Week 3 HW responses

Week 3 HW responses

by Brianna Michelle Singleton -

  1. Weaver et al propose that among rats, maternal behavior towards newborn pups influences their cortisol response to stress via epigenetic mechanisms that change the expression of glucocorticoid receptor gene for the rest of the pup’s life.  They argue that because epigenetic patterns are established at specific developmental periods, there is extreme time sensitivity to when the pup is exposed to particular maternal behaviors (licking and grooming, in this case), and maternal behavior before or after that sensitive period window is not as important.   Do you think this mechanism is relevant in humans?  If so, what behaviors are most analogous to “maternal licking and grooming”?

  • I disagree, to a greater extent, but there is some truth to the statement. First, I do believe that there are certain timeframes that show the greatest benefit for expressing certain behaviors. Studies have shown that children learn multiple languages better at a younger age. They are better able to decipher certain sounds that become more difficult as we age. Also, reading to children during the first five years has a profound impact on how well children do throughout school. A parent’s ability to read, value in education in early childhood and accessibility to books may also be reasons as to why children do well later in life. Second, I don’t believe that humans are incapable of changing a behavior if certain behaviors didn’t occur during a certain milestone. Unlike rats, we have personalities, drive, motivation, hopes and aspirations that can override developmental milestones. Seminal writers in child development, like Erikson and Piage, posit the idea that there are ideal times for certain stages of development. However, I doubt that two white men in the 50’s and 60’s took into account the reality of people of color when they decided their timeframes. The combination of genetics, epigenetics, environment, opportunities, luck, and personal drive is more important than any sensitive period.   

 

2.  Provide a brief proposal for a study that would allow you to assess whether epigenetic modifications in humans in response to maternal behavior influence subsequent health of the human (feel free to choose any health or behavioral outcome you think you can do this with, e.g., dementia or depression or smoking). Bonus if you can explain how you would approach this if we assume that the relevant epigenetic changes are tissue specific and occur in the brain.

 

  • The best study would have to be with twins, but anything other than an observational study would be unethical. We know from research which behaviors are healthier or safer than others. To subject a twin to something that is unhealthy wouldn’t be wise or fair. Ethics aside, I would do a study having one twin to mind puzzles for 1hour/ day and consume a particular dose of Ginko every day from ages 40years old to 55 years old. The other twin can live their life as they please. The purpose is to see if there is a golden window of time where we can take preventative measures against dementia.

 

3. Gruenewald, in contrast to Weaver, emphasizes the cumulative effects of SES adversity on a multi-system allostatic load measure.   Do you think that the Gruenewald findings are consistent, inconsistent, or unrelated to the Weaver findings?  Explain.

  • Gruenewald and Weaver are telling the same story at different times in the continuum of the human lifespan. The theme for the 2012 American Public Health Association conference was health determined by who your mother is and what your zip code is. Weaver touches upon the “who your mother is” aspect. Genetics does matter, but only about 10% according to Dr. Tony Litton of the California Endowment. What happens in the womb does matter.  Epigenetics is the bridge between the ‘nature vs. nurture’ argument that was very popular up until recently.

  • Gruenewald continues the life story after genetics and epigenetics to environmental factors that determine health and quality of life. I really liked the article. I don’t think they missed anything about the determinants of health. The only thing I can contribute is my fondness for the Marxist idea as social capital (more or less everything Gruenewald talks about) is not just the things you accumulate or the experience and opportunities that a person has. Social capital is a form of social relationships. It is not a coincidence that the people in your circle have about the same amount of resources that you do. Wealth is not an independent thing; it is a social interaction among a community. For instance, even though I haven’t lived in my hometown for over 10 years I’m still relatively as well off as my close friends that I kept from high school. I know it is more complicated than that, but that is the gist of it.

 

4. Hertzmann and Boyce argue that “it is not genes or environment, nor is it genes and environment, but rather it is gene-by-environment interactions that influence developmental trajectories.”  To what extent do you think that GxE interactions can contribute to major disparities along racial/ethnic, socioeconomic, or geographic dimensions?

  • For next year, I would add “historical” in that list. We can pick a plethora of atrocities that have occurred since the pilgrims arrived at Plymouth Rock. I would like to focus on redlining. Both of my parents grew up in areas that were predominantly black and relatively safe. Their parents were probably limited to renting or buying homes in those areas because of redlining.  When they became adults, those areas were  “bad and crime-filled.” Now the hipsters are moving into those neighborhoods. By the time they were able to purchase a home, they had moved into a predominantly white neighborhood. Sometimes I wonder if they got a fair interest rate comparable to their neighbors or if they were lucky they bought a home in an area that had yet to become a desirable place.

  • Red-lining, segregation, and gentrification alone probably caused so many different possibilities of higher risk to negative health outcomes for communities of color. However, there is a push and pull between opportunities and obstacles. I don’t know “to what extent do ... GxE interactions can contribute to major disparities” because the people of color that exist today have evolved through the recent and far removed historical oppression that has been inflicted on our ancestors. I have come across articles that said slavery had changed the genetic makeup of African Americans. (I only skimmed it, but it seemed convincing.) I believe some of the evolutionary genetic and cultural changes have been good and other aspects are detrimental to our health.

Re: Week 3 HW responses

by Maria Glymour -

Brianna,

There is so much here I cannot do justice to this response.  Working backwards:

> There was some research arguing that the selection process created by high mortality rates during the middle passage led to genetic differences in African Americans. That research was debunked. I can dig up references for you - I think the idea lives on because it's an easier explanation for health disparities than structural inequality. 

> Historical events are definitely manifested in and fundamental contributors to contemporary racial/ethnic, socioeconomic, and geographic inequalities. This is an incredibly important observation -I think core to understanding the persistence of disparities - and it's amazing how limited the heatlh research evaluating the impact of things like segregation/desegregation of schools, redlining, discrimination in the GI bill implementation, etc has been to date. 

> Epigenetics just happen to have the word "genetics" in the label.  They are fundamentally about a nurture or environmental mechanism.  

> Check out some of your classmates' ideas for research approaches to evaluating epigenetic influences in humans.  It is indeed hard and I'd love to know whether you think the Bucharest Early Intervention Study was ethical.

Maria

Re: Week 3 HW responses

by Brianna Michelle Singleton -

Hi Maria

" There was some research arguing that..That research was debunked." Thank you for bringing this to my attention. I can spend some time finding the articles. I may even find some other new information in the process.

 "Epigenetics just happen to have the word "genetics" in the label." I remember hearing about a epigenetic study where they had identical mice, but different diets. On mice grew up to be an orange fat mouse and the other was a skinny white mouse  After listening to yesterday's lecture, I realized that I've been missing the huge part about how acetylation, methylation, and phosphorylation   

"I'd love to know whether you think the Bucharest Early Intervention Study was ethical." 

 

My first reaction to the study was:

  • We, as a society, generally prioritize doing research for the sake of research. Common sense could have told you that there is a difference between being institutionalized or being placed in a foster care institution that was better equipped.
  • Is the government really the best advocate for the kids? Did they (whoever that individual person was or collective group of people were) truly have right to consent on the behalf of a the children? Would they have done it for their own kids, nieces, nephews, grandchildren, etc? My answer would be ‘no’. These children are beyond any standard of vulnerability and their lives didn’t need to be subjected to a Russian roulette.

My second reaction was:

  • Discussion about vulnerable populations truly triggers me. I had decided that this was unethical before I found out that the results of the study eventually benefitted all of the participants and prevented other children from being institutionalized.
  • This example made me ponder if the meaning of “the means justify the end”. Clearly, IRB and the Nuremberg Code have been put in place so that we don’t manipulate people’s lives just so we can see how bad of an outcome can be reached. However, many children benefitted from the results of the Bucharest Early Intervention Project. Which leads me to my final thought….
  • We live in a horribly imperfect world. Not everything will be solved by following common sense and avoiding the question if, “the means justify the end?” Yes, the government could have placed all of the children in the foster care agencies without doing the research. However,  government and other decision makers always have to balance competing priorities (like a finite amount of money, resources, and capacity) when faced with an alternative that feels like a common sense approach.
  • Also, common sense isn’t always the right answer. We do research, and think about the consequences and parameters, because ideas that have good face value may also have dangerous repercussions.   

Re: Week 3 HW responses

by Maria Glymour -

Brianna,

For the Bucharest Early Intervention Study, I am not sure it's completely fair to call this an "ends justify the means" situation because the existence of the study did not harm any child.  No child was worse off by virtue of being in the study (to the best of our knowledge). I do not think that anything they could have learned would have justified placing a child in an orphanage who would not otherwise have been so placed.  But still, it is unclear (to me) when it is okay to say "well, usual care here is awful, but we are still going to randomize some children to usual care because there's no way we can pay for all of these children to receive high quality foster care", and when it is incumbent to say "this is so awful we will have nothing to do with it, not even to demonstrate that it is awful".  This kind of ethical problem comes up a lot in health. 

To me, the Bucharest study seemed justified: the orphanages themselves were not justified, but given the facts on the ground, the research that helped some children have loving foster families was okay. Not an easy question and always always worth casting a critical eye.

Maria

Re: Week 3 HW responses

by Brianna Michelle Singleton -

I guess what bothers me is that some children were randomized into a better situation and other kids were left initially left behind. Any study where investigators let a situation run its natural course- when there is a clear better alternative- is reminiscent of Tuskegee. I realize that Bucharest is not nearly as unethical as harmful. Maybe if I were in the room when investigators had the conversation about "well, usual care here is awful, but we are still going to randomize some children to usual care because there's no way we can pay for all of these children to receive high quality foster care" I would feel differently.

Just because the children were already in institutions doesn't automatically mean that creating a study about their living condition doesn't do any harm.

I'm also bothered that the people who consented on their behalf may or may not have had the children's best interest in mind.  

Also, we can only judge the study in hindsight; good things resulted from the study. But what if it didn't? What if the results were used for general knowledge (only published in journals for the use by other scholars), but not for changing policies and practices? In this situation, the children who remained in the institutions would not have received any of the benefits of the study and that, to me, is a harm of being in the study. 

I really like your point: 'the orphanages themselves were not justified'. This sums up the entire study. And I really appreciate your feedback. 

Re: Week 3 HW responses

by Jason Thompson -

I agree that the ethical rationale of the BEIS is questionable. A central argument of the PIs was that the benefits of foster care vs. institutional care wasn't settled scientifically at the time of the study so they needed a randomized design to infer a causal relationship between foster care and superior developmental outcomes (see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC300808/). I don't find this ethically persuasive because the issue of the study's justifiability rests not on whether the existing literature *definitively* favored foster care, but on whether continued institutional placement constituted an unacceptable harm to the children given the deprivation they'd already suffered and the *reasonable foreseeability* of further harm in the treatment-as-usual condition. As support for this point about forseeability of harm it is instructive, I think, to imagine other examples of experiments where similarly the gold standard of scientific proof not only didn't exist but *couldn't* exist because any  endeavor to generate evidence meeting that standard would be self-evidently wrong, for instance the BMJ's satirical article: "Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomized controlled trials" -- see: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC300808/

Re: Week 3 HW responses

by Brianna Michelle Singleton -

That article is awesome! You posted the link twice; I think the first link was supposed to be about BEIS.

I really like your point about how there are some things we can't study " gold standard of scientific proof not only didn't exist but *couldn't* exist because". 

Re: Week 3 HW responses

by Jason Thompson -

Glad you enjoyed it!

Here is the first article (about the BEIS, by Fox & Nelson) that I'd meant to post:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4158102/