Supreme Court gene patent decision means little for eczema research

Following last week’s decision by the US Supreme Court that human genes cannot be patented, I’d say nothing has changed for eczema patients.

What I mean is that it makes little difference to eczema therapies now or in the future whether companies can obtain US patents on human genes.

I see two major issues: moral and commercial. Morally, I feel it’s a great triumph that even the famously conservative justices of the Supreme Court—who we really expected to side with big bucks, as they seem reliably to do—unanimously affirmed that nobody can own naturally-occurring human DNA. No company can own a piece of my genetic heritage.

Commercially, the issue is intellectual property. I work in biotech, and every day I hear about how it’s crucial for companies to control their IP. No investor is going to back a company that can obviously be sued in the future or that is developing a product that could instantly be copied by a competitor without penalty.

The loser in the decision was Myriad Genetics, which owned the US patent on BRCA1 and BRCA2, two human genes in which mutations increase one’s chances of getting breast cancer. (From what I can tell, Myriad had patents on the normal genes as well as common cancer-linked mutations.) Myriad had exclusive rights to DNA tests that could determine whether patients had mutations. Now many other companies are developing similar tests, and the competition will drive down the price of the tests.

That’s great if you want to get tested for breast cancer. But what does it mean for companies that are developing diagnostic tests for other conditions? These companies may abandon their efforts. Or the companies may never get started.

At least that is what one commercially-minded person whose views I respect tells me.

The Faster Cures blog, conversely, makes the point that patenting DNA could, and has, led to R&D on diseases being blocked by legal obstruction. Lilly, apparently, spent eight years fighting Harvard, MIT and others over the rights to one particular gene, NF-kB. Presumably lots of money got spent that might have gone to actual research instead of lawyers.

But for a gene patent to be useful, there must first of all be a strong link between genetics and disease. Eczema, despite being known to have a strong genetic component, has not been definitively linked to genes except in the case of filaggrin. There are a few mutations that seem to correspond to particularly severe eczema but they don’t occur in many people.

In any case, the sequence of filaggrin was made public in 2006 so the point is moot—once made public, an invention can’t be patented. (I searched the US Patent and Trademark Office database and didn’t see anything.)

Also a diagnostic test is only useful if it gives you information you can act on. There’s no point telling an adult that they have severe eczema, because they already know that. And if parents learn that their child is at risk—not guaranteed—of developing eczema, what can they do to prevent it?

Not much that I know of.

Diagnostics aside, how might a gene patent be useful?

Many drugs or biotherapies being developed affect how genes are regulated—how the process of turning their information into protein is amplified or damped. Perhaps owning a gene patent would let you control work that other people are doing to regulate that gene. We’ll never know now! What is certain, though, is that if you had a gene patent and lots of money, you could probably intimidate other companies by threatening them with expensive legal action.

I don’t think enough is known about eczema at this point that a gene patent would have been a factor. Look at the existing therapies and the few in the pipeline (such as Anacor’s). They are all either anti-inflammatories or calcineurin inhibitors. They don’t affect genes directly.

Researchers are starting to put together useful models of how itch signals get transmitted from the skin to the brain. For itch, we wouldn’t be interested in a diagnostic, but we would like to have a therapy. It’s conceivable that one or two genes may turn out to be key, and we might want drugs to regulate them. But gene patents would not be necessary for scientists or companies to do that work.

In short: last week’s Supreme Court decision, while morally important and laudable, will have little effect on the field of eczema research and therapy.

Filaggrin mutations cause distinct pattern of eczema in children

The giant protein filaggrin has several vital functions in skin. People with mutated copies of the filaggrin gene (FLG) are at risk of developing eczema that begins earlier and is more severe than usual. A new population study by Danish scientists (published in the journal PLoS ONE) now shows that children with FLG mutations develop a distinct variety of eczema, with emphasis on exposed areas such as the cheeks and the backs of the hands.

The research, led by Hans Bisgaard at the University of Copenhagen, could in the future help doctors diagnose children at risk of developing eczema and design personalized treatment for them—including therapy that could change the course of the disease.

The researchers analyzed data from the Copenhagen Study on Asthma in Childhood, which comprised 411 children born to mothers with asthma and followed them over the course of seven years, with checkups every six months (or more often, if eczema flares warranted). The scientists tested DNA from the children, checking to see if they had one of the two most common FLG mutations, known as R501X and 2282del4.

The results were not as cleancut as one might like. Roughly 15% of the 170 children who developed eczema had FLG mutations. But so did 7% of the 212 children who did not develop eczema. So clearly having mutated FLG does not guarantee eczema, and there are other factors at work to compensate for the mutation or cause disease to develop even if you have good filaggrin.

The researchers found that, in general, short- and long-term symptoms of eczema were worse in children with mutated FLG; and the disease set in earlier and flares tended to cluster in certain areas, most importantly  the cheeks and backs of the hands.

What is your child’s eczema like? Or what was yours like as a child? Does it fit this pattern? I seem to remember it concentrated on the backs of my knees and the insides of my elbows. But over the years it has moved around a lot. Maybe we will see scientists develop a catalog of eczema subtypes caused by known mutations.

Sperm for sale cheap. Only one small problem

Last night I was watching the first episode of the TV series "Parenthood" on Netflix. There's a scene where one of the male characters gets out of bed, where he's just had sex with his girlfriend, and opens the fridge to find a vial of frozen sperm--not his--from a sperm bank. "It's very high-quality," she says (or something like that). "It's from an Olympic athlete who was also a Rhodes Scholar."

Why this successful stallion was selling his baby batter for $50 a pop (I admit ignorance of the going rate) is not discussed, but the scene did make me think.

The prurient aspects of sperm donation disappear into the background when a single woman decides to have a baby. She's concerned only with quality. And from my experience with mothers, they want nothing but the best for their babies, whether it's a stroller, a crib, a nanny...or their DNA.

But what is quality? And, relevant to this blog, if I hypothetically donated to a sperm bank, would any woman want to buy it?

Here are the selling points: I'm a decent-looking guy, in shape, highly educated. No major health problems run in my family.

Or do they? Does eczema count as a major health problem? I think it probably would, for a prospective mother shopping for sperm. There's almost no cash discount that would make any of the yuppie moms I know choose my vial if they knew I was likely to pass on the genes for eczema.

Evidently my wife made the calculation at some level. She wasn't buying it like shoes on Zappos though. Things would have gone differently.

I bet sperm shopping is like a high school dance, but worse. Everyone wants a hot partner, but the reality is that there are only so many to go around. Nevertheless most people find someone to go to the dance with. That's not the case with sperm; the "best" vials are probably in high demand, while the others sit on the shelf. Dog and horse breeders know that you get fine animals only if you start with the best material.

I don't know what point I want to make, only that I would surely correct the errors in my own DNA if I could and if it would do any good; and that this thought experiment makes it clear that all human lives are valuable--especially to the people like me who are living them. Chance and environment play major roles in how a human being turns out.

By saying this, I do not mean that I am in the "pro-life" camp when it comes to abortion or euthanasia, but just that the vast majority of people have something unique and worthwhile to offer, and that in the big picture, eczema doesn't make that much of a difference.

Eight new genetic targets for eczema treatment

A group of scientists has found eight new genetic locations linked to eczema in the Japanese population.

Eczema is a disease on which genetics has a strong influence. New data of this type could highlight previously unknown genetic causes for which it might be possible to develop treatments.

The scientists, led by Mayumi Tamari at RIKEN in Yokohama, conducted a genome-wide association study, or GWAS, on a group of about 1500 eczema patients and 8000 controls, and validated their results on a similar group. They published their results in the journal Nature Genetics.

DNA is built of two strands, each of which is a string of molecular fragments called "bases"--A, C, G, and T--paired with its complementary base (the two complementary pairs are A/T and C/G) In a GWAS, researchers select a number of bases (in this study, 600,000) that are known to vary in the human population, and identify which locations, if any, contain bases that are more common in people with a certain trait (in this case, eczema).

The Japanese scientists conducted their study to identify new locations in addition to seven other candidates, including filaggrin, that had previously been found in Caucasian and Chinese patients. The eight new locations were found in or near genes important in skin barrier function; adaptive immunity (white blood cells and antibodies); the inflammatory response; and vitamin D processing.

My own take on this is that GWAS studies in eczema patients continue to highlight the mysterious nature of the disease and how far we are from anything approaching a cure. If there are 15 known, quite different, genetic locations associated with eczema, exactly which ones should scientists focus on to try to develop treatments? The disease is remarkably complex and the best hope for new treatments would seem to be an unanticipated discovery of a new or repurposed drug.

Filaggrin mutation means more persistent eczema

The super-protein filaggrin helps skin cells take their proper shape as they develop into the upper, outer layer of skin; in its last step, it disintegrates into molecules that help the skin lock in moisture. Back in 2006 a landmark discovery showed that mutations in the filaggrin gene made it likely that the gene’s owner would develop eczema. But even though filaggrin is the poster child for eczema genetics, not that many eczema patients—only about 15%—have mutated copies of the gene.

Now researchers led by David Margolis, a professor of dermatology at the University of Pennsylvania, have shown that, among children with eczema, those who have filaggrin mutations are more likely to experience persistent eczema symptoms than those who do not.

The scientists analyzed data from the Pediatric Eczema Elective Registry (PEER), an ongoing 10-year registry maintained by Novartis to monitor the long-term safety of using pimecrolimus 1% cream. The new results are in press at the Journal of Allergy and Clinical Immunology.

The difference is subtle: at any time up to about four years of follow up (the period covered by the study), a child with a filaggrin mutation and a history of eczema is roughly 50% less likely to have clear skin than a child with two good copies of filaggrin. [Thanks to Margolis for helping me understand odds ratio.]

Interestingly, the authors noted that although all the mutations they studied were “null” mutations—that is, if you have one of these mutations, that copy of filaggrin doesn’t get produced at all—children with different mutations responded differently to treatment with topical steroids. Kids with the most common mutation, R501X, were most likely to need to use steroids to clear their skin. The authors don’t have an answer why this might be so.

Three new eczema mutations discovered. Is this useful?

A large-scale genetic study recently identified three new locations in the human genome at which mutations are linked to eczema. Two of the locations are near genes thought to be important in dividing and developing skin cells; the third is near a cluster of genes involved in chemical signaling.

The study was published in Nature Genetics, a high-ranking journal. It is actually a meta-study, which re-analyzes data from 30 other studies, totaling more than 11,000 people affected with eczema and more than 40,000 unaffected controls. I don't know how meta-studies account for all the differences in methods and objectives, but I am impressed with the numbers. Generally when it comes to genetics bigger is better.

The question for a patient is: how is this information going to lead to a therapeutic (e.g. new drug)? At this point the researchers don't even know what the genes in the mutated regions do. (None of the mutations were actually IN genes; they were in regions BETWEEN genes.) To get to a therapeutic, you'd have to identify how the mutations affect proteins, what the proteins do, and find drug targets on those proteins, screen for drugs that work, and proceed through the whole billion-dollar death march to FDA approval.

Basically, we're not going to see something in our lifetime from this. Our kids might though.

The authors do at one point say "These observations...support the claim that atopic dermatitis encompasses distinct disease entities rather than being one illness, as is reflected by the current, relatively broad and inclusive concept of this condition." It is possible that within a decade or so we could see direct-to-consumer genetic tests that could tell you what subtype of eczema you suffer from, and you or your doctor could use this information to pick a treatment that might be more effective.

The Eeyore within me says that I'd most likely find that my type was the least treatable. Would I want to know this? Curiously, yes. I found out a few years ago that I carry one copy of the most common mutation for cystic fibrosis. Not good news, but it gave me a small sense of power to have the information.

A day at the geneticist

Cindy posts that her family's been having a hard week. I do admit I've wondered how it goes in larger families; once one child comes home with a flu or something, does that inevitably means it goes around and everyone gets it? Even in our family of four, often just because a kid has a cold doesn't mean that the parents will get it, but it's almost guaranteed that the other kid will pick it up. Voov acquired a viral fever from her cousin at Xmas, and then had some congestion, so we had to have the humidifier on every night. We were going to put the humidifier away, but then Shmoop started getting congested too. And now he most likely has an ear infection. (And a rare, for him, incidence of eczema behind his knees.) The fun never stops!

Voov's eczema has been moderate for a while, so that's why I haven't mentioned it. Some on her scalp though. Whenever she gets stressed about anything, even momentarily, her hands shoot up to her head and she starts scratching away. I have to laugh because I do the same thing, even though I'm all grown up. It's a reflex.

Eczema isn't the only nonstandard feature Voov came equipped with. She's also had a few weird things with her eyes; she took a long time to learn how to walk and talk; and her face looks a little odd--her forehead's kinda bulgy, and her eyes look far apart. Taking everything together, her pediatrician advised us to get a genetic consult to determine whether she might be suffering from some syndrome. So that's what we did today-- went in for the consult.

We saw an MD and a genetic advisor, who asked us all kinds of questions about medical conditions in our families (we had also come with a stack of photos of family members so the docs could compare Voov's face with the photos) and took measurements of length ratios of her fingers to palms; torso to legs; pupil-to-pupil vs. width of the bridge of the nose, etc. At the start, the docs were almost too caring and friendly--it was unnerving, like they were preparing for us to freak out if they found something was wrong. But in the end their initial conclusion was that Voov had no obvious syndrome (although the bridge of her nose is very wide). Which was a huge relief, of course. However, they did suggest that we get done a procedure called "array comparative genomic hybridization," which I'd never heard of, and which consists of comparing stretches of Voov's genome to standardized DNA from "normal" people and looking for deletions and insertions.

Since there's no pressing need to get this done, I'm actually not keen on it. I could imagine that the test might turn up some deletion or insertion that might be associated with a fractionally increased risk for some condition, and then we'd just have something new to worry about. Hidden B wants to get it done, though. She says she wants to know, and that we might find out that (for example) we should get Voov's heart checked out, or at the very least, we'd be contributing her genetic information to a databank that would help other parents.

I can't really argue otherwise-- if there's something definite we could act on, we need to know. The thing is, what's more likely is that there won't be anything definite, or there might be something definite that we can't do anything about. I know that much is true about genetic information.

Fantastic filaggrin article

I'm genuinely excited today. I found something much more interesting than the usual crop of eczema news. In the magazine The Scientist--which has a tradition of features that have a strong strain of narrative writing--that is, story, rather than just a gaggle of facts and jargon--I found an article written by Irwin McLean, a professor at the University of Dundee in Scotland. McLean is the lead author of the landmark papers that reported, first, mutations in the filaggrin gene that cause ichthyosis vulgaris, a dry, scaly skin disorder; and, second, that the same mutations caused (or greatly increased the risk of) eczema.

Please read McLean's article. It is effin' awesome. It's written by an expert and as riveting a read as you'll find anywhere, if you're interested in eczema science.

Here's McLean's explanation of why filaggrin matters:

Filaggrin is crucial for the formation of the stratum corneum, the layer of dead cells at the surface of the skin, and also for the hydration of this crucial barrier layer. People who have mutations in one or both copies of the filaggrin gene produce dry and flaky skin that is permeable to allergens or chemical irritants. When the barrier is broken, foreign material is able to pass through these skin layers. We think that childhood eczema—which usually first occurs within the first few months of life—is an indication that foreign pathogens and irritants have passed through an abnormally porous skin layer, activating a strong allergic immune response, and thus priming the body to react to antigens that it would not normally encounter by this route. Later in life, when the child’s immune system comes into contact with those same allergens, perhaps through the lungs, it reacts aggressively, causing the inflammation in the lungs that results in shortness of breath. In fact, many children with eczema have multiple allergies to house dust, pet hair, and other substances.

McLean tells the story of how he and his team identified the mutations in the filaggrin gene (FLG). FLG is a remarkably difficult gene to sequence and was one of the last to be conquered by the Human Genome Project. It's very large, and contains 10 (or, sometimes, more) identical subunits, which means that if you start sequencing somewhere in the middle, as is done in a shotgun approach (where you sequence a lot of small bits and join them up like a jigsaw) you can't be sure if you're sequencing just one of the subunits, or more than one, or all of them at the same time. "It was as if nature was having a joke at our expense," McLean writes.

The team managed to identify the two mutations in ichthyosis vulgaris-- but then one of the scientists, Alan Irvine, pointed out that many of the patients in the subject group also suffered from eczema, many more of them than were in the control patient group. (It's this kind of insight that drives scientific discovery.) McLean, Irvine, and colleagues ran a statistical analysis on their patient group, which was very small by epidemiological standards--only 50 affected patients, and 200 controls, instead of thousands--and found that the  measure of significance, the "p-value," indicated beyond a doubt that there was a link between eczema and the mutations.

At the end of the article, here's McLean on what's next.

The question now is how to prevent eczema, asthma, and allergies from occurring in patients with the susceptibility mutations in their filaggrin gene. If it were possible to find a cure for eczema in adults, could we also cure asthma, or would it be too late, with the immune system permanently primed against allergens? I would argue that it might at least help. If the skin barrier is not repaired, then the immune system will constantly produce more antibodies in response to allergens that continue to get past the barrier. Stopping that assault may have some beneficial effects. The alternate possibility is that we may need to prevent eczema in young children before they become sensitized. If the latter proves true, would it be sufficient to curb eczema early in life, as the immune system develops? These are all questions we are gearing up to answer...

...We’ve also started to look for ways to help the body replace filaggrin at the cellular level. We are currently searching small-molecule chemical libraries for new classes of compounds that might induce skin cells to produce more filaggrin protein. Results look promising, and we are hopeful that in a few years’ time, new drugs or creams that enhance skin-barrier function will be available to treat these common diseases.

From McLean's biography we learn that he briefly worked at a biotech company, which is good news for us: he probably has some idea of how cures get from the benchtop to market.

I'm going to argue that HERE is where we need to put our money from philanthropic donors. Now that McLean and his team of leading scientists have found these mutations and laid bare the role of filaggrin in eczema, we need to help entrepreneurial scientists translate this research into startup companies or intellectual property that can be licensed to big pharma or biotech companies such as Genentech. THIS, the proof-of-concept stage, is where funding in the area of $100k can make a difference to an academic lab-- the difference between the science turning into real cures, or languishing in the pages of the scientific literature.

Badge of honor

At the bottom of the right-hand column you'll notice a snazzy new badge. End Eczema has been recognized! By that fine institution, www.medicalassistantdegree.com. If you click on it, as I did, you'll end up on a page listing nineteen blogs. "Score!" I thought to myself. "A whole host of eczema blogs-- the vibrant blogger community I always knew was out there!"

Unfortunately, on closer inspection, all of the other blogs, if not dead, either have been quiet for months or clearly have no scientific merit. Or any kind of merit. Sigh. Eczema Mom and Cindy: L'eczema blogging community, c'est nous.

But I'll wear the badge with pride, at least until a better one shows up. It's like having a degree in blogging from the University of Phoenix.

Speaking of academic institutions, today I found a syndicated newspaper column in the LA Times online, written by Henry Bernstein, senior lecturer in pediatrics at Harvard Medical School. A reader asks him "what can I put on my 3-year-old grandson to treat his eczema?" According to Bernstein, those of us with eczema can expect to have

• Dry, scaly skin
• Plugged hair follicles that make bumps (usually on the face, upper arm and thighs)
• Swelling around the lips
• Darkening of the skin around the eye

Dry, scaly skin: check. Plugged hair follicles? Swollen lips? Dark circles around the eyes? Is this how they teach dermatologists at Harvard to diagnose eczema? I'd rather my dermatologist had a diploma from the University of Phoenix. Oh yes, Bernstein does get around to answering the question in the end: you should be putting moisturizer on your grandson. Duh!

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As you can see, I have been inspired by the holiday spirit.

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I learned that the company 23andMe in Mountain View, CA has a special deal out on personal genetic sequencing. For $99 you can send in your spit and find out your risk of developing 175 different conditions. Atopic dermatitis is one of them. If you're reading this, I suspect you already know what your risk is-- but FYI, they appear to be testing whether you possess one of the two common mutations of the filaggrin gene.

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In my last post, I mentioned that another Bay Area company, Anacor, has an interesting anti-inflammatory drug in the pipeline, a boron-based compound. I should have mentioned that I find it interesting because it is most likely not a steroid, and won't have the side effects of steroids-- though it will inevitably have other side effects. I'd like to know how it works and what strength it might be (compared to the US steroid scale).

And something else I'd like to know: is anyone making an anti-ITCH cream instead of an anti-inflammatory? Is anyone addressing itch neural fibers rather than just reducing the blood flow to the skin?

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Here's a story about another experimental drug: this lady, in England, suffered from hand eczema that became debilitating-- affected her right hand so that she could hardly use it for anything, and looked so nasty she had to wear a Michael Jackson-style single black glove. She was put on steroids, of course, and given UV treatment, which did nothing. What appears to have put her eczema in remission is a drug called alitretinoin, which is sometimes prescribed for Kaposi's sarcoma.

What is alitretinoin doing to relieve eczema? I'm not sure. At least it's not a complete shot in the dark for a dermatologist to prescribe: here's a story describing how a clinical trial of alitretinoin in Europe and North America cleared up hand eczema in ~50% of treated patients. I believe hand eczema (on the palms, not the backs) can often be triggered by rubber gloves or exposure to certain metals. A few years ago, I had eczema on the soles of my feet-- I think it was the hot, humid climate of Washington, DC, that was to blame-- and it was intolerably itchy. Denise Hyland has my full sympathy.

A tale of two itches

As SK is cavorting across the continent, I will take the opportunity to introduce myself as a guest blogger on End Eczema. You can call me Dr Sib.

As mentioned in previous posts, I share in approximately half of SK's genetic pool, being his sister. Unfortunately for me, our genetic overlap appears to include a faulty filaggrin gene that has been the root cause of much unhappy scratching by us both. And, while I've certainly spent my fair share of time shredding my own skin with my 10 digits, I have to confess that this particular organ is fairly intact at the moment, my atopy manifesting itself more at the asthma end of the allergy spectrum.

I attribute this happy state of affairs, based on a sample size of 1 (myself), in part to my geographic locale. My eczema has never been as flared as it was for the 12 months I spent on Vancouver Island on Canada's western coast. There, I spent the entire time bleeding into my sheets at night, tossing and turning with the torment, and avoiding showers because the chlorine in the water burned too much to bear on a daily basis. No dietary measure had any effect. Nor did the usual routine of steroids and emollients that I had come to rely on in the past.

Musing back, I realize (quite ironically for reasons that will become clear in a moment) that I never consulted a physician during this time, nor did it even occur to me to do so. Essentially, anything I had learned about managing my eczema up to this point had been from personal experience and the advice of fellow sufferers. It was well known amongst this same cohort, that our family doctors had proven to be pretty useless when it came to treating our dysfunctional skin. At the same time, I had never been referred to a dermatologist, so I assumed I was stuck with things as they were, bad as they were.

Now, as a first year resident in family medicine, what do I do with this memory? I admit I do feel it reveals a certain incompetence on the part of the family doctors I've had in the past in managing atopic dermatitis. The time I've spent with dermatologists thus far in my training has suggested that family doctors have a tendency to be far too cautious when it comes to the use of topical steroids, particularly in children and adolescents. I seek to rectify the problem in myself by taking a special interest in the dermatological complaints of my patients. And, I hope I have a well-developed capacity to empathize fully with the impact a symptom as 'harmless' as ITCH can have on an individual's life. Finally, I feel the drive to be competent in diagnosing, counseling, and managing this problem in my own patients. For me, this will mean an extra rotation in dermatology during my residency training.

My story brightened when I moved back east, first to central Canada (Ontario), and then to the Maritimes. My skin healed of its own accord. While I used to attribute my temporary misery to some quality of the water to which I was exposed, I've come around to assuming there must have been an environmental allergen triggering me, be it mould in the basement apartment I was inhabiting, or some type of noxious pollen circulating in the botanical breezes of the west coast. Either way, I'm left a number of habits/superstitions that I use to ward off a recurrence: I never miss a full-body moisturizing after a shower/bath. I don't expose my skin to long, hot soaks. And, I'm aware that every coffee, every alcoholic beverage, and every spicy meal exacts a toll that may tip me over the edge into a flare.

Big genetics

Genetics is all pretty abstract until you find out something about yourself. I only know one thing for sure about my own genome-- I have one copy of the most common mutation for cystic fibrosis. I found this out when Hidden B and I had prenatal screening done about four years ago. The estimated chance of having this mutation is about 5%, so I was unpleasantly surprised. I'm defective! (And each of my kids has a 50% chance of being a carrier.)

On the genetics front, big big news today, although I didn't see anything appear in a major outlet. Maybe I missed it-- more likely is that the news was too complex and not attractive enough for the average reader for newspaper editors etc. to assign the story to reporters.

You'll find decent writeups at Nature News and GenomeWeb. A gigantic international research coalition, the 1000 Genomes Project (nearly as many authors as genomes) published a paper in Nature describing how they sequenced about 880 human genomes. I'll leave out the details, which, frankly, are lost on me, but the point of the work was to get a handle on how our DNA varies from one human to the next. An astonishing quote from the abstract:

"On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders."

Hoo boy. The authors are saying, in essence: each of us is a factory reject. If we each carry 250-300 genes that ought to work but don't, imagine how much redundancy is built in. If a gene is broken, there are others to compensate for it.

This is why it's so hard to find connections between single genes and diseases. It's why scientists think it's a big deal to find that about 20% of children with eczema have loss-of-function mutations in FLG, the filaggrin gene--because 20% is a large number! (Before I studied molecular biology, I would have thought scientists would only care about mutations that were found in, say, 75% of patients with a given condition.)

And EACH of us has 50-100 variants that put us at higher than average risk for a random grab bag of inherited conditions. Tay-Sachs, anyone? Alzheimer's? If you ask me, there's no need to extend the human lifespan. I don't need to discover how many weird things I might develop if I live past 85.

A much lower-profile item: some journal called Nature Precedings (appears to be a catalog of NIH project summaries) reports an ongoing project of interest to you and me: "Skin Microbiome in Disease States: Atopic Dermatitis and Immunodeficiency." Julia Segre and Heidi Kong at the NIH are studying patients with eczema and two immunodeficient conditions to profile the populations of bacteria and other microbes that live on our eczematous and non-affected skin--and in our nostrils! (A while ago, I don't have the reference, someone discovered that nasty bacteria hide out in our nostrils. So stop picking your nose.)