The news has been abuzz about this "Miracle Serum". How does it work, and will it do any good ? Let's delve into some of the news that has been breaking this week.
Holy crap, They brought Ebola Patients to the US !
Yes, I heard about this too, and there really isn't much reason to panic about this. Our main weapon against Ebola is knowledge. Once we identify someone with Ebola, we can isolate them, and neutralize the threat they pose to others. The two individuals who have been brought over are isolated by some of the toughest biosecurity available.
But why did they bring them to the US ?
For a start, they are US citizens, they have a right to seek treatment back in their home country. The facilities in the US are better. They are going to be treated at Emory University Hospital, which has specially designed facilities to deal with Ebola.
Oh right, I get it, so if you're rich and white, suddenly people start caring….
I'm going to stop you before you get your social justice warrior armour on, because there is one fact you really need to understand before you get your rage on. The main reason they are being brought here is to test out some new experimental therapies against Ebola. They aren't just patients, they're guinea pigs.
Imagine if the opposite had occurred, if some US biotech had parachuted in to guinea to administer untested and barely validated treatments on the populace. What will happen if the US gets accused stealing citizens away from their sovereign nations to be experimented on in US Laboratories ?
You can try to rationalise this however much you like, it's still wrong !
Look, I'm not saying you don't have a point, I just wanted to give you a different perspective on the situation, because the ethics can be a lot more complicated than you might first imagine.
Pharmaceutical companies can't just parachute into a country with whatever untested drugs they feel they can throw at people. They need time to plan with local governments, co-ordinate with hospitals and communities.
This outbreak caught everybody on the back foot. No-one expected it to appear in West Africa, and no-one predicted it would become such a huge catastrophe. Even if they did, we still would have been caught short, because there hasn't been much investment in curing Ebola.
Wait, why wouldn't Pharmaceutical companies want a cure for Ebola?
Its not so much that they don't want a cure for Ebola, but that they couldn't find anyone to pay them for a cure for Ebola. They are companies, not charities, subject to the whims of their shareholders.
Ebola is still a very rare disease. Tuberculosis, HIV, Malaria and measles all kill magnitudes more people than Ebola. So already, there is a very small market for a cure.
Add to this, Ebola tends to afflict the poorest countries in Africa. The healthcare systems need to prioritise their funds for all the other diseases that kill more of their people than Ebola.
Pharmaceutical shareholders know the profits made for an Ebola cure would barely cover the costs of the research, let alone pay off a reasonable dividend. I know, it sounds cynical and heartless, because it is cynical and heartless. But the people making those decisions may just be trying to make sure your pension plan pays out.
So what are the treatments being given to these two US citizens?
The US citizens we are talking about are Dr Kent Brantly and Ms Nancy Writebol. The details of their treatments haven't yet been published in a scientific journal yet. I'll tell you what I know so far, and most of it will be focussed on Dr Brantly.
For those of you who missed my previous FAQ, Dr Brantly was working in Liberia on behalf of Samaritan's Purse to bring this outbreak under control. With early treatment, it's possible to bring down the mortality rate of the virus to 60%. Once you survive Ebola, you are immune. You can only get Ebola once.
Nobody really knows exactly what helps some people survive the disease, but it probably has a lot to do with them developing an immune response against the disease. Specifically, people need to develop antibodies to the virus, which will neutralise it.
Wait, I'm gonna stop you right there. What are Antibodies?
Antibodies are proteins produced by the immune system to fight disease. They stick to the surfaces of viruses. When they do this, they can immobilise viruses, stopping them from attacking the body. They also act as an alarm system for all of the rest of the immune cells. When an immune cell spots an antibody that has bound to it's target, it can send out signals to summon more immune cells to that area, to mop up any other viruses that happen to be around.
Okay, hold on, how do antibodies know to target Ebola?
They don't. Not really. If you want to know about how they do this, we need to talk about the cells that create these antibodies. They are called B-cells. They are born in the bone marrow. They don't yet have the ability to make antibodies. But they do have the genes for making them.
If they are to grow up and defend the body, they need to be prepared for any disease that could show up. The immune system however has come up with a clever system to make sure that these B-Cells will be able to respond to nearly anything.
You see, as the B-Cells mature, they scramble up the genes used to make antibodies. This way, they get nearly every combination of antibody possible. B-Cells that produce antibodies which bind to human cells are screened out during this process. When they come out of this process, they all have the capability to create a specific antibody to a protein not found in the human body, which could potentially belong to a pathogen.
If a B-cell happens to find a pathogen with proteins that match its antibody, it divides to produce more cells that become factories for antibody production.
So in really simplified terms, antibodies are generated through a random process to recognise proteins that don't belong to the human body. You have so many B-cells that there could be multiple types circulating in your body right now with the ability to recognise different proteins found in Ebola. When you get an Ebola infection, these need time to recognise it and create antibodies against it. Ebola usually doesn't give them that time, acting very fast to disable the immune system, and usually killing the host before any of the response have a chance of having an effect.
But if you do survive Ebola long enough to develop antibodies to it, your survival chances start to look a lot better. Survivors of Ebola tend to have lots of antibodies against it. These antibodies could explain why Ebola can't re-infect these people.
Okay, that's all well and good, but how does that help Dr Brantly ?
The main issue with Ebola is that it works too fast for it's human hosts to develop antibodies to it. So what happens if you give patients a dose of antibodies targeted at Ebola ?
In theory, these antibodies could knock back the virus long enough to allow patients to develop an immune response and clear the virus on their own.
Where are they going to get these antibodies ?
From Ebola survivors, of course. Dr Brantly was responsible for helping people survive Ebola, and they were more than happy to repay the favour. He was given a blood transfusion from a 14-year old former patient, so that his antibodies could help Dr Brantly.
Did it work?
It's hard to tell. Allow me to explain.
This isn't the first time this treatment has been tried. In 1995, in Kikwit, Democratic Republic of Congo, eight patients were transfused with blood from Ebola survivors, and only one died after treatment. But, when you pull up the statistics, and calculate the probability that they would have survived without the transfusion, everything becomes a lot less rosy.
All eight of these patients were female, and admitted alongside thirty three other patients who did not receive the treatment. This is our control group.
Another key factor in an Ebola infection is that the longer you stay alive, the more likely you are to recover completely. We all know that overall, Ebola has about a 90% mortality rate without any medical interventions. But, if a patient makes it to seven days, that goes down to approximately 50%.
The patients that qualified for the study were given the transfusion after 10 days, which already means they were selecting from a pool of patients that had a better chance of surviving the outbreak than average. So when everything was taken into account, and the proper statistics were done..... it didn't actually look like the transfusions helped all that much.
However, that's no reason to write this off as a treatment. The problem with this study is that they were testing their drug on patients who were already on the verge of getting better. If they gave it to people at a much earlier stage of infection, we may have a completely different story to tell.
However, the people treating Dr Brantly and Ms Writebol were were willing to try anything, even a mysterious untested "Miracle serum".
What the hell is this "Miracle Serum"?
This "Miracle Serum" is a cocktail of artificially created antibodies targeted specifically against Ebola, developed by the US and Canadian government in case Ebola was ever used as a biowarfare agent.
The theory behind this treatment is the same as for the transfusions. Give patients antibodies, which will knock back Ebola infection long enough for an immune response to develop.
What's so special about these antibodies ?
When a person develops an antibody response to Ebola, they usually end up creating, not one, but multiple antibodies against the disease. However, just because they bind to Ebola doesn't always mean they are effective. Remember, antibodies are generated in an almost random way. Some might be able to attack Ebola right in it's weak spot, others might have barely any effect at all. Imagine them as a superhero team, some of them are Batman, others are more like Robin. Not awful, but not Justice League material.
A number of organisations have been working on developing antibodies targeted to Ebola's weak points. Mapp Biopharmaceuticals (funded by the US Government) have been working on a cocktail of three antibodies, called MB-003. The University of Manitoba, in association with the Public Health Agency of Canada, have been developing a different cocktail of three antibodies called ZMab.
ZMab has shown some promise in Rhesus macaques, saving one hundred percent of them, so long as it was administered within 24 hours after they were first exposed to the Ebola.
But both of these companies have been struggling with a problem. It's really difficult to make these antibodies reliably in human cells in a petri dish. It's expensive, and the human cells don't always get the structure right.
So there have been companies trying to correct for this, by using the cells of other organisms to grow these antibodies. This is where we have to meet two companies, LeafBio and Kentucky Bioprocessing. They have been contracted to producether MB-003 and ZMab antibody cocktails in a relative of the Tobacco plant.
Hold up a second, are you saying Tobacco cures Ebola? Excuse me while I go to the shops to nab some delicious death sticks !
Hold on there kiddo, that wasn't what I was saying at all. These are genetically modified plants called Nicotiana benthamiana. It's native to Australia, and yes it does give a sweet nicotine high, but that's not the important bit here.
The genes for each of the antibodies within the cocktail were found by Mapp biopharmaceuticals and the University of Manitoba. They gave these genes to LeafBio, who put these genes into tobacco plants, and then handed them over to Kentucky Bioprocessing for larger scale manufacture of the antibodies.
These plant antibodies showed that these could save 60% of macaques if given up to 48 hours after they were first exposed to the virus, or 40% survival if administered when the Monkeys began to develop a fever. Not exactly great odds of survival, but better than the Macaques in the control groups, who all died.
Not long before this outbreak started, LeafBio were also contracted to start production of ZMab as well as MB-003. These cocktails were mixed together to create a new drug, called "ZMapp".
At some point last week, Emory University and Samaritan's Purse, asked for samples of the drugs from Kentucky Biosciences to use on Dr Brantly and Ms Writebol. There wasn't much ZMapp available, they were only making it for research purposes.
Early reports of the outbreak stated that Dr Brantly refused to take ZMapp, instead ensuring the Ms Writebol was treated with it first before he left for the US. Now, it looks like more of it has been made, and the two are now receiving it as part of their treatment.
Will it work?
There are a couple of things you need to keep in mind. Firstly, ZMapp was designed to be used for people working with Ebola in a Lab. If an accident happens, like a vial drops onto the floor, researcher know they have been exposed and can get treatment immediately. ZMapp was designed to be administered before any symptoms show up.
In an Ebola outbreak, people don't generally know the exact moment when they get infected. They only know when symptoms show up, and even then, only after a doctor recognises those symptoms as Ebola.
Dr Brantly and Ms Writebol have been sick for at least nine days before they were given ZMapp. The bad news is that there aren't any studies that show antibody based treatments have any effect on survival when administered in this time frame. The good news is that if they've lasted this long,they already had a better than average chance of surviving.
If they do survive, it will be very difficult to tell whether it was due to ZMapp, or whether they would have survived anyway. This drug hasn't been properly tested for safety or efficacy in any trials yet. Like I've said before, Dr Brantly and Ms Writebol are guinea pigs.
So, should we be giving this treatment to other people ?
That decision may already be out of our hands. This drug is already being fast-tracked for production, with Phase 1 trials already planned for next year. There is already a growing number of people calling for this cure to be brought in, even before we know whether it actually works. Liberia's assistant health minister Tolbert Nyenswah told the Wall Street Journal
"The population here is asking: 'You said there was no cure for Ebola, but the Americans are curing it?'"
What's the harm of giving this drug to people ?
Again, without safety trials we don't know. But we run the risk of giving people a drug that doesn't work. There are already unscrupulous people who have been selling fake vaccines, and fake cures. Up until now, it was accepted that there was more or less nothing people could do against Ebola. The merest hope of a genuine cure will further embolden con-artists, and send the wealthier amongst the sick westwards where they believe a cure may be found.
But if there is hope, no matter how small, surely we should give all of these people the same chance as our countrymen !
Yes, you are completely right.
We should press this into trials as soon as possible, before this outbreak burns itself out. But we need to have the co-operation of the governments, and the consent of the people. There have been too many instances where Pharmaceutical companies have outsourced unethical clinical trials to poor communities in Africa. When one company does that, it sort of undermines the trust in the next company that wants to come along with a brand new drug it wishes to unleash on the populace.
In the case of this outbreak, we need to ensure that the people who actually have the jobs of administering these treatments are involved in the process. The people receiving these treatments also need to understand what is being done for them.
This isn't a case of making a few phone calls and dropping in on nations with bandoliers stocked with syringes. The diplomacy and bureaucracy will take time and patience. That's a difficult pill to swallow when there are people dying right now.
We need to focus on the methods we know actually work. Containment, Containment, Containment. As ever, knowledge, hard work and discipline is our best defence against the spread of Ebola. Panic, misinformation and outright lies are as much our enemies as the disease itself.
References and Further Reading
Ebola hemorrhagic fever, Democratic Republic of the Congo, 1995: determinants of survival.- Detailing whether transfusions could help fight Ebola infections. Prepare to be disappointed.
Successful treatment of ebola virus-infected cynomolgus macaques with monoclonal antibodies.- Study which shows ZMab completely protects Macaques from Ebola, if administered within the first 24 hours of infection.
A study describing the production of a plant antibody in a relative of the tobacco plant, wherein they present the implication that the plant is more reliable at constructing the antibody than human cells.
Nicotiana plant infiltrated with Agrobacterium Tumefaciens for reasons a bit too complicated to go into here. Uploaded by Wikimedia user: Chandres
EDIT 8/8/14- added an extra paragraph