It’s not a sale if your left hand pays your right.

Left… 23andMe: Right! Google (the world’s most successful mass computation company… and the most profitable)

Left… deCODEme: Right! deCODE (a genomics research company)

Left… Navigenics: uhhhhhh…. You don’t sell your test at a 250% mark-up from your competitors if your plan is to build the biggest genomic database first. However, you might lie about how the real market is “for the database” later when nobody buys your product… and hope that nobody remembers that the “customer” for that database is already supposed to be fronting the losses of your business.

I’ve heard chatter that some people are upset because 23andMe is likely getting special pricing from Illumina and that they are selling their tests ludicrously below cost.

23andMe isn’t operating by the meritocratic rules of business of profitability because of their private connections?

Gosh gee golly! That just ain’t how alls I remember learning the American Dream back at the ol’ high school like.

Well, don’t worry. Good ol’ Midwestern morals always win in the end, and attempts to nuke the market by artificially lowering the price are never rewarded.

I promise.

23andMe has dropped their price by $600, and some have cited this and me as harbingers of doom.

First, when I say that an industry is “dead,” that doesn’t mean that all businesses shut down overnight and nobody buys anything ever again. It means that the assumptions of a business model seemed flawed with reasonable confidence. So, by that model, new businesses are unlikely, and existing businesses will evolve or fade away. Fly-by-nights may vanish overnight, but that’s why they’re called fly-by-nights.

So, relax.

Second, everybody knew that 23andMe would drop their price from day one. The test was too expensive. The science was getting cheaper. Everybody said so; everybody knew this. BEHOLD! 23andMe’s new product is marginally better and 60% cheaper. If you paid $1000 for 23andMe.v1, and you are pissed, and you demand a refund —you are a fool.

So, as expected.

Yes, I’ve heard the chatter. “But you know, DTC genomics really makes their money from selling the results to pharma…” But that’s speculative revenue from a product that doesn’t quite exist, not cash flow from paying customers now, and companies pay expenses in cash, not VP BIZDEV! “partnerships.” If investors actually believed this story, they would fund companies that sold tests for much less than thousands of dollars to build this database and sell it. They don’t believe this, so instead they funded companies that sold tests for thousands of dollars, hoping that the brand and operational experience built in the meantime would give them an advantage if a market for genomic databases materialized.

The story is that Coriell is building that genomic database. GO PAY ATTENTION TO CORIELL. They offer real medicine and do real science!

Not relevant to the “database sale discussion” is deCODE Genetics, a genomics research company, who probably trusts itself to use its own deCODEme genomic data for its own genomic research

Now: The faerie tale about DTC startups selling data to pharma is dead; let’s talk like adults about real customers who pay cash money for real products.

Which startup can make sales?

23andMe.

Which startup has the best product?

23andMe.

Which startup has the best brand?

23andMe.

Which startup has money and talent to operate and evolve despite an increasingly skeptical investor community and a dead business model?

23andMe.

Which startup is so loved by the media that Rupert Murdoch will smell his own piss to be in their blog?

23andMe.

Which startup was founded by one of the most powerful, richest families in the world?

You’re right, I did lose a million dollars last year. I expect to lose a million dollars this year. I expect to lose a million dollars *next* year. You know, Mr. Thatcher, at the rate of a million dollars a year, I’ll have to close this place in… 60 years.

Haha, I was just kidding. Real customers paying for real products doesn’t matter in this business.

People, 23andMe isn’t going anywhere. They are the Bill & Melinda Gates Sergey & Anne Brin Foundation, Silicon Valley style. Anne Wojcicki is married to Sergey Brin, so 23andMe has access to all the talent, connections, and capital 23andMe would ever need to make 23andMe work. Thus, assuming 23andMe doesn’t do anything egregious, they will exist for as long as Mrs. Anne Wojcicki Brin pleases it to be so. If 23andMe shuts down, it won’t be for some mundane reason like the bills weren’t paid, it will be because Anne felt like it. One thousand Coriells wouldn’t change that.

What, does that offend your meritocratic, democratic, American dream sensibilities? Too bad. Go get an Ivy+ degree and marry your own richest man in the world.

People like 23andMe. I like 23andMe. People buy 23andMe tests. I bought a 23andMe test. They’re the best, they can make sales, they have the best product, and someday, they might even “sell” their database to Google. So what? Doesn’t matter. All of that is just something plus infinity.

End of story.

History Remembers Navigenics:

Navigenics thought that they could be Internet Doctors, but they sell premium commodity non-medical medical information, exclusively available to everyone on the web. What do medical specialists charge? Durrr, let’s put a picture of a doctor on our website charge that!

If anybody in medicine was ever going to take Navigenics seriously, Coriell quite clearly dispelled that idea. They don’t have customers, doctors hate them, scientists don’t trust them, Navigenic’s product sucks compared to 23andMe, and unicorns carried their database-pharma-sale story back over a rainbow to happy magic land. Who cares what Navigenics thinks anymore?

As for consumers? I am a fan and customer of 23andMe. You found me. We exist. I challenge anyone to find a single happy customer of Navigenics.

Navigenics: at least they didn’t commit insurance fraud.

History Remembers deCODEme:

I really want to like deCODEme. I do. Not because deCODEme is so great, but because they flew me to Iceland once for a job interview, and I appreciate that. Sure, too many people gave me the “run away unless they pay” speech, but they still have a special place in my heart because, let’s face it, Iceland is kind of a cool country. Maybe the Icelandic government will bail them out, or maybe Kari will hop into a viking ship and raid England or something. But, sorry, deCODEme is just not competitive with 23andMe, and until I’m convinced otherwise, when I say DTC genomics, I mean 23andMe. But, they’ll continue to exist as long as deCODE does someway or another. Running a Ruby-on-Rails website is cheap.

deCODE did start a new blog, though. Check it out! deCODEyou

NOTE: “VP BIZ DEV!” is to be read as if you are barking a college football slogan while chugging a natty and wearing a jersey featuring no less than one food stain.

(update: what do teachers think of the PGEP?)

Dana Waring and colleagues at the Personal Genetics Education Project have put together an excellent set of resources for teachers and professors. The first few lesson plans are freely available for download at http://genepath.med.harvard.edu/WuLab/pgEd/curricula.html.

For example, the first lesson plan is geared toward a general discussion of ethical questions regarding genetic testing and possible consequences. Discussion centers on the story of a young girl who, after watching her grandfather’s decline due to Huntington’s, decided to get herself tested and the fallout that ensued upon learning she tested positive.

There has been much media hype lately about genetic tests and genome wide SNP tests from companies such as 23andme and Navigenics, yet, many do not have a working understanding genetic testing and its implications. Waring does a good job discussing the possible negative outcomes of having a genetic test, and she demonstrates why it’s so important to consult with a physician or genetic counselor before getting a high penetrance genetic test such as the one for Huntington’s. Students are forced to think about the issues at hand and how genetic testing will play a large role in not only their medical futures, but also their day to day lives.

I’m looking forward to reviewing more of Dana and her team’s material, and I hope professors and teachers who read Think Gene will consider taking advantage of this educational resource and integrate it into their curriculum. This generation of students will be the first to have to make decisions about genetic tests, and I feel it’s our duty to properly educate them so they are prepared.

Andrew says:

UPDATE: What do secondary education teachers think about Waring’s Personal Genetics Education Project?

Jane Yates, a veteran teacher (and my mother) writes:

The Personal Genomes 101 summary is a great quick resource. The lesson plans could be helpful to a teacher, but they should list which national and state standards to which it relates. Teachers probably would not use the PowerPoint slides. I don’t think that the lessons would be used much by High School teachers, however, it is a great resource for a student who would be assigned a biology research paper or an English position paper.

Josh: Dr. Marth brings up some very good points. Many signaling molecules in cells are not just composted of proteins, but may be molecules that are a combination of protein and sugar (glycoprotein) or protein and fatty acid. Fatty acids alone may be signaling molecules, such as fatty acid derived prostanoids via cyclooxygenase (COX) that play a role in pain signaling. Since these molecules are created by enzymes, studying the genome or proteome alone is not sufficient to understand diseases caused or influenced by defects in them.

Why is it that the origins of many serious diseases remain a mystery? In considering that question, a scientist at the University of California, San Diego School of Medicine has come up with a unified molecular view of the indivisible unit of life, the cell, which may provide an answer.

Reviewing findings from multiple disciplines, Jamey Marth, Ph.D., UC San Diego Professor of Cellular and Molecular Medicine and Investigator with the Howard Hughes Medical Institute, realized that only 68 molecular building blocks are used to construct these four fundamental components of cells: the nucleic acids (DNA and RNA), proteins, glycans and lipids. His work, which illustrates the primary composition of all cells, is published in the September issue of Nature Cell Biology.

Like the periodic table of elements, first published in 1869 by Russian chemist Dmitri Mendeleev, is to chemistry, Marth’s visual metaphor offers a new framework for biologists.

This new illustration defines the basic molecular building blocks of life and currently includes 32 glycans (sugar linkages found throughout the cell) and eight kinds of lipids (which compose cell membranes) along with the more well-known 20 amino acids that are used to make proteins and the eight nucleosides that compose the nucleic acids, DNA and RNA.

“These 68 building blocks provide the structural basis for the molecular choreography that constitutes the entire life of a cell,” said Marth. “And two of the four cellular components are produced by these molecular building blocks in processes that cannot be encoded by the genes. These cellular components – the glycans and lipids – may now hold the keys to uncovering the origins of many grievous diseases that continue to evade understanding.”

Currently, the vast majority of medical research looks to the human genome and proteome for answers, but those answers remain elusive, and perhaps for good reason.

“We have now found instances where the pathogenesis of widespread and chronic diseases can be attributed to a change in the glycome, for example, in the absence of definable changes in the genome or proteome,” Marth said, adding that, as biomedical researchers, “we need to begin to cultivate the integration of disciplines in a holistic and rigorous way in order to perceive and most effectively manipulate the biological mechanisms of health and disease.”

“What is important is that no one has composed it and laid it out so clearly before,” said Ajit Varki, M.D., Distinguished Professor of Medicine and Cellular and Molecular Medicine and founder and co-director of the Glycobiology Research and Training Center at UC San Diego School of Medicine, and chief editor of the major textbook in the field, The Essentials of Glycobiology. “Glycobiology, for example, is a relatively new field of study in which researchers at UC San Diego have much expertise, and Dr. Marth’s work further illustrates the importance of these glycan molecules.”

Marth believes that biology should become more integrative both in academic and research settings. “I’m one who believes that we don’t need to sacrifice breadth of knowledge in order to acquire depth of understanding.”

Source: University of California - San Diego

A unified vision of the building blocks of life. Jamey D. Marth. Nature Cell Biology. September 2008 - Vol 10 No 9. doi:10.1038/ncb0908-1015

Slobodan Cekic writes in response to How Much Data is a Human Genome:

Now, please do take a look at your fingertips. You ll see the fine lines of your fingerprint pattern. It is unique, and can be used to identify a human; so fine and even much finer structures are defined in your organism.
Now, how high would be only 3D positional information content needed to describe a human?

You would need to position single cells, define the inner structure of particular cell types, describe the form of single nerve cells (dendrites)…etc

Now how many cells are there in the human organism?

Without any calculation, we can see the information quantity to describe a human in uncounted Terabytes. Human chromosomes contain , as calculated here, 740 MB.

So, why for the God’s sake do we believe that the whole of our hereditary information resides in the genes?

740MB is the size of a reference human haploid nucleotide base string, not the data necessary to describe a mature human.

We believe that most of our hereditary information resides in genes because it does. However, a genome, as you say, cannot possibly fully describe a mature human. A genome is more like a brief mathematical equation used to produce beautifully complex fractal design when fed with ambient noise and interpreted as colors and coordinates on a screen.

Arguably, as other commentators have noted, this isn’t enough to describe a genome. Cytosine can be methylated —like a fifth base. Sometimes, a sequencing machine is unable to assert a base, and an extra bit would necessary to report these “no calls.”

But in reality, humans don’t have a “reference genome.” Almost every cell has its own pair of genomes, and these tend to diverge as they accumulate mutations and errors. To be pedantic, to record your Real and Complete Human Genome, one would have to sequence every strand of DNA in your body instantaneously.

Yet, these trillions of strings of millions of bases can be understood as that 740MB reference human genome like a field full of flowers can be understood as a photo of daisy.

With the “all-natural new-age herbal remedy” niche has already well-commercialized, what territory shall the ambitious huckster stake? Fortunately, the brash misapplication of science spews an unending stream of hopefully salable magic.

Now, two new online dating services promise to find your “scientific match” by testing your DNA.

[note: manually enter links; I will not promote dubious sites with html links which are rewarded by search engines and referral traffic]

The least dishonest (and most expensive) is Scientific Match [scientificmatch.com]. For a mere $1,995.95 and cells scraped out of your cheek, you too can be “physically chemically” matched to your magic sweetheart… that is, if you’re not a felon. Scientific Match is quite adamant about this in their terms and conditions. By comparison, a 23andMe genomic test is $1000, a test which is by all indications is a vastly more comprehensive and scientifically-reputable test. (Scientific Match does not explicitly state for which genes they test and how they interpret results.)

So what exactly does Scientific Match test? From http://www.scientificmatch.com/html/about_physical_chemistry_defined.php :

Physical chemistry is based on the immune system. When we analyze your DNA, we look exclusively at your immune system genes. So, quite literally, when we say that two people have “chemistry”, we’re saying that their immune system genes are perfectly matched with each other.

By perfectly matched, we mean different. After we analyze your DNA, we match you with other people who have different immune system genes from yourself.

So, encouraged by one weak study about girls smelling sweaty tshirts, they test a few random genes associated with the major histocompatibility complex, match people different test results, and then throw all that crap out and match people willing to pay $2000 for a dating service “based on science.”

Just to be clear, we don’t know of any scientific evidence suggesting that our technology will predict who you’ll fall in love with or even be emotionally attracted to. But the experts clearly see incredible potential in the power of chemical attraction.

…

As long as you’re matched with the right person, and you’ve got chemistry, then it doesn’t matter if it’s via your sense of smell or some (possibly other) chemical sensing system. The fact is, chemistry–and its effects–is real. The specific communication process, though, has yet to be definitively proven

Oh right! Just redefine “chemistry” to mean “anything” and “then it doesn’t matter!” Yet, what has been proven is that if you’re willing to spend $2000 on a dating service, you’re probably willing (and desperate enough) to believe that it works. Therefore, it probably will.

The Scientific Match’s competitor is the shabbier and cheaper Gene Partner [genepartner.com]. Gene Partner is like Scientific Match except that it costs a mere $200, its website sucks, and it’s “in collaboration” with the “Swiss Institute for Behavioral Genetics”. Hilariously, from the “Swiss Institute’s” website [sibeg.org]:

SIBeG is affiliated to GenePartner GmbH (Switzerland) which reserves the right to patent any profitable findings prior to publication.

Surprisingly, SIBeG has yet to publish any research. Hm…

The science may be bunk, but do these services work? Popular online dating review forums make no mention of these services. My suspicion is that because the expenses of running a website and outsourcing simple genetic tests to labs are negligible, and thanks to the generous media blitz by the gullible prole American media, both sites will continue to scratch out a small profit on the internet until their founders get bored. Thus, gullible singles will continued to be matched with about the same rate of success as sites with comparable service fees and web interfaces for the next ten years or less. Hooray for the miracles of genomic science.

Note: the New York Times also mentions the “sweaty tshirt and dating” study. Ok, I admit, it’s a facinating subject, but sorry, the science doesn’t exist yet.

Did anyone actually read GINA (Genetic Information Nondiscrimination Act) before lauding it for protecting the public or condemning it as over-regulation?

From GINA at The Library of Congress:

Prohibits a group health plan from requesting or requiring an individual or family member of an individual from undergoing a genetic test. Provides that such prohibition does not: (1) limit the authority of a health care professional to request an individual to undergo a genetic test; or (2) preclude a group health plan from obtaining or using the results of a genetic test in making a determination regarding payment. Requires the plan to request only the minimum amount of information necessary to accomplish the intended purpose.

So, according to this:

1. Health plans can require the results of a genetic test to make a decision regarding payment.
2. Assuming having one’s genome available to make medical decisions makes health care more effective and efficient, premiums cannot be adjusted to account for the savings.

Um, isn’t this is the worst for both effective health care and patient fairness? Doesn’t this mean that health plans can simply demand any genetic test when deciding payment (and hold that decision hostage to get that test… and what if a decision is urgent)? Doesn’t this mean that health care will be institutionally less effective because rather than instituting a single, preventive genomic test to be consulted to make better medical decisions for one’s entire life(which GINA makes illegal), instead, patients will only get ad-hoc and myopic genomic tests as demanded by health plans for payment decisions? Won’t this make health care less effective while creating a new market for inefficient, interventionist specialty genomic tests?

So, what happens when a project like the Coriell Personal Medicine Collaborative shows that using genomic personalized health care makes health care better and cheaper?

I’m embarrassed that I relied on the hype surrounding GINA and didn’t read the law to form my own opinions.

Further, if I’m right about this (I want to consult a lawyer),  I’d be deeply embarrassed for the journalists and industry representatives who should have noted this rather than publishing fluffy, feel-good fed PR. Hypothetically. I’m going to get a legal opinion before I start stomping around, naming names, and posting links!