4 ms·

IIRC from when Moderna started getting hot back in 2012 the preclinical trials weren’t going well. I think those were running ca. 2004–2005. Moderna took the in

IIRC from when Moderna started getting hot back in 2012 the preclinical trials weren’t going well. I think those were running ca. 2004–2005. Moderna took the infectious disease approach.

mlyle 3y ago
This is an oversimplification, but: Moderna mostly took an initial infectious disease approach because extant mRNA formulations at the time provoked too much of an immune response that neutralized the effectiveness of subsequent dosing. There's a goldilocks amount of immune response you want-- too little and the immune system doesn't learn the antigens you'd like, but too much makes it miss the mark and focus too much on the formulation of the vaccine itself. For a cancer vaccine that you want to dose multiple times (9 times in this study) to keep up peak immune response this is a problem. For infectious disease, where some early sensitization of the immune system can be enough, it's not so bad.
- make3 3y ago
  huh that sounds exactly like machine learning overfitting vs generalization
  - shadowgovt 3y ago
    Interesting analogy and it may not be wrong. The acquired immune system basically includes a feature where it can squirrel away some of the white blood cells that fought an infection in the past at the site of the infection. This is a subset of the cells that were activated by the chemicals that were found during the infection. But the immune system doesn't have a great way to distinguish the chemicals that actually cause illness from ancillary chemicals that may have been present during the infection as well. This is one of the root causes of allergies... you get sick with, say, rhinovirus at the same time that the pollen count is really high and your immune system defeats the rhinovirus but squirrels away both the white blood cells that were activated by the rhinovirus and the ones that were activated by the basically harmless chemicals on the surface of pollen grains. Then the next time allergy season comes around, your nasal passages and lungs fill up with pollen grains and the white blood cells close to the surface that were squirled away due to that old rhinovirus infection activate and trigger your immune system to respond to the pollen.
  - closewith 3y ago
    Well, over-fitting is a term borrowed from biology (and generalisation from economics), so not surprising in grand terms. Maybe the real surprise for some is that not everything was invented in the valley.
    - make3 3y ago
      that's definitely not what I meant or implied; it makes sense that the immune system is a classifier of sorts

IIRC from when Moderna started getting hot back in 2012 the preclinical trials weren’t going well. I think those were running ca. 2004–2005. Moderna took the infectious disease approach.

mlyle 3y ago

This is an oversimplification, but: Moderna mostly took an initial infectious disease approach because extant mRNA formulations at the time provoked too much of an immune response that neutralized the effectiveness of subsequent dosing. There's a goldilocks amount of immune response you want-- too little and the immune system doesn't learn the antigens you'd like, but too much makes it miss the mark and focus too much on the formulation of the vaccine itself. For a cancer vaccine that you want to dose multiple times (9 times in this study) to keep up peak immune response this is a problem. For infectious disease, where some early sensitization of the immune system can be enough, it's not so bad.

make3 3y ago
huh that sounds exactly like machine learning overfitting vs generalization
- shadowgovt 3y ago
  Interesting analogy and it may not be wrong. The acquired immune system basically includes a feature where it can squirrel away some of the white blood cells that fought an infection in the past at the site of the infection. This is a subset of the cells that were activated by the chemicals that were found during the infection. But the immune system doesn't have a great way to distinguish the chemicals that actually cause illness from ancillary chemicals that may have been present during the infection as well. This is one of the root causes of allergies... you get sick with, say, rhinovirus at the same time that the pollen count is really high and your immune system defeats the rhinovirus but squirrels away both the white blood cells that were activated by the rhinovirus and the ones that were activated by the basically harmless chemicals on the surface of pollen grains. Then the next time allergy season comes around, your nasal passages and lungs fill up with pollen grains and the white blood cells close to the surface that were squirled away due to that old rhinovirus infection activate and trigger your immune system to respond to the pollen.
- closewith 3y ago
  Well, over-fitting is a term borrowed from biology (and generalisation from economics), so not surprising in grand terms. Maybe the real surprise for some is that not everything was invented in the valley.
  - make3 3y ago
    that's definitely not what I meant or implied; it makes sense that the immune system is a classifier of sorts