Just because you’re a saint doesn’t mean you’re not infectious

Update: Kaci Hickox’s real friends should have a good long talk with her about her over-reaction to the quarantine for a very good reason.  Hickox does not know what her infection status is.  That’s because the diagnostic for ebola isn’t accurate until a person displays symptoms.  If it turns out that in a couple of days she does get sick, she and all her defenders who are trying to make her out to be a martyr to New Jersey’s oppressive public health system are going to suffer a severe backlash that will undermine their credibility.  Is that wise?? I mean, with all of the lunatic Republicans ready to seal the US off from the rest of the world, do we really need a potentially sick Nurse Hickox to become a poster child for ebola?  I’m surprised that they aren’t thinking about this and begging Hickox to dial it back and set a better example for others to follow.

Also, I am going to reiterate my suggestion to the politicians to work on getting employers to pay the salaries of employees who are involuntarily quarantined, make it possible for those who can work remotely to do so, and prevent discrimination when they return to work.  It’s part of their civic duty.  Oh, and get the states that refused to extend Medicaid to pay for the treatment of indigent patients.  Better to get in front of the problem now.  Ebola is not the only nasty disease in the world.

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I’m blogging from my iPhone because I am irritated with nurse Kaci Hickox’s pathetic whining about being put in quarantine when she returned from Sierra Leone after she treated ebola patients.

Apparently, she is taking umbrage at the fact that she was quarantined in NJ and they were terse with her.  She doesn’t have a fever, says she.  But Dr. Spencer also thought he was magically free of ebola when he returned from West Africa. He was so confident of his superpowers to fight off infection that he rode the subway while he was just shy of being violently ill.

Presumably, Dr. Spencer and other healthcare workers should be aware that they are not invincible and should keep themselves off of public transportation. But we have learned, much to our chagrin, that overconfidence trumps sanity and consideration for the lives of others. I don’t think a travel ban is necessary or useful but it is apparently necessary to keep an eye on health care workers if for no other reason than to keep major metropolitan areas from freaking out.

Quarantines used to be common back in the olden days when we didn’t have cures for deadly diseases, nurse Hickox. (See this PBS Nova primer on the history of quarantine) You are not special. Ebola doesn’t care how self-sacrificing you are.  If you are truly as good and wonderful as you say you are, you will take an old cold tater and wait out your time in isolation. You aren’t a criminal. Just a possible carrier. Grow up.

More on the quarantine: Viral infections don’t have a political ideology but our responses to them apparently do.  Republicans are nauseatingly reflexive when it comes to saving themselves at the cost of pissing off every other interest and people who voluntarily put themselves in danger to aid others.  Some lefties have their minds so wide open that their brains have fallen out and they move too far in the “there’s nothing to worry about, you stupid yahoos” camp.

There most certainly is something to worry about.  The epidemic in West Africa is a genuine crisis that has global implications if it is not controlled.  Ebola has no cure and we don’t know if any vaccine developed so far is safe or effective.  Likewise, we don’t know if ZMapp even works.  Add to this the absence of a “pee on a stick” diagnostic that would allow us to identify infected people before they potentially get on a subway and throw up on everyone within a three meter radius. This is no time to become complacent.

Quarantines are not prison sentences and anyone exaggerating the horrors of involuntarily detention in New Jersey* due to possible infection of a deadly disease is as careless and irrational as the morons calling for us to seal off our borders.  Stupidity, like viral infections, does not respect political affiliation.

One more thing: Yes, Yves, all bodily fluids are potentially infectious once people start getting sick.  Since we don’t know when they will cross that threshold from being merely fatigued to feverish, sweating and throwing up, it’s best they stay away from public transportation.  And here’s something else that is really disturbing: the ebola virus can persist in semen for up to three months after a victim has cleared it from the rest of his body.  So, there, Yves.  Look it up.

* Kaci Hickox’s complaints about her treatment sound like a litany of first world problems.  She was given a granola bar when she told her detainers that she was hungry.  She was held in a “tent” on the grounds of the hospital and it was unheated.  Please.  We’re having a nice Indian Summer here in the Northeast.  Put a fricking sweater on. (Now, she’s complaining to her mother that cell phone reception sucks in her isolation unit.  It’s NEWARK, for Pete’s sakes.  Cell phone reception is notoriously spotty anywhere in the Newark-Manhattan area.  New Jerseyans have to put up with this all year round.  The cell tower is not singling you out.)  Really, you’d think she’d just spent a month at Club Med instead of one of the poorest countries in the world.  I’m embarrassed for her.  Apparently, she’s never volunteered to provide health care in parts of North Philly where there is genuine American hardship and poverty that is rapidly devolving into third world conditions.  Hard to believe she made the front page of the NYTimes with her sob story.

In which I differ with Derek Lowe over NIH funding

Typical private industry lab circa 2014

Derek Lowe, blogmaster over at In the Pipeline, took issue with NIH Director Frances Collins contention that if the NIH budget hadn’t been cut in the past decade, we might have had an ebola vaccine by now.  I remarked on the Vox article about this very same topic last week.  However, I’m siding with Collins on this topic.  True, he might be using the very scary disease of ebola to make his point but it is a valid one.

To get an idea of what the NIH has been up against, I recommend that readers review the congressional testimony on the ebola outbreak from last week.  I believe it was Anthony Fauci who laid out the problem.  It goes like this:

1. The NIH identified the need for an ebola vaccine about a decade ago.
2. (This is the crucial part) The NIH is engaged in basic research.  We are talking very, very basic research.  Like, identifying the genes and sequences and making them available to other researchers, or studying how the virus works and propagates, or figuring out which enzymes chop up the viral proteins, or how the viral proteins are exposed to the rest of the body.  That’s the kind of research the NIH does.  And sometimes, the research is so preliminary that there are mistakes that get published that industrial labs have to figure out when they try to replicate the results in the lab.  Not a criticism.  It happens.  You only have so much money to do the research and sometimes, it’s not enough to double check your results.  I get it.  But it does make it harder for your private industry partners to figure out what’s going on and sometimes means that projects need to take detours to unpack mechanisms and rerun assays and such.  In other words, REAL RESEARCH.  That’s just the way science works, much to the finance industry’s chagrin.
3. So, the NIH tried to get a private industry partner to help finish the research on the vaccine and develop it.
4. But during the same decade, private industry was going through a chaotic destructive process brought on by the “patent cliff”.  That is, the blockbuster drugs that fueled industry research suddenly went off patent.  In response, the shareholders who were not about to take a haircut just so some lab rats could continue to do research for them, decided to take the money and run.  That precipitated Pharmageddon, where I and my colleagues got tossed out of corporate labs by the hundreds of thousands.
5. The NIH couldn’t find a private industry partner until the last couple of years when Glaxo Smith Kline (GSK) decided it would take a risk and start working on one.
6. In the meantime, in the last couple of years, the Republicans have lost their freaking minds over the budget and would rather let every government institution rot in hell before they would approve any funding.  This is about the same time we wrote a blank check to AIG, and other lords of the finance industry (see Neil Barofsky’s book).  Then the Democrats came up with this great idea of a sequester, you know, to call the Republicans bluff.  And the raving mob that calls itself the Republican party took the deal and slashed NIH funding by 20%.  The Democratic leadership that came up with the boneheaded, backfiring sequester idea should be kept away from sharp objects for their own safety.
7. So, to recap: NIH needed a vaccine but couldn’t find a private partner for nearly a decade.  Private industry contracted at a time when additional research and development is crucial.  Regular NIH funding is not sufficient for it to develop a vaccine on its own.

This would probably be a good time to insert some Paul Krugmanesque graph that shows the equilibrium between private and public investment in scientific research.  This one should show that when private industry stopped funding research, the corresponding expected increase in public spending was notably absent.

Derek has a libertarian streak and works for one of the last small molecule drug discovery companies in Cambridge.  That’s not necessarily a bad thing but it does skew his perspective just a tad.  Not only that but Derek is operating in the old world order when we tested every therapeutic treatment to death.  That’s clearly not happening with the ebola treatments.  Those suckers have been fast tracked like nobody’s business.  We are treating ZMapp like it’s a cure for ebola when it’s nothing of the sort.  It’s just that it’s the only thing we’ve got.  ZMapp is so early in development that back in the old days of real drug discovery, it might have been killed in a project portfolio review before it ever made it to development.  And the vaccines?  Well, normally, they’d go through many stages of development and testing for safety, efficacy, and side effects with an expanding number of trial recipients at each stage before it was approved by the FDA.  Forget that.  In this epidemic in West Africa, with number of exposures increasing exponentially, no one has time for these niceties (though I can just see some lefties screaming about how we killed West Africans with an untested vaccine that triggered a cytokine storm or autoimmune disease.  Wait for it.  You know it’s going to happen.  There will probably be a movie about it featuring some ruggedly handsome Liam Neesom type and a earnestly beautiful lady scientist detective out to uncover the awful truth of corporate exploitation of poor third world citizens.).

The real world is not so simple but there definitely is money at the bottom of this mess.

I’ve worked on both sides of the problems in both industry and in academia, if only briefly.  But I got a good look at what it’s like to do research on NIH grant money and it’s not pretty.  Most of a principal investigator’s time is spent preparing grant applications.  It’s very bureaucratic and, I suspect, very political.  If there isn’t a retrospective analysis on the amount of grant money that goes to the Ivies that leave the rest of the academic labs starving for funds, there really should be.  Not every breakthrough has to happen at Harvard.  The polio vaccine, for example, was developed in Pittsburgh.  Oh, yeah, how many of you knew that Jonas Salk worked for the University of Pittsburgh? True story.

And yet, it was about a year ago that I got a call in my office at Pitt from a researcher in the immunology group who had just lost her job because of the sequester.  It was last year at about this time that we had to cut back sharply on ordering chemicals and lab supplies for my lab because grants were on hold, also due to the sequester.  Even today, I see positions at Pitt for the kind of work that I used to do but the hours are part time.  Really??  You expect scientists to do protein production, extraction and crystallization experiments on a part time basis?  That’s the craziest thing I have ever seen.  You can’t just interrupt an experiment half way through the week because you’ve run out of hours.  That makes me think that the people posting the positions aren’t serious about how many hours they expect the researcher to be available.  It’s deceptive and weird and unrealistic.  But that’s life on soft money.  Here today, gone the next.  Yet the cells still need to be fed, lysed, protein collected, spun, purified, etc, etc, etc.

Friends, Americans, countrypersons, this is no way to run a research infrastructure.  Ok, sure, it’s the way to run a research infrastructure if you don’t want to do it like Americans used to do it.  If you are content to run a research infrastructure like Bolivians do it, fine, do it this way.  But don’t complain later that nothing of significance happened on the science front from 2008 onward.  Don’t complain that the NIH is not telling the truth about funding.  It can’t be all things to all people without a steady funding mechanism that isn’t going to be subject to violent shocks brought on by crazy people who get elected to Congress.

Here’s the bottom line.  If liberals expect the NIH to do all of the things that they *think* it already does, it needs more funding.  It needs waaaaaaaay more funding than it already has.  It needs as much funding as private industry used to pump into its own research coffers but no longer does.  It needs billions and billions more.  It has to become what private industry used to be but no longer wants to be.

And if Republicans are committed to free enterprise at all costs, it’s going to have to get tough with private industry drug discovery and force it to take on research that it sees as unprofitable.  It needs to have a serious talk with the bonus class and shareholders about greed at the expense of public health.  Isn’t that what the GOP is all about?  Morality?

That’s just the honest truth.  The NIH is not private industry.  If we want the NIH to replace private industry, which has abandoned certain, critical research areas because it can’t make the kind of profits that shareholders demand nowadays, we need to put more money into the NIH and fund researchers properly and seriously.  That is the point that Frances Collins has been trying to make.

Liberals have a complete misunderstanding of what the NIH does or is capable of doing.  Libertarians have an inflated view of what private industry can do, sometimes because they are living in one of the last holdouts of productive private industry drug discovery (that could end at any time, so don’t get too comfy, Derek).  But once you have lived in both worlds, you can see what a shambles the whole system is.  It’s unsettling and alarming.

We’re Royals and other updates

Just for the record, we’re Royals fans for this World Series in honor of Katiebird who lives in Kansas.

Oh, and there’s a confirmed case of Ebola in NYC.  This time it’s a doctor who just returned from West Africa and *should* have been keeping himself off of public transportation.  Alas, he took a train from Manhattan to Brooklyn to go bowling the night before his temperature soared to 103º.  Way to go, Dr. Spencer.  You’re giving Texas a run for its money.

Let’s see if Belleview Hospital and the dirty effing hippies who run NYC do a better job of containment.  I’m going to bet that Manhattan takes it in stride.  I mean, it’s not like two planes smashing into the tallest buildings around.

Still no reason to panic.

Cue the Lorde tune:

Why Ebola spread in Dallas: Americanism

Lorenzetti’s Allegory of Good Government, 1339

We’re number one.  That’s what we always tell each other.

We have the best health care in the world.

Our public safety institutions are number one in the world.

We  are the richest country in the world.

We are supremely over confident.

How many people know that when Dr. Kent Brantley and Nancy Writebol returned from Liberia with ebola that their care was paid for by Samaritan’s Purse?  I’ll bet a lot of us just assumed that the US government picked up the tab for the flight, biocontainment units, ZMapp doses and hospital stays.  Not so.  So, who is paying for the transport and treatment of Nina Pham and Amber Vinson?

Probably a few more of us have questioned whether money was behind the shoddy care that Mr. Duncan got in Texas.  I have.  I’m betting that his lack of insurance and status as a foreign national had a lot to do with why he wasn’t immediately isolated when he first came to the hospital and why he was left in the ER for hours, some nurses say days, before he was transferred to a critical care unit.

As for the best health care in the world, the nurses were very unprepared for ebola.  The biggest chunk of the blame goes to the hospital.  It’s a hospital for the middle class and those who can afford the best health care in the world.  That’s where people go to have their babies and bypass operations.  Maybe they didn’t associate their kind of hospital with an epidemic in a third world country.  Bad things happen to THOSE people over there in Africa.  Not their kind of people in Dallas.  At best, that’s a benign form of American narcissism.  We’re so used to having clean water and streets and good food.  So, why should the hospital get all Girl Scouty and be prepared for a situation that will never happen to it?  Training for such an eventuality takes time from nurses doing their duties and time is money.  It’s the American way.

The CDC seems to have vastly overestimated the outcomes of our educational institutions, especially our K-12 schools, where everyone should have a pretty good understanding as to where Liberia is.  But then again, Liberia was a state created by former American slaves in the 19th century and Texas is a state notorious for trying to rewrite the past when white Americans might have done bad stuff to anyone.  But still, don’t these ER intake people, nurses and doctors watch the news??  At least one nursing supervisor seems to have been on the ball and insisted on moving Mr. Duncan to an isolation unit instead of letting him shed viruses all over the ER but she was shot down by her administration.  Still, you’d think that a hospital so concerned with its reputation and profits would have been more proactive in limiting the damage that his presence was causing.  Not so, apparently.

And what was the hospital thinking when they gave antibiotics to Duncan when they hadn’t bothered to find out whether he  had a bacterial infection that required them?  Does Texas Health Presby Hospital routinely overprescribe antibiotics?  Is this a hospital or a student health center?

What were Republicans and Democrats thinking when they cut the budget for the CDC by 12% and the NIH by 20%?  Friedan said yesterday that $30 million was restored earlier this year in an “anomaly”.  How the hell are you supposed to prepare for emergencies if you never know what your budget is going to be from one year to the next?  We complain about administrators making decisions for our health care instead of physicians but our bigger problem is that we have politicians making decisions for our disease fighting institutions.  Should the CDC and NIH know in advance what diseases are going to become epidemic on some kind of 5 year plan and ask for the right budget money in advance?  Or are their functions compromised by their unreadiness brought on by this reckless political posturing?

And everyone, politicians, journalists and people who should know better, is under some mistaken belief that the private sector is going to step up and perform the tasks in research and disease prevention that the CDC and NIH were created to do.  But they’re too busy trying to reap profits for the shareholders to engage in such money sucking activities like research. Meanwhile, we underfund the NIH and CDC.  Is that so Republicans can point to what a sh*%%y job government does?  Are they paying no attention to how our scientific infrastructure is being dismantled in this country and concentrated on a few narrow therapeutic areas?  They are leaving a gap that no one is able to fill.

This may be the richest country in the world but the riches are hoarded by some pretty selfish individuals and we don’t seem to be able to get our act together to force them to give up their loot for the greater good.

A little ray of hope came through yesterday when I saw that some television content providers are breaking away from the package deals offered by cable companies to allow viewers ala carte channel selection.  That’s great because eventually I will no longer have to subsidize right wing propaganda from Fox News or be forced to pay for Fox to mislead unsuspecting American viewers.  I’m betting that a lot of like minded individuals across the country will drop Fox from their lineup the second they are able to do it.

But the damage may already be done.  The Senate may fall into Republican hands this November and in the next two years, the predators who have been stalking us since FDR got us out of the Great Depression will finally be able to finish us off.   The willfully ignorant elderly and angry white males will finally stick a fork in us, and allow the extremists to carelessly destroy Social Security, roll back women’s rights and plunge us back into recession with unrestrained austerity.  The only thing that will stand between the power extremists and us will be Barack Obama.  That right there is a very depressing scenario.  But maybe he will have the courage to stand aside when we finally pick up our torches and pitchforks.

We have been living a myth of our greatness.  We’ve been in denial about how government works.  We have told ourselves lies about how we can “starve the beast” that once made our country a formidable force of good around the world.

I’m only glad that the ebola crisis here will be under control before the next session of Congress begins and before the gung-ho, American exceptionalists who take over show us just how unexceptional we are to the hunters who prey on the young, old, and weak.

Section from Lorenzetti’s Effects of Bad Government, 1339

 

More speculation and budget numbers at Angry Bear Blog.

Live Blogging the Congressional Hearings on US Ebola Response

Disclaimer: This is not a panic/hysteria site.  We’re interested in learning all we can about the US response to the disease and whether our governmental institutions are funded adequately to respond optimally.

With that in mind, you can watch the hearings online at PBS.org.  So far, we have had opening statements from the CDC (Friedan), NIH (Fauci), BARDA (Robinson), FDA (Borio) and a representative from Texas Health Presbyterian Hospital.

The most notable announcement so far was from Anthony Fauci from the NIH.  He says that Nina Pham will be transferred to the NIH this evening for further treatment.

Also note that there will be a lot of Republicans and Democrats on this committee who voted to cut the budgets of these institutions when they approved the sequester.  So, keep that in mind when you listen to these bloviators.

And, now, on with the live blog.  Geeks are encouraged to comment because I’m pretty sure there is going to be technical information presented, especially wrt to drug discovery efforts.

 

Clueless scientist asks a very dangerous question

How the world sees scientists. Thank you, Underdog.

Note: Congressional hearings on the US Ebola efforts are going on right now with representatives from CDC, NIH, BARDA, FDA and others.  You can watch it here.  If anyone wants a live blog, let me know.  I invite other geeky types to watch and summarize, especially those of us with knowledge of the drug discovery/biotech area.

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No, it’s not me.  I admit to being clueless sometimes but not when it comes to the distribution of information.

I’m talking about Leonard Adleman who wrote an Op/Ed in the NYTimes about how easy it would be to revive smallpox.  The reason it would be theoretically easy is because the sequence for the smallpox virus is available online.  So, some really clever evil genius with a garage lab could potentially order up a copy of the gene from one of the synthetic gene specialists in South San Francisco and piece the sucker together using, oh, I don’t know, a variola, vaccinia or orthopox virus just hanging around.  It sounds complicated and might take some time, and if the independent researcher was born in the 80’s, there’s a good chance he’ll die of the disease if he’s not careful.  But it is possible.

Personally, I’m more concerned about reviving the 1918 influenza strain and getting it to go airborne, which, if I recall correctly, was successfully done a few years ago in Europe.  From what I remember, the researchers on that team suppressed the sequence.  Funny, I can’t seem to google that info.  Hmmm…

But getting back to Adleman, he’s not so keen on us just publishing the sequences on public databases.  Maybe it would be better if we just restricted access and only let the professionals see them.  That’s just nuts for a couple of reasons.  The first is that through the years, I have noticed that the sciences are full of people with psychopathic tendencies.  Fortunately, most of them get promoted out of the lab into management.  But just because they might be working at a prestigious lab with unrestricted access to information doesn’t mean they’re not out to get us.  After all, we still don’t know who did the anthrax attacks and I’m pretty sure it wasn’t a garage biologist.

The second reason is, referring to smallpox especially, we have a vaccine for that.  Oh sure, there will be plenty of thirty year olds who may be at risk but an outbreak would be limited.

And for the people who have extraordinary skill in making lethal viruses, I have a perfect solution: HIRE THEM!  Jeez, why in god’s name would you lay off hundreds of thousands of talented people and have them stew over the MBAs and shareholders who wrecked their careers??  Especially when there are auction sites where they can buy discounted equipment from mothballed labs?

I can’t see a teenager doing this, although we do have a lot of malicious computer viruses so who knows.  But they would have to be trained.  Just getting the sequence is not enough.  It’s not like writing code and you can’t get all your information from a book.  Maybe grad students would be capable if they’re motivated, so you tyrannical PIs out there should be on your guard.  But cooking up stuff in a lab takes practice and some good mentors to teach you how to do it.

In other words, it is possible that some well funded hostile country could fund this kind of work by sending some grad students to study in Dr. Adleman’s lab, for example.  He and his students would always have access to sequence data. But smallpox is not a threat and the other diseases are not so easily made.

But the best reason for not restricting access is that it once again takes out of the public domain millions of sequences for genes and proteins that the independent benevolent researcher has access to.  I think it’s great that the US publishes to the NIH PubMed and the European Mol Bio Organization provides this information for free to anyone who wants it.  Without sequence information, and the tools to process it, small, entrepreneurial companies would not have access to it without paying a fee.  That fee, like the high costs of accessing journal articles, could be a substantial barrier to admission to new businesses and new cures for diseases.

Think of it this way, without the information from sequence databases, Mapp Biopharmaceuticals, the company that discovered ZMapp, might never have gotten off the ground.

It’s unlikely that I’m going to produce an ebola protein in the lab but I’m glad that someone published the sequence data so that another lab could make them, crystallize them and publish 47 different protein crystal structures to the web for anyone to access, including a former drug designer in Pittsburgh.  That means a lot to me.  And maybe some crazy kid out there who likes looking at these things and enjoys protein folds and modeling as much as I do will be inspired to find a cure for ebola and other diseases.

What worries me is that the fear that Adleman is producing will lead to those sequences being locked away forever so that only the rich and well connected have access to them.  It would be the equivalent of the Patriot Act.  We wouldn’t know what we had lost until the new Dark Ages descended on science.  Do we really want to leave this information in the hands of only those who can afford to access it?

 

 

Ebola Updates: Still no reason to panic

Another big headline at the NYTimes: A Second Healthcare worker in Dallas has tested positive for ebola.

Is anyone shocked?  Please raise your hand where I can see you.

Didn’t think so.

Update: So, now we find that the second nurse who was infected was on a plane from Cleveland to Dallas the day before she reported symptoms.  Ahhh, now here is where Americans should start to get concerned.  Americans get around.  That is, it’s  relatively easy to jump on a plane for a weekend getaway, though why anyone would want to go to Cleveland is beyond me.  Sorry about that, Cleveland.  And Pittsburgh is only a few hours from Cleveland by car.  Nevertheless, there is still no reason to panic, though the CDC seems to think the passengers on that flight need to be tracked down. The nurse landed in Dallas-Ft. Worth on Monday night at 8:16pm and reported symptoms on Tuesday. That is a very tight timeframe so passengers probably have more of a reason to be concerned but not panicked. But the bigger problem is that it will be harder to keep ebola in Texas if infection rates blossom.

Reminder: Back in May, I went to a user group meeting in Cambridge, MA where I met several researchers who had just come back from a visit to the CDC.  They reported that the budget cuts had demoralized the CDC and researchers there sometimes didn’t know who they reported to or who was in their group.  That’s not a slight on the CDC.  It has been a world renowned institution but if you starve it for funds, it is going to have problems.  If you do it over a period of 14 years, it’s going to have BIG problems.

I’m copying a few comments I made in a previous thread on the latest ebola news.

On the CNN report about the Nurses Union that is speaking out for the Dallas health care workers, Katiebird may be posting on this later once she has tracked down some information.  These are just my uninformed, idle speculations to the news that Texas Health Presby Hospital may have put its employees and others at risk:

I read that CNN article late last night and I was shocked but not surprised, if that makes any sense. Shocked because the hospital was caught so unprepared and was really botching it. But unsurprised because it made a lot of sense in how the infection was spread to this nurse. No health care worker in their right mind wouldn’t take the utmost precautions given the media frenzy over ebola.

I could only conclude that the hospital itself was at fault for being caught off guard and, probably, considering cost over treatment protocol. After all, who was going to pay to isolate Thomas Duncan? Rick Perry turned down medicaid expansion and the Texas legislature has severely cut back on state board of health offices. Laissez faire apparently means anything goes when it comes to profiting off of health care and Duncan was a money sink.

The 90 minutes gap where Duncan was with other patients before he was isolated may have referred to the emergency room. Here’s my best guess: The ambulance dumps Duncan off at the ER with a barf bag. He has to sit there with other sick patients while calls are being made to the hospital administrative staff to decide how to admit him. He’s a foreign visitor, not even an immigrant, with no health insurance, dumped on Texas Health Presby Hospital. He doesn’t qualify for Obamacare, there’s no medicaid for him either because, hellloooo, Americans, especially those living in the south, don’t want to pay for the health care needs of foreigners. Are there funds set aside in Texas to manage a highly infectious disease like ebola? Are you kidding?? Decisions, decisions. The hospital might have thought of transferring him elsewhere but I’m betting the other facilities said they were no better able to care for him. It’s your problem.
Damn, Duncan could wipe out the profit for the entire year, what with the isolation and ruining ventilation and dialysis equipment, not to mention how to get rid of hazardous waste.

So, he sat in the ER for 90 minutes, vomiting and sweating all over the chairs and gurneys, before the hospital decides it doesn’t have a choice anymore and has to take him. Who knew how many people came in contact with him while he was shedding billions of viruses? Poor Nina Pham probably did what she was instructed to do with very little CDC oversight.

On the ebola forum symposium held yesterday at the Johns Hopkins School of Public Health that was held yesterday:

Peter Jahrling showed all of the possible drug treatments in the pipeline. It’s a joke. No, seriously. ZMapp looks like the best bet but the company can only make about 20 doses in its next batch. It’s not their fault. They’re just overwhelmed by the scale and logistics.

A couple of vaccines are being tested in the field. And they have to have a control group so 1/3 of the participants are getting Hepititis C vaccine. It can’t be helped but the participants must know that some of these people are going to die. There’s no way around it. That’s the way science is done. And these vaccines are not in anyway ready for FDA approval.

Other treatments are even less ready. Interferon actually makes the infection worse. There’s an interesting research topic. What is it about the cell signaling that makes interferon treatment worse? Then there are a couple of “drugs”. Honestly, I think biologists are analyzing the high throughput data. They think any hit is a drug. The compounds presented may have some efficacy (probably in the millimolar range from the looks of them) but they’re not very bioavailable and the toxicity could be a major problem.
So, in short, we’re pretty much screwed if we can’t get West Africa back under control and the infection spreads.

Not that we have much to worry about here in the US. We don’t. But it’s not very reassuring to me that we are sooooo far behind in the drug discovery area on infectious diseases. Again, shocked but not surprised.

The symposium can be found here. Most of it is School of Public Health academics trying to one up each other on modeling the progress of the disease. It got to be too insidery and less informative after awhile. Jahrling’s presentation was more straightforward, to the point and alarming. If the general public truly understood what Jahrling’s presentation was saying, they’d never vote for another budget slashing Republican. Ebola is only one of a number of devastating infectious diseases that we are not prepared to deal with because we cut funding, blocked nominations, and let private industry, dominated by shareholders and billionaires, dictate the research and manage the pipeline portfolios. It’s baaaaad.

About quick and dirty drug design using publicly available ebola virus crystal structures and the funky vocabulary that goes with it, this is a little primer on what I was initially thinking and about some of the obstacles:

FASTA is a format for amino acid sequences. Every protein has a sequence of amino acids and they are all unique. Families of proteins are related to one another. You can perform an evolutionary trace on a single protein if the sequence of that protein over time has been determined. The FASTA sequence is stored in publicly available databases. The NIH allows access to these sequences for researchers and provides tools to search them. One of these search tools is called BLAST. It can do sequence alignments. So, if you have a fragment of a sequence or a new sequence, you can search the database to find the entire sequence or similar sequences. I used to use a related tool called BLASTp. That allows the user to find protein sequences that have been crystallized and are stored at the RCSB.

So, let’s say you have a protein that you know has mutated away from its original source. In this case, we are talking about the ebola viral proteins. The crystal protein I referred to last night was from a strain found in Zaire, in a place called named after a nurse called Mayinga. But the newest outbreak of ebola is located in West Africa and it is a different strain, therefore, different mutations in the amino acid sequence.

If you designed a drug based on the Zaire Mayinga strain, it may not be effective against the West Africa strain because the amino acid sequences may be different. But we can make a homology model of the new viral protein structure if we know where the new mutations are. It’s the next best thing to a experimentally determined crystal structure.

The questions to ask are: do all of the viral proteins mutate at the same rate? We would know by looking at the latest FASTA sequences and mapping them onto the structure. Can we identify a binding site? The protein I looked at yesterday processed RNA. I can make an educated guess as to where this occurs. But when it oligomerizes, that is, forms a new structure by self assembly, it has a couple of different binding sites. That is, the binding sites of each subunit to the subunits adjacent to it can also be targeted for drug design. I worked briefly on a different oligomer previously and it was possible to create a drug like entity called a paptamer by extracting a chunk of the secondary structure of the subunit and modifying it very slightly. This prevented the subunits from self assembly, or so the theory goes.

But in the ebola protein I looked at yesterday, the protein-protein interactions between subunits appeared to be dominated by beta sheets, which relate to one another along parallel and antiparallel strands. So, extracting a piece of this binding surface would be difficult if not impossible. Another, more complex and time consuming drug design process would need to be done. If it were just a matter of a helix, it might have been a different story. So, this viral protein target might not be amenable to quick and dirty drug design work and it might have to be abandoned for another ebola protein.

In any case, the FASTA sequence is very informative. It has likely been deposited at the NIH. They usually do that for Flu viruses and you can track mutations as they zip around the world. But I’m not sure we have the very latest info for ebola.

Ok, that was long.  I’m going to eat lunch.

 

 

Ebola Post: Request for papers

Given that the number of cases of ebola in Africa is rising exponentially, and given that ZMapp is not going to be available in sufficient quantities any time soon, is it possible to find/screen for a small drug entity or protein aptamer that would interfere with the oligomerization of ebola matrix proteins or inhibit the action of other ebola virus proteins?

I think the answer is yes.  The RCSB, the publicly available repository of protein structures, has over 40 ebola virus proteins, some deposited this year.  I have to assume that someone(s) is screening ACD or other compound databases with docking programs to find potential hits.  It would be great if those of us who used to do this type of work would also be able to contribute.

However, while the structures are available, and much work can be done just using the structures, the papers that are associated with them frequently are not.  The journals involved can charge up to $33/copy for each paper.  This cost is prohibitive for most independent researchers.  Come to think of it, so are the applications I used to use to dock libraries of compounds into structures.  But even with the limited public software, we could still get a lot done if we were able to read the papers for free.  Like I said, reading the structure papers is not absolutely necessary but it can be helpful.

So, if there is anyone out there who has influence with PubMed, could you look into it?   Also, is anyone aware of a crowdsourcing effort to design drugs based on these structures?  Just give a shout out if you know of one.

One more thing: It would be very helpful to know the latest mutation data in FASTA format in case homology models need to be created on currently available crystal structures.  I see that the octamer was crystallized in 2002 and is from strain Zaire Mayinga.  If I’m not mistaken, the current epidemic is from a different strain. (though this protein may be more resistant to mutations?  Dunno.  Need to read the papers.)

Freaky Weird Prescience (Ebola Post)

Well, it’s not looking good on the ebola front.  We still don’t know why the nurse in Dallas has ebola despite all of her precautions but I’m still not panicking.  My relatives in Houston are probably safe, though what did they say during the Black Death?  Run fast, go far, stay long?  Ok, that’s not really funny and is only encouraging a kind of hysteria that isn’t helpful.  Two ebola patients in Texas does not an epidemic make.  Then again, it’s Texas.

Nevertheless, there is a some speculation that the virus has become more virulent.  Peter Jahrling of the National Institute of Allergy and Infectious Diseases says this may be due to the increased viral load in infected individuals:

You’re seeing all these patients getting infected, so people think there must be aerosol spread. Certainly, it’s very clear that people who are in close contact with patients are getting a very high incidence of disease and not all of that can be explained by preparation of bodies for burial and all the standard stuff. But if you are to assume that the differences in virus load detected in the blood are reflected by differences in virus load spread by body secretions, then maybe it’s a simple quantitative difference. There’s just more virus.

Jahrling says that HIV was actually a hotter disease, primarily because carriers weren’t obvious and were able to spread the disease easily.  It also helped that HIV attacks cells in the immune system, which prevents a vigorous response.  But it’s a little hard to make this argument when comparing it to ebola.  HIV is a long, slow death and we now have drug cocktails to treat it.  Ebola is quick, excruciating, bloody and the lethality is alarming, especially because the treatment options are so few.

Which brings me to the next bit of bad news.  Frances Collins of the NIH says we might have had a vaccine for ebola except our politicians, with anti-governmental fervor, cut funding to those very institutions that might have helped to develop one.  I’d heard from researchers I met in Cambridge who had recently been to the CDC that morale was pretty low and disorganization was high.  Then, I lived through the summer of sequester when university research groups lost a sizable chunk of their funding as grants became more and more unattainable.  Layoffs quickly ensued.

One of the reasons I have been reluctant to pursue a job in research is because the money isn’t there anymore and I’m really sick of layoffs.  And let me make it clear that while scientists like to get paid fairly for the work they do, they don’t work for the money, for the most part.  They just like the work.  It can be frustrating and maddening and discoveries take a long time.  But it is also intensely rewarding in a way that money isn’t.  That’s not to say that we don’t have our own caloric requirements and shelter needs.  Also, no one likes to be exploited.  But bankers and Jack Welch types don’t understand the nature of science or the vast majority of people who do it for what is turning out to be a vanishing living.  But I digress.

The problem is that the patent cliff spooked pharma shareholders and they abandoned American research in search of get-rich-quick schemes and foreign research that isn’t ready for prime time.  At the same time, rabidly anti-government Republicans, abetted by complacent Democrats, have been slashing research budgets.

This is not the same America that we had in the post World War II days.  This is an infrastructure that is rapidly being gutted.  If you have any doubt of how bad things are, consider that Mapp Pharmaceuticals is virtually the only company on the planet with a possible treatment for ebola (we won’t know how the GSK vaccine is doing for awhile yet) and it is a small company in San Diego facing a logistical nightmare.  How does it grow the monoclonal antibodies and purify them on a scale to meet the urgent need of thousands of patients around the world?  Where is the CDC/NIH/Private Industry SWAT team that can get this off the ground?  We are asking this company to do the impossible on a massive scale in such a way that would attract every class action lawyer in the country if there wasn’t a health care emergency.

But it’s even worse than that.  As Collins says, ebola is only the tip of the iceberg.  The vast majority of us will not die of ebola.  We’re going to suffer from other maladies that no one is studying right now.   The funding is low on antibiotics, certain central nervous system disorders, heart disease, etc.  Companies just stopped working on these diseases because the research was expensive and shareholders didn’t think the profits were high enough.

All of this is happening when there is a revolution in biology.  The most ironic aspect of this problem is that thousands of trained researchers have been sidelined right at the same time that there is more than enough work to keep every one of them extremely busy for the rest of their lives.  There’s a profound disconnect between the people who are experienced enough to do the work and the funding mechanisms, either private or public, that will allow it to get done.

I see a lot of fuming on the ebola twitter feed about how scientists should just step up and get it done.  We’re all going to be saved by scientists.  How this is going to happen without funding is anybody’s guess.  It takes money to buy the equipment and reagents and research the papers and feed these scientists who everyone seems to think are going to be self-sacrificing for the betterment of mankind and to save their asses from some exotic African disease.  But as soon as the crisis is over, will we go back to chain sawing through the NIH budget?

From what I can see, neither private industry or our political leaders are taking the threat seriously.  So, I stand by my earlier prediction.  It’s going to take a plague to focus the nation’s attention on our crumbling research infrastructure.  It might as well be ebola.

 

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.