Book Review: Blood Matters by Masha Gessen

4 stars. Loads of interesting information, quite a lot of science content and quite well explained with some weak spots. Unpleasant emphasis on Israel. 

• Lots of interesting case studies from Amish and Mennonite communities:
•  The Amish don't reject medicine because it's not a distraction from community, unlike TV. That said, they don't have insurance and use community crowdfunding,
• They have extremely high carrier frequencies of some diseases e.g. Old Order Mennonites have a 10% carrier frequency of maple syrup disease, and glutaric aciduria type 1 hits the Amish
• VERY inbred. There's a case study of a family where the parents are double first cousins -- their mothers were sisters and their fathers were brothers. Out of their 8 or 9 children, 4 had Maple Syrup Urine Disease and 2 had Severe Combined Immunodeficiency. Does sound very sad though, because a lot of these families lost loads of children.
• unfortunately the author was then very irritating, repeatedly, by calling leucine 'lucene'. Is it the ...Israeli spelling?? It was interesting though that a treatment for a kid who's breaking down all their protein stores and has overly high levels of amino acids is to give them 4000 calories a day IV to force their body to make protein.
• Interesting story of domino transplants with MSUD patients, or 'gene therapy by liver transplant' even though it doesn't really involve genes at all. You put a healthy liver from a cadaver into the MSUD patient, which gives them enough of the enzyme to get by, and then put the MSUD patient's liver into a man dying of liver cancer, who had enough of the enzyme in the rest of him to make it work. 
• Some kind of insane seizure disorder: 'the babies seemed to start seizing in utero and after birth continue to have thousands of seizures a day''
• This quote from a doctor treating these populations using genetic medicine: 'Gene therapy will be practised one patient at a time'. Which isn't great for efficiency but I guess makes sense since (nearly) everyone is different genetically.

• Has a long quote from some scientist saying cystic fibrosis and other diseases got high carrier frequencies, not from selective advantage for heterozygotes as I've heard in lectures. I'll hold the boat on that one.

• Selective abortion for disability
• apparently Russian women have on average over 2 abortions each in a lifetime
• Someone called having a deaf child 'such a burden', which wasn't very nice
• Wrongful birth lawsuits mean that doctor must pay parents of children with a defect that could've been caught in utero or pre-implantation So doctors can't intentionally give someone a child with achondroplasia, deafness, Downs even though some people want that e.g. as company for their kid with the same condition.

• Quotes from a visit to a genetic testing/ancestry company:
• 'DNA-testing equipment tends to fall into two categories: things that look like printers and things that look like toasters'
• 'You stopped that because it was kind of creepy?' I asked.   'No', Amy smiled, clearly confused. 'Because our craniometer broke.' (about the company having skull measurements of people).

• Genetics of behaviour: 
• scientists have domesticated wolves, foxes, minks, wild rats by breeding them to be friendlier
• if you put stranger rodents with the MAOA gene knocked out in a cage together, you'll be collecting dead bodies every day. They actively kill each other rather than just posturing in fights.

• Section on intelligence VERY annoying because of (a) Jewish supremacy (b) physicist supremacy
• She says of the common Ashkenazi Jew disease Gaucher's disease: 'Five of the patients were physicists' (out of 322 patients studied), to show that they're sooo intelligent
• Ashkenazi Jews apparently have the highest intelligence of any ethnic group measured. 3% of US population but 37% of winners of US national medal of science and 40% of American winners of nobel prize in science and economics. The disproportionateness bothers me.
• talks about the possibility of selection for intelligence explaining how frequent Jewish diseases are
• imagine writing a significant portion of a chapter on how smart and great your ethnic group is. Bit cringe. 

• Honestly a lot of what she said about Israel really annoyed me, probably because Israel is bad and should not be praised
• Interesting bit about how the victims can do the dangerous thing, which I guess is in the same sort of way that the affected group can reclaim a word but the oppressing group can't: 'The German woman felt she had no right to move into the post-Nazi era. We, being Jewish, could use the privilege of historical victimhood to make that decision for ourselves. So Israel would lead the world in the science and application of medical genetics.' [grammar paraphrased]
• The closeness of Nazi eugenics to contemporary genetics: many racial hygienists went on to second careers as human geneticists, and twin studies to test heritability are now going on for many taboo subjects such as propensity to violence, crime and alcoholism, likelihood of getting diseases, and Jewish intelligence

• She had a ton of material on Jews, I know she's a Jew herself but it seemed a bit excessive. Some of it was interesting though.
• Jewish tradition forbids epileptics from marrying in case it's passed on (without knowing the genetics)
• Dor Yeshorim tests for Ashkenazi Jew diseases (common ones in that population); people are tested as adolescents and then call Dor Yeshorim with two ID numbers. If they are both a carrier for the same recessive disease, they'll be given genetic counselling over the phone, otherwise they'll be told they're a match. It's for organising arranged marriages.
• Ashkenazis have a very high carrier frequency of recessively inherited diseases e.g. 1/27 are carriers of Tay sachs. Some of the major diseases are enzyme deficiencies (e.g. Tay Sachs is deficiency of hexosaminidase A), often lipid storage diseases.
• There was a bunch of stuff on the history of Jews and on finding the ancestors of the Cohenim. 

• Nazi & Soviet approaches to genetics 
• in the Soviet Union genetics was banned, former geneticists were working as housekeepers and street cleaners
• one woman had worked as a preschool teacher until she was outed as a geneticist and fired
• Nazi Germany actually didn't allow sterilising heterozygote carriers of diseases apparently, which is I guess better than I thought they'd been
• Genetics globally is now big on making sure decisions are made by the patient and that genetic counselling is non-directive.

• Unnecessary descriptions of people and their appearances, which to be fair is unfortunately common to a lot of popsci writers

• Preimplantation sex selection - 
• There was a rabbi who was a Cohen, and Cohens get a special place in the synagogue. He was infertile so they wanted to get a sperm donor, but a son from the donor wouldn't have really been a Cohen (can only be passed down biologically) so they couldn't legitimately take part in the ceremonies and he'd have to either live a lie or tell people he was infertile, which he didn't want to do. So they did preimplantation sex selection for a girl to avoid the problem.
• Now (in Israel?) they're allowed do preimplantation sex selection if they already have four or more children of the same sex. rabbi cohen so go for a girl with the donated sperm. allowed choose if youve already have 4 of the same sex
• She says people have always wanted to control the sex of their child and something like 'now that we finally have the technology to, we ban it?' Yes Masha, yes we do. 

• Spare parts babies born to be a donor for their older sibling. Molly had Fanconi's anaemia, so Adam was made for her, he donated umbilical stem cells to her when she was 6. The Reproductive Genetics Institute defend this by saying well it can take years to find a suitable donor and by that time the child might be dead, or there'll be side effects coz it won't be an exact match. This is a 100% match.  

• Huntington's disease - talked about the experience of seeing a parent have it and learning you have the gene for it so will almost certainly get it and go through the same horrors as they did, both physical and mental. The waiting game sounds awful, and I can see why some people don't get tested.

Book Review: Pandora's DNA by Lizzie Stark

2 stars: Very little science, and not as much research or interviews with major players as I would've liked.

Pandora's DNA is the story of Lizzie Stark's family history of breast and ovarian cancer, her BRCA mutation and the decision of what to do about it: risk dying young like her female relatives did, undergo intense surveillance for the foreseeable future, or take preventative action like a double mastectomy.

If I'd known it was just that, I probably wouldn't have read it; I'm sure lots of people would enjoy it but I'm not really interested in a personal history. The subtitle claimed it would also be about the science of the BRCA mutations, and I think I saw a Goodreads review saying the book had too much science content for them, and that's why I read it, because I like popular science books with a very high science content.

Instead there was a lot about her female relatives' experience of breast cancer, mastectomies and dying young, talk of family reunions, etc., which I just wasn't interested in. Obviously it's a fine and important topic to talk about, but I went in expecting a science book so it was jarring and unfulfilling from that perspective.

She did have some parts that interested me, and I think she did at least avoid some common genetics faux pas by saying it's a mutation in the gene that's the problem, not having the BRCA gene itself, and I think she even clarified that there are multiple possible mutations that could cause the effect. It was quite interesting learning about how researchers used Mormon and Catholic families (in Utah and Ireland respectively, I think) to track down the genes because they have large families and, at least for Mormons, good genealogical record-keeping so they could track who in a family was affected by breast or ovarian cancer (the prevalence of which can be greatly increased by having a BRCA mutation).

But even in the more sciencey parts there were problems. Mainly I just didn't feel like she was necessarily the best person to write this book. Yes, she had personal experience of the issue, but in my opinion a hallmark of good non-fiction of this sort is having interview access to major players in the event so you can get insight into it that people couldn't get just by Googling/doing a bunch of archival research (which is also important! But if the people are alive you might as well just talk to them). For example, there was a section I was looking forward to about the company Myriad Genetics trying to patent the BRCA gene and the whole debate about whether or not it's fair to patent a gene (or a test for a form of that gene). I thought she might talk to people on each side of the issue, maybe an exec from Myriad or one of their lawyers, but she just said things that seemed quite Google-able and talked to one person who didn't seem super involved in it and thus didn't have a ton of information. I might be misremembering the details slightly but it did seem lacking there and disappointing in its lack of detail.

The book was quite anticlimactic as well; she gets the double mastectomy partway through, then just spends ages wondering whether to get her ovaries removed but I'm not sure if she ever decides.

Overall, quite disappointing.

Book Review: the Philadelphia Chromosome by Jessica Wapner

3 stars: interesting topic and history but science too dumbed-down

Disclaimer: Unfortunately I'm just catching up on all these reviews after exams, so it's been months since I finished the books.

The Philadelphia Chromosome by Jessica Wapner chronicles the discovery of Gleevec, the drug that's turned Chronic Myelogenous Leukemia from a fatal to a chronic condition people live with for decades. 

The first part is about the biology of cancer and Chronic Myelogenous Leukemia specifically. There are some interesting parts, like the discovery of the translocation between chromosomes 9 and 22 that created the fusion oncoprotein BCR-ABL, and how this was seen in the microscope and the protein was discovered using immunoprecipitation. She also talked about the study of cancer-causing viruses like the Rous Sarcoma Virus and how these gave researchers a clue that cancer was a genetic disease. I did like learning a bit about the history, about how the researchers did it, but unfortunately it did feel very dumbed down in terms of the actual science. 

When she talked about the central oncoprotein that's the distinguishing feature of CML, she definitely dumbed it down which was annoying since I've covered them in college. Now maybe I'm not the target audience but it was still very frustrating to see the tyrosine kinase described as 'powering up' a protein [or whatever her exact words were] when what it does, adds a phosphate group to a tyrosine residue, isn't actually that complicated, especially if you use diagrams. I understand why she did it like that but I'm just reviewing it in terms of my own experience reading it. If you're less interested in the biochemistry e.g. if you're reading it as a patient or family member of one, as many people do, then it might work for you.

In the next part, Wapner talked more about the process of discovering Gleevec and the various scientists who spearheaded it, especially Brian Druker. Druker was originally a doctor and apparently got sick of not being able to help his patients, so became a scientist to find a treatment. There was a lot of talk about other scientists and their various movements between labs that I've forgotten but basically it amounted to finding a drug that would combat the overactive BCR-ABL fusion protein (tyrosine kinase) in test tubes, and then bringing that to market via a pharma company. It was a long journey, from getting something that worked in a test tube to trying out different formulations of it, figuring out how to industrially produce it, figuring out how to make it digestible so it could be taken orally, and doing toxicity testing on various animals after doing them on human cells in a test tube. The drug showed some liver toxicity in dogs(?) and there was a huge amount of pushback from the pharma company, partly because CML is quite a rare disease so it mightn't be super profitable, but eventually it got through and into clinical trials. 

Once it was finally in clinical trials, people were (pretty much literally) dying to get into them. They were testing the new drug against a competitor (IIRC) and Gleevec worked so well that they ended up switching everyone onto Gleevec because it was cruel to let people continue on a clearly inferior drug. The drug also had a good safety profile and people could take it up to quite high doses. 

When the drug went to market it was a huge success story; CML used to be a (slow) death sentence most of the time, but now people live normally with it and just take a pill, some derivative of Gleevec the tyrosine kinase inhibitor, every day.

CML was an interesting case because it's usually caused by the chromosomal translocation that creates the BCR-ABL fusion protein, resulting in an increased number of white blood cells until the person eventually goes into a painful 'blast crisis' and dies. Previously a major treatment for it was interferon, which gave the person symptoms of flu for as long as they were taking it and basically made their lives hellish with lots of physical flu symptoms and depression and fatigue. It also stopped working eventually and the person would progress to blast crisis. So Gleevec was pretty great. People want a 'Gleevec for every cancer' but unfortunately that won't be so easy because CML is special in having that very specific, targetable fusion protein which means it can be killed without harming normal cells. It was definitely a boost to looking at cancer as a genetic disease and figuring out how to treat it from there, though.

Review: March 2018

COLLEGE: By this point in the semester I was doing two new modules, Ecosystems & Global Change and Infection & Immunity, and continuing with Stats. Infection & Immunity was the module I decided to switch into Biology to do but I actually ended up not liking Immunology or stuff about antibiotics at all really, and I was pretty sick of Microbiology. I did however like the last week of Infection & Immunity, which was about genetics.

I actually found Eco quite interesting, even though the first half was heavily plant-based; before I'd only seen plants taught via 'here's their anatomy here's how they reproduce' whereas now it was all just ''here are the challenges plants face in this environment (biome) and here are the strategies they have evolved to get around it' so it was a lot more logical. We did it biome by biome, including desert, chaparral, tropical rainforest and other types of tropical forest, temperate forest, boreal forest, tundra and peatlands, and finished with a lecture on climate change. The second half of the course was marine ecology, which I didn't find quite as interesting as it was more like geography with bits on how lakes and estuaries form rather than a pure adaptations-based approach, but still not bad. 

I was also continuing Stats, which sadly had not lived up to its promise and involved a lot of derivations on the board and homework assignments involving things that had been too long or tricky to do on the board during the lecture, which is surely the opposite of how it should be. I did like Markov chains when we did them, though, and the little bit we had on algorithms wasn't bad. 


STUDY: I was properly doing my study/extra reading at this point, following this Excel spreadsheet (yellow means I completed it and the date is when it was done; it broke down right before exams but I was still doing a lot of the stuff, just on a different schedule and somewhat differently) and writing notes/learning each book chapter or doing Maths problems.















JOB HUNT: I knew I'd be working with Aoife doing research at this point so I was just applying for funding. During March I applied for the Laidlaw Scholarship which is a research funding and leadership programme over two years.

MODERATORSHIP CHOICES: Moderatorship choices were due on the 13th of April so March held many moderatorships holding information sessions to convince us to sign up for them. The Molecular Medicine one held by the School of Biochemistry and Immunology was good, and the students there spoke highly of it; unfortunately, so did the Genetics one (although none of their students were there because they'd all been given the afternoon off to go protest in Take Back Trinity!). Aoife also set me up with a Genetics student and we talked about the workload and lots of other things.

The actual decision was in April so I'll leave that discussion for the April Review.

TAKE BACK TRINITY: Speaking of TBT, that was a big protest students held in response to the Provost announcing that supplemental exam fees were increasing from nothing to 450 euro. The protests were amazing. There were some online ones, like students mass-one-starring Trinity's tourist attractions (which it relies on), and then it got physical, with students blockading the Book of Kells and then starting an occupation of the Dining Hall. Trinity reacted to that very badly from a PR perspective and apparently told students that if they left the Dining Hall they wouldn't be allowed in, refused them access to bathrooms and wouldn't let people drop food in, and said if they moved to certain areas in the building armed guards would come. In support, other students then occupied Front Arch and the Exam Hall. There's probably more to it that I'm forgetting but anyway it was great, I'm so proud of all the protestors, and they won! The Provost eventually dropped the fees entirely. They were also fighting for other demands like fee confidence for international students who were having their fees raised year on year during their degree. 

CHEMISTRY BROAD CURRICULUM: I talked about this in the February post but technically the final and me receiving glues as a reward (???) happened in March.

LEON'S BIRTHDAY & SNOW: Leon turned 21! And there was snow! So we went out frolicking in it for a while, which was really nice.

NETSOC AGM

Netsoc, Trinity's Internet Society, had its AGM and I ran for Events Officer and got it! I was quite nervous but after I made my speech one of the two people running against me dropped out saying something like 'OK I'm convinced' so that was a nice confidence boost. Here's a picture of the new committee with our Easter Eggs. Also, Leon got Auditor! (which is Trinity's word for Chairperson). 

PHYSOC AGM


Physoc also had its AGM and I was outgoing Secretary so I gave my lil speech about what you need to do and also generally heckled. One nicely dramatic moment was when there was a tie for I think Treasurer (which we knew because our auditor ran in and snatched the constitution off me) and then suddenly I discovered that I was still holding my vote, it hadn't been collected. So I knew I was the deciding vote. 

I hadn't actually intended to run for committee again but I ended up getting Honorary Contrarian which is just a position voted on by the outgoing committee to keep someone on outgoing committee on to heckle and/or generally help out.

READING: 

In March, I read The Way of Kings part 1 by Brandon Sanderson (which was brilliant, even though I usually don't like fantasy) after much campaigning by Leon, The Philadelphia Chromosome by Jessica Wapner, which is about the chromosomal abnormality that usually causes Chronic Myelogenous Leukemia and the process of developing Gleevec to treat it as well as cancer genetics more generally (though much less technical than I would've preferred), and Pandora's DNA by Lizzie Stark, which is about living with BRCA mutations and having a familial history of breast cancer and the decision of whether or not to get a preventative double mastectomy (sadly didn't have much genetics and was mostly just her talking about her personal experiences, which wasn't really what I signed up for; even in the parts I expected to be interesting, like about the company trying to patent the BRCA gene, she didn't have access to any major players in it so it just didn't seem super professional or like she was best placed to write it). 

Review: February 2018

Very long time no see but here I am since exams are finally over, to record what little I can remember of the past few months. 

COLLEGE: In February I had 4 modules going on: Genetics, Microbiology, Behaviour and Statistics. I really liked some parts of Genetics and wasn't as interested in others, didn't like Microbiology at all, found Behaviour OK but sometimes boring, and loved the idea of Statistics but definitely did not like the way it was taught as our questions weren't answered and the lectures and homeworks were very theoretical whereas the exam was quite practical and seemed very different to the lecture material. Anyway, I'll have a post up on each module in a bit.

STUDY: I was doing a bit of study for the exams by this point and made an Excel spreadsheet with my plan to do a chapter of extra reading from some textbook each night up to exams (I ended up sticking to it quite well). Unfortunately because of Schols and getting straight back into studying I never really got a break and was quite burnt out and unhappy through second semester.  

Cool things today:

1. Pretty snow ❄ ❄ ❄
2. Went to library and took out:
- my old fave Lehninger 💖💖💖
- Lodish Molecular Cell Biology 😊😍❕😁☺️😊 pic.twitter.com/DhY2pq0OX7

— Elle Loughran (@frizzyroselle) February 27, 2018

SUMMER JOB: I was really trying to sort out my summer job by this point. Ideally I wanted to do research but I at least needed to get something because y'know, I gotta eat and have accommodation. I reapplied to work where I worked last summer, and made a long list of pharma companies to ring to apply to. I also emailed Trinity Careers service asking them to put me in touch with one nearby company that only interacts with students through their Careers service, but they were unhelpful and just said Trinity doesn't do that. Another email was to the Senior Tutor asking what to do since some jobs wanted a letter from my college tutor but my one said she doesn't write recommendation letters, her job is just to get me through college, and didn't get a reply. 

BUT things ended up great on the summer job front overall -- I'd been put in touch with Prof. Aoife McLysaght, a very awesome genetics professor in Trinity, by Dr. Shane Bergin who I know from conferences and things, back in November, and we'd arranged to meet in February. I was super scared of the meeting as I thought it'd be typical businessy interview questions like 'talk about a time you solved a problem' or 'tell me why I should hire you' which I find really difficult and nervewracking, but it was brilliant! I just went in and we sat on couches and talked about biology! Apparently it was impressive that I'd 'read and understood' her papers, I kinda thought that was the bare minimum but yeah it was great and we just had a really fun conversation talking about biology so I wasn't even nervous, and then she said she'd be happy to have me! She also got me an exemption to be allowed do genetics without the prerequisites just because she thought it'd suit me!

Towards the end of the month I applied for funding for it from the Wellcome Trust with Aoife's help. 

CODING: I worked on my programming skills by doing a course in R on DataCamp. Did you know R uses <- instead of = as the assignment operator? Weird. I'm certainly not fluent in R but I did learn enough to use it to check bits of my Stats homework for the rest of the semester (because R is a stats language). 

CHEMISTRY BROAD CURRICULUM: That bloody group project continued into March (imagine a 14-person group project that lasts 6 months) with the presentations. Our team, which was doing the Chemistry of Solar Panels, made it through the semi-finals (which were actually very good, I was really impressed by everyone's presentations, they were genuinely interesting even though I heavily dislike Chemistry) and into the finals, where unfortunately we didn't place (there were some significant technical issues and other things at the start). Surprisingly I did win one of the Best Speaker prizes and also got a goodie bag for being Secretary. The goodie bag contained, oddly, several types of glue: superglue, Pritt Stick, sellotape...

READING: I finished reading Behave, the tome on all the (neurological, evolutionary, psychological, cultural..) reasons for human behaviour by Robert Sapolsky, and What Makes Biology Unique by Ernst Mayr. 

SNOWSTORM: Towards the end of the month and into March, Storm Emma and the Beast from the East arrived and we got a Red Weather Warning and had to stay inside as the whole country went into lockdown from 4 pm! It was very exciting and also very pretty seeing the blizzards from the comfort of inside.

Here's a photo of our balcony and the ground below covered in snow. The shape there is an empty Quality Street box we left out there that got filled to the brim with snow and was icy for ages afterwards.