Re: Ebola (slightly geeky)

The crystal structure of the homo 8-mer assembly from the ebola virus.

I’ve been meaning to write something about this topic because I’ve been warning for a couple of years now that we haven’t paid much attention to infectious diseases.  Recently, Lambert over at Correntewire, sent me a blurb from Mapp Biopharmaceuticals from January 2014.  This is the company that is making the monoclonal antibodies that have been given to a couple of patients.  You can read the link to the Mapp announcement from earlier this year at this site.  Lambert asked me for my assessment of this announcement.  

Basically, this looks like a public relations announcement with the purpose of attracting venture capital.  The monoclonal antibody was produced in tobacco plants.  There’s nothing weird about that anymore.  Molecular biology techniques are making this easier to do.  It is possible to insert a human gene into a plant or insect cell or e. coli and have that organism pump out your desire product.  You can even tweak the organism’s protein making machinery.  For example, bacteria produce limited set of amino acids because they reproduce rapidly.  Their protein machinery is simpler and more efficient than a higher order organism.  In order for them to produce properly folded human proteins, you can engineer them to use a more human ribosome or use a synthetic gene that codes for a more narrow set of amino acids.  In this case, the monoclonal antibodies were produced in tobacco plants so there must have been some not so insignificant tinkering going on for it to produce human antibodies.  

[Sidenote: I’m finding it amusing to watch the initial reactions of the anti-GMO crowd to the concept of growing human antibodies in tobacco plants.  What kind of ethical dilemma must be going on in their heads as they weigh the idea of ebola victims having to consume GMO medication in order to save their lives?  But I know that in the event of some side effect or inefficacy, I can count on them to be the first ones to scream about forcing untested, imperfect medications on a disadvantaged (but critically ill) population.  Wait for it, you know it’s coming.]

Mapp tested their therapy post infection on 7 primates but 4 of 7 primates died.  That’s a lethality of about 60%, which is in line with the present epidemic.  I’d have to read the whole paper but I don’t think they’ve proven anything yet, or at least this interview doesn’t show conclusively that the monoclonal antibody was any more effective than the immune response produced by the monkey itself.

So, to summarize, this antibiotic therapy is in the very early stages of development.  In my previous life, we would say it’s in the pre-development stage, nowhere near ready for clinical trials.  There’s not enough data to say that this treatment has better outcomes than the body’s natural ability to fight a viral infection.  There’s no proof that the patients who received this treatment did not benefit from the support they received from the team of physicians that treated them.  The body does have the ability to fight and recover from viral infections as long as it doesn’t succumb to the symptoms of infection in the meantime.  It is possible that the patients who received Mapp’s treatment were in better shape physically than the typical ebola victim and the antibody treatment was just the icing on the cake.  What would be more instructive is if the monoclonal antibody was given to many, many more patients during the first or pro-dromal phase of the infection and observe whether the lethality of ebola drops accordingly.  

I can understand the desperation of the countries involved and why anyone who is infected would want to take these antibodies (I would!) but this looks to me like very early research.  Back in 2011, when I went to a big proteins conference in San Diego (back when I was still gainfully employed {{sigh}}), researchers producing antibodies and other proteins were still in the “it’s an art” phase.  That is to say, we know a lot about the mechanisms by which organisms produce proteins and such but we still don’t understand all of the details in order for them to not aggregate or to get them to fold properly or even to know how to snip genes in the right places to get the vectors and organisms to express, then extract and purify the resulting proteins.  It’s going to take a long time, a lot of research and a lot of money to figure it all out.

Now, this is not to say that Mapp Biopharmaceuticals doesn’t have a winner on its hands.  It’s only to point out that Mapp needs a lot more funding and clinical trials before this is a “go to” treatment for ebola.  And that’s the sad thing.  Many small start ups like Mapp have up front research costs but can’t do the clinical trials.  (This is why I only want to do contract work from my home when it comes to the pharma industry. Job insecurity is extremely high.)  They aren’t ready for an IPO but if they don’t get funding from somewhere, they may have to shutdown their early research in order to move into development.  Those sobering facts may fly under the radar to most Americans because ebola is far, far away and not likely to affect anyone we know.  But woebetide the day when there’s an American version of a deadly virus without a vaccine or a cure when our champions are small, underfunded and understaffed.  

Just sayin’.

For more on the ZMapp treatment for ebola, see this followup from the BBC, especially the third video.  I see that there are several crystal structures from the ebola virus.  Hmmmm, I wonder if Mapp has considered a paptamer to interfere with protein-protein interactions in the homo 8-mer assembly…  (Call me)