It’s Friday of the second week of classes. I’m already frazzled and worn out — I get home at night, slump into a stupor, and fall asleep by 10. This is not good, especially since I don’t have this excuse: sex makes squid exhausted.
All I’m doing is teaching, teaching, teaching. Clearly the squid are wiser than I am.
Calm down, people. Nobody is making human-pig hybrids, even if the news is making a big deal about it. To be honest, I’m not even very impressed with the utility of the experiment, although it is interesting and technically accomplished. It’s being touted as a step in developing pigs with human-derived organs for transplants, and no, I just don’t see it.
The experiments involve xenografts in the blastocyst; that is, they take pluripotent stem cells from one organism, and inject them into the embryos of a different species at a very early stage of development, when the embryo is a hollow ball of cells with an inner cell mass that will eventually become the fetus proper. Then they look for incorporation of the injected cells into the embryo.
It doesn’t always work. The inner cell mass doesn’t necessarily accept these alien cells, or the injected cells don’t thrive in this unusual environment, so you might do the injections, implant the resultant hybrids, and when you open up the host days or weeks later, your injected cells are all gone. It is non-trivial to get this to work, so what they’ve accomplished is technically impressive.
It was a lot of work, too. They injected 2,181 pig blastocysts with human pluripotent stem cells, cultured them in vitro for a few days, and had 2075 embryos that were then implanted in masses of 40-50 embryos into host pigs (which implies that many would be expected to be lost), and collected 186 embryos about 4 weeks later. This is a good yield — I’ve done experiments with much lower rates of success — but the real question is whether any of the human cells were incorporated into the pig embryos.
It worked! They got incorporation of human cells into the pig embryos. Unfortunately, there are a few problems: one is that the embryos with incorporated human cells were significantly retarded in their growth. This ought to be expected; just the timing of development for the two kinds of cells will be out of sync, so I’d actually have expected even greater problems. It’s promising that they got incorporation at all. The other problem is that the incorporation was very low: 0.001% of the embryo’s cells were human. Uh, that’s not very good. If you’re trying to generate organs grown in pigs that have exclusively human antigens, even 99.9% human isn’t going to be good enough — it’s going to trigger an immune response when transplanted.
None of these cells made up the majority of cells in any organ, even; the experiment doesn’t really test the feasibility of accomplishing that, and I suspect that trying to increase the percentage of human cells is going to also increase the incompatibilities and lead to greater and greater rates of developmental failure. They do have some interesting ideas for increasing the rates, though. If the host pig cells are transgenically modified to make them unable to make a pancreas, for instance, any pancreas in the pig would have to be derived from human cells. It would still be infiltrated with pig-derived nerves and blood vessels and connective tissue, though, so that’s insufficient to create a transplant-ready organ.
As pure basic research, it’s a good experiment, and I’ll be interested to see how much further it can go — if nothing else, it’s going to expose evolutionary disparities in development between different mammalian species. The head investigator has an appropriate perspective on it, I think:
Scientific American: So this is very, very basic biology?
JCIB: So I feel that there has been a little bit of exaggeration of where we could go with this now. If you look on the Internet you see images of chimeras between human and animal. And I feel that that’s a little bit of exaggeration. It’s true that it works very nicely between rat and mouse — just this experimental protocol that I am telling you. It’s only a couple of months ago that we have been able to put human cells into another animal. In this case in a mouse and realized that they can differentiate in the three germ layers. The three germ layers are the mesoderm, ectoderm and endoderm that will give rise to the more than 250 different cell types. So that’s a major accomplishment I will say. But from there, dreaming that they will generate a functional structure, I think we’re going to need time and a lot of luck.
So we need to go for a lot of basic research still. It’s my own feeling, of course. There are other people who think that tomorrow we are going to create human organs. And I wish that I am wrong and they are right, but I think it will take time.
Yes! It’s basic research, which is a grand and worthy thing. It’s too bad so much of the press coverage can only grasp it in terms of making organs for human transplantation — I doubt that this approach will ever work for that, but will instead teach us more about development and evolution and molecular biology.
We need more of this kind of truth-telling:
Donald Trump is a proven liar. He lies often and effortlessly. He lies about the profound and the trivial. He lies to avoid guilt and invite glory. He lies when his pride is injured and when his pomposity is challenged.
Indeed, one of the greatest threats Trump poses is that he corrupts and corrodes the absoluteness of truth, facts and science.
This is the straight talk you don’t usually get in our cautious, conservative, cozy-with-evil media: you get “euphemisms like “unsubstantiated,” or “unproven,” or “baseless.”” This has to stop.
We all have to adjust to this unprecedented assault on the truth and stand ready to vigilantly defend against it, because without truth, what’s left? Our president is a pathological liar. Say it. Write it. Never become inured to it. And dispense with the terms of art to describe it. A lie by any other name portends the same.
Our president is a LIAR. Say it loud.
Our legal fund has reached its goal of $20,000 in less than 5 days! It feels good to know we have that level of support.
Don’t stop, you can keep adding to the pool, but now we get to pay our lawyer in full, and push the case on to the next step. Depending on how that goes, we may have to ask for more donations, but for now it’s all smooth sailing.
Has anyone thought about marching into the Oval Office and explaining to the resident that this was all just a psychological experiment?
It might just work, you know. Time to go home, Donnie.
I’m trying to do weekly assessments of how my new class is going…and also to have a regular record of concerns and successes so I can remind myself of what not to do next time I teach the course. We’re wrapping up a rapid survey of a few developmental systems just to expose them to some of the concepts of the field first; last week we blitzed through early polarity formation and gastrulation. This week we covered neural tube formation and neural crest on Tuesday, and this morning it was limb formation and craniofacial development.
One of my concerns is that it’s really easy for me to dominate the class hour. Yeah, just trigger me with a few phrases like apical ectodermal ridge, progress zone, and zone of polarizing activity, wind me up, and I’ll happily talk about cool experiments and nifty results for a few hours, my eyes glazing over as I forget that those students are there. That’s bad. I have to slap myself out of that habit. And as I mentioned last week, it’s not helping that it’s 8am and the students eyes are a bit glazed over, and I’m concerned about drawing them out to talk more. My ideal class would be one where I just help answer questions for the entire period.
I’m happy to say that, while they aren’t quite at that point yet, the students are warming up and I’ve been getting a few sharp questions, including some that I was unable to answer, which always leaves me overjoyed. Challenging stuff! It’s the best!
It also helped that the last half of today was something completely different: I gave them a short review paper that was rather densely technical on craniofacial development. I warned them that I was throwing them into the deep end of the pool to start with, so we struggled our way through all the acronyms and unexplained syndromes and weird little genes. We puzzled out the molecular basics for common developmental problems, like cleft palate, and more exotic and severe ones like Bartsocas-Papas syndrome (if you read the paper, you might not want to follow up by googling the syndromes, because you’ll encounter lots of tragic children). I learned a few things myself, like how common ribosomopathies are in these craniofacial disorders — there are genes like TCOF1 which produce proteins that act specifically in the nucleolar regions to regulate ribosome expression in specific tissues, and haploinsufficency leads to all kinds of failures in cell migration and differentiation.
I got even more questions. That’s good — I wasn’t looking forward to a semester of talking at nodding heads. I’m beginning to relax a little now.
Next week will be even more of a shock. I won’t be leading the discussions at all — I’ll be the one sitting back and answering questions. Tuesday will be student-led reviews of the stages of human embryonic development, with discussions of clinical correlates. Each student has been assigned a tiny snippet of the sequence to explain to us. Thursday they all have to explain The Triple Helix to me. Next week is all about student engagement!
The comedians are going to be busy.
He really is a sad little man. He did a White House interview with ABC, and you’ll never guess how it ends…with Trump giving a tour of the collection of photos he has had mounted on the wall that ‘prove’ he had the biggest inauguration crowds ever. The interviewer smiled and failed to mention that the data show he is wrong, that he persists in insisting on this lie after being shown the evidence that his claim was false makes him a liar, and that his obsession in denying his unpopularity as president makes him petty and unfit for office.
But then, the interviewer probably hopes to get invited back, so he was avoiding asking those pointed questions that might annoy the buffoon-in-chief.
Our legal fund has hit $17,486 — we’re really close to our primary goal of $20,000. We’re breathing a sigh of relief right now, since this is going to mean our legal costs for this first phase of the battle will be met (our lawyer is working on venue issues and other such significant preliminaries — it seems silly to have a trial in Ohio, where none of us live, and where Carrier did not live until right about the time he put together his lawsuit). Once that’s all settled we’ll know better what direction the case will go.
He’s supposed to be a smart guy. Maybe he’ll realize this is a losing argument for him, he’ll drop the whole thing, and we can all get back to writing, teaching, doing science, fighting for justice, and crushing Donald Trump, all much better uses of our time and money.
The year’s celebrity death toll begins its inexorable rise: Mary Tyler Moore has died. I tried to tell you, there was nothing special about 2016, 2017 — every year — will kill again and again and again.
P.S. I don’t hate spunk.
A little history lesson: the United States has not always been a major player in scientific research. In fact, Europe has a longer research tradition, and before WWII the US was looked upon as a bucolic place that had the advantages of a great deal of natural resources, but with only scattered centers of academic excellence, and most of the research was done by the independently wealthy at private colleges. I remember reading about Edwin Conklin, a big name developmental biologist at the turn of the last century, and being rather surprised that all of his work at marine stations was paid for out of his own pocket, a fact of life that was taken entirely for granted at the time.
All the big state colleges that are the backbone of our research efforts now were founded as either agricultural schools or normal, or teaching, schools. They were not intended to be major research centers. You’d go to State U to learn how to farm, or in a few place, mine, or how to become a public school teacher. In my grandparents’ day, that was the default: you’d scrimp and save to send the oldest son to college to prepare him to inherit the family farm, and maybe you’d send the oldest daughter off to learn to be the local school marm.
That all changed with WWII and the work of Vannevar Bush, who saw an opportunity to harness the potential brain power of the country. You don’t think Europe hoped for our entry into the war because we’d bring in high tech wonder weapons, do you? We were a big reserve of manpower for cannon fodder and iron for ships and artillery. The Brits (and the Germans) were the eggheads. Bush was the man who transformed everything in this country, providing resources through the U.S. Office of Scientific Research and Development to fund innovative science and cultivate an atmosphere that valued research at our universities. Everything that we appreciate about American science flowed out of the investment of federal funds in the research enterprise via the OSRD, which eventually metamorphosed into the National Science Foundation, the major source of basic research funding. (The National Institutes of Health (NIH) is also huge, but as you might guess from the name has more of an applied research focus on biomedical research, although plenty of basic research also gets smuggled in).
A chill should run down your spine when Trump’s pick for the Office of Management and Budget, Mick Mulvaney, suggests that … what might be the best question: do we really need government funded research at all.
The context of that question was a rambling post in which he raised a whole lot of, to his mind, unanswered questions about the Zika virus.
Brazil’s microcephaly epidemic continues to pose a mystery — if Zika is the culprit, why are there no similar epidemics in countries also hit hard by the virus? In Brazil, the microcephaly rate soared with more than 1,500 confirmed cases. But in Colombia, a recent study of nearly 12,000 pregnant women infected with Zika found zero microcephaly cases. If Zika is to blame for microcephaly, where are the missing cases? According to a new report from the New England Complex Systems Institute (NECSI), the number of missing cases in Colombia and elsewhere raises serious questions about the assumed connection between Zika and microcephaly.
He was wrong about just about everything, as the linked article explains, but still what strikes me is that he’s pointing out all these difficulties, and raising all these questions (see those question marks? Scientists are the people who bring up those question marks and then try to answer them), and he’s then using the questions as a reason to avoid funding the process of resolving them. This is a man who doesn’t understand the whole point of research, to the point that he considers the possibility of not funding it at all. He’d like to roll back American science to the 1920s.
I can tell you personally what that would be like: you’d reduce American science to places like my lab. I’ve worked at Research 1 universities, and this is a whole ‘nother animal. I have no federal funding — a few of my colleagues do get small NSF grants now and then, but it’s hard to persuade the agencies to support small schools, especially when grant money is incredibly tight. I have a tiny lab space that also does double-duty as a class lab when I teach small upper level courses (many of my colleagues across the country will be jealous: they have no lab of their own, but do have classroom space that can do double-duty as a research lab when they aren’t teaching). I keep up with small supplies — pipettes, paper towels, that sort of thing — with maintenance money from the department.
My chief research tool, a microscope, was purchased with a state grant, part of the building fund that paid for renovations of the old science building and construction of a new wing. It isn’t really my scope; it’s a shared resource for all of the biology faculty that just happens to be kept in my lab.
I’ve been lucky in that I do have an independent, but small, revenue stream. All the additional equipment in my lab, like my digital camera system and animal maintenance stuff, is paid for with…blogging money! Yes, real student research is being supported by those obnoxious ads you see springing up around here. Now try to imagine a world-class biology research unit (not mine) with dozens of grad students and a gang of post-docs and a couple of technicians and the latest, cutting edge research tools that burn through reagents that cost more than my annual salary trying to support themselves by creating a popular blog and sprinkling it with ads for the latest fad food that will help you lose weight.
That isn’t going to happen.
The kinds of research I can do are limited. The latest project is one that Edwin Conklin would have understood perfectly in 1905, using tools that would have been considered high-tech in 1978, but I think we’ll be able to eke out a little bit of useful data, a tiny contribution to the body of evidence. My main contribution is that I can teach students to think like scientists, even with our limited resources, so they can go off to research careers at bigger places…which would cease to exist if Mick Mulvaney had his way.
I am not complaining about my situation. This is actually what I wanted, a place where I could focus on teaching, didn’t have to spend all my time writing hard-to-get grants, and could still work independently in a small lab. It’s perfect for me. It is not at all ideal if you want a national source of advanced research. You’re just going to have a lot of people like me training eager, ambitious kids for possibilities that you’ve eliminated.
That’s not the worst of it.
Suddenly, the federal government has decreed that USDA scientists may not talk about their work in public. This is antithetical to the whole point of doing science!
The EPA has frozen all of its grants. Environmental scientists have also been told they can’t communicate with the public.
The CDC has pre-emptively canceled a climate change meeting. Why? I suspect they’re battening down the hatches, preparing for some lean years, and investing in a meeting that will just get canceled by the administration is an unwise choice.
The National Park Service is being censored. Badlands National Park has had tweets deleted that discussed the evidence for climate change. “Rogue” elements of the park service have resorted to disseminating information under aliases.
All this in just the first four days of the Trump regime taking office. It takes far less time to demolish an institution than it does to build one up. Vannevar Bush’s contributions took decades to bear fruit, and Trump is determined to burn them all down in days.
And taking a wrecking crew to science isn’t even the worst thing he has done! He aims to wreck public education with the appointment of Betsy DeVos — even my small lab becomes pointless if that stream of eager, ambitious students dries up. Congress is busily trying to prohibit all family planning. How’s this for irony?
Making it (Hyde) permanent is not just important for the moral fiber — fabric of our country, but you’ll see millions more lives saved by us taking this important action,House GOP Whip Steve Scalise, R-Louisiana, told reporters Tuesday.
I remember Henry Hyde, corrupt Catholic, philanderer and adulterer. That his name is invoked at the same time as the words “moral fiber” is amazing hypocrisy.
So, in this time of turmoil, when injustice rules and inequity thrives, when all is to be subordinated to the selfish greed of a small number of extremely wealthy white people, I fear that the loss of American science is a tiny problem and will be lost in the chaos. It is shaping up to be an early casualty, though, and when faced with a thousand losses, triage is hard, and terrifying. We are looking at devastating losses to humanity on all fronts, thanks to the fact that we have elected an incompetent demagogue to lead the country, who is propped up by a political party that has become a garbage fire of epic proportions.
We’re doomed.
But we need to keep fighting for everything, every step of the way. A Scientist’s March on Washington is being organized. I don’t think it can have the impact of the Women’s March — we don’t have the numbers — but maybe if it’s a march intended to focus on one-on-one lobbying with congress, and to getting the press engaged, it can help.
Ultimately, though, the only thing that’s going to make a big difference is to depose the tyrant and banish him to a cozy retirement home where he can watch a lot of TV and do no further harm. We also have to basically delete the entire Republican party and grow a new, rational opposition party, one that will give the Democrats an incentive to actually do effective good for a change.
More on the Scientist’s March on Washington — it’s very preliminary, but I’ll be keeping an eye on it.
