How not to die when working in the lab – Biosafety

What’s your biggest concern for your safety when walking into work each morning? That you’ll get a papercut or burn your tongue on your morning coffee? Maybe if you’re in a higher risk profession (like a contractor) you’re worried about something falling on your head.  As a scientist, may researcher enter the lab every day and have to worry about being infected by what they are researching!

blood tubes

Blood tubes collected for our biobank

Human tissue and blood may contain viruses like HIV or hepatitis that’s just needs entry into your body through a cut or in the mucus membranes of your nose. Or maybe you’re working with viruses like the flu to see how they infect cells. And what of those people who are studying the deadliest diseases like Ebola – how do they study these diseases or work to develop vaccines or treatment drugs without getting Ebola themselves? BIOSAFETY!

Wow. Boring. Right? Well, kind of. I spent this last week taking a refresher course on biosafety and the reading was DULL, but sitting down to think about all of the implications it becomes fascinating.

The thing is, anything that would infect you is likely invisible.  If you’re working with human tissue or blood, you can see the blood but not what might be inside of it (bacteria or a virus) that could infect you.  And if you drop a blood tube on the floor, you can see the pool of blood but not the microscopic aerosolized droplets in the air just waiting to be inhaled. So how does a scientist take care of these hazards not just so they don’t get sick but so they don’t infect the public as well?

Good news is that scientists think about this a lot.  First, depending on what you’re working on depends on how careful you have to be. Compare this to the difference between giving a 4-year-old plastic play-doh scissors versus sharp surgical scissors – they have different risks associated with them and you’d treat the kid using them in different ways.  In the same way, working with things that are not known to infect humans and cause disease (like bacterial cells) don’t need to be handled as carefully as those that cause deadly diseases that are spread through the air (like Ebola).  This is what defines the “risk group” on a scale of 1-4, where 1 is the lowest risk and 4 is the highest. The play doh scissors or bacterial cells would be Risk Group 1 and the sharp surgical scissor or Ebola virus would be Risk Group 4.

This then helps researchers figure out what protective measures need to be taken – also called Biosafety Levels (abbreviated as BSL) 1-4.  For example, level 1 can be done in the laboratory out in the open wearing a lab coat and gloves.  Level 2 requires research to be done in a biosafety cabinet so that anything that spills or is aerosolized is contained.  Level 3 is for agents that cause moderate to severe disease and in this case the experiment needs to be completely contained in a glove box or in a special room with controlled air flow. Level 4 is for agents that cause lethal disease that has no treatment or cure (like Ebola). In this case the BSL-4 is what you may see on TV or movies where researchers are fully enclosed in a “space suit” to prevent any contact between the person and the agent.

biosafety

In my lab, we regularly work with human tissue and blood and because the tissue or blood may be infected with certain biological agents, they are considered risk group 2. We always wear a lab coat and gloves and work inside a hood.  When moving these tubes from one place to another, we make sure that there are at least two layers of containment – the blood tube is the first layer and this is inside a plastic bag as the second layer. We also get re-trained every year to make sure we remember how to handle spills (just in case).

Now because we’re all morbid creatures, I’m sure you’re wondering what’s happened when this hasn’t worked. Here is an article about the most common infections acquired in the lab and how they were acquired.  For more newsy stories, here is a story about a researcher who contracted plague in the lab. Eek! Definitely reinforces the importance of being careful in the lab.

Happy New Year!

fireworks

Thanks to Flickr

Happy New Year, dear readers. Hope you had a fabulous holiday and 2016 has been treating you well so far. Have you started the year with New Year’s Resolutions?

I always make lots of resolutions, but find that they are far more effective when shared with people – to keep me accountable. Personally, I’m working on becoming fit, in my own way.  I’m going to climb the seven major peaks in Phoenix this year.  Seems reasonable to climb one per month. I’ve also started a gratitude journal to force me to focus on the positive, especially in a world filled with bad news and the ease with which a person can slip into negativity.

I also asked my staff to come up with professional New Year’s Resolutions.  Of course, I had to participate as well. My professional goals this year include being more proactive in working with clinicians to initiate and collaborate on projects involving the biobank.  You would think that researchers are researchers, but clinical and basic research are so different (see here to learn why).  I’m so much more familiar working with basic researchers, so this goal really pushes me out of my wheelhouse.  Should be fun!

And finally, what are my goals with this blog?  I appreciate all my readers who have hung science_tshirtin with me this first year as I get the ball rolling. I’m so devoted to my mission of sharing and explaining science to the public, and I’m grateful for this venue to be able to do this. But I want to and need to do more! This year, I’ll be posting more about scientific news while still providing fundamental explanations of biology, science, research, ethics and how science works. I’m going to work on shorter articles (faster to read). I also want to make some videos showing how things really work in the lab.  Maybe some video interviews with interesting scientists too.  If you have ideas, let me know! I’ll also be posting more my blog’s Facebook page. So even if you’re a blog subscriber, please also “like” my Facebook page to get even more awesome scientific information.

2016 promises to be a fabulous year! I hope you’re able to accomplish all of your goals, and I look forward to you following along as I try to accomplish mine.

What is Informed Consent for Research Subjects?

informed_consentAs I mentioned in my last post, the Institutional Review Board (or IRB) has a responsibility to review and monitor all human subject research to help ensure that the subjects are treated ethically.  But how does the patient know what they are getting into if they are interested in participating in  a research study?

One of the key parts of the Belmont Report (that report that sets the rule for human subject research) says that subjects must be treated with respect.  A huge part of this is to inform research subjects about the research, the risks, and the possible benefits. Because of the importance of informing the subject, most research studies involve providing the potential participant with an Informed Consent Form (ICF) that the they must read, understand, and sign before joining a clinical trial.  This informed consent form is reviewed by the IRB and usually much discussion goes into whether it is clear (ideally 6th-8th grade reading level), accurate, and informative.

So how do investigators or the IRB know what to inform the potential participant about in this informed consent? Well the government tells us – of course! The intuitively named Title 45 CFR 46 subparts A, B, C and D outline the rules and regulations for human subjects research.  Because this is the government’s stupid way of naming things, the easier name used for these rules is the Common Rule. This rule outlines what’s needed in an informed consent form (paraphrased directly from the Common Rule):

  1. A statement that the study involves research, an explanation of the purposes of the research and the expected length of the subject’s participation, a description of the procedures to be followed, and identification of any procedures which are experimental.
  2. A description of any reasonably foreseeable risks or discomforts.
  3. A description of any benefits to the subject or to others which may reasonably be expected from the research.
  4. A disclosure of appropriate alternative procedures or courses of treatment, if any, that might benefit the subject.
  5. A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained and that notes the possibility that the Food and Drug Administration may inspect the records.
  6. For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained.
  7. An explanation of whom to contact for answers to pertinent questions about the research and research subjects’ rights, and whom to contact in the event of a research-related injury to the subject.
  8. A statement that participation is voluntary, that refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and that the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.

The intent of the informed consent is for the subject to actually be informed.  This means that the investigator needs to clearly and honestly explain the research to the subject.  For example, when we provide informed consent for patients to provide tissue samples for the biobank, we tell them that their tissue may be used for any type of future research, it may be used to create commercial products but won’t financially benefit them, and that we won’t be able to provide any research results back to them.  In this context, participating in the biobank may sound like a raw deal.  However, we also explain how the tissue they donate will be used by researchers to better understand diseases and develop new treatment. Therefore, even though they may not directly receive benefit, they may benefit others with their disease in the future.

The potential participant is also given the chance to ask all the questions that they have about the study.  They can ask to bring the consent home to read it.  They can ask their doctor about it. Then after they are fully informed, they decide if they want to sign it or not. If not, that is okay.  It’s up to the patient if they want to participate and the investigator cannot do anything to coerce the patient to sign or participate.  At the same time, if the patient does decide to participate, they may leave the research study at any time with no penalties. Their participation is entirely voluntary.

One other quick note about making sure the patients are fully informed…the Common Rule has added additional safeguards in the case “when some or all of the subjects are likely to be vulnerable to coercion or undue influence.” These vulnerable subjects include children, prisoners, pregnant women, handicapped, or mentally disabled persons, or economically or educationally disadvantaged persons. For example, you don’t want to force imprisoned people to participate in research just because they are in jail or poor people to participate just because you are paying them a lot of money to participate.

The US Office of Human Research Protection is working on changes to the Common Rule right now (it’s called a Notice of Proposed Rulemaking – these silly government names).  The original re-write was sent out to the public for review in 2011.  The updated version was made available in September of this year (look at that for the glacial swiftness of the government!) for even more review.  It has many proposed changes that will affect human subject research and research using human tissue samples. To learn more about what this means for clinical and other research, check out the recent story from NPR.

Overall, the purpose of informed consent is to make sure anyone volunteering to participate in a research study knows what they are getting into. If you are interested in a clinical research study, can you find more at clinicaltrials.gov or talk to you physician.

Institutional Review Board (IRB) – Keeping Research Subjects Safe

Xmas

I was working over the holiday weekend, but at least I was working in my decorated living room with a fire going (the high in Arizona was only 66 today!!)

Hope you had a fabulous Thanksgiving weekend! Four day weekends are great, and even I took some time off to enjoy the holiday with my husband and the puppies.  And then I got back to work because I have an Institutional Review Board (shortened usually to the acronym IRB) meeting in two weeks and the committee has eight new protocols to review. This likely means very little to you, but the IRB is what ensures that the rights and welfare of humans participating as subjects in a research study are adequately protected. And here’s why that’s important…

In a previous post, I explained clinical research.  Clinical research studies new drugs or devices to determine if they are safe or effective. As you can imagine, at a world-class hospital, we have hundreds of clinical trials. You can check out information about these clinical trials by following the links for the Barrow Neurological Institute, St Joseph’s Hospital and Medical Center and the University of Arizona Cancer Center at Dignity Health.  Physicians and surgeons are studying new treatments for many different cancers, devices like the NovoTFF for glioblastoma, and comparing new drugs or combinations of drugs to current treatments to see if the new regime works better.

Now if a  company wants to test a new drug, they can’t just pick up the phone and ask their physician buddy if they could just use a few of their patients to test some stuff out. But why not?  Honestly, it’s because at one point researchers did some pretty crappy things in the name of science.  Thins like Nazis studying prisoners against their will and in the US and scientists who studied the untreated progression of syphilis in black patients in Tuskegee, Alabama from the 1930s-1970s. In these and other cases, the welfare of the patient (who is called a subject once they are part of a research study) wasn’t considered AT ALL and what the subjects had to endure was truly awful.

To avoid this from happening in the future, in 1974 the government passed the National Research Act, which resulted in the Belmont Report. From this, three ethical principles were developed in the treatment of research subjects:

  • Respect for persons.  This respect includes allowing them to make their own informed decisions about participating in the research.  This also means that the researcher conducting the study needs to be honest and not try to deceive or coerce patients into participating in the study. For example, the researcher can’t tell the patient that the research will be painless and cure their disease if they know it won’t.
  • Beneficence: Basically this ensures that the researchers do no harm to the research participants – for example, like the harm done during WWII or in untreated syphilis patients.
  • Justice:This is to avoid taking advantage of the patient or a vulnerable patient population.  For example, there are special rules to prevent taking advantage of prisoners or children. This principle also tries to make sure that all research participants receive benefit equally.

protocol for IRB reviewThese ethical principles have been developed into processes that are regulated by the Food and Drug Administration (FDA) and Department of Health and Human Services (specifically Office for Human Research Protections). How does the government make sure these regulations are followed?  Any institution that is performing human subject research has to obtain a Federalwide Assurance, which essentially registers the hospital or university with the government and assures the government that the hospital will follow the ethical rules and guidelines to conduct this research.

For each project or clinical trial involving human subjects, the investigator needs to put together a proposal – what we call a protocol.  This protocol includes information about exactly what is going to be done to the subjects, what the risks are, what the alternatives are for treatment, and how the subject’s safety and confidentiality will be safeguarded. This protocol is the sent to the IRB along with LOTS of other documents about how the patient will be informed about the research (in Informed Consent Form), whether or not the investigators have been trained to perform the research, and information about the drug or device being used.

The IRB is responsible at individual institutions for making sure that patients who become subjects in human subjects research are treated with respect, beneficence and justice while also decreasing the potential risks and letting the patient know what these risks are. The IRB reviews each new protocol (which is exactly what I am doing this weekend!) and at the IRB meeting (which is once a month from 7-9AM), the investigators present their protocol.  The IRB members then ask questions to the investigator and discuss the research after the investigators leave the room.  What do we discuss? It’s confidential for individual studies, but we may talk about how the study is being performed and identify possible problems with the study. We may also talk about the informed consent (what the patient reads to learn about the study – more on that in the next post) and if it accurately explains the research and the risks. We then can vote to approve the study, to send the protocol back to the investigator to answer questions or modify the protocol or to reject the study.

After the study has been approved, the IRB is also responsible for monitoring active research projects.  For example, we receive annual reports that let us know how many people have decided to participate in the study. We also monitor “adverse events.” Adverse events (or AEs) are any event that isn’t anticipated.  This can be anything from nausea to a broken leg to a rash to a missed appointment to death (death is considered a serious adverse event). Whenever an AE happens, the IRB is informed so that if it seems like there are too many of one type of AE, we can take measures to avoid them or tell the subject about an additional risk or shut the research project down.

My participation on the IRB is a responsibility I take seriously because I want any patient who comes to the facilities I work at to understand the research that may be made available to them.  And this understanding includes knowing what the research is all about and what risks the research entails. This is why I’m spending my holiday weekend reviewing research protocols for the IRB.

What’s it like getting a science PhD?

By AdmOxalate (Own work) [CC BY 3.0 (http://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons

Cold Spring Harbor Laboratory by AdmOxalate (Own work) CC BY 3.0, via Wikimedia Commons. This is where I went to grad school.

In my last post, I talked about how to get into graduate school.  This post will be about how PhD programs in the sciences are structured and how they work, because I’ve realized from lots of conversations with my non-scientist friends and family – no one really knows much about this!

There are fundamental differences between getting a PhD in the sciences and getting one in anything else. The first main difference is that you don’t have to pay for a PhD in the sciences, and in fact, they pay you.  Don’t get excited – they don’t pay much. The current NIH stipend rate is $22,920 per year (only about $2900 more in 2015 than what I received in 2001).  Tuition and this stipend are paid for in different ways depending on the school.  Some schools have endowments that support graduation positions. For example, I was supported by an institutional endowment made by the Beckman Foundation for my first two years of graduate school. Some schools rely on the students working as Teaching Assistants (TAs) helping to teach undergraduate courses to support some or all of their tuition or stipend.  In many cases, the research laboratory that the student works in pays for the tuition and stipend using their grants. Graduate students themselves also can apply for funding, which along with helping fund their position, is a prestigious resume entry.  I applied for and was awarded a National Science Foundation (NSF) Graduate Research Fellowship that supported my last few years of graduate school.

The second main difference between a science and non-science PhD is that there is NO WAY that you can work and get your PhD at the same time. Don’t get me wrong, you work. You work your butt off every day all day, but not while making money at another job. With the nature of scientific research, there isn’t time to have another job, and in most cases, it isn’t allowed by the institution anyway.

What is a graduate student so busy doing?  The graduate program at the WSBS, where I went to school, was designed to be very different from the traditional American graduate school model.  I’ll start by describing, generally (since all grad schools are different) traditional programs and then describe my program. Most PhD programs are expected to last between 4-7 years. The first two years are filled with a few key activities:

  • First two years: Traditional classes at the graduate level that cover scientific topics more deeply than an undergraduate program
  • First year: Rotations. These are short (usually 3 month) stints in a laboratory to figure out if you like what the research that lab is doing and whether or not you’d want to do your PhD thesis research there. This is also the chance for the head of that lab (also called the Principal Investigator or PI) to figure out if they want to have you in the lab for the next 4-6 years.
  • End of second year: Qualifying Exam. This exam, also called the comprehensive exam at some schools, is an enormous exam that is like the trigger for the institution to determine if you go forward in the PhD program or not. Usually held at the end of the second year, if you pass, you move on to nearly exclusively doing research in the lab to complete your thesis.  If not… well, I don’t think I know anyone who didn’t pass after at least a few tries.
  • Third year until you graduate: After the first few years, most of the time is spent in the lab. There may be required Teaching Assistant responsibilities or other required seminar classes (like Journal Club), but this varies by school. Then there are the thesis committee meetings.  Pretty early on in each student’s research project, a committee of 3-5 faculty at the university are invited to participate on your thesis committee.  Their job is to provide a set of eyes (other than the PI of your lab) to make sure you’re moving in the right direction. They approve the thesis proposal and meet with you regularly (in a traditional program, this might be yearly) to keep you on track. They are also the committee that reads and evaluates your thesis dissertation and holds your defense (more on that shortly).

As I mentioned, this traditional system is a bit different from what I went through at CSHL.  The philosophy of WSBS is to shorten the time frame from matriculation to graduation to 4 years while also maintaining academic excellence.

  • First semester (4 months): This is the only time I took core courses – what my mom called “Science Boot Camp”.  These classes were unique because instead of learning facts out of textbooks we learned how to critically think about, write about, and present science. The classes focused on reading journal articles, scientific exposition and ethics, and particular scientific topics in depth like neuroscience and cancer.
  • Second semester (4 months): After the first semester, we had three one month rotations that allowed us to explore our scientific interests to help decide on a thesis laboratory or just allow us to try something new. I did rotations in a lab that used computers to understand lots of scientific data, a lab that used microscopy to figure out how a cell worked, and a lab that studied apoptosis (where I ended up doing my thesis research). Also during this time, we did our one required teaching experience at the DNA Learning Center. Here we taught middle and high school students about biology and DNA.  The idea was that if we could explain science to kids, we could explain it to anyone.
  • End of year one:  After the first year, we took the Qualifying Exam.  For my QE, I had two topics assigned to me (Cancer and Cell-Cell Communication) and I had to learn everything about these two topics in one month. A panel then grilled me for nearly 2 hours on these topics, and fortunately, I passed.
  • Years 2-4: The classes are only held in the first semester and the rotations only held in the second semester so that we could focus on what we were doing at all times. No excuses. So after the qualifying exam we were expected to focus on all research all the time. The one exception being the Topics in Biology courses held each year.  The Topics in Biology courses were held for an entire week (7am-11pm) and gave you the chance to interact with experts in various fields both to extend your scientific knowledge and to critically think about new problems.
Photo Nov 15, 9 24 23 PM

My thesis. It’s about 1.5 inches thick. Or as my hubby said “That’s your thesis? Impressive, baby”

Doing research was intense lab work punctuated by intense meetings.  FYI – intense lab works mean 8am-7pm (or later) Monday through Friday and usually the weekend too (and by weekend, I do mean both Saturday and Sunday).  And let’s not forget the 4am time points when you have to go into the lab just to check on your experiments every 4-6 hours for 24 hours straight. But back to the intense meetings…The first intense meeting was the thesis proposal defense, which was held in the second year. This was where you told a committee of 4-5 researchers what you were going to research for the rest of grad school, they quizzed you for 1-2 hours and then gave you the go ahead (or not) to do that work. The next set of intense meeting were the thesis committee meetings every 6 months to keep each student was on track. Again, 1-2 hours of presenting and critical evaluation of your work by committee.  At some point, the committee gives you the “green light” to start writing your thesis, you take all of the work from the past 3-4 years and put it in a massive document called a dissertation. The thesis committee reads it, you present the work in front of them and all of your family and friends, and then again, you spend 2 hours in a room with your committee answering every question they can think of – aka “defending” your thesis.

Cathy_graduation

My PhD graduation day with two of my classmates. I’m in the center

As I write this, I realize that my thesis defense was 9 years ago next week. How time flies. After the defense, you have your PhD and officially graduate whenever the ceremony is held – in my case in May of 2007. I graduated 5 years after I started – just slightly longer than the expected 4 years for the Watson School. Was it easy? Nope, not even a little bit (ask my mom). Would I do it again? In a heartbeat.

This post is dedicated to my classmates and my friends in graduate school – you know who you are.  Without you, I wouldn’t have made it. And to my mom, who convinced me at least twice, not to quit.

How do you get into a PhD program in science?

When I was very young, my uncle died from lung cancer. I wasn’t allowed to see him before he died (his wishes). There was a part of me that thought it was my fault that he dies because he didn’t listen to my pleas that he should stop smoking. That’s when I decided that I should cure cancer. At the time, I had no idea how to do that, but by the time I was in high school, I realized it would involve getting a PhD.  Other than a great uncle (on the other side of the family) that I barely knew, no one else in my family had a PhD, so I was the trailblazer in figuring out how it all works. In this post and my post on Thursday, I’ll write about how to get into graduate school and then what the program is like once you get there. More accurately, I’ll write about how I got  into grad school and what grad school was like for me since I know that everyone’s experience is different.

So how do you get into a PhD program? Let’s skip the fact that you’ll need an interest in science, good grades in college and likely do undergraduate research. Also, one difference between science PhDs and other PhDs is that you aren’t expected to get your Master’s degree first. You can apply straight from undergrad, and the idea is that you get your Master’s degree on your way towards the PhD.  If you leave the PhD program at a certain point (usually after you take a qualifying exam), you’ll leave with a Master’s degree. In fact, other than maybe having more research or other experience, there isn’t much of an advantage to getting a Master’s before your PhD degree versus not.

The first step needed before applying for grad school is to take the general GREs exam along with a subject-based GRE exam.  These are standardized tests like the SAT or ACT but for graduate school.  The subject-based exam feels like the biggest and longest test you’ve ever taken for a particular subject.  I took the Biology subject test (I could have taken the Biochemistry subject test, but I heard it was a lot harder, so I just studied by butt off for the Biology one instead). For most grad schools, these exam scores are critical.  Just like if you get a good score on the SAT you can get into high ranking colleges, high GREs scores help you get into grad programs at the Harvards and Yales of the world.

Just like undergrad, you have to send in your applications with the ever-important personal statement.  This statement has to talk about why you want to go to grad school, but also why that school and the researchers at that institution are of interest to you.  When I advise current undergrads about choosing a PhD program, the most critical part is to apply to schools that have research labs that do the research that you are interested in.  Once you get into the graduate program, as I’ll talk about in detail in my post on Thursday, you spend years of your life in this research lab so if there isn’t a research lab you like, don’t even bother applying to that school.

phdAfter applying, the graduate schools interested in you invite you for an interview.  This isn’t a one hour, chat with a guidance counselor type of interview.  This is a weekend of interviews with distinguished faculty grilling you about your undergraduate research (assuming you had some) and asking critical questions to determine how clever you are and whether you’d be a good fit for the school. I went on three interview weekends at Harvard Medical School, Johns Hopkins and the Watson School of Biological Sciences (WSBS) at Cold Spring Harbor Laboratory (CSHL)(where I eventually attended). The CSHL interview by far was the most intense with over a dozen interviews in one day including one with Nobel Laureate Jim Watson who was the chancellor of the lab at the time. My favorite “words of wisdom” from Dr. Watson at that interview were to always select research projects with a 30% chance success. Less than that, you’d be wasting your time and more than that, the project is too obvious and wouldn’t make a big impact on the field. This may sound a bit masochistic – setting yourself up for likely failure – but this is the life of a scientist!

Usually there are dozens of candidates invited for the interview weekends so the schools also plan bonding time among the candidates and the current grad students. This could be a dinner out, a party thrown by one of the current grad students, or a trip to NYC to see a Broadway show.  To this day I’m still friends with people that I interviewed with even though we both chose other grad schools.

After the interview, the waiting game begins. I remember the evening that I received the call saying that I was accepted into the CSHL program (the one I really wanted to attend). I was in my dorm room at Boston University and I get a phone call – keep in mind this is before cell phones so they called the landline in my room. I thought it was a prank call from my friend Greg and I told him (more than once) that this wasn’t a funny joke. No joke – the Dean of the school was called to let me know about my acceptance. I received the official acceptance letter in an email minutes later.

wsbs_2001

My WSBS Class entering in 2001. I’m the one sitting on the double helix

I actually got into all of the graduate programs that I applied to, which caused a bit of a problem because my dream had always been to attend Harvard. My decision, then, to attend the Watson School was confusing to my parents, who had heard of Harvard but never Cold Spring Harbor Laboratory.  Why was this my choice? The research at CSHL was incredible  – every scientist was engaged with their work like I had never experienced in my undergraduate career. It was inspirational to think about being a part of that. CHSL had also just started their graduate program – I would be in the third entering class – and their program focused on learning how to learn and how to think in a way that was different than any other graduate program out there (more on that in the next post). I wanted to be a pioneer in this program. And finally, the culture suited me. I went to a large undergraduate institution with classes of 300 people and anonymity amongst thousands of classmates. In graduate school, I wanted to be part of a small class where I could really be challenged and learn from a close-knit group of peers. My WSBS class had six students, including myself, that constantly challenged me to think faster and smarter and become the best scientist that I could be.

 

Why do nerds wear glasses?

me_inlab_glasses

Me in the lab 8 years ago

I remember my junior year of high school, leaning over the boy who sat in front of me in class to copy his notes because I couldn’t see the board. Yes, I did think he was cute, but in this case, I just really wanted to know what the teacher was writing.  That’s when I first got glasses.  My vision dive-bombed from there and by the time I got LASIK two years ago, I had -4 prescription with astigmatisms in both eyes. My Dad has always had glasses, and my sister had glasses but  her eyes corrected themselves over time (lucky duck). My mom just started wearing glasses full time last Friday.  She’s had readers for a while, but now she needs them to see both far and close.  Because glasses were so new to my mom, we spent a lot of time on our daily phone call Friday talking about them, and she ended our discussion by exclaiming “Cathy, you should find out why so many smart people wear glasses. Is there a reason for it or is it just a stereotype that nerds always wear glasses? You should write about this on your blog.” I didn’t have high hopes when I started looking into this, but actually, there are a lot of scientific papers looking into this topic.  Is there anything to the stereotype of nerds wearing glasses and if so, why?

One of the more recent studies exploring this topic was from the Gutenberg Health Study out of Germany.  Started in 2007, they are studying cardiovascular diseases, cancer, eye diseases, metabolic diseases, diseases of the immune system and mental diseases in over 15,000 German subjects.  They want to understand how genetics and the environment contribute to these diseases. From looking at 4,800 of these subjects between the ages of 35 and 74, they found that nearsightedness correlated with the amount of time spent in school: 53% of college graduates were nearsighted versus only 24% of people who’d dropped out of high school. This result was mirrored in a study in the United Kingdom studying over 100,000 subjects: 27% of the people they studied has nearsightedness and it was more common amongst those with higher education. Same results from a study looking at people throughout Europe. So there is actual scientific evidence that people with more education are more likely to wear glasses.

nerd

Thanks Wikipedia for the image

Does this mean that nearsightedness makes you smarter? Or does a person develop nearsightedness because they are studying? Or is it genetic?  Let’s start with the last option first.  The Gutenberg study looked at 45 genetic markers and found that they were only weakly associated with nearsightedness. So there likely is a genetic component but it’s not well understood. What has been shown more conclusively is that lack of light is highly correlated with nearsightedness.  In other words – more time indoors, the more likely that you’ll need glasses.  Studies have looked at whether adding more light to classrooms decreases nearsightedness, and in fact it does! (see this study in China and this one from Australia). Lack of light may actually cause a person to have to wear glasses!

But why would the lack of outdoor light cause nearsightedness? One option may be that it’s because kids are inside looking at screens or reading.  This could then stress the eyes or affect proper eye development. One study did find that the more time spent doing “close work” like reading or writing correlates with the need for glasses.  In this same study, they didn’t find any correlation with being indoors and staring at the TV or iPad and nearsightedness – so it’s not the screen time, it’s the studying!

Another study looked at Vitamin D levels (Vitamin D is created by interaction of ultraviolet B and other chemicals in the skin) and found that people who were nearsighted were also more likely to have lower vitamin D levels.  This is something you might expect if these folks also don’t go outside as often (because they’re too busy inside reading or doing homework???) But whether or not Vitamin D deficiency causes nearsightedness or if taking more Vitamin D could “cure” nearsightedness is another matter – and totally unknown.

So why do nerds wear glasses? Scientists can’t exactly say yet, but it’s likely a combination of genetic and environmental factors that are just beginning to be understood. Until then, you may want to look at the studies that are saying that it doesn’t matter if you are nearsighted or not or smart or not.  You should still wear glasses because in a British study, over 40% of people perceive that people wearing glasses makes a person look smarter and more professional.  I wonder now that I got LASIK if I should get myself a pair of fake glasses?  Just in case I need to “look smart.”

 

Why can’t you get anything done? Activation Energy

I was having drinks the other day with an amazing scientist and physician.  She started talking about getting things done and how some people have the “get-it-done” gene and some people don’t.  The people who don’t either don’t ever get things done or work really hard to develop something that looks like the get-it-done gene. I think that whether a scientist or not, this feeling is very familiar.  Like those times when you know that you have to make an important phone call or answer a time-sensitive email and instead you end up doing 15 different work related (or unrelated) tasks instead of what you need to get done.  Or even better, my favorite technique, cleaning your desk instead of starting a new project. My excuse? “Having a clean and organized desk will help me work better when I get started”, but we all know that it’s really just a solid way to procrastinate.

My most recent difficulty on getting something done was starting to write a manuscript that I was invited to write in June and had a very clear mid-September deadline.  Not only did it have a deadline, but there were collaborators that had to contribute to the manuscript, so I had to be on top of things. What was the problem?  I had all the information gathered to start writing. I had ideas in my head of what I wanted to write. I had a motivational deadline. My problem was activating what my colleague called the “get it done” gene, but I call activation energy.

You may recall this term from your high school chemistry class.  The technical definition is that activation energy is the minimum amount of energy required to start a chemical reaction.  If you think about it another way, it’s the energy barrier standing between chemicals and the chemical reaction that will turn those chemicals into products.  In some cases this activation energy may be really huge and a lot of energy is needed for the chemical reaction to take place.  In other cases, the temperature may change or an enzyme may be present that decreases this amount of energy needed for the reaction to take place.
activation_energy
This is IDENTICAL to those large and small barriers that you face when you are trying to get things done.  Some things, like cleaning your desk (especially while avoiding other tasks) is easy to start.  It takes very little activation energy to go from messy desk to cleaning (your chemical reaction) to the desk being clean (the product of your chemical reaction).  On the other hand, despite all your best efforts, some projects – like starting to write a manuscript –  have a really high activation energy and are really hard to get started.  Whether it’s easy or difficult to start, whether the activation energy is big or small, the end product is the same – a completed project. That’s what makes activation energy so annoying.  You know that you’ll eventually get to the same place whether you struggle at the beginning to get it started or not.

So I’ve tried to trick myself into decreasing the activation energy for the projects I just can’t seem to start.  I’ve “pretended” to get real work done by printing out papers I need to read, writing outlines, or doing online research.  These activities don’t have a high activation for me and therefore seem really easy and unrelated to the larger project.  But the trick is that these activities are actually helping me with the bigger project!  It’s like incrementally decreasing the activation energy through each low activation energy, easy activity.

There are other ways to decrease the activation energy too.  For example, I just read an article in The New Yorker reviewing a book called “SuperBetter” about gamifying your life.  If something difficult comes up, find a way to turn it into a game.  One of the examples was to turn challenges into a “quest” where you challenge yourself to achieve a particular goal as if you were in a game. What a fun way to decrease the activation energy when starting a project.  Make each step part of the massive, exciting, dangerous quest to navigate the twists and turns of writing a manuscript or making a presentation or developing a cool new product.

My other favorite technique to decrease activation energy is similar to the gamification idea, but is completely reward based.  For example, I will challenge myself to write one page or one section and then I will reward myself with a low fat chai tea latte from Starbucks or a few minutes surfing Facebook. It’s amazing what creating these mini-successes does to make overcoming that energy barrier.

And in case you’re wondering, I did finish that manuscript, several weeks early and with great success.  It only took multiple tiny tasks and a half a dozen chai tea lattes.

What is that? A pipette!

pipetteMost of the time, biologist in the lab aren’t working with things that they can see. You need to look at cell under a microscope, proteins using X-Ray crystallography (for example), and DNA and RNA by various methods like gel electrophoresis or cell staining (see more about visualizing DNA here).  Many experiments require scientists to manipulate DNARNA or proteins in small liquid volumes to do experiments to understand the sequence of these molecules, to discover what other molecules they bind to, or to change them to figure out how they work in cells. To manipulate these small volumes, we use a tool called a pipette (shown at left) – also called a micropipette to be even more precise. It’s similar in concept to the baster you have in your kitchen that sucks up liquid when basting your turkey, except it’s for much smaller volumes and is exquisitely precise.

Pipettes come in different sizes, and the size of the pmulti_size_pipettesipette determines the volume that they can dispense (see picture at right).  They dispense microliter (abbreviated as “ul”) volumes of liquid. To give you an idea of scale, 1 drop of water is about 50ul.  One milliliter (ml) is1000ul, which is the largest micropipette volume you can dispense, and there are about 44ml in a shot of vodka. These are small volumes we are talking about!!

The sizes shown to the right dispense up to 2ul (called a “p2”), 200ul (“p200”), or 1000ul (“p1000”). By spinning the plunger on the pipette, you can change the volume that is dispensed within the range that the pipette allows.  You then put disposable tip to the end of the pipette and suck up that volume of liquid. As an example, check out the photo below of the p1000 dispensing 600ul of water and the p200 dispensing 20ul of water.  The image to the left is the pipette tip filled with that volume and to the right is the water in a tube. This type of tube is used every day in the lab and is called an eppendorf tube. IT can hold 1.5ml (or 1500ul) of water. These small plastic tubes have attached caps that can snap the tube closed to allow you to mix the contents or do whatever is needed for the experiment (like heat it up, cool it down, spin the contents, etc). And if you’re wondering why they are called “eppendorf” tubes, it’s after the name of a German company called Eppendorf that is one manufacturer of this kind of tubes (similar to how the brand Kleenex is now synonymous with tissues)

pipette volumes

Maybe you’re wondering why scientists have to use such small volumes?  One reason is because there isn’t a large amount of DNA or RNA or proteins in cells, so when it’s isolated, it doesn’t take up a large volume. As an example, if you isolate the genomic DNA from  5 million cells, you would isolate 10-30ug  of DNA. That’s MICRO grams of DNA – or 0.00003 grams.  As comparison, a grain of salt weighs more than 1200x more than the amount of DNA that you would isolate from 5 million cells!  And this is all in just 50ul of liquid.  Very small amounts! The good news is that working in large volumes isn’t really needed because most experiments don’t need a large quantity of materials to get the answer. Not to mention that working with larger volumes for experiments would be more expensive.  If you are doing an enzymatic reaction, a larger volume reaction would require more enzyme.  To get an idea of what this would cost,  a very common reaction cuts DNA with restriction enzymes, which are essentially super-specific DNA scissors. These restriction enzymes cost several hundred dollars per tube and you use 0.5-1ul for every 50ul reaction.  If you did a reaction in a large test tube of 10ml, you’d need 200 times more enzyme and would go through hundreds or thousands of dollars if enzyme for each experiment.  Labs are not that rich!

Fortunately scientists have developed techniques and equipment, like the micropipette, that can manipulate, detect and analyze incredibly small amount of DNA or RNA or proteins. For most bench scientists, learning how to use a micropipette is done on day one (I learned how to use one in high school at City Lab) and pretty soon becomes second nature.  In grad school, I pipetted so much that there were days I’d go home with a sore thumb or pipetting  calluses. However all this practice did pay off.  I picked up a pipette for the first time in 8 years a few weeks ago to start doing experiments in my new lab. After all these years, it was just like riding a bike – or in this case just like “using a pipette”.

Sci Snippet – Who reviews papers?

ReviewingThis blog is called “Things I Tell My Mom” for a reason. These are all things that I really do talk to my Mom about.  In fact, after posting about the trials and tribulations of publishing a paper, my Mom asked who these reviewers are anyway.

Reviewers are usually (hopefully) in the same field as the researcher so they have a background knowledge that will allow them to evaluate the research carefully and thoughtfully based on what is already known in the field. The editors select several (usually 3) reviewers who each review the manuscript independently. The good news is that in an ideal world, these well-informed reviewers will be in the best position to provide the journal with insightful feedback.  The bad news is that they may like what you’re working on so much that they provide suggestions for lots of additional experiments, steal the ideas in the paper and then quickly publish them before you get a chance. Is this “scooping” ethical? Nope. Does it happen? Yup.  Often? Probably not that often.

You also have to keep in mind that the reviewers know who the authors of the paper are, but the reviewers comments are anonymous. So if you get a poor review, you don’t always know if it’s because the manuscript is terrible or if the reviewer is someone who you are competitive with professionally or don’t get along with. As my Dad aptly said, “That system sucks.” This is in part why some journal are starting to offer double blind review (described in more detail here).

Beside this apparent conflict of interest, reviewers are also active researchers and therefore super busy people. If the reviewer doesn’t take the responsibility of reviewing seriously, this can mean one of two things – it will take a lot of time for them to get to reviewing the paper (dragging out the waiting) or they will look through it quickly and provide a crappy review. Crappy reviews can reject great papers or accept terrible papers. It’s an imperfect system. Some of this imperfection is highlighted on this hilarious and depressing website S**t My Reviewers Say Tumblr.

Also, keep in mind that reviewers don’t get compensated in any way for reviewing – it’s part of a scientist’s service to the scientific community. I have been a reviewer many times, and I take the job very seriously and try my best to provide a fair, complete review in a timely manner – and I expect to receive the same when I submit manuscripts as well. This is the ideal, but not always the reality.

For more Sci Snippets, click here.