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.

The difference between basic, translational and clinical research

When I started as a researcher, I had no idea that there were different types of research.  I don’t mean that some scientists study cancer and some scientists study Alzheimer’s disease.  I mean entirely different kinds of research that have fundamentally different methods, sources of funding, and purposes. Today’s post is going to outline three main types of research in the biological sciences: basic, translational and clinical research.

Basic Research:

science_image

By en:User:AllyUnion, User:Stannered (en:Image:Science-symbol2.png) [CC BY 3.0 or GFDL], via Wikimedia Commons

 Right off the bat, I need to be super clear that basic research is NOT research that’s easier to do or simpler than any other type of research.  It is just as complex and just as hypothesis-oriented as other types of research.  However, the goal of basic research is to  understand at a very basic level some aspect of biology.  Also called fundamental research, basic research doesn’t require that the outcome of the research can cure a disease or fix a problem.  That being said, basic research often does create the foundation that is required for other researchers to apply to solving a problem. I like how basic research is described on WIkipedia as “Basic research generates new ideas, principles, and theories, which may not be immediately utilized but nonetheless form the basis of progress and development in different fields”  This research can be in biology, physics, math, environmental sciences or any other scientific field. So what are some examples of basic research in biology?

  • Understanding the proteins and pathways that result in cells dying by apoptosis
  • Developing technology to better determine the 3D structure of proteins.
  • Creating mathematical models representing population growth in cities over time
  • Studying how leaf litter affects the ecosystem (an actual active funded grant at TGen here in Arizona)

This research is often funded by the government, specifically the National Institutes of Health, which funds 50,000 grants to more than 300,000 researchers at more than 2,500 institutions around the world, and the National Science Foundation, which funds 24% of all federally-funded basic science research in the United States.

Translational Research:

mouse_for_research

By Maggie Bartlett, NHGRI. [Public domain], via Wikimedia Commons

Translational research is how basic research and biological knowledge is translated into the clinic.  Often called “bench-to-bedside” or research (referring to the research bench and the patient’s bedside) or “applied” research (of applying basic research to solve a real-world problem), this research is needed to show that a drug or device works in some living system before it is used on humans. This is the research that happens after the results from basic research are obtained and before clinical research.

For example, if a drug is found in the lab that targets a protein that is thought to cause a disease like cancer, the drug will first be tested on animal models.  The animal model may be a mouse that has been genetically altered so that it develops that specific kind of cancer or a mouse that has human cancer cells injected into it (like the patient derived xenografts I described in a previous post). The drug will then be used on the animal to see if it is safe or if low doses are so toxic that the animal dies. Whether or not the drug hits the targeted protein or cell type can also be tested in mice.  For example, if the drug is supposed to kill brain tumor cells, researchers would want to make sure the drug was able to pass the blood brain barrier of the mouse.  Finally, if the drug is supposed to kill tumor cells, researchers would want to check that the tumor shrinks, the cells die, and/or that the survival of the mouse is extended from using this treatment. Often, drugs are “weeded out” at the translational research stage saving millions of dollars and years worth of time and effort in clinical trials.

Translational research isn’t just for drug development.  It is also useful for devices. For example, to develop a device that can diagnose diseases in third world countries, where access to electricity and high tech labs is more difficult.

Clinical Research:

blood_tube_for_research

By Tannim101 [CC BY 3.0, GFDL or CC BY 3.0], via Wikimedia Commons

Clinical research is what is performed in a healthcare environment to test the safety and effectiveness of drugs, diagnostic tests, and devices that could be used in the detection, treatment, prevention or tracking of a disease.  The cornerstone of clinical research is the clinical trial.  There are 4 basic phases to a clinical trial.  Each phase is performed sequentially to systematically study the drug or device.

  • Phase I: This is the first time the drug or device has been in humans and it is used on a small number of patients in low doses to see whether or not it is safe and what the side-effects may be. At this point, the clinicians are not trying to determine if the treatment works or not.
  • Phase II: In this phase, more patients are treated with the device or drug to test safety (because more side effects may be identified in a larger, more diverse population) and whether the drug or device is effective (in other words, does it work?).
  • Phase III: This is the phase that focuses on whether the drug or device is effective compared to what is typically already used to treat patients.  It’s used on a large group of people and “end points” like increase in survival or decrease in tumor size are used to evaluate its effectiveness.
  • Phase IV: These trials are done after the drug has gone to market to see if it works in various populations .

There are several different types of clinical trials depending on who is funding them. Some clinical trials can be initiated by a doctor or group of doctors.  These are call “physician-initiated” or “investigator -initiated”  studies and are often used to determine which type of treatment works better in patient care.  For example, there may be two treatments that are commonly used to treat a disease. Investigators may initiate a study to figure out what treatment works better in what patient population.

The kind of clinical research you may be more familiar with are drug companies who are working to develop a drug or device.  These companies will “sponsor” (aka “pay for”) a clinical trial.  They work with clinicians at one or more medical institutes to use their drug or device in a particular way (depending on the phase of the trial) and the clinicians report back the results, including whether there were any side effects to the treatment. At the end of the clinical trial, if the treatment or device was a success, the drug company can apply to the Food and Drug Administration (FDA) for approval to use the drug in the general population.  Bringing a drug to market is a timely and extremely expensive process estimated at over 10 years and $1.3 Billion dollars per drug. Much of this time and cost is due to high cost of conducting the clinical trials.

If you are interested in what clinical trials are currently available in the United States, all clinical trials are registered on ClinicalTrials.gov.  Anyone can search this database to see if trials are available for them to participate in.

Overall, each type of research needs to understand the other, and researchers need to work together to successfully understand our world and to come up with solutions to prevent, diagnose and cure disease.

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.

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.

Did your steak sit on the counter overnight? What experiments I did at work last week

I was at a party last night telling my non-scientist friends about my week at work.  For the first time since I left my post-doc 8 years ago, I spent multiple days in the lab doing experiments!! We had a few drinks at this point, and in their lapse of judgement (thinking I may not give them a descriptive answer at a party) they asked me what my experiments were about.  I did not disappoint, and told them all about my experiments.

This party was a BBQ and even though I’m a vegetarian, most of my friends are huge fans of meat.  So I started by asking them about steak.  If you bought a steak that you weren’t going to throw on the grill right away, you might freeze it and cook it later.  When you take it out of the freezer, how do you know if the steak is still of high quality?  Maybe it sat on the counter overnight before being put in the freezer.  Maybe the freezer lost power during a storm, the steak defrosted and when the power came back on, the steak froze again.  Maybe the steak wasn’t even good when it got to your house – maybe it sat on the butcher’s counter for a few days, forgotten about, before being put into the display case for you to buy. It may be nearly impossible to tell by just looking at your frozen steak if any of these events happened and whether or not these events would affect the steak’s quality.

frozen tissue

Steak image courtesy of Steven Depolo under a Creative Commons License

This is something that we deal with daily as biobankers. To remind you, we collect human tumor samples for researchers to use to better understand diseases and to develop improved treatments. Ideally these tissue samples are very quickly frozen (as described in this blog post) and kept frozen.  Like the steak, there are a lot of “variables” that may affect the quality of the tumor tissue sample – including the same issues that a steak may have – like sitting at room temperature for too long or freezing and then thawing and then freezing again. And also similar to the steak, it’s nearly impossible to tell by just looking at the tissue sample if any of these things have happened. Except, instead of affecting whether or not your dinner tastes good, with tumor tissue samples, research results that are essential for drug or biomarker development for brain tumors are affected.

How do we handle this little problem?  We have to use a proxy for quality – something that we can analyze directly that will tell us whether or not the tissue sample is of good enough quality to be used for certain research purposes.  In this case, the proxy is RNA.  RNA is a great molecule to look at because it’s found in every cell, but it’s also unstable because of its natural enemy RNases. When these RNases are active (when the tissue sample is warm or at room temperature) they will function like little PacMans to chomp on the RNA, turning it into smaller and smaller pieces. When frozen, the RNases are inactive and can’t chomp on RNA.  So if you look at how chomped up/small the RNA is in tissue samples, you can figure out whether the quality of the sample is good for your experiments.

rneasy column

A tiny filter (seen as the white line inside the pink tube) binds to the RNA.

This is what I did last week in the lab. How did I do this? First, I had to get the RNA out of the tissue sample. To do this, you have to separate the cells from one another, which essentially like grinding up a steak in a meat grinder. You then have to bust open the cells to get to the RNA.  You do that by adding something that works a lot like soap that opens up the outer coating of the cells.  From there, you can isolate the RNA by adding ethanol (an alcohol) that makes the RNA no longer dissolved in the liquid (what we call “precipitating” the RNA).  From there we isolate the RNA on a column – exactly like the pink one you see on the right. The white line inside the pink tube is like an RNA filter that traps RNA while letting all the other cell bits flow through. Then you use water to get the RNA out of the filter.  How much RNA do you get at the end?  Imagine an eye drop worth of liquid that contains 10 micrograms of RNA.  That’s 0.0001 grams and for comparison, a grain of rice weighs 0.015 grams.  It’s not a lot, but it’s enough to know if your sample is good or not.

screentapes

These ScreenTapes can analyze 16 RNA samples at one time. They are about the size of a long box of a glass slide or a ling box of matches

You still can’t “see” the RNA to know if it is all in one piece or if it’s been chomped up by RNases just by looking at this tiny bit of liquid in a tube.  You still have to analyze it, and to do this, I used a cute little machine called a TapeStation (I honestly have no idea why it’s called this, since the “ScreenTapes” that you use for the analysis – in the photo at left – look nothing like Tapes to me). This machine separates the RNA based on size (you can see that by the black lines in the image below).  There are two main sizes it looks at – these separate into to peaks (called 16S and 28S). If these RNAs have been chomped up, there won’t just be two peaks (or two black lines), but lots of little peaks of smaller sizes. This will indicate that the RNases were activated for some reason and the quality isn’t as good. In my experiments, the results were awesome and the RNA was of good enough quality for most experiments.  It also meant that the tumor tissue was handled really well when it was collected and didn’t sit on the counter or get thawed and frozen again, for example.

TapeStation

The two peaks are a graphical image of the separation of the RNA shown by the dark lines on the right.

Now you may be wondering, “what about my steak?” I honestly cannot encourage you to do this level of analysis to see if your steak’s RNA is high quality.  Then again, you just want to eat the steak – not do thousands of dollars of important experiments with it.  So let’s just consider the steak a useful scientific analogy and go start your grill – I’ve heard there are some steaks in your freezer.

Thanks to Kelli and Alia for asking me what experiments I’ve been doing and inspiring this blog post. 

How do you find a biomarker? A needle in the haystack.

biomarker_useBiomarkers are biological substances that can be measured to indicate some state of disease.  They can be used to detect a disease early, diagnose a disease, track the progression of the disease, predict how quickly a disease will progress, determine what the best treatment is for the disease, or monitor whether or not a treatment is working. Biomarkers have the potential to do so much, and identifying biomarkers for different steps in the health/disease continuum would help doctors to provide each individual with targeted, precision healthcare.  Biomarkers have the potential to save billions of healthcare dollars by helping prevent disease, by treating disease early (when it’s usually less expensive to treat), or by targeting treatments and avoid giving a treatment that won’t be effective.

spotthedifferencesWith all this potential, you would expect doctors to be using data from biomarkers to guide every single healthcare decision – but this isn’t the case quite yet.  First scientists have to find these biomarkers – a process often referred to as biomarker discovery.  I like to compare finding a biomaker to those “spot the differences” games where you have to look at two images and circle what is different in one picture compared to the other.  This is exactly what scientists do when finding a biomarker, except instead of comparing pictures, they are comparing patients.  And it’s not an easy game of “spot the differences” it’s complicated: the pictures are small and there are tons of details.

Let’s imagine a scenario that a scientist might face when wanting to find a biomarker for the early detection of pancreatic cancer.   Cancer is caused by mutations in the DNA, so you decide to look for DNA mutations as your biomarker for pancreatic cancer. So how do you “spot the differences” to find DNA biomarkers for pancreatic cancer?  First, you will need patient samples – maybe tissue or blood samples from a biobank that already has samples from patients with pancreatic cancer.  If samples aren’t already available, you will have to initiate a study partnering with doctors to collect samples from pancreatic cancer patients for you.  You will also need the second “picture” to compare the pancreatic cancer “picture” to.  This second picture will be samples from people who don’t have pancreatic cancer (scientists usually call this group the “control” group).  Then you have to “look” at the two groups’ DNA so you can find those differences.  This “looking” is often done by some genomics method like sequencing the DNA. This is where a lot of the complication comes in because if you look at all of the DNA, you will be comparing 3 billion individual nucleotides (the A, T, G, and Cs we’ve discussed in earlier posts) from each patient to each of the controls.  Even if you just look at the DNA that makes proteins, you’re still comparing 30 million nucleotides per patient.  And you can’t just compare one patient to one control!  Each of us is genetically different by ~1%, so you need to compare many patients to many controls to make sure that you find DNA that is involved in the disease and not just the ~1% that is already different between individuals.  But wait, we’re not done yet!  The biomarkers that you identify have to be validated – or double checked – to make sure that these differences just weren’t found by mistake.  And before biomarkers can be used in the clinic, they need to be approved by the Food and Drug Administration (FDA)

biomarker_discovery

From http://www.pfizer.ie/personalized_med.cfm


Whew… that was a lot of work! And so many people were involved: lead scientists who directed the project and got the money to fund it, researchers who do most of the work, computer people who are experts at crunching all of the data, and maybe even engineers to help run the equipment. Finding the biomarker needle in the biological haystack is difficult and takes time, money, and lots of people.  This is one of the reasons why there are only 20 FDA approved biomarkers for cancer (data from 2014).  But just because it’s difficult, doesn’t mean it’s impossible.  Furthermore, this effort is necessary to improve healthcare and decrease healthcare costs in the future.  It just might take a bit more time than we’d all like.

If you want to read more about the challenges and some of the solutions to biomarker discovery in cancer, take a look at this scientific article.  Or read about some successes from right in our backyard at Arizona State University on identifying biomarkers for the early detection of ovarian cancer and breast cancer.

 

Why did I leave the lab? My career path.

I received a question over email about why I’m a program manager and no longer doing research at the bench.  You may remember how I originally got into science and why I love science so much, but ultimately I have decided to “leave the bench” (which is what scientists say when they no longer work in the lab or run their own lab) and transition into program management.  Here’s why.
The start of this transition happened during graduate school.  I loved working in the lab and the thrill of discovery.  I even figured out how to deal with the constant failure that I think all PhD students encounter in their experiments on a daily basis (but that’s a topic for a whole other post).  At the same time, I knew that I was a bit different from most scientists because I was very socHTial and enjoyed talking about science as much as I enjoyed doing it.  So during graduate school, I found different opportunities outside of the lab to see if I liked and was good at science communication. I wrote a few articles for the Harbor Transcript (my graduate school institution’s magazine – check out my article about my graduation here) and I interviewed researchers on camera for the Cold Spring Harbor Laboratory Annual Symposiums (you can actually still find these interviews online, for example here and here).  After I graduated with my PhD, I did a short research project as part of my postdoctoral fellowship (aka postdoc), but realized that I wanted to spend more of my time away from the bench.
This transition was initiated in part because of the experiences I described above in wanting to communicate science, but also because I realized that if I moved forward on the research path my life wouldn’t have the balance that I wanted.  To give an abbreviated idea of what this research path would be like, after one or two 4-6 year stints doing research in other people’s laboratories as a postdoc working every weekend, I would maybe able to get a tenure track job at a university where I could start my own lab.  I would then be responsible for starting a research program, finding grant funding, and publishing for my career survival and the survival of everyone who worked in my lab.  Just to clarify, I am glad that there are so many people (many of whom are my graduate school colleagues and friends) that take this route.  It works for them, they are amazing at it, and they perform the amazing scientific research that changes the world.  I just knew it wasn’t the path for me.
me_in_the_lab

Me in the lab at Arizona State University

So when I went to look for jobs, I specifically looked for positions where I could be a part of a lab or involved in science, but not have to do lab work in the same way as I would if I were working toward that tenure track position.  That’s how I became the Scientific Liaison (essentially an awesome name for a program manager) for a biorepository of plasmids at Harvard University (before we moved it all to Arizona State University). This was appealing because I was part of a scientific center, so I could still be involved with the research, but I could also do so many other things! My job included writing grants, building websites, doing marketing and outreach, writing papers, giving talks, teaching undergraduate classes, working with the public to better understand science, doing strategic planning, learning how to budget, managing people etc etc. It provided me with a balance that I craved along with something new and interesting to do or learn every single day.  I’m now the program manager for a biorepository that collects and stores tissue samples for research at a hospital, and again, I love that I get to be a part of other people research but also do so many other things that I enjoy doing.

As a final note, often a PhD scientist who chooses to get a job doing anything besides having their own lab in a tenure track research position is said to have an “alternative career.”  I (along with many others) insist that these are not “alternative” careers, but rather just careers. Exciting, scientifically stimulating, important careers. As I look at my graduate school colleagues, many of them are successful researchers on the tenure track, but I have just as many colleagues who are in business development, consulting, marketing, editing and on and on.  All of them still use their scientific background and the skills learned in graduate school, like critical thinking, every single day in their successful careers.

What is a scientific society and why do you join them?

secret_societyWhen I first met my husband, he saw on the top of my pile of mail a magazine for the “Protein Society“.  He proceeded to ask me about the secret handshake and our underground rituals. And what about the outfits?  Are there robes?  There must be robes!  That’s when I realized that  most people know nothing about professional scientific societies.  Since I’m spending this entire week at a scientific meeting for the International Society for Biological and Environmental Research (or ISBER – pronouced “is-burr” – for short), my blog posts this week are going to be all about scientific societies and scientific meetings.

In science there may be hundreds (thousands?) of professional societies.  They can have membership based in the United State or can be international.  They can have a broad focus like the Protein Society or a very specific focus, like ISBER. They can have hundreds of members or thousands.  The American Association for the globalpeopleAdvancement of Science boasts over 120,000 global members!  There are many purposes for these societies. They bring scientists with similar interests together so that they can share ideas.  As a group, the society can also have a single voice to collectively educate the public to explain certain controversial pieces of research or to advocate the government to attempt to change laws, policy or funding affecting scientists. Many societies have their own journals and provide a forum to publish articles of particular interest to that group of people.  For example, the official ISBER journal is Biopreservation and Biobanking.  Depending on the society, they could be managed by hired staff, a subcontracted management group, or exclusively by the member volunteers.  For example, ISBER is managed by Malachite Management Inc., and I volunteer on the Membership and Marketing Committee (to help recruit new members) and the Programming Committee (to help plan the annual meeting).  Societies also provide support for young researchers through networking, mentoring, education and career opportunities.  And this brings us to the annual meeting, which most societies also have, in various locations around the country or around the world to bring researchers together to talk about their research, network and learn.

To give you an example of different kinds of scientific societies, I have listed below the societies that I have either been a member of or attended a meeting (and presented in one form or another) for.

Because I’m trained as a cell and molecular biologist, most of my society affiliations are related to that, however there are scientific societies for Neuroscientists (people who study the brain), Microbiologists (scientists who study bacteria and other microbes), Physicists, Mathematicians, Physicians, and on and on.

Since I’m at the ISBER Annual Meeting this week, my next blog post will be all about meetings and what exactly we do at them (besides drink cocktails).

Is there no such thing as a stupid question?

hole_knowledgeQuestions are central to being a scientist.  The scientific method starts by observing the natural world and then asking questions to figure out why things are they way they are.  Because so much is already known, a lot of these questions can be answered by teachers, scientific articles, or the internet (with a generic warning about being cautious about what you find online).  Invariably, you will bump up against a wall where nothing more is known.  In graduate school, we were challenged as scientists to find where there is a hole in the scientific knowledge, develop a hypothesis to explain what might fill this hole and then ask even more questions, through experimentation, to fill the hole. But questions aren’t just important for a graduate student,  They are important for everyone.  The reason that you’re reading this blog is to get your questions answered, and to better understand science and your health.  You life depends on your scientific literacy and your willingness to ask questions (as so aptly written about it this Slate article).

I want to help you gain confidence asking questions, so I’m going to start with my trials and tribulations in graduate school because I often felt inadequate at asking questions.  That may sound ridiculous to you, but as a young scientist at a world-renowned research institution, asking questions served one of three purposes: 1. It helped you better understand something, 2. It helped the person you were questioning by adding something insightful to the conversation or 3. It made yourself look smart (or look like a smart ass) by asking a question that will baffle the person you’re asking.

jurassic parkI was usually really good at asking questions to better understand something.  I was completely okay and confident that I didn’t know everything.  In fact, I may have been a bit too okay with not knowing things, to the point that I wouldn’t trust my thoughts and ideas when talking to other scientists (more on that later).  My absolute favorite example of my young inquisitive mind is what I now affectionately refer to as the “dinosaur question”.  In our neuroscience class we were talking about vision and how the rods and cones of the eye connected to the brain to form images.  My most pressing question was “If all we have left of dinosaurs is their skulls – so no idea of their rods and cones and neurons – why do we know that some dinosaurs could only see movement”.  Now this truly baffled my instructors until one of them finally asked me, “what evidence do you have for this piece of information” and I confidently responded “Jurassic Park!”.  Although the question may have been a bit dumb, I think it’s important to ask all of the questions you have since they are all learning experiences (even if it in the end, you don’t get an answer about dinosaurs)

As for the second type of questions – the insightful question – when asked in a gracious questionguyand truly inquisitive tone, can help clarify someone’s research, help them think of something they haven’t thought of before, or help make a connection between something new an interesting.  These are fabulous questions leading to new trains of thought and opening up fascinating conversations.  These were a challenge when I first started as a scientist because I didn’t have a lot of background knowledge that I could bring to the table.  Not only that, I lacked the confidence to speak up when I thought I had an interesting idea to add to the conversation.  It was only after hearing the exact same question or insight that I was going to ask, asked by someone else enough times that I gained the confidence to finally chime in.

The third type of question is my least favorite.  I’m sure that this isn’t just done by scientists, but far too often people ask a question where the main intent is to make yourself look smart.  And in the meantime, you end up making yourself look mean-spirited and the person your questioning feel bad.  Now don’t get me wrong – there are times when someone really doesn’t know what they are talking about and probably some serious questioning is needed, but it’s the spirit in which this is approached that makes all the difference.

So why am I writing a whole blog post about asking questions?  My goal is to help empower you by giving you answers to your questions through my blog posts, to provide you with information that will give you more confidence to ask more questions to your doctor, to your colleagues, or to me (and your question may even be featured on my blog!), and to help you in your path toward science literacy.  Remember, at one time, we are all asking dinosaur questions or aren’t confident enough to speak up, but there is no such thing as a stupid question so ask away!

Is love part of your DNA?

Happy Valentine’s Day!  On a day where people are overdosing on chocolate and champagne and whispering sweet nothings into each others ears, I want to tell some stories.  Three short stories (well, two stories and a research paper) that have to do with love.  And maybe not exactly love, but attraction, sex and genetic compatibility.

The Three Fs

When I was in graduate school, the research faculty at my institution (which, by the way is 125 years old and has created an awesome video about the laboratory here) focused on a lot of different scientific topics ranging from understanding cancer better to figuring out how the brain works.  Each Friday, we held “In House”, which was a seminar that the entire institution attended and one faculty member spoke about their recently published research.  My favorite line of all time from one of these seminars was a neuroscientist discussing the “The 3 F’s” that drive all life:  Feeding, Fleeing, and Mate Selection.

Ba dum tsssh…

No Genetic Disappointments

Photo Feb 14, 10 16 17 AMI think that every person on the planet has had their fair share of dating duds. I was no exception, however my Mom’s method for handling these less than ideal suitors was at times hysterical.  Typically, when people think about compatibility they consider whether one person is a night owl and the other person likes to wake up early or if they both enjoy the same hobbies.  However, my Mom decided to appeal to my scientific side and focus on genetic compatibility.  In particular, we discussed how we wouldn’t want my future children to end up with less than desirable personality or character traits through combining their “loser” genes with mine!  Well, scientifically, it doesn’t exactly work that way, but it was an entertaining topic of conversation.  So much so that when I met the author Tom Wolfe and had the opportunity to chat with him over coffee and dinner when he was researching “I am Charlotte Simmons“, I discussed my Mom’s argument in detail. When he inscribed my first edition of his “Bonfire of the Vanities” book, it charmingly said “To Cathy: with fond hopes there will be no genetic disappointments”

And you thought he should do his laundry

One of my favorite experiments (and well covered in the press) studied attraction using sweaty T-shirts.  The researchers had men wear a T-shirt for 2 days, and then women were asked to smell the sweaty T-shirts and decide which she found most attractive.  The interesting result, published in 1995, showed that women were more attracted to the scent of men who were more different from 6555 010them genetically.  The researchers determined this genetic diversity by looking at a set of genes call the Major Hisocompatibility Complex (or MHC, for short).  This is a family of genes that make proteins that mediate immune response.  There are 10 different MHC genes in humans, and each of these 10 MHC genes are slightly different genetically in different people.  These differences are what, for example, result in rejection in organ transplants or skin grafts.   These differences, however, are also what the researchers in the sweaty T-shirt experiment found attracted people to one another. The more different the MHC of the T-shirt wearer was from the T-shirt smeller, the more attractive the smeller found it.

Why did the researchers think that these “opposites attract”?  Honestly, they weren’t entirely sure.  One of the hypotheses was that it could be a way to increase diversity of these important immunity genes to improve our defenses against disease.  But does it really matter?  Because now your significant other will have a reason not to do the laundry – to be more sexy in the name of genetic diversity!