Wednesday, May 29, 2013

“That’s Nice, Sweetie”


I’m sure I’m not the only one who has experienced this: I give my parents an update on how my projects are progressing in the lab, and they just nod and reply, “That’s nice, sweetie.” This essentially means, “Good for you but I really don’t know what you’re talking about, and it would take too long to try to understand.” No problem, I totally get it; scientific research by nature is very esoteric and uses a completely different language. All of us scientists know that what we are researching is extremely important and will one day improve society by discovering the laws of nature, saving lives by curing a disease, saving the world by protecting the environment, etc. (to put it mildly). And it only bothers some of us that non-scientists don’t understand why what we are researching is important.

But it does bother me to hear “That’s nice, sweetie,” and that should have been my first clue. The reality is that many other professions face this same conundrum: I have a lot of computer programming friends, but I have absolutely no idea what they do – something about coding and C++, but that’s about it. The difference is that my programming friends are well-aware of the fact that I wouldn’t understand what they do on a daily basis because I am not a programmer. More importantly, I’m not supposed to understand what they do – that’s why they have these jobs and I don’t, so there’s no need for me to worry because they know what they’re doing. Still more importantly, it really doesn’t bother any of them that I don’t understand what their jobs entail. And this is the major difference – why was I getting so frustrated knowing that others didn’t fully appreciate the advancements I was making in my field? Why did I need to have this validation? Was this really just my problem or was it their problem?

Then I decided to try something new and talk to non-scientists about other people’s research instead of mine. I interviewed other scientists and wrote articles about their recently published work and the progress they are making in their labs to help address disease diagnosis and other health-related issues. For some reason, this worked out so much better! Scientists and non-scientists alike commended me on my writing skills and specifically enjoyed reading about the research I was highlighting. “Why couldn’t you write something like this about your own research?” my parents asked. (Sigh.)

The lesson I learned is to continue to be passionate to get people to understand science research, but just try talking about someone else’s research so it’s not so personal. You know that you have spent hours slaving away in the lab, and you know the other researchers did, too, but it’s still more removed. And the other researchers will really appreciate that you took the time to highlight their work! We’re all in the same boat, so if nothing else, we can pay it forward and help out our fellow scientists.

If you’ve experienced the same burden of not being able to accept the fact that others do not understand the importance of scientific research – don’t worry, just go with it. Make this problem into a solution – turn it into something useful! You just need to find the right topic to write or talk about and the right audience. There’s no reason this could not turn into a career, either. There are many great forums, such as “Science Caf├ęs,” for recruiting an audience and discussing important research with them. I’m also a member of a group on campus that organizes a series of talks at the public library to discuss current hot-topic science issues, so that the local community can better understand what the actual problems and solutions are for these issues (and ultimately be appropriately informed on these issues when deciding how to vote). We are discussing everything from hydrofracking to personalized genome sequencing, and there is always a large audience that is very enthusiastic and receptive to the talks!

So if you ever hear “That’s nice, sweetie” after describing your research, don’t get frustrated – just think, “Challenge accepted.”

Tuesday, February 12, 2013

Why It Doesn’t Help to Discuss “Why Women Still Can’t Have It All”

I must begin by saying that I have never had a “real job,” other than summer internships or other similar short-lived experiences during my time as an undergraduate and now graduate student. Being stuck in the infamous bubble of the “Ivory Tower” has undoubtedly kept me sheltered from the “real world.” However, I feel that I can still comment on the topic of women in the workplace, specifically women in academia. A few months ago, a study was published (http://www.pnas.org/content/early/2012/09/14/1211286109) showing the results of a social experiment: when professors were sent identical applications for a laboratory manager position in their lab (the only difference being that half the professors received an application where the individual was male, and the other half received an application where the individual was female), it was shown that the professors (both male and female) were more likely to hire the male applicant and pay him more, even though the female applicant had the exact same qualifications. This paper has gotten much publicity because it was the first study to truly conduct a controlled social experiment where the only variable was gender, and the outcome was that there is evident gender bias in academia.

After “Science faculty’s subtle gender biases favor male studentswas published, I had the privilege of attending a panel discussion about the results of this study.  The lead author of the paper, Corinne Moss-Racusin, mentioned that she was surprised that there was so much criticism because many others have also published that there is gender bias in academia; this is certainly not a new concept, especially in the sciences, which is traditionally a male-dominated field. Additionally, Moss-Racusin said that now that we know this gender bias exists, it’s time that we do something about it, and that this discussion about what to do must include both genders in order to move forward. I couldn’t agree more.

There were some men in the audience (although some of the comments they made were confusing or not that helpful), but at least it wasn’t a situation in which we are just preaching to the choir. As an aside, I compared this scenario to another situation in which I attended a forum about careers outside of academia for women PhDs, which featured a few women panelists. I remember noticing that there was one guy present, and I thought, “You know what, good for him; he attended the discussion because he wanted to hear what these panelists have to say because they are smart, successful individuals who would have a lot of great advice.” (The same was not true, however, of the freshmen writing seminar I took in undergrad about women’s literature; there was one male student in our discussion group, but he didn’t last; he switched to another class after the first session. But hey, at least he signed up and went to one session.)

I think every woman knows that there is still gender bias, even if she has not experienced it herself, and there will probably always be some gender bias. Don’t get me wrong, though; I’m happy that I didn’t grow up in the 1950s, and women’s rights are certainly a very severe issue in a number of other countries compared to the US. Still, we should always strive for what we believe in, and we have the right to do so. It’s time to move forward and have the discussions that we really need to be having: gender bias exists, so what are we going to do about it?  

Anne-Marie Slaughter’s article in “The Atlantic,” titled “Why Women Still Can’t Have it All,” (http://www.theatlantic.com/magazine/archive/2012/07/why-women-still-cant-have-it-all/309020/)  has also gained much publicity/notoriety. Her article addressed the ever-present dilemma of having to choose between raising a family and having a productive career. Again, my life will never be as busy as hers has been, and I probably have not experienced anything in the “real world” compared to what she has gone through, but I feel that even the title of this article isn’t helping us move forward as a society. It’s not helpful to say that women can’t have it all, especially if you are a woman. Furthermore, it’s really not helpful to discuss whether or not women can have it all. If we want to be equal, then we have to just say that we are equal. Discussing whether or not women can have it all indicates that we are not equal to men because men would never have this type of discussion; a man would never bother to write this type of article about his gender. I’m guessing it’s also less likely for a man to say in a thank-you speech for a prestigious award that he couldn’t have gotten to where he is today without the support of his spouse, but a successful woman almost always has to say that the reason (or at least part of the reason) for her success is because her spouse was so supportive and helpful. If you want to thank your spouse, please do so, but otherwise let’s just be proud of our accomplishments, man or woman.

Slaughter is being considered to be the next President of Princeton, which is another hot topic; if she wants the job, then she will become very busy again, but I’ve gotten over my frustrations with her article and decided to say good for her; she is very talented, and I’m sure she will find a way to handle it, if that’s what she wants. Same with Hillary Clinton running for President; I couldn’t think of a better woman for the job, and it would be amazing if she does want to do it. However, we all heard about her fainting, and she has said in many interviews that she is looking forward to just relaxing and spending time with her family after finishing her term as Secretary of State, so if that’s what she wants to do, then good for her, too. (This is still more interesting than discussing Michelle Obama’s bangs. I love Michelle Obama; she is an amazing role model and has so much to offer to our country that talking about her bangs is insulting to her intelligence.)

Monday, December 17, 2012

Should Human Genes Be Patented?


Recently, there has been much controversy regarding whether it is legal for human genes to be patented; although genes have been patented in the past (~20% of all human genes have been patented over the past 30 years), the case regarding the patenting of BRCA1 and BRCA2 genes by Myriad Genetics has resulted in a landmark opportunity for the Supreme Court to rule on whether any patent on any human gene is legal. The Yale Student Science Diplomats discussed this case, now known as Association of Molecular Pathology (AMP) v. U.S. Patent and Trademark Office (USPTO), and its potential implications with Prof. Daniel Kevles of the History Department and the Law School. The discussion was titled, “Human Genes and Human Rights.”

During the discussion, Prof. Kevles provided the Diplomats with a detailed history of gene patenting, as well as the specifics of the case against BRCA1/2. These genes have been linked to hereditary breast and ovarian cancer, in which up to 8% of women with breast or ovarian cancer have mutations in BRCA1/2. The story began in 1990 when Mary Claire King located the BRCA1 gene on chromosome 17. A race quickly ensued to discover the exact location of the gene, which Myriad Genetics won in 1994 and again in 1995 for BRCA2. Myriad applied for 7 patents for these 2 genes in 1997 and 1998 and received them in 2001. Just a few weeks ago, the Supreme Court accepted claims against these patents for review. However, the legal history of this case dates back to 2009, when the American Civil Liberties Union (ACLU) and the Public Patent Foundation filed a brief against the USPTO and Myriad Genetics. This was the ACLU’s first patent case, and it drew enormous interest by various groups: the plaintiffs were the patients, physicians and medical researchers who claimed to be disadvantaged by these patents, and the defendants were biotech and trade associations who claimed that the patents were necessary to stimulate progress in biomedical research.

It is important to note that Myriad does not hold patents on the naturally occurring gene in the body, as only a product that is “markedly different” from a product of nature can be patented, as previously ruled in 1911 by patenting adrenaline in its crystallized form isolated from the body, as well as patenting a genetically-modified bacterium in 1980. Rather, Myriad’s BRCA1/2 patents are for (1) the isolated DNA of the genes, (2) fragments for the genes to be used as probes for sequence identity, and (3) a diagnostic test for comparing an individual’s genetic sequence with known mutations/variants associated with breast and ovarian cancer, in which the holder of the gene patent receives a royalty for each administered test. These patents provide Myriad with the right to exclude all others from using their “invention;” only Myriad can conduct the BRCA1/2 diagnostic test and disclose the results of the test to a patient. Because of this monopoly, Myriad charges $3500 for the diagnostic test, which some health insurances will not cover. Furthermore, a patient cannot ask for a second opinion because Myriad claims that their diagnostic test is the “gold standard,” and clinicians and researchers cannot develop new diagnostic tests or even evaluate the accuracy of Myriad’s test.

For these reasons, the ACLU claimed standing to suit based on the technicalities of the test, as well as a violation of human rights. Regarding the diagnostic test itself, Article 35 Section 101 of the Constitution states that a patent can be awarded for a new and useful machine or manufacturing process or an improvement on such a process, or a new composition of matter. Myriad claims that their patent on the isolated DNA is in fact a new composition of matter because the ends of DNA are altered slightly upon extraction. However, the counterargument is that this actually does not matter because the base pair identities are still the same in the isolated form, and this base pair information is what is important for the diagnostic test. Regarding the case against human rights, the ACLU claims that holding a monopoly on this diagnostic test is denying patients of fundamental information and violates the 1st Amendment. Furthermore, the patent restricts progress in conducting research on these genes.

In March 2010, Judge Richard Sweet ruled in favor of the plaintiff because he claimed that there was no actual process involved in the diagnostic test; rather, it was simply a “mental act” of comparing an individual’s BRCA1/2 sequence with other DNA sequences known to be associated with breast and ovarian cancer. Therefore, the patent is not for a new composition of matter and is thus illegal. Myriad appealed this ruling, and in 2011 three judges from the Court of Appeals for the Federal Circuit (CAFC) ruled again: they also said that the diagnostics test was not patentable; however, they ruled against Sweet  2 to 1 on the patentability of a new composition of matter, and thus this aspect of the patent was upheld. The ACLU then appealed to the Supreme Court in early 2012; at the time, the Supreme Court did not look at the case but instead asked the three judges to reconsider their ruling based on another recent case, Mayo v. Prometheus, which disallowed a patent on the process of administering a drug and measuring changes in a metabolite afterwards; this case concluded that anything that retards the progress of science cannot be patented.

Prof. Kevles explained to the Diplomats the importance of understanding the background of the two judges from the CAFC who ruled against Judge Sweet and the one judge who upheld Sweet’s ruling. Prof. Kevles said that the first judge who ruled against Sweet, Judge Alan Lourie, is a former chemist (I’ve never heard of a scientist turned judge, so this was interesting for me to hear!). This judge determined that the “expansive issues” (i.e. the human rights issues) should be excluded from consideration, and that the patentability of DNA should be treated like any other chemical molecule. The second judge, Judge Kimberly Moore, is a former electrical engineer (!) and also said that the isolated DNA was patentable because it has such an obvious use for the biotech industry. Lastly, the third judge, Judge William Bryson, who upheld Sweet’s ruling, used to work in the Department of Justice and stressed the importance of the human rights issues associated with the case, as well as the restriction of the progress of science.

Now that the Supreme Court has agreed to examine this case, how should they rule? The main issue is whether isolated DNA is considered a new composition of matter and can be patented. The patent prevents anyone besides Myriad Genetics from making, using or selling information concerning the isolated DNA of the BRCA1/2 genes and any mutations, variations or rearrangements of this DNA.  There are many stakeholders in this case: on the one hand, competition in the biotech industry can be strengthened with the security that research findings can be patented (and more competition should fuel better research); on the other hand, patients do not have proper ownership over their own medical information, and other medical researchers who may be studying BRCA1/2 may be forced to halt their research due to issues with violating Myriad’s patents.

Prof. Kevles explained that this case boils down to property rights vs. human rights, and that these patents have so far only benefitted the biotech industry and are not for the greater good of cancer research and diagnosis.  He explained that this case has much more at stake than a patent for a new pharmaceutical because you can always develop another drug; however, DNA by nature is “unsubstitutable” and you cannot “invent around it.”  It is also interesting to note that Myriad has had difficulties obtaining patents in Europe, as EU law states that a patent cannot be awarded if it is “contrary to public order and morality.” Prof. Kevles also mentioned that many biotech companies have ownership over other genes, but these companies issue licenses for others to research these genes and have not experienced the same problem that Myriad is now faced with. However, I would be curious to know if these genes are simply “less interesting” or “less controversial” than Myriad’s BRCA1/2. Or, is it truly just as profitable to accrue licensing fees than to have a patent monopoly on a gene?

It is also worth noting that whole genome sequencing technology is actually cheaper (and the price keeps decreasing) than Myriad’s diagnostic test (although sequencing used to cost more before this patent battle started), so any trained scientist could hypothetically  sequence BRCA1/2 (and every other gene) in an individual’s DNA and compare this to the published sequences readily available online. However, the problem is that only Myriad Genetics knows what the appropriate disease variants of these sequences are (without other researchers confirming that the research on these variants is scientifically sound). The nature of scientific research is to have a transparent, peer-reviewed evaluation of your research, and the patents get in the way of this entire process and destroy the foundation of how research is conducted and validated.  Scientific research, especially critical research on cancer diagnostics, is for the betterment of society as a whole, and no company or other entity should have a monopoly on this process. In addition, the civil rights arguments of this case are extremely relevant and should not be ignored; in today’s society, there should be no question regarding whether a patient should have the right to all of his/her medical information using the best diagnostic tools available.

Still, it seems that there needs to be some kind of decision that will not allow for a similar case to be brought to the Supreme Court in the future. As Prof. Kevles said, Myriad does not want these patents just to be “evil;” they have a reason for doing so that they feel is valid. Every biotech company has the right to make a profit from their research, and patents may seem like a secure way to protect their investments for 20 years. However, this case has become so notorious because the genes in question have been linked to breast and ovarian cancer (I’m sure this would not be an issue if Myriad was studying plant genes, for example). I believe that the Supreme Court should decide that different rules need to apply in these situations where human health is at risk, and thus genes that can be used as cancer diagnostic tools should not be patented; this is the only way to allow for progress of scientific research and progress within our society as a whole. However, along with this ruling comes another Pandora’s Box regarding healthcare and insurance coverage for the information associated with an individual’s personal genetic sequence.

This landmark case will be addressed in June 2013, so stay tuned for the Supreme Court’s ruling!

Thursday, September 20, 2012

What am I researching in the lab?

As a PhD student working in a lab, I am studying "microRNA function during aging in Caenorhabditis elegans". But what does any of that mean?? Let's break it down:

microRNA = 
-type of gene that is found in humans and also found in many other animals we study in the lab, as well as plants
-these genes are non-coding RNAs because they do not follow the "central dogma" of molecular biology, which is that DNA makes RNA makes protein. Instead, these genes make RNA, but then the RNA never codes for a protein. Instead, this RNA, which is short in length and why it is specifically called microRNA, binds to other coding RNAs and causes degradation of these RNAs and/or prevents these RNAs from coding protein. 
-as molecular biologists have thought for a long time that RNA is only an "intermediary" and has no functional role, the discovery of these microRNAs with a regulatory function was very exciting and opened up a whole new field of research. Humans have over 1000 microRNAs, so there is a lot to study regarding in which cells/tissues the microRNAs are expressed and which coding RNAs they target!

aging = 
-the biological process for how living things "get old"
-many different types of genes are involved in controlling aging, including microRNAs, which shows that aging is a programmed process and not just a random occurrence
-I am interested in studying microRNAs and aging to learn how we can promote healthy aging by preserving youthful genetic features

Caenorhabditis elegans = C. elegans = 
-the model organism I am using to study the process of aging, as it is much too difficult to study human aging because we live for so many years!
-C. elegans is a simple animal, called a nematode or roundworm. It only lives for 2-3 weeks, which makes it very easy to study aging of C. elegans in the lab and conduct many experiments
-C. elegans also has microRNAs (~150), many of which have homologous sequences to human microRNAs, so I am interested in studying how these microRNAs affect C. elegans aging: in which tissues and when are the microRNAs expressed? what happens to the worm's lifespan when you get rid of the microRNA? 

So, I can learn about how C. elegans microRNAs affect its aging processes and extrapolate how the microRNAs may work in humans! To conduct actual human studies, scientists have set up longitudinal aging studies to follow study participants over many years; a small blood sample that you would provide at a routine doctor's visit could also be used to look at the function of all of your genes at the time the blood sample was taken using various lab technologies. 

The dilemma of federal funding for science research

Recently I attended Capitol Hill Day, which is organized twice a year by the Coalition for the Life Sciences, an alliance of several organizations focused on science policy. I encourage all scientists (grad students, postdocs, professors) to participate in this event! During Capitol Hill Day, our group of scientists met with staff members of various senators and representatives to discuss the importance of long-term, sustainable federal funding of biomedical research. The National Institutes of Health (NIH) and the National Science Foundation (NSF) are primarily responsible for funding research at universities, but there is a threat that this funding will be reduced significantly in the next fiscal year. In a dire economy, it is difficult to make decisions about what takes precedence in terms of receiving funding from the government; however, we scientists urged Congress to understand that the situation is already very bad, and we fear that if funds are cut even further, this will result in a complete standstill of science research across the country.

The NIH and NSF fund grants for science research at institutions nationwide; without these grants, it would be impossible for a laboratory group to continue to conduct research. New professors are especially desperate for these grants; the lack of funding is part of the reason why it has been shown that only a meager 5% of science PhDs end up becoming tenured professors. In this new age of technological advancements, there are many new sophisticated techniques that scientists can use to conduct their research in a thorough and comprehensive manner; however, these technologies can be very expensive, and most laboratories will require multiple federal grants to cover the costs. We should not deny scientists the opportunity to conduct the best research possible, as the biomedical discoveries being made in labs across the country directly affect the well-being of us all, now and in the future. For example, I am studying the genetics of aging, i.e. factors - separate from your surrounding environment - that are already "encoded" within you that determine how long you may live. As the American population continues to live longer, it is becoming increasingly critical to understand the process of how aging actually occurs, so that we can work towards developing therapies for promoting healthy aging in all individuals.

I will admit that some scientists are better than others in terms of explaining to the general public the importance and relevance of their research, which I feel is a real misfortune because the research of biomedical scientists is directly related to improving the quality of life of the general public! This disconnect could be responsible for the stereotype of scientists as elitist or unapproachable (which is of course not true), and improving communication between scientists and the general public (and especially those responsible for funding research) could alleviate any confusion and increase awareness regarding the importance of our research.

Besides funding new or continued research grant proposals, the NIH and NSF also provide funding to institutions for training grants for PhD students. I was surprised to learn that most of the people I met with on Capitol Hill did not realize that training new science PhDs is one of the critical uses of federal funding! I have witnessed a generation of young, intelligent individuals committed to conducting science research and helping our country be a leader in biomedical discoveries; we have received federal support along this journey, of which we are extremely thankful. However, the problem we now face is that our government needs to follow up on its investments - all of these new PhDs who wish to continue conducting research and start their own labs cannot do so because of the lack of funding for new research grants. I personally feel that all this potential in current and future generations of scientists is quickly fading away.

Another example of how federal funding is used is developing science education outreach programs. Scientists including myself have volunteered with an outreach program called Family Science Nights, which is an after-school program where scientists set up demo lab experiments that elementary and middle school students can do; parents are also encouraged to work with their children to do the demos, as well. These programs promote scientific curiosity, learning how to apply the scientific method, and doing hands-on experiments to get both students and parents interested and excited about science. The Family Science Nights also encourage students to design their own science fair project by the end of the school year and participate in the city-wide Science Fair. These science outreach programs are critical because we as lab scientists have access to materials and equipment that are simply not available in the average public school because they are too costly. Additionally, the volunteers can be mentors and role models for the students, acting as real-life examples of what you could become if you study and enjoy doing science. I believe there should be many more relationships developing between public schools and university scientists across the country. Nationwide, students are performing very poorly in science compared to other subjects. According to the College Readiness Benchmarks set by the standard-test makers, ACT, only 30% of high school graduates met the "benchmark" of being likely to pass a first-year college course in science without remedial classwork. It is clear that we need to act now to improve science education, starting with younger children and continuing through high school.

Lastly, I will mention that without these grants from the NIH and NSF, we will not only lose future generations of science PhDs, witness many university labs shutting down and ceasing research, and dissolve any outreach programs in the schools, but the future of that city's local economy will also be disrupted on a large scale. Every science lab indirectly employs many other workers, including marketing, production and distribution of all the products and equipment we use in the lab, other start-up companies founded on research done in the lab, etc. Scientists do, in fact, have a large contribution to the economy.

      Overall, I had a very positive impression of my meetings with the congressmen's staff; we engaged in fruitful discussions about where scientists stand regarding the importance of federal funding of science research, and where the government stands regarding how to allocate said funding. It seems that there are still many decisions left to be made before the budget for the next fiscal year is complete, so I remain cautiously optimistic that funding for biomedical research will be maintained at the highest level possible.

During the Capitol Hill Day that I attended, there were about 20 graduate students, postdocs and professors representing states from all over the country; I enjoyed meeting all these scientists with a similar interest in advocating for sustainable federal funding for biomedical research. We all had our own personal stories to explain to the congressmen's staff exactly how this funding is so critical for the work we do on a daily basis, as well as how our research directly impacts the economy. There was also a staff member from the Coalition for the Life Sciences present at all of these meetings to help us get our points across. For example, one of the main goals for this Capitol Hill Day was to ask Congress to protect the NIH and NSF from sequestration, which will go into effect January 1 unless a vote is made beforehand. This would result in a 22% cut for the NIH and 29% cut for the NSF over 9 years, which would have an unrecoverable effect on each of our labs in particular and on the biomedical enterprise as a whole. Additionally, we stressed to Congress that the increase in federal funding for biomedical research has not been above inflation since 2003, so we have already witnessed the impacts of constricted funding. We had the opportunity to meet with congressmen's staff from our state as well as from a few neighboring states; although there was limited time to get our points across, I really enjoyed my discussions with the staff members, who all seemed to be very receptive to our cause and interested to hear our personal accounts. It was very clear to me, though, that without the Coalition for the Life Sciences organizing and facilitating all of these meetings, it would have been extremely difficult for me to actually have these discussions.

Scientists today need to include advocacy as part of their job description; we all need to spend more time being involved with programs like Capitol Hill Day or being grassroot advocates for the Coalition for the Life Sciences, where we can make our voices heard and ensure that the funding for our research will still be here for years to come. During Capitol Hill Day, I had the pleasure of listening to a briefing by Dr. Siddartha Mukherjee, who presented a historical perspective of how cancer research has changed over the years, which is also described in his book, "Emperor of All Maladies". At the conclusion of his talk, Dr. Mukherjee stressed to the audience the importance of funding for research to help address issues like the costs of personalized therapies, developing better clinical trials, and training young scientists. He made it clear that all of the research he was describing, as well as any future prospects of continued biomedical research, would not have been possible without scientists advocating for NIH and NSF funding. Following in Dr. Mukherjee's footsteps, I have invited one of the senators from my state to come visit our university's laboratories and see the research we are conducting; I hope this can be an example of how to solidify a relationship between scientists and Congress now and in the future.



Friday, July 20, 2012

Worms in space: Spaceflight slows aging of the model organism C. elegans

I study genetics of aging in the nematode worm Caenorhabditis elegans. C. elegans is a simple animal model organism that has been studied in the lab for a few decades. The adult roundworm is about 1mm long and consists of about 1000 cells. Conveniently, the fate of every cell division from fertilization until the worm reaches adulthood (which takes about 3 days) has been mapped out by scientists, so that we know exactly how every cell division occurs in order for the worm to develop into an organism of multiple tissues and specialized cell types. Additionally, scientists have also sequenced the entire C. elegans genome, so we can study any gene with any particular function of interest. These two key features, along with many other lab techniques that have been well-established when studying worms, make C. elegans an attractive animal model system. Scientists may utilize C. elegans to study neurobiology, development, stem cell biology, etc. I utilize C. elegans as a model for studying aging because many genes important for regulating aging process (such as genes in hormonal pathways, genes involved in nutrient uptake, and genes expressed in the mitochondria) are conserved from C. elegans to humans. Additionally, C. elegans adult worms only live for 2-3 weeks, so I can easily conduct multiple experiments over the entire lifespan of a worm in a short amount of time.
              While perusing through recent scientific articles about C. elegans aging, I came across an article by Yoko Honda and colleagues, entitled “Genes down-regulated in spaceflight are involved in the control of longevity in Caenorhabditis elegans” (Scientific Reports 2: 487, 2012). Here is the article link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390002/pdf/srep00487.pdfThe title immediately caught my attention, not just because I am interested in genes that regulate longevity in C. elegans, but mostly because these scientists studied longevity of C. elegans in space! Their research is literally out of this world! (Sorry for the cheesy pun.)  Oftentimes a space exploration will also carry some lab specimens along for the ride, so that we can learn more about how spaceflight impacts living things. Honda and colleagues claim that studying the impact of spaceflight on C. elegans aging is important because soon humans will be spending more time in space as we explore other planets or colonize the moon. These statements are a bit far-fetched because our daily lives will not resemble an episode of “Futurama” any time soon; however, we can argue that studying the effect of spaceflight on aging is intriguing from a physics standpoint; remember learning about Albert Einstein’s theory that if you travel into space and come back to Earth, you will be much younger than you were supposed to be? This is part of the theory of relativity: the faster you travel through space, the slower you will travel through time.
             By using C. elegans as a model system, Honda and colleagues have shown that this is actually true – worms do slow down the natural process of aging when they are in space! The researchers were able to make this claim based on a few findings from their research. They utilized data from the International C. elegans Experiment First Project, in which they compared data from “space-flown” vs. “ground control worms” over a 16-day period, where the worms were either on ground for 16 days or were or ground for 5 days and then space-flown for 11 days.
In the first experiment, the scientists looked at the accumulation of protein aggregates consisting of 35-glutamine repeats. It was previously shown that these aggregates accumulate with increasing age in the worm; in fact, these are the same type of aggregates that accumulate in the brain of patients with polyglutamine diseases like Huntington’s Disease. The researchers tagged these aggregates with a fluorescent protein in order to easily count the number of aggregates under the microscope by looking at the amount of fluorescence. They saw that spaceflight reduced the accumulation of these polyglutamine aggregates, in which worms of the same age that were space-flown had fewer aggregates than worms that were not space-flown. As accumulation of these aggregates is a biomarker for aging, this means that the space-flown worms were aging more slowly!
           The second experiment which showed that spaceflight slows down worm aging was conducted by using a DNA microarray, which is a technique to measure changes in gene expression between two different conditions. (This is where the sequenced genome of C. elegans comes in handy because the DNA microarray allows you to look at many, many genes at once.) For this experiment, scientists compared gene expression between space-flown vs. ground control worms. There were many genes that were either up- or down-regulated compared between the two different environmental conditions. However, Honda and colleagues analyzed this data and noticed that seven genes important for neuronal and endocrine signaling were down-regulated in the space-flown worms compared to the ground control worms. By applying certain lab techniques to worms that were not space-flown, the researchers saw that inactivation of these same seven genes resulted in increased longevity of the worms. Therefore, when these genes are not functioning, the worms live longer, which means that these genes antagonize longevity. Since the space-flown worms had much lower expression levels of these genes, this indicates that the space-flown worms were aging more slowly than their ground control counterparts. The researchers went on to demonstrate that, for three of these seven genes, there is less accumulation of polyglutamine aggregates when the genes are inactivated, further indicating that these genes antagonize longevity when functioning normally.
Honda and colleagues concluded from these experiments that C. elegans worms age more slowly due to a neuronal and endocrine response to cues from their space-flight environment, as compared to worms that are aging and are not space-flown. By utilizing this model organism, the researchers demonstrated through a few experiments that biological aging is, in fact, affected by space flight, just as Albert Einstein had predicted.

Monday, May 7, 2012

Comment on "Science PhD Career Preferences: Levels, Changes, and Advisor Encouragement"

Recently an article was published by Saeurmann and Roach in PLoS ONE, entitled, "Science PhD Career Preferences: Levels, Changes, and Advisor Encouragement." Here's the link to their article:

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036307

This article examined how many PhD students in the sciences become less enthused over the course of their PhDs about staying in academia after graduate school. It seems that there are more and more PhD students who want to pursue "alternative careers," like working in industry or government instead of doing academic research.

As a biology PhD student, I agree with the authors that there should be additional "mechanisms" to prepare PhD students for pursuing these alternative careers that can complement the advice given by a thesis advisor to stay in academia. However, I would also like to point out that not all professors assume that PhD students will also want to become professors, and that academic researchers can also be knowledgeable about alternative careers outside of the "university ivory tower," such as if they start a biotech company or the like.

Additionally, I do not think it is necessarily "bad" that PhD students are exploring careers in different settings outside of academia; I think that we acquire many skills during our graduate education that would be extremely useful for working in government, industry, law, publishing, or other kinds of careers. What needs to change is how PhD students can identify these essential skills that can be transferred outside of the laboratory, and how these skills can be properly marketed.

For example, here is a list of some of the major skills any PhD student will have acquired by the end of his/her graduate education, which could be a great skill set for many different types of careers:

1. Teaching courses at the undergraduate, graduate, or other levels (like mentoring a younger student): developing assessments, grading assessments, organizing lesson plans, lecturing, leading discussions, etc.
2. Writing and revising manuscripts and designing figures for publication in peer-reviewed journals: primary research (summarizing your new contributions to the field) or reviews (summarizing everyone's research and the history, current status, and future directions of the field).
3. Presenting data in a variety of different settings: group meetings, departmental meetings, PhD committee meetings, traveling to small or large conferences - each presentation needs to be tailored for these different types of audiences.
4. Applying for grants or fellowships: this also involves tailoring your research description and plans for future research depending on the types of funding that are available.
5. In addition to presenting and writing about their work, graduate students also spend a great deal of time critiquing and examining others' work, either in their field of study or in a completely different field; it's extremely important to be knowledgeable and the most up-to-date in a particular topic, as well as to be wary of any competitors.
6. Working in a laboratory on a daily basis involves creating an independent schedule, planning ahead by the hour, day, week, or month (each type of experiment may require a different length of time), analyzing data, interpreting data, envisioning possible outcomes or potential explanations for unexpected outcomes, and constantly re-organizing your schedule to adjust for these outcomes.
7. Time management for dealing with 1-6 above, all of which is usually done on a daily basis.