishi Toda of Kobe University, discovered four important loci for Parkinson’s named PARK16, BST, SNCA, and LRRK2. Information was taken from 2011 patients with the disease and 18,381 healthy individuals, all of Japanese descent. In the US, Dr. Andrew Singleton of the NIH led researchers to confirm the SNCA locus and add a new one: MAPT. Their sampling consisted of 1713 patients, and 3978 healthy volunteers followed by 3361 patients and 4573 volunteers, all of European ancestory.

Why am I giving you all these numbers? To prove a point. We are talking about tens of thousands (30k+) of people each having their genome analyzed on the cheap. That’s remarkable, and something that would have been unheard of just five years ago.

The two teams confirmed that PARK16, SNCA, and LRRK2 are important loci for all Parkinson’s patients. Interestingly, MAPT was only an indicator for European ancestry, and likewise with BST for Japanese ancestry.

As SNP genetic analysis gets even cheaper, and whole genome studies fall within the budget of research institutions, we are going to see more and more studies like these two. Already individuals can gain access to affordable SNP analysis, and soon the same will be true for whole genome sequencing. That means that you will be able to know for yourself which important markers you carry that may indicate a predilection to an illness. Armed with such knowledge we will all be able to take better control of our health. Hang in there everybody, we’re making progress. (Not so) slowly but surely.

[photo credit: Kristen Ryder]

Kaiser has collected more than 100,000 genetic and medical profiles using spit collection kits like this one.

It stands to reason that if you want to perform genetic research, you are going to need some genetic samples. While you could always go out and collect your own, Kaiser Permanente is doing much of the work for you. Since the end of 2008, the healthcare provider has been gathering a collection of DNA samples and medical histories from thousands of its customers as part of their Research Program on Genes, Environment, and Health (RPGEH). The goal is to create a database that will enable researchers to discover links between our genes and the diseases we develop. As of the end of summer, KP has collected more than 100,000 saliva samples and their corresponding health records from volunteers. By 2013, they hope to reach half a million. That’s a lot of spit. Watch experts from KP explain their project in a clip from ABC’s The View From The Bay after the break.

BioBanks are large collections of genetic and medical information. They are formed by convincing huge numbers of volunteers to submit DNA samples and answer detailed surverys about their health and where they live. All that effort comes with a big payoff: the data in a BioBank can be used to find statistical correlations between genes and increased risks of diseases, and to determine how those risks are affected by the factors in someone’s environment. With a large enough BioBank, and the time to analyze it, scientists could discover the effects of our genetic code, and lead the way to new treatments for all manner of illnesses. They could also predict negative reactions to medications or even find new environmental links to disease.

The first 100,000 samples for the KP biobank is focused on Northern California residents with an average age of 65. As such, it is uniquely poised to study how diseases deteriote our bodies as we age, as well as study the aging process itself. Kaiser is pairing up with UC San Francisco to determine the length of telomeres in the samples. Telomeres are the redundant blocks of genetic information seated at the ends of chromosomes. Elizabeth Blackburn, who won the 2009 Nobel Prize in Medicine for her work on telomeres, is associated with the project. Data from the KP biobank may then be a boone to longevity researchers like those associated with the Methuselah Foundation. Further volunteers will include those 18 years and older.

While the biobank is a privately collected resource it should be available to many smaller research teams even at unaffiliated universities. Initial funding for the project was a $8+ million grant from the Robert Wood Johnson Foundation’s Pioneer Portfolio, subsequently boosted by a US National Institute of Health (NIH) grant of about $25 million.  The DNA processing is handled by Affymetrix, based in Santa Clara, who will analyze the samples for single nucleotide polymorphisms. SNPs are the single genetic variations that scientists link to many important traits. (Many readers will recognize the importance of SNPs from our discussions of 23andMe and the DNA Electronics handheld gene analyzer – SNP Dr.) Affymetrix will look at about 700,000 SNPs for each sample. Understandably, KP expects it will take another 2 years before the biobank is ready for most research applications.

If you are interested in contributing to the KP biobank, you can begin the survey on the RPGEH website. Samples will only be taken from Northern California Kaiser Permanente customers aged 18 or older. All collected data is “de-identified” in several stages so that volunteers can be assured of their anonymity and that no information discovered will affect their coverage. Prospective volunteers are encouraged to read the Winter 2009 newsletter to learn more.

Of course, Kaiser isn’t the first to build a substantial biobank. The UK already has 500,000 samples collected, though not tested, another sign of that country’s dedication to getting to the top of the biotechnology field. Mayo Clinic has a much smaller biobank (near 20,000) that is specifically tailored to their research interests. 23andMe, the personal genomics company, has been pursuing a “research revolution”, gathering DNA samples and allowing volunteers and donors to select which diseases the data will be applied to first.

While the specter of privacy invasion looms near any large collection of personal information, I am very much in favor of these biobanks. Small research teams simply do not have the resources to collect data sets of these sizes but could greatly benefit from the larger statistical samples. The greater the number of teams active in genetics, the greater the benefit we will all receive from their discoveries. Whether at Kaiser Permanente, or some other biobank, the anonymous but detailed donations of genetic material should help everyone live healthier and happier lives.

[photo credit: Kaiser Permanente, RPGEH]

[video credit: ABC The View From The Bay]

DNA Electronics' SNP Dr. will allow you to find important genes in your DNA in less than 30 minutes.

If your computer and your DNA had a baby, it would be the SNP Dr. from DNA Electronics. SNP Dr. is the world’s first hand held semi-conductor device that will be able to read your DNA in about 15-30 minutes. I was able to chat with DNA Electronics CEO Prof. Chris Toumazou who is also the founder of Toumaz Technologies, the company that brought you Sensium. Toumazou let me in on how SNP Dr. will change medicine and genetic testing, and what we can look forward to in the future of semi-conductors and biology.

The current means of looking at your genetic code involves actual looking. Optic sensors help to pour through your DNA and discover variations. That technique is slow and difficult to scale down. Semiconductors, though, are getting faster and smaller every day. So a semiconductor device like SNP Dr. can be cheap and easily produced at a hand held size. Imagine a world where genetic testing could be done with just some spit, a cotton swab, and your iPhone.

A single nucleotide polymorphism or SNP (pronounced ‘snip’) is an interesting single-gene variation in your DNA. Geneticists have discovered hundreds, many of which can indicate proclivities to disease, physical traits, or negative reactions to medicines. Companies like 23andMe can test your DNA to see which SNPs you have. The SNP Dr, still in early prototyping, has a semi-conductor processor (a ‘SNP chip’) that reads your DNA by looking for a SNP. Which SNP? Depends on what you need to do. Are you a doctor trying to make sure you can proscribe someone a medicine without it killing them? Soldier checking for biological weapons? Farmer trying to figure out which seeds you should plant to avoid parasitic infestation? DNA Electronics could develop a SNP chip for any of the above.

Making semiconductors and biology play nice

Prof. Toumazou’s background is in semiconductor design and engineering. He developed the ultra low power technology for IT applications that was adapted into medical sensing devices like Sensium. While working with a group trying to develop a cochlear implant, Toumazou started to realize that, “biology doesn’t need the higher precision of digital processing…The [modern] world is digital, but human space is analog.” Analog signals and processing mean lower power consumption and tinier devices.

But analog signals drift, which is problematic when you want to measure chemicals in body fluids like potassium, glucose, or urea (all one time projects of Toumazou). So what signal in your body doesn’t drift? The one that’s got all the important information anyway: your DNA.

With specialized molecules (polymerases) you can get reactions with DNA that release protons. That’s an electrical signal you can track with semiconductor technology. Get the right kind of reactions going, and you can detect all the changes in DNA. Find when base pairs switch and you can start reading your genetic code just by measuring changes in electrical signals. It’s like deciphering Morse Code when there is just four letters in the alphabet (GTCA). SNP Dr. represents one of the world’s first looks at combining DNA logic with CMOS technology.

So can I buy one today?

Semiconductor technology is well explored and well understood, so it’s no surprise that the semiconductor side of SNP Dr. is well underway. When the UK launched its Life Science Blueprint initiative to strengthen government support of biotech in Britain, guess what they got to see at the labs of Imperial College? Check out the prototype version of SNP Dr in the video below (0:28). Yep, that’s Prime Minister Gordon Brown and Lord Drayson.

The current SNP Dr. prototype can actively demonstrate a number of SNPs on a single chip, but there’s still a good deal of work to be done for a cotton swab of spit to interface with information technology. Toumazou says that they are already working with Pfizer, and other pharmaceutical companies on predicting drug responses in patients.

Prof. Toumazou is confident SNP Dr products can be developed and launched fairly quickly. Unregulated uses of DNA testing (such as having 23andMe looking at your genetic traits) could start adopting SNP Dr within the next 1-2yrs. Genomic studies, drug responses, and infection detection are all highly regulated, rightfully so, and will take a little longer to approve the new technology. According to Toumazou, These more rigorous uses of SNP Dr. will probably be seen in 2-5 years.

A SNP Dr. in every home

CTO Dr. Leila Shepherd works to bring SNP Dr to market.

In terms of the overall business model, integrating genetics and semiconductor chips is still a very new field and a number of opportunities may emerge, from selling the handheld SNP Dr, to producing new and updated disposable SNP chips on a regular basis. But no matter where the most revenue may lie for DNA Electronics, you can bet they are going to make a big impact. For a couple of hundred dollars, almost any professional could buy a SNP Dr, a whole bag of SNP chips and get to testing. Doctors, farmers, soldiers, forensic scientists, cosmetic counter artists, personal trainers, or just the interested layman could suddenly test themselves and others for important genetic traits. Some of that activity is bound to be regulated, but it still leaves plenty of room for the SNP Dr. to find its place in the world.

It may be a very important place. With the ability to create new SNP chips at the rate of current silicon technologies (ask Intel how fast that is) we could see SNP Dr. become a rapid response tool in the fight against biological threats. Terrorist weapons? Sure, but think about infectious diseases like swine flu, blights on crops, or allergies to medicines. If scientists can find a SNP, DNA electronics can build a SNP chip for it. “Anything that has a defined sequence,” says Toumazou, is fair game. After all, “it’s not discovery, it’s matching.”

In fact, concentrating on matching doesn’t just make SNP Dr. fast and reliable, it also makes it a logician. Toumazou says that SNP chips could be geared towards boolean logic. Does this organism have gene X AND gene Y? That enhances the applications we’ve already discussed and makes the technology a boon to synthetic biology. Anything a scientist can define a sequence for, DNA Electronics can help them detect in minutes. Genetic engineers will be able to search and sort their creations for traits nearly in real time. That’s going to lead to some amazing developments.

An ounce of prevention

As I’ve said before, Toumazou is also the brains behind Sensium which will help health monitoring. Along with SNP Dr, we start to see a clear trend: the more you know, the healthier you can live. Toumazou is working to “change healthcare in the future, if you want to call it healthcare.” Maybe the new paradigm is lifestyle management or lifecare. Why wait until you are ill to learn what will make you sick? Why wait until you are fat to learn how much exercise you need? Working with your doctors, human and hand held, will help answer these questions before they become problems.

Which is really the promise of merging semiconductors with genetics. Cutely named devices are great, but widespread improvements in healthcare are better. The possibility that anyone with the interest could affordably test themselves for genetic traits is amazing. That may alter the way we think of genetic information, our health, or even our identities. These are game-changing trends, and it’s exciting to see them make their way to market. Hopefully DNA Electronics, and Prof. Toumazou will develop the biological sampling side of the SNP Dr. as quickly as planned so that we can start seeing the benefits of those trends in a few years.

After that, its back to breeding different technologies to produce crazy offspring devices. Particle colliders and Twitter…Tweetbomb?

[photos courtesy of DNA Electronics]

[video credit: Number10TV]

23andMe is a personal genetics firm that allows individuals to test their genome for key genetic markers. These markers take the form of SNPs (pronounced ‘snips’), single nucleotide polymorphisms. A standard test that grants you access to information about ancestry, health, and traits costs you about $399. A research version is available for just $99. Basically all you do for either option is spit in a special tube and then mail it to the company.

The 23andMe research revolution is pretty straight forward. The company needs volunteers and sponsors to help in genetic testing for 10 diseases: migraines, psoriasis, severe food allergies, arthritis, celiac, lymphoma/leukemia, multiple sclerosis, ALS, epilepsy, and testicular cancer. Sponsors get to vote on which disease will be prioritized. Besides sending in some spit, volunteers will also be entering a lot of health information online in order to find correlations between genes and diseases. There’s no guarantees that the genetic testing and correlations will lead to any worthwhile data, but you have to admire 23andMe for getting out there and shaking things up.

The research revolution isn’t 23andMe’s first foray into a democratic approach to genetic testing for diseases. As we mentioned a few months ago, they sought out 10,000 volunteers for a Parkinson’s study. While there may be some statistical problems with the way that 23andMe solicits volunteers (everyone has to have at least $99, right?) the activism portion of their approach is laudable. With this new push for research, there’s a good chance that some insight will be made into at least one of the ten diseases mentioned.

In the future, other diseases will be added to the list, and past data will be leveraged into the new tests. That’s a lot of bang for your genetic buck. Just to show you how easy the submission process is, here’s a video from health advocate and strategist Jen S. McCabe:

You know, I don’t want to turn this post into a wholesale endorsement for 23andMe and their research revolution, but I’m definitely in favor of it. The idea of democratizing research while still keeping it meaningful is tremendously motivating. 23andMe is setting the basis for future debates on genetics just by affirming an individual’s rights to know more about their own genetic code. As we’ve said in previous stories, the company sits at the crossroads of genetic testing and internet community building that will be a powerful meme going forward. Even if this particular research revolution doesn’t yield results, one eventually will.

Brin appears to have sunk $10 million into this series B round, while Google has put in $2.6 million.  As if the financial investments weren’t controversial enough, apparently Google and 23andme have entered into some sort of leasing agreement, though the details of this agreement are not available.

For those with their heads in the sand, there are two major types of personal genome sequencing out there.  In the first type, your entire genome is sequenced – every single one of your 3 Billion base pairs.  This procedure is expensive and time consuming, and although companies like Complete Genomics are poised to bring this ability to the masses for about $1,000 per individual in the next year or two, the price is currently much higher.  For the masses who cannot wait for the full genome sequencing from the likes of Complete Genomics, an alternative is to have more than 1 million of the most important or interesting chunks of your DNA, called SNPs, analyzed for much less than $1,000 today.  There are two major players in this space, 23andme and Decodeme.  As we reported earlier, Decodeme is facing imminent bankruptcy, and this latest round of funding shows that even for industry front runner 23andme the market is a tough place to be.

Although the future for personal DNA sequencing is eventually going in the direction of full sequencing of every single base pair, 23andme offers a valuable service in the near term that is charting new ground and helping to pave the way for the ongoing genetics revolution.  Given that the future seems to be in whole genome sequencing, rather than with SNPs, the long term future of 23andme seems perilous…I would not want to be one of their investors for the long term.

Ethical investments and economic viability of the company aside, you gotta hand it to 23andme for being an innovative and leading company in the field of genetics.  They have really stirred things up: making genetics cool, bringing real genetic tools to the masses, and proposing bold initiatives for conquering disease.  Most notably perhaps, our earlier story on the 23andme initiative to gather DNA samples from at least 10,000 people as part of a massive effort to identify genes that may be at the root of Parkinson’s disease is laudable.

Now with more money in the bank, 23andme should be able to plug along for another year or more and further the genomics revolution.  Lets wish them well, for we need all the help we can get to achieve the promise of genetics.

(Disclosure: In my previous career I worked at Google)