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Ebola: Experimental drug ZMapp is '100% effective' in animal trials

bbc.co.uk

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Re: Ebola: Experimental drug ZMapp is '100% effective' in animal trials

#41

Post by krschultz »

state wrote: post #8

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 straightforwar…

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.

Re: Ebola: Experimental drug ZMapp is '100% effective' in animal trials

#42

Post by hga »

krschultz wrote: post #41
state wrote: post #8

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 straightforwar…

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.

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 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).

Re: Ebola: Experimental drug ZMapp is '100% effective' in animal trials

#43

Post by hga »

skosch wrote: post #10
kqr2 wrote: post #7

In this NYT article: http://www.nytimes.com/2014/08/30/world/africa/study-says-zm... It mentions that all 3 control group animals died. Does anyone know why the control group is so small compared to the test group of 18?

I would hazard a guess that we know Ebola to be pretty close to 100% lethal, and if you know that three out of three control animals died, then the virus is "working" and there's no need to sacrifice many more animals.

Exactly. The control group is there to, for example, make sure your culture of Ebola is really that, viable and so on. If they didn't get sick, let alone die, you'd know your experimental group results were invalid.

Monkeys are also very expensive animals to do research on, and no one likes to kill them, or at least we don't tend to have the same sentiments about mice and rats.

Re: Ebola: Experimental drug ZMapp is '100% effective' in animal trials

#44

Post by colanderman »

Crito wrote: post #39
colanderman wrote: post #37

Earlier quoted context omitted.

Ya, too bad humans with terminal diseases can't give consent to receive experimental treatments. Better to forcibly test on a being that can't say "no".

Even if the established/widely accepted standards of ethics made human testing in lieu of any animal testing the clear ethical choice, it still would not be practical. Think about it, how would you work on potential cures of ebola in the (several times many year long: http://en.wikipedia.org/wiki/List_of_Ebola_outbreaks ) gaps between ebola outbreaks? Deliberately infect humans to be used as test subjects? Put all re…

There are many practical things we do not do because they are unethical.

For example, bombing military forces using human shields as cover. Very practical, considered unethical and hence not practiced. (Same applies to the inverse, using civilians as shields.)

Eugenics, practiced to advance the human genome by artificial selection. Practical, not ethical!

During war, placing people of the same race as the enemy into concentration camps. Practical, no longer considered ethical, thankfully!

Testing drugs on the clinically insane and on criminals, or of humans of different races. Practical, not ethical.

Enslaving people of a different race to work plantations. Practical! No longer considered ethical!

-------------

For testing between outbreaks, how about instead of your strawmen, we try infecting lab-grown specimens of non-sentient tissue with Ebola? This is the 21st century, we can grow entire organs [1]. Even barring that, tissue from organ donor cadavers can be used.

[1] http://www.telegraph.co.uk/science/science-news/10275996/The...

-------------

And one more thing:

Deliberately infect humans to be used as test subjects?

Why do you see this as different/worse than deliberately infecting other primates?

Is it because they do not have advanced technology?

Is it because they do not speak our language?

Is it because they cannot resist us?

Is it because they are not chosen by your God?

Is it because they look different than you?

Is it because you have no social links with them?

Is it because, despite overwhelming scientific evidence to the contrary, you believe them not to be capable of thought and feeling?

Something else I haven't listed?

Everyone who downvotes me, I challenge you to answer this question. It's the least you can do if you don't doubt yourself.

Re: Ebola: Experimental drug ZMapp is '100% effective' in animal trials

#45

Post by maxerickson »

Alex3917 wrote: post #38
anigbrowl wrote: post #35

Earlier quoted context omitted.

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.

> 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.

It isn't produced in a commercial tobacco cultivar:

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#Pharmin...

Re: Ebola: Experimental drug ZMapp is '100% effective' in animal trials

#47

Post by Crito »

colanderman wrote: post #44
Crito wrote: post #39

Earlier quoted context omitted.

Even if the established/widely accepted standards of ethics made human testing in lieu of any animal testing the clear ethical choice, it still would not be practical. Think about it, how would you work on potential cures of ebola in the (several times many year long: http://en.wikipedia.org/wiki/List_of_Ebola_outbreaks ) gaps between ebola outbreaks? Deliberately infect humans to be used as test subjects? Put all re…

There are many practical things we do not do because they are unethical. For example, bombing military forces using human shields as cover. Very practical, considered unethical and hence not practiced. (Same applies to the inverse, using civilians as shields.) Eugenics, practiced to advance the human genome by artificial selection. Practical, not ethical! During war, placing people of the same race as the enemy into…

Let me guess, you'd be opposing a cure to ebola even if it didn't involve animal testing because "Why do you think that it is okay to kill poor hapless ebola?"

> "Why do you see this as different/worse than deliberately infecting other primates? Is it because they do not have advanced technology?"

Sure, let's go with that one. Humans are able to research and eradicate diseases, but monkeys are not. Humans therefore have a greater inherent worth.

Go proselytize somewhere else.

Re: Ebola: Experimental drug ZMapp is '100% effective' in animal trials

#48

Post by hga »

contingencies wrote: post #46

Does anyone know why the WHO reporting frequency seems to be irregular? Recently it seems to be timed with the release of defensibly bad versus downright scary figures. https://en.wikipedia.org/wiki/2014_West_Africa_Ebola_virus_o...

I would suspect that reporting figures to the WHO, which I'll add is not providing a whole lot of help, is a rather low priority to these countries.

Plus the way this epidemic is playing out in the 3 major countries makes the figures altogether iffy (Nigeria is an obvious exception, with one index case caught quickly).

Re: Ebola: Experimental drug ZMapp is '100% effective' in animal trials

#49

Post by colanderman »

Crito wrote: post #47
colanderman wrote: post #44

Earlier quoted context omitted.

There are many practical things we do not do because they are unethical. For example, bombing military forces using human shields as cover. Very practical, considered unethical and hence not practiced. (Same applies to the inverse, using civilians as shields.) Eugenics, practiced to advance the human genome by artificial selection. Practical, not ethical! During war, placing people of the same race as the enemy into…

Let me guess, you'd be opposing a cure to ebola even if it didn't involve animal testing because "Why do you think that it is okay to kill poor hapless ebola?" > "Why do you see this as different/worse than deliberately infecting other primates? Is it because they do not have advanced technology?" Sure, let's go with that one. Humans are able to research and eradicate diseases, but monkeys are not. Humans therefore h…

> Sure, let's go with that one. Humans are able to research and eradicate diseases, but monkeys are not. Humans therefore have a greater inherent worth.

So would you agree with the statement that Westerners have greater inherent worth than Australian aboriginal adults? After all, they don't have the technology or knowledge to research and eradicate diseases.

How about vs. the Amish? They choose not to engage in such research.

How about a normal human adult vs. an invalid?

I'm curious where you draw the line.

> "Why do you think that it is okay to kill poor hapless ebola?"

> Go proselytize somewhere else.

I feel sorry for you, that you are both so easily offended and lacking in debate skills that your response is so childlike.

I was hoping you'd could provide a level-headed counterargument to mine, as I'm open to challenges to my worldview. Sadly it seems you're little more capable of checking your emotions than everyone else who downvoted because they disagree with me.

Re: Ebola: Experimental drug ZMapp is '100% effective' in animal trials

#50

Post by dnautics »

state wrote: post #20
rch wrote: post #15

Earlier quoted context omitted.

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://w…

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.

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.

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