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articles, October 2016

CRISPR Interference Battle: Still Duking It Out?

At the moment in the USPTO office, a fierce battle is occurring between two scientific teams over patent rights associated with core CRISPR/Cas technology. On one side of the dispute is Jennifer Doudna’s team from UC Berkeley. On the other side is Feng Zhang’s team from the Broad Institute of MIT and Harvard. Both teams were the first labs to demonstrate that the Cas9 enzyme can be directed to cut specific sites in isolated DNA. It will be intriguing to find out who is finally the victor of this contentious debate.

The story of the patent dispute has been lengthy and drawn-out. Jennifer Doudna’s team first filed for patent rights over CRISPR/Cas technology back in May of 2012. Feng Zhang’s team subsequently filed their patent application in December of that same year. Interestingly, Zhang’s team beat Doudna’s team to the punch over patent rights because in October of 2013 they submitted their application for expedited review. Expedited review required the Broad to undergo “accelerate examination,” where they were required to respond quicker to questions asked by the USPTO office. Due to the expedited reviewing process, the patent was ultimately granted to Zhang’s team in April of 2014. Shortly after this event, eleven other CRISPR-related patent applications were  filed by the Broad Institute. To counter-attack the Broad’s prompt monopoly over CRISPR-related patents, Doudna’s team requested a patent interference against all CRISPR-related patents filed by the Broad. The USPTO office finally declared the patent interference in January of 2016.

Historically, a patent interference has been a procedure to resolve disputes between two parties over who was the “first to invent.” However, in March of 2013 the USPTO altered the patent system from “first to invent” to “first to file.” Under these new rules, Doudna’s team would have won the CRISPR patent rights because the team was the “first to file” their patent. But since both parties filed their patents before March 2013, the interference procedure defaults under the outdated “first to invent” rules.

The “first to invent” rule has blurred the lines of who is the true proprietor of the patent rights. For over nine months, both parties have been providing evidence claiming they were the “first to invent.” The Broad asserts that Zhang’s team was the first group to demonstrate that CRISPR/Cas technology has applications in editing genes in mammalian cells. They argue that Doudna’s team only described using CRISPR/Cas in bacteria, not in eukaryotes. This distinction is important because some of CRISPR’s most lucrative, future applications will be in gene editing therapies for human diseases. Doudna’s team countered the Broad’s argument by claiming that although her team only demonstrated the use of the technology in bacteria, transferring the technique to mammalian cells was “obvious” and any “person of ordinary skill,” such as a postdoc, could have made that inference. This observation is also important because one of the hallmarks of patentability is that an invention cannot be obvious to a person of ordinary skill. Doudna’s team asserts that the obviousness of the Broad’s patent would make it invalid. The Broad subsequently counter-argued that the shift from bacteria to mammalian cells was “anything but obvious.” This type of back-and-forth between the USPTO, UC Berkeley, and the Broad has been continuing for the last nine months and updated details of the case can be viewed on the Broad’s CRISPR Patent Interference Updates webpage (reference is listed below).

Patent interference cases can last up to two years before appealing to the Federal Circuit. Due to the intense, ongoing clash between the two academic teams, attorneys expect the end date of the CRISPR patent interference case to be sometime in 2017. However, a recent twist in events may close the case completely by the end of this year. This past week, UC Berkeley attorneys submitted a 2013 dated email to the USPTO office. This email was from Feng Zhang to Jennifer Doudna describing his team’s first, published CRISPR paper and mentioning that he has been “very inspired” by her team’s work. This is enough evidence to imply that Zhang’s team had adapted from Doudna’s team’s work and that Zhang’s team was not the “first to invent” the CRISPR/Cas technology. The Broad understands that it’s difficult to counter this piece of evidence. Since the submission of this email, the Broad has asked patent officials to remove four CRISPR-related patents from the interference case in hopes that they can demonstrate novelty of the patents in other ways that are separate from the initial Zhang team’s CRISPR patent. If the Broad can separate these patents from the interference case, then both UC Berkeley and the Broad can walk away with some intellectual property. We will see in the forthcoming weeks how the case plays out.

Although intellectual property was at stake for the two scientific teams, the interference case has been rather unusual in nature. Why has the fight been so bitter and acrimonious? One explanation could be that it’s not the academic institutions that are footing the legal bill for the case but the biotechnology companies that are relying on licensing the patent. Both Doudna and Zhang have started up genome editing companies and if one of those companies has proprietary rights over the CRISPR/Cas technology, that company can collect huge royalties from patent licensing. Perhaps another reason why the dispute has been rancorous is because Doudna and Zhang have their eyes set on a Nobel Prize. CRISPR/Cas technology is revolutionizing the way we do basic science research, the way we treat diseases, and the way we practice agriculture. For these reasons it’s very likely that the scientists behind the technology will receive a Nobel Prize. Regardless of the outcome of the patent interference, the scientific community is certain of one thing: CRISPR has definitely made its mark in patent law history.

References:

  1. CRISPR Patent Interference Updates. Retrieved from https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/crispr-patent-interference-updates
  2. Begley, S. (2016, August 16). CRISPR patent fight: The legal bills are soaring. Retrieved from https://www.statnews.com/2016/08/16/crispr-patent-fight-legal-bills-soaring/
  3. Cohen, J. (2016, October 5). Dramatic twists could upend patent battle over CRISPR genome-editing method. Retrieved from http://www.sciencemag.org/news/2016/10/dramatic-twists-could-upend-patent-battle-over-crispr-genome-editing-method
  4. McCall, A. (2016, June 5). The CRISPR Clash: Who owns the groundbreaking, DNA altering technique? Retrieved from http://www.ipwatchdog.com/2016/06/05/crispr-clash-dna-technology/id=69650/
  5. Ledford, H. (2016, September 21). The Titanic clash over CRISPR patents turns ugly. Retrieved from http://www.nature.com/news/titanic-clash-over-crispr-patents-turns-ugly-1.20631
October 2016

Presidential Candidates Talk Science: Where They Stand on 20 Important Issues

by Nafis Hasan, Drew Hooper, & Kayla Gross

Science policy, though intertwined with many other aspects of national and international issues, is not the usual focus of a presidential election and often boils down to just a few questions during a debate. In an effort to change this narrative, in 2008, several scientific and engineering organizations initiated a challenge to the presidential candidates by asking them to participate in a science-focused debate. By crowdsourcing questions, ScienceDebate.org presented the candidates with 20 questions addressing the most immediate and important STEM-oriented issues that affect the American public and published their answers online. In its third iteration, this movement has recently posted the 2016 candidates’ responses.

With the election drawing nearer, we decided to review their answers and provide summaries which are listed below.

Clinton Trump Johnson Stein
Innovation
  • Establishes education, especially in computer science, as foundational for improving national innovation
  • Improve open access between government-funded scientists and private sector groups for “commercialization of research results”
  • Reduce barriers for entry into free markets to allow entrepreneurs to flourish
  • Emphasis on space exploration & “research & development across the broad landscape of academia”
  • Reduce tax burden allowing more private investment in innovation
  • Government should not pick winners and losers by imposing priorities
  • Requests for Applications skew science towards “fashionable topics”
  • Reduce Pentagon spending to free up dollars for innovation investment
  • “Level playing field” with living wage and paid sick leave will lead to more innovation
Research
  • Concerned about US “underinvestment in research”
  • Improve funding for (1) young investigators and (2) “high risk high reward” and/or long-term projects
  • Improve efforts towards sustaining “viable space program” and institutional research
  • Government should get out of the way, allow scientists to determine regulations
  • Private companies will invest in basic science research
  • More transparency in funding to reduce waste
  • Top priority is climate change
  • Science policy should better reflect preferences and needs of citizens
Climate Change
  • Acknowledges the severity of climate change and its consequences.
  • Proposes 3-tiered plan to reduce fossil fuel dependence through technological advancement, increase investment and reliance on cleaner energy alternatives and cut energy waste.
  • Also proposes to increase jobs in the clean energy sector.
  • Launch $60 billion initiative to partner with local govts for cleaner energy alternatives.
  • Believes climate change to be a hoax created by the Chinese, as evidenced by his speeches, and still refers to it in quotation marks.
  • Believes that limited resources would be better spent in other avenues such as clean water and food production.
  • Acknowledges the threat of climate change and the contribution of humans to it..
  • Believes that market forces will be able to bring tangible reductions in carbon emissions rather than governmental regulations and international treaties.
  • Believes climate change to be the “greatest existential threat that humanity has ever faced”.
  • Proposes a “Green New Deal” which will create 20 million jobs and completely switch to clean energy sources by 2030.
  • Also proposes to end subsidies to fossil fuel companies and phase out nuclear energy.
  • Advocates for more investment in sustainable agriculture and infrastructure.
Biodiversity
  • Emphasis on preventative approaches to protect at-risk species from becoming endangered
  • International collaboration for research, information sharing, & conservation efforts
  • Necessary to move away from “special interests” controlling decisions about federal land
  • Innovation, free trade, and prosperity will enable better environmental protection
  • Private ownership of land leads to better stewardship
  • Ban pesticides that threaten pollinators
  • Invest in clean air and water, zero-waste manufacturing processes, and sustainable agricultural practices
Internet
  • Advocates internet to be kept as “a space for free exchange, providing all people equal access to knowledge and ideas.”
  • Proposes to build on Obama administration’s “Cybersecurity National Action Plan” and put in place a Chief Information Security Officer.
  • Cyber attacks to be treated just as any other attack and will be responded with serious political, economic and military approaches.
  • Believes that the govt should not “spy on its citizens”.
  • Any attack on the Internet deemed to require “utmost protection”, and a “proportional response” to “eliminate any threat to internet infrastructure”.
  • Advocates for protection of user privacy and encryption.
  • Wants to scale back National Security Agency’s role to provide cyber defense rather than being on the offensive.
  • Proposes more education on cyber security.
  • Propose to keep the internet free by supporting public broadband, supporting net neutrality laws, negotiate international treaties to ban cyber attacks with the UN’s help.
  • Opposes the “Online Piracy Act” and other legislation that would “undermine freedom and equality on the internet”.
Mental Health
  • Implement changes to health care system so that mental health & physical health are considered and treated in tandem
  • Improve awareness and training of medical & other professionals in mental health areas
  • Increase federal support to states to improve treatment options
  • Recognizes that “a comprehensive solution set must be developed”
  • Delivery of treatment is the key challenge, and state solutions are better than federal ones
  • Drug war prevents treatment by criminalizing drug abusers
  • Implement Medicare for All, including mental health care, Supplemental Security Income for mentally ill, and public education on mental illness
  • Provide rehabilitation services for mentally ill prisoners
Energy
  • Proposes a “smart energy policy” that will be at the intersection of economy, environment and security concerns.
  • Advocates for more usage of cleaner energy sources, with a short term focus on solar power.
  • Also wants to discourage fossil fuel dependence by cutting subsidies, investing more in clean energy technology and infrastructure.

*Also see “Climate Change” answer for more details.
  • Believes achieving “energy independence as soon as possible” as the goal of the US govt and American people.
  • Proposes said goal can be achieved by “exploring” all possible energy sources.
  • Also believes that the market will determine the best sources of energy for consumers.
  • Government interferes with proper acquisition and use of energy
  • Nuclear power is underused and overregulated
  • Market will dictate use of renewable energy sources
  • Rapidly transition to 100% clean energy
  • End fracking, offshore oil drilling, and nuclear power by pulling subsidies
Education
  • Committed to implementing improved computer science education at the primary, secondary, and collegiate levels to meet current job market needs, especially in underrepresented populations
  • Education models need to be changed as “one size fits all” does not work and thus should be determined at the local or state versus federal level
  • Will “allow market influences” to improve education
  • Federal standards are unnecessary and counter-productive
  • Rely on competition among states to incentivize high academic achievement
  • Pre-school through university should be “tuition-free and world-class”
  • Replace Common Core based on input from educators, parents, and communities
  • Increase federal funding of public schools
Public Health
  • Establish consistent budgeting for rapid responses to public health crises
  • Expand training programs as well as available resources to current government divisions
  • Resources are limited and thus assessment of areas with most need is required
  • Federal government’s role should be limited to “superbugs” and epidemics that cross state lines
  • Health data should be shared, not proprietary, to better monitor trends
  • Save money through a more preventative approach to public health
Water
  • Wants to work with both public and private sector to provide clean, safe water and improve water treatment technology.
  • Proposes to build a multi-agency “Western Water Partnership” to improve access to clean water.
  • Also proposes a “Water Innovation Lab” to develop novel technology for better water resource management.
  • Acknowledges the crisis and proposes to invest in infrastructure development to provide clean water to everyone.
  • Proposes increased desalinization approach and better infrastructure to meet the demands of clean water.
  • Failure to protect water supply as in Flint, MI is criminal
  • Federal government should step in when local and state officials fail or engage in misconduct
  • Investing in infrastructure will ensure clean water and prevent future crises
Nuclear Power
  • Fund research for advances in nuclear power
  • Reduce amount of weapons-grade nuclear material globally
  • Continue to rely on nuclear power as important part of energy independence
  • Maintain robust safety and security standards, and continue using nuclear power
  • Invest in newer, safer, less wasteful types of reactors
  • End nuclear power subsidies, and phase out nuclear power completely by 2027
Food
  • Proposes to increase investment in sustainable agricultural practices through the “Beginning Farmer and Rancher Development”.
  • Proposes to invest more in rural business through “Rural Business Investment Companies” that would drive growth and jobs in rural areas.
  • Believes that the market forces should be able to provide the agriculture industry with the best solutions.
  • However, also believes that food availability is a
    “national security issue” and therefore federal govt should be involved to provide a safety net for farmers.
  • Federal management of agricultural, including subsidies, has created imbalances
  • Label GMOs and regulate to make sure they are safe
  • Support regenerative agriculture and sustainability
Global   Challenges
  • Proposes to appoint US’ first “Special Envoy for Climate Change” and lead the world in responding to climate change. Also proposes to build a global “Climate and Clean Air Coalition” on an international level and make climate change a major diplomacy issue.
  • Also proposes to build a “Rapid Response Fund” to respond to national and international crises.
  • Wants to make sure that the US is experiencing economic growth due to his belief that “a prosperous America is a much better partner in tackling global problems”.
  • Use diplomacy and trade to engage with the world and solve global problems
  • International institutions should be strengthened to tackle climate change and pandemic disease
Regulations
  • Employ environmental, health, and energy regulations that “use the best available science”
  • Keep, rescind, or add regulations based on science
  • Balance economy with protection of citizens
  • Federal regulations should be reduced wherever possible
  • Patients in extremis should be free to use experimental medicine
  • FDA should be used more for informing the public about risk and less for regulating therapies
  • Rely on science advisors to formulate regulations
Vaccination
  • Globally eliminate childhood diseases through vaccination
  • Educate parents about dangers of not vaccinating their children
  • Bridge “innovation gap” between research and production of new vaccines
  • Invest in comprehensive vaccination program as a public service
  • Federal government should assist in the event of national or regional outbreak
  • Engage with partner countries to combat international outbreaks
  • Universal health care needed to ensure everyone has access to critical vaccines
  • Increase public trust in regulatory agencies by removing corporate influence
Space
  • Wants to build on current progress in US’ space exploration by ensuring funding for NASA’s programs.
  • Supports a “strong space program” from employment and educational perspectives.
  • Propose to work on a global scale to expand space exploration.
  • Space exploration should be encouraged in the private sector
  • Lead international collaboration to ensure that space technology benefits all people
  • Sign International Treaty for the Demilitarization of Space
  • Leave space exploration and research agenda up to scientists, not military or corporations
Opioids
  • Proposes a $10 billion initiative to fight the opioid epidemic by expanding the “Substance Abuse and Treatment block grant” and other federal-state partner programs.
  • Recommends “rehabilitation and treatment over prison for low-level and non-violent offenders”.
  • Wants to “stop the inflow of opioids” into the US.
  • Drug laws and “crony capitalism” of legal opioid sales have largely driven the opioid addiction crisis
  • Decriminalize and reschedule drugs, particularly cannabis
  • End the war on drugs and focus instead on research, education, and treatment
Ocean Health
  • Proposes to “oppose efforts in Congress that seek to weaken” established regulations on overfishing. Also wants to “act globally to address the fisheries crisis” and proposes better tracking of seafood sources.
  • Also wants to protect coastal habitats and coral reefs.
  • No mention of oceans, fishing, coral reefs or coastal habitats in answer.
  • Focus on protecting our own coastlines and territorial waters
  • Ocean pollution and over-harvesting will depend on international agreements and market forces
  • As part of total climate change response, conserve fish stocks and coral reefs “with or without Congress” (i.e. through executive action)
Immigration
  • Proposes to “staple” a green card to Master’s and PhD degree holders in STEM fields.
  • Proposes to support “start-up visas” for tech entrepreneurs from abroad to invest in the US.
  • Wants to streamline immigration process for “lawful residents” for easier naturalization, as mentioned in her comprehensive immigration reform.
  • Rebukes the tech companies for abusing the H1-B visa program.
  • Endorses “legal” individuals for extended stay in the US after achieving their degrees, however, was unclear on which status they would fall under.
  • Believes that a “robust” H1-B visa program will increase growth, innovation and wealth.
  • Wants market forces to determine immigration of labour and would streamline the immigration process for all labor types and skills.
  • Supports the H1-B visa program, and believes immigration issues should be studied within a global economic context.
  • Supports more “international development and demilitarization”.
  • No specific comments on “scientists and engineers who receive their graduate degree at American Universities.”
Scientific Integrity
  • Supports open access to government-funded findings through implementation of incentives for scientists to “share data, code & research results”
  • Invested in bolstering public trust in scientific findings, preserving non-partisan nature of science research, and maintaining penalties for fraud & dishonesty
  • Committed to eliminating political bias in research as “science is science and facts are facts”

 

.
  • Increase transparency to reduce influence of political interference on scientific integrity
  • Respect diversity of thought in research centers
  • American public distrusts scientific regulatory agencies because of corrupting influence of pharmaceutical corporations
  • Stop the “revolving door” between political and corporate positions, and “clean up” regulatory agencies to improve public trust in science

And finally, members of our writing team have provided their opinions on where these candidates stand when it comes to STEM:

Andrew Hooper: The perennial policy debate in the U.S. boils down to a critical role for the federal government in ensuring parity and safety through regulation from the perspective of the political left (Clinton, Stein), versus the stifling of creativity and market forces by over-regulation from the political right’s point of view (Trump, Johnson). Thus there is a greater burden on Clinton and Stein to provide detailed agendas for tinkering with regulations and bureaucracies to improve them, while Trump and Johnson tend to fall back on broad statements about the free market, federal overreach, and misspent tax dollars, promising massive overhauls to get the federal government “out of the way” of entrepreneurs, innovators, and educators.

Nafis Hasan: The US govt’s scientific policy, since World War II, has largely focused on development of a technocratic superpower, with a delicate balance maintained between environmental and economic concerns. As such, the obvious split between the centre and left-leaning candidates (Clinton, Stein) and the right-leaning ones (Trump, Johnson) is reflected on how this status should be achieved. Both Clinton & Stein advocate federal govt’s regulations in areas of concern such as climate change, energy and water, whereas Trump (in cases where he does acknowledge the crises) and Johnson are more likely to put their trust in the free market, a Friedmanian ideology that wreaked economic havoc in countries where it was tested. While Clinton seems to have the most thought-out plans for all the 20 topics covered, she is lacking in concrete details in some cases; it is also concerning that Clinton doesn’t openly support protection of user privacy and data encryption, which the other three candidates have all favored. Stein, true to her party’s namesake, favors a much stronger stance on climate change, water and energy crises; however, her plans might be deemed a bit too “idealistic” for the American public’s and legislators’ tastes. Both Johnson and Trump, while making a few good points, advocate for measures that would largely remove federal regulations and govt programs that have kept the standard of living in this country from free-falling. By and large, the choice for the next President of the US should be quite obvious for the scientific community.

 

For related reading on these topics, check out:

 

October 2016, Techniques

Top Techniques: The Basics

Western Blot

PCR

IHC

Immunoprecipitation

articles, Community, September 2016

Elisabeth Adkins graduates as the first Tufts JAX Track Ph.D.

Written by Alex Fine

Not all experiments at The Jackson Laboratory take five years to complete. But one day last month, a group of JAX scientists gathered to see the results of a five-year experiment. The presentation by Tufts University Genetics Program student, Elisabeth (Liz) Adkins, described a newly defined cell in the immune system, a cell that when multiplied excessively could contribute to autoimmune diseases such as lupus or rheumatoid arthritis. But the five-year experiment was even bigger than Liz’s newly defined cells. The other experiment was Sackler’s collaborative partnership with The Jackson Laboratory, and it had yielded measurable success: Liz is its first Ph.D. graduate!

A little over five years ago, the Sackler School and JAX created a new graduate program, the “JAX Track,” that would allow students to enroll with the explicit intent of conducting their thesis research at JAX. Located in Bar Harbor, Maine, The Jackson Laboratory is a world-renowned institution where mammalian genetics is at the forefront of research. JAX hosts Ph.D. students from universities in the US and abroad during some portion of their thesis research.

Tufts JAX Track students might be drawn to JAX because of the laboratory’s history and reputation in mouse genetics, or they might have been at JAX as a summer student and fallen in love with the place, or they might have been told about the resources and community from a mentor who had valued their own time at JAX. But the question, five years ago, that faced JAX and the Sackler School was: were there students who wanted a uniquely JAX experience during their Ph.D.? And would it work? Together, Sackler and JAX faculty thought they had the right ingredients: a strong translational research group at Tufts and wide strengths in mammalian genetics at JAX. But it took the students, and especially Liz Adkins as the pioneer student, to put it together and meet the high expectations.

Adkins joined the JAX Track on the strong recommendation of her undergraduate mentor, Tom King, who had worked with Eva Eicher at JAX during his scientific training. As Liz said, “I also knew that if I wanted to do mouse research – and I did – that there was no better place in the world to do it than at JAX.” Liz’s graduate school career began in the two months before her Sackler orientation, during which she attended the Short Course in Medical and Experimental Mammalian Genetics and had a short research rotation, both at JAX in Bar Harbor. She then moved to Boston to complete her first semester of coursework at Tufts with the rest of her Genetics cohort before returning to Maine to resume her laboratory rotations. At the end of her first year, Liz joined the research group of JAX professor Derry Roopenian for her thesis research. Roopenian studies autoimmune disorders, pathologies that arise when our body’s immune system starts fighting our body. Adkins wanted to understand the process by which B cells, the immune cells in our bodies that produce antibodies, become corrupted to produce antibodies against our own cells and tissues instead of exclusively against foreign invaders like bacteria or viruses.

As we all know, a Ph.D. requires a lot of work. There are hours and hours in the lab, at the microscope and the cell sorter, and reading papers and trying to figure out why results are different than you thought they would be. Adkins had the added challenge of helping to shape the JAX Track program. Although the Sackler and JAX faculty had a clear vision of the program’s mission and the overall structure, there were challenges along the way that no one anticipated – and which Adkins, initially as the sole student, helped solve. “I knew there would be hiccups helping pilot a new program, but I love a challenge and this was one I was happy to take,” recalled Adkins. “Communication lines are open over the geographical distance separating the two institutions. Faculty at both institutions are pulling together and there is a mutual sense of pride in what we all have accomplished,” added Mary Ann Handel, the JAX Track director in Bar Harbor. Thus today, thanks to the efforts of Liz, other Genetics students, both in the JAX Track and in Boston, and the Sackler and JAX faculty, we can all call the program a success!

Liz Adkins moves on from her successes and outstanding work at Tufts and JAX to a postdoctoral research position, studying basic questions about how stem cells remain immortal. And she will continue to teach, an interest she developed during her time as a Sackler student at JAX. She leaves with a sense of accomplishment – in her research and her life – and appreciation for the JAX Track’s unique scientific environment. “Five years later, I have absolutely no regrets,” said Adkins. “I know it helped shape me into the person and scientist I am today, and I feel extremely well prepared for the future.” So yes, in a very personal way, Liz has shown the JAX Track works!

articles, Events for Students, September 2016

ICYMI: Dr. Rafael Luna & Telling Science Stories

Hi, Sackler! I’m a fourth year student in CMDB who is terrified of the fact that she just called herself a Fourth Year. Like some of you out there, I am surprised at how quickly my time at Tufts is passing by, and I am panicking about my career and life objectives. That is why I have made the conscious decision to start attending as many PDA and GSC seminars as I can, to better understand my options and to expose myself to the people who can best explain them to me. For your benefit I will be writing up an “ICYMI” (in case you missed it), a take on what went down and what I learned that you will be able to find in this newsletter. My first piece recaps a seminar hosted by the Tufts PDA titled “The Art of Scientific Storytelling,” given by Rafael Luna, Ph.D. Happy September, everyone!

Would The Lion King still be as exciting if Scar weren’t in the picture? How about if “the circle of life” weren’t really critical to survival in sub-Saharan Africa? Pride rock would be meaningless and Simba would have nothing to fight for, right?

Fortunately for all you kids of the 90’s who like to occasionally belt out a little song called “Can You Feel the Love Tonight,” Walt Disney’s classic film incorporates a dire antagonist to challenge Simba and thus creates stakes to fight for, making The Lion King the compelling tale we know and love.

On August 18th, Rafael Luna, Ph.D. came to Tufts to talk about how basic storytelling elements—a protagonist, antagonist, conflict, scene, resolution, and stakes—make not only for a great Disney plotline but also an impactful and powerful title for a scientific manuscript. Dr. Luna is a biomedical research fellow at Harvard who has applied this method to the design of dozens of his own manuscripts, as well as those of his clients and collaborators. He explained that, by weaving together the above listed elements, you not only construct a more informative and intriguing title, but you also inform the structure and progression of your manuscript’s contents.

Dr. Luna began his seminar by having the attendees name all the specific storytelling elements from The Lion King: the protagonist = Simba, antagonist (or a secondary, supporting role) = Scar, conflict = regency, scene = Africa, resolution = reclaims, stakes (i.e. research impact) = the circle of life. No matter how you combine these characters and themes, you are able to wholly summarize the story. For example: “Simba defeats Scar in a battle for regency in Africa and reclaims the circle of life.” Or: “The circle of life in Africa is reclaimed by Simba as he defeats Scar in the battle for regency.” The possibilities go on and on.

Having established this, we moved on from cartoons to something slightly more relevant to our purposes, like Dr. Luna’s 2012 Cell Reports publication, C-terminal domain of eukaryotic initiation factor 5 promotes start codon recognition by its dynamic interplay with eIF1 and eIF2β. This title prepares us for a story that is primarily about the “protagonist,” C-terminal of eIF5, supported by the “antagonists” eIF1 and eIF2β. The “scene” is set at the start codon, and the “stakes” are start codon recognition. Finally, dynamic interplay summarizes the “conflict,” and we find ourselves with a complete and all-encompassing title. Throughout the seminar, we continued to analyze several other manuscript titles in order to identify how they were successful and how they could be improved.

The manner in which the title is structured can also help determine how the rest of the manuscript is written. If, for example, you are researching how a drug interacts with a certain protein, you can either structure your title such that the drug is the protagonist and the protein is the antagonist, or vice-versa. Depending on your findings, one should make more sense than the other. The implications go even further, since whether the drug or the protein plays the protagonist determines if your paper should be submitted to Nature Pharmacology or Nature Biochemistry.

Incredibly, Dr. Luna’s method is a tool with which any story can be titled and thus, organized. In just one hour, he provided us with a technique to help create accurate, informative, and complete titles. From there on out, it’s hakuna matata: no worries, for the rest of your days…

If you’re interested in learning more about Dr. Luna’s method, his book The Art of Scientific Storytelling is available for purchase on Amazon.com!

articles, Events for Students, September 2016

TUNECC makes a case for collaborative competition

The annual Tufts New England Case Competition (TUNECC) is a unique, student-organized venture that brings together outstanding teams of graduate students and postdoctoral fellows from multiple disciplines and institutions to solve a current life sciences business problem. Each year, the TUNECC Executive Board together with the Center for the Study of Drug Development (CSDD) choose a relevant topic that incorporates both therapeutic and business components to be the focus of the all-day case competition and following panel discussion. Previous years’ topics included new market entry assessment of biologics and post-merger and acquisition integration strategy for a large pharma and an antibiotics biotech. This year the teams tackled Research & Development (R&D) productivity of immuno-oncology field on the example of Juno Therapeutics, a T-cell therapy clinical stage biotech. In addition, a career fair ran throughout the competition, facilitating more opportunities for related conversations and also networking between participants and sponsors.

Two weeks prior to the competition–which took place on August 5th–the assembled teams received their case and were given ten days to brainstorm and structure solutions to the proposed problem. At the competition, the teams presented their proposals in several rounds that were judged by representatives from contributing sponsor companies. For this third year of TUNECC, 17 teams consisting of students from a total of 17 academic institutions nationwide participated, with 5 teams competing in the final round. A first-place prize of $2000 was awarded to the team JT Consulting Solution from Tufts University & Boston University, while second place went to Pennovation, a University of Pennsylvania team ($1000), and third place to Chiron Consulting, a team of students from Vanderbilt University, University of Rochester, University of Arizona and Duke University ($500).

The participating teams this year were highly competitive and deeply engaged in the subject matter, which carried over into a lively discussion during the panel discussion portion of the event. Representatives from sponsoring companies spoke to their experiences with managing company growth and investment to maximize R&D productivity, or rather “doing the best science you can do but also being the most productive.” This conversation evolved as the panel went on, touching on where and why the industry is struggling, the pros and cons of small biotech versus ‘big pharma’ models, and hurdles to approval, pricing, and regulation in drug development. The depth and breadth of the discussion showed how closely intertwined these topics are when considering science in the business setting.

In addition to the high degree of participant engagement, the variety of Tufts programs (multiple Sackler and Medford graduate programs as well as the School of Medicine) and academic institutions from across the country represented at TUNECC is a key component to its continual success. Such cross-institutional collaboration encourages broader thinking and discussion by providing new and different perspectives for each participant to consider when tackling life sciences business problems. The increasing commitment of sponsors from life sciences consulting business sectors also strengthened the event, with the number of sponsoring companies increasing to 11 total this year, almost double the number at the event’s initiation. Not only did this impact the case competition itself but also the day-long career fair and topical panel discussion by providing richer opportunities for forming cross-discipline connections. This achievement was a highlight for this year’s TUNECC Chair Alexandra Taracanova (Pharmacology), who commented that it was rewarding to see “industry being supportive…and interested for what we offer as an event” and was very satisficed by “great talent at Tufts being supported by corporate firms.”

Jennifer Nwankwo, PhD (Pharmacology ‘16) was presented with The Founder’s Award of Excellence for founding, leadership and continues support of TUNECC since the day of its inception in 2014. Additionally more past TUNECC executive members and participants, Julia Keith, PhD (Microbiology ‘15) Hailing Yang, PhD (CMP ‘15), Julie Coleman, PhD (Neuroscience ‘16), Michael Baldwin, PhD (CMP ‘15), and Ben Dake, PhD (CMDB ‘15), attended as judges, sponsor representatives, or simply enthusiastic observers this year, providing the event with increased continuity and a strong network of individuals who return and share their experiences in transitioning from academia to life sciences business.

TUNECC will continue to build on its great momentum in the coming year under the direction of Andrew Coleman (Neuroscience). Applications for new Executive Board members will open in December while applications for case competition teams will open sometime in Spring 2017 for the 4th Annual TUNECC in late Summer 2017. To find out more about TUNECC and previous events visit our website.

Corporate Sponsors: Back Bay Life Science Advisors, The Decision Resources Group, Clarion Healthcare, McKinsey & Company, Putnam Associates, CBPartners, Simon-Kucher & Partners, The Boston Consulting Group, L.E.K. Consulting, ClearView Healthcare Partners, and TechAtlas Group of RA Capital Management.

Additional Support: Tufts Center for the Study of Drug Development and Sackler School of Graduate Biomedical Sciences.

articles, Community, May 2016

Sackler Spotlight – Bina Julian, PPET and Jen Nwankwo, PPET

This spring, two outstanding Sackler students–Bina Julian (PPET) and Jen Nwankwo (PPET)–were awarded the Tufts Presidential Award for Citizenship and Public Service. Established in 1999 by former university president John DiBiaggio, this award honors both undergraduate and graduate students who have shown substantial commitment to and achievements in building community through service and leadership. To highlight these accomplishments, we interviewed Bina and Jen about the work that led to their nomination and eventual awarding as well as what they do at the bench as well (note: at the time of publishing, Jen was out of town, thus we will update this article once we get a chance to talk with her).

Can you tell us about the work that led to you being nominated for this award?

Bina: I have a really strong desire to help people achieve their goals by increasing their self-awareness and connecting them with opportunities. And a parallel desire to figure out how to scale that impact when something works well…probably because I’m an engineer. That’s what drew me to the Tufts Biomedical Business Club (TBBC).

Our TBBC team runs like a small startup. From the beginning, we all saw the potential to connect Tufts students with professional resources, the Boston biotech community and each other. So we each went out and made connections [see Collaborator List] and designed ways for our members to learn and practice the business of science [see About TBBC]. Soon opportunities started coming to us, external groups reached out to collaborate, and our members were being recruited for jobs. I’m really proud of what we’ve built and how many people we’ve helped over the years.

Receiving this award especially acknowledges the work past and present TBBC leaders have done to shape TBBC into a sustainable and engaging training ground.

 

Box 1: Tufts Biomedical Business Club

TBBC is a way for researchers to gain industry awareness and professional development.  Members get introduced to TBBC by attending our seminars featuring business leaders in several areas including venture capital (Bob Tepper, Third Rock), biotech startups (Sandra Glucksman, Editas), and consulting (Chris Von Seggern, ClearView).  Many take a step further and participate in one of our self-guided initiatives, like Case Study Group, Biotech Journal Club, Biotech Buzz or hosting a speaker.  Others gain critical business experience by competing in our Tufts New England Case Competition (TUNECC) or the Gordon Institute’s Tufts $100K New Ventures Competition.  Regardless of whether or not our members become PIs, entrepreneurs or consultants, we hope their time with TBBC empowers them with the network and perspective to pursue a successful career.

Recent TBBC Connections

Internal Connections: TUSM Advancement Office, Sackler Graduate Student Council, Sackler Dean’s Office, Gordon Institute, Tufts Entrepreneurial Leadership Program, Tufts Center for the Study of Drug Development, Tufts Clinical & Translational Science Institute, Tufts Entrepreneurial Network (of student leaders), Tufts Entrepreneur Society (undergrad group), Tufts Institute for Innovation, Tufts MedStart, Tufts MD-MBA Program  , Tufts Office of the Vice Provost Office, Tufts Postdoctoral Association, Tufts Tech Transfer Office, TUSM Public Health and Professional Degree Programs

External Connections: Venture Café, Biotech Connection Boston, Boston Entrepreneurs and Advanced Degree Meetup Group, Northeastern Biotech Entrepreneurs, Boston University BEST Program, Hopkins Biotech Network, MIT Biotech Group, Harvard Graduate Consulting Club, Yale Graduate Consulting Club

Guest speakers from: Back Bay Life Science Advisors, Biologics Consulting Group, Biomille, Brean Capital, BrightMed, Campbell Alliance, Center for Integration of Science and Industry, Bentley University, ClearView Healthcare Partners,Cowen and Company, Cyta Therapeutics, Decision Resources Group, Dyax Corp., Edits, Flagship Ventures, Foundation Medicine, Foundation Medicine, Genzyme, Google, Health Advances, LLC, Johns Hopkins Technology Ventures, LEK Consulting, MPM Capital, Novartis, NYU Entrepreneurial Institute, Polaris Ventures, Propel Careers, RA Capital, Simon-Kucher & Partners, T2 Biosystems, The Isis Group, Third Rock Ventures, Thomas, McNerney & Partners, Tufts Center for the Study of Drug Development, Tufts Gordon Institute, Tufts Institute for Innovation, Vaxess Technologies, Visterra, Inc.

How do you feel that your work connects to your current and future research/career goals?

Bina: I think it highlights the kind of impact I would like to have and scale up. I’d like my future career to bring together my skills as an engineer, a scientist, an educator and a “connector.”

What was the experience of being nominated like?

Bina: I actually had no idea I was being nominated. I have Jaclyn Dunphy and Julie Coleman to thank for going above and beyond to find this award and gather recommendation letters from current and former TBBC executives. When I got the award email and learned what they had done, I was incredibly moved and humbled.

[The Presidential Awards Ceremony took place on April 21st, 2016.  Awards were presented by Tufts University President Anthony Monaco, Tisch College of Civic Life Dean Alan Solomont and nominators.  Watch segments from the awards ceremony here.]

How would you like to see your work continued past your time at Tufts? How do you feel your efforts currently support that vision?

Bina: I hope that TBBC will continue to have an impact and that our connections within and outside of Tufts stay strong. It’s encouraging to meet engineering, policy, medical, dental, nutrition and even veterinary students at our events; they bring such different perspectives to our discussions and also connect Sackler students with opportunities happening at other institutions.

I hope future leaders extend TBBC’s mission with fresh ideas and diligently assess the needs of its members so TBBC stays relevant. Most of all I hope that future TBBC leaders make a conscious effort to not only hone their own leadership skills, but also invest in the professional development of their teammates.

The only way any of this vision will survive is if everyone gets involved – students, faculty, administration, alumni, and the biotech community at large.  We’re a completely student run organization with a multi-year, personal commitment to produce high quality events and initiatives for our members. Whether its volunteers, event ideas, business workshops, speaker connections, conference discounts, alumni mentorship, job/intern opportunities and of course financial support – the executive team welcomes donations in all forms!

Last but not least, can you tell us about the work that you do in the lab?

Bina: I’m a Pharmacology and Experimental Therapeutics grad student working with Dr. Alan Kopin, who directs the Molecular Pharmacology Research Center at Tufts Medical Center. The Kopin lab studies G Protein-Coupled Receptors (GPCRs), a superfamily of 7-transmembrane receptors known for modulating a wide array of intracellular signals in response to extracellular stimuli. These cell receptors are considered highly “druggable” as they are targeted by nearly 40% of FDA approved drugs.

Cells use GPCRs to sense cues in their environment and make decisions. I study a GPCR subfamily of chemokine receptors, whose primary function influences decisions surrounding cell migration. My thesis work characterizes a rather understudied chemokine receptor called CCR6. Notably, CCR6 is highly expressed on and influences the migration of Th17 cells – an immune cell type whose aberrant recruitment to inflamed tissue is associated with several chronic inflammatory diseases. Many are interested in the therapeutic potential of CCR6, yet few tools exist to tease apart and modulate CCR6 receptor signaling.

In the lab I’ve developed molecular tools and assays that can enable screens to identify and characterize CCR6 modulators.  Most recently I established a Bioluminescent Resonance Energy Transfer (BRET) assay to measure beta arrestin recruitment to CCR6.  Most people know that GPCRs signal through G proteins as their name suggests, but they have an alternative pathway mediated through beta arrestin.  The BRET assay allows me to observe dynamic protein-protein interactions with CCR6 and tagged signaling molecules.  We are also interested in how naturally occurring variations in CCR6 affect signaling and if these alterations could predispose individuals to disease.

CCR6 plays a complex role in inflammation at the level of individual cell types and the field needs tools to tease apart its influence. And unlike the reputation of its GPCR superfamily, chemokine receptors have had little drug development success (only one FDA approved compound modulates the migratory function of its chemokine receptor target). Overall I hope the insights from our study of CCR6 variants as well as the genetic constructs and assays we’ve developed can be used by both immunologists and pharmacologists to translate this work to help patients.

April 2016, articles, Community

Implicit Bias: A Conscious Discussion of Unconscious Actions

It is no secret that unconscious biases penetrate various realms of society; from hiring decisions (Lebowitz, 2015) to medical care (Blair, Steiner, and Havranek, 2011) and even foul calls in the NBA (Schwarz, 2007).

But what about implicit bias in our everyday lives? Does it really play a role in who we form relationships with, or the way we interact with others, or even the way we perceive a stranger?

Implicit bias refers to attitudes or stereotypes that affect our understanding, actions and decisions in an unconscious manner, according to the Kirwan Institute for the Study of Race and Ethnicity, which publishes an annual Implicit Bias Review . Unlike explicit bias, which reflects the attitudes or beliefs that one endorses at a conscious level, implicit bias is judgment and/or behavior that results from subtle cognitive processes that often operate at a level below conscious awareness and without intentional control.

Recent claims of overt and covert discrimination on college campuses and in policing raise the question: How does someone’s unconscious reaction to people of a different race, religion or sexuality influence their judgment and behavior? Psychologists and social scientists working within this field do not have a concise answer to explain how implicit bias manifests in everyday life, as it is hard to rule out alternative explanations.
In other words, implicit bias can and does happen, but it is complicated to prove.

“Some biases seem obviously pilogowrong, like treating equally qualified people differently when hiring or promoting,” said Calvin Lai, director of research for Harvard’s Project Implicit. “Every day biases are hard to wrap our heads around because they’re so much more personal, and you can point to other reasons.”

Similarly, structural factors beyond your control might come into play. If most of your friends look like you, or you tend to date people of the same race as you, it could largely be just a reflection of the demographics in your community.

However, research shows that those relationships, along with the interactions and experiences that come from them, are key contributors of implicit biases. These biases begin forming at a young age and are easily reinforced into adulthood through social settings and mass media.

“When you think backwards, what you think is normal is really cultural pressure that pushes you into bias, implicit and conscious,” said sociologist Charles Gallagher, chairman of the Department of Sociology and Criminal Justice at LaSalle University in Philadelphia.

Hanging out with friends that look like you isn’t necessarily a bad thing, especially if they’re nice people! However, research suggests that implicit biases and stereotypes, both positive and negative, are maintained through persistent lack of contact with others beyond your “in-group,” that is people who share certain characteristics.

The good news? We are not helpless to combat implicit bias. It can be mitigated through intervention strategies, starting with recognizing where it might exist in your life and seeking exposure to people and experiences beyond your regular circles.
Psychologists and social scientist who study implicit bias are working to gather more data with the goal of making people more aware of their unconscious decision-making and its consequences.
Harvard’s Project Implicit features a battery of “implicit association tests” where participants can measure levels of implicit bias around certain topics based on the strength of associations between concepts and evaluations.

“The goal of the organization is to educate the public about hidden biases and to provide a ‘virtual laboratory’ for collecting data on the Internet.”

If you’re interested in measuring your levels of implicit bias (almost everyone displays bias in some way, according to the experts!), here are a few tests you can take:
Understanding Prejudice: Implicit Association

Test Look Different: Bias Cleanse

 

References
2015 State of the Science: Implicit Bias Review. (2015). Retrieved from; http://kirwaninstitute.osu.edu/my-product/2015-state-of-the-science-implicit-bias-review/
Blair, I. V., Steiner, J. F., & Havranek, E. P. (2011). Unconscious (Implicit) Bias and Health Disparities: Where Do We Go from Here? The Permanente Journal, 15(2), 71–78.
Grinberg, E. (2015). 4 ways you might display hidden bias every day – CNN.com. Retrieved from; http://www.cnn.com/2015/11/24/living/implicit-bias-tests-feat/
Lebowitz, S., Jul. 17, 2015, 9, 022, & 2. (2015). 3 unconscious biases that affect whether you get hired. Retrieved from; http://www.businessinsider.com/unconscious-biases-in-hiring-decisions-2015-7
Schwarz, A. (2007, May 2). Study of N.B.A. Sees Racial Bias in Calling Fouls. The New York Times. Retrieved from; http://www.nytimes.com/2007/05/02/sports/basketball/02refs.html

articles, March 2016

Sackler website calendar now available in iCal format

The Sackler calendar is a great resource for the community, but its current form does not follow Internet calendar format standards, which limits its utility.  A majority of Tufts community members utilize digital calendar packages like Google Calendar, Apple Calendar, Microsoft Outlook, Mozilla Thunderbird, and others, to keep track of their schedules and subscribe to shared calendars, but the Sackler calendar cannot be used with these programs because it is served as an RSS feed and not an iCal one. The RSS standard was designed for syndication of articles and other news-like data, while iCal is the standard for Internet calendars. Fixing this mismatch will require structural changes to the Sackler website, but the timeline for such changes is not known.

To solve this problem, I have written a script that automatically retrieves the publicly available event information from the Sackler calendar and presents it in a format that calendar programs can utilize. I’ve also made some improvements to the presentation of events, so seminar title will now appear in the event name if it is available. Additionally, the room number will appear alongside the building address in the location field of the event, and has been formatted in a way that allows mapping programs to ignore the room and focus on the address if directions are needed. This code will work until the Sackler calendar URL or the event information formats change, but my hope is that the script will no longer be necessary once that happens. The iCal feed is available at http://sackler.danielsenhwong.com/calendar.ics, and can be imported as a calendar subscription in most calendar software packages. This feed is set to automatically update every morning at 4 AM, but the refresh frequency of common calendar programs varies. Instructions for some of the most popular applications are included below. This calendar is not compatible with either Outlook 2011 for Mac or the Outlook Web App (2010) available from Tufts at http://exchange.tufts.edu for reasons that are beyond my control, but should work with Outlook 2007 and newer versions for Windows.

The Sackler calendar is only as useful as the information that is provided to it, so individuals responsible for planning and scheduling events should continue to submit their event information to it by using the website form: http://sackler.tufts.edu/Calendar/Submit-an-Event

 

Google Calendar (calendar.google.com)

Adding an iCal feed to Google Calendar To add the Sackler calendar to your list of calendars, open Google Calendar. Click the downward-pointing triangle to the right of “Other Calendars” that appears along the left side of the page, and select “Add by URL” from the menu. Enter the URL http://sackler.danielsenhwong.com/calendar.ics in the text box and click “Add Calendar”.  The new calendar should appear in the list, and the events will populate your calendar in a few seconds. Google Calendar will refresh this feed every few hours. The iCal feed can only be added to Google Calendar from a computer, and not the Android mobile phone application.

 

Apple Calendar (Apple OS X)

Adding an iCal feed to Apple CalendarTo add the Sackler calendar to your list of calendars, open Apple Calendar, and select “New Calendar Subscription…” from the “File” menu. Enter http://sackler.danielsenhwong.com/calendar.ics as the Calendar URL in the text box and click “Subscribe”. The new calendar should appear in the list, and the events will populate your calendar in a few seconds. By default, Apple Calendar only updates calendar subscriptions once per week. To change the update frequency, right-click (Control+click) the “Sackler Website Calendar” entry in the list of calendars and select “Get Info”. The update frequency can be changed by selecting a different interval from the “Auto-refresh” option list.

 

Microsoft Outlook 2013

Adding an iCal feed to Microsoft OutlookTo add the Sackler calendar to your list of calendars, open Outlook and go to the Calendar pane. Select “Open Calendar” and “From Internet…”  from the middle of the “Home” ribbon across the top of the screen. Enter http://sackler.danielsenhwong.com/calendar.ics as the Calendar location in the text box and click “OK”. The “Advanced…” button will open a menu allowing you to change the name of the Calendar and the description I have provided. Click “Yes” to subscribe to the calendar. The new calendar should appear in the list, and the events will populate your calendar in a few seconds, after Outlook finishes processing the feed.

Mozilla Thunderbird (mozilla.org/thunderbird)

To add the Sackler calendar to your list of calendars, open Thunderbird and go to the Calendar view. Select “New…” then “Calendar…” from the “File” menu. Select “On the Network” as the location for the calendar, and then click “Continue”. Select “iCalendar (ICS)” as the format, and enter http://sackler.danielsenhwong.com/calendar.ics as the location in the text box and click “Continue”. Thunderbird doesn’t read the given calendar name, “Sackler Website Calendar”, from the iCal feed, so give the calendar a name of your choice and click “Continue” to complete the process.