Middlesex

Reading (a work of fiction this time!):
Middlesex by Jeffrey Eugenides (2002)

This was quite the interesting read.  Eugenides tells the story of Cal[liope] Stephanides who was born with a 5-alpha reductase deficiency syndrome, or in other words, a hermaphrodite.  This was particularly interesting because it explore the idea of gender identity from both a social and biological/genetic perspective. Calliope was born with the genetics for a male but was raised female until the age of 14.  This novel tracks the gene that caused this syndrome down through 3 generations, ending with the second birth of Calliope as Cal.  What’s interesting is that Eugenides does end up using a lot of his own family history for the background, to make it that much easier for him to write about a topic that he has not personally experienced.  Two fun articles:
My Big Fat Greek Gender Identity Crisis
A Novelist Goes Far Afield but Winds Up Back Home Again

It’s a long one (500+ pages), so I’m only going to talk about a few passages that stuck out to me as I was reading.  When I say “he,” I will be referring to the protagonist, but with references to the character being ‘Calliope’ or ‘Cal’, depending on which point in his life I’m describing.  References to the author will be by his last name.  The first of these moments of pause I experienced comes at the bottom of page 37:
Now we know we carry this map of ourselves around.  Even as we stand on the street corner, it dictates our destiny.
As a popular author, Eugenides did of course get through some research to evaluate how he was going to treat genetics.  However, this gross simplification completely discounts environment.  Eugenides (directly after this statement) describes how everything down to our nervous twitches can be attributed to genetics.  I can imagine that at the time he was reading this, mainstream views of genetics pretty much agreed with this statement.  The humane genome was fresh, and in the process of discovering this information, people were convinced that everything could be found in your genes.  Now we know a bit better and so this statement really stuck out to me.  It’s such a simplification of the environment to play a role in our development.  I’ve definitely noticed myself pick up certain quirks based on the people around me, and this changes over the years of my life.  Also, it cheapens the idea that we get to chose anything about the way that we are.

Next point fell on page 297:
There is no evidence against genetic determinism more persuasive than the children of the rich.
Genetic determinism, or the idea that the way we turn out is based completely on our genes, is a topic that you may remember us commenting on before.  While this is a comical reference to the concept, I think it speaks volumes about what is actually true.  And while ultimately for Cal, genetics win out, that is not the case in every situation.

The final two quotes come from the description of Dr. Luce (the leading authority on human hermaphroditism) and the work that he had done.
..Luce argued that gender is determined by a variety of influences: chromosomal sex; gonadal sex; hormones; internal genital structures; external genitals; and, most important, the sex of rearing. Drawing on studies of patients at the pediatric clinic at New York Hospital, Luce was able to compile charts demonstrating how there various factors came into play, and showing that a patient’s gonadal sex often didn’t determine his or her gender identity.  (Eugenides 410-411)
All of the preliminary study described from pages 435-437 where Eugenides writes up a report by Dr. Luce stating that Calliope, despite having an XY genotype clearly identifies in all ways as a girl, and therefore supports his own theory.
These descriptions of Cal[liope]‘s situation, while detailed, still make for an incomplete picture.  There is a vague medical description and an intense discovery process, but little afterward.  Cal undergoes a process by which he discovers his gender identity, but what I feel is somewhat lacking, is what happens afterward.  We know that Cal chose to stay as he was, and identified as male, but what were the decisions for staying as he was physically?  My understanding is that surgery was not done to anatomically adjust external genitals and it would have been cool to have a description of what decision process would have been like.  In the same way that we were able to see how the discovery of carrying the BRAC1 or BRAC2 gene led to making a decision in Joanna Rudnick’s documentary In the Family (2008) that we watched a while back.  I acknowledge the difference between a documentary and a fiction novel, but even as a piece of fiction, it would have been interesting to see how the decision-making process would have been interpreted.  In one of the articles linked above, Eugenides mentioned that he had never met a hermaphrodite before, and I think that that would have been invaluable to the process of writing his book.

I feel like, in general, the process is more important to people than what happens afterward.  Eugenides did a good job describing the process of discovery, but then it dropped off at the consequences of that discovery.  I believe this functions the same way for the thylacine as well.  There is great documentation of the entire process, the significance of getting one protein to work, or the successful recovery of a full mitochondrial DNA, but then what happens after?  We have this full genome and then what?  The scientific discovery itself is so exciting that consequences are overlooked.  True, the stated purpose is to learn about evolution, but what about the effects of the newly developed technology?  That will be applied to new areas, and even the thylacine itself will become of more use than just evolutionary knowledge because once it exists, it’s out there.  Even from an economic sense, this object/technology will exist, a market will be created for it, and a profit will stand to be made.  By virtue of that alone, there will be a lack of control over it.

Identity in your Genes

Readings:
Nelson (2008) Bio Science: Genetic Genealogy Testing and the Pursuit of African Ancestry
Stevens (2002) DNA and Other Linguistic Stuff

There are lots of complicated procedures that claim to have found a genetic basis for race.  Nelson’s article (my primary focus) speaks a lot about particular cases where individuals were looking for information on their ancestry, but genetics fell short of expectations.  I’m actually going to go bit by bit with reactions from reading this article.

Nelson begins by examining the idea of finding your ancestry to the extent that she describes various resources available to all peoples (though she focuses on African Americans) to help determine where in Africa their origins lie.  We start with the process of how exactly it is that these things are determined.  There is a patrilineal approach that involves tracing a virtually unchanged DNA from Y-chromosomes across generations and a matrilineal approach that traces through mitochondrial DNA that gets passed down only from the mother.  Using a combination of these two methods, it is possible to match with existing groups in different regions of Africa and try to locate a place of origin.
This form of analysis was made possible by the ambitious Y-DNA and mtDNA mapping research that resulted in theories about the times and places at which various human populations arose…Based on a match with the mrDNA-derived L1 haplogroup, a customer employing this test can receive a result indicating that her ancestors lived in Africa approximately 100,000 years ago.  (Nelson 2008)
While I do understand the idea of locating in the present-day groups based on genetic similarity, the idea of tracing back in time is a foreign concept.  Nelson unfortunately does not go into much more detail than just this quote.  And how it is that geneticists are able to say with any certainty that specific genetic similarities occurred at certain points in time?  Nelson does make a good point that many cultural groups had passed through West Africa at some point in time on their way off the continent and so many people received information that linked them with West African origins.  But that doesn’t necessarily indicate origin so much as trace an ethnic or cultural group across its history.  For more information on some of these groups, check out these links: National Geographic’s Genographic Project, Family Tree DNA.  With projects like Family Tree DNA, once analysis has been completed, you even get a fancy looking certificate:

There is also skepticism not only based on the methods of inference, but the technology itself.  A woman named Pat had gone through with genetic testing and was actually very trusting of the methods.  With the Tuskegee syphilis experiment in the very recent past, that is a frequent road block for people who do not have the exposure to genetic analysis that Pat did.  Pat worked in a crime lab where genetic analysis was used to free innocent suspects, and so was confident in the ability of DNA to tell the truth.  But even so, upon further delving into other companies and seeing the similarities that were coming from her colleagues who had also received the tests:
Nevertheless, the preponderance of similar ethnic lineage findings among her genealogist colleagues, and the inconsistency of her genetic result with the family genealogy she had laboriously assembled by conventional means, led Pat to conclude that ‘we still technically don’t know who we are’.  (Nelson 2008)
Her response actually made me stop and I had to sit for a few moments before continuing.  Pat had spent time tracing out her family genealogy through more conventional means, and had set up genetic analysis as the end-all statement of truth.  When genetic analysis was inconsistent with what she had found, everything she had done outside of DNA testing suddenly was thrown up in the air again.  The ability for a technology, which is still largely imperfect in this case, to cause you to doubt all other types of evidence is strange to me.  It’s been interesting reading about genetic technology and identity because it’s something that I can’t necessarily agree with as being a definitive statement of who I am.  I think it’s unfair to say that your history, your meaning, who you are can all be found in genetics.  Knowing who you are (historically even) is based upon experiences.  Nelson had also described how one woman, upon discovering her Ghanaian roots, had gone out and bought a flag, and suddenly was able to find this “family” to identify with.  Sure, genetics opened up this whole other world she never would have thought of, but its strange to think how one test will completely change how you see yourself.  But that then speaks to our constant desire to find a meaning, find an identity.  In a diverse culture like in the US, where individualism is so prized, and it’s all about figuring out who you are in relation to other people.  In searching for who we are, we look for groups to identify with and now it seems that this kind of identification is more and more starting to come from genetics.

When examining DNA in this way, what we’re trying to do is piece together across history, a tracing of the human species.  There is absolutely an evolutionary element to it.  Beyond finding specific loci of similarity among DNA, pretty soon (once technology catches up), we’ll be looking to trace the evolution across not just specific cultural or ethnic groups, but also across the human species in general.  So much of the motivation for the Tasmanian Tiger project comes from wanting to evolutionarily understand the world.  Once we go beyond tracing ethnic groups, the next step is to take it to a macro-level understanding of the human race in general and see what we can learn about evolution through that.  An easy way to examine evolution genetically it is through looking at animals who had been around for a particularly long period of time and only disappeared in the recent past (like the tiger).  In this way, we have evidence for a species that was fairly stable genetically across its existence and with something like the tiger it is easier to find genetically similar animals that we could possibly make connections to.  Not that the findings would necessarily support current theories of evolution, but nonetheless, sequencing genomes opens up the possibility for making connections across history and creating a time-spanning map of life on earth.

Databanks part II

Readings for today:
Chapter 3 of To Know Where He Lays by Sarah Wagner

Background on the Srebrenica Massacre

Wagner describes the process of databanking the DNA from individual remains from the massacre and the process of forensic and DNA analysis to determine the identities of those who were killed.  The event itself led to many technological innovations, which started with forensic investigation:
The chaos of the commingled, disassociated, and partial skeletons that lay within the secondary mass graves eventually gave rise to another innovation: a forensic application of genetic science unique in scale and in method that finally offered a means of resolving the missing persons issue by matching blood samples of surviving family members with bones samples from recovered mortal remains.  (Wagner 86)
The process was started in 1996 with a strictly forensic team.  Despite the best efforts, Wagner mentions that only 70 individuals were identified based on this process by 2000.  The pace was slow and so it paved the way for the application of DNA technology, with a lot of it being dependent on the formation of databanks that would be able to quickly and much more precisely identify individuals from the mutilated remains:

Synthesizing data for each missing person, these Excel spreadsheet records compelled action, their very form creating an “instrument, a tool, a means to an end—Action.” The act of documenting their names formally recognized them as missing, and that state of absence demanded a public response.  Furthermore, the lists marked the first attempts to establish a central database for the victims—individual profiles a computer software program would one day sift through in its search for matches between the mortal remains of the missing and the blood of the surviving family members.  (Wagner 92)
Overall, DNA trumped forensic analysis, not just in speed of recovery but also in accuracy:
Over and over, I saw how the recognition of an identifying item had led them down the wrong path, only to be corrected by the use of the outsourced DNA testing.  (Wagner 100)
There is no doubt that, in contrast with last week’s post, DNA databanking is a very useful tool.  And I do believe that used in contexts outside criminal handlings, databanking for the purpose of finding identity should be encouraged.  The organization heading much of the project, ICMP, has been greatly beneficial.  In a constantly modernizing world, the idea of a databank, especially for such a humanitarian cause, it hard to ignore.

Identifying missing persons through the sophisticated instrumentation and presumable unassailable evidence of DNA testing provided yet another plane on which the invested Western governments could attempt social repair in postwar Bosnia.  First, cast as science in the service of “truth,” it promised to transcend the politics of the region…Second, it was manifestly humanitarian. (Wagner 80)

Thus the project of identifying Srebrenica’s missing, as it expanded into a region-wide effort to identify all of former Yugoslavia’s missing, drew together opposing constituencies around the common goal of accounting for and commemorating the missing. (Wagner 90)

My worry is that while people are being rallied around this good causes, the ideas of databanks will spread beyond this situations.  We’ve already seen databanks with enCode in Iceland go awry, and so who’s to say that the same won’t happen as a result of this event?  Don’t get me wrong, I’m absolutely sensitive to the cause and I’m all for it, but let’s hope that these companies will choose to use this vast power only for good.

But you’ve got to wonder, that once we get to a point where things are sequenced, and everyone is figured out, where will our individuality lie?  The distinguishing characteristics people (or at least government) will identify you with is the appearance of certain proteins on your genome.  If the idea of DNA databanking caught on and was mandated beyond missing persons cases, it will do exactly what we didn’t want Social Security numbers to do, to change people to a string of code.

So let’s say hypothetically that this won’t happen for people, because we value ourselves beyond the building blocks we’re made up of.  But what about animals?  All this work on the DNA of the thylacine, as well as the many other animals who have been cloned or had their DNA sequenced could very well lead to a databank of animals.  When this happens, I just wonder if we’ll ever get to a point where we manufacture animals.  Getting low on animal A?  Well, we’ve got the code on file, let’s just make a few more. Having this kind of power at our disposal I think would lead to less of a concern of actually preserving and respecting the creatures we share this earth with.  It doesn’t matter how we use or deplete resources, we need to leave only enough so that they have a small environment to live in, and if we kill too many of them we’ll just make a few more.  I’ll be the first to admit that this is probably an exaggeration, but with the track record we’ve got as a human race, will we know when to stop?

Biobanks

Reading for today:
Rose The Commodification of Bioinformation (2001)

This was a particularly interesting study of the exploitation of the somewhat isolated population of Iceland.  Rose examined the progression of a particular genetics research company called deCode from it’s initial presence to the state that it’s in in 2001, when the article was published.  Even today, their website touts it’s leading in research and statistical analysis:
deCODE is a global leader in making sense of the genome – in linking variations in the sequence to phenotype. Our work is driven by our world-leading statistics team, who put their know-how in to work for you: maximizing the data you get from your samples and then taking you from data to discovery. (deCODE)

Rose raises a lot of concerns in the article about the privacy of the information being provided to deCode.  It seemed like a happy enough idea:
The possibility of tailoring drugs to patients with particular genotypic profiles offers better value for money for the drug budget coupled with less discomfort and danger to patients.  (Rose 10)
It seems like a company that would be able to take information and cut down on drug costs because of the specificity with which they could cater their research.  But something not so great has been the collection of data, and the limited opportunities to opt out.

Internationally accepted standards of good practice would require not only informed consent for the first DNA analysis but that the researchers should seek separate consents for each subsequent analysis or secure informed consent to a series of subsequent tests.  Thus, deCode’s technocratic and commercially driven language of ‘has value’ appears to set aside consideration of the ethical requirements demanded by human genetics.  (Rose 17)
Only current adults were able to opt out, and data once submitted could never be removed.  In addition to issues of opting out, issues of consent for each testing phased were circumvented and not much else has changed.  From a Science Insider article written January of 2010:
To further its search for disease genes, the company plans to begin whole genome sequencing of 2500 DNA samples from its database. It will not need to recontact these individuals for consent because their original consent agreements cover whole genome sequencing, Stefansson [CEO] says.   (Kaiser 2010)

The company’s cheerful website highlights it as a do-good service to the community but it is difficult to ignore all the criticisms it had received in the past.  DeCode actually filed for bankruptcy in 2009 and was brought under the leadership of another company, much to the shock of those who’s information was held within the HSD database.  A TimesOnline article discusses some of the conflict that was sparked when news of bankruptcy was released, with concerns over the new potential uses of genetic information, especially because of the blanket consent forms issued at the start.

Even news clips put a positive spin on volunteering to be in the database.

But even with this spin, Rose points out in her article that these genetic consistencies among the population in Iceland aren’t necessarily as homogeneous as researchers want to believe.  Claims are made as to the Viking heritage of the whole country, but immigrants are simply ignored, and the bottleneck instances used to justify the homogeneity of the population are not valid enough to draw the conclusions that members of deCode are drawing.

The compilation not only of genetics but of health records in general is on the rise with companies pushing for the consolidation of medical records for ease of access, etc.

The desire to create compilations of information is not a foreign idea, nor is it necessarily a bad one.  But my hesitation comes in when there is uncertainty as to whether or not this information would be used for purposes beyond what is specified because deCode has already proven that it is easy for companies to create blanket consent forms so that once you’ve participated for whatever reason, your genetic information is lost to you and can be used for whatever else the company needs, and can in some cases be sold to other parties.  There does need to be transparency when it comes to dealing with genetic information and its advancement.  The Tasmanian tiger sequence of DNA is still in the introductory stages of having been sequenced, but what happens to the technologies when they are given over to the general public?  The sequencing techniques will become available to whatever genetic company wants to use them, or by the same people funding the current research, and then that sort of technology will be expanded and used for other purposes.  Luckily for us, the thylacine is extinct, no objections can be raised (it’s an animal anyway) in using its DNA to advance sequencing technologies.  But again, once these technologies are available to the general public, then what?

who you are is in your genes..?

Readings:
Jasanoff, “Just Evidence:  The Limits of Science in the Legal Process“  (2006)
Steinhardt, “Privacy and Forensic DNA Data Banks” (pages 173-196 of Lazer, ed., “DNA and the Criminal Justice System“)
^ page numbers for this author will not reflect that of the actual book but instead a .pdf file used in the course
Fun link to explore: The Innocence Project

Biologists today, for example, accept without question the double helical structure of DNA and the chemical composition of the base pairs that make up its two intertwined strands.  There are taken as undeniable facts, not contingent in any way on the circumstances of their discovery…Science may be a social activity, but when executed correctly, the results are viewed as no longer bearing traces of human subjectivity.  (Jasanoff 330)
To [collect DNA samples from arrestees] is to equate arrest with guilt and to empower police officers, rather than judges and juries, with the power to force persons to provide the state with evidence that harbors many of their most intimate secrets and those of their blood relatives.  (Steinhardt 14)

These two statements seem to be a bit unrelated, but I think provide an interesting summary of the viewpoints of the two authors.  Jasanoff spends his pages talking about the way in which DNA is used, or is an influence, in the court system.  Steinhardt talks about the legality of what is permissible by various states with respect to holding onto DNA samples after legal proceedings and the points at which DNA testing can be introduced in a case.  Overall, the impression I seem to get is that Jasanoff puts little merit into the impact DNA testing can have on a case while Steinhardt seems to believe that the general public does, in fact, take genetic evidence as final.  These different viewpoints, I believe, might stem from differing perspectives on what the relationship is between an individual and their genetic sequence (which is where the title of today’s post comes in).

In practice, the degree of doubt in a juror’s mind depends on an advocate’s success or failure in arousing or allaying misgivings, whether about the heinousness of the crime or about the nature of the evidence, or both.  Forensic science, in other words, cannot rule out doubt on its own, but only as it is represented, and contested, in court, as a component of a larger story.  (Jasanoff 334)
This is where I’m more inclined to lean toward Jasanoff’s view on genetics in general, but at the same time, I do have the same skepticism over DNA databases as Steinhardt.
First, I am skeptical because there is a long history of function creep in databases.  Despite the initial promises of their creators, databases created for a discrete purpose eventually take on new functions and purposes…Finally, I am skeptical because as long as we continue to hold on the millions of biological samples, the temptation to use them for purposes that go beyond law enforcement identification will simply be too great.  (Steinhardt 2)
Steinhardt goes on to examples of the progression of DNA collection in the US.  His fears are completely valid because some of the loose wording in state statutes on these issues open up these data banks to any number of government organizations.  I wouldn’t doubt that before long, we’ll see health insurance companies taking genetic backgrounds on potential clients, and having access to this information because of the state.  It does, then, open up for all sorts of new discrimination in that sense.

Steinhardt does, however, also take the privacy angle where he asserts that your genetic code is one of the most secret and personal thing about you.  While a statement of secrecy about it is true, seeing as most people don’t even know it themselves, approaching DNA in this way limits the individual to just that.  My challenge to all of you out there is to think about what identifies you.  Is it something in your DNA, can the essence of an individual be found in their DNA?

Although all forms of scientific activity strive as far as possible to find correct answers to problems, the context in which an investigation is carried out necessarily affects the kinds of conclusions it reaches.  (Jasanoff 333)
True for all areas of science.  So often, the strived after goal has a way of changing the interpretations of experimental results.  I think this is true not just in the legal system but in genetic analysis as well.  So this thylacine: manipulation of genes has allowed for scientists to run with the idea that all genes from this animal can be functional if brought back.  The got one protein to work in mice, but who’s to say that they could, in fact, get every protein to be functional should they decide to bring back the animal?  How do they know that different environmental factors/conditions wouldn’t affect the expression of the gene in different ways, trigger something different, and not actually lead to a successful creation?  There is such a focus on being able to genetically get something to work, that I think environmental factors aren’t really getting fair consideration.  In the same way that DNA evidence will not for sure convict or not convict a suspect, getting a few proteins to work won’t necessarily lead to a healthy living thylacine.

I had mentioned not too long ago that a side affect of the thylacine project could definitely be the opportunity to understand evolution from a genetic standpoint.  That’s giving genes way too much credit.  In areas of little understanding, people are quick to assign cause to a specific factor.  For most of us who cannot comprehend committing a felony, it can be relieving then to find there might be a genetic predisposition.  We don’t want to believe that people really choose to do wrong, that people choose to harm others and so the more we can blame away to other factors, the better.  In that same way that we still don’t really understand evolution and extinction of species, or want to assign blame to ourselves, it would be nice to be able to blame extinction on genes and take ourselves out of the picture.  In the same way that we don’t want to believe that humans want to cause harm to other humans, we don’t want to accept that we (inadvertently or not) led to the destruction of any living being.  Voila: thylacine project.