January 13, 2014

Getting my Pharmacia LKB Multidrive XL online... now with 3D printing!

Quite a while back, I bought a used Pharmacia LKB Multidrive XL on eBay. It's a gel electrohphoresis power supply that can output up to 3500 volts at several hundred milliamps.
There was a problem, though: Whenever I tried to use it, it just gave me the error "Invalid connector". The unit didn't come with a manual, so I was stumped as to what exactly this error meant.
Searching for the manual online didn't yield anything besides a few old forum posts with broken links. The manufacturer, Pharmacia, had since been bought be Amersham, which in turn had been bought by GE Healthcare. It seemed like a long shot, but I rang up the GE Healthcare customer support and asked for the manual. They were amazingly helpful and sent me a PDF.
Armed with the manual, I learned that the error I was getting was connected to one of the many safety precautions that were built into the device.
First off, the unit has four power outlets. All four need to be plugged in with something, either a power cord or a dummy connector - otherwise, the unit won't output anything. 
I eventually came across the three dummies that came with the device while moving. I thought that might fix the problem, but the device still gave me the same error.
Reading the manual further revealed that the device's safety measures include what the manual calls coded sleeves - specific pieces of plastic that are slid over the dummies and power plugs. In a dummy, they don't do much except be there, but for the power cord, they code for the voltage which the cord is rated for - 500V, 1000V, and 3500V, respectively.
And it turned out that this coded sleeve was missing for the power cord.

So in a leasurely Sunday afternoon session, mltn and I set about reproducing the missing sleeve. mltn attacked one of the sleeves with a slide ruler and rebuilt it in openSCAD. We then printed the thing on an Ultimaker at the Raumfahrtagentur, and - lo and behold - it fit and worked on the first try.

Rendering of the model for the generic coded sleeve. To accommodate the limitations of our 3D printer, all four legs of the sleeve as well as a bridge to hold them up (cylinder on the very right) were included; the bridge and the two middle legs were then snipped away after printing.

Well, almost. Since the recognition of the sleeves employs light sensors, and there happened to be transparent filament in the Ultimaker when we printed, we had to paint the printed sleeve with a black marker.
I hooked up a multimeter to the Multidrive and confirmed that it was really putting out the set voltage. Which is particularly satisfying as a search for replacement parts for this unit yielded - unsurprisingly - nothing.
We only made the lowest, 500V version of the coded sleeve since I was unsure what the cable and connector that came with the unit had been rated for, but it's nevertheless satisfying to turn a non-operational device into a pretty nifty gel electrophoresis power supply with a bit of 3D printing.

Granted, it would have been possible to make this work with a few well cut-out pieces of cardboard or acrylic, but somehow, making an actual sleeve seemed a little more robust.

Anyway, here's the quick-and-dirty OpenSCAD code for the sleeve:
difference () {
 hull() {
translate([14,0,0]) cylinder(r=7.5, h=31);
 hull() {
translate([14,0,0]) cylinder(r=7, h=31);

translate([7,-8.5,8]) rotate(270, [1,0,0]) cylinder(r=1, h=5, $fn=100);
translate([7,-8.5,27.5]) rotate(270, [1,0,0]) cylinder(r=1, h=5, $fn=100);
difference () {
translate([21,-0.6,0]) cube([10.5,1.1,33.5]);
  hull() {
translate([23,-0.7,6.25]) rotate(270, [1,0,0]) cylinder(r=1.75, h=1.2, $fn=100); 
translate([24,-0.6,4.5]) cube([8,1.2,3.5]);
 hull() {
translate([23,-0.7,13.85]) rotate(270, [1,0,0]) cylinder(r=1.75, h=1.2, $fn=100); 
translate([24,-0.6,12.1]) cube([8,1.2,3.5]);

 hull() {
translate([23,-0.7,21.75]) rotate(270, [1,0,0]) cylinder(r=1.75, h=1.2, $fn=100); 
translate([24,-0.6,20]) cube([8,1.5,3.5]);

 hull() {
translate([24,-0.6,28]) cube([8,1.2,6]);

minkowski() {
 translate([19,-0.6,31.5])rotate(270, [1,0,0]) 
    cylinder(r=0.5, h=0.6, $fn=100);
     cube([3,0.5,3]); }
translate([32,0,0]) cylinder(r=1, h=28);

January 5, 2013

Yet another overly ambitious Todo list

2012 has passed (and I have to say, thank Eris it did), and 2013 is upon us. Say what you will about arbitrary counter resets and new year's resolutions; the start of a new year is a convenient time to reflect, to look back, and to look forward. Another motivation for this reflection is that I just completed my diploma thesis at long last; so naturally, there's the question of: What next?

And so I thought I'd record here what I'd like to do in 2013 - at a minimum, I may be able to go back to this post in a year's time and compare my goals then and now, and to get a sense of what I thought I might be able to accomplish in one year vs what I actually did accomplish. So here goes, in no particular order.
  • Go snowboarding. Not a given, seeing as I live in a place where both mountains and snow are scarce to non-existent.
  • Visit some of the European biohacking groups. High on my list are BiologiGaragen in Copenhagen, La Paillasse in Paris, brmlab in Prague, London Hackspace, MadLab in Manchester, and Cathal's lab in Cork.
  • Explore Amazon's EC2.
  • Push the Berlin biohacking efforts forward.
  • Get back into the habit of going swimming regularly. Because swimming is awesome.
  • Visit old friends who are scattered across the globe.
  • Explore the European arctic further.
  • Explore the science-y potential of the Stattgarten urban gardening project. That includes breeding, instrumenting, botanical drawing, microscopy, and more.
  • More microscopy.
  • Reading, lots of it.
  • Convert my recently acquired apartment from a place where I keep my boxes of stuff into a place that feels like home.
  • Get the University of Reading's self-cloning experiments kit and work with it.
  • Explore the possibilities of genetic manipulation without a BSL1 license.
  • Implement and test the transilluminator concepts that have been living in my drawer for way too long.
  • Try Sanger sequencing.
  • Try commercial sequencing.
  • Learn more about metagenomics to a point where I can carry out a small metagenomics project.
  • Collaborate with some of my favourite people on some interesting projects.
  • Collaborate more in general.
  • Implement and test the lab-in-a-backpack concept that has been living in my drawer for way too long.
  • Moar bioinformatics.
  • Draw and paint.

November 29, 2012

A tale of three cities

(Disclaimer: This post is about a toilet door. Yes. You read correctly. A toilet door that has come to mean a lot of things.)

Once upon a time, there was a group of people who had spent all their lives in a kingdom where women were considered commodities and things of value only if they pleased the eye. Believing that every human being should be regarded as such, they were frustrated with this, and so they decided to go out into the world and find a more accepting place. They came upon a fork in the road that led into three different directions; they decided to split up and promised to send each other word on what they found on the end of each road.

Each group came upon a magnificent city at the end of its respective road, full of technology and science and art and wonder, where strangeness and new perspectives and possibilities of being seemed to be around every corner. However, those three cities were not all the same; and the respective groups soon came to experience very different things in them.

All three of the groups were initially full of wonder, but the group that had stumbled upon the city of Primo soon found monuments in the city that depicted scenes they knew all too well from the place they had fled: scenes where women were depicted as things to be looked at and used, even to their visible discomfort. The group went to the city elders and expressed their discomfort at these monuments, and how it reminded them of the place they had just fled. The elders convened, and ruled that these monuments had been there before the newcomers had arrived, and that they were works of art that were not to be disturbed, that they were a part of the city's tradition, and that the newcomers should just learn to ignore them - even more, that the newcomers had come to this town as strangers, and if they wanted to be citizens, they had better learn to adapt. The group, which was made up of the more polite and shy people from the original trek, submitted to this ruling, and did as they were told - they tried to adapt so they wouldn't risk being expelled from this city of technology and science and art and wonder. But inwardly, they withdrew a little, and even though they still savoured the promises of the city, they never really felt like they were at home anymore; they kept to themselves more, and felt reluctant to contribute to all the exciting things that were going on in the city.

The second group, the one that found the city of Secundo, also found the same kinds of monuments in that city. Like the first group, they went to the elders, and like the first group, they received the same response. Only this group was made up of the more rebellious people, who felt they had taken enough shit in their lives, and that they hadn't set out for a better place, only to find one that made their hearts beat fast with joy, and then discover that it endorsed the same kind of crap as the place they had come from. This group stuck their heads together, and they decided to rebel. In a dark and stormy night, they snuck out, and they remade the monuments into something that wouldn't remind them of the place they had just left. When the monuments' defacement was discovered, there was an almighty shitstorm that left everyone involved covered in hostility and brown, smelly goo. If you, esteemed reader, want to find out what eventually happened to the city's inhabitants new and old, I advise you to check Twitter.

The third group found a city named Tertio at the end of their road. Like the other two cities, it was a marvellous place. But again, like the other two cities, it contained monuments like the ones in Primo and Secundo. And the third group, like the ones in Primo and Secundo, went to the city elders. Only in this city, the elders listened to the concerns of the newcomers. They recognized that newcomers to their city meant an enrichment, and that it was important that they, too, feel at home, so that they would contribute to the city's culture and help it thrive. The elders did not really understand what made the newcomers' group so upset about the monuments, but saw that if it was a big deal for them, then it was worth examining whether these monuments were really important enough to jeopardise the newcomers' company and potential. The elders came to the decision that the monuments were not worth that; they ruled that the citizens and the newcomers should sit down together and come up with new and more inclusive replacements for these old monuments. The ensuing meeting was long and fraught with frustration on both sides, but eventually, the old citizens and the newcomers discovered that there were other, equally beautiful monuments that would represent everyone's dreams. So they got to work and made the city an even more wondrous place. And everyone lived happily ever after, or something.

November 15, 2012

Life after the diploma thesis, or: my case against a PhD

I'm 34 pages into my diploma thesis (target is around 100 pages, including everything), and the deadline for handing it in is Decembre 28th. Time to think about life after the thesis.

I've been toying with the idea of going for a PhD, since I really, really want to do science. And if you want to do science, getting a PhD is the way to go, right?

But after mulling this over for quite a while, I've almost arrived at the conclusion that, no, for me, a PhD is not the right way to go. I'd like to lay out my reasoning and my plan here; who knows, maybe I'll get some useful input before making a final decision? Or maybe I'll make my decision anyway, and leave this as input to others who are in a similar situation.

One of the points that came up when talking about the issue with my parents was: making a living. Really. Me and my three siblings were raised by a single dad at the low-income end of the spectrum. Much as my older siblings, I started earning my livelihood when I was 17. I know that if I fail financially, my parents and grandparents would give anything to help me out, but they just don't have the resources themselves. Seeing as I've been working fairly successfully as a software developer and security consultant for the past 12 years, it would be foolish bordering on irresponsible to throw this away for an uncertain academic career by disappearing into the depths of a PhD programme. I hardly need to mention that software technology as well as IT security are fast-paced fields - if I decide to drop out for three years, I can't really expect to get back in afterwards.

Another point has to do with the above-mentioned work experience. I've been used to working as a freelancer, on my own terms; I've seen quite a bit of The Industry(tm). Meaning: I've seen too much to accept subordination easily. I've actually had squabbles about this with my thesis advisor, who nagged me about "taking my future seriously", all while I was juggling the responsibilities I had signed up for to pay rent and other unpleasantries (literally; we're talking contracts and penalties and fines here) and my thesis work which is taking place in an ivory tower. This makes me think that I wouldn't take kindly to the slightest hint of being used as a scientific wage slave. I pretty much know that every time my PhD advisor would be nagging me about this paper of theirs they want me to contribute to, I'd be thinking "You know, I made the decision to do this PhD at quite a monetary expense; don't you dare act like it's a privilege to do your work." So, whether these thoughts would be misguided or not, I'm guessing conflict would be pre-programmed.

Then there's the thing that from all I know, doing a PhD is a specialization exercise. Go deeper. But I don't want to go deeper, I want to go broader. This seems to be what makes me enthusiastic and happy and what makes me do good work: going broad. I don't really see how that fits in with what's expected of a PhD student.

So, taking all this into account, I've all but settled for going for an alternative. I'll try to make my own PhD. I'll try and see whether I can't do science on my own terms. There's a vague plan there that might me a combination of "transitioning to bioinformatics as a service" and "independent scientist". The idea is extremely vague, but I have a very roughly sketched plan. We'll see how it pans out.

November 2, 2012

Addition: Questions around personal genomics - sharing vs. privacy

There was something bugging me while writing my last post on some issues with personal genomics, because I seemed to remember I had another point that I wanted to bring up. Now it came back to me. The point was about the technicalities of sharing genomic data.

Now, the last post was mostly me bitching about the current mode of personal genomics, 23andme and all, and how I don't think it's a good idea to hand over your genomics data to some US-based company with very clearly stated commercial interests. (Just to summarize on that: Having commercial interests is not a bad thing in itself in my book, but I'm a bit of a tough sell if you want me to share my data for what seems like mostly your commercial interest, and doubly so if these data are not exclusively mine to disclose.)

But there is another point worth discussing around the topic of personal genomics which is a little more forward-pointing, maybe. Let's say we agree that personal genomics are here to stay. Let's say that getting your genome, or portions thereof, sequenced becomes part of  diagnostic routine, or even part of your routine medical examinations. That is, your genomic data or parts thereof become part of your medical record. How do we handle that?

As far as I can tell, there has been a certain separation of competences and sharing of data on a need-to-know basis even among your doctors. Professional discretion or not, it's fairly unnecessary in all but some freaky, borderline sci-fi cases, to share your cardiologist's findings with your dentist. And I think that's a good set of walls right there.

Now, with all these genome-wide association studies, lots of potential markers for all kinds of medical conditions and predispositions for behaviours showing up, I wonder whether we can come up with a scheme that empowers a person to share some, but not all of their genomic data with whomever they choose. Some results from a SNP genotyping may be relevant to a dentist. Some may be relevant to a gynecologist, such as a genetic predisposition for breast cancer, but others you may feel uncomfortable sharing with anyone but the persons you've elected to be trustworthy on certain subjects - say, markers that are associated with predisposition to addictions, or clear indications for Huntington's disease. At this point, I have to disclose, again, that my background is in computer security, and in this field, I've come to appreciate the concept of Defense-in-Depth. One of the things this concept teaches you is to only grant access on a need-to-have basis, and having grown up in a privacy-conscious environment, I think this is a good operating principle.

So, for me, the question is, how do we enable people to partially share their genomic information on a need-to-know basis? How do we implement this technologically, and how do we implement this UI-wise? I think that answering this questions is worthy of the engineer's attention, because a success at solving this problem means that we don't have to choose between privacy and the benefit of data sharing - that we may get to have both, with the individual having the power to make an informed and enforceable choice between these two extremes.
This may also have quite an impact on crowd-sourcing genomics projects that rely on people sharing data - they may benefit from individuals who are confident that they can make an informed and enforced choice concerning the disclosure of their genomic data.

Any ideas on how to achieve this are welcome, but I have a hunch that the much-condemned digital rights management (DRM) technology may actually see a use-case that is in the service of the informed individual, rather than being a servant to commercial interests.

If you have any suggestions regarding this, drop me a line/comment.

October 13, 2012

Some issues with direct-to-consumer personal genomics

There are a few issues on the personal genomics boo-hah that I've been meaning to write down, so, time for a brain dump. Context: The cost of sequencing DNA is dropping, fast, companies like 23andme have been offering direct-to-consumer SNP genotyping at affordable prices for quite a while now, and they even recently started offering exome sequencing for around 1000 dollars.

(Explaining the lingo: a SNP is a single nucleotide polymorphism - a single base in the genome where at least 1% of the population under study have a different "letter" than the rest. The exome is the set of all exons in the genome; very roughly speaking, it's the subset of the genome that codes for proteins and functional RNA. That doesn't mean the rest of the genome is junk, but the exome is a handy, sufficiently interesting subset that can already be sequenced at relatively low cost.)

And now, to the issues I mentioned. For me, the two major ones are "Analysis and interpretation" and "Information content and privacy".

Analysis and interpretation

One thing that irks me is this: at this point in time, with our current understanding of all things biological, personal genomics is little more than a geeky (although admittedly shiny) toy. Marketing it as anything more is just plain dishonest. Yes, there are some things genotyping and genome sequencing can tell us, but for a healthy individual, these are few and far between, to say the least. Do you smell snake-oil?
Apart from this problem of our still limited understanding, extracting information from sequencing data still requires a lot of work, with a little bit of voodoo on top of it. And I mean, a lot of work - expensive work, that needs to be carried out by skilled analysts.

On top of that, of course, there's the thing that a person's genomic information is only a small part of the picture. Methylation patterns, somatic mutations in a subset of an organism's cells, gene expression levels in response to stimuli or in dependence of the cell and tissue type, translation rates, protein-protein interactions, involvement of the immune system, or the gut microbiome are just examples for other parts that play a role in determining an organisms biological state. To borrow a metaphor from another field: If you're trying to reverse engineer a heterogenous distributed computer system, and you start out by dumping the firmware of one component - that would be the equivalent of exome sequencing. It's a part of the picture, for sure, but it's only a small first step towards understanding the entire system. Just something to keep in mind.

Information Content and Privacy

Another issue, and one that has kept me away from services like 23andme: Information content and privacy. I find it unnecessary to rehash the obvious privacy implications here, I just want to draw attention to two things:

Number one, 23andme in particular is an American company, that is under American jurisdiction. I'm sure you all remember some of the cases in the recent past where law enforcement agencies have approached Web 2.0 services with requests to hand over the personal data of individuals under investigation (off the top of my head, I recall cases involving Twitter, but I'm sure there are more). The SNP genotyping data that 23andme keeps in their databases is more than sufficient to match it against a biological sample and possibly get an ID this way.

(Additional note: DNA Forensics for law enforcement currently does not use SNPs for identification, but STRs. The reason for this is, um, legacy. The databases that have been built up over the last decades are based on STRs, and moving to a different marker system - one based on SNPs, for example - would mean a lot of cost and effort. However, that doesn't mean a law enforcement agency cannot also get their labs to do SNP genotying on a sample if this seems useful.)

Number two, which is the more important one in my decision to stay away from 23andme: My genome also contains a load of information about my relatives. That means, if I decide to submit my genomic information for storage on the servers of a company, without being able to reliably tell how long this data is going to stay there and where it will eventually end up or what it will be used for in 50 years' time, then I also make this decision for my parents, my grandparents, my siblings, and their children - even the ones that aren't born yet. And I have come to the conclusion that I just don't have the right to make this decision for them.

October 6, 2012

Update: Biotinkering, laws and regulations

Benjamin commented on the post "DIYBio and biotinkering - Laws and regulations in Germany":

The legal issues are pretty simple actually - you just cannot do any genetic engineering (including bacterial transformation) in your garage. Simple as that. Sorry.
Since writing the original post, I've learned that this is not completely true. You can do some genetic engineering even without a BSL 1 license - namely, "self-cloning". The legal text is a bit mushy on the subject, but essentially, you can genetically engineer known-to-be-safe organisms if you use only sequences that are naturally found in this organism, or one that is "phylogenetically close", provided you don't release the result into the environment.

I've talked it over with the office that is responsible for granting BSL licenses, and they suggested it may be OK for a biotinkerer to, for example, modify E. coli K12 with elements found in E. coli. The University Reading offers a kit, "The Transformer Protocol", which implements just that. It's aimed at teachers, students, and other experimenters who don't have access to a BSL 1 lab but want to learn about the basic procedures of bacterial transformation. The fine people of MadLab in Manchester have actually used this kit in one of their workshops recently.

Conceivably, it would also be within the bounds of this "self-cloning" provision to rearrange (inducible) E. coli promoters and E. coli genes to get externally inducible expression of some gene of interest - not exactly ground-breaking science, but probably fun, and a good way to get one's feet wet.

I think it would also be possible here to rearrange/recombine traits of different, say, apple cultivars (provided, of course, that you know which genes are associated with these traits, but that's a different problem). I'd want to talk this over with said office before I actually try it, though - better safe than sorry.