Happy Birthday Russell!
Hope you have a great day celebrating all the good things you’ve done and all the good times you’ve had.
I sympathise with the feeling of suddenly reaching that age that I thought was “old”. It’s a combination of accepting that my knees aren’t 18 and appreciating the things I’ve discovered I really love doing that I never would have considered when my knees were young.
I’ve appreciated the work you did to create this community and I wonder if we might find this space where slightly longer form conversations can take place will have its time in the sun again.
Have fun and dance all night
I think Soon is right - the pandemic revealed people.
As a scientist doomscrolling the scientific literature I was aware of the pandemic a couple of months before it really hit us here. It revealed my own low tolerance for folks who were ignoring the coming problem or pretending they personally didn't need to do anything about it. I sent some terse and probably career limiting e-mails during that time.
As it became clear that NZ wasn't magically immune to the virus spreading, it revealed a health system that was remarkably underprepared. Who knew that a couple of decades of underfunding would make us particularly vulnerable.
Fortunately, and somewhat to my surprise, the politicians in charge listened to the scientists and health professionals and acted on their advice. NZ had to respond that way we did because we simply had fewer ICU beds and fewer trained staff than most of the developed world. And remarkably that pressure revealed a leadership capable of making hard decisions quickly and willing to change tacks as new information came to hand.
It revealed a science community willing and able to drop everything to contribute. Yes there were naysayers, but for the most part scientists made themselves available to help, to explain, to support, to explain again and to just be part of society. We know many of their names now, for some that's proven to be unpleasant as some trolls came out from under the bridges, but for the most part it's nice to see experts treated with respect and their expertise valued.
On the local front as lockdowns came into force we suddenly saw what our city could be like without cars - families out walking and cycling - people just calm and willing to smile and wave - from a social distance. And yeah that distance actually felt social.
Sadly we've lost that again as Auckland drivers reassert their control of the city. I find it strange that the same people who smiled and waved from a bike are now swerving in front of me to get wherever a few seconds faster.
And now we wait for us and the world to get vaccinated. In some ways I think the next 6 months will be harder. We have friends and families in places where the virus is effectively uncontrolled. We watch as leaders around the world with less skill than our own make appalling decisions that will result in thousands of deaths. Our lives are a weird kind of normal, survivors guilt might be overstating it, but there is something wrong about being able to have our holidays while this continues.
Sorry shouldn't end on a down note. I think NZ has come through this so far stronger than it was a year ago. I think we value things a little bit differently now and I think that's a good thing. Yeah there are things about NZ that are still badly wrong but it feels like there is confidence we can fix shit that is broken - is that revealing a covert optimist?
Because I'd rather name this year for the good thing that came from it
RNA dependent RNA polymerase =RdRp
It's the enzyme that uses the viral RNA template to make viral RNA and is pretty much unique to viruses. There are enzymes that can do this in animals but they are very tightly regulated and quite different from the viral enzymes. that's what makes them such a good target for drug design.
Just a comment about drug design - it's part science part craft. There are computational methods for guessing what might work if you know the 3D structure. And there are clever screening methods that can find fragments of compounds that you can stick together to get better binding. But there is a huge amount of trial and error involved as well. And when you have something that works in your screen you then need to figure out if it works in cells and mice and humans.
The SARS-CoV-2 genome is not converted to DNA during viral replication. It’s RNA to RNA.
Meep right you are. It does still mean the virus uses an RNA template to make the RNA strand which is the unusual step that doesn't really exist in humans.
It’s not immediately obvious why some of them inhibit viral enzymes and not enzymes our cells use.
The reason is the enzyme that incorporates them is different from any of the host enzymes - that difference is enough to develop an analog that affects one enzyme but not the other. And yes you can make such analogs that are immensely toxic to humans.
I still can’t get my head around what the endgame of a virus is –
Hi Ian, you can't anthropomorphize this, it's just a virus. It evolved in bats and exists now because it is well adapted to the bat biology. Bats have a very different immune system that allows them to tolerate many more infections with little harm.
In humans this virus just replicates the same as it did in bats. It doesn't have an endgame or aim. It could wipe out all humans and then die off itself and it wouldn't "know". And it's ancestor would still exist in bats.
TLDR entirely reasonable that these drugs work
also science funding is good
It's highly likely any effective treatment protocol will involve a nucleotide analog for reasons noted in the main post.
It's worth noting treatments for viral diseases are uncommon because the immune system handles viruses very very well.
That means most treatment attempts are likely to come after the immune system has done it's job.
For viral diseases where for one reason or another you can't wait for the immune system we rely on vaccines - again essentially relying in the immune system.
Where neither of those options are available the treatments focus on bits of biology that are different between the virus and the host - that usually means targeting the enzymes that replicate the viral genome or process the viral protein. Both of which use mechanisms that are not present in humans and hence are reasonable targets for drugs (since they won't kill the host).
One of the best targets is the genome replication enzymes because they do something that is very uncommon in humans - convert RNA into DNA - this means the viral enzyme that does that can be blocked without harming the host. Nucletotide analogs are king amongst these. Cold sore creams, real ones not the fake homeopathic ones, contain acyclovir which is a nucleotide analog that kills herpes virus.
The problem is most of these nucleotide analogs are cheap to make and many of them cure the disease so no long term treatment is required. That's why big pharma don't bother with them - because the profit is piss poor.
This is another reason why you should harass your local MP into funding government funded research - because that's the money that funds people like Siouxsie Wiles.
Totally agree Hebe.
As a cyclist the shared paths have always been a nightmare. You never know if the dog will stay put or if the child will decide to run across the path in front of you and pedestrians can turn on a dime much quicker than a cyclist can avoid.
The idea that they should be forced into one space is another consequence of the planners dedication to the the car. No-one, not cyclist, not pedestrian, not scooter, not even a bus can be allowed to restrict the car. And so all us unimportant humans get shoved into one tiny space that we share to the best of our ability. But it doesn't work.
And now in the time of lockdown I avoid all the bike paths and ride on the roads because with fewer cars they are spaces I can ride with ease and all the pedestrians on the paths can walk without worrying I might not be able to stop if they wobble or step in an unexpected direction.
I would say that my bell (a Kong) seems to be easier to hear - except if the person has their headphones on :(. It's a lower pitch and easier on older ears.
One thing I hope will happen is that so many people are discovering they really can walk or cycle to the local market and they might just continue.
Cars are useful and valuable, but we've seen them dominate beyond their real value - no small part because of huge marketing by the car industry.
This enforced, slower world of lockdown has given people a chance to see that the car isn't as necessary as they thought.
And there's also the extra sense of community walkers and riders have, we wave and nod and say hi in a way that you just don't get in a car and now everyone is experiencing that community. Maybe just maybe it will last.
Nice to see the community popping up again. Be nice to see a few more of the old faces here too.
Without wishing to be depressing I wanted to link this article.
It’s been doing the rounds and is pretty clear on what is guesswork and what is known which is a refreshing change.
We’re stuck at home doing some work stuff as we can. Concentration is utterly shot. Hopefully we’ll be allowed in to work to prevent some of our precious plants from dying but for now we’re locked out.
Anyway stay safe all.