Future: here we are.

NY Times headline : Chinese Scientists Edit Genes of Human Embryos, Raising Concerns. Since work with the Crispr system has shown that gene splicing can be quick and easy in many systems, the scientific community has been urging restraint on human embryo manipulation until such time as we’ve had to think about all the ethical complications of being able to do so.
Lots of people are going to be getting into this, very fast. They don’t care that changing an embryo’s genetic makeup might be the wrong thing to do. They care that they can be paid big time for doing so. Well, eventually. Once it actually works. Though maybe even if it works a little bit once in a while.

What the Chinese article showed was that trying to splice a gene into an embryo (ones already declared to be non viable), specifically a normal copy of beta-globin gene, to correct a very serious genetic condition known as beta-thalessemia, was a disaster. That was their basic question – could you do it. They weren’t trying to fix a real case and have a child born from their experiments. (well, yet...)

In a collection of cells, some underwent the editing as planned. In others, a similar gene was incorrectly targeted. In others still, a variety of mutations happened. Overall, it was a mess, far, far from generating a viable embryo.

So there’s a ways to go before this new gene splicing kit allows anyone to make babies to order.

What I think is that calls to go slow and think it through before diving in, calls to wait for national and international guidelines, may have little effect on ambitious labs trying to be first across the finish line. Scientists are asking for a ban on such research, but bans on cloning or embryonic stem cells didn’t stop such research from happening, only drove it toward different funding and/or different countries.

A bit of paper

Actually, a file sent by email.

But yes, folks, we are officially
ACCREDITED
by the COFRAC.
We were pretty sure we would be, but it makes a certain difference to have that certificate in hand.

Break out the champagne!

Superpower: variant detection

Warning! Highly technical post today!

This week is pretty calm at the lab, with nearly half our staff on vacation. That means 4 of the 5 diagnostic techs. Since we're pretty far behind in signing out cases, I've been picking up some of the slack in reading sequences. All our sequences are read twice, to maximize the chances of actually seeing any variants that are there, and getting them onto the summary table with the right name and all.

You'd think with all the sequence alignment software that's been out there for so very, very long, that you'd barely need one person to read all the sequence, let alone two. Differences should just pop out. Gotta be blind not to notice one bold red base in a whole field of grey.

Weeeeellll, it's not always so easy as that.

This particular case we signed out last year as having no mutation. But it bugged me, because the patient's tumor had all the signs of mutation in this one gene. Not everyone with all the signs has an inherited mutation, but most of them do. All the analytical steps checked out, though. No mistakes in testing the right sample or anything.

These days with every new analytic series, we include a rerun of something we've run before. So in the current series I reran this sample.

Because 80% of my techs are out on vacation, there wasn't anyone to do the second read of the sequences this week, so I've been doing some of that, both to stay in shape and to move things along. But what's this? Oh, look, a little secondary signal when there should only be one.

The software missed it, because it's just a little bump, far below the 35 % threshold to be flagged. The technician missed it. Really, the second signal accounts for less than 20 % of the signal at that position. Maybe just 10 %. Sometimes we have little peaks at around 10 % in all the samples, though only on one of the two strands of the DNA. Just artifacts when they're systematically present like that. Certain exons are notorious for this sort of thing - you can't get rid of it, and it means nothing.

This one is different. The second peak is only in this one sample out of the 47 in the series. It's present on both strands. The rest of the sequence is nice & clean. And the kicker is that the normal signal is diminished (which doesn't happen with artifacts). The two signals added together equal the intensity of the normal signal in all the other samples.

Hmmm. Normally, inherited mutations are 50-50, because you have one mutated and one normal copy. The patient's family history clearly indicates an inherited mutation, not one that is new in her and doesn't affect all of her cells. No reason for me to look for something 85-15.

So I have my computing guy dig up the archive of this bit of sequence for the first time we ran the sample. This time you really have to look for it, but it's there. No way anyone would have caught that.

There can be technical reasons why a mutation might not show up 50-50. In special genetics cases it might just not be 50-50, like when you have a chimera (a patient whose cells do not all come from a single fertilized egg, but who is a mix of two, only one of which carried the mutation in question) or a mosaic (where the mutation was not present in the egg or sperm, but happened in the early rounds of cell division so that only a subset of the cells in the body have it). Then there's the technical case where there is a second sequence variant farther on which just happens to sit within the sequence of the primers we used to amplify the bit in question - and the amplification of the mutant copy is much less efficient than for the normal copy.

We'll be looking into all that. A chimera will have this lopsided ratio at any sequence variant in the gene, and there are plenty of neutral variants to look at. A mosaic we should be able to rule out, based on family history. And the technical case we can resolve by designing new primers farther away and capturing that second variant. Oh, and the bugaboo of DNA labs, the sample itself is contaminated with a second person's DNA. We'll be looking at an independent sample from the same person, just to be sure.

the Anthropocene

Anthropocene, sure, of course, but when did it start?

1945 has been proposed, because the advent of atomic bomb testing provides a geological marker of change detectable worldwide.

The Holocene, which we used to live in before deciding that those of us alive today really do have our own "cene", started some 11,600 years ago. It's divided into Ages, the Neolithic, Bronze, and Iron, capped by an Industrial Era.
None of those periods started in a particular year. None of those boundaries is anywhere near as sharp as we seem to want this one to be - except perhaps the Industrial Era. You could argue that the invention of the steam engine represents the start of that Era. But you could argue for other events too.
It's only because we're closer to it that people insist on a sharp boundary for the Anthropocene.
1945 doesn't make any sense to me. Surely the whole of the Industrial Era belongs in our new cene. Surely if we're defining the Anthropocene as the era where human activity is the main driving force of how the planet is, then you have to go back farther than that, to the Bronze Age and earlier. For thousands of years now, the influence of human activity in the clearing of forests, widespread proliferation of domesticated food animals, replacement of grasslands with cultivated crops, and the ocean acidification, soil erosion and atmospheric changes that were and still are consequent to that, places the beginning of the Anthropocene at around 5000 years.
More or less. Depends on where you look; depends on what you mean. There's no global geological event marking the start of this human-dominant period. In some places it's earlier than in others. Agriculture goes back 9000 years in Southwest Asia, but only 3000 in Central America. A million years from now, Geologists will not look at that as such a big difference. If only we had that perspective. In the meantime, it looks like the anthropocene will retain its lower-case, informal a.
There's no use in trying to pin a year on the change, and pinning it on 1945 is just hubris - Here we are not even a lifetime into our new Cene and we already know that that year was It? (Had the Cold War ended differently, perhaps! But it didn't.)
Welcome, fellow H. sapiens sapiens, to today.

Short tour of obscure parts of France

So Thursday it was Marseille, by train. They've cut back service terribly, so we had to go through Lyon. That isn't too bad, since the Lyon-Marseille leg is by TGV, whereas the old 'direct' route took its time down the Allier gorge and stopped all over the place. Probably we got there just as fast.
I will say about the cutbacks, though, that they're nonsense - you have to go through Paris to get from Clermont to Bordeaux. Just look that up on a map!
Saw nothing of Marseille - just station to meeting venue to hotel to station.
Had a really early train from there to Lyon on Friday. I hate being late, but did they have to reserve the 6:44 when the 7:10 would have gotten me there in time? And then, a 6am taxi to the station for a 7 minute ride? I did have a leisurely breakfast once in Lyon. Once at the meeting site, however, it was wait wait wait for the others who were also coming up from Marseille, but on later trains, sometimes significantly later trains that did not get them to the CLB until nearly 11.
Later, I hop into Mariette's Alfa as she pulls up to our agreed rendez-vous spot and it's on to Grenoble. The Mercure near the bridge club has a jacuzzi and a sauna. The jacuzzi is too cold and the jets too weak, then the sauna we fail to find the dial to turn up the heat but spend a pleasant moment in the warm. Pasta. I crave pasta for dinner. Right there at the hotel, tagliatelle carbonara on the menu. Heavier than I'd hoped but delicious.
Saturday, a stroll around the city to confirm that, really, there is nothing much to see in Grenoble. Pff. Time to play bridge!
We are cursed.
We start off on a bad foot, forgetting a conventional call that means I actually have zero to three cards of the suit named, but plenty plenty in the red suits. Our opponents pass quickly. They can tell we have screwed up, and I play 3 clubs with a singleton in my hand and just three little ones on the board. All our glorious diamonds get ruffed by the bad guys.
Alright. A fiasco like that is not worth getting mad about. It's just too extreme. A story to tell. (see? I'm telling it again!) The only good thing about it is that it's clearly M's fault, and this cuts short her usual way of explaining over and again what I have done wrong. Not that she doesn't have some occasion for that later, but there is a clear reduction in volume.
But we do not recover from the poor start. One hand we are too timid to bid game, the next we try to be more assertive and get stung going too far. The hands we do right, it's our adversaries who do something right on their side. Hard to fathom we come out of the day 21st out of 40 pairs.
Scored big for dinner, though, with friends who did about as well as we did.
Sunday we take the small roads over to Hauterives, to see the Palais Idéal du Facteur Cheval. A rural postman at the turn of the 20th century dreamt up this crazy palace.
(photo picked from the internet) Today it's an historical monument, with the middle third covered in scaffolding as they make some repairs. Curious thing. M says it used to be quite colorful, but the shells have all lost their luster and even the different colors of stone are subdued by cement dust.
Love the mention "Defense de rien toucher" built into it (on the very right of the photo). So much so that I picked up the t-shirt. Gotta get a t-shirt now and then. Especially as it was about 77°F out, and I had packed for much cooler weather (it's barely April!).
From there down to Romans sur Isère, where we find nothing of interest except the wonderful Jacquemart

(another image picked from the internet) that was just about the strike the hour, literally. A sort of Uhr-Hammer.
Monday morning started with a stroll to a chapel overlooking Tain-L'Hermitage. Not really in the mood for wine-tasting. We just took a short walk and left.
Then a blip on the map, the hamlet of St Cyr. There's a nicely kept-up medieval church that we admired driving by, and just by chance caught a glimpse of a cloister-like area. Gotta stop for that. Seems it was a convent at one time, and the tiny courtyard is quite nice. The interior of the church still has its frescoes all up most of the walls and ceiling, sadly in need of restoration.
Outside, M railed against all the badly-done restoration work on the older buildings (as she had been doing since Grenoble). Personally, I find most of the restoration quite decent; and adapted to people's lives today. We no longer want tiny windows, or doorways even short people have to stoop to enter. If a wall giving onto the street is smooth and harmonious, should I be outraged that the windows used to be different? No. Things change. Let them.
From there to St Etienne. St Etienne is one of the ugliest towns in the country. I have to come here occasionally to get a visa at the Algerian consulate, but this time M gets sort of lost in parts of town I hadn't seen before. Feh. Oh, yes, that is the School of Mining. Very impressive. (yeah, not.)
As an architect, M appreciates architecture. So we're off to Firminy to see the celebrated works of Le Corbusier there.
Oh. Such concrete. Pity concrete ages so badly.
Hey, I didn't say it was pretty architecture! Just look at the way that concrete structure all hangs on a single support, freeing up the space underneath!
Uh, yeah.
Le Corbusier, master of cement. Leonardo of concrete. Genius of reinforcement rods.
May I go now?
We have to see the church. It's a whole city he set up here - apartment blocks, stadium, sports facility, indoor pool, and matching church. Unique among churches (aside from it looking like an ugly concrete blob from the outside. Which I admit is not unique among churches elsewhere, but it's not usually the thing in France.), this one you have to pay to visit. Because it's an historical site, and there are informative displays inside. (Now, how is that unique among churches here?!) So we go in, and yeah, it's better on the inside than on the outside. Not at all warm or welcoming or inspiring adoration. But better. The painted light wells are kind of cool.
Having paid to see what should be free, we walk the few yards over to the pool, which has a row of windows high up that might be quite nice from inside.
There's an employee just going in as we approach and see the sign that the place is closed. So M asks if we can go in and see the building.
No, we can't. It's closed.
We understand it's closed for swimming. We just want a look at the windows. We've paid our ticket, and the guy didn't say anything about the pool being closed! (of course, this same guy insisted that the church was not a consecrated, working church, and thus not subject to the law about being open to the public - which he was wrong about because everywhere inside are indications of it being a currently active parish church, vestments in the back room and all.) So M starts haranguing this poor woman to let us in, and she won't, not even for visitors from far, far away who have come here to this pit of a town for the express purpose of seeing Le Corbusier's oeuvre in person and who cannot come back another day for the next million years.
In a snit, we leave.
It's time to go home.
Please may we go home?
Good idea.

Boing!

‘maybe tomorrow’, and two weeks go by, like magic.

Just how it is these days.

The weekend was great. Saturday : gardening, then bridge. Sunday : gardening, Easter lunch, then more gardening. Monday : shopping for gardening stuff, then gardening.

My manual lawnmower officially died. It probably would have lasted a lot longer if I’d only taken care of the thing, cleaning off the grass wrapped around its parts, tightening any loose screws… But I’m far too lazy for that sort of boring stuff, and when something finally worked itself loose and got lost in the too-high weeds, it was the end of the mower.

Repairing the thing would be more trouble than it was worth so I let myself be convinced of the virtues of an electric mower. Which is not as quiet as hoped. But it does cut the lawn efficiently.

JP gave it quite a workout for its inaugural mow, going out to the farther trees that have not been mowed under for about 5 years now. Apparently my cherries and apples could have fewer worms in them if only I would not let the weeds grow under the trees. We’ll see if that works.

Even a shiny new mower cannot get everything right in a single pass, so at my next opportunity I’ll re-mow and get all the stuff that simply flattened against the ground last time.

Though, the next opportunity may well be three weeks from now, by which time the next mow will be overdue anyway.

It’s a bit cold in the mornings still for planting the veg patch. We did put in some stuff. Can’t resist that sunny afternoon sky. Potatos, onions, garlic, carrots, radishes. Some garlic has already come back from last year, and the celery has sprouted from the freeze-thawed ruins of last year’s plants. Strawberries cleared of their invading weeds.

The veg patch might get more elaborate every season, but the real work this year will be out front. Gone, the scraggly rose bushes. Gone, the weeds and the infesting ivy. The irises and tulips and azaleas will be moved to temporary quarters while the soil is thoroughly turned over and freed of blackberry brambles and other unwanteds. In will come a variety of flowering shrubs, in different colors and seasons. Lilacs of all colors, a butterfly bush, forsythia, lots of stuff.

It’s almost too bad I get to play the League final of the Open Pairs this weekend in Grenoble. Almost a shame to play the League final of the Mixed by Four next weekend (though that one we get to play ‘at home’). All that bridge keeps me out of the yard and under artificial lighting! Sitting on my butt.

And the camillia got replanted. It's much happier out there than in the kitchen.