Together Everyone Achieves More (TEAM): Lessons from Biotech

“Don't think you are the smartest person in the room, to be a successful company you never should be.”—Mathew Sowa


Regardless of where you are working, good science is driven by active curiosity and asking good questions. The differences come in how you approach answering those questions. Continuing our ongoing discussion about biotech careers, this blog will describe some key differences between academia and biotech along with some advice on how to utilize what you learn during your academic training to succeed in biotech. A huge thanks to Michelle Lin (Research Scientist at CRISPR Therapeutics, ~1 year in biotech), Mathew Sowa (Director at C4 Therapeutics, 5+ years in biotech), and Hariharan Jayaram (Associate Director at Editas Medicine, Inc., 6+ years in biotech) for sharing their experiences and advice!

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When asked about the biggest difference in day-to-day life in biotech vs. academia, all of our biotech colleagues agreed that team meetings now make up a much larger fraction of their time. This fact is especially true as you move up the corporate ladder; bench time quickly shifts towards more meetings focused on both scientific and strategic planning. Dr. Lin commented, “Some days I have as many as 10 meetings!”

 

The many meetings have much to do with the teamwork required for a biotech to succeed. Dr. Jayaram commented, “The biggest differences between biotech and academia are team work, the demands on rigor, reproducibility, and the end goal. Here is an example to illustrate how teamwork works and why it is so important in biotech. If you are characterizing a protein, many people might be involved and the group could have one or even two project leaders. One person may design the clones and express and purify the protein, another person may design and carry out the biochemical assays, and a third person may perform all the cell biological characterizations required to understand its behavior in cells.” In academia, all of these aspects might be a part of a single postdoc's project. Dr. Lin noted, “As a postdoc, you have to be a master of your project, controlling every aspect and learning every technique required for your project.  In industry, we work as a team and thus you're never alone if you're struggling with any aspect of your project. You utilize everyone's expertise to help drive the project forward.” Dr. Sowa agrees stating, “Academics, though often times collaborative, is still mainly an individual's effort, rarely including more than one or two additional people assisting with a project in an ongoing and meaningful way (though author lists can still be large due to lots of smaller contributions). If a biotech company is to succeed, all people involved have to work with each other and as importantly, work effectively together. If the project/program fails, typically so does the company and all of the people in it, regardless of how well each individual has done his/her work. In academics, if a project fails, the lab does not disintegrate as there are always multiple projects running (especially in larger labs).”

 

Teamwork is also important to increase rigor and reproducibility. Dr. Jayaram points out that “The increased scale and multi-team execution of a project allows for a more rigorous characterization. Teams are well suited to explore and analyze results from many angles to make sure all data is well characterized--no matter how routine or un-"sexy" the question.  This is particularly important when the end goal is to proceed towards clinical validation." 

 

In addition to team meetings on science, meetings discussing strategic plans and timelines are critical at a biotech. Strategizing where to put limited resources to ensure the biggest return is key to success. Unlike academia where we often let the science naturally unfold and follow interesting offshoots, which could take years, biotech is a moneymaking venture where time is the most precious commodity. Projects must stay focused to succeed, as the ultimate end product is a therapeutic. Dr. Sowa commented, “in biotech, there is a genuine sense of larger purpose - that is, the work being done is leading to something "real" (the drug) that will change people's lives for the better. It does not matter how many or in what journals papers are published, the only thing that really matters is that there is a new drug produced that will treat a human ailment/disease. I think it is that tangible goal, the physical drug, that truly differentiates academic science from biotech and keeping that goal in mind is where the initial similar "basic science" paths diverge.” 

 

Despite the many differences between academia and biotech, the basic principles of science and success remain true. Many skills you acquire as a Ph.D. student and postdoc prepare you for a job in biotech. Dr. Jayaram advises, “cultivating curiosity and thirst for problem solving coupled with seeing the bigger picture and focusing lines of inquiry are invaluable skills for success learned during PhD and postdoctoral training.” Dr. Lin pointed out that “people have the misconception that industry jobs are very constant, a 9-5 schedule, doing the same things over and over again, etc. While it may be true in some instances, the career path is also what you make of it.  If you choose to be a 9-5 person, you will be treated as a 9-5 person.  You can either choose to treat it as a job or as a career. You can work as hard as postdocs, sometimes even harder if you choose to and bring more value to the company.  Any career, whether it's in academia or industry really is what you make of it.”

 

Whether in industry or academics, it sounds like teamwork is a fun and effective way to do science!

 

Last bit of advice: Be humble and surround yourself with brilliant colleagues!

 

** The opinions in this piece do not reflect the opinions of CRISPR Therapeutics, C4 Therapeutics, or Editas Medicine, Inc..


Teresa V. Bowman, PhD
Publications Committee Member
Former Chair, New Investigators Committee

Assistant Professor, Department of Developmental & Molecular Biology
Assistant Professor, Department of Medicine (Oncology)
Albert Einstein College of Medicine
Bronx, NY
 

Non-scientific ways to approach the “reproducibility crisis”

Reproducibility is in crisis; or at least that is how 90% of more than 1500 researchers responded to a Nature survey conducted a few months ago (1). The statistics out of the survey are shocking. 70% of researchers have failed to reproduce another scientist’s experiments. The Nature editorial and the following special articles about reproducibility have brought back an old concern - can we trust scientific publications? The same concern was discussed in a workshop two years ago, held jointly by the NIH, Nature Publishing Group, and Science (2). Although the workshop triggered novel guidelines in grants and publications, the results from the Nature survey reveals that there is still “space for improvement.”

Last year, Science, published an article about reproducibility in psychological sciences (3). The “Reproducibility Project” recruited hundreds of scientists to perform 100 replication studies, and the results were shocking - fewer than half were repeated successfully. This raises more concerns, if two studies reach different conclusions, how can you tell which one is right? As an exacerbating factor, just imagine that one of the studies was performed by a big and well-recognized lab, and the other was performed by a smaller group; further, consider the potential outcome if that smaller lab is trying to publish it after the more well-known group- they are likely to face an uphill battle or end up publishing in a more obscure journal.

Reproducibility is essential to building scientific knowledge. My former mentor, Dr. Mayani (Oncology Research Unit, IMSS, Mexico City) always uses the phrase “on the shoulder of titans” (referring to the story of the Gemini, a NASA project before Apollo) as an analogy for how any new discovery is supported by an old one (the same analogy was also used by Iorns and Chong in reference 4). So every paper that can’t be reproduced affects other papers, causing a so called “domino effect.”

The scientific community is addressing the reproducibility crisis in many ways. PLOS One, launched in 2012, has a Reproducibility Initiative (5), which aims to provide a platform to publish validations studies. In 2013, Nature announced (6) new initiatives, most of which were focused on eliminating the length restrictions on the methods sections, encouraging authors to publish supporting data and share detailed methods. The NIH has revised grant applications and published a webpage focused on reproducibly (7), encouraging rigorous statistical analysis, data sharing, transparency in reporting, and sharing best practice guidelines. However, these new policies are not enough to encourage authors to publish validation studies, if they are not supported by grants. Fortunately, new grants are emerging that will focus on the specific objective of validating previous reports. For example, this year the Netherlands Organization for Scientific Research (NWO), launched a fund dedicated to replication studies with over $3.3 million USD for 3 years, but similar mechanisms are needed elsewhere if we have a serious commitment to addressing the issue.

Are the initiatives from the journals and funding agencies going to be enough to overcome the reproducibility crisis? In my opinion, they will reduce it, but they will not eliminate the problem. I think that there is a risk that most of the initiatives will target only novel discoveries or new technology. If we consider the possibility that most of what is published can’t be replicated in full, it will likely be impossible to secure sufficient funds to repeat even a small fraction of the current body of research. This is especially challenging given that we are dealing with a related “grant crisis”, limiting the number of studies funded due to worldwide budget cuts to research. 

I think the reproducibility crisis requires us all to re-think how we perform and publish science. As a brainstorming exercise, which will hopefully inspire others to think about this topic beyond reading this post, I have found inspiration toward ways to improve our scientific practice from outside of the field and shared them below.

From cocktails to the bench

Before attending our annual meeting in Kyoto last year, I had the opportunity to visit Tokyo. I was amazed by the city, but mostly by their people. One who stands out was Hidetsugo Ueno, a mixologist and owner of the High Five bar. He is well-known because he has no menu at the bar, and he customizes each drink to each client. But this is not the reason I was inspired by Ueno. He is also famous for his ice diamond carving technique. I have read about him, but I have to say that watching him preparing a drink was outstanding. Every step was performed with perfection - the way he pours the drink, shakes it, and places the ice into the glass. Every detail was considered - the quality of their products and the level of attention he puts into every step, repeated carefully over and over. You could see how proud he is of what he is doing and that he is driven by his passion. He made me think of a “simple” drink as a piece of art. And he was not the only one “mixing” at the bar; the same experience could be derived from any of his personnel, which is likely the result of his good training. The lesson from Ueno about reproducibility was to pay attention to the quality of all aspects of your activity, from the “reagents” to the execution of the “methods” and most importantly the training all your personnel, so that you get the same reliable and high quality results from any of your team members.

Medals come from good execution of the fundamentals as much as novelty

I was unexpectedly inspired by gymnastics as I watched the recent Olympic games with my sister, who is a former gymnast. She explained to me that while every routine is made up of “free” exercises, which are new and chosen by the gymnast,  each also has obligatory exercises, a set of movements that must be integrated to ensure a good score. So I thought about having “obligatory experiments” for each paper, a solid foundation which consists of the repetition of former experiments (to validate them and encourage reproducibility) together with the novel assays (the “free exercises”). Given our focus on “new” ideas, I think might be better to try to establish a precedence to include a proportion of replication experiments on each paper, instead of having a 100% validation paper. Perhaps we can offer to include (and tolerate as a reviewer) a fair percentage (like 10-20%) of repetition of key experiments and or validation of reagents that support our current observations as a “requirement” for any publication. This would extend and better illustrate the general principles of the approach then is currently included in most “methods” sections, providing enough information so the reader does not have to look up all the prior data and/or methods to understand (or believe) the experiments shown. Obviously, this would require a commitment not only at the level of the researcher and manuscript reviewer, but the editors, funding sources and even, when applicable, animal oversight committees. Whether it is a total validation study or a 10-20% validation paper, I believe it is essential that any validation attempt and results are published as part of the full report of each new scientific publication.  Related, together with most of my colleagues, I think we need to discourage the use of blogs or social media to publish validation results, which can discredit our colleagues and  lack scientific rigor, including peer review and a clear mechanism for response from the original authors.

The Devil’s advocate and science’s “worst sin”

I think I can use an Al Pacino quotation for any example in life or science, but for this blog I like his quote on his role on the movie: “Vanity, My Favorite Sin”. Scientists are under a lot of pressure not just to publish, but to publish novel findings. There is a time limit for grants, graduate theses, postdoctoral stays, which can contribute to the growing phenomenon of “rushing science”. Related, publishing what is perceived as a truly novel story often leads to recognition by ones peers, including further speaking opportunities, additional funding and even extra institutional support. As scientists, and especially for new investigators, we need to build our careers with firm steps, with studies that can be not only validated, but that are solid foundational knowledge “stones”. We must fight back the seduction of publishing a preliminary, but novel finding, and the fear of someone else publishing it first. We should avoid sending out a manuscript before is truly ready, with similar results derived from a variety of assays and with all the appropriate controls and alternative explanations considered. A solid story will presumably have a longer life then a quick flash, later proven to be not quite right.

The reproducibility crisis is dangerous. It can send the wrong message to the public, with both bad and good science losing credibility, but most importantly:  this crisis is dangerous to scientists. We count on each one of us to build our knowledge further. In science we are never alone, even if we have never met the author of a paper, we owe him/her for the previous contribution and for being the “giant” from which we based our hypothesis. Scientists have a very important job that we have to perform with excellence and passion. Science has no space for mediocrity. Findings should be judged by the rigor and quality of the experiments behind them, and not only on novelty. Scientists are always pushed to find novel and useful knowledge, which may or may not be equal to hard work and excellence. To me, the current model in science is analogous to paying a traffic policeman by the number (or amount) of tickets written, and not because he/she performs their job with ethics and quality. This crisis will end when employers, funding bodies, and publishing houses recognize scientists for the way they conduct science, including long-term impact and use by others as a foundation for new discovery, not for the short-term surprise of their findings.

Acknowledgments

I want to thank Trista E. North (BIDMC Harvard Medical School) from the ISEH Publications Committee for all her help editing this blog post.  I would also like to thank my former mentor, Dr. Hector Mayani, for all the lessons I have learned from him.

Citations:

1. Baker Monya. Is there a reproducibility crisis?. Nature. 2016;533:452-454.
2. https://www.nih.gov/research-training/rigor-reproducibility/principles-guidelines-reporting-preclinical-research
3. Open Science Collaboration. Estimating the reproducibility of psychological science. Science.205:349(6251).
4. Iorns E and Chong C. New forms of checks and balances are needed to improve research integrity. F1000Res. 2014 May 28;3:119. doi: 10.12688/f1000research.3714.1. eCollection 2014.
5. PLOS Blogs. http://blogs.plos.org/everyone/2012/08/14/plos-one-launches-reproducibility-initiative/
6. Announcement: Reducing our irreproducibility. Nature. 2013;496(7446):398 10.1038/496398a
7. https://www.nih.gov/research-training/rigor-reproducibility  

 

 

Eugenia (Kena) Flores-Figueroa, PhD

ISEH Publications Committee Member

 

Oncological Research Unit at the

Mexican Institute of Social Health (IMSS)

Mexico City, Mexico

Interview with Current President David Traver about the Upcoming 45th Annual Scientific Meeting of the International Society for Experimental Hematology (ISEH)

In advance of the upcoming 45^th Annual ISEH Scientific Meeting, we spoke with current ISEH president David Traver, Professor of Cellular and Molecular Medicine at the University of California San Diego, about the highlights of the upcoming meeting in his current hometown and his thoughts on the society.

What is the focus of this year’s ISEH meeting?

 

We have tried to maintain the excellent breadth in all major areas of hematopoiesis research, with cutting edge talks across each discipline.  For example, we have a superb lineup of speakers in our Gene and Cell Therapy session, as well as a variety of thought leaders in our Leukemia and Developmental Hematopoiesis sessions.  As always, we have also worked to highlight our best young scientists at the meeting.

 

Are there any new formats/features that are not to be missed?

 

Yes, speaking of our trainees, we have started a new Pre-meeting Workshop this year for 50 of our young scientists.  It will feature posters and several short talks by students and fellows.  This format will encourage informal interactions among our trainees and mentoring by several noted scientists in the field, including Jim Palis, Nancy Speck, Anna Bigas, Dan Kaufman, Marella de Bruijn, Mick Milsom, Sofie Singbrant, and Merv Yoder. 

 

Are there any particular speakers that you are excited are participating this year?

 

Well, as president it has been particularly fun to invite three of my favorite scientists to speak in the Presidential Symposium – Nancy Speck, Leonard Zon, and Gordon Keller.  This will really be a special treat to feature them together at our meeting in August.

 

What makes ISEH special?

 

ISEH has always been my favorite meeting as it is large enough to attract the top speakers in the field but small enough to feel like family.  There remains a core group that nearly always attends, making sustained interactions possible over the years.  In addition, it is the best meeting that I attend in regard to fostering meaningful interactions between our young scientists and the leaders in the field.  I think this is due to both informal scientific discussions over posters / trainee sessions and “Meet the Expert” style social sessions over drinks. 

 

How long have you been involved with the society?

 

My first real talk came at an ISEH meeting when I was a graduate student in Irv Weisman’s lab.  I remember being terrified to present in front of what seemed a huge and intimidating audience.  But the talk went well and served to introduce me to many of the fantastic scientists in our field that I continue to interact with today.

 

Is there an advantage to joining a society as a student or postdoc, rather than wait until it’s clear you will remain in the field?

 

I think so.  Aside from the obvious financial incentives, being part of the ISEH provides a real sense of community.  I recall being impressed at how easy it was to approach many of the brand-name scientists in the field when attending my first few ISEH meetings.  Their encouragement helped me want to stay and succeed in science, and within the hematopoiesis field in particular. 

 

Do you have any dream goals for the meeting or the society in years to come?

 

I hope that we can continue to improve the impact of our journal, Experimental Hematology.  It is the key to keeping our society and meeting going strong.  Most of our funding comes from the journal, so improving the quality of manuscripts submitted is more important than most realize.  We have seen a large increase in submissions over the past year, with similarly large increases in downloads from the website.  If we can keep this up, the impact factor (IF) should improve over the next few years.  With the journal publishing only a moderate number of papers per month, it actually doesn’t take a huge increase in citations to move the IF up in a significant manner.  If we can accomplish this, more will submit their work, with further increases in the IF to create a positive feedback loop.  This is key to maintaining a strong society and to continue our great meetings for years to come. 

We hope to see you at the upcoming ISEH meeting! To learn more about the meeting in San Diego this August 25-28, visit the ISEH website.

David Traver, PhD

Current ISEH President

 

Professor of Cellular and Molecular Medicine

Professor of Biology, Section of Cell and Developmental Biology

UC San Diego School of Medicine

La Jolla, CA USA

 

 

 

 

 

Trista E. North, PhD

Chair, ISEH Publications Committee

ISEH Board of Directors

 

Associate Professor of Pathology

Harvard Medical School

Beth Israel Deaconess Medical Center

Boston, MA USA

 

 

 

 

Transition from academia to industry: An interview with Elizabeth Paik

We have all read many articles about the possible career choices of a scientist. The usual dilemma is between industry and academia. We have talked about this in previous blogs but the more information we get the easier it is to make a wise choice. Of course we all have opinions about the pros and cons of such a choice but what I always find best is to ask people who have experienced both. That is why I turned to an old colleague and friend, Elizabeth Paik, and asked her some questions regarding her experiences in both academia and industry.

Can you describe to us your scientific career?
I started my career at Harvard Medical School, as a graduate student in Dr. Len Zon's laboratory. My thesis work focused on understanding a role of CDX transcription factors during embryonic hematopoiesis. Through ChIP-seq, knockdown and overexpression studies in zebrafish, I showed CDX transcription factors control expression of hematopoietic transcription factors - SCL and LMO2.

Towards the end of my PhD, ES and iPS field was blooming, and I got fascinated by how stem cells can be used to study human diseases. At the same time, I wanted to pursue translational research, having focused on basic biology during my PhD. I joined Dr. Lee Rubin's group at Harvard Stem and Regenerative Biology department. While in his lab, I used human iPS-derived dopaminergic neurons to study Parkinson’s disease. I also co-developed a purification method for midbrain dopaminergic progenitors to establish cell-based therapies for Parkinson’s disease.

After finishing my third year as a postdoc, I started my first job in industry as a scientist at CRISPR Therapeutics. I have been at CRISPR for nine months now, and it has been a very exciting and fulfilling experience.

Why did you choose to continue your career in industry?
I joined industry to pursue my interest in translational research. When I was a graduate student, colleagues in the Zon lab had discovered prostaglandin E2’s role in enhancing HSC self-renewal. Following the initial discovery, my adviser founded a biotech company focusing on translating this discovery into therapy. That was the first time when I saw how findings from an academic laboratory can be translated into therapies, and how industrial research can enable this transition. I thought being part of this later process would be very fulfilling.

I also liked the aspect of teamwork in industry. During my postdoc, I was working on a pharmaceutical company-funded project. The project was a highly collaborative one, where myself and two other postdocs worked towards establishing a stem cell therapy for Parkinson's disease. It was really exciting to work closely with them, and knowing that teamwork is a key in industry, I thought it would be a great fit for me. 

Do you use the knowledge that you received during your academic career for your industry career?
Being a research scientist, my daily job includes bench work, and designing experiments. I use skill sets that I acquired during my academic career every day. Back in graduate school, I had to custom-build many molecular biology tools because zebrafish had fewer ready-to-go reagents compared to other mammalian model organisms. Now that I am in a brand-new CRISPR field, I cannot rely on ready-made tools and even if there were tools out there, I have to run stringent quality checks on them. Therefore, my molecular biology skill sets earned during PhD years are extremely handy. 

Do you think it is easy to transition from academia to industry?
I think getting the first job in industry can be quite challenging. A lot of it depends on whether you are a good fit to the job requirements and the company culture. Because the job search can take a long time, it is important to stay positive through the process.

Do you feel you advance your scientific knowledge in industry?
Yes. Being in a small company, I need to be flexible and open to expand my knowledge of experimental tools and be creative regarding new ideas. For example, I learned a lot about the genome editing field since joining CRISPR Tx. 

What is the difference between research in academia and industry?
In industry, projects are goal-oriented, and have deadlines. You are expected to plan and execute in a timely manner so that you can achieve the milestones. You should be able to prioritize and efficiently use your resources to meet these expectations.

What would you advise someone who is lingering between an academic career and a career in industry?
I would actively reach out to people who already have a job in an industry and find out what it is like to work there. When I reached out to people, many candidly shared their experience, and I found it very helpful.  

Hopefully Elizabeth’s experience will be handy to many people looking for alternative careers out there. The key message is that transitioning to another job never wastes your prior knowledge. However, it takes time to find the right fit so you have to be patient, optimistic and take advice from the right people

Disclaimer: The views expressed here are solely those of the author and do not represent the views of the CRISPR Tx.





Elizabeth Paik, PhD
Scientist at CRISPR Tx
Cambridge, MA USA






Eirini Trompouki, PhD
ISEH Publications Committee Member

Group Leader
Max Planck Institute of Immunobiology and Epigenetics
Freiburg, Germany
http://www.ie-freiburg.mpg.de/trompouki

Research: the science of overcoming failure

"Perceived failure can become the catalyst of profound re-invention"
Conan O'Brien

On a cold Spring Sunday morning in western New Hampshire, Conan O’Brien, a Harvard alumnus, stood in front of 1,700 Dartmouth students for a commencement address. After initially teasing them about having an inferiority complex (as part of the Ivy League Colleges) he then said something that was as unexpected as it was wise, “Whether your fear it or not, true disappointment will come, but with disappointment comes clarity, conviction and true originality.”  For those who are not familiar with O’Brien’s work, he is not a scientist, although his speech seemed to be tailor-made for research. He is a very famous comedian that experienced failure shortly after reaching his lifetime goal (O’Brien became the host of the Tonight Show but was fired soon thereafter).

Scientists face disappointment and/or failure on a daily basis; a failed experiment, a rejected paper or grant. However, failure does not naturally lead to clarity, conviction and true originality; you have to make it happen. For young students, failure can sometimes lead to the premature departure from graduate programs, changing careers or even depression. Those who have walked the scientific path long enough have learned that failure is just a step along the path to success and that overcoming failure is an essential part of your training. So as a young scientist, try to embrace your failures and, as Dr. Peter van Galen, suggests, revel in the brief successes to get you through the low points,  “It is pretty rare for an experiment to confirm your hypothesis, so you have to savor the times that it happens. The percentage of experiments that yield 'publication quality' data is probably less than 10%, and it’s these rare events that have to keep you going for months of disappointments."

Dr. Hector Mayani, remembers that as a student and a young investigator, failure was depressing, but after 20+ years as an independent scientist he learned how to manage it. As he stated, “failure still knocks at my door every now and then. I still do not like it, but the difference is that I have learned how to handle it.” We should not fear failure, but change our paradigm about it; for Dr. Sean Morrison, failure is an opportunity, he recognized that “You learn more from the failures than from the successes. Failures aren't fun but the experiences can make you a better scientist.” 

It’s not personal, it’s…. science
 Being positive about facing failure does not mean that failure or rejection will not affect you, but the advice of Dr Fernando Camargo, is to not take it personal, which he admits “it is very difficult." Dr Hal Broxmeyer, agrees that “No one appreciates or likes to receive a rejection, be it a submitted manuscript or grant application. I doubt that there is anyone, regardless of status or position, who at one time or another has not had a rejection letter," he continued, “the key is to move on and to try deal with and learn from the process."

Minimizing our chances for failure
 As a student and young investigator, your first “failure” is at the bench, and no matter what you do, you will eventually have to face failure, but it is also true that you can “minimize” your chances by following the advice of Dr. Toshio Suda who recommends:

1. Re-read your protocol again and create a checklist before experiments. 
2. Remember that preservation of samples are always a part of the experiment protocol and label them accurately.
3. Simulate your experiment like a surgeon before conducting it.
4. Write a detailed record on your lab notebook; maybe even jotting down the weather or events of that day may help reviewing the record in the future.

After overcoming and conquering your bench work, the next step is to publish it and we asked Dr. Hal Broxmeyer for advice on this matter,  “My advice to young investigators in my lab or who I have mentored is not to send a piece of work out until it is ready to go. If rejected, fix it perhaps with advice and help from others, and send it out again to another journal. I would hope that the new investigators won’t have too many rejections, but rejections are inevitable."

Tips on how to overcome failure
Dr. Margaret Goodell, shared her five tips on how to overcome failure:

1. Wallow in self-pity for 24 hours if it is an R01, or a whole weekend (not more) if it is a bigger grant. Similar when your papers get rejected.  Keep your chin up and use your humor for your trainees who are feeling even worse.
2. Don’t take it personally - take the high road and try to forgive your Luddite reviewers (even when you are “certain" you know who they are). Even the most successful investigators have been dragged through the mud on numerous occasions, so take comfort that you are in great company.
3. Don’t over-analyze the reviews. If you can address the problems and get the grant or paper accepted, then do so. Otherwise, move on, submit elsewhere or write another grant.  Don’t let any single event have too much importance.
4. Success in science is a marathon, not a sprint. So continuing to move forward in the face of little setbacks will win the game in the end.
5. Make sure there are other things in your life to make you happy when you are miserable with your science!   

After receiving the notice of a rejected paper, Dr. Hal Broxmeyer’s advice is “to read the critique to see why the paper or grant was rejected, and then put the critique away for a few days and try not to think about it. Once you have “cooled off”, try to re-read the critique with an open mind. Usually, but not always, the critique will contain constructive comments that may help you to revise the paper or grant to make your body of work better. This may take extensive additional thought and experiments and many months of work but it is usually worth the effort. Then, send it out again to another journal or granting agency, unless the journal or agency that rejected it seems to be willing to see a revised work, I know a number of investigators who have fought rejections, but this has not worked well for me."

Don’t fight your data
When you feel that you reach an “ending point” with you data, Dr. John Dick, mentioned in an interview² that “You have to go forward” and that you should have to be careful about your results and what is “an experiment telling you and what it isn’t." You have to analyze your results and be honest with your findings. Dr. John Dick advises to analyze and think, “This is the result that I found, and this is how I did my assay, and this is what I think I can interpret, and this is what I think I can't."  Peter van Galen adds “Although endurance is very important, it is also crucial to know when to quit. If your project is not going anywhere, don’t hang on to it for too long."

Conclusions
Your scientific career will be built on both failures and successes. As scientists, we overlook failure and even try to avoid it at any cost, when we should actually be trying to learn from it and accept it as “part of the job”. Science is not an easy path to walk, and no matter how much experience you may have, you will continually have to battle failure throughout your career. So you always have to remember why you are doing science, as Dr. John Dick mentioned in an interview², “You should be doing experiments because you want the answer. You shouldn't be doing it looking over your shoulder that someone might beat you to the answer," sometimes that answer will not lead you to success, or may contradict your hypothesis, “but if an experiment is worth doing, it's worth doing even if there are a number of people also trying to get the answer. If someone else gets there first, it just means that you can go on faster to the next question."

Acknowledgments
We want to thank all our interviewees that shared their advice for the elaboration of this article (in alphabetical order):

• Dr. Hal Broxmeyer, Distinguished Professor, Mary Margaret Walther Professor Emeritus, Professor of Microbiology/Immunology, Program Leader, NCI-Designated Indiana University Simon Cancer Center, Program on Hematopoiesis, Heme Malignancies, and Immunology;
• Dr. Fernando Camargo, Associate Professor at Boston Children's Hospital and Harvard University Department of Stem Cell and Regenerative Biology;
• Dr. John Dick, Canada Research Chair in Stem Cell Biology and Senior Scientist, Princess Margaret Cancer Centre, University Health Network , Professor, Department of Molecular Genetics, University of Toronto Director and Program in Cancer Stem Cells, Ontario Institute for Cancer Research (OICR);
• Dr. Margaret Goodell, Professor and Director of the Stem Cells and Regenerative Medicine Center at Baylor College of Medicine, in Houston, Texas;
• Dr. Hector Mayani, Professor and Head of the Oncological Research Unit at the Mexican Institute of Social Health, Mexico City;
• Dr. Sean Morrison, Director of the Children's Medical Center Research Institute at UT Southwestern, the Mary McDermott Cook Chair in Pediatric Genetics and Investigator of the Howard Hughes Medical Institute;
• Dr. Toshio Suda, Professor, Department of Cell Differentiation, Graduate School of Medicine, Keio University;
• Dr. Peter van Galen, Postdoctoral Research Fellow at Massachusetts General Hospital

Eugenia (Kena) Flores-Figueroa, PhD
ISEH Publications Committee Member

Oncological Research Unit at the
Mexican Institute of Social Health (IMSS)
Mexico City, Mexico





Stephen Sykes, PhD
ISEH New Investigators Committee Member

Assistant Professor
Fox Chase Cancer Center - Blood Cell Development and Function Program
Philadelphia, PA
https://www.foxchase.org/stephen-sykes


References
1. Conan O'Brien Video in YouTube:  https://youtu.be/KmDYXaaT9sA

2. Nature Reports Stem Cells
Published online: 26 March 2009 | doi:10.1038/stemcells.2009.47
http://www.nature.com/stemcells/2009/0903/090326/full/stemcells.2009.47.html