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]

23andMe is hunting for connections between genetics and athletics, especially as we age.

Back in October, 23andMe generated a little PR buzz by examining the genetic codes of 100 current and former NFL players and comparing them to non professional athletes. That genome wide association study (GWAS) didn’t actually turn up any remarkable results. Yet the GWAS wasn’t the first or last of 23andMe’s attempts at determining how genetics shapes athletics. Their SNP tests include examinations for key gene variants which may code for muscle growth and sprinting prowess. They have an associated study to find genes linked to sports injuries. Teaming up with the National Senior Games Association, 23andMe is offering discounts to older athletes who get tested and submit athletic surveys. They even offered free testing at the Palo Alto Senior Games (see page 15 of this pdf). No doubt about it, 23andMe is taking strides to understand the genetic variations that help some become athletic stars and force others to sit on the bench.

23andMe has made throwing DNA studies at a topic of interest into something of a hallmark for the company. They’ve worked hard collecting samples for an extensive test on Parkinson’s Disease. Likewise, they’ve begun a “research revolution” aimed at letting users determine which diseases will receive the benefit of their ever growing DNA sample collections. The NSGA study shows that 23andMe is at it again, focusing on what helps us age gracefully and athletically. The work also suggest that 23andMe is actively throwing its weight behind learning about the key genetic ingredients for athleticism at all ages.

I’d like to thank Daniel MacArthur of Genetic Futures for providing great insight into the NFL GWAS and Palo Alto Senior Games study. He points out that the NFL study was simply too small to really generate any meaningful correlations between gene variants and athleticism. 100 samples, even of outlier athletes, isn’t enough. However, MacArthur also points out that the thousands of samples taken for the NGAS study, and other 23andMe endeavors (i.e. the Parkinson’s study) could yield major insight.

What that insight will be is unclear. While a few genetic variants, such as a mutation in the ACTN3 gene, may provide an edge for athletes it’s unclear how big of a factor genes are in determining your physical prowess. As I was recently informed by Malcolm Gladwell’s book, Outliers, the greatest determinant for your success in a sport may be the month in which you are born (due to asymmetry in training over a lifetime). A host of genetic variants that give you a 15% better chance at naturally stronger muscles or a more resilient cardiovascular system may be small compensation for breaking your leg at age nine and choosing to pursue writing over track and field. It’s hard to know if/when/how genetics will trump experience when it comes to something as broad as athleticism.

Still, all things being the same, your genes are likely to form an important part of your athletic potential. Understanding that potential could not only help us compensate for our bodies’ natural tendencies it could lead to treatments for those with debilitating illnesses. Already, we’ve seen scientists pursue gene therapy to harness some of the incredible strength benefits of myostatin blockers in order to help fight muscular dystrophy. With companies like 23andMe discovering new genetic variants linked to life-long athletic talent, we may one day see therapies that could ramp up anyone’s athletic potential to match that of the beefiest NFL line backer.

[image credit: 23andMe]

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.

It seems so simple, right?

The simple fact is that current genetic testing isn’t able to predict complex abilities such as emotional control, IQ, or focus. Doing so based on just 11 genes is farcical. The day you may be able to predict height, physique, and hearing acuity based on genetic tests is coming soon, but it’s not here yet. Again, as Genetic Future points out, current genetic models are based on European genomes not Asian ones, and have proven ill-equipped to even predict height. The idea that a quick genetic test could serve as an aptitude test is ludicrous at this point in time.

By charging $880 USD, and claiming to use real genetic sampling techniques (capturing 10,000 cells from a single saliva swab), the Children’s Palace is presenting the facade of legitimate science. A facade that CNN doesn’t address at all in their video. They focus entirely on if parents should use genetic testing, ignoring the blatent fraud that Dr. Xinhua is committing. The first question reporters should always ask about a technology is, “does this really work?” Right now, CNN is simply legitimizing a group whose claims are a few years too soon.

Dr. Xinhua is exploiting Chinese parents’ dedication to their single state-allowed child. These parents believe in science and want to use it to help their child as much as possible. That attitude alone speaks volumes for the future of the genetic testing of children. While the Children’s Palace is riff with misrepresentation, the possibilities they propose are becoming more likely as time passes. Already we’ve seen that certain babies could show us the most likely genes that key for muscle strength. Prenatal screening for a few genetic defects is already common place, and could expand indefinitely in the future. By the end of this year, sequencing the entire genome of an individual may become financially feasible for most couples. Parents the world over, not just in Chongqing, are going to use that technology to whatever advantage they can.

Which may not be a bad thing. I know that movies like Gattaca have guided us to believe that genetic determination of offspring will lead to a rigid class based society. That’s science fiction. Genetic evaluation of children, or even designer babies, can never accurately control or predict the full range of human ingenuity and success. Instead, DNA testing is likely to help us guide our everyday lives to balance our genetic predispositions. Do you have the gene that increases your risk of heart attack? Get more cardiovascular exercise and watch your diet. Will your child have the gene that allows them to metabolize caffeine quickly? Go ahead and let them try coffee earlier. Genetic testing only works in conjunction with environmental stimulus.

Whether you’re opposed to genetic testing of children, or support it, it is coming. Each year brings us closer to reliably identifying the purposes of our genes. We can fight over the moral implications, or debate if one technique works better than another, but the science will still be available. The ability to understand the genetic makeup of our children isn’t here today, but it will be very soon. Anyone who tells you different is trying to sell you something.