On Genetic Testing

Not if Direct-to-Consumer Genetic Testing has a say!

A study was recently conducted on over 2000 people who had undergone genetic testing to see how the test had affected their lives. The researchers tried to find out if these people were they more nervous about their future due to the test, and if they were, then were they taking any measures to remain more 'healthy', . The point was to understand the effects of 'direct-to-consumer' genetic analysis kits (unsupervised by certified genetic counselors) on the people that took them. The researchers expected a change in the behavior of most of these people- perhaps their anxiety levels should have increased as a result of their tests?

Surprisingly, that wasn't the case at all. Most of the people who took the tests seemed just as 'happy' as they were before, and said that the test had not led to major changes in their daily habits.

This confused me as well. If you don't care about the results (which is what I gathered from this study), then why would you bother taking the test in the first place? Isn't the point of the test to find out if you could be the victim of a potentially life-threatening disease in the future? Surely you would make sure you try to stay as 'healthy' as possible to delay (if not prevent) the onset of the disease? I guess the fact that it's directly available to them at a low cost is one reason to go for it. But to spend time on the test and then shrug it off with a simple 'meh' is also unheard of, at least by me. But what goes through a person's mind before they decide to take this test?

Before I read this study, I read an article on genetic testing earlier this quarter, called 'DNA as Destiny' by David Ewing Duncan, the link to which can be found here. This article is certainly not one of my favorite ones, because I think it has a very negative tone. However, after reading the article 'DNA as Destiny' was the first time I formed an opinion on what goes through a person's mind before they decide to take the test. To me Mr. Duncan sounded like a person who is extremely paranoid concerned about his future and I found his reactions to the littlest details about genetic testing quite hilarious interesting. But to be very honest, if I knew of someone who was taking this genetic test, then this is one of the two ways I would expect them to react (even if not to such an extreme extent).

The other reaction I would expect is for the test-taker to not do anything after they receive the results. By that I mean, 'live life to the fullest', without worrying about tomorrow, and over-indulging in things they enjoy, even if it physically harms them. After all, everyone will die one day or another, some will just know of their impending death wayyyyyyy in advance.

Having read this article, I'm thinking whether I'll ever take this test. Honestly, I don't know. After reading the 'DNA is Destiny' article, I decided against it. Even though my opinion hasn't changed in favor of genetic testing (I don't think I like it too much, especially when it's available for pretty much anyone and everyone to use), but now there's a part of me that's starting to think 'why not'? As for how I react if I find out that I will develop diabetes (I probably will- everyone in my mother's side of the family has it) or Alzheimer's or schizophrenia, I have absolutely no idea, nor any inclination to ponder over the subject any more than this.

Link to paper: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1011893

The Cure for Cancer

Yes, I love comics. Especially when they prove a point I'm trying to make, which phdcomics often do.

The last paper we studied this quarter in the RSP journal club was one about prostate cancer. Surprisingly enough, it was my turn to select a paper and this was the one I came up with. And prostate cancer and/or genomics isn't something Environmental Scientists normally deal with.

But I chose this paper because it made no sense to me when I first read it. Normally, I don't go into papers involving intense genetics, but for once it really bothered me that I couldn't understand this paper's contents. And my best chance of understanding this paper was through the RSP journal club, and that turned out to work fine.

So cancer and it's complexities is something that noone fully understands, as we had discussed last week (refer: comic posted above). Prostate cancer, in particular (which this paper studied) causes 32,000 deaths annually, and over 200,000 new prostate cancer cases are reported each year, and most of these patients die because of it. Therefore, understanding the genetics of prostate cancer is of vital importance. That is exactly what this study tried to do.

They conducted pair-end, massively parallel sequencing on the tumor and compared the DNA from the tumors of of seven patients with compared it with  'normal' DNA. Now, this method of sequencing, can safely be called the newest and most amazing technology in genetic analysis. It is computationally heavy, and comparatively much faster than 'regular' sequencing. It's almost like sequencing thousands of strands at the same time! And to process that amount of information is even harder than running the analysis. So it's no wonder that this study was the first whole genome sequencing analysis of prostate cancer.

And the researchers came up with interesting results. I was recently discovered that chromosomal rearrangements, particularly recurrent gene fusions occurs in prostate cancer cells, which led to the idea that other genomic rearrangements may also play a more important role in the development of prostate cancer.

And the researchers were right in believing so. Here's what they found:

• 3 tumors with rearrangements that led to the disruption of CADM2 (I'll be honest: I have no idea what the role of CADM2 is, but I'm working on trying to find that out. I'll update this post when I do!)
• 4 mutations that resulted in disruption of either PTEN, a prostate tumor suppressor, or MAGI2, which plays an important role in the formation of tight junctions (read previous post on cervical cancer)
• A median of 3866 somatic base mutations per tumor (that's a lot!), which is similar to those in breast cancer.

While we were discussing the paper, I remember someone suggesting that some of these mutations might be the effect, rather than the cause of prostate cancer, because there wasn't a distinct pattern in the mutations of these seven tumors. I think that's an interesting theory, and something for scientists to definitely think about over the next several years. If anything has been made clear because of this fantastic study, it's the fact that cancer is probably even more complex than we had imagined, which is certainly saying something!


 Link to paper: I don't have it! I'm sorry. But I'm still looking. Here it is: http://www.nature.com/nature/journal/v470/n7333/full/nature09744.html#/landscape-of-genomic-alterations

Also, take a look at this:

And this:

Calreticulin, CD47 and Cancer

Cancer is a subject that has always baffled me, and I'm sure I'm not the only one. We recently discussed a paper in the RSP Journal Club about how our immune system tried to fight cancer and it's one discussion I truly regret missing. Surprisingly enough, the paper made enough sense to me while I was going through it on my own, and in this post, I'll try to present to you the information I could make sense of (forgive me for not going into the details of the 'methods' section- I'll probably confuse myself if I even tried right now. In any case, the results take the cake this time!)

So this paper studied the effects of Calreticulin (CRT) and CD47 (Cluster of Differentiation-47) and in cancer cells. I vaguely remembered learning about CRT in high school, but had to googled its exact function for the purpose of understanding this paper. So CRT is a protein found in the endoplasmic reticulum (ER). It binds to distorted proteins and stops them from leaving the ER.

So what CRT does is sends a signal to the immune system, which helps the immune system detect and destroy foreign particles through a process known as 'phagocytosis', which is basically how a cell 'eats' (fun fact of the day: 'pinocytosis' is how a cell 'drinks', i.e. engulfs a liquid particle).

What this study discovered was that cancer cells, in fact, express CRT to a large extent, certainly more than normal cells do (these are called pro-phagocytic signal). In doing so, they're, in a way, sowing the seeds for their own destruction.

Why, then does our immune system not destroy cancer cells? What prevents these cancer cells from being 'eaten'?

The answer to that is a protein known as CD47, which gives anti-phagocytic signals to the immune system, counterbalancing the pro-phagocytic signals that the immune system receives from CRT. These signals are also produced by the cancer cells in large amounts, which helps the cancer cells serve their best interests.

So the next step in this study, I suppose, is to look for a way to block the expression of CD47. However, this is more complicated than it sounds, because CD47 expression must be blocked only in cancer cells, and CRT growth must also be regulated, to ensure that normal cells are not being destroyed by the immune system.

It seems strange to me that cancer cells would produce CRT, which could destroy them and then produce CD47 to counterbalance CD47 when their job would be made much easier by not producing the former at all. But then, if CRT wasn't produced by them, would our immune system have come up with a way to fight the cancer? I guess cancer research always raises as many questions as it answers.


Link to paper: I'm sorry, but only the abstract is available for free. Here's the link to that: http://stm.sciencemag.org/content/2/63/63ra94.abstract

Computer Science Problem? Biology has the Answer!

The last time I had a class on computers was in 7th Grade, and I wasn't very good at it. To be very honest, complicated computer-related things often confuse me (I did surprisingly well in my Geographic Information Systems- GIS- class. I'm definitely learning!).

A couple of weeks ago, in the Research Scholars Journal Club, we were discussing a paper about a computing problem known as 'Maximal Independent Set' or MIS. I was discussing it with a friend of mine a little while ago, who happens to be a software engineer, and we were discussing how this problem is almost like a game of chess (yes, I use lots of analogies to make sense of things I do not understand initially). Chess is all about looking ahead, and making your moves based on what you think the opponent might do, and then planning your next move accordingly and so on. Experts can sometimes look ahead upto several moves, but there's only so much you can predict. This computing problem is similar in the sense that there are a few 'leader nodes' and several 'non-leader nodes' in a local network, and they must interconnect in a way (almost like a spiderweb) such that no two leaders are connected and each non-leader is connected to at least one leader. The complication arises from the fact that there's so many leaders and non-leaders, that you can only tell who your neighbors are upto a certain degree, and without full confidence- if this were a game of chess, you would have to look ahead lots of moves, and even then you may or may not win. Thus, this computing problem is far more complicated than it sounds.

As it turns out, fruit flies have found a way to solve this problem that has baffled computer scientists for a long, long time. During neurological development in fruit flies, a number of bristles can be observed. Through a randomized selection process, some cells are chosen to be 'Sensory Organ Precursors' or SOPs (the 'leaders'), while others are not ('non-leaders'). The SOPs express a large amount of 'Delta' protein, and the surrounding cells had a protein called 'Notch' protein. The Delta protein, essentially, sends signals to its surrounding cells, which, with the help of Notch protein, can understand that there are SOPs in their vicinity. This message prevents them from becoming SOPs themselves, and so no two neighboring cells as SOPs.

That's a very good description of what I've been trying to say in last 2 paragraphs. It's taken directly from the paper.

So once again, biology saves the day, giving computer scientists another reason to rejoice!


Link to paper: http://www.sciencemag.org/content/331/6014/183.full

What Causes Cervical Cancer?

We recently read a paper published in the Journal of Virology that talks about a protein, the E6 a viral oncoprotein that has a PDZ binding motif, and is believed to be produced by strains of HPV (Human Papillomavirus) that causes cervical cancer (that's a lot of information in one sentence!). PDZ is the acronym for an exceptionally complicated term, with a relatively simple purpose: it holds together transmembrane proteins and the cytoskeleton (from what I can understand).

So the paper we studied the effects of the E6 protein in cervical cancer. Here's how that works:
The experiment tried to study the effects of E6 proteins on MAGI proteins, which are associated with the formation of tight junctions.  Tight junctions are basically one of the factors responsible for holding two cells together, and allowing them to communicate with each other. E6 disrupts the functions of MAGI proteins, which disrupts the fuction of tight junction. Because of this, cells can no longer tell whether they should divide or not (since they no longer know if there's a cell next to them), which leads to unregulated growth of cells.

The researchers started with infecting HeLa and CaSKI (2 kinds of cell lines) cells with HPV. They then knocked down E6 in some cells, and left the cells for a period of 72 hours, after which they came back to check the effects that the E6 had on the cells that still contained the oncoprotein.What they discovered was remarkable: the cell components (including MAGI-1) that had E6 bound to it were getting destroyed, whereas the ones without E6 were functioning normally.

This, in my opinion, is quite a significant discovery in cervical cancer research. Since we've managed to figure out one of the causes of the problem, we're one step closer to finding a solution for it. But science still has a long way to go before we figure out better treatment methods to cervical cancer.


Link to paper: http://jvi.asm.org/cgi/content/full/85/4/1757

How many ants does it take...

...to solve the Towers of Hanoi? About 501 or less.

This study was conducted on Argentinian ants by a group of scientists that were using natural systems as a "source of inspiration for computer algorithms designed to solve optimisation problems". Before explaining the results obtained, let's look at the methods that the scientists used.

Two sets of experiments were conducted: Group tests and individual tests.

Group tests: 30 colonies containing 1000 workers and 2 queens, and 30 colonies containing 500 woekers and 1 queen were starved for 3 days.

Half of each of the colonies were given access into a 'maze' which was 1 m long and consisted of 64 idential hexagons aligned in a rhomboid. These were the 'pre-exposure trials'. The next set of ants were made to enter the made from one end. A food source was placed at the other end of the maze, and the scientists tried to observe how long it took the ants to figure out the shortest, or the 'optimal' path to the food, which happened to be the one along the edges. The surprising bit? The correct path was one in over 30,000.

Individual tests: 100 ants were starved for 3 days, and the ants were was put into the maze one at a time. The total distance the ants had to travel did not exceed 42 cm. After 8 minutes in the maze, the ant was taken out, and another was placed on the opposite end of the maze, to ensure that the pheromones from the first ant did not affect the behavior of the next one. 15 ants were tested in this way.

The results showed that other than the smaller (500 workers) colony, 93.3% of the times, the ants  not only found the optimal path, but did so in less than one hour. When the shortest path was blocked, 90 to 93.3% of the colonies with exposure were able to find the next shortest path, and 73.3 to 78.6% of the colonies without pre-exposure achieved this! Individual ants, as it turned out, walked much faster than ants in groups.

This experiment made me think what would happen if the same experiment was conducted on humans. I recently saw an NPR video that talks about how humans can never walk in a straight line if they're not aided by the sun, or other fixed points. Here's the link to that:

Now, this study isn't the same as the one done on the Argentinian ants, but would humans be able to solve the Towers of Hanoi as efficiently as ants did, if they can hardly walk in straight lines? Without antennae on our heads, I'd say probably not.

"According to a new paper published in the journal Science, reporters are unable to thrive in an arsenic-rich environment."

Towards the end of 2010, headlines all over the world reported an astonishing discovery: NASA scientists had discovered a bacterium that “not only metabolizes the normally toxic element (arsenic), but also seems to incorporate it into its DNA and other molecules in place of phosphorus”. This news sparked an ongoing controversy in the scientific community.  The way this news was reported by the media insinuated that NASA scientists had found “alien life on [Earth].”  What if the reports were true and accurate? How does it matter to science, and what does it tell us?

The answer to that lies in basic biochemistry. It has been known for years that all forms of life depend on basically six elements: carbon, oxygen, hydrogen, nitrogen, phosphorus and sulfur. These elements make up most of the macromolecules found in living cells. According to evolutionary biologists, the fact that DNA and RNA are the genetic materials for all life forms is proof of the fact that all life on Earth stems from the same source. In other words, it has been suggested that any living form that utilizes something other than these six elements to sustain life did not have the same evolutionary origin as everything on Earth did.

Through their experiments, Felisa Wolfe-Simon, along with other scientists, conducted experiments on a strain of GFAJ-1 bacteria, isolated from Mono Lake, California. They found bacteria that grow in an arsenic rich environment, and hypothesized that these bacteria use arsenic in their metabolic pathways. To test this hypothesis, they cultured some of these bacteria in an even more arsenic rich and phosphorus deficient environment than that of Mono Lake, hoping to find interesting results. 

So what did really happen? It turns out that the researchers never did find bacteria that used arsenic in place of phosphorus in metabolic pathways under natural conditions. Instead, they cultured some, and forced the bacteria to grow in a medium which they weren't doing too well in (at least, not when compared to the one living in a phosphorus-rich environment). 

Another problem with the specific research methods was the way the DNA was extracted by the authors. They used Phenol/Chloroform to separate out the soluble portions of the cell, including DNA and RNA. They then 'scanned' the contents using Inductively Coupled Plasma Mass Spectrometry (ICPMS), and noticed the presence of arsenic. The conclusion that can be drawn from this experiment is that some of the soluble cell contents (which may or may not include DNA/RNA) contain arsenic. In order to prove the presence of arsenic in the DNA, further purification of the DNA must be done.

Scientists all over the world has concluded that this research plan was not 'perfect'. However, despite the harsh reviews that the authors of this paper have received in the recent past, I do think that further research should be carried out in this field. I disagree with those that think that this paper should not have been published: there's a good reason researchers conduct literature reviews on experiments that they're trying to conduct. If anything, this paper serves as a good example of what to do differently in case the arsenic content in these bacteria is ever studied again (which I'm sure it will be, given the publicity that this project has gained).

Link to paper: http://www.sciencemag.org/content/early/2010/12/01/science.1197258.short

Media Reports: http://www.sciencemag.org/content/330/6009/1302.full

http://www.nature.com/nature/journal/v468/n7325/full/468734a.html 

Fun Facts about Arsenic:  http://web.ebscohost.com/ehost/detail?hid=104&sid=e7ba62db-ca3b-44fb-96cc-0c542649476a%40sessionmgr114&vid=2&bdata=JnNpdGU9ZWhvc3QtbGl2ZQ%3d%3d#db=ulh&AN=9887515

[[Three people, two women and a man, stand looking at a laptop screen, which is sitting on a desk. The woman with a ponytail is pointing at the screen.]] Ponytail girl: Our arsenic-based DNA discovery is cool, but these reporters are expecting life on Titan! Our press conference will be such a letdown! [[Ponytail girl turns around to face the other girl.]] Ponytail: Okay, we need to make it more exciting for them. How do you make an event entertaining? Girl #2: Dunno, I suck at parties. Music, I guess? [[Ponytail girl turns back around and leans over to start typing on the computer, while the other two look on. The other girl puts her hand to her chin.]] Ponytail: WikiHow says you can "serve cocktails and hors d'oerves that fit the theme of your event." Girl #2: Easy enough! [[Ponytail girl stands at a podium on a stage, the man stands amongst the audience with a tray. All the audience members are either dead or dying, having fallen onto the floor or slumped over in their seats.]] {{Title text: According to a new paper published in the journal Science, reporters are unable to thrive in an arsenic-rich environment.}}