23andMe may have provided the wrong results to as many as 96 customers for its genetic testing services. According to statements made on the 23andMe blog, human error was behind the mistake at LabCorp which provides the Silicon Valley company with its genetic processing. A single 96-well plate used in processing samples was incorrectly placed. Comments accessible only to 23andMe customers reveal that the mix-up caused serious distress among some of those affected (as reported in Genetic Futures and New Scientist). While a relatively minor mistake, 23andMe’s error comes at a bad time, as congress gears up to investigate genetic testing and the FDA considers restricting the industry. The future of SNP-based personal genomics is starting to look troubled.

Genetic testing is an exciting field. New discoveries into the secrets of genes are being discovered every day, and 23andMe itself is looking for genetic indicators for athleticism as well as markers for disease. Yet the industry of personal genomics is struggling with gaining widespread acceptance. The FDA spooked Pathway Genomics (a 23andMe competitor) from retailing its test kits at Walgreens, and congress is looking into the efficacy of such tests. What can someone really learn from spitting into a cup and having their SNPs analyzed? Well, they can learn some vague (and not so vague) suggestions about their health, and their ancestry. Beyond that…well the industry is still in its infancy.

Whether or not it will make it to adulthood is unclear. 23andMe isn’t the only personal genomics service which has flubbed its results. Peter Aldhous (of New Scientist) caught DeCode Genetics in a large mistake when reviewing his results from the struggling company. There’s also the looming threat that whole genome sequencing (which analyses more than 99% of a person’s DNA) may become cheap enough to directly compete with SNP-based analysis.

I am a fan of direct-to-consumer DNA analysis, as I think that every one has the right to freely access and review their genome. However, such access is virtually meaningless if consumers don’t have confidence that the information they receive is not only theirs, but also pertinent to their lives. As always, Daniel MacArthur from Genetic Futures provides some great insight into the issue. His review of 23andMe’s error reminds us that consumers must still be very cautious when receiving genetic analysis, double checking and verifying results before using that data to make health care decisions. I whole-heartedly agree.

23andMe has taken steps to keep the same mistake from happening again. From now on a customer’s sex will be used to double check that they receive their personal results (one wonders why this wasn’t done in the first place). Corrected data for each customer affected by the mix-up was sent out on June 8th.

Despite these stumbling blocks in the industry, I think it’s clear that personal genomics will continue to advance in the years ahead. There’s just too much amazing research into genetics for that not to happen. Yes, right now DNA testing can provide few certain answers, but at some point in the future genomics will be able to give us truly meaningful insight into our health and our lives. Whether or not that future arrives in time to save SNP-based direct-to-consumer companies is unclear. Hopefully 23andMe will be able to overcome this mistake and regain customer confidence. As an industry, 23andMe, DeCode, Navigenics, Pathway Genomics, and the rest need to better define (and possibly expand) what they can offer to the public in order to secure their position in the promising future of genetic testing.

[image credit:23andMe (altered)]
[source: 23andMe blog, Genetic Futures, New Scientist]

Meet the Wests, first family of recreational whole genome sequencing.

John West is very familiar with whole genome sequencing (WGS). He was a general manager with Illumina after they acquired Solexa, where he had been CEO. So it’s no surprise that John West hired Illumina to sequence him, or even that his wife Judy followed suit. What has caught attention is that he asked his daughter Anne (17), and his son Paul (14) to be sequenced as well and they agreed. This marks the first time that an entire family has publicly undergone WGS without any pressing reason to do so (such as researching a genetic disease). While some may view this as “recreational sequencing” I think that John West is simply ahead of the game. Could the West kids learn something unpleasant about their genes? Sure, but knowing your genome is going to pay big dividends in the years to come. Ethical concerns about having children sequenced are understandable now, but in the future it may be considered unethical not to sequence your children as early as possible.

According to the Times Online, West paid something close to Illumina’s retail price for the sequencing service, that’s nearly $50k a piece or $200k all together. There are relatively few people able or willing to pay that much to peer into the DNA of their families. Complete Genomics, who we see as Illumina’s chief rival, is on the road to providing WGS at a much cheaper rate -$10k or less. Both companies are aiming to hit a $1000 price tag as soon as possible. What few could do at $200k, many will be able to afford at $4k and so, from an economic perspective at least, it seems very likely that we’ll be able to sequence our families soon.

Will we want to? Understanding one’s DNA is the key to benefiting from the growing body of research about genetics. Genetic testing can give you early warnings about devastating illnesses like Parkinson’s, diabetes, and heart disease. We may also need WGS if we are ever to take advantage of certain forms of gene therapy. Those are good reasons for every individual to get sequenced, but there are benefits for families sequencing together as well. As West points out in the Illumina press release, sequencing an entire family lets you explore the importance of variations in the same gene on opposing chromosome copies (compound heterozygote), and may provide insight into medical conditions.

For now, the possible benefits from genetic testing are relatively small, but they are likely to grow with every year. Is the same true for risks of genetic testing as well? Let me be clear here, there is no physical risk to being sequenced – DNA is simply extracted from a saliva or blood sample. The ‘risk’ is how the information provided by WGS could affect one’s life. If you had a large disposition to Alzheimer’s would you want to know? Would learning about it depress you irrevocably? In that case, maybe ignorance would be bliss.

Nonsense.

I’m not a big fan of ignorance, and I can’t see it getting any more appealing in the years ahead. Yes, there is always an emotional weight to learning about a medical condition. That knowledge, however, can often be put to good use, helping us seek treatment that is needed. Even if you have a genetic disposition to a disease with no known cure or associated therapy, wouldn’t you at least want to know that before you start having children?

It all comes back to the kids. When Anne and Paul West agreed to be sequenced, they set an interesting precedent: non-adults consenting to genetic testing. They had, a few years earlier, agreed to a more basic SNP test from 23andMe. More qualified ethicists than I can debate whether a non-adult has to (or even can) consent to a medical procedure. What interests me is whether or not there is any downside to knowing your DNA. There is a concern that once someone’s DNA is on file insurance companies, employers, and potential mates would all rifle through that data looking for reasons to treat you poorly. Who knows, maybe they would, but I doubt we will let it get to that point. All around the world nations are taking steps to outlaw genetic discrimination (including GINA in the US). We won’t have to viciously protect our DNA from being searched, and even if we wanted to, we probably wouldn’t be able. $1000 WGS will eventually get even cheaper (years down the line) and DNA is easy to come by. Unless you’re going to guard your precious bodily fluids every second of every day, someone would eventually be able to spy on your genes.

In other words, I don’t think there was much legal/social risk to what Anne and Paul agreed to, and any risk they did expose themselves to the rest of us will soon be exposed to anyway as well. And for the record, while at least one of the West parents submitted their genome to the NCBI database neither of the children’s DNA was made public at this time. They’ll be able to make that decision for themselves when they turn 21.

So if you’re like John West or I, you probably see WGS for the family as a net-positive. Good chance for improving your own medical care, little risk of being ostracized from society for being a genetic leper. If more people take that view it’s likely that the age at which we will want to genetically test our children is going to get lower. Already there are preconception and prenatal genetic tests to help parents decide to have (or prepare for) children with a chance for genetic illness. Such testing effectively helped eradicate Tay-Sachs from the Jewish community. When it costs less than $1000 to sequence someone, it seems very likely that many parents will opt for the test immediately after (or perhaps even before) birth.

That could lead to unprecedented healthcare opportunities. Right now, our understanding of how DNA relates to disease susceptibilities is based on handfuls of SNPs and small groups of genes. This understanding will seem primitive in a decade. There is so much to learn, so many interactions between genes to trace, so many medical histories to explore and tie in with genetics. We are going to know a lot more in the years ahead and taking advantage of what we know is going to necessitate sequencing at some level. Why not get your child’s WGS done as soon as possible so that you can maximize the possible benefits?

Instead of asking if it is ethical to genetically test children, let’s imagine a time when not testing a child could be seen as a health risk. There are many illnesses in childhood which may have a strong genetic component (various cancers, diabetes, etc). Many of these diseases can be treated better with advanced warning. If you were a parent, wouldn’t you want that warning? If everyone got their children tested for these diseases, it may eventually seem negligent if your child wasn’t sequenced. I think we will be entering such a time sooner than we think. In that case, John and Judy West’s decision to get their children sequenced (and their children’s consent to the WGS) isn’t ethically questionable, it’s demonstrating laudable foresight.

For those wishing to read more about the ethical concerns surrounding the West family’s sequencing adventures I recommend Marc Henderson’s article in the Times Online. Genetic Future author Daniel MacArthur’s analysis of that article is also great reading. In the end, I think the debate centers as much on the fear of changing humanity as anything else. Genetic screening before conception is not such a long jump from making designer babies, and we recoil from the idea of breeding humans the way we breed livestock. Still, parents may reconsider their prejudices against such concepts when they are presented with the ability to help their children be smarter, healthier, and happier. Even if we completely outlaw all genetic selection for embryos, WGS will still be a valuable tool for understanding and dealing with the genes we receive naturally. DNA is data, and sequencing gives us access to that information. It’s hard to argue against knowledge and those that do rarely have the final say in how technology develops.

[image credit: College Hill Life Sciences]
[source: Illumina Press Release, Times Online, Genetic Future]

Complete Genomics is pushing down the costs of sequencing the human genome.

It’s getting progressively cheaper to sequence your entire genome. Earlier in June, Illumina announced it would provide sequencing for close to $50k, half of their original price. Not to be outdone, Complete Genomics just released on Monday that it had gathered $45 million dollars in funding. The Silicon Valley based company is planning to use that money to further develop their streamline sequencing operations so that they can offer a complete genome for just $5000 by next year. CG’s goal is to finish 10,000 sequences by years end 2010. Even though that’s later than we had hoped, it’s still a whole lot of DNA and at the cheapest price for a whole genome seen so far. The question is, can they really pull it off?

We’ve been looking for a company, any company really, to break the $1000 price mark for a complete genome sequencing sometime in the next few years. That’s about the point where retail sales of the service will explode. With their exponentially decreasing price tag, Complete Genomics might be on that path. However, we know of at least one company that is trying to reach that goal by the end of this year. Stay tuned for that story in the next few weeks.

If you’ve never heard of Complete Genomics, read our first and second story to catch up. Basically they use a common form of short read sequencing and throw in a ton of computer power to sequence a human genome. Interest in personal genomics is escalating as genetic links to diseases are discovered. 23andMe already offers some testing for such diseases and is hoping to gather samples for further clinical trials. By providing the entire genome for perusal on the cheap, CG could make it economically feasible to expand that research into many more illnesses. Already, we’ve shown you how some facilities are erroneously promising to predict a child’s aptitude based on genetic sampling. Perhaps with the cheap sequencing CG could provide, scientific research will match pace with the growing demand for such testing.

Daniel MacArthur of Genetic Future was able to pry CG head Cliff Reid to provide some details in how they hope to achieve their goals. First, Reid disclosed that the test won’t be offered directly to consumers, but rather through retail providers such as Knome and 23andMe. That means the price you or I will see could be considerably higher than $5k. Whatever the retail price, Reid promises 120 billion base pairs sequenced, 98% of the genome, with just one error in 10,000. That’s considerably better stats than what CG offered in February (92% of genome, about one error in 1,000).

Between now and year’s end 2009, Complete Genomics will focus on its dozens of customers currently in the line up. These include the Broad Institute out of MIT and Harvard which announced it was purchasing at least 5 genomes from CG in March. The Broad Institute reportedly paid $20k for each of their genomes which might be taken as the current baseline price for CG customers. If so, that’s a factor of four that the company has to make up between now and next year.

But scaling is no problem for genome sequencing. Remember that it took 15 years to sequence the first human genome, but the next 6 were done in 24 months. Now we’re talking about doing thousands a year. That’s just nuts and one of the amazing parts about sequencing that I love. Exponential growth is sexy science. And it’s supposed to be one of CG’s strengths. They just finished their first genome in the summer of 2008, and are now on schedule to finish 100 by the end of 2009. Current estimates of finishing 1000 by mid 2010, and 9000 more by the end of that year fit within the exponential growth curve. As MacArthur points out, most of these sequencing services will likely be purchased by researchers in genomic and cancer studies. So the demand is also there.

How can CG scale so quickly? By remaining inflexible but efficient. Their process doesn’t rely on making huge improvements in sequencing technology. Or finding a new sequencing technique. It comes down to streamlining the process. Stick to one task, human genome sequencing, miniaturize whenever possible, fewer reagents means lower costs, and build build build. You can bet a huge portion of that $45 million is going to expanding their facilities in Mountain View.

Who provides the cheap genomes is probably less important than the change it will create. While scientific research will undoubtedly benefit first, the public at large will likely become a dominant consumer. Genetic information is on the journey to becoming one of the most important sets of data someone can know about themselves, with insights into disease, aptitudes, and longevity. Give us the chance for cheap access to that info and you’ll never run out of customers. Just a little while longer, it’s bound to happen.