What does the “typical” career of a scientist look like

I kind of hate this title. It’s horribly discouraging for young scientists to assume that there is a “typical” career path.  However, over the past 50 years or so, there has been an “expected” path for all “real” scientists to take.  All of the quotation marks are implying that this isn’t the case – it hasn’t really been the case for the past 50 years and it certainly isn’t the case now.  But there was an expectation from the senior scientists and colleagues surrounding you that this is the path to take. (note: this is coming from the point of view of a biology PhD, which I have experience with.  This may be entirely different for other science degrees like math or engineering)

You start with graduate school. Three to six (or seven or eight or nine or ten!!) years of working in a laboratory and writing a thesis.  Hopefully along the way, you’ve written a few grants and peer-reviewed publications.  You’ve networked with colleagues in your field and found great mentors that have helped you along the way.  Before the thesis has even been written and defended, you take all of this hard work, and wrap it up into a curriculum vitae to send to principal investigators (also referred to as a PI) of laboratories that you might be interested in working in as a postdoctoral fellow (also called a post doc). If the PI has space (meaning funding) and is interested in your work, they may invite you to interview. During the interview, you will give an hour long presentation of your PhD work and the rest of the day will be spent with the PI and others in his/her laboratory talking about what they do, how they do it and whether or not you’re a good fit for the lab.  Most PhD graduates go on multiple post doc interviews.  I went on three before I realized that I didn’t want to do a postdoc.

Once you are offered a postdoc, you usually move to a new state and a new institution. There is a stigma that doing a postdoc at the same place that you do you PhD, even if it’s in a different lab, will not provide you with a varied enough research experience.  You are encouraged as a postdoc (and as a scientist, in general) to be okay with moving around. If you’re married, you and your spouse have to figure it out. Have kids?  Same deal.

So what do you do as a postdoc?  You do research in a laboratory, but with more independence than a graduate student.  You are often responsible for writing grants and supervising undergraduate and graduate students.  You are expected to work just as hard – nights, weekends, whatever it takes.  And now, your goal isn’t to graduate, but rather to get enough publications in high profile journals that you can get a faculty position.

How hard can this be?  There have been a lot of articles on this topic, so I won’t rehash here (you can read more in a recent Nature article about the “Future of the Postdoc“) except to say that there are more postdocs than there are faculty positions – BY A LOT. So you really have to stand out. Plus, you have incentive to get a faculty position because postdocs are not paid very well – the NIH salary cap for first year postdocs is $47,000.  Keeping in mind that this is not a 9-5 job, but usually a 60+ hour per week job.

How do you know you’ve completed a postdoc? You don’t.  You either feel like you can start applying for faculty positions or not.  If not, you may want to do a second postdoc.  It’s not uncommon for people to do two 4-6 year postdocs before applying for faculty positions.

Now, I don’t have personal experience applying for faculty positions, but I have many friends who do.  The process of applying is like applying for many other types of jobs except there is an application “season” so that acceptances will come out in advance of a new academic year. Of my friends who have applied for faculty positions, the fewest jobs someone has applied for is about a dozen, but it’s not unheard of to apply for 40 or 50 positions with the hope of getting a handful of interviews.

Because this is so competitive, location is only a passing consideration. You may love Florida, but you’re moving to Minnesota if the best job offer is there. There’s also this fascinating phenomenon in science called the “two body” problem (see more in an interesting Scientific American article). This is when both partners are scientists and looking for jobs in the same place at the same time.  It’s an incredible challenge, and I know many people who have lived in different states from their partner for months to many, many years.

Although a faculty position isn’t the end of a journey – there still tenure, inventing something and start a company, moving to a new institution and all the other ups and downs that come with a job – this is the “typical” goal of many scientists. And it’s a wonderful goal.  It’s a hard road to tread, but without dedicated researchers willing to take the time and sacrifice needed to get to this point, there would be far less scientific innovation and discovery happening in the US.

On a personal note, when I was in graduate school, I distinctly remember a conversation I had with an unofficial academic mentor (thank you Bill Tansey for being so supportive all those years). I was getting close to graduating and he asked me what I wanted to do when I graduated, since he expected that I was applying for postdocs with the goal of becoming a faculty research scientist. I hadn’t once considered taking this typical career path (you can read more about my journey here). But I remember feeling proud that he thought that I could. It actually made me realize that even though I wanted to take a different path, that it wasn’t from lack of intelligence or academic ability. It’s just that we all take our own path, and mine wasn’t going to be “typical.”

 

 

 

Stem Cells to Treat Spinal Cord Injury

Journal Club: Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury

Written by DePaul, et al. in the journal Scientific Reports. The complete article is here.

Background: Stem cells are unique in that they can divide indefinitely and can turn into multiple different types of cells (see image below).  For example, during human development, embryonic stem cells have the ability to turn into all of the different cell types throughout the body – such as liver cells, lung cells, and skin cells. Embryonic stem cells are called pluripotent stem cells for this reason.  Stem cells have also been found in adults, but they are usually able to turn into only one or several types of cells (called multipotent stem cells).  Scientists have thought that this ability for stem cells to continually grow and turn into different cell types could be harnessed to treat a number of diseases that involve cell death, including spinal cord injury.

Stem cells - wikipedia

By OpenStax College [CC BY 3.0], via Wikimedia Commons


The authors of this paper are interested spinal cord injury (SCI).  When the spinal cord (the bundle of nerves that goes down your back) is injured when something disrupts the vertebrae (like it being hit during a car accident) this can tear or push on the spinal cord.  This causes damage to the nerves and prevents electrical signals between the body and the brain from being transmitted properly, often resulting in paralysis. The authors were interested in studying whether stem cells could help reverse the damage that’s caused by this type of injury.

Results: In this publication, the authors isolate stem cells called multipotent adult progenitor cells (MAPCs) from the bone marrow. To break this down, “multipotent” means that the stem cells can turn into several different cell types. “Progenitor” cells are actually more specified than stem cells – stem cells can divide forever, but progenitor cells can only divide a certain number of times. “Adult” means that these cells are taken from the adult bone marrow.

Because you can’t just inject cells into humans with spinal cord injury (that would have to be a clinical trial WAY down the road once there is evidence that it works in animals), the authors use a “model” of spinal cord injury in rats. Technically – they crush the rat’s spine (eek).  In case you’re interested, here’s the device they use to do this. The rat then has decreased mobility and inability to urinate on it’s own – like what might happen in the case of a paralyzed person with a spinal cord injury.

The researchers injected multipotent adult progenitor cells into the rat after injury to see if they reverse these mobility and urination effects.  Interestingly, when MAPCs are injected into a rat vein the day of injury, nothing happened. However, if the MAPCs are injected 1 day after injury, the rats recover some mobility and the ability to urinate on their own compared to rats without treatment.

One might assume that the MAPCs do this by going to the injured area of the spinal cord and re-growing nerve cells.  However, the authors found that this wasn’t the case.  In fact, the MAPCs moved to the outside edges of the injury and even more to the spleen (see image below).  The spleen is where many of the body’s immune cells are stored. In spinal cord injury, the immune system is a double-edged sword.  The immune system cleans up the damage from the injury itself but also attacks the injury and makes more damage.  There is evidence from this paper that the MAPCs in the spleen decrease the damaging effect on the spinal cord injury from the immune cells in the spleen.

figure 6 SCI

Figure 6 from the paper. The green dots are labeled multipotent adult progenitor cells (MAPCs). They are labeled green so that you can see where they are located in the rat’s body.

Conclusion: This paper presents a promising result that provides hope for this type of therapy in spinal cord injury patients.

What’s been going on?

It’s been a while since I’ve been able to blog.  I have lots of reasons, but one of the big ones is that I’ve been writing and editing for some other sites!

In mid-January, I wrote an article for the ISBER News Blog (ISBER stands for the International Society for Biological and Environmental Repositories – the premiere biobanking society in the world). The article entitled “Have you joined the ISBER social network? Facebook!” is all about how to get started on Facebook and how to get more involved with ISBER through that social media outlet.  If you aren’t on Facebook already, you may find the first half of the article useful.  Once you join, you can follow the “Things I Tell My Mom” Facebook page where I post often about interesting science I find around the web.

From this experience, I was named the new Assistant Editor for the ISBER News Blog. This was announced in a very funny article from the current editor Rick Michels called “Bringing in Backup.” I’m super excited about this new role and have jumped right in to help edit lots of interesting articles from the biobanking world.  I hope many of them will be interesting to the public, and I’ll be sure to share them either through this blog or on my Facebook page.

As part of my job, I endeavor to educate the public on the importance of biobanking in enabling cancer research. To both work towards this goal as well as to talk about the Biobank’s support of World Cancer Day, I wrote an article for the Barrow Neurological Institute blog about what our Biobank does to help cancer research. You can find that article here.

And because that’s not nearly enough, my first article for GotScience.org was published today. GotScience is a fabulous website with the goal of increasing the public awareness about science – a perfect fit for my goals and dreams! I adapted an article that I first published on this blog for GotScience about “What is a biobank?” (I think you can see a theme emerging). Please check it out along with the other articles on GotScience!

Finally, I’ve been helping out an editor friend of mine at PN Online – a magazine to help people who are wheelchair bound. I contributed to an article about this great new ALS research called “Early ALS Treatment.” I adapted my work for this article to a journal club blog post that you can read here.

I promise I’ll be back to writing on this blog soon, but until then, enjoy the articles I shared above!!

#WeCanICan #WorldCancerDay

A year ago tomorrow, I posted my first blog post. A year and nearly 100 posts later, I maintain the same mission I started with: to empower you with scientific knowledge so that you can make more informed decisions about your health.

February 4th is World Cancer Day, and they are running a social media campaign called “Talking Hands” so that people around the world can say how they take action to help prevent and fight cancer.  Besides what my biobanking team and the other clinical research teams are doing at St. Joseph’s Hospital and Barrow Neurological Institute to fight cancer, this blog is my personal contribution. I hope that in some way this helps you feel empowered to ask questions about yourself and your health, and in the case of a cancer diagnosis, feel better prepared to tackle your road ahead.

What can you do?

Photo Feb 02, 8 26 24 PM

Sci Snippet: Cancer vs. Tumor: What’s the difference?

It doesn’t matter to you what word you hear if you or a loved one is told by a doctor, “You have cancer” versus “You have a tumor.” Either way, there’s a wave of fear that is likely sustained through months, years, or a lifetime of treatment. It’s a diagnosis that nearly everyone has been touched by, so it’s something that everyone has talked about at one time or another.  The words tumor and cancer are typically used interchangeably, especially by people who are not in healthcare.  But it helps to know that there is an important distinction between cancer and a tumor when describing a mass of cells growing somewhere in the body.

The most important point is that a tumor DOES NOT mean cancer.  A tumor is a whole bunch of cells growing out of control (think of it as the cell turning on the gas pedal for cell division) creating a mass somewhere in the body.  Cancer, on the other hand, means that these cells have the potential to move and invade other parts of the body.A tumor can be benign (not cancer) or malignant (cancer).

Image of a benign meningioma. Thanks to Wikipedia for the image.

Image of a benign meningioma. Thanks to Wikipedia for the image.

What does it mean to be benign? A benign tumor still a huge mass of cells, and even though it may not spread to other parts of the body (the definition of malignancy and cancer), the mass could grow so large it presses against vital organs requiring surgical removal or causing death.  An example of a benign tumor is a meningioma.  This is a brain tumor that grows out of the covering of the brain and spinal cord, called the meninges, and although they do not typically spread to other places in the body (so they are not considered cancer), they do put pressure on the brain and spinal cord and usually have to be removed and may be treated with radiation.

benign_malignant

Thanks MedicineNet.com for the image

Cancer, on the other hand, is a tumor that has the potential to spread to other parts of the body, which is called malignancy.  This is one of the reasons that cancer is called cancer – from the Greek meaning crab because of the crab-leg like projections that are found in tumors that are invading neighboring tissue.  Tumors may be benign, malignant, or transition from something benign to something malignant.  For example, in the breast, masses of cells can form like papillomas that are a benign tumor that will not spread to other areas of the body. However, a breast cancer diagnosis implies that the breast tumor has the possibility to spread.  The only way to know whether a lump is a papilloma, breast cancer or something else is through a doctor and a biopsy.

It’s also important to note that not all cancers involve a tumor.  A great example of this are blood cancers that involve the increased growth of a particular type of blood cells, but will not have a tumor.

And in case you’re wondering where cysts fit into this, these are sacks filled with fluid, air or some semi-solid material. Cysts can be caused by a number of things including infection or clogging of glands. They may indicate a risk factor for a tumor or cancer, but are not cancerous themselves.

 

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.

Journal Club – A mutation in mice to study ALS

Amyotrophic Lateral Sclerosis (ALS) is a debilitating neurodegenerative disease that affects neurons in the brain, brain stem, and spinal cord. When these neurons die, it affects the connections that they have to muscles throughout the body resulting in muscle weakness that affects speaking, swallowing and breathing leading to paralysis and eventual dead.  The cause of ALS isn’t known in 90-95% of cases.  However, recently scientists have identified a mutation in a gene nondescriptly called “chromosome 9 open reading frame 72,” which is abbreviated to C9ORF72.  This mutation results in six nucleotides, GGGGCC, being repeating up to 1000 times within this gene in ALS patients.  Even though this is the most common mutation found in ALS patients, it’s still unclear exactly how these repeats affect neurons or the progression of the disease. The two hypotheses that are most studied are that the mutated C9ORF72 makes mutated RNA transcripts (RNA is the molecule that usually helps DNA be translated into proteins) or makes unusual proteins called dipeptide repeat proteins (DRPs), each of which can aggregate (clump) together and disrupt the normal activity of the neurons leading to neurodegeneration.

neuron_als_c9ORF72

The pink dots show clumped up RNA from the many many repeats in the C9ORF72 gene. Each panel shows these clumps in different areas of the mouse brain. Taken from the article Peters et al. 2015 Neuron

In two recent publications in the journal Neuron, researchers have used mice as a model system to look at how these large GGGGCC repeats in C9ORF72 affect the mouse nervous system.  Why use a mouse? First, scientists know how to experimentally change the mouse genome in order to add hundreds or thousands of repeats to a single gene, like C9ORF72.  Second, mouse and human genes are about 85% identical, so if scientists can understand how a gene like the mutated C9ORF72 affects neurons in mice, it may also help scientists understand how it works in humans. Third, by creating a mouse “model” of ALS, scientists can use this model to better understand ALS and to test potential future therapies (it’s worth noting that only one drug currently exists for ALS and it typically extends life only by a few months).

In each article, the mouse model was slightly different – one had a mutated C9ORF72 with 500 GGGGCC repeats and the other varied between 100-1000 repeats. However, both sets of researchers found the same results.  The mice had aggregated RNA transcripts and DRPs in their neurons just like what are found in human patients with ALS, but none of the mice had behavioral changes or neurodegeneration that are seen in human ALS patients.  So why didn’t the clumped up RNA and proteins cause neurodegeneration in mice like they do in humans?  There are lots of potential reasons – including the fact that even though mice and humans are similar, there are still lots of differences and mice may respond to these aggregated RNA and proteins differently than humans.  However, the authors of these papers suggest that other environmental and/or genetic factors along with the aggregates caused by the C9ORF72 mutation must be involved in developing the neurodegeneration.  It may also mean that getting rid of these aggregates before neurodegeneration occurs may prevent development of ALS.  Now that these mice are available to study, they should help in identifying the other factors involved in ALS development along with developing possible treatments for this debilitating disease.

Want to read the articles?  Unfortunately, they are behind a paywall, but you can see the abstracts here:

O’Rourke et al. (2015) C9orf72 BAC Transgenic Mice Display Typical Pathologic Features of ALS/FTD. Neuron. Volume 88, Issue 5, p892–901, 2 December 2015 Article

Peters et al. (2015) Human C9OFR72 Hexanucleotide Expansion Reproduces RNA Foci and Dipeptide Repeat Proteins but Not Neurodegeneration in BAC Transgenic Mice. Neuron. Volume 88, Issue 5, p902–909, 2 December 2015 Article

Read the Article from PN News that I contributed to here

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.