No one could have predicted… (Ebola post)

How did it get in??

I’m sure you’ve seen the headlines this morning.  Another ebola patient turned up in Texas.  This time, it’s a health care worker who was at the hospital when Mr. Duncan came back in the ambulance.  This person was wearing protection, or so the hospital says.  Given the way that the ambulance ignored the family when they were screaming about Duncan vomiting all over the sidewalk, who knows what precautions the hospital actually took once he got there.  Ok, let’s assume that they were as rigorous as they said they were.  The fact that someone got infected anyway suggests that either the virus became a lot more infectious or that the health care worker was extraordinarily unlucky and something managed to seep through the latex anyway.

I’m going with another option.  I’m going to guess that the hospital got wise only after Duncan came in by ambulance and that the gloves, mask, full body armor and shield got implemented only after the hapless health care worker (Hapless from now on) was exposed.  The hospital may not have had time to explain the precautions everyone needed to take until after someone had touched the vomit with their gloves and then scratched their faces.

Well, it was bound to happen to someone else in Texas.  I’m still not panicked.

Last night, I caught up with Nova on PBS, which produced an episode on Ebola that ran last week.  You can view Surviving Ebola on Nova here.  This program delves more deeply into the monoclonal antibody treatment, ZMapp.  As I suspected, producing the proteins in ZMapp is a bit of a logistical challenge.  It has not been scaled up and growing the tobacco is only half the battle.  According to this segment, it takes just as long to purify the protein as to grow it.  Actually, that doesn’t sound right either.  It used to take me and my partner about 3 days to lyse the cells, spin the pellets, make the buffers, run the columns and check the fractions with electrophoresis.  I’m not sure how it differs with antibodies though.  Like I have mentioned before, antibodies tend to aggregate, or so I’m told, and purifying any protein is still a bit of an art form.  So, maybe they have additional steps to go through before it can be used in humans.

In any case, Hapless is probably not going to get ZMapp.  Let’s hope they caught this infection in time for other treatments to work.

Stupid and Irresponsible ZMapp Conspiracy Theories

I’ve written a couple of times about ZMapp, the monoclonal antibody treatment for ebola infection.  Short summary: ZMapp is a cocktail of three monoclonal antibodies, in other words, human proteins, that were genetically engineered to grow in tobacco plants.  Yes, it sounds like FrankenPharma but it’s perfectly normal to do it this way.  ZMapp is produced by company in San Diego.  In it’s PR blurb from January of this year, the company producing it, known as Mapp Biopharmaceuticals, indicated that they had tested ZMapp in 7 primates, 4 of which died.  If you are assuming that all primates will die of ebola, that’s not too bad but in the current outbreak, the lethality is about 60% so this result is nothing to write home about. (note that the in the Business Insider article linked below, the company claims to have improved their success rate in primates but there’s still no proof that it works in humans.)  In other words, the public is grasping at this very early research as if it were the holy grail and it’s not.  The best thing about ZMapp is that it draws attention to the fact that our research for infectious diseases is woefully underfunded.

In any case, Mapp is all out of ZMapp.  Business Insider has some info about what’s going on, which gems nicely with what I’ve been saying:

And scientists acknowledge that despite the new efforts, they may not be able to produce more than a few hundred treatment courses by early next spring. That will be far behind the international demand and will confront officials with life-and-death challenges of rationing and priorities.

“The biology just doesn’t allow you to do it tomorrow,” Alan Magill, a programme director at the Gates Foundation which is helping to organise ZMapp development, told The New York Times .

[…]

The doses with which the US aid workers were treated were manufactured from biologically-engineered tobacco leaves grown at a facility in Kentucky, but it only has extremely limited production capacity.

Officials with the Department of Health and Human Services are now in advanced talks with a Texas company that could produce the drug in millions of tobacco plants.

The New York Times also reported that the US government and two of the world’s biggest charities — the Gates Foundation and the Wellcome Trust – are in talks to arrange for production of ZMapp in animal cells. That is a more conventional production method in the biotechnology industry and could allow for greater overall production, but the initial stages of development will take longer. “We’re going with multiple manufacturers,” a federal official said,

BusinessWeek has reported on the delays in federal bureaucracy that held up research of the drug for up to four years.

“That’s why we don’t have an Ebola countermeasure,” said Robert Kadlec, a consultant and public health physician who held high-level posts in biodefence in the Bush administration. “We failed to invest enough dollars to have it mature.”

Part of that failure to invest might have something to do with Republican assholes writing Op/Eds in the NYTimes claiming that you’re washed up as a scientist after the age of 36 , which is about 4 years after you finish your last starvation diet salaried post-doc.  After that age, you don’t deserve the limited funding from NIH grants as some young whippersnapper who has just started his career (and has about 4 years to make his name in the world before it’s all over).  Funny, I started feeling my mental cheerios about two years before I was laid off.  Whatever.  Ahhh, Republicans, always expecting to get some new major breakthrough from hard working intelligent people without spending any money at all.  Typical. I’m going to address that idiotic Op/Ed at a later time, once my blood pressure has returned to normal.

Like I said yesterday, if production of ZMapp is really that crucial, the government or the Gates Foundation can hire a couple thousand currently unemployed, laid off American pharma researchers who used to do protein production.  Or they can let us just sit on our asses while Rome burns.  Their choice.

In the meantime, I’ve read a post on another blog that suggests that there is a new conspiracy theory about the availability of Zmapp.  According to this theory, the Dallas ebola patient, Thomas Duncan, is not getting Zmapp not because Mapp ran out of supply.  No, he’s not getting it because he’s black.  In fact, there’s discrimination going on and that’s why black people won’t be getting it.

uh-huh

That’s ridiculous and stupid and anyone who thinks that or spreads that rumor has not been paying attention to the logistics of producing this cocktail of human proteins in tobacco plants.

To the contrary, I would go so far as to say that the only person in the United States who probably has a stash of ZMapp for his own personal use is a black man.   In fact, the White House physicians and Surgeon General wouldn’t be doing their jobs if they didn’t corner the market on whatever was left for the president’s exclusive use.  It only makes sense.  You don’t want your president dying on you from ebola.  (This possibility is extremely remote but he does shake a lot of hands)  It’s bad optics and it’s bad for the country, assuming he can actually get ahead of this crisis and be proactive on this one thing after six years of being constantly behind the curve, too cautious and deferential to the ultra wealthy on every other crisis.

So, you know there’s that.

In general though, Americans should continue to think of ebola as a disease without a cure.  If you get it, you will have to rely on your body’s own defenses to fight it off.  So, don’t get it.  Racism has nothing to do with it.  Racism *might* have something to do with poorer people having access to insurance or health care in Texas and several other states.  But when the ZMapp is gone, you can’t make tobacco plants grow any faster, no matter who you are or how much money you’ve got.

 

A reminder about ebola treatment

There are a couple of articles about the guy who arrived from Liberia who turned up at a Dallas hospital with ebola.  One is from the DailyMail (UK), which sounds like breathless hysteria inducing gossip mongering, and the other is from Reuters.  I’m going with Reuters for veracity.  In either case, it sounds like this could be serious.  Wait, here’s one more from NBC.

The patient, Thomas Duncan (I’m not using the middle name because he’s not a criminal), reportedly carried an infected pregnant woman to a hospital in Liberia.  That woman later died from the illness.  Then, he takes a flight to Texas.  He’s allowed on the flight because he is symptom free.  Ok, that’s mistake number one.  He probably should have been held in quarantine for the length of time of the incubation period, which can be up to 21 days.  Actually, it probably doesn’t matter if the quarantine happened in Liberia or Texas, though presumably it mattered a great deal to his fellow passengers.  Nah, I’m going with my gut here.  If you’re trying to leave Liberia or one of the other most heavily infected countries, you should be subjected to a quarantine to prove you’re not a carrier.  If Liberia couldn’t do it, Texas, or some other connecting way station in the US, should have.  But then, this is Rick Perryland.  My condolences to relatives that live there.  I know they didn’t vote for him.

Come to think of it, there’s probably going to be a backlash against the African community in Texas that Perry will likewise fail to prevent.  And Texas has all those gun totin’, constitution wavin’, do gooders.  If there is a spread of ebola, plugging one of the patients and allowing infected blood to spill all over Dallas is probably only going to exacerbate the problem.

Which leads to the next issue.  According to the DailyMail (remember, gossip mongering), Mr. Duncan went to a hospital in Texas complaining of symptoms and told the health care workers that he had just arrived from Liberia.  That’s L-I-B-E-R-I-A.  You know, the place with all the sick and dying ebola victims?  That have the same symptoms that he was displaying?  They sent him home with antibiotics.

Now, either somebody wasn’t listening to him or they have the stupidest treatment team in the world in Dallas.  Antibiotics are completely useless against viruses.  I’m going with option one- someone wasn’t listening.  Well, you know, there was probably a language barrier.  I’ll leave it at that.

The NBC article says that Mr. Duncan’s nephew had to call the CDC after the initial treatment in Dallas.  Even he figured out that the health care professionals in Dallas weren’t taking this seriously:

Health officials have acknowledged that Thomas Eric Duncan, 42, was initially sent home from Texas Health Presbyterian Hospital in Dallas when he showed up on Sept. 26 complaining of fever and abdominal pain. He had to return two days later in an ambulance.

That was the day “I called CDC to get some actions taken, because I was concerned for his life and he wasn’t getting the appropriate care,” Duncan’s nephew, Josephus Weeks, told NBC News on Wednesday night. “I feared other people might also get infected if he wasn’t taken care of, and so I called them to ask them why is it a patient that might be suspected of this disease was not getting appropriate care?”

Weeks added that he hoped “nobody else got infected because of a mistake that was made.”

Maybe the insurance time clock alarm went off and the hospital thought he looked remarkably well that morning.  It was probably just a coincidence.

So then Mr. Duncan’s condition worsens.  His family calls an ambulance to take him to the hospital. Before he gets into the ambulance, he vomits all over the sidewalk.  His family is screaming their heads off in panic.  We have no direct evidence that the ambulance team recognized the danger to themselves or others or whether they called a HazMat team or whether they sprayed the area with chlorine and took all of the family members immediately into quarantine.

Hey, this is a convenient time to remind all those right wingers out there that even if you don’t have insurance, the ER is not allowed to turn people away!  Yes, a man in Duncan’s condition can make repeat visits to the ER and vomit all over the chairs while he patiently waits there for hours to see a doctor while the other health care workers obliviously prepare another dose of antibiotics.

Do we know whether Mr. Duncan has insurance?  He’d better because no one in Texas without insurance is allowed to get ebola.  Perry didn’t expand Medicaid. Update: Duncan is not an American citizen.  He’s just here for a visit.  So, we can guess that one of the reasons why the hospital didn’t keep a sick Liberian who was showing signs of possible ebola infection when he first showed up is because they were concerned with the costs.  Oh, yes, my best beloveds, hospitals are more than willing to toss sick people out when it starts to get too expensive for the insurance company.  We have been there.

We really need an investigation of the behavior of the hospital that discharged Mr. Duncan to discover whether this was the result of a bad cost-benefit calculation.  Did the hospital just take a wild bet that Mr. Duncan did not have ebola so they wouldn’t have to keep him in an expensive isolation unit?  Enquiring minds want to know.

Now we come to the treatment phase for Mr. Duncan.  It turns out that ZMapp, the monoclonal antibody (not antibiotic, pay attention, there is a difference), is no longer available.  The DailyMail calls it a “miracle” treatment.  That’s not surprising for the DailyMail but it is misleading, stupid and demonstrates a complete lack of understanding on the part of the “journalist”.  ZMapp is an experimental treatment that had an n of 7 primates before it was thrown into humans.  If the barrier for proving efficacy was that low when I was still in drug design, my project teams would have made the companies I worked for billions several times over by now and would have cured obesity, depression, alzheimer’s disease, multiple sclerosis and several different kinds of cancer.  In other words, there’s not much evidence that ZMapp has cured anything yet.  Sure, a couple of patients took the drug but they had excellent care here in the US and that alone might have been enough to cure them.  The body *will* recover on its own if it can stay well enough to mount a vigorous immune response.

Anyway, ZMapp monoclonal antibodies are grown in tobacco plants.  My lab partner had more experience in growing proteins in plants so she could probably talk about this in more detail.  But from my own experience growing proteins in insect cells and e coli, I can tell you that the amount of protein recovered could be minute and the amount varied based on the conditions the cells were grown under.  Grow them too fast or neglect them for even half an hour and you might have to start all over again.  Growing in tobacco plants would seem to give the company a little more control over the product but it still takes time.  Then there is the issue of purification, which still can seem like an art form in some cases.  And the damn things have to fold properly AND they have to not aggregate, which I understand is an issue with antibodies.  They loves to aggregate.  Even if they grow the tobacco at lightening speed and collect as much ZMapp as they can, it’s going to be small quantities of an unproven drug.

Come to think of it, you have to wonder why governments, including our own, are not calling on all of the out of work drug discovery professionals to lend a hand.  Oh, that’s right.  We’d have to be paid and as we all know, government isn’t good for anything.

So, don’t count on Mr. Duncan to receive any miracle cures.  Let’s just hope he gets decent care in Texas to help his body ride out the storm.

In the meantime, I have read that Glaxo Smith Kline (GSK) is trying out a vaccine.  I haven’t heard a lot about this but vaccines are generally good things, unless you’re Jenny McCarthy or some clueless control freak, overeducated but bored, suburban helicopter mom who managed to get through college without ever taking a basic biology course.  How much you wanna bet a whole lot of them in Texas suddenly get religion when it comes to vaccines, demanding on TV with righteous indignation that GSK provide freebies of an almost untested, non-FDA approved vaccine? There’s a satire just waiting to be written but it really isn’t funny.  Anyway, I hope it can produce some kind of immune response but it’s probably too late to help Mr. Duncan.

As for the rest of Texas, let’s hope it can survive the bumbling first responses.  Since Mr. Duncan returned to the US, he has had ample opportunity to infect his girlfriend’s kids- who go to school. (See paragraph above)  His poor girlfriend is probably in jeopardy if they had sex without a condom because the virus can persist in semen for a time even after the patient recovers. Well, I’m still not panicking but I’d feel a lot more confident about a vigilant response if Mr. Duncan had landed in Hawaii where everyone is insured, there’s a whole ocean separating the islands and there’s a history of treating people with infectious disease.

Somedays, it just seems like Texas is giving the rest of the country the finger.