Fluorescently tagged cultured HeLa cells

HeLa, the VIP of cell lines

By  Gesa Junge, PhD

A month ago, The Immortal Life of Henrietta Lacks was released on HBO, an adaptation of Rebecca Skloot’s 2010 book of the same title. The book, and the movie, tell the story of Henrietta Lacks, the woman behind the first cell line ever generated, the famous HeLa cell line. From a biologist’s standpoint, this is a really unique thing, as we don’t usually know who is behind the cell lines we grow in the lab. Which, incidentally, is at the centre of the controversy around HeLa cells. HeLa was the first cell line ever made over 60 years ago and today a PubMed search for “HeLa” return 93274 search results.

Cell lines are an integral part to research in many fields, and these days there are probably thousands of cell lines. Usually, they are generated from patient samples which are immortalised and then can be grown in dishes, put under the microscope, frozen down, thawed and revived, have their DNA sequenced, their protein levels measured, be genetically modified, treated with drugs, and generally make biomedical research possible. As a general rule, work with cancer cell lines is an easy and cheap way to investigate biological concepts, test drugs and validate methods, mainly because cell lines are cheap compared to animal research, readily available, easy to grow, and there are few concerns around ethics and informed consent. This is because although they originate from patients, the cell lines are not considered living beings in the sense that they have feelings and lives and rights; they are for the most part considered research tools. This is an easy argument to make, as almost all cell lines are immortalised and therefore different from the original tissues patients donated, and most importantly they are anonymous, so that any data generated cannot be related back to the person.

But this is exactly what did not happen with HeLa cells. Henrietta Lack’s cells were taken without her knowledge nor consent after she was treated for cervical cancer at Johns Hopkins in 1951. At this point, nobody had managed to grow cells outside the human body, so when Henrietta Lack’s cells started to divide and grow, the researchers were excited, and yet nobody ever told her, or her family. Henrietta Lacks died of her cancer later that year, but her cells survived. For more on this, there is a great Radiolab episode that features interviews with the scientists, as well as Rebecca Skloot and Henrietta Lack’s youngest daughter Deborah Lacks Pullum.

In the 1970s, some researchers did reach out to the Lacks family, not because of ethical concerns or gratitude, but to request blood samples. This naturally led to confusion amongst family members around how Henrietta Lack’s cells could be alive, and be used in labs everywhere, even go to space, while Henrietta herself had been dead for twenty years. Nobody had told them, let alone explained the concept of cell lines to them.

The lack of consent and information are one side, but in addition to being an invaluable research tool, cell lines are also big business: The global market for cell lines development (which includes cell lines and the media they grow in, and other reagents) is worth around 3 billion dollars, and it’s growing fast. There are companies that specialise in making cell lines of certain genotypes that are sold for hundreds of dollars, and different cell types need different growth media and additives in order to grow. This adds a dimension of financial interest, and whether the family should share in the profit derived from research involving HeLa cells.

We have a lot to be grateful for to HeLa cells, and not just biomedical advances. The history of HeLa brought up a plethora of ethical issues around privacy, information, communication and consent that arguably were overdue for discussion. Innovation usually outruns ethics, but while nowadays informed consent is standard for all research involving humans, and patient data is anonymised (or at least pseudonomised and kept confidential), there were no such rules in 1951. There was also apparently no attempt to explain scientific concept and research to non-scientists.

And clearly we still have not fully grasped the issues at hand, as in 2013 researchers sequenced the HeLa cell genome - and published it. Again, without the family’s consent. The main argument in defence of publishing the HeLa genome was that the cell line was too different from the original cells to provide any information on Henrietta Lack’s living relatives. There may some truth in that; cell lines change a lot over time, but even after all these years there will still be information about Henrietta Lack’s and her family in there, and genetic information is still personal and should be kept private.

HeLa cells have gotten around to research labs around the world and even gone to space and on deep sea dives. And they are now even contaminating other cell lines (which could perhaps be interpreted as just karma). Sadly, the spotlight on Henrietta Lack’s life has sparked arguments amongst the family members around the use and distribution of profits and benefits from the book and movie, and the portrayal of Henrietta Lack’s in the story. Johns Hopkins say they have no rights to the cell line, and have not profited from them, and they have established symposiums, scholarships and awards in Henrietta Lack’s honour.

The NIH has established the HeLa Genome Data Access Working Group, which includes members of Henrietta Lack’s family. Any researcher wanting to use the HeLa cell genome in their research has to request the data from this committee, and explain their research plans, and any potential commercialisation. The data may only be used in biomedical research, not ancestry research, and no researcher is allowed to contact the Lacks family directly.


question mark for american science

How Science Trumps Trump: The Future of US Science Funding

 

By Johannes Buheitel, PhD

I was never the best car passenger. It's not that I can't trust others but there is something quite unsettling about letting someone else do the steering, while not having any power over the situation yourself. On Tuesday, November 8th, I had exactly this feeling, but all I could do was to sit back and let it play out on my TV set. Of course, you all know by now, I'm talking about the past presidential election, in which the American people (this excludes me) were tasked with casting their ballots in support for either former First Lady and Secretary of State Hillary Clinton or real estate mogul and former reality TV personality Donald Trump. And for all that are bit behind on their Twitter feed (spoiler alert!): Donald Trump will be the 45th president of the United States of America following his inauguration on January 20th, 2017. Given the controversies around Trump and all the issues he stands for, there are many things that can, have been  and will be said about the implications for people living in the US but also elsewhere. But for us scientists, the most pressing question that is being asked left and right is an almost existential one: What happens to science and its funding in the US?

The short answer is: We don't know yet. Not only has there been no meaningful discussion about these issues in public (one of the few exceptions being that energy policy question  by undecided voter-turned-meme Ken Bone), but, even more worryingly, there is just not enough hard info on specific policies from the future Trump administration to go on. And that means, we're left to just make assumptions based on the handful of words Mr. Trump and his allies have shared during his campaign. And I'm afraid, those paint a dire picture of the future of American science.

Trump has not only repeatedly mentioned in the past that he did not believe in the scientific evidence around climate change (even going as far as calling it a Chinese hoax), but also reminded us of his position just recently, when he appointed  known climate change skeptic Myron Ebell to the transition team of the Environmental Protection Agency (EPA). He has furthermore endorsed the widespread (and, of course misguided) belief that vaccines cause autism. His vice president, Mike Pence, publicly doubted  that smoking can cause cancer as late as in 2000, and called evolution “controversial”.

According to specialists like Michael Lubell from the American Physical Society, all of these statements are evidence that “Trump will be the first anti-science president we have ever had.” But what does this mean for us in the trenches? The first thing you should know is that science funding is more or less a function of the overall US discretionary budget, which is in the hand of  the United States Congress, says  Matt Hourihan, director of the R&D Budget and Policy Program for the American Association for the Advancement of Science (AAAS). This would be a relief, if Congress wasn’t, according to Rush Holt, president of the AAAS, on a “sequestration path that […] will reduce the fraction of the budget for discretionary funding.” In numbers, this means that when the current budget deal expires next year, spending caps might drop by another 2.3%. Holt goes on to say that a reversal of this trend has always been unlikely, even if the tables were turned, which doesn't make the pill go down any easier. Congress might raise the caps, as they have done before, but this is of course not a safe bet, and could translate to a tight year for US science funding.

So when the budget is more or less out of the hands of Donald Trump, what power does he actually possess over matters of research funding? Well, the most powerful political instrument that the president can implement is the executive order. But also this power is not unlimited and could for example not be used to unilaterally reverse the fundamentals of climate policy, said David Goldston from the Natural Resources Defense Council (NRDC) during a Webinar hosted by the AAAS shortly after the election. Particularly, backing out of the Paris agreement, as Trump has threatened to do, would take at least four years and requires support by Congress (which, admittedly, is in Republican hand). And while the president might be able to “scoop out” the Paris deal by many smaller changes to US climate policy, this is unlikely to happen, at least not to a substantial degree, believes Rush Holt. The administration will soon start to feel push-back by the public, which, so Holt during the AAAS Webinar, is indeed not oblivious about the various impacts of climate change, like frequent droughts or the decline of fisheries in the country. There was further consensus among the panelists that science education funding will probably not be deeply affected. First, because this matter usually has bipartisan support, but also because only about 10% of the states' education funding actually comes from the federal budget.

So, across the board, experts seem to be a reluctantly positive. Whether this is just a serious case of denial or panic control, we don’t know, but even Trump himself has been caught calling for  “investment in research and development across a broad landscape of academia,” and even seems to be a fan of space exploration. Our job as scientists is now, to keep our heads high, keep doing our research to the best of our abilities but also to keep reaching out to the public, invite people to be part of the conversation, and convincing them of the power of scientific evidence. Or to say it with Rush Holt’s words: “We must make clear that an official cannot wish away what is known about climate change, gun violence, opioid addiction, fisheries depletion, or any other public issue illuminated by research.”

 


From Bed[side] to Bench: Involving Patients and the Public in Biomedical Research

By Celine Cammarata

 

Many of us doing biomedical science never really see patients, the very people our work will hopefully one day help. But what if we did – what if those individuals who will eventually be using our research on a daily basis were in fact involved in the work from the start? How would research change?

 

This is the concept underlying the movement toward Patient and Public Involvement or PPI, a title that (logically enough) refers to efforts by researchers and institutions to engage patients and members of the public in the process of biomedical research and, in doing so, fundamentally change the way scientific information is created and disseminated. Traditionally, the flow if information between science and society was seen as relatively unidirectional, with researchers passing scientific knowledge down to an uninformed, receptive public. More recently, however, there has been a growing recognition that information flow from the end-users of research back to investigators is also critical.

 

One way to accomplish this is to directly incorporate those users – broadly defined as patients, caregivers, members of the public rather than clinicians or practitioners - into the research process. A prominent definition of PPI is “research being carried out ‘with’ or ‘by’ members of the public rather than ‘to’, ‘about’ or ‘for’ them” (INVOLVE). Individual instances of PPI can be quite variable, though most engage users in some form of advisory role, often through interviews, surveys, focus groups, and hosting users alongside researchers on regularly-meeting advisory groups (Domecq et al., 2014). PPI is represented at all stages of research, from inception of project ideas through the data collection process to implementation of findings and evaluation and is most prevalent in research that is either directly related to health or social issues and services.

 

A primary driving force behind PPI is the belief that input from users will push research toward questions that are more relevant to those users. Individuals with first-hand experience of an illness or other condition are thought to hold a particular kind of expertise and therefore able to craft more immediately relevant research questions than an academic investigator in the field might.

 

One important stage at which patients and the public are having an impact is by working with funding agencies to establish research priorities. For instance, the UK’s NHS Health Technology Assessment program involves users alongside clinicians and researchers in the development and prioritization of research priority questions. Members of the public were engaged in several different stages of the process, from initial suggestion of research ideas through to selecting topics that would be developed into solicitations for research. Analysis revealed that overall these lay members exerted an influence on the research agenda approximately equal to that of academic and clinical professionals (Oliver, Armes, & Gyte, 2009).

 

PPI can also increase the relevance of individual studies, with specific examples including: users of mental health services shifting outcome measurement in a study of therapies to improve cognition away from psychological tests in favor measuring performance on daily activities; the investigation of environmental factors such as radiation, which researchers originally considered negligible, in a study of breast cancer; and the development of new assessment tools to measure the mental and psychological condition of stroke victims in a study that initially planned to focus only on physical health outcomes (Staley, 2009).

 

Users may express particular suspicions or hunches about their condition that they believe should receive further investigation, may increase pressure on investigators to clearly state how their work will contribute to the public, and may challenge whether a project is even conceptualized in a way relevant to those who experiencing the situation in question, helping to determine whether a research problem is truly a “problem” at all. An excellent example of the impacts of PPI in research commissioning is the Head Up project, an entirely user-driven project in which patients with motor neuron disease working with one of the CCF programs pushed for research on an improved supportive neck collar.

 

PPI may also help increase the up-take of research findings because user’s are generally able to relate to and communicate with other users and practitioners in a uniquely meaningful way. Patients and members of the public may help to write up study findings, present at conferences or, importantly, bring findings directly to the user community.

 

Of course, nothing comes without a cost. A number of challenges in conducting PPI have consistently been identified, including: insufficient time and funding; tension over roles on the project and difficult relations between academic researchers and users; lack of training for both users and researchers; and a tokenistic attitude toward PPI on the part of investigators. Still relatively little is known about the precise effects of PPI or best practices. However, these are active areas of scholarship. Also of note is the relative lack of PPI in basic science research; PPI is predominantly relegated to applied health and social research. An important step in furthering PPI would be to establish who the “users” of basic research are, whether PPI in basic research is likely to be beneficial, and how the practice could be implemented.

 

Overall, it is clear that the end-users of research can be incorporated into setting the research agenda, designing studies and communicating results, and suggests that such user engagement can increase the relevance of research and the dissemination and adoption of findings.


Cake decorated with open access symbol

Open access: the future of science publishing?

By Florence Chaverneff

On the eve of receiving the Nobel Prize in Physiology or Medicine in 2013, Randy Schekman shook the scientific world in an altogether different manner when he announced in the Guardian newspaper he and his group would boycott the three leading scientific journals. These bastions of scientific publishing have long been held on a pedestal by the research community the world over and regarded as depositories of excellence in science. Their reputation is tightly associated with high ‘impact factors’, a parameter determined by article citations, and which Schekman judges to be a "gimmick" and a "deeply flawed measure, pursuing which has become an end in itself – and is damaging to science". Yet, career advancement in academic research is heavily – if not exclusively– reliant on individuals getting their work published in these high impact scientific journals, which Schekman calls "luxury journals", comparing them to bonuses common on Wall Street, and from which "science must break [away] ". He deems that "the result [of such a change] will be better research that better serves science and society". The Nobel Prize awardee touts the open access model for scientific publishing, presenting it as all-around anti-elitist, which…it is.

 

In 2001, the Budapest Open Access Initiative defined open access for peer-reviewed journal articles by its "free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself".

 

This is how open access makes for a more level playing field: by allowing immediate dissemination of scientific findings without restrictions, and by accepting articles without highly demanding criteria, while maintaining sound peer-review practices. This comes in sharp contrast to the 300 year old model of subscription-based scientific publishing, accepting limited numbers of articles in each issue, and requiring exceedingly demanding standards for acceptance. This results in significant publication delays and considerable time effort spent polishing articles for publication. Time which could be spent… doing research.

 

While many in the community will agree on the benefits granted by this still recent and evolving model of science publishing, open access journals, being less established than older household names, and lacking in their majority an impact factor, may not appear as prime choice for researchers. The question then can be posed: what would it take to bring about a shift in attitudes where open access publishing would be favored? Granting agencies and academic institutions, which contribute to setting the standards for scientific excellence need to start being more accepting of non-traditional models of scientific publications, and judge on quality of research, and not solely on journal impact factor. National policies encouraging open access publishing are also paramount to support such a shift. Moves in that direction are underway in the UK with a policy formulated by the Research Councils, and in the European Union with the Horizon 2020 Open Research Data Pilot project, OpenAire. In the US, the Fair Access to Science and Technology Research Act and the Public Access to Public Science Act aiming "to ensure public access to published materials concerning scientific research and development activities funded by Federal science agencies", if passed, would be a step in the right direction.  All else that is needed might be a little time.

 


A Graduate Student's Browser History

Thalyana Smith-Vikos

We’re all guilty of having 10 internet browser tabs open at once on our laptops, but which websites should you be surfing while waiting for that incubation to finish? For “new” and “old” grad students alike, it’s important to balance researching specific details on your project with staying informed about the world outside of your bench. Take the time to give yourself perspective on how your research can be added to the body of scientific knowledge, as well as what is expected of you and what you should expect of yourself as a graduate student. Here are some tabs you can keep open that will meet these requirements:

Something outside your field of study

Staying up-to-date with the latest scientific publications (especially if they have nothing to do with your research) requires a lot of effort, but if you can put aside some time every day (or at least every week) to read about the latest news, it can be a pleasant experience! Start by taking note of which journals usually publish the most important articles in your field, and then browse the table of contents for these journals to see what other articles were published. Also, visit the homepages of Nature, Science, Cell, and other journals in these publishing groups to see which new research stories are highlighted. Lastly, visit the communications/public affairs website for your university to see which of your colleagues got published! (Obviously, these suggestions are in addition to using Scizzle and following our Scizzle Blog!)

Something outside of academia

As Science magazine is distributed by AAAS, the magazine’s website also contains the latest science policy news updates regarding decisions on federal grants, regulatory procedures, etc. It’s also worth your while to read Scientific American and the science sections of the New York Times, Huffington Post, and any other news sources you subscribe to, just to get a sense of how science research is portrayed to the public. This can also help improve your conservations about science with non-scientist friends and relatives! (Another plus for Scizzle Blog: in addition to highlighting the recent literature, we also have many other posts of interest for any scientist.)

Something career-related

It’s never too early to start thinking about your career, especially if you don’t want to stay in academia. Networking with professionals in other fields may seem intimidating, but never fear, LinkedIn is here! I am always surprised to learn how many PhD students are not on LinkedIn: everyone should be on LinkedIn! It’s the best way for you to display an abridged version of your CV for any potential employer to view. Yes, we are students, but we should also be establishing ourselves as professionals at the same time. Start by connecting with your friends and alumni from your PhD program, and you will quickly learn how large your networking circle actually is through 2nd and 3rd-degree connections. Join discussion groups and post on forums regarding your research interests or general scientific interests, careers outside of academia, alumni organizations, etc. Start following companies where you might be interested in working and make a note of how often they have job postings.

Something fun

Science can be very frustrating, especially after repeating that PCR for the third time and still getting a blank gel. To let off some steam and commiserate with other PhD students, I recommend visiting whatshouldwecallgradschool.tumblr.com. This website contains an extensive list of the many unhappy (and some happy) moments we experience as graduate students, accompanied by hilarious GIFs to illustrate these feelings. I also suggest visiting phdcomics.com, which is a comic strip (started by formed PhD student Jorge Cham) with recurring grad student characters who have to TA classes, write grants, perform experiments, attend happy hours, and anything else you can think of. Being able to laugh about all of these experiences will preserve your sanity throughout grad school!

 


Follow the Yellow Brick Road

Neeley Remmers

Have you ever been asked the question, “Oh, you’re getting your PhD, what do you plan on doing with that?” I get asked that question on average 5 times week or more when I’m trying to explain to someone outside of scientific research what it is I do. Explaining the career-path of a scientist is no easy task because quite frankly, there is no defined career-path like for our profession like there is for other professions. For example,  if you’re ambition was to become an M.D. the path is has been cleared for you – you go to medical school, take your boards, do a residency, complete a fellowship, and finally get a position as an attending physician. However, for those of us who either have or are obtaining our PhD’s in science, there is no yellow-brick road for us to follow. Ask any professor or senior scientist how they got to their current position and you’ll find that no two career paths are the same.

One reason for the lack of a clearly defined path may be because there are so Read more


Spreading the Wealth: The Importance, and Challenge, of Disseminating Science

Celine Cammarata

The relationship between scientists and the broader public is not always an easy one; many outside the field view science as somewhat unapproachable, while researchers are generally not trained to communicate their work to non-scientists and may find such activities prohibitively time consuming.  Addressing these issues in a recent manifesto aimed directly at investigators, neuroscientist and author David Eagleman gives a compelling argument as to why scientists should strive for greater public dissemination of their work.

While acknowledging the challenges of sharing research with the public, Eagleman provides a systematic series of reasons why doing so is nonetheless worthwhile and important.  Some of Eagleman’s reasons focus on Read more