Thursday, March 16, 2017

Higher resolution discrimination: The GOP wants to allow employers to require genetic testing

This morning, Ed Yong published an article that takes on issues that we at the The Mermaid's Tale care very deeply about.
Link to article
The consequences for important medical research are not going to be pretty.

And I can't help but be angry about this for threatening to take away the fun of genetics too. If we can't have some control over our genetic testing, we can't do it for fun, for education, for finding out more about ourselves, for the awe of it, for innerspace exploration in the technology age. They're taking that away from us by eroding GINA.

I have lots of other thoughts... like about how this fits in so nicely with (not all of) the right's racist/eugenics inclinations.

And juxtapose this view from the political right where there is full-on acceptance of actually-more-than-genetics-can-even-deliver against their anti-science politics and policy...

It's like science is totally fine for Republicans as long as Mother Nature is a dictator.

If it's more complicated than that, then deny it, defund it, bulldoze it. The reality is, genetics is largely probabilistic; it is not a dictatorship. It's just so hard to convince people that it isn't. The ideological drive to justify behavioral differences and socioeconomic inequality with Nature above all is just too strong. If it's Nature, then we don't have to do the hard work of addressing the problems because Nature is Nature is Nature. This is really old thinking that really new knowledge (both through lots of science and lots of lived experience and lots of humanities and lots of art) has overturned but has not managed to catch on all that well. Along with new knowledge we get increasing understanding of genetics so these ancient beliefs can just be spouted by politicians using new-fangled science jargon.

This is really hard to write about today as all the stories about the proposed (and highly probable) budget cuts to science and the arts are blasting through my newsfeeds. It's overwhelming me today. I'm feeling hopeless and angry on behalf of science, art, knowledge, medicine, humanity, humans, children, teenagers, grown-ups, geezers. It's too much today.

But, back to Ed's article, I do need to put this here because it mentions that I have taught with 23andMe and longtime readers of the MT might know about that:

I don't teach with 23andMe anymore. I was doing it for as long as my university would pay for the kits. It was totally voluntary and students had to read Misha Angrist's book and endure long discussions and pass a quiz before deciding whether to go through with the testing. It was so powerful for teaching evolution, genetics, anthropology, etc... and we critiqued the hell out of it. My university said I needed to pay for the kits through course fees from now on. Before any of these threats to GINA, I decided not to do that and to stop using 23andMe. Now, even if my university reconsidered and funded the kits, I still wouldn't take it up again as a teaching tool.

Tuesday, February 28, 2017

Replacing the Affordable Care Act -- what's so complicated?

Nobody knew health care could be so complicated? Er, except everybody but Mr Trump.  And yes, it's a huge behemoth of a system, but the devil is in the detail.  It's when you throw in all the special interests, political considerations, back-scratching, etc. that it quickly gets complicated.  But before all that happens, there are only three basic choices when it comes to providing medical insurance, and they are easy to grasp.  Choosing among them, though, has become much more of a political choice than an unloaded purely economic one.

Here's what we had before the Affordable Care Act (ACA): private insurance, either from one's employer or purchased individually.  For this to work, of course, just as any other business, insurance companies must make a profit, and that's harder when customers get sick; purchasers actually using their insurance isn't good for the bottom line.  That's why there's so much talk about people with "pre-existing conditions".  These are people who insurers know will cost them money and that's why people with "pre-existing conditions" were essentially uninsurable before the ACA, except as members of large employee pools comprised primarily of healthy people who had to buy in as a condition of their employment.  And that's why insurance companies used to charge women, older people, smokers, and so on more; they were more likely to cost money.  And that's why insurance companies also had policies such as lifetime caps on benefits.  To stay in business, insurers have to make a profit.  It's their reason for being.  This system can work well for healthy people and insurance companies.

The second option is something like the ACA, where everyone, pre-existing condition or not, can buy insurance -- an appropriate thing to point out on Rare Disease Day 2017.  As with auto  insurance, the only way this is financially viable is if everyone is required to buy in; just as good drivers subsidize unsafe drivers, healthy people subsidize people more likely to use healthy insurance.  Thus, the hated "mandate", the requirement that everyone buy in or be penalized on their taxes.  Many detractors of the ACA believe the mandate can simply be eliminated, that a replacement for the ACA can cover as many people, as cheaply, without one.  But, that's impossible. This is the same kind of privitized system that has worked without major snags for many years in Switzerland, for example. There, insurance is compulsory, and insurance companies must offer a basic plan which they aren't allowed to profit from although people can purchase bells and whistles, which is how the insurers make a profit.

The third option is the public option, often these days described as Medicare for all.  Government-supplied health insurance, paid for by tax dollars.  It's cheaper than the first two options in large part because it's non-profit, and the infrastructure required by private insurers to validate or deny claims doesn't exist.  National health has worked well in many rich countries for decades, keeping costs down and providing access to medical care to all.

And that's it.  There's no other "terrific" "cheaper" alternative anyone has thought of that can replace the ACA. The only options are a system that's totally private; something like the ACA with its mandate; and national health.  Unfortunately, this wasn't very well explained when President Obama was working on the Affordable Care Act, and it's not being explained now.  The Republicans in control of Congress aren't going to give us national health; and while it seems that many of them would be happy going back to what we used to have before the ACA, opinion polls are showing that people are less and less happy with that option.  Will Trumpcare be Obamacare renamed, then?  We'll have to wait and see.  

In any case, whatever system we adopt, we've still got problems.  Although the rising cost of medical care in the United States has slowed some with the ACA, at almost 18% of GDP health care spending here is the most expensive in the world, far exceeding that of any other high-income country, most of which have national health care (e.g., source).  In part it's because of the high cost of medical care, the higher use of expensive technology (e.g., MRI's, mammograms and C sections) and the exorbitant cost of pharmaceuticals.  And this is even with limitations imposed by insurance companies to control costs.  In addition, the cost of individual premiums has soared for people who aren't eligible for government subsidies to help cover the cost of insurance, in part, because fewer healthy people have purchased insurance than companies anticipated.  And deductibles and co-pays have risen sharply.  Insurance companies still have to turn a profit to stay in the health insurance marketplace.


Source
And, all this spending hasn't made us healthier than people in countries that spend even considerably less.


Source

So,  even if Trumpcare is as terrific and as cheap as we've been promised, it's hard to see how it will cut the high cost of medical care, and make us a healthier nation.  That is complicated, especially when private profit, rather than public health, is its fundamental basis.

Friday, February 24, 2017

Reproductive Health Funding and Why it Matters

Conflict and war can have an enormous impact on demography and population health. When active fighting breaks out in an area it can lead to large and chaotic population movements - if you’ve been paying attention to the news about conflict in the Middle East you’ve most likely seen images of huge populations fleeing countries like Syria and Iraq and the resulting influx of millions of refugees arriving in places such as Europe.

The chaotic settings in which these populations find shelter are often rife with sanitation, hygiene and other problems. Difficult, strategic decisions must be made on behalf of humanitarian agencies regarding how best to allocate limited funding to properly address the needs of these populations. Unfortunately reproductive health isn’t normally a high priority – although it really should be. One of the best ways to improve the health of a population is to address morbidity and mortality in very early childhood. Everyone in a population goes through the childbirth bottleneck. Everyone has a biological mother. Targeting these age and sex groups can have far-reaching impacts.

An IDP (internally displaced person) camp along the Thailand-Myanmar border. Photo by Suphak Nosten


Most of my work focuses on health issues along the Myanmar-Thailand border and while there has been a decrease in fighting recently, in the very near past there was active civil war and sporadic flows of refugees seeking safety in the mountains on the Thai side of the border. By the early 1980s there were many small refugee and internally displaced person camps scattered along the border. In the mid-1990s (between 1994 and 1998) most of these smaller camps were consolidated into one of 9 currently existing camps. Today, Maela refugee camp, roughly 60 kilometers north of Mae Sot, Thailand, is the largest of these camps with a current population of roughly 37,000. It has been in existence now for over 30 years.

One thing that is easy to miss in an age of constant news bombardment is that these populations, these refugee camps, don’t just disappear with the news cycle. Sometimes refugee camps last for a very long time. Today there are second-generation refugees who were born, and continue to live, in Maela camp.

Shoklo Malaria Research Unit, a field station of the Mahidol-Oxford Tropical Medicine Research Unit, operated the only antenatal clinic in Maela camp until this past December (2016). Recently we analyzed records and data from our experiences in providing contraceptives to refugee women in this long, drawn-out refugee setting. Given the current dire refugee situation of the world, we thought our experiences might have relevance not only for the current refugee situation but also for the future, given that many people will likely be living in large refugee settings for the foreseeable future.

The first thing that became obvious from our analysis is that obtaining a good understanding of basic demographics can be rather difficult.  Information really is a first casualty of war – gaining a handle on data about the population can be difficult even decades later. Furthermore, population counts can have political implications, or conversely, population estimates are sometimes the result of political sentiments.  For Maela camp there are two main sources of population counts – one comes from the humanitarian agency that provides food (the Thai-Burma Border Consortium (TBBC)) and the other is from the United Nations High Commissioner for Refugees (UNHCR) that provides humanitarian and social services. Until very recently UNHCR counts have systematically been much smaller than TBBC counts.

Population estimates have varied widely by the reporting source. We estimated the reproductive age female population for Maela camp by year using data from both TBBC (black) and UNHCR (blue) population estimates.  A loess curve (solid line) is fit to the data points and 95% confidence intervals for the curve are shown in dark gray.


Our data also show that, when provided in a socio-cultural appropriate manner, men and women in refugee settings willingly uptake contraceptives. The population we work with can properly be considered a high fertility (or natural fertility) population meaning that, with some exception, families are large and people are happy with that. But even in a high fertility population contraceptives have important health implications.  Men and women should be able to regulate their family size and spacing if they choose. Unintended pregnancies can result in incredible burdens, especially in already difficult settings, with health consequences for children, families, and entire communities leading to intergenerational transfers of poverty and nutritional deficits [1,2]. Households with few working-age adults and many dependents tend to be households with economic and nutritional deficiencies.




We also note that funding has a huge impact on the uptake of contraceptives and even the type of contraceptives that are chosen. Yes, men and women in the camp chose to readily use contraceptives, but the availability of contraceptives and the type of contraceptives available were directly influenced by funding. In this setting and in others, most of that funding could best be described as “rescue funding”, with reproductive health services normally operating on small and dwindling budgets but occasionally being “rescued” by a new source of funding. Given the importance of reproductive health (including the availability of contraceptives) and the dependence of reproductive health services on funding, funding agencies should carefully consider what they fund and should give careful consideration to funding cuts.


It is hard to draw direct, causal relationships between something like reproductive health funding and reductions in morbidity and mortality because there are complex relationships between health care delivery and health outcomes. However, we do know that during the time that SMRU operated the antenatal clinic in Maela camp both maternal and neonatal mortality decreased drastically. From 1986 to 1990 there were about 499 maternal deaths for every 100,000 births while in 2006 – 2010 there were 79 per 100,000 births [3].  In 1996 there were approximately 43.5 deaths for every 1,000 neonates and by 2011 there were 6 per 1,000 [4,5].

When funding was available, refugees in Maela camp willingly chose to use contraceptives leading to safer, better-planned pregnancies, which leads to health improvements of mother and child. A focus on reproductive health in conflict and refugee settings is extremely important and can have a drastic impact on population health. When people are given the opportunity to be more in charge of important parts of their lives, they are more likely to break out of difficult poverty cycles, and subsequently go on to live healthier lives. We believe this is a good thing.

photo by Suphak Nosten


1. Wagmiller Jr RL, Adelman RM. Childhood and intergenerational poverty: The long-term consequences of growing up poor [Internet]. Columbia University Academic Commons. 2009. Available: http://hdl.handle.net/10022/AC:P:8870

2. Corak M. Do poor children become poor adults? Lessons from a cross country comparison of generational income mobility [Internet]. IZA Discussion Paper. 2006. Available: http://ftp.iza.org/dp1993.pdf

3. McGready R, Boel M, Rijken MJ, Ashley E a., Cho T, Moo O, et al. Effect of early detection and treatment on malaria related maternal mortality on the north-western border of Thailand 1986-2010. PLoS One. 2012;7. doi:10.1371/journal.pone.0040244

4. Luxemburger C, McGready R, Kham A, Morison L, Cho T, Chongsuphajaisiddhi T, et al. Effects of malaria during pregnancy on infant mortality in an area of low malaria transmission. Am J Epidemiol. 2001;154: 459–465. 

5. Turner C, Carrara V, Aye Mya Thein N, Chit Mo Mo Win N, Turner P, Bancone G, et al. Neonatal Intensive Care in a Karen Refugee Camp: A 4 Year Descriptive Study. PLoS One. 2013;8: 1–9. doi:10.1371/journal.pone.0072721


Friday, February 3, 2017

Save the Planet? Nonsense! But still.....

One hears a lot of Doomsday pleas that we should cut back on our consumption of carbon fuels, eat less meat, fish less, and so on--or else!  Or else what?  Or else, as it's often expressed, we'll destroy the planet!  Scientists speaking to each other about agricultural sustainability or climate change use less excessively inflammatory rhetoric, though even they can engage in catastrophism when the public media cameras are on.  Concern for the future is understandable, but exaggeration is not sensible if you stop to think about it. Crying "Wolf!" can backfire, because the Earth is not in imminent danger!




Human activity, even if we let our population rise to 10 or more billion and burn every single last chunk of coal and drop of oil, will not destroy the Earth.  No amount of energy conservation and sustainability will save the Earth from destruction, because it's not headed that way anyhow, and people haven't the power to destroy it (though, would we be able to come close with a nuclear WWIII?).

Indeed, it's possible that imminent catastrophe rhetoric reinforces the reactionary view that this is scientific nonsense and we should just close climate-change government-sponsored web sites and de-fund environmental science.

Part of the problem is that this is like the frog in a boiling kettle: the water gets hot so gradually that the frog doesn't notice it until it's too late.  We humans are not very good at long-term thinking or planning, perhaps because longterm thinking wasn't possible or useful as we evolved, when each day's food, safety and mates were what was at stake.  When change is slow, as global warming is, people often feel less inclined to self-denial today in exchange for a viable tomorrow.

In addition, sociologically speaking, climate change messages can be seen as a scientific or 'left-wing' elite telling everyone else that they have to scale-down, while at least some have noticed the fact that the same elite fly all over the world to have meetings, promote their books, and deliver their message (and flying is among the worst CO2 polluters).

In fact, most of what is being said by science, even taking scientists' vanities, frailties, and grant-hungers into account, is basically right.  The climate clearly is changing, the seas rising, agricultural patterns changing, many species endangered.  Of course, there have always been changes in patterns of rainfall, temperature, and vegetation, though the time scale generally has been glacially slow, so to speak, with the possible occasional exception of major meteorite strikes or huge volcanic eruptions etc.  The current speed is one reason human activity seems surely to be at least partially responsible.
Another important point isn't that climate is changing, but that the pace we're seeing today may not be reversible even if our behavior is contributing, because our ability to change the course of geoclimate might be limited.

But that doesn't mean that the science-deniers and their ilk hiding their head in the sand are right. They're as self-willed ignorant as scientists say they are.  They are pretending that the science is wrong, when the real truth is that they don't like the answers the science is giving us.

The real risk
If climate is always changing, and Save the Earth is a misleading slogan, the problem is that even if the Earth is not in danger, we are!  And that is the very, very personal and selfishly short-sighted reason that we should slow down global warming if we can, increase use of renewable energies, keep funding climate sciences, and so on.  Let's take a look at the wolf that really is at our door, and making enough evidentiary noise that we can't miss it.  What is at stake is not the Earth, but the kind of constancy we, like any species, rightfully feel comfortable with.

In fact, climate change does pose very serious, very real, and potentially dire risks. There are at least a few likely, foreseeable consequences of climate change:
1. Threatened lifestyles.  On the more mundane side, having to change where and how we live, what we eat, how we interact with each other, and so on, are major dislocations of lifestyle.  Being animals, we like our 'territory' to be familiar and feel safe.  The levels of ill-will and unhappiness that would ensue major cultural upsets due to climate change and its consequences, would be upsetting to a great many people. There may indeed be changed patterns of wealth, lifestyle, disease in us and/or our animal and plant food sources.  We may exhaust some minerals vital to our technological support systems. Even peacefully, gradually adapting to a lower-consuming lifestyle could avoid this, but would be disruptive; even if we lived very well in lower-consuming times in the past, social and psychological factors will be strained if our life-ways are changed too much or too fast. 
2.  Mass dislocation.  Most cities and urban concentrations are near natural waterways.  That's because they were founded over many centuries when water-borne trade and transport of goods etc., the stuff that makes concentrated populations possible, was the only real means of large-scale transportation.  So, if water levels rise along coasts and major lakes or rivers, or if waterways dry up, there will be dislocations that make todays middle east refugees look like tiddly-winks by comparison.  If tens of millions of Londoners and New Yorkers (not to mention residents of China or India) need to relocate, they'll have to go where there already are people.  This mass internal migration will be seen by the 'recipients' as 'Yugely' more of a threat than refugees today pose. 
3.  Exacerbated inequality and suffering.  Other large-scale dislocations of many sorts will mean economic deprivation for some who were well off, and new privilege for others.  Climate change alters agricultural areas, drying some up and making others flourish. Food being one thing people really do fight over, one can anticipate major economic dislocation and very large-scale competition for the new food producing areas, by those whose breadbaskets dried up.  This means war and potentially on a massive scale.  With 10 billion people, and industrial-scale weaponry (including nukes), the suffering will potentially be massively unprecedented.
In the overall scheme of things, a few island populations imminently needing relocation is an enormous event for the islanders but not a terribly large event globally.  But when cities become inundated, and food hard to come by, when refugees number in the many millions, and they're armed, well, that may be a definition of Arm-aggedon (forgive the pun).

We should be talking turkey to the public. Even if climate change is human-accelerated, it is not the first time there has been major climate change.  The Earth, and even the human species, will survive it.  Scientists should not be pressed by the intentionally uneducated into over-stating the case.  The planet is not in danger.  But in a sense there really is a wolf knocking at the door, and it is worth saving the planet as we know it.

What is in danger is our way of life.  And that's something humans kill for.

Friday, January 27, 2017

Evolution as a pachinko history: what is 'random'?

We discussed a Japanese pachinko machine in an earlier post, a pinball machine, as an example of the difference between randomness and determinism, in an evolutionary context.   Here we want to use pachinko machine imagery in a different way.

The prevailing, often unstated but just-under-the-surface assumption is that every trait in life is here because of natural selection.  Of course, for a trait to be here at all, bearers of its ancestral states up to the present (or, at least, the recent past) were successful enough to have reproduced.  It would not be here if it were otherwise, unless, for example, it's itself harmful, or without function but connected to a much better, related trait since genes are usually used in many different bodily contexts and may be associated with both beneficial and harmful traits.  Most sensible evolutionary geneticists know that many or even most sites in genomes tolerate variation that has either no effect or effects so small that in realistic population sizes they change in frequency essentially by chance.





However, the widespread default assumption that there must be an adaptive explanation for every trait usually also tacitly assumes that probabilism doesn't make much difference.  Some alert evolutionary biologists will acknowledge that one version among contemporary but equivalent versions of a trait can evolve by chance relative to other versions.  But the insistence, tacit or expressed, is that natural selection, treated essentially as a force, is responsible.  The very typical view is that the trait arose because of selection 'for' it, and that's why it's here.  And speaking of 'here', here's where a pachinko analogy may be informative.

If a bevy of metal balls tumbles through the machine, each bouncing off the many pins, they will end up scattered across the bottom ledge of the machine (the gambling idea is to have them end up in a particular place, but that's not our point here).  So let's take a given ball and ask 'Why did it end up where it did?"





The obvious and clearly true answer is 'Gravity is responsible'.  That is the analogue of 'selection is responsible'.   But it is rather an empty answer.  One can always say that what's here must be here because it was favored (that is, not excluded) by fitness considerations: its ancestral bearers obviously reproduced!  We can define that as 'adaptation' and indeed in a sense that is what is done every day, almost thoughtlessly.

Gravity is, like the typical if tacit assumption about natural selection, a deterministic force for all practical purposes here.  But why did this ball end up in this particular place?  One obvious answer is that each starts out in a slightly different place at the top, and no two balls are absolutely identical. However, each ball makes a different path from the top to the bottom of the obstacle course it faces. Yes, it is gravity that determines that they go down (adapt), but not how they go down.

In fact, each ball takes a different path, zigging and zagging at each point based on what happens, essentially by chance, at that point.   This one might think of as local ecosystems on the evolutionary path of any organism, that are beyond its control.  So, in the end, even if the entire journey is deterministic, in the sense that every collision is, the result is not one that can, in practice, be understood except by following the path of each ball (each trait, in the biological analogy).  And this means that the trajectory cannot be predicted ahead of time. And in turn, this means that our interpretation of what a trait we see today was selected 'for' is often if not usually either basically just a guess or, more often, equates what the trait does today to what it was selected to be, expressed as if it were an express train from then to now.

And this doesn't consider another aspect of the chaotic and chance-affected nature of evolutionary adaptation: the interaction with the other balls bouncing around at the same time in such an obstacle course.  Collisions are in every meaningful sense in the game of life, if not pachinko, chance events that affect selective ones, even were we to assume that selection is simple, straightforward, and deterministic.

The famous argument by Gould and Lewontin that things useful for one purpose, such as 'spandrels' in cathedral roofs, are incidental traits that provide the options for future adaptations--life exploits today with what yesterday produced for whatever reason even if just by chance.  The analogy or metaphor has been questioned, but that is not important here.  What is important is that contingencies of this nature are chance events, relative to what builds on them.  Selectionism as a riposte to creationism is fine but hyper-selectionism becomes just another often thought-free dogma.  Darwin gave us inspiration and insight, but we should think for ourselves, not in 19th century terms.

A far humbler, and far less 'Darwinian' (but not anti-Darwinian!), explanation of life is called for if we really want to understand evolution as a subtle often noisy process, rather than as a faith.  Instead, even serious biologists freely invent--and that's an apt word for it--selective accounts, as if true explanations, for almost any trait one might mention. It's invented because some reason is imagined without any direct evidence other than present-day function, but then treated as if directly observed, which is rarely possible. Here is an interview that I just came across that in a different way makes some of the same points we are trying to make here.

Everything here today is 'adaptive' in the sense that it has worked up to now.  Everything here today is also a 4 billion year successful lineage, that all made its way through the pachinko pins.  But these are almost vacuous tautologies.  Understanding life requires understanding one's biases in trying to force simple solutions on complicated reality.

Thursday, January 19, 2017

Relatedness is relative: How can I be 85% genetically similar to my mom, but only related to her by half?

First of all, no. I am not the lovechild of star-crossed siblings, or even cousins, or even second cousins. 

This is a gee-whiz kind of post. But the issues are not insignificant.

Hear me out with the background, first, before I get to the part where my eyes bug out of my head and I pull out my kid's Crayola box and start drawing.

If you've learned about sociobiology, or evolutionary psychology, or inclusive fitness, or kin selection, or the evolution of cooperation and even "altruism," or if you've read The Selfish Gene, or if you've been able to follow the debate about levels of selection (which you can peek at here)...

... then you've heard that you're related to your parents by 1/2, to your siblings by 1/2 as well, to your grandparents and grandchildren by 1/4, to your aunts and uncles and nieces and nephews by 1/4 as well, and to your first cousins by 1/8 and so on and so forth.  (Here's some more information.)

So, for example. For evolution (read: adaptationism) to explain how cooperative social behavior could be adaptive in the genetic sense, we use the following logic provided by Bill Hamilton, which became known as "Hamilton's Rule": 

The cost to your cooperation or your prosocial behavior (C) must be less than its benefit to you (B), reproductively speaking, relative to how genetically related (r) you are to the individual with whom you're cooperating. That could have come out smoother. Oh, here you go:

C < rB, or B > C/r

If you're helping out your identical genetic twin (r=1.0), then as long as the benefit to you is greater than the cost, it's adaptive.

C < B, or B > C

If you're helping out your daughter (r = 0.5) then as long as the benefit to you is greater than twice the cost, it's adaptive.

C < (1/2)B, or B > 2C

So already, the adaptive risk to helping out your daughter or your brother is quite higher. And it's even harder to justify the cooperation between individuals and their sibs' kids, and grandkids, especially ESPECIALLY non-kin. But, of course creatures do it! And so do we.

As relatedness gets more distant and distant, we go from 2 times the cost, to 4 times, 8 times, 16, 32, 64 etc... You can see why people like to say "the math falls away" or "drops off" at first or second cousins when they're explaining where the arbitrary line of genetic "kin" is drawn.  If you offer up a curious, "we're all related, we're all kin," someone out of this school of thought that's focused on explaining the evolution of and genes for social behavior may clue you in by circumscribing "kin" as the members of a group that are r = 1/8 or r = 1/16 but usually not less related than that.

This has long bothered me because we're all genetically related and so much cooperation beyond close kin is happening. And it's been hard for me, as someone who sees everything as connected, to read text after text supporting "kin selection" and "kin recognition" (knowing who to be kind to and who to avoid bleeping), to get past the fact that we're arbitrarily deciding what is "kin" and it seems to be for convenience. I'm not doubting that cooperation is important for evolutionary reasons. Quite the contrary! It's just that why is there so much math, based in so many potentially unnecessary assumptions about genes for behavior, gracing so many pages of scientific literature for explaining it or underscoring its importance? 

(It could just be that as an outsider and a non-expert I just don't understand enough of it and if I only did, I wouldn't be gracing this blog with my questions. But let's get back to my reason for posting anyway because it's potentially useful.)

Right. So. Even for folks who aren't part of evolution's academic endeavor, it's obvious to most that we're one half dad and one half mom. The sperm carries one half of a genome, the egg another, and together they make a whole genome which becomes the kid. Voila!

There's even an adorable "Biologist's Mother's Day" song about how we've got half our moms' genome... 


... but there's biology above and beyond the genes we get from mom (and not from dad). And that song is great for teaching us that the rest of the egg and the gestational experience in utero provide so much more to the development of the soon-to-be new human. So "slightly more than half of everything" is thanks to our mothers. Aw!

But, genetically, the mainstream idea is still that we're 50% our mom. 

I teach very basic genetics because I teach evolution and anthropology.And I'm not (usually) a dummy.* I get it. It's a fact! I'm half, genetically, my mom and I'm also half my dad. 

r = 0.5

Okay! But, given these facts about relatedness and how it's imagined in evolutionary biology, facts that I never ever questioned, I hope you can see why this report from 23andMe (personal genomics enterprise) blew my mind:

Percent similarity to Holly Dunsworth over 536070 SNPs (single nucleotide polymorphisms or, effectively/rather, a subset of known variants in the genome; Click on the image to enlarge).
I am 85% like my mom and I am at least 76% like my students and friends who are sharing with me on 23andMe. Names of comparisons have been redacted. As far as I know, this kind of report is no longer offered by 23andMe. I spat back in 2011/12 and the platform has evolved since.

Okay, first of all, it is a huge relief that, of all the people I'm sharing with on 23andMe, the one who squeezed me out of her body is the most genetically similar to me. Science works.

But that number there, with my mother, it is not 50%. It's quite a bit bigger than that. It says I'm over 85% the same as her.

What's more, I am also very similar to every single person I'm sharing with on the site, including example accounts from halfway around the world. Everyone is at least 60-ish% genetically similar to me, according to 23andMe. I know we're all "cousins," but my actual cousins are supposed to be 1/8th according to evolutionary biology. How can my mom be related to me by only one half? How can my actual cousins be only an eighth (which is 12.5%)? 

What is up with evolutionary biology and this whole "r" thing?

Hi. Here is where, if they weren't already, people just got really annoyed with me. Evolutionary biology's "relatedness" or "r" is not the same as genetic similarity like that reported by 23andMe.

Okay!

But why not? 

Let me help unpack the 85% genetic similarity with my mom. Remember, it's not because I'm inbred (which you have to take my word for, but notice that most everyone on there is over 70% genetically similar to me so...).

It's because my mom and dad, just like any two humans, share a lot in common genetically. Some of the alleles that I inherited from my dad are alleles that my mom inherited from her parents. So, not only is everything I got from her (50%) similar to her, but so are many of the parts that I got from my dad. 

Let me get out my kid's arts supplies.

Here is a pretty common view of relatedness, genetically. In our imagination, parents are not related (r = 0) which can lead our imagination to think that their alleles are distinct. Here there are four distinct alleles/variants that could be passed onto offspring, with each offspring only getting one from mom and one from dad. In this case, the sperm carrying the orange variant and the egg with the blue variant made the baby.


1. (Please, if you're horrified by the "r" business in these figures, read the post for explanation.)
But few genes have four known alleles, at least not four that exist at an appreciable frequency. Some could have three. What does that look like? 

The green allele doesn't exist in the next example. As a result of there being only three variants for this gene or locus, mom and dad must share at least one allele, minimum. That means, they look related and that means that, depending on which egg and sperm make the kid, the kid could be more related to mom than to dad. 


2. (Please, if you're horrified by the "r" business in these figures, read the post for explanation.)
Now here's where people who know more than I do about these things say that the kid is not more related to mom than dad because she got only one allele from mom and that keeps her at r = 0.5. 

Well, that's just insane. What does it matter whether she got the allele from mom or dad? I thought genes were selfish? (Sorry, for the outburst.)

Again, I realize I'm annoying people and probably much worse--like stomping all over theory and knowledge and science--by mixing up the different concepts of genetic similarity (e.g. 50%) with "r" (e.g. 0.5) and horribly misunderstanding all the nuance (and debate) about "r," but I'm doing it because I'm desperately trying to know why these two related ideas are, in fact, distinct. 

One last pathetic cartoon. 

In this third example, as is common in the genome, there are only two alleles/variants in existence (at an appreciable frequency, so not accounting for constant accumulation of de novo variation). An example of such a gene with only two known alleles is the "earwax gene" ABCC11 (there's a wet/waxy allele and dry/crumbly one). Here, the two alleles are orange and blue. Most humans in the species will have at least one allele in common with their mate for a gene with two alleles, and it's not because most humans are inbred, unless we want to redefine inbreeding to include very distant relatives (aside: which may be how the term is used by experts). 


3. (Please, if you're horrified by the "r" business in these figures, read the post for explanation.)
But as a result of the chance segregation of either the blue or orange allele into each of the gametes, two people with the same genotype can make a kid with the same genotype. 

And of course, making a kid with your same genotype is the only possible outcome if you and your mate are both homozygous (i.e. where both copies are of the same variant so that leaves no chance for variation in offspring unless there is a new mutation). 

So, I wandered a little bit away from my point with these drawings, but I had to because I wanted to get down from where my imagination has me (us?) with "r" versus how things really are with reproduction. We are baby-making with vastly similar genomes to ours, so we are making babies with vastly similar genomes to ours. 

So, I do see why biology says I'm related to my mom by one half. But, on the other hand, what does it matter if I got the thing I have in common with my mom from my mom or whether I got it from my dad? Because I got it. Period. It lives. Period. 

[Inserted graf January 20, '17] Saying it matters where I got the similarity to my mom keeps us at r = 0.5. Saying it matters only that I inherited DNA like hers keeps us always, all of us, at r > 0.5 with our parents and our kids because any two babymakers share much of their genome.

And the fact that this (see 2 and 3) happens so often is why I'm a lot more than 50% genetically like my mom, and the same can be said about my genetic similarity to my dad without him even spitting for 23andMe. 

So, here we are. I don't understand why our relatedness to one another, based on genetic similarity, is not "r."

I hope it's for really beautifully logical reasons and not something political. 

Because...

If "r" was defined by genetic similarity, then would cooperating with my 76% genetically similar students and friends be more adaptive than the credit I currently get from evolutionary biology for cooperating with my own flesh and blood son? 

If "r" was defined by genetic similarity, then could we use the power of math and theoretical biology to encourage broader cooperation among humans beyond their close kin? 

So many questions.

Maybe I should re-learn the math and learn all the other math.

Nah. Not myself. At least, it wouldn't come fast enough for my appetite. Maybe someone who already knows the math could leave a comment and we could go from there... 

And it would be worth it, you know, because despite my relatively weaker math skills, I bet we're more than 50% genetically similar.





*from 23andMe: "You have 321 Neanderthal variants. You have more Neanderthal variants than 96% of 23andMe customers."

Wednesday, December 28, 2016

Post-truth science?

This year was one that shook normal politics to its core.  Our belief in free and fair elections, in the idea that politicians strive to tell the truth and are ashamed to be caught lying, in real news vs fake, in the importance of tradition and precedent, indeed in the importance of science in shaping our world, have all been challenged.  This has served to remind us that we can't take progress, world view, or even truth and the importance of truth themselves for granted.  The world is changing, like it or not.  And, as scientists who assume that truth actually exists and whose lives are devoted to searching for it, the changes are not in familiar directions.  We can disagree with our neighbors about many things, but when we can't even agree on what's true, this is not the 'normal' world we know.

To great fanfare, Oxford Dictionaries chose "post-truth" as its international word of the year.
The use of “post-truth” — defined as “relating to or denoting circumstances in which objective facts are less influential in shaping public opinion than appeals to emotion and personal belief” — increased by 2,000 percent over last year, according to analysis of the Oxford English Corpus, which collects roughly 150 million words of spoken and written English from various sources each month.  New York Times
I introduce this into a science blog because, well, I see some parallels with science.  As most of us know, Thomas Kuhn, in his iconic book, The Structure of Scientific Revolutions, wrote about "normal science", how scientists go about their work on a daily basis, theorizing, experimenting, and synthesizing based on a paradigm, a world view that is agreed upon by the majority of scientists.  (Although not well recognized, Kuhn was preceded in this by Ludwik Fleck, Polish and Israeli physician and biologist who, way back in the 1930s, used the term 'thought collective' for the same basic idea.)

When thoughtful observers recognize that an unwieldy number of facts no longer fit the prevailing paradigm, and develop a new synthesis of current knowledge, a 'scientific revolution' occurs and matures into a new normal science.  In the 5th post in Ken's recent thought-provoking series on genetics as metaphysics, he reminded us of some major 'paradigm shifts' in the history of science -- plate tectonics, relativity and the theory of evolution itself.

We have learned a lot in the last century, but there are 'facts' that don't fit into the prevailing gene-centered, enumerative, reductive approach to understanding prediction and causation, our current paradigm.  If you've read the MT for a while, you know that this is an idea we've often kicked around.  In 2013 Ken made a list of 'strange facts' in a post he called "Are we there yet or do strange things about life require new thinking?" I repost that list below because I think it's worth considering again the kinds of facts that should challenge our current paradigm.

As scientists, our world view is supposed to be based on truth.  We know that climate change is happening, that it's automation not immigration that's threatening jobs in the US, that fossil fuels are in many places now more costly than wind or solar.  But by and large, we know these things not because we personally do research into them all -- we can't -- but because we believe the scientists who do carry out the research and who tell us what they find.  In that sense, our world views are faith-based.  Scientists are human, and have vested interests and personal world views, and seek credit, and so on, but generally they are trustworthy about reporting facts and the nature of actual evidence, even if they advocate their preferred interpretation of the facts, and even if scientists, like anyone else, do their best to support their views and even their biases.

Closer to home, as geneticists, our world view is also faith-based in that we interpret our observations based on a theory or paradigm that we can't possibly test every time we invoke it, but that we simply accept.  The current 'normal' biology is couched in the evolutionary paradigm often based on ideas of strongly specific natural selection, and genetics in the primacy of the gene.

The US Congress just passed a massive bill in support of normal science, the "21st Century Cures Act", with funding for the blatant marketing ploys of the brain connectome project, the push for "Precision Medicine" (first "Personalized Medicine, this endeavor has been, rebranded -- cynically? --yet again to "All of Us") and the new war on cancer.  These projects are nothing if not born of our current paradigm in the life sciences; reductive enumeration of causation and the ability to predict disease.  But the many well-known challenges to this paradigm lead us to predict that, like the Human Genome Project which among other things was supposed to lead to the cure of all disease by 2020, these endeavors can't fulfill their promise.

To a great if not even fundamental extent, this branding is about securing societal resources, for projects too big and costly to kill, in a way similar to any advertising or even to the way churches promise heaven when they pass the plate. But it relies on wide-spread acceptance of contemporary 'normal science', despite the unwieldy number of well-known, misfitting facts.  Even science is now perilously close to 'post-truth' science. This sort of dissembling is deeply built into our culture at present.

We've got brilliant scientists doing excellent work, turning out interesting results every day, and brilliant science journalists who describe and publicize their new findings. But it's almost all done within, and accepting, the working paradigm. Too few scientists, and even fewer writers who communicate their science, are challenging that paradigm and pushing our understanding forward. Scientists, insecure and scrambling not just for insight but for their very jobs, are pressed explicitly or implicitly to toe the current party line. In a very real sense, we're becoming more dedicated to faith-based science than we are to truth.

Neither Ken nor I are certain that a new paradigm is necessary, or that it's right around the corner. How could we know? But, there are enough 'strange facts', that don't fit the current paradigm centered around genes as discrete, independent causal units, that we think it's worth thinking about whether a new synthesis, that can incorporate these facts, might be necessary. It's possible, as we've often said, that we already know everything we need to know: that biology is complex, genetics is interactive not iterative, every genome is unique and interacts with unique individual histories of exposures to environmental risk factors, evolution generates difference rather than replicability, and we will never be able to predict complex disease 'precisely'.

But it's also possible that there are new ways to think about what we know, beyond statistics and population-based observations, to better understand causation.  There are many facts that don't fit the current paradigm, and more smart scientists should be thinking about this as they carry on with their normal science.



---------------------------------
Do strange things about life require new concepts?
1.  The linear view of genetic causation (cis effects of gene function, for the cognoscenti) is clearly inaccurate.  Gene regulation and usage are largely, if not mainly, not just local to a given chromosome region (they are trans);
2.  Chromosomal usage is 4-dimensional within the nucleus, not even 3-dimensional, because arrangements are changing with circumstances, that is, with time;
3.  There is a large amount of inter-genic and inter-chromosomal communication leading to selective expression and non-expression at individual locations and across the genome (e.g., monoallelic expression).  Thousands of local areas of chromosomes wrap and unwrap dynamically depending on species, cell type,  environmental conditions, and the state of other parts of the genome at a given time; 
4.  There is all sorts of post-transcription modification (e.g., RNA editing, chaperoning) that is a further part of 4-D causation;
5.  There is environmental feedback in terms of gene usage, some of which is inherited (epigenetic marking) that can be inherited and borders on being 'lamarckian';
6.  There are dynamic symbioses as a fundamental and pervasive rather than just incidental and occasional part of life (e.g., microbes in humans);
7.  There is no such thing as 'the' human genome from which deviations are measured.  Likewise, there is no evolution of 'the' human and chimpanzee genome from 'the' genome of a common ancestor.  Instead, perhaps conceptually like event cones in physics, where the speed of light constrains what has happened or can happen, there are descent cones of genomic variation descending from individual sequences--time-dependent spreading of variation, with time-dependent limitations.  They intertwine among individuals though each individual's is unique.  There is a past cone leading of ancestry to each current instance of a genome sequence, from an ever-widening set of ancestors (as one goes back in time) and a future cone of descendants and their variation that's affected by mutations.  There are descent cones in the genomes among organisms, and among organisms in a species, and between species. This is of course just a heuristic, not an attempt at a literal simile or to steal ideas from physics! 
Light cone: Wikipedia

8.  Descent cones exist among the cells and tissues within each organism, because of somatic mutation, but the metaphor breaks down because they have strange singular rather than complex ancestry because in individuals the go back to a point, a single fertilized egg, and of individuals to life's Big Bang;
9.  For the previous reasons, all genomes represent 'point' variations (instances) around a non-existent core  that we conceptually refer to as 'species' or 'organs', etc.('the' human genome, 'the' giraffe, etc.);
10.  Enumerating causation by statistical sampling methods is often impossible (literally) because rare variants don't have enough copies to generate 'significance', significance criteria are subjective, and/or because many variants have effects too small to generate significance;
11.  Natural selection, that generates current variation along with chance (drift) is usually so weak that it cannot be demonstrated, often in principle, for similar statistical reasons:  if cause of a trait is too weak to show, cause of fitness is too weak to show; there is not just one way to be 'adapted'.
12.  Alleles and genotypes have effects that are inherently relativistic.  They depend upon context, and each organism's context is different;
13.  Perhaps analogously with the ideal gas law and its like, phenotypes seem to have coherence.  We each have a height or blood pressure, despite all the variation noted above.  In populations of people, or organs, we find ordinary (e.g., 'bell-shaped') distributions, that may be the result of a 'law' of large numbers: just as human genomes are variation around a 'platonic' core, so blood pressure is the net result of individual action of many cells.  And biological traits are typically always changing;
14. 'Environment' (itself a vague catch-all term) has very unclear effects on traits.  Genomic-based risks are retrospectively assessed but future environments cannot, in principle, be known, so that genomic-based prediction is an illusion of unclear precision; 
15.  The typical picture is of many-to-many genomic (and other) causation for which many causes can lead to the same result (polygenic equivalence), and many results can be due to the same cause (pleiotropy);
16. Our reductionist models, even those that deal with networks, badly under-include interactions and complementarity.  We are prisoners of single-cause thinking, which is only reinforced by strongly adaptationist Darwinism that, to this day, makes us think deterministically and in terms of competition, even though life is manifestly a phenomenon of molecular cooperation (interaction).  We have no theory for the form of these interactions (simple multiplicative? geometric?).
17.  In a sense all molecular reactions are about entropy, energy, and interaction among different molecules or whatever.  But while ordinary nonliving molecular reactions converge on some result, life is generally about increasing difference, because life is an evolutionary phenomenon.
18. DNA is itself a quasi-random, inert sequence. Its properties come entirely from spatial, temporal, combinatorial ('Boolean'-like) relationships. This context works only because of what else is in (and on the immediate outside) of the cell at the given time, a regress back to the origin of life.