Editor’s Note: This week TIME Magazine is naming the 23andMe Personal Genome Service™ its Invention of the Year, an honor that the publication has previously bestowed on innovations such as the iPhone and YouTube. This post by Director of Products Alex Wong (back row, second from right) offers a glimpse at how 23andMe came to be, and what makes it such a powerful tool for exploring your DNA.

We’re thrilled that our product has been named TIME Magazine’s 2008 Invention of the Year. But what exactly did we invent? To answer that question, let’s to go back to the early days of 23andMe … .

I first met our co-founders Anne and Linda, together with Serge and Brian, our first two employees, in the summer of 2006 at a bakery in downtown Palo Alto, Calif.. As they were explaining the basic concept behind the company, Linda reached into her bag and pulled out a CD with “Aveys” written on it in magic marker.

“What’s that?”, I asked.

Her reply: “It’s my family’s genomes!”

That’s a first, I thought to myself — pulling genomes from a handbag. I was hooked. I knew I wanted to join 23andMe and help make this possible for everyone and their family.

But we had a long way to go. DNA chip technology was still fairly new, something that only researchers had access to. Linda, having worked at a DNA chip company, was able to get her own family genotyped. But unless you had an in at a research lab or one of these companies, getting your own genome just was not possible. Even if you did manage to get the genomes of you and yours on a CD, all you’d find when you looked at it would be a bunch of giant, indecipherable text files filled with “rs” numbers and A’s and B’s. These are the raw data files of SNP information that the DNA chip analysis produces.

How to make sense of all that data? The good news was that years of research, starting with the Human Genome Project and the International HapMap Project, had produced a wealth of publicly available information about human genetics. The bad news was, it was all locked inside databases designed by researchers, for researchers. Want to know what one of your SNPs means? A logical place to start, you would think, would be dbSNP, a massive database of SNPs run by the National Institutes of Health.

Good luck. Assuming you can wade through its dense user interface, make sure you get your alignment, genome build, major and minor alleles, orientation, and stranding right, or you’re liable to get your interpretation backwards and think you’re supposed to have wet earwax when you really have dry! Don’t know what stranding, genome builds, or any of those other things are? Trust me, you’d rather not.

Not only did these government and academic databases sport slow and unfriendly user interfaces, but some of them also had data quality and consistency problems and few of them were linked together.

So it was going to require more than just building a website to make all the fruits of ongoing genetic research accessible, useful, and compelling to regular people like you and me. We had to create a whole architecture and process for cleaning up, aggregating and integrating all of this human genetic information, combining it with an individual’s own genotype data, running comparisons and algorithms on it, blending it with great educational content, and serving it back to our customers through a friendly user interface — all in under 500 milliseconds, which is how long you have before people start to complain that your website is slow.

On top of that, we wanted personal genetics to be social, so our customers could see their genetic data in context and learn about what makes us all different and similar at the same time. That meant building in the ability for customers to share their data with family or friends without sacrificing privacy or security.

It’s taken the combined talents of all the different kinds of people we have at our company, from bioinformaticians, to engineers, to writers, to UI designers, but we’re all so excited about having made it possible in 2008 for anyone with $399 to explore their own genome.

Of course, if you’d like to rock it 2006-style, you can still get your own gigantic text file full of SNPs using our Download Your Raw Data feature. You can even burn it onto a CD and stick it in your handbag!

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Meet Marcela, a product manager at 23andMe. A product manager represents the customer’s needs while also considering engineering constraints and business requirements. Her most recent projects were focused on building the user experience of those who participate in research through 23andWe and helping to build the burgeoning 23andMe community.

Marcela on the 23andMe Service:

“I was born in South America, but both my mother’s and my father’s ancestors came from Japan. I found it unsurprising to learn that my paternal haplogroup was one that is only found in Japan today, and that one-third of the Japanese population can trace its paternal ancestry to the people who first arrived in Japan, crossing an ancient land bridge that no longer exists. (A woman has the same paternal haplogroup as her father, her brother, or any male in her father’s line. I learned mine by sharing genomes with my father!) However unsurprising it was, though, I was delighted to learn that this piece of history was preserved throughout all the recent migrations in my family. At the same time, I find it fascinating how long-ago migrations are represented in our genetics — through haplogroups and their predicted migrations or the details in Ancestry Paintings, such as the one shown for the sample Uyghur woman.”

“I’m also really passionate about 23andWe. Right now, people think of genetics as a blueprint, as an answer to the question, ‘What are my chances of having a certain trait?’ However, research in genetics is telling us so much more than that now.”

“It’s helping scientists understand more about the pathways involved in certain diseases and it’s leading to changes in health care and treatments. For example, understanding the genetics behind Age-related Macular Degeneration (AMD) caused scientists to start looking at the condition as an immune disorder.”

“Even research on some of the less serious traits on our site can turn out to be extremely valuable — researchers can study traits that are present in a large percentage of the population to learn about the basic mechanisms behind more rare conditions. The work of some scientists studying the photic sneeze (sneezing in the sunlight) could lead to insights into the biology of epilepsy. Studies of caffeine metabolism might lead to greater insights into other, more complicated drug pathways.”

“Another aspect of genetics research is helping us understand who we are and why we are that way. How did culture and biology interact to make some populations lactose intolerant and others not? What other details in human history and migrations will research in genetics uncover? Why is it that 90% of the population (including me) is right-handed? Genetics may answer only a few of these questions, but I’d be amazed to learn those few answers.“

Marcela on being a 23andMe employee:

“I studied Human Biology and Computer Science, and my honors thesis dealt with privacy in genetic databanks. I never imagined that I would find a job that combines my interests in product management, consumer internet software, and genetics.”

“I love the challenges at work. I want to design the experience of using our site so that my parents can easily understand the wealth and detail of genetic information we provide. We balance many different considerations in our site. Privacy is always our primary concern, but we also want people to learn from friends and family members. We want to make scientific studies accessible, but without losing the important details. We provide such a new type of information that we’re constantly building and rebuilding features based on the many perspectives in the 23andMe team and the many pieces of feedback our users send.”

Think you’d like to join the team? Check out our jobs page!

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This is Fashion Week in New York City, a twice-yearly spectacle where designers, models, celebrities and the merely style-obsessed meet to consider next season’s top looks. 23andMe managed to lure a few hundred people away from the catwalks Tuesday night to consider the beauty that lies within — DNA.

Our Fashion Week spit party was sort of like a Tupperware party, except instead of buying plastic containers the guests were invited to deposit a saliva sample into one. And instead of taking place at a suburban ranch house designed by Richard Neutra, our spit party went down at the spectacular Manhattan headquarters of IAC/InterActiveCorporation, designed by architect Frank Gehry. The building resembles white curtains billowing in a fresh breeze off the Hudson River. Two gigantic high-resolution video walls line the lobby; the larger one is 118 feet long and 11 feet high.

23andMe team members were on hand to explain the features of our new v2 chip, our new community features and our partnership with the family history site Ancestry.com. Guests also had the opportunity to purchase our Personal Genome Service™ and produce their saliva samples on the spot (but only if they’d waited the requisite 30 minutes after consuming an hors d’oeuvre).

You can see some photos here, or click here for a slide show with more party pics.

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Photos by Monica De Armond

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Brian spends his days deep within the heart of the 23andMe web infrastructure. He is a software engineer with long experience in the biomedical field, having previously supported pharmacogenomics and brain imaging endeavors. In addition to being ready and willing to automate himself out of a job, Brian is obsessed with producing beautifully designed, well factored code. An engineer friend once referred to him as a member of the “Order of the Golden Ziggurat” (a shadowy society of engineers fanatically devoted to code beauty). Brian also sometimes works on user-facing features, and actually enjoys writing javascript, though his command of the dark art of CSS cannot match that of the UI wizards he works with.

Brian on the 23andMe service:

“Understanding that knowledge is power, I’m excited to know as much as possible about myself. 23andMe empowers its customers (including me!) by providing them with a wealth of new personal information that would have been completely inaccessible just one year ago.”

“I am also very excited about 23andMe’s prospects for generating novel research results from genome-wide association studies. The expense of collecting enough data to derive relevant findings from an association study is simply prohibitive for most traditional research groups. Overcoming that expense by the economy of scale puts 23andMe in a unique position to pioneer a more productive and fundamentally new paradigm for genetic research.”

Brian on being a 23andMe employee:

“The group I work with here is like an engineering SWAT team. I’ve learned much more from them in the past nine months than I would have working independently or with a company that invested less time finding and selecting the best. The emphasis placed on security is also unparalleled. Knowing that the engineers responsible for our core security infrastructure have come straight from top positions in the online finance industry gives me great confidence in the security of my genetic data. Of course we have plenty of fun here too – Rock Band, Segway polo, movie nights, and meals provided!”

Think you have what it takes to join Brian in engineering? Check out our jobs page!

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Cary, a software engineer at 23andMe, works on a wide variety of systems, from processing raw data from the lab to working on the customer-facing website. Most of the site is developed in Python on top of MySQL and Apache, all running on Linux. Cary has mostly worked on the backend of the website, and most recently worked on large parts of the 23andWe infrastructure.

Cary on the 23andMe Service:

“I really like the genetic comparison feature. It’s interesting to see both how close we all are genetically and how human migration patterns are reflected in our genetics.”

“Also, my parents are 23andMe customers too, and it’s been interesting to see through the Compare Genes feature that I’m more similar to my mother than my father in genes that relate to circadian rhythms and pigmentation. I do have my mother’s complexion and eye color, and I’m a night person just like her (my father’s a morning person).”

“I also have a personal interest in 23andWe, the research part of 23andMe. In addition to having worked on the feature, I’m also interested in the research opportunities provided by it. I, my mother, and her father all suffer from congenital anosmia – the lack of a sense of smell. Little is known about it because it’s very rare and not considered very serious (and generally isn’t, unless there’s a gas leak). It would be almost impossible to fund a traditional research project on congenital anosmia, but perhaps with the low-cost research opportunities afforded by 23andWe, we’ll finally be able learn more about its genetics.”

Cary on being a 23andMe employee:

“I joined 23andMe as a software engineer after studying computer science at Stanford. I had previously been interested in biology, but my engineering classes didn’t leave me with too much time to study the hard sciences. It almost feels like I haven’t left school because I’m still learning new things every day.”

“I feel lucky to have joined such a great company – although I started right out of school, I was given real responsibilities right away, and quickly saw my contributions go live on the site.”


Think you have what it takes to join Cary on the engineering team? Check out our jobs page!

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We want to ensure that we always present our users with a delightful and empowering experience as they explore their genomes. We are continuously improving the design of all dimensions of our service because they all converge to influence the user experience (UX) of 23andMe – the experience a user will have while interacting with our service. This is where User Experience Designer Iram Mirza comes in.

“The most valuable (and fun) part of designing the user experience for 23andMe is iterating on new and existing solutions,” says Iram.

“We obviously can’t always come up with the best solutions the first time around. Once a design is created, we test it with users to get their feedback and check the design against usability rules of thumb regarding what makes a website easy for people to use and understand. Based on the collective feedback, we adjust the design to make it more usable. Once designs go live on the www.23andme.com site, we continue gathering feedback from customers and use it to inform our future work.”

“I really encourage users to come chat with us about their experiences with 23andMe,” she says.

If you’re in the San Francisco Bay Area and interested in being a subject for usability testing, send an email to help@23andme.com to schedule a time to come in an meet Iram. If you can’t visit, that’s ok too. You can always just send us questions or suggestions you might have.

Iram on the 23andMe service:
“I think of 23andMe as a unique network. I love being able to share and compare my genetic profile with my family members who are also 23andMe customers.”

“My sister and I now know there is a good chance we could be organ donors for each other — we used the Family Inheritance feature to compare our genomes.”

“We also learned that my genetics indicate that I can’t taste the bitterness in things like Brussels sprouts, while my sister’s data show that she can. Neither one of us likes Brussels sprouts (there’s more to hate than just bitterness!), but it’s true that I can tolerate bitter vegetables more than she can.”

“And my Ancestry Painting for Chromosome 8 is a work of art! The blend of colors reflects my Asian and European ancestry (I’m from Pakistan). Many people were intrigued when I used an image of this chromosome as my profile picture on Facebook!”

Iram on being a 23andMe employee:
“I love the energy in the office. Everyone is excited about being part of the team and working towards designing the ultimate service for our customers. I appreciate the willingness of everyone here to listen to wild new ideas — and that I’ve had the luxury of implementing a few of them!”


Think you have the right stuff to join forces with Iram on the product team? Check out our jobs page now!

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Denali is responsible for ‘quality assurance’ at 23andMe. She is a software engineer obsessed with producing software that works, in all cases, at all times. After years of writing buggy software, debugging it, and adding more bugs, a-hem ‘features’, she finally decided it was time to start writing correct software. As a full-blown test-driven development and test automation believer, Denali believes if it’s worth testing, it’s worth automating. She designed and implemented an automated test harness and reporting system that offers broad, deep and comprehensive testing, eradicating the need to hire manual testers. She hopes to replace herself by developing software that can generate comprehensive tests without human direction.

Denali on the 23andMe service:
Denali says that her data regarding HIV/AIDS Infection was the coolest thing she has learned about so far from her 23andMe genetic profile (which she got free as one of the many perks of working for 23andMe).

When HIV infects a cell, it latches onto a protein that is encoded by a gene called CCR5. But some people have an unusual version of the gene, in which 32 DNA bases are deleted. People with two copies of this unusual version of the CCR5 gene are resistant to the most common strain of HIV (though protection is not complete).

“Our data says that both me and my husband have one copy of CCR5 gene with the 32 base deletion,” said Denali.

Research has shown that while people with this genotype aren’t resistant to HIV, they do often experience a slower progression to AIDS if they are infected with the virus.

Denali’s son has a 50/50 chance of inheriting the unusual form of the CCR5 gene from each of his parents.

“This means that our son has a 25% chance of having two copies of this version of the gene. We haven’t gotten him genotyped yet, but we gleaned this information about him already from our data,” she said.

Denali on being a 23andMe employee:
When asked what it’s like to work here, here’s what Denali had to say:

“The people who work here are hands-down cream-of-the-crop. I learn from all of them constantly. We also have many different kinds of experts speak regularly. Every single one of my coworkers is exceptionally talented and contributes a tremendous amount to the company, which is rare for most businesses. It is like working on an elite educational research project, except I am getting paid like a professional.”

Think you have the right stuff to join forces with Denali in engineering? Check out our jobs page now!

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We also met Grant Wood of Intermountain Healthcare, based in Salt Lake City, Utah. From his point of view as a health IT strategist, GINA’s protections make it easier for genetic data to be integrated with electronic health records (EHRs), which Intermountain maintains for about 55% of Utah’s residents. Intermountain Healthcare recently won a grant from Microsoft to develop tools for adding family health history to Microsoft HealthVault. We talked about how useful it would be to add data from genome-wide scans to EHRs, which include a wide range of clinical data in addition to family history. Patients and clinicians would benefit from knowing the genetic component of risk, and researchers could perform genetic association studies against a much larger range of phenotype data than has been studied before.

The day ended with a screening of the deeply moving documentary In the Family. The film centers on Joanna Rudnick, who wrote, produced, and directed the film. Learning of her family history of breast and ovarian cancer, she gets tested for mutations in BRCA1 and BRCA2, and tests positive for a mutation that gives an estimated 80-90% lifetime risk of breast cancer and a 40-60% lifetime risk of ovarian cancer. (23andMe does not provide information on breast cancer mutations in the BRCA1 or BRCA2 genes.)

During her journey, Rudnick interviews a number of very brave women to see how they deal with their own discovery that they carry a potentially lethal genetic payload: whether and when to have ovaries or breasts removed, how to share information with relatives, the guilt of “passing on” a mutated gene.

Rudnick not only captures her emotions and the effect of what she learns on her relationship with her significant other and her family, but brings several other dimensions into the discussion on genetic testing. We see how a teenage girl reacts to the possibility that she might also carry a BRCA1 mutation. We also see how men—who can also get breast cancer, but more importantly can pass BRCA1/2 mutations to their daughters—confront their genotypes (over pints of beer, of course).

I was particularly struck by Rudnick’s exploration of the attitude of some African Americans toward testing and participation in clinical research. Historical memory of the Tuskegee experiments and racial discrimination in general has led some African Americans to be suspicious of researchers’ intents. Poverty, which disproportionately affects African Americans, also has an effect on whether one wants to get tested. To paraphrase one astute woman: “Enough stuff already happens to black people. Black people don’t go looking for more stuff.”

In the Family will come to PBS on P.O.V. on October 1, 2008. I highly recommend it.

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Consider Erin Mendel, a member of the family whose data is visible both to customers and holders of free demo accounts. Using the Compare Genes feature (reproduced below), you can see that among the genes associated with pigmentation Erin is closest to her brothers and mother, and less like her father Greg.

The Cards You’re Dealt

Assign each of your grandparents a suit – spades, hearts and so on – in a deck of cards. In the game of inheritance, their chromosomes (or chunks of genes) are shuffled (or recombined) and then dealt to their children so that each grandparent contributes one chromosome out of each pair. Your dad then ends up with 23 chromosomes of one suit from his father, and 23 of another from his mother. Your mom has a similar set of paired chromosomes from her two parents. So when your parents’ chromosomes

are shuffled, mixed together and dealt in turn to you and your siblings, you end up with a mix of chromosomes bearing all four of your grandparents’ suits. The illustration on the right shows the proportion of her genes that Erin inherited from each grandparent.

Since each child’s genetic information is produced by shuffling and dealing a new hand from the same genetic deck, there are going to be segments on their chromosomes where siblings are completely identical (having gotten the same suits from mom and dad). If a pair of siblings got the same chromosomal segment from one parent, but not from the other, they will be what geneticists call “half-identical.” In general, parents are half-identical to their children everywhere, because they passed their offspring one out of each pair of chromosomes. The exception is when two parents are related to each other.

Family Comparisons
Using the Family Inheritance option, Erin can see which segments she shares in common with various members of her family.

On the Genome-Wide Comparison chart, bars representing the 22 chromosomes and both X and Y chromosomes can be dark blue (representing a full match), light blue (“half-identity”), white (no match) and gray (not enough information). Below is a comparison of Erin and her father, showing only the first six chromosomes. Erin is only half-identical to her dad throughout her genome because one of her chromosomes out of each pair came from her mom Lilly.

So what does this all mean? Let’s consider the following example. When Erin compares herself to other people at the immune system compatibility trait, she sees red triangles above a region of chromosome 6 known as the MHC, or major histocompatibility complex. The human MHC is known as the HLA (human lymphocyte antigen) system. These genes determine how the immune system recognizes and distinguishes bacteria and other foreign invaders from the body’s own tissues. Aside from tests to verify that the blood types of donor and recipient match, the HLA system is what gets checked to minimize the chances that a transplant recipient’s immune system will reject the organ or tissue donated.

Because they are unrelated, Erin’s parents Greg and Lilly have no identical segments in the HLA system so they probably wouldn’t be a good match for each other. One’s histocompatibility, as this gene harmony matching process is known, is inherited.

On the other hand, Erin might decide to make sure her brother Ian gets great birthday and Christmas presents from now on. When Erin does the one-on-one comparison with Ian using the Family Inheritance option, the results on the right suggest that he might be the best match for her if she ever needs a new kidney or some bone marrow. With “completely identical” HLA systems, the chances are good that they could donate marrow or a kidney to each other without immune rejection.

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The Genetic Alliance was founded in 1986 as an umbrella organization for different disease advocacy groups. Today, Genetic Alliance focuses on five areas of public policy:

• Genetic discrimination
• Genetic testing
• Open access to NIH-funded research
• Newborn screening
• Stem cell research

23andMe is closely aligned with Genetic Alliance on these issues—but most especially the first two. At 23andMe, we believe that individuals have a right to keep their genetic data private; so we supported the Alliance’s advocacy of the Genetic Information Non-Discrimination Act (GINA), which protects U.S. citizens against insurance or employer discrimination based on genetic data. Thanks in part to Genetic Alliance’s efforts, GINA was passed and signed into law last April. On Thursday, 23andMe co-founder Linda Avey and I will participate in the Alliance’s Genetics Day on the Hill 2008, where we will continue to discuss important science and policy issues with legislators and their staff.

We at 23andMe also believe that individuals have a right to high-quality genetic data and their interpretation. Because of the recent flood of genome-wide association studies, regulatory bodies are finding challenges in dealing with the new types of genetic information increasingly available to consumers. One of our goals is to work with various stakeholder groups to reach a consensus on how to address these challenges. On July 13, 23andMe’s Senior Director of Research Joanna Mountain will represent 23andMe in a panel called “Direct to Consumer Genetic Testing: Revolution or Risk?”

So keep an eye on this space if you want a peek into the intersection of science and policy. I’ll be attending and blogging about several interesting workshops.

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