Curing HCV – Private companies stand on the shoulders of taxpayer funded research

An estimated 2.7-3.9 million Amuricans are infected with the Hepatitis C Virus [a fact based on testing by the Centers for Disease Control (which receives its funding from the Department of Health & Human Services)].  60-70 % of these people will go on to develop up chronic liver disease (1), many of whom will require blood transfusions to stay alive.  People born between 1945 and 1965 account for 75% of these infections (2).

Gilead Pharmaceuticals, a publicly-traded company, developed Harvoni, which is as close to a cure for Hepatitis C Virus as you can get.  So we should ditch government-funded research and let the private sector come up with new drugs, right?

<WRONG>

Long before it came up with its cure, there was a lot of government-funded research that got the field to the point where it was profitable for Gilead to even think of developing a cure.  To pick just three points in time where grant money from the Department of Health & Human Services was required (there are hundreds, maybe thousands more):

(1975) Scientists at the National Institutes of Health had to discover that there were humans hepatitis cases caused by an unknown virus. (here)  [National Institutes of Health is a part of the Dept of Health & Human Services]   At the time Hepatitis A and Hepatitis B viruses were known but HCV was not. HCV itself was actually discovered in ~1979 by Michael Houghton while at Chiron, corporation yes, but he didn’t do it in a vacum.

(1993) The laboratories of Charles Rice at  Washington University in St Louis and Stephen Feinstone at the Food and Drug Administration had to discover how many different genes and proteins the virus has (here) [funded by a grant from the US Public Health Service, which is part of the Dept. of Health & Human Services and presumably FDA (an agency within Dept of Health & Human Services) paid Feinstone’s salary]

(2000) The laboratory of Charles Rice had to discover the role of the NS5a and NS5b proteins in HCV infection (here) – these are the targets of Gilead’s Harvoni [2 grants from US Public Health Service]

Look for yourself – the grants that paid for the research are always listed in scientific publications.

So we have a cure for a virus infecting millions of baby boomers because the federal government funded work that produced discoveries that finally made it profitable for private industry to look for a cure.

Find your US Representative here.

Find your US Senator here.

 

(1) – https://www.cdc.gov/hepatitis/hcv/hcvfaq.htm

(2) – https://www.cdc.gov/hepatitis/populations/1945-1965.htm

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New to me: Annulate Lamellae

When you teach cell biology over and over again you end up looking at a lot of textbook figures showing the inside of the cell, and that has a stupidizing effect.  Everything is so present and accounted for; the endoplasmic reticulum blooms out of the nuclear membrane, the Golgi body between the ER and the plasma membrane, mitochondria, ribosomes and vesicles swim around in the cytoplasm.  Each textbook figure, while slightly different to avoid  the copyright of the last cytoplasmic artist, is just like the last and the next.  Rarely do you learn anything new by looking at these pictures. Enter the annulate lamellae.

I stumbled upoon it in papers describing the neoblast cells of Planarian worms (here) while reading up on why my students would have THREE Planaria in a dish resulting from cutting ONE worm in half three weeks ago.  Some of these cells are described as having no ER (what??) and sometimes the ER that is seen is

“apparently detaching from the nuclear to move out into the cytoplasm”

I’m sorry, what?

I realize how little I actually know about the dynamics of the ER.  Every picture of every cell I have ever seen just had one, but those were pretty much all cartoons, which apparently are not real life.  But this is just the observation of one author from 1969 – back before they invented restriction enzymes, so what the hell could they possibly know?

Annulate lamellae are described in the same breath as the ER that is divorcing the nuclear membrane and I can’t tell if they are a subset of the ER or a completely different thing.   Are these a thing that people still study?  I have come across cool tidbits like this before that end up being the one time mentions, never to be described again, so I search Pubmed for “annulate lamellae” and whoa:

169 papers come up, second to the last one being a 2015 PLOS One paper claiming that AL have nuclear pore complexes in them, despite being little islands in the cytoplasm (I’m sorry, repeat that again?).  A Google search gives a decent “about 22,300” hits showing that they have been found in human oocytes, sperm, tumor cells, yeast cells.  However it does not have an entry in Wikipedia and thus does not officially exist.

All of this only shows how small my brain is, my capacity to forget what I “learned” as an undergrad, or my lazy habit of relying on textbooks, or all three.  It certainly leaves me grateful to Johns Hopkins for access to full text PDFs of articles from ye oldde tymes.  Can’t wait to hit my human-disease-centric grad students with a paper about a flatworm cells this summer 🙂

 

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Writing to think

After being merged with GSU, GPC (now PC) faculty got an email offering us $2,000 to convert one of our courses to a “writing intensive course”, part of Georgia State’s Writing Across the Curriculum program.  Willing to do anything ethical for cash, emboldened by the lowering of entropy in my life over the past year and eager to take advantage of a benefit of aforementioned merger, I accepted. Well, I applied and they accepted me.

In the past I have included plenty of writing in my courses, with the firm belief that what they know doesn’t matter if they can’t communicate it in a complete sentence that is appropriate for their audience.  Not that I thought it wouldn’t be any work, but this didn’t look to be all that different from what I have already done.

Then I read the required reading (uh oh) for the mandatory conference this week, and uh, it turns out that I don’t teach students how to think by writing at. all.   I have focused on the finished product for so long that I lost sight of the fact that I myself use writing to develop thoughts.  Ugh, such a boring post, but kind of an important development in my head: figure out how to show my students to use writing to think critically.

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Interesting ignorance – Stentor

In majors Biology lab last week we (un)covered the protists.  One of the many living critters we looked at was Stentor. How is it that I have managed to know so little about such an amazing Genus?  I should have had students take videos, but the actual oohs and ahhs from students seemed enough at the time.  Here is one off youtube:

If you aren’t impressed: these are giant one-celled creatures that can be up to 1mm long.  In fact, they are clearly bigger than the rotifers we also saw in these cultures, and those are (admittedly small) ANIMALS.  Single celled organism that is bigger than a multicellular animal with a mouth, intestines, anus, nerves, eyespots & other ORGANS.  No?

Let’s try this: when they aren’t hunting around for food (in ponds, Stentor are normally found in freshwater ponds) they hold on to something and extend out to look like a trumpet:

Not impressed?  They have fibers inside them that run the length of the cell that allow them to contract very quickly (they can contract themselves much faster than your muscle cell). It looks like they aren’t made of the fiber systems we know about in all other cells (microtubules or actin).  Stentor has both microtubules and actin, its just that these don’t appear to be made of them.

polh037p

See those purple-ish spots?  Those are its nucleus (it has several actual), which is pinched off into little balls. If you cut this cell into pieces, each piece will regenerate a whole cell identical to the original.   Scientists in 1896 discovered that, as long as the fragments were bigger than 70-80 microns in diameter, they could regenerate the whole cell. Your cells don’t do that.  There is a lot of “How in the HELL does it pull THAT off?”.  For instance: how is it that the cytoplasm doesn’t leak out all over the place?

cuttingstentor

A piece of Figure 33 (in the subsection “Minced Stentors”) of The Biology of Stentor, Vance Tartar (1961)

Its both sad and wonderful that Stentor is understudied.  Sad because there is so much to be learned by looking at organisms distantly related to us, but because these don’t cause disease in humans or food crops there is very little grant money to study them.  Wonderful because science requires ignorance.  Finding interesting ignorance that is accessible to students can be difficult sometimes, but in this case its right out there in a scoop-full of pond water.

_____

The Biology of Stentor, Vance (1961)

Marshall Lab website (UCSF)

Stentor coeruleus. Slabodnick et al Current Biology 2014

 

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Would I know a misperception if I saw it?

Thinking a lot about student misperceptions recently while actively measuring their prevalence in all my classes this semester.  Writing these thoughts up on this blog helps me to connect the thoughts I have in the fragmented time that I actually can focus on this sort of thing.  I am trying to read all of the references given by AAAS’s Project 2061 misperception database. (here)

From: “The effects of instruction on college nonmajors’ conceptions of respiration and photosynthesis”  Journal of Research in Science Teaching Volume 27, Issue 8, pages 761–776, November 1990

Picture1

I would say that assuming that students who select these two options are completely naïve ignores the possibility that students are including “minerals” in their definition of food and that they have a typical lack of commitment to consistency in their answers that many novices have. By analogy, imagine a parent gets a survey from their child’s school district. They are not experts on early childhood education, and most likely do not perceive all or any of the value of the survey questions, much the same as students who can not perceive all or any value to the questions they get in class beyond it’s contribution to their grade. If that survey asks how much time your kids spend studying in front of the TV and you select “not at all” but then in another question it asks how much information  your child gets from watching tv shows and you select “sometimes”, those two are at odds to the person asking the question but might not be to the parent. It is possible that the parent has their own idiosyncratic interpretation of the question (“what exactly is meant by studying?”, for instance) that allows the “not at all” and the “sometimes” answers to be consistent with each other. It is also probable that, much like many non-majors students, the parents are not truly interested in the question to the point where they are going to carefully make sure that their answers are 100% consistent with each other. Like many students, parents are answering the questions because they know or feel they have to, and that motivation is going to affect whether they are completely committed to showing what they do and don’t know or believe.

Interesting to me how this resembles strands in a wonderful book I am reading on the importance of ignorance in scientific research, a book that if you have read this post down to here, you really should read. (link)  If one is trying to approach teaching and student learning in a scientific way, to what extent are we permanently ignorant of what a student is truly thinking and how committed to their answers they are?

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Is cerebral palsy genetic?

I honestly knew very very little about CP.  After a couple hours of reading this morning, I would shave a micron off the “v” in one of those verys.

The causes are numerous, from prenatal infections to exposure to methyl mercury to preterm birth.  I was a little  surprised to learn that it isn’t rare, occurring in just over in 1 in 500 births. The causes look mostly non-genetic to me, but of courses genetics affects everything.

Several research papers, some free like this one show that having a specific variant of the APOE gene correlates with increased severity of CP.  Interestingly, that same variant increases your chance for Alzheimer’s disease very dramatically (see here).  This gene variant doesn’t appear to cause CP, only to make it’s pathology more severe.  The ApoE protein is involved in moving fat-soluble vitamins, cholesterol and lipo-proteins around in the body, activities that are important for keeping neurons alive and happy.  The ApoE4 version of the protein doesn’t do a great job at this ( it appears to bind these things too tightly (here) but this is one paper and I don’t know jack about this area).

Several genetic diseases of metabolism might masquerade as CP.  This paper describes over 54 genetic diseases with CP-like symptoms, most of which were treatable to some degree.  Some of these had to be treated since birth, others get better with treatment even later in life.  These genetic diseases are rare, some based on the report of one patient.

Using Google to look up genetic diseases in that paper I found this incredible site which just happens to be put out by the authors of that paper.  The site is focused on treatable genetic diseases that cause intellectual disability.  Yet more evidence against  intelligent design.

References

Leach EL, Shevell M, Bowden K, Stockler-Ipsiroglu S, van Karnebeek CD. Treatable inborn errors of metabolism presenting as cerebral palsy mimics: systematic literature review. Orphanet Journal of Rare Diseases. 2014;9:197. doi:10.1186/s13023-014-0197-2.
LIEN E, ANDERSEN GL, BAO Y, et al. Apolipoprotein E polymorphisms and severity of cerebral palsy: a cross-sectional study in 255 children in Norway. Developmental medicine and child neurology. 2013;55(4):372-377. doi:10.1111/dmcn.12086.
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Cubes versus naked women (books please)

What is YOUR choice?

What is YOUR choice?

In Sanjoy Mahajan’s 2009 course on teaching he states that

You know if you know anyone who’s a symphony orchestra player, they say, oh yeah, the best way to start hating music is to be a professional musician. They love music, and then they had to do it for pay, in all of a sudden they don’t like as much anymore, not all of a sudden, but slowly. So there are many, many studies about that– motivation.

So what you want to do really is to find intrinsic motivation. And so the difference between extrinsic and intrinsic motivation is fundamental. And what you want to try to do is create the environment always where the motivation is intrinsic, so that the questions are interesting.

So what that means is you don’t want to use bad questions that people don’t have an interest in, and then force them to be interested because you give them extrinsic motivation.That’s a fundamental bad choice, and then it’s being solved with the fundamental wrong approach.

Not being someone who can hear something like that and not want to see those “many many studies” for myself, I did some searching and found what looks to be the first publication in these “many many” (here). The experimental setup is pretty simple.  Research subjects, all students in an undergradaute psychology course  (who had to be the most well understood group of humans during the 1960s).  Importantly, Deci is honest in saying that the students were required to participate as a part of their introductory course, which right away sends up little red flags about their motivations, but moving on….

The subjects came to 3 sessions where they sat in a room “at a table with the puzzle pieces in front of them, three drawings of configurations to the right of them, the latest issues of New Yorker, Time, and Playboy to their left, and the experimenter on the opposite side of the table. ”  The puzzle was Parker Brothers Soma.  At each session they tried to make various designs with the cubes.  One group was paid $1 during the second session, the control group was not.  In the middle of each session, the experimenter leaves the room.  There is a mirror in the room.  Red flag #2: unless you are part of an pre-contact native tribe from South America, aren’t you always aware that mirrors in these situations are ALWAYS 2 way, and that you are being observed, and that you should do the OPPOSITE of whatever you would normally do by yourself.  But moving on….

For 8 minutes they are observed and the number of minutes they play with the puzzle cubes during this free period was counted.  Interestingly, the group that was paid DOES spend less time messing around with the cubes.  They repeat the experiment in different ways (verbal rewards don’t substitute for money, but the group that is verbally encouraged plays with the cubes more) and get similar results.  Its a small N, but interesting.

I am sure there is a lot of literature that follows this study.  And there are all kinds of reasons for me to suspect my own, untrained conclusions when I am so far out of my field.  But it seems to me that all they could conclude is whether the subjects did or did not play with the cubes, not whether they enjoy playing with the cubes. Being behind an obvious (I am assuming) two way mirror isn’t exactly a free-choice situation.  It certainly isn’t a situation in which I would pick up a Playboy magazine, that’s for sure.  Wouldn’t play with the cubes either.  Hopefully I would have brought my own book in with me.

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