6 ms·

I'm surprised that so much of the coverage of ZMapp doesn't include the fact that the drug is produced in tobacco plants. To me, this is the single most intere

by state 12y ago

I'm surprised that so much of the coverage of ZMapp doesn't include the fact that the drug is produced in tobacco plants. To me, this is the single most interesting and impressive fact. It's also likely the main reason why "the limited supplies will not help the 20,000 people predicted to be infected during the outbreak in West Africa." Scaling production of antibodies grown in plants can't possibly be straightforward.

rch 12y ago
DARPA thinks it's a scalable method, at least for producing flu vaccines: "Accelerated Manufacture of Pharmaceuticals (AMP), companies in four states are building facilities where they can quickly produce vaccine-grade proteins grown in the cells of tobacco plants. Once they produce the proteins, the goal is for each company to scale up its process to produce 100 million doses of H1N1 flu vaccine per month." http://www.defense.gov/News/NewsArticle.aspx?ID=61520 http://www.defense.gov/News/NewsArticle.aspx?ID=61520
- state 12y ago
  Right. It certainly seems like a much more scalable way to produce antibodies. It's just getting all the infrastructure in place that's going to be a challenge.
  - rch 12y ago
    That article was from 2010. I hear this place is pretty impressive: http://nctm.tamu.edu/facilities.html http://nctm.tamu.edu/facilities.html
  - dnautics 12y ago
    It's actually not very scaleable. The yield is incredibly low. Processing plants is also difficult because you have to deal with a bunch of stupid stuff like tough cell walls, etc. I'm not even sure that the glycosylation patterns that tobacco puts on the antibodies are human-compatible (i.e. problems could occur if you try to use tobacco-derived antibody therapeutics in a patient more than once). The choice to use tobacco was very likely a symptom of "if you have a hammer," common in biology and chemistry, where some tobacco researcher (tobacco is a well-studied model organism) wrote a convincing grant with a handful of accurate but marginal improvements over contemporary systems (in this case glycosylated vs. unglycosylated) that would enable commercialization, and downplayed some of the setbacks (low yield). Meanwhile other technical approaches have matured that are really good at tackling those problems but without the other setbacks... but just weren't awarded seed money.
- dnautics 12y ago
  DARPA is misinformed about a lot of things and has the money to afford being so especially if a few long shots work out. Tobacco is not scaleable for rapid response because of the amount of time it takes to verify and grow a plant clone. The goal with pandemic flu is to get a rapid response vaccine kit for first responders, then to stage in higher-scaled vaccines. [1] Ebola is similar. Unfortunately ZMAPP has this technical debt where their testing and validation is tied (understandable from a scientific and legalistic viewpoint but maybe not necessary the best outcome) to production in tobacco. There are better systems now, I'm thinking the new system called 'pichia glycoswitch'. [1]http://stm.sciencemag.org/content/5/185/185ra68.short http://stm.sciencemag.org/content/5/185/185ra68.short Disclaimer: i used to work for the VI and witnessed the researcher D. Gibson come in after the 'timed experiment', where he had a special fedex truck come in at 3am to pick up the package from his private residence; he joked that his neighbors must have thought he was dealing drugs. Although I generally dislike the scientific product coming out of the VI, this was one I had immense respect for.
nsxwolf 12y ago
It's about time tobacco paid us back in the health department.
anigbrowl 12y ago
I've seen it widely mentioned, but most of the commentary on it went along the lines of 'take that, health Nazis!', as if this was the culmination of a years-long effort by Smokers Against Ebola.
- Alex3917 12y ago
  > as if this was the culmination of a years-long effort by Smokers Against Ebola. In some ways it is though. Research using marijuana is currently illegal, even if it gets FDA approval. And if tobacco were similarly illegal, then this research also could have never happened.
  - maxerickson 12y ago
    It isn't produced in a commercial tobacco cultivar: http://en.wikipedia.org/wiki/Nicotiana_benthamiana http://en.wikipedia.org/wiki/Nicotiana_benthamiana I expect that they used it because it is a fairly robust species as much as anything else. I guess the nicotine doesn't really factor into the choice: http://en.wikipedia.org/wiki/Pharming_%28genetics%29#Pharming_in_plants http://en.wikipedia.org/wiki/Pharming_%28genetics%29#Pharmin...
krschultz 12y ago
I agree that it's not straightforward, but there are lots of industrial processes that take as long as growing a plant. Scaling physical production is always a huge problem. There have been years where it was difficult to manufacture the flu vaccine in the required quantities, and I believe that generally involves incubating the vaccine in an egg.
- hga 12y ago
  The membrane cells of chicken eggs (the egg itself is of course one cell). When I last looked at this, during the swine flu pandemic, companies typically get 3 doses of antigen per egg. And this is a very slow process for new strains, first a seed culture has to be created by serious specialists that will both grow well in eggs (can be hard for avian flu...) and expresses the correct surface antigens. Much better approaches like this company's https://en.wikipedia.org/wiki/Protein_Sciences https://en.wikipedia.org/wiki/Protein_Sciences are desperately needed if a killer flu is someday brewed (this tends to happen in an animal that is simultaneously infected with two strains of flu, so it's not mutation per se).

by state 12y ago

rch 12y ago

DARPA thinks it's a scalable method, at least for producing flu vaccines: "Accelerated Manufacture of Pharmaceuticals (AMP), companies in four states are building facilities where they can quickly produce vaccine-grade proteins grown in the cells of tobacco plants. Once they produce the proteins, the goal is for each company to scale up its process to produce 100 million doses of H1N1 flu vaccine per month." http://www.defense.gov/News/NewsArticle.aspx?ID=61520 http://www.defense.gov/News/NewsArticle.aspx?ID=61520

state 12y ago
Right. It certainly seems like a much more scalable way to produce antibodies. It's just getting all the infrastructure in place that's going to be a challenge.
- rch 12y ago
  That article was from 2010. I hear this place is pretty impressive: http://nctm.tamu.edu/facilities.html http://nctm.tamu.edu/facilities.html
- dnautics 12y ago
  It's actually not very scaleable. The yield is incredibly low. Processing plants is also difficult because you have to deal with a bunch of stupid stuff like tough cell walls, etc. I'm not even sure that the glycosylation patterns that tobacco puts on the antibodies are human-compatible (i.e. problems could occur if you try to use tobacco-derived antibody therapeutics in a patient more than once). The choice to use tobacco was very likely a symptom of "if you have a hammer," common in biology and chemistry, where some tobacco researcher (tobacco is a well-studied model organism) wrote a convincing grant with a handful of accurate but marginal improvements over contemporary systems (in this case glycosylated vs. unglycosylated) that would enable commercialization, and downplayed some of the setbacks (low yield). Meanwhile other technical approaches have matured that are really good at tackling those problems but without the other setbacks... but just weren't awarded seed money.
dnautics 12y ago
DARPA is misinformed about a lot of things and has the money to afford being so especially if a few long shots work out. Tobacco is not scaleable for rapid response because of the amount of time it takes to verify and grow a plant clone. The goal with pandemic flu is to get a rapid response vaccine kit for first responders, then to stage in higher-scaled vaccines. [1] Ebola is similar. Unfortunately ZMAPP has this technical debt where their testing and validation is tied (understandable from a scientific and legalistic viewpoint but maybe not necessary the best outcome) to production in tobacco. There are better systems now, I'm thinking the new system called 'pichia glycoswitch'. [1]http://stm.sciencemag.org/content/5/185/185ra68.short http://stm.sciencemag.org/content/5/185/185ra68.short Disclaimer: i used to work for the VI and witnessed the researcher D. Gibson come in after the 'timed experiment', where he had a special fedex truck come in at 3am to pick up the package from his private residence; he joked that his neighbors must have thought he was dealing drugs. Although I generally dislike the scientific product coming out of the VI, this was one I had immense respect for.

nsxwolf 12y ago

It's about time tobacco paid us back in the health department.

anigbrowl 12y ago

I've seen it widely mentioned, but most of the commentary on it went along the lines of 'take that, health Nazis!', as if this was the culmination of a years-long effort by Smokers Against Ebola.

Alex3917 12y ago
> as if this was the culmination of a years-long effort by Smokers Against Ebola. In some ways it is though. Research using marijuana is currently illegal, even if it gets FDA approval. And if tobacco were similarly illegal, then this research also could have never happened.
- maxerickson 12y ago
  It isn't produced in a commercial tobacco cultivar: http://en.wikipedia.org/wiki/Nicotiana_benthamiana http://en.wikipedia.org/wiki/Nicotiana_benthamiana I expect that they used it because it is a fairly robust species as much as anything else. I guess the nicotine doesn't really factor into the choice: http://en.wikipedia.org/wiki/Pharming_%28genetics%29#Pharming_in_plants http://en.wikipedia.org/wiki/Pharming_%28genetics%29#Pharmin...

krschultz 12y ago

I agree that it's not straightforward, but there are lots of industrial processes that take as long as growing a plant. Scaling physical production is always a huge problem. There have been years where it was difficult to manufacture the flu vaccine in the required quantities, and I believe that generally involves incubating the vaccine in an egg.

hga 12y ago
The membrane cells of chicken eggs (the egg itself is of course one cell). When I last looked at this, during the swine flu pandemic, companies typically get 3 doses of antigen per egg. And this is a very slow process for new strains, first a seed culture has to be created by serious specialists that will both grow well in eggs (can be hard for avian flu...) and expresses the correct surface antigens. Much better approaches like this company's https://en.wikipedia.org/wiki/Protein_Sciences https://en.wikipedia.org/wiki/Protein_Sciences are desperately needed if a killer flu is someday brewed (this tends to happen in an animal that is simultaneously infected with two strains of flu, so it's not mutation per se).