[1]: https://www.biorxiv.org/content/10.1101/2021.01.07.425740v1
[2]: https://www.biorxiv.org/content/10.1101/2020.12.31.425021v1
This is effectively impossible as the virus is dependent on a functioning spike protein in order to infect cells, and the machinery involved with the mechanics of the spike are extremely delicate. Errant mutations that would cause compositional changes to the shape of the protein are almost guaranteed to cause functional failure. Using terminology, this is what we call a highly conserved area.
In both cases for the South African or UK strain, if you take a look at the areas where mutations have occurred, you’ll see that the code responsible for generating the spike protein is basically completely unaffected. This will generally hold true for any successive future strains.
The ancestors of this virus were bouncing around between a relatively small set of humans and animals for a while before becoming SARS-CoV-2.
Now with a significant portion of the world infected, it does not seem unreasonable that it would mutate. Although at that point it probably would not be considered the same virus anymore.
This generally happens when a virus from another animal (and thus with a slightly different version of the receptor) adapts to humans.
Basically, a gradient descent from a very different starting point ending up in a different local minima.
The question is, is the spike protein at a local minima (very probably quite close to it), and could it jump to another local minima then? Most likely not.
It's possible it will evolve to make our antibodies slightly less effective, likely as a trade off for infectiousness, but incredibly unlikely the spike protein would evolve to be unrecognizable to our immune systems. Historically, this doesn't happen all that often, except for viruses with chronic infections over years that can do a deeper search over the gradient, but even then it generally takes years to decades.
Generally though, within the context of machine learning, one of the benefits of gradient descent, especially when stochastic, is that we can get past those local minima humps. Does this hold less true with respect to the process of sequence mutation that viruses go through?
No vaccine is training the body on the exact antibody to raise, it’s training it to (hopefully, because sometimes the stochastic process missed) recognise particular epitopes.
Important to also note that generally (and particularly during early infection) there will be many antibodies that recognise parts of an antigen.
Affinity Maturation through somatic hypermutation is one of the most amazing processes the body does - look it up or for a very brief summary look at my notes on page 32 (or the whole mechanism of adaptive immunity from 27) with a little diagram on page 28
https://www.dropbox.com/s/4ldgs4v9y99anm8/BCHM%203072%20Note...
Still, at this day my hope is that we'll be able to do the body's work even better at some point using computer designed antibodies (or similar) at least for therapies. There are some notable bottlenecks in the adaptive system where antigen fragments have to be broken down and shown to potential antibodies and this is a bit different between humans etc. The human antibody molecule is also very large and it's particular design doesn't fit some epitopes you'd want to hit (not an expert on it but I remember one of the HIV proteins having an area you'd want to train on but that can't accommodate the antibody variable fragments well).
Could you please explain in simpler terms what this means?
Also another scenario: say that we get yearly Covid shots that contain the latest strains, would these accumulate over the years and start interacting with each other?
The first is mostly a question of how similar they are. Best case original vaccine covers all strains without modification, worst case you need 50 different vaccines. But the most likely combination is a mix where you might need say 5 vaccines, each of which over an overlapping subset of the 50 strains to various degrees of effectiveness.
That said the immune system is extremely complex, but here is a simplified version, which gives a reasonable overview: https://microbenotes.com/cells-of-the-immune-system/
what does this mean in plain words? this SA variant has a totally new evasion system?
what exactly are we dealing with here? what causes it to rapidly mutate like this?
Essentially, each replication means mutation, and over time, variants emerge. Think of why you need a seasonal flu vaccine and not one flu vaccine.
An E to K mutation converts a surface negative charge to a surface positive charge. So if your antibodies were expecting a negative charge and therefore putting positive charges near that place when they attach to the virus, the polarity on the mutant has now shifted and the antibodies will be repelled from the mutant virus.
It warms to see that the similarities of some aspects of biological life to the current AI/ML terms has entered the lexicon, well at least on HN crowd. The fact that it makes a lot of sense to use those terms hints that we might indeed be on the right track to building AGI and understnding the life itself in general.
But there is also the danger of false analogies doing damage, by creating the illusion of understanding something because the wording feels familiar.
There are no doubts similarities, but that does not mean, it is the same.
That happened a couple of times already with progess in technology and then simplified applied technical models to biological life.
So sure, I think so too, that we are on the right track, I am just a bit more hesistant.
Note that this process is NOT backpropagation.
"The fact that it makes a lot of sense to use those terms hints that we might indeed be on the right track to building AGI and understnding the life itself in general"
Nope, it's a residual of the fact that AI stole ideas from other fields, and ran with the terminology as marketing. Sometimes even to the point of extreme divergence from the original ("neural" nets).
It's really not typical. Even in all of the human cold coronaviruses, only one seems to be evolving its spike protein, and it does so quite slowly.
If it was typical, we wouldn't see the amazing efficacy of vaccines against endemic diseases.
Think of it like antibiotic resistance - our crappy attempt at lockdown was like not finishing the course. We gave it loads of places to multiply but didn’t finish it off so it just adapted
Even if you could make this fix in a day, it'll take months to get FDA approval, and then you still have to manufacture and distribute it. And by that time the populous will have gotten immunity the old fashion way.
I see no evidence we are doing that.
> works against a key mutation in the highly transmissible new variants of the coronavirus discovered in Britain and South Africa
> The variant in South Africa carries two other mutations in the spike protein (E484K and K417N, among others) which are not present in the U.K. strain
This three day old article also anticipated this study results:
> While scientists believe the U.K. variant is not likely to affect the efficacy of the vaccines currently being rolled out in the West, there is more uncertainty regarding the other strain.
https://www.cnbc.com/2021/01/06/south-africa-covid-strain-a-...
I’m guessing they are both of the same “strain” but of different “variant”. But I don’t know enough about how virus taxonomy works to validate that. Sounds like two levels of mutation...
I have no knowledge of biology whatsoever.
But also not square one because it takes literally a day to redesign mrna vaccines for new variants. Then hopefully they can be approved faster the second go and manufactured/distributed more quickly.
But I’d say all northern hemisphere countries should do their best to focus on local elimination in summer 2021. Most of europe had it in reach summer 2020 but decided to reopen early and keep the virus at a low level.
That was an abject failure. It probably only would have taken another month of heavy restrictions to eliminate.
The mutations we’re seeing in the winter of high case volumes caution against doing another cycle like this.
I agree. Everywhere should've pursued elimination strategy like Australia and New Zealand, and even at this late stage would be the best option.
Australia and New Zealand were very unusual in having that possibility, not everyone could have followed such a strategy. The EU had to move thousands and thousands of migrant agricultural workers from Eastern Europe to Western Europe for the harvests, otherwise there would have been scarcities of common foodstuffs. Also goods move through Europe largely through freight trucks that mean drivers moving about, not container shipping like the two island nations you mention.
We have freight trucks from the US too! A lot of obstacles are not, in fact, insurmountable. The actual issue is that most places weren’t aiming at elimination.
As you might remember, there was a shortage of tests the first time that the EU needed to move its agricultural workers en masse (which happened already in the spring – harvests in Spain are more or less continuous, unlike Atlantic Canada where it is much more restricted seasonally). Also, many of those agricultural laborers live in precarious working conditions that the state has little insight into, and arranging any kind of isolation on short notice was not possible.
The EU was not aiming at total elimination because the virus had already spread throughout the bloc practically before the authorities were even aware of it and again, these are not island nations.
You could have kept internal border controls except for essential work. We did that in Atlantic Canada. Australian states did that. We’re just as integrated as the EU is! We never had a border at any point in our history. So we set one up.
There are non islands that more or less eliminated it. China, vietnam for example.
Harder in the EU? More complicated? Absolutely. But the policy the EU pursued was an abject failure, so merely saying “there would have been difficulties” doesn’t show that elimination would have been worse. The places that reduced covid better generally saw better economic results too.
Lack of internal borders in the EU is one of the most important features of the bloc, both in terms of maintaining close integration that could prevent more intra-European wars and in terms of mere everyday convenience. I would gladly sacrifice the demographic most at risk of COVID (about half of all deaths in the EU so far have been in care homes) in order to avoid internal borders.
Also, China has been able to eliminate COVID (and even that is subject to doubt) only through civil-rights violations that the West would not tolerate. Pointing to China and saying "They did it, so the EU could too" misses the point. Vietnam was able to avoid a surge in COVID cases only because they hadn’t yet got the huge number of cases that the EU had first without even being aware of it; of course if somewhere else is already suffering, and you aren’t, you can close the borders and avoid the problems from the start.
This isn’t realistic. Fatigue with COVID restrictions has already set in across Europe: people are wearing masks in sloppy ways (not covering the nose, or even just putting the mask over their chin) and returning to socializing or even leisure travel. The authorities know this, and while they can do things like keep restaurants and theatres closed, they appear to feel little democratic mandate for using the police to enforce strict social separation between individuals. And that is in the winter: once the warm weather comes back, expect even more flaunting of restrictions.
1. The virus is seasonal. Substantially less restrictions are needed over the summer. Outdoor socialization really isn’t high risk
2. School is out. This naturally lowers spread
3. A bunch of people will be vaccinated. This will surely make it easier
4. We’ll probably have new rapid tests by the summer. They go a long way to reducing spread without much inconvenience. Michael Mina has been banging his head against the wall for months to get people to listen: these can be as effective as lockdowns and much less burdensome.
5. At least some countries will figure this out, go for elimination, and require a vaccine/negative test for entry and make travel arrangements with other covid zero areas
Now it might be the vaccines work perfectly, no mutant strains escape them, and we won’t have a repeat of this in fall/winter 2021/22.
But if that scenario does seem likely them elimination is overwhelmingly the best option. And society that can’t pull itself together to do that will live in a purgatory.
The “inconvenience” in the USA (besides outright coronavirus deniers and people who flout restrictions in contempt of expert and professional public health officials) is that there is no guaranteed paid sick/isolation leave if one is ordered to go into isolation. Given that 40% of Americans have less than $400 for a “rainy day”, going to work while sick may be necessary. Also, in a lot of cases, no job: no health insurance, which is tragic and consequential during a pandemic.
You also need to have a strong public health system in place well in advance, where citizens already have been following and adhering to prevention programs for a long time, along with trust in the system. The EU countries generally do better with this, in the most general sense, but it depends on the country. For example, there are published reports of what percent of the country’s population washes their hands every time after they use the restroom. Some of the more “eastern” EU countries (which are now westernized) do way better that west/north Europe.
Also, some countries routinely issue self-isolation orders for 14 days, and the police will check, multiple times. In some countries these fines are over $1,200 for the first offense, and for the second offense, it’s $20,000. Both of these fines are unaffordable for the majority of the population.
Anyways, my point is that rapid self tests do work, but it requires a properly functioning government, with a strong public health system, and a cooperative public that trusts their officials and adheres to public health recommendations well before a pandemic occurs.
So over the long run there’s much more turmoil of the type you speak of. But I agree the US needs a better system for letting the contagious stay home.
Perfect needn’t be the enemy of the good though. If, say, 45% of people could isolate, then having them know they’re positive could help too.