Cavalcade of Mammals

The CRISPR gene editing system is a major technical advance. It does open up the near term possibility of making a few small changes to a human embryo’s DNA, but I don’t find that particularly interesting or alarming.

What makes CRISPR better than previous tech for gene modification is that it works at high efficiency–1% to 60% with very high specificity. I read a recent paper testing CRISPR on human embryos that reported 50% effectiveness. Given a handful of embryos to work with, there is a very good chance of making a single change in one embryo.

We have very little knowledge or technology for making positive changes to animals which is a huge limitation to genetic ‘engineering’. Mostly what is understood are disease causing (or predisposing) genetic variants. So a single change (maybe in a few years, a handful of changes?) can be made to a human embryo. There are other limits to modifying human embryos apart from lack of knowledge. The more time an embryo or human embryonic stem cell is cultured, the more it is manipulated, the greater the chance of something going wrong, and the child being born with problems. This tech is great for manipulating animals in the lab. If many or most of them have the genetic change, great! If some are born with defects, cull them, or breed another generation and use those in experiments (often the first generation has non-genetic defects that breed away). But these are huge problems if you are working on humans, because things that increase the risk of getting a damaged child are not desirable.

Long term (100-1000 years), when increases in understanding of biology make improvements (or significant changes of any sort) in humans possible, I think what we’ll see is that the people with the least concern for child welfare will be the most willing to experiment on them.

The really exciting possibilities CRISPR opens up is in genetic treatment of human disease in the tissues of kids and adults. There is delivery tech (well tested viral vectors, and a host of other methods) that can get CRISPR into a good percentage of cells (10% to 50+%) in many tissues, and once there, CRISPR will edit a good fraction of those cells. For many diseases, fixing a genetic defect in 1%, 10% or 20% of cells is enough to treat the disease, so genetic treatment of host of diseases is now possible. Things like hemophilia, some muscular dystrophy, maybe Huntington’s Disease, metabolic diseases, Parkinson’s disease, and on and on. There will be a lot of exciting advances turning that ‘possible’ into actual treatments for different diseases over the next decade or two.

The other major effect of CRISPR tech is that it makes animal experimentation faster and cheaper, and will accelerate basic biological research. We still don’t know what the majority of indivdual genes do, let alone how they work in complexes and networks in cells.

Picked up a GeneTac 1000, a biochip scanner. Here are teardown pictures:
Here is the unit:

Teardown pictures. The unit has a self-contained lamp module that plugs into the main controller unit (EG&G Optoelectronics, Model # 300mXT-04, lamp module LM-300MX). Can’t find much about it–looks to be a 300W lamp. The center of the unit has a CCD camera, a Nikon lens, and a big custom lens, and two sets of filters. The slide carousel is on the other side.

Recently Gao et. al. published “An Estimate of the Average Number of Recessive Lethal Mutations Carried by Humans”. They studied a Hutterite group in South Dakota, highly inbred (63 founders 13 generations ago). From serious genetic diseases common in this population, they determine the number of deleterious variants present in the founders. They find that 0.29 recessive lethal alleles per haploid genome. Since some lethals manifest before birth, they double the estimate to 0.58.

This gives an expected 1.8% increased chance of a genetic disease from two first cousins.

Gao, Z., Waggoner, D., Stephens, M., Ober, C. & Przeworski, M. Genetics 199, 1243–1254 (2015).

I was sent a link to a blog post, “This Mama Isn’t Scared of the Shmeasle Measles” by Megan Heimer.

I’ll run through the post in a minute, it contains a whole lot of nonsense. First, some links to reliable info:
CDC measles info
CDC Manual for Surveillance of VPD: Chapter 7: Measles
Measles week posts by an immunologist

Now, on to the post…

(more…)

Hybrid balloon / vehicle approaches

Saw a recent news item about JP Aerospace. They are working on a two step to orbit approach. The basic plan is to put a large lighter than air (LTA) craft at 200,000 ft, and then accelerate it using a ion thruster to reach orbital velocity.

So I was interested in how this would work, and what the basic parameters (mass, thrust, time) are for approaches of this type.

The benefit of starting from a high altitude is very low air pressure. A balloon can provide steady support so a low thrust vehicle has time to accelerate.

Orbital velocity is roughly 9500 m/s.

What size solid fuel rocket would be required to put a 10 kb payload into orbit?

Bit of local history I never knew about. I had noticed, but no one ever mentioned the court case…

“But the fight didn’t end there; it just moved to the courts and the states. The 1970s saw a tidal wave of high-profile civil rights lawsuits taking aim at restrictive zoning laws, virtually all of which were lost. Most crucially, in 1977 the Supreme Court upheld a law that banned apartment buildings in the Chicago suburb of Arlington Heights, denying an affordable housing developer’s claim that the law made integration almost impossible. (At the time, Arlington Heights had about 27 black residents out of a population of 64,000. In the nearly four decades since, its zoning has largely remained intact, and its black population is still under 1,000.)”

One of the best ways to fight inequality in cities: zoning By Daniel Hertz

OK, this is quite annoying. It was plenty annoying when I was at a univerisity and 90% of the articles were available at publication, but that 10% always included a handful of important articles so it has always been a PITA. So now I’ll start future blogging!

I’ll tag interesting articles when they get published and follow up when I can actually read them. Many journals now are open access, but some release an article six months or a year after publication. Or sometimes the pdf gets posted. So I’ll tag intertesting articles when they hit the news and write a follow up when I can read them. Because titles and abstracts aren’t enough for articles with useful information!

Duration of urination does not change with body size. Patricia J. Yanga, Jonathan Phama, Jerome Chooa, and David L. Hu. PNAS vol. 111 no. 33p11932–11937.

BTW, PNAS used to release articles at publication. When did they go dark?!

Have the time displayed by colored liquids in glass tubes, either a column of liquid or a large segment. The time tube can be straight or circular.

Move the liquid by a mechanism where brass gears compress a bellows. The brass mechanism would be driven by a microcontroller.

Could new measures substantially improve public health?

What would be the effect if, say, 90% of the country wore filter masks for one week, and concentrated on washing hands?

Infection is a chain, one individual infects one or more others, and an infection gets passed on. That is how disease persists–for most infectious agents, not in one person for months on end, but passed serially every few months as an individual gets infected, and over a few weeks mounts an immune response and fights it off.

An infectious agent requires a basic reproduction factor, an R₀, of more than one. If R₀ > 1, an infection is growing more common, if R₀ < 1, an infection is disappearing. For more diseases, for infection to persist it must spread.

Currently there are constant but weak efforts to reduce the spread of infection–encouraging the sick to stay home and hand washing. Vaccines for influenza. But what if a serious effort was made? A big effort could not be sustained, at least not in the US culture.

But what would be the effect of a large, short effort? If infection transmission can be stomped down for a short period, but long enough to break the chain of infection, it might have a large effect on public health. I wonder if this has been modeled?

Here’s an interesting graph comparing disease prevalence before vaccines and now:

This is quite a strong correlation, but how do we know that vaccines caused the diseases to become so rare? Did vaccines causes disease incidence for all these diseases to bottom out, or is it something else, say a coincidence, or maybe all diseases are just disappearing because Americans are healthier today?

So more information is needed. The first thing to consider is that all infectious disease hasn’t gone away. The cold is still as common as ever. Kids still get sore throats and ear aches. There are also the ones I don’t think about or haven’t heard of, like RSV, croup, Fifth disease. And looking at adults, clap, HPV, and gonnorhia are at epidemic levels. So infectious disease is still very common, but the worst diseases have become rare–the ones for which general vaccination is practiced .

Another line of evidence that vaccines are what stomped out the targeted diseases is the timing. They didn’t all disappear at once, not even close. What was observed is that each disease dropped off after widespread vaccination became common.

Here’s a study that looked at incidence for several disease in the US over decades: pdf

If you look at page 4, they summarize incidence over time for 8 diseases. At the top they summarize incidence. The colored section of the graph is detailed regional data. The grey vertical bar shows when widespread vaccination was introduced–a different year for each disease. After the vaccine is introduced, the disease incidence goes way down. Note that for smallpox, it was better vaccines replacing ones started in the 1800’s, so no grey bar is shown.

Here’s a simpler graph of measles from the CDC site:
CDC measles

So it isn’t general health or healthier people with immune systems that prevent disease causing a gradual decline in infectious disease. Instead, the incidence of a specific disease drops when the vaccine is introduced.

Rotavirus

And here’s one of the new vaccines–for rotavirus. Nearly all kids used to get it: “four of five children in the US had symptomatic rotavirus gastroenteritis, one in seven required a clinic or emergency department (ED) visit, one in 70 was hospitalized”. The vaccine was introduced in 2006 and the disease has already become much less common: CDC Surveillance of Rotavirus

See fig 4 especially.

So what I conclude from these lines of evidence is that the introduction of widespread vaccination for a disease causes it to become much, much less common.