Ariane Panzer, PhD

We Should be Concerned About What Happened at the CDC

Thu, 06 Feb 2025 12:00:00 -0800

On February 1, 2025 the Inside Medicine Substack reported that the US Centers for Disease Control and Prevention (CDC) ordered agency scientists to withdraw research manuscripts under consideration for publication at medical or scientific journals. The directive, which was emailed to staff members on January 31, included a list of “forbidden terms” researchers must strip from their work.

Banned terms include gender, transgender, non-binary, LGBT, biologically male, biologically female, and more. Removal of these terms is meant to ensure the CDC’s compliance with 47’s executive order stating that the federal government will only recognize two sexes, male and female, and that these sexes are not changeable.

Requiring scientists to remove these terms from their manuscripts is a direct threat to their ability to conduct rigorous research and will have devastating effects.

Negative Impact on Research

When I worked as a scientific editor at a medical journal, we required our authors to report patient characteristics and demographic information in Table 1 of their manuscript. This is a common practice across medical journals.

One piece of information in this table is the number of males and females included in the study (which is unfortunately interchangeably labeled with “sex” or “gender” and often does not account for non-binary folks). If the study has an even balance, readers can be more assured that the study conclusions are applicable across biological sex variations, instead of centering male biology as was the case for the majority of clinical studies before 1993.

Information in Table 1 not only helps readers better judge and interpret study conclusions, it can also help healthcare providers develop policies.

Let’s consider a paper by Thronhill and colleagues published in the New England Journal of Medicine reporting on cases of mpox during the 2022 outbreak. In Table 1 the authors report the sex and sexual orientation of people included in the study. Of the 528 individuals with laboratory-confirmed mpox infections, over 99% were male and 96% identified as homosexual, suggesting this outbreak disproportionately affected gay men.

This knowledge can inform healthcare professionals about which populations may benefit from enhanced testing and education. Additionally, given the short supply of vaccines during the 2022 outbreak, this knowledge helped identify which groups should be prioritized for vaccination.

Present and Past Destruction of LGBTQI+ Research

While censoring terms in research manuscripts will negatively impact major studies in multiple disease areas, what is more insidious is that the banned terms target LGBTQI+-related research.

How can scientists communicate research on LGBTQI+ topics if they can’t use the clear and accepted language? The answer is they can’t.

And that’s exactly what this administration wants. They are actively trying to destroy LGBTQI+-related research in yet another attempt to erase LGBTQI+ people.

This directive is especially disturbing because destroying LGBTQI+ research is a play right out of the Nazi handbook.

When Adolf Hitler became chancellor in 1933 he established policies aimed at eliminating Lebensunwertes Leben (“lives unworthy of living”) from Germany. One result of such policies was the destruction of Berlin’s Institut für Sexualwissenschaft (Institute for Sexual Research).

Opened in 1919 by Magnus Hirschfeld, a gay doctor who recognized the existence of variations in sexuality and gender, the Institute for Sexual Research was meant to be a place of “research, teaching, healing, and refuge”. In 1930, the first modern gender-affirming surgery was performed there.

The institute also had a massive library on sexuality that included rare books and protocols documenting the surgical process for male-to-female transition. But when the Nazis pillaged the institute on May 6, 1933, they burned over 20,000 books from the library, erasing research and knowledge that benefited the LGBTQI+ community.

Hirschfield not only provided life-saving medical care for his patients, he also fought against the criminal code that made homosexuality illegal (Paragraph 175) in Germany and provided jobs for individuals he had helped transition who couldn’t find work.

His dedication to the LGBTQI+ community is what we scientists should emulate today and we can do that by fighting to protect LGBTQI+ research.

What Can the CDC Do?

47 is trying to instill fear and chaos.

Leaders at the CDC must speak candidly but privately to their employees about this. The legality (or lack of legality) of the directive should also be discussed and employees should know that the executive order the directive is based on could be challenged in court.

The Inside Medicine Substack quoted an official from the CDC saying “I’ve got colleagues pulling papers over Table 1 concerns.” This is preemptive obedience and should be discouraged.

I understand that employees may worry about losing their jobs if they refuse to comply, but if no one is prepared to fight then tyranny awaits.

Examples of resistance from other organizations may be a good source of inspiration for CDC employees.

A thread posted on Bluesky by librarian Jennifer Goodland talks about how the library she worked at weaponized bureaucracy in response to PATRIOT Act-mandated requests for patrons' borrowing history.

The librarians at her branch banded together to delete and shred that information. They also stopped tracking patrons' reading history, but that wasn’t all.

“We added a Patriot Act compliance officer to our org chart. This person was a real employee.
Well, WAS. The office of Patriot Act compliance would be assigned to whichever employee had just left our library. And gosh, it’s just such a mess around here, you know.”

Goodland’s library branch ultimately didn’t fulfill a single PATRIOT Act request.

Other creative strategies of resistance could be used too. The “Simple Sabotage Field Manual” may offer a good starting point.

The manual, written during World War II by the head of the Office of Strategic Services William Donovan, describes methods for normal people to resist decrees by being “particularly annoying.” Suggestions include pretending that instructions are hard to understand or being “as irritable and quarrelsome as possible without getting yourself into trouble.”

I hope CDC employees band together (or unionize if possible) and prepare to fight. There is power and protection in numbers, and scientists must show politicians we will absolutely not back down from our convictions.

What Can Medical and Scientific Journals Do?

Journals should come out with statements supporting LGBTQI+ research and the scientists conducting this research. On February 4, editors at the BMJ censured the CDC order and called on journals and editors to resist.

Journal editors must also come up with strategies to address this censorship of science. This could start with highlighting a common requirement of medical and scientific journals, that research manuscripts adhere to the American Medical Association (AMA) Manual of Style. This manual includes guidance on the correct and preferred language to use in scientific publications.

Using appropriate and consistent terminology helps make research more clear, more accurate, and less biased. Not only does this make research more rigorous, it also better serves the populations studied.

Alternative Approaches

Scientists at the CDC were ordered to withdraw manuscripts being considered for publication in journals, but what about preprint servers?

Research can be submitted for free and disseminated for free on sites like bioRxiv and medRxiv. While these preprint servers don’t offer traditional peer review, papers are still reviewed by bioRxiv and medRxiv staff and volunteers and can be commented on. Perhaps publishing a manuscript on one of these sites may fly under the federal government’s radar.

Or maybe we need to completely flip things on their head and come up with new terms. If we can’t use the term “transgender women” we could replace it with another term that is popular with some in the community, “the dolls”. If a scientist can call a COVID variant FLiRT it seems anything can go.

Final Thoughts

47’s executive order stating that there are only two sexes is not only medically inaccurate but seeks to erase LGBTQI+ people, their experiences, and any research that supports them. When science is censored, it becomes impossible for scientists to conduct and disseminate research that can improve our world. We scientists must fight for the accurate and ethical reporting of science and advocate for the people we intend to serve with our research.

My Mental Health and Graduate School

Mon, 24 Jan 2022 18:54:48 -0800

I gave my PhD exit talk on Tuesday September 13th, 2021, but afterward I didn’t feel like celebrating, I just felt burnt out.

During my PhD I never felt like I was making enough progress. This constant thought was heavily influenced by the fact that there was only one model of “PhD success” I was aware of, and my PhD journey didn’t adhere to this model. My dry lab data weren’t enough. The interesting wet lab results I got here and there weren’t enough. The only way I could graduate was by putting together a comprehensive, multidisciplinary research story.

I become increasingly stressed as my graduate school years ticked by. This feeling was further amplified by things like a lack of expertise in my lab for many of the experimental methods I was trying. While I was able to get some of the techniques I taught myself to work, other methods–like mass spectrometry–were impossible to teach myself how to do, and I couldn’t find people with both the expertise and the time to help me.

The more overwhelmed I became the more singularly I focused on my research. I didn’t give myself time to do or deal with much else. I knew there were other aspects of my life, and some were given attention, but most I decided didn’t matter as much as finishing my PhD. I put these other things–reading fiction, creative pursuits, nourishing myself properly, sex, processing my emotions–in separate boxes, taped them shut, and shoved them deep into the recesses of my mind. I told myself I’d come back to them but only after I graduated.

Some of the things I boxed up seemed small, but actually had a larger negative impact than I thought. When the chronic stress manifested in my having breakdowns every other week I went to see my nurse practitioner. I told her about my history with depression and was prescribed sertraline, which I hadn’t had to take in 10 years but which definitely helped. With the onset of the pandemic, I started having a much narrower definition of who I was and had fewer areas in which to find happiness. Then I had my first panic attack in December 2020 and decided to start seeing a therapist.

Finally–without that comprehensive, multidisciplinary research story–I graduated. I was out of the lab and out of academia, but I still was not OK. I was tired from constantly being asked to preform to prove my intellect. Tired of comparing myself and beating myself up for not being as successful as other UCSF graduate students who publish in Cell, Nature, and Science. Tired of judging the worth of what–if anything–I had contributed to science and questioning whether I even deserved my PhD.

I wanted to feel nothing and think nothing. So the first thing I did after graduating was nothing, and the kindest thing I did for myself was to not allow any self-judgment.

After a while of nothing my brain started turning on again, tuning back in to my thoughts and feelings. There were two thoughts that came up the most: “Will I ever love science again?” and “Who am I now?” I felt like graduate school had destroyed something I once loved and caused me to lose my sense of self. I was angry, frustrated, sad, judgmental, trying to figure out how things ended up this way. I took a moment to grieve (and still do at times).

Then I had to let go of what I was told success as a PhD student was supposed to look like. I had to let go of the PhD student I thought I should have been. I had to learn to appreciate the journey I went through even though academia made it feel wrong, made me feel undeserving of what I earned. Only then could I create space to celebrate the scientist I had become.

When I stopped beating myself up–essentially reinjuring myself–I finally started to heal. And I did three things that helped:

I started just reading postings for science jobs. Over time, the more postings I read the more I felt that there were science jobs out there that interested me. Hooray, my love for science wasn’t dead!
I updated my CV and when I saw all my accomplishments laid out over two pages damn did I feel good!
I celebrated my graduation by buying myself a commemorative coffee mug.

I’ve slowly been digging out the boxes I hid away in my brain during my PhD, opening them, and facing what’s inside. It’s not easy. Negative thoughts from my past still reverberate like echoes in my mind, but I’m trying to replace those thoughts with kinder ones. It’s taking longer than I hoped to work through everything, but I’m starting to redefine my (often unrealistic) expectations, show myself more compassion, and be okay with where I am in this process. I’m not working, but I’m applying to jobs. I hope to return to science soon with some new endeavor which I think will help me continue to heal.

And now for some advice for current/future PhD students in the hopes it will make your experience even 1 µL easier:

Try not to define yourself by your PhD. Being a researcher is not the only thing you are, it’s only one piece of who you are.
Don’t put every other aspect of your life on the back burner. When you do this the failures you face during your PhD hit you harder and you lose other sources of success and happiness in life. I, for example, would have been even more lost without having science communication as an outlet.
Every PhD journey is different. Don’t let others dictate what success should look like for you, come up with your own definition.
Let yourself know that gradual progress is still progress and celebrate incremental successes.
Clearly define expectations. Yours, your advisors, your committees, your PhD programs. And keep checking in about these expectations as they may change. If I had done this earlier I think I would have saved myself a lot of anguish.
Listen to your body. Feeling hungry? Eat! Head hurts? Start by drinking water, you might be dehydrated (this was the case for me A LOT). Been sitting a while? Stretch and take a brief walk. Only when you take care of yourself can you do your research well.
A PhD is a marathon with lots of stress inducing pit stops. Don’t shove stress down, release it with things like: a 3 min dance party (thanks lab storage closet!), a deep breathing exercise (thanks Headspace and Calm!), a laugh (thanks friends!), or a cry (thanks single stall bathrooms!).
When things get tough, identify the parts of science you love and try to incorporate those into your schedule more. For me, reading or talking to people about their cool research always energized me and helped rekindle my love for science.
Show yourself compassion. Would you say what you are saying to yourself to a friend? No? Then shut up, brain!

Hope this advice and/or hearing about how I processed my graduate school experience helped. And if you need it my Twitter DMs are open.

Image description: A large coffee mug with a sun-yellow handle and interior. The outside of the mug is white with black font. The words “Miss” “Ms.” and “Mrs.” are crossed out thus the text reads: “It’s Dr. Panzer actually”. Dr. Panzer is written in a fancier, cursive font to add emphasis.

Bacterial Strategies of Host Colonization

Thu, 16 Dec 2021 16:20:30 -0800

Our environment exposes us to a vast array of microorganisms some of which populate our microbiomes. Research on microbiome assembly has largely focused on host features that dictate habitability, but bacterial features that promote colonization of a host, especially in non-pathogenic organisms, remain poorly understood. In the August issue of Cell Host & Microbe, Robinson et al. investigate bacterial strategies of host colonization and identify a mechanism by which bacteria use chemically regulated motility to promote rapid immigration into the host.

To identify bacterial traits that promote bacterial colonization of the host, Robinson and colleagues carried out an evolution passaging experiment in germ free (GF) zebrafish. Generation zero was inoculated with a zebrafish gut commensal isolate Aeromonas veronii and subsequent generations were treated with the pooled gut-associated Aer01 populations from the previous generation. This process was repeated for 20 generations following which genomes of isolates from different passages were sequenced and compared to the genome of the ancestral strain. One A. veronii gene commonly mutated in evolved isolates that outcompeted the ancestral isolate for host colonization is a gene the authors named spdE.

Structural evidence showed that spdE encodes a diguanylate cyclase enzyme with two functional domains: a tandem PAS/double Cache (tPAS/dCache) domain in the periplasm and a GGDEF (diguanylate cyclase) domain in the cytoplasm. Biochemical experiments revealed that the tPAS/dCache domain binds the amino acid proline—and to a lesser extent valine and isoleucine. SpdE appears to be involved in production of the second messenger cyclic diguanylate (c-di-GMP) as inhibition via ligand binding or deletion (ΔspdE) resulted in decreased intracellular c-di-GMP. Inhibition of SpdE also increased cell motility, reduced biofilm formation, and offered a competitive advantage for host colonization. Importantly, the authors found that the amino-acid ligands of SpdE act as chemoattractants for A. veronii cells. This motility response to SpdE ligand availability worked independent from chemotaxis (movement along a chemical gradient) as proline was still somewhat capable of attracting a chemotaxis defective strain (ΔcheA). Furthermore, reduced immigration into the host observed in ΔcheA compared to WT strains was rescued upon inhibition of SpdE, suggesting that even in the absence of chemotaxis, SpdE provides an advantage for host colonization.

Finally, the authors sought to determine the source of these environmental SpdE ligands. Compared to GF fish-conditioned flask media (FC-FM), A. veronii cells in conventionally reared FC-FM showed a trend toward increased motility and reduced biofilm formation, thus suggesting that the presence of a complex microbiota increased availability of SpdE ligands. Supernatant from GF fish treated with a bacterial collagenase to free proline from the amino-acid rich host protein collagen also increased cell motility, offering a potential mechanism by which the gut microbiota augments environmental SpdE ligands.

Taken together, Robinson et al. showed that host-emitted amino acid cues produced by the resident microbiota inhibit SpdE production of c-di-GMP which, in turn, promotes increased bacterial motility and enhanced colonization of the host. This work not only revealed a novel mechanism of bacterial chemokinesis that seems to optimize bacterial chemotactic tracking and movement toward a host, but also provides new insight into the principal of microbial succession. In their experiments using CR fish, the authors noted a high amount of variability in A. veronii motility responses. This was likely due to variation in the composition of host microbial communities and their different functional capacities for liberating proline from host sources. Zebrafish containing microbiomes with less microbial collagenase activity, for instance, would emit lower concentrations of amino acids into the environment. This would reduce the capacity for A. veronii to colonize the host, thus offering evidence of how a host’s microbial community history can impact new species colonization. Future work in other model organisms will be of great interest for understanding the contribution of bacterial chemokinesis to host colonization under non-aquatic living conditions.

The Importance of TGFβ to Skin Tissue Resident Memory T Cells

Sun, 12 Dec 2021 16:15:19 -0800

CD8+ tissue resident memory (Trm) T cells are long-lasting immune cells retained at peripheral tissue sites where they can mount a rapid and robust local response to previously encountered microbial pathogens. In the epidermal compartment, Trm cell development is critically dependent on transforming growth factor β (TGFβ). This cytokine, produced in a latent form, is activated in skin by keratinocyte-expressed αvβ6 and αvβ8 integrins, and skin CD8+ T cells exposed to active TGFβ show upregulated expression of the surface molecule CD103. CD103 can bind E-cadherin on epithelial cells ultimately promoting skin retention of Trm T cells.4 In an article published earlier this year in Immunity, Hirai et al. use a series of sophisticated mouse experiments to determine the source of TGFβ and its role in supporting epidermal Trm cell residence.

To establish whether continued exposure to TGFβ was necessary for long-term maintenance of CD8+ Trm cells in the skin, the authors generated CD8+ ovalbumin-specific transgenic T cells (OT-I) engineered to express a tamoxifen (TAM)-inducible Cre-recombinase that ablates the gene encoding TGFβ receptor type 2 (Tgfbr2). These cells were adoptively transferred into recipient mice who were subsequently infected via a skin scarification method with vaccina virus expressing ovalbumin (VV-OVA). 42 days after infection—a timepoint by which Trm cell populations would have formed and differentiated—TAM was administered to induce deletion of Tgfbr2 and 30 days later epidermal sheets were collected. The authors found that post-infection ablation of Tgfbr2 led to a significantly reduced number of epidermal Trm cells.

Following this, Hirai and colleagues generated mouse models in which the gene encoding TGFβ (Tgfb1) could be inducibly excised from keratinocytes or CD8+ T cells. Loss of Tgfb1 expression in CD8+ T cells, but not keratinocytes, effected Trm cell numbers. Importantly, Trm cells lacking Tgfb1 did not negatively impact Tgfb1+ cells in close proximity, leading the authors to conclude that Trm cell maintenance depends on autocrine TGFβ.

Unlike in other tissues, Trm cell differentiation in the skin does not depend on secondary encounter with cognate antigen. Indeed, non-specific inflammation caused by local administration of agents such as the sensitizing hapten 2,4-dinitrofluorobenzene (DNFB) can efficiently recruit T effector cells to the skin where they can differentiate into bystander Trm cells. Bystander Trm cells also depend on TGFβ as, like their antigen-specific counterparts, this population is absent in mice lacking keratinocyte expression of TGFβ-activating integrins. The authors thus sought to understand the relative importance of active TGFβ to these different Trm populations. For these experiments, OT-I cells were transferred to wild type mice following which the left flank was infected with VV-OVA while the right flank was topically treated with DNFB. Both treatments recruited and maintained similar numbers of OT-I Trm cells. However, when αvβ6 and αvβ8 integrin-mediated TGFβ activation was blocked post-infection, only bystander Trm cell numbers were significantly reduced. Importantly, bystander Trm cells exposed during the differentiation phase to VV-OVA or in which TGFβ receptor signaling was genetically enforced were better able to persist following αvβ6 and αvβ8 inhibition. These data indicate that Trm cells that have encountered cognate antigen are more resilient than bystander Trm cells in epidermal environments where TGFβ is limited.

To compare antigen-specific and bystander Trm cell fitness in a TGFβ-competitive environment, the authors used the same OT-I adoptive transfer and flank-treatment regimen as above, but also treated a distal site (the abdomen) with the antigenically distinct sensitizing hapten oxazolone to generate oxazolone-specific CD8+ T cells. Following oxazolone challenge, these cells were recruited to flank skin where they would compete with Trm cells for local TGFβ. Reduction in Trm cell numbers was observed at both the VV-OVA and DNFB-treated sites, but bystander Trm populations were consistently lower than those of antigen-specific Trm cells. In OT-I cells where TGFβ receptor signaling was genetically enforced oxazolone challenge no longer significantly impacted Trm cell numbers. Thus, newly recruited CD8+ T cells decrease Trm cell retention with a preference toward displacing bystander Trm cells. When Trm cells are given a genetic advantage for accessing TGFβ, however, they are better able to compete with newly recruited CD8+ T cells. Together, this indicates an important role for TGFβ in regulating Trm cell populations and their persistence in the epidermal compartment.

Finally, the authors carried out transcriptomic profiling to understand the mechanism driving the competitive advantage antigen-specific Trm cells have over bystander Trm cells. While differences were not observed in TGFβ related pathways, bystander Trm cells did show increased expression of histone gene variants associated with chromosome silencing. This suggests that bystander Trms may be less epigenetically poised to quickly respond to changes in environmental TGFβ levels than antigen-specific Trm cells.

Hirai and colleagues not only demonstrated that CD8+CD103+ Trm cell residency is supported by autocrine TGFβ, but also revealed competition for active TGFβ as a mechanism for preferentially maintaining antigen-specific Trm populations over bystander Trm populations in the epidermal niche. Although this research focused on skin, it is possible these findings could be extended to CD103+ Trm cells found in other tissues such as the gastrointestinal tract or lung. The mechanisms by which this molecule is maintaining memory programming and whether this cytokine is of equal importance to CD103- Trm cell populations remain to be determined. Overall, this increased understanding of the role TGFβ in Trm cell maintenance could enable the rational design of vaccines and immunotherapies capable of enhancing tissue-specific immunity.

Inflammatory Mediators of Pre-Term Labor

Tue, 19 Oct 2021 18:08:35 -0800

Intrauterine infection/inflammation (IUI), also known as chorioamnionitis, is a condition that occurs when bacteria from the urogenital tract ascends to the uterus and infects the membranes surrounding the fetus as well as the amniotic fluid. It is well established that IUI contributes to preterm labor and can led to devastating health outcomes for both the pregnant individual and the fetus. Not all IUI cases end in preterm delivery, however, thus necessitating research to identify the specific inflammatory mediators that drive IUI-induced preterm labor.

A recent study in PLOS Biology sought to address this gap in knowledge using non-human primate models of IUI in which pregnant rhesus macaques were intra-amniotically injected with either live Escherichia coli or with the gram-negative bacterial membrane component lipopolysaccharid (LPS). While neutrophil infiltration into maternal and fetal placental tissue and upregulation of pro-inflammatory cytokines were observed in both LPS and E. coli treated animals, live bacteria induced the greatest increase in expression of inflammatory markers, including interleukin-6 (IL-6) and prostaglandins PGE2 and PGF2α. Importantly, preterm labor was only observed in E. coli treated dams and occurred even after antibiotic administration in 6 of 8 treated dams.

The authors next wanted to determine the anatomical location of these pro-inflammatory signals and used a novel technique, dual RNAscope fluorescence, to co-localize IL6 and PTGS2 mRNA expression with activated neutrophils (defined as being myeloperoxidase (MPO) positive). MPO+ neutrophils expressing PTGS2 were observed in the maternal tissue (decidua) and the outermost fetal tissue (chorion) in both treatment groups, however, far more MPO+PTGS2+ neutrophils were observed in the innermost fetal membrane (amnion) of animals treated with E. coli. Additionally, epithelial and mesenchymal cells were found to express IL6 and these IL6+ cells were only observed in the amnion of animals treated with E. coli.

Finally, Cappelleti et al. compared the chorioamnion-decidua tissue gene expression profiles of E. coli-exposed animals that did or did not experience preterm labor. Tissue from the preterm labor group showed upregulation of genes involved in neutrophil-mediated immunity and degranulation and regulation of IL-6 production.

This study is one of the first to define inflammatory features of infection capable of triggering preterm birth. Specifically, Cappelletti and colleagues showed that the magnitude of the inflammatory response and the upregulation of specific pathways–such as those related to IL-6 and prostaglandin production–are critical contributors to preterm labor. Literature in the field of immunology often focuses on the presence and clearance of inflammation, however, this research demonstrates the importance of understanding the specific mechanisms underlying different tiers of the inflammatory response. Of further interest was the observation that IUI-triggered preterm labor could not be rescued by antibiotics as the inflammatory environment persisted despite bacterial clearance. Thus, a deeper understanding of the immunological microbiological, and pharmacological processes existing at the complex maternal-fetal interface will be necessary for the creation of novel intervention strategies to protect against infection induced preterm labor.

Is AI Too Smart For Our Own Good?

Sat, 01 May 2021 10:08:05 -0800

Can scientific achievements become so advanced that we lose sight of our own humanity? This thought was weighing on the mind of science and technology journalist Jacob Ward during a Synapse-sponsored lunchtime talk with students on Tuesday, April 16.

At UCSF we think of science as a subject we study, but science can also be used as a lens through which we view and deepen our understanding of other subjects.

Ward, a Berggruen Fellow at Stanford’s Center for Advanced Study in the Behavioral Sciences, uses this lens in his work as a journalist and technology correspondent for NBC news.

He recently pondered the ethical considerations of scientific advancements after profiling writer Anna Todd whose work was discovered with the help of an algorithm created by the company Wattpad.

The algorithm compares the language of uploaded stories to the language of successful novels and identifies stories that may be the next book or movie sensation.

Thanks in part to Wattpad’s algorithm, Todd became a New York Time’s bestselling author with five published novels and a film adaption now in theaters.

This ability of Artificial Intelligence (AI) to perfectly carry out an activity that seems inherently human led Ward to reflect on the ramifications of technological advancements mimicking human creativity.

“[AI] will give you the most likely answer just out of [the input you give it], and we in our brains tend to confuse that with some sort of intelligent machine that is looking at the world and is making a better decision than human beings could,” said Ward.

“[The problem with] pattern recognition machine learning is that you create these feedback loops that nobody ever ends up seeing. And it’s especially hard to look at because the people who build the pattern recognition systems don’t even know why the AI came to the conclusion it did.”

For example, said Ward, consider the impact of AI on art. Ward covered a story about Mario Klingemann who taught an algorithm his taste in art. The algorithm then used the input paintings Klingemann fed it to generate new works of art.

This piece was considered so significant that it sold at Sotheby’s auction house in February for over $50,000. That generated no small amount of controversy.

“There was an MIT philosopher who wrote this whole [piece] about how you should not confuse this kind of work with real creativity,” said Ward. “Real creativity is held within the human soul, and this is just a simulation.

“My question is if it does such a good simulation and you can’t tell the different who cares? [People] don’t care, they’re going to sell you this stuff.”

In addition to the invisible attitudes being shaped by human interactions with AI, Ward is also interested in how technological and scientific advances are pushing humans into other new ethical dilemmas — for example the new field of genoeconomics, which Ward wrote about in a recent New York Times article.

Genoeconomics works on a principal familiar to biologists and medical doctors, that variations in the human genome can be associated with different outcomes.

Instead of applying these genetic variations to medical outcomes, however, sociologists are now applying them to social outcomes.

Ward talked to University of Southern California economist Daniel Benjamin who co-led a study comparing the DNA of over one million people to identify genetic variations that could predict the likelihood that an individual would graduate from a four-year college.

“I and a bunch of critics that I interviewed asked ‘What’s the point of this? Isn’t this going to do more harm than good?’” said Ward.

Researchers told Ward that discovering genetic disadvantages related to learning could help the education system identify and correct for them.

They also suggested that their work could strengthen the findings of the Perry Preschool Project, an ongoing research study tracking preschool students and the impact early education has on their life trajectories.

Despite these good intentions, Ward saw a hole in these explanations.

The majority of participants in the Perry Preschool Project have been African American, whereas Benjamin’s study only captures genetic variations in white people.

That’s because the study’s genomes came from cohorts assembled by the Estonian Genome Center, Iceland’s deCODE Genetics, the UK Biobank, America’s 23andMe, and other predominantly white nations.

“There’s a long history of porting learnings from upper-class white people over to other communities that never really works out,” said Ward. “They have no way of [applying] this research to African Americans, and yet they are talking about using it to help people in school. Nobody needs more help in the United States right now than black people in terms of economic disparities and educational disparities.”

Ward shared his reservations on genoeconomics at a conference by the Social Science Genetics Consortium. He compared the genetic predictors in Benjamin’s study to another example of a well-intentioned invention being misused, Alfred Binet’s IQ test.

“It’s the same idea, and people wound up using the IQ test to exclude whole swathes of the world from immigrating to the United states,” Ward told them. “Eugenics was born out of that. Why would you mess around with this?”

The response at the conference was not positive.

“I got shouted at by a whole bunch of people,” Ward said.

According to Ward, the scientists said “science is about the free, unrestrained discovery of as much new information as possible. It’s not our job to say ahead of time this is not something we should pursue because it’s too dangerous.”

Ward was still dubious.

“I feel like we’re at a place technologically and scientifically [where] we’re so out ahead of our ability to see that we are being played, much less our ability to create an ethical framework for how we’re going to use these [scientific and technological advances],” Ward said.

“Is there a mechanism for evaluating the work before it’s done? [Does anyone ask] should this be done? How do we get this conversation going?”

Ward still hasn’t settled on an answer.

Originally published in Synapse – The UCSF student newspaper on April 23, 2019

Sexual Harassment Process Troubles Complainants

Thu, 01 Apr 2021 09:30:39 -0800

Several UCSF students came forward with their stories of academic sexual misconduct involving individuals who are still at UCSF last October after a briefing of the National Academies of Science, Engineering and Medicine (NASEM) report on sexual harassment of women in science. The study showed that despite the policies and procedures in place, 50 percent of women experience unwanted sexual harassment in academia.

One survivor who shared her story is UCSF alum Grace, whose name we have changed to protect her identity.

It was interview weekend when Grace became interested in working with Richard Schneider.

“I was talking to another professor and then he pulled me aside and said, ‘you don’t want to work with that professor you want to work with me,’” she recalled. “I thought he was really committed to being a good mentor. I guess that’s what I thought at the age of 20.”

Grace started school at UCSF a year later and when she needed to choose a faculty advisor for a project she asked Schneider.

“For a long time I thought ‘he is so invested in my academic success,’” she said. “He’d have these really long, intense meetings with me.”

Initially, her meetings with him were one hour, but over time their meetings grew longer.

Then he started to schedule their meetings around lunch.

“He would invite me out to lunch and say, ‘Oh let me grab my jacket cause it’s actually a lunch date.’ And I just thought ‘Oh, that’s funny.’”

Grace was interested in joining Schneider’s lab, so when he invited her to the department holiday party she agreed to go.

“He told me if I was joining his lab, or considering it, it would be good for me to meet the whole department and learn about what everyone is doing,” Grace said.

“He kept bringing me drink after drink and that’s when I thought, ‘this seems unhealthy.’ Then he told me I was being too weak to handle myself and if I didn’t join his lab that would mean I was too afraid.”

With a keen interest in Schneider’s research Grace decided to join the lab, and her relationship developed beyond that of mentor and mentee.

“It took me a long time to realize his interest in teaching me wasn’t [really] in teaching me,” Grace said.

Her romantic involvement with Schneider, who was married, made Grace feel increasingly isolated. Eventually, Grace did end their romantic relationship, but she still felt uncomfortable and didn’t know how to leave the lab environment.

Unclear about the resources available to her Grace started to talk.

“In personal discussions if I mentioned that so-and-so was harassing me, people would say ‘Oh gosh, let’s not talk about this again or we’ll have to report it,’” Grace said.

“A professor might say ‘I’ll try to [take care of that]’ but then [didn’t], or ‘maybe let this one slide.’ So there was very much a sense that it had to reach a certain severity before getting reported. But if it was a certain severity, they also didn’t want to report it because people would get into actual trouble.”

At first Grace accepted this. Reporting Schneider, she believed, could negatively impact her own studies and reputation.

Once her advising committee signed off on her thesis, however, she spoke to two people she felt she could trust.

Grace’s complaint initially led to mediation, but later launched a formal Title IX investigation to determine if university policy on sexual violence and harassment had been violated.

“[A group of UCSF lawyers] interviewed me and [said] ‘the investigation is beginning’ and that was it,” Grace said. “What they did in the background, like interview other people, I have no idea.”

In a Title IX investigation, campus investigators interview witnesses and gather information. The evidence is then assessed, a report written, and a conclusion made.

Grace faced difficulties when others were unwilling to speak up about Schneider’s behavior.

“Legally [the Title IX report] was probably laid out accurately, but what was left out is that they couldn’t follow up on any related experiences from his previous trainees,” Grace said. “They were afraid to speak because they were still in academia, so they said they would not come forward at all.”

In July 2013, the Title IX report was completed and found that Schneider was in violation of university policy.

Schneider did not immediately respond to a media inquiry for comment on this article.

Almost two years later, in February of 2015, Grace received a letter of resolution from the university describing the disciplinary actions imposed upon Schneider. He was demoted and a formal letter of censure was put into his academic personnel file, and would remain for four years, until February 2019.

By this time Grace had not only left UCSF, she had left science.

“I floated around for a couple of years not doing anything because of the trauma,” Grace said. “I would get panic attacks going to interviews. I didn’t think I could survive in any place I had to work with a man, which was literally everywhere.”

More Transparency Called For

Meanwhile, UCSF trainees are unaware of Schneider’s violation of the UC policy on sexual harassment. Schneider received the Dentistry School’s Mentor of the Year award in 2016, one year after the letter of censure was put in his personnel file. Trainees are still working alongside him, and that is causing concern among those who are aware of his history.

A UCSF trainee Ada, whose name we changed to protect her identity, said she was shocked when she found Schneider’s name on Professor Julie Libarkin’s database cataloging cases of academic sexual misconduct and violations of relationship policies.

The account of the misconduct was especially disturbing, Ada said, because it appears the professor does not understand that he is in a position of power.

“The professor thinks it was consensual, but structurally it can’t be,” Ada said. “It seems like he thinks what he did was okay, and he’s adding to a culture here that communicates tolerance of sexual harassment.”

She talked with her Principal Investigator. She talked with her friend. She did what she could to process this information, but beyond that there was nothing else to do.

That was until she heard a first-year student mention working with Schneider.

“I couldn’t say anything to her, it would just [look like] me shit talking a professor,” Ada said. “It was a long, several month process of [figuring out] ‘how do I tell her?’ The NASEM briefing is what pushed it.”

Ada ended up informing the student indirectly, by having another UCSF trainee send an email with a link to the pertinent information.

“This is a discussion she should be having with an administrator,” said Ada.

Ada’s story was a shock to Grace.

“My main goal with reporting my advisor was to make sure that he didn’t see any more students,” Grace said.

Complaint Process Adds to Trauma

Danielle Fasani, a pharmacy student at UCSF, spoke of similar difficulties with the system when she was sexually harassed by a fellow student during her second year.

“It wasn’t the investigator making me feel this way, just the overall process making me feel like I had done something wrong somehow,” said Fasani of her experience with the Title IX process at UCSF. “It didn’t really occur to me [to think of myself as] a victim until the end of it.”

After talking through her options with Campus Advocacy Resources and Education (CARE) Advocate Denise Caramagno, she decided to make a formal complaint with UCSF’s Title IX Office.

According to University of California policy, Title IX investigations should be completed within 60 business days, however, extensions can be granted for complex cases.

“The respondent kept submitting more and more text messages, and every time that happened I had to respond to it,” Fasani said. “So it seemed almost impossible to put an end to this thing.”

Extensions in Fasani’s investigation meant the process took six months to complete.

“It was frustrating that things kept getting extended,” Fasani said. “A lot of the time they would not inform me beforehand that there was going to be an extension, so I would be waiting at the deadline [wondering] ‘why is there no decision?’”

One measure put in place during the investigation was a mutual no contact directive, which meant that neither party could contact the other directly or indirectly through another individual.

Fasani, however, found this directive difficult to enforce.

“In my case the respondent kept harassing me by cutting off my conversations with other people,” she said. “One night he stood outside my apartment and he was yelling, but there was no way for me to prove this.

“The issue is there is no distance component [to the no contact directive], so he could get as close as he wanted, and being in the same program, that was pretty frequent. I ended up getting a restraining order, but that’s something that I had to do on my own.”

Despite these difficulties, Fasani felt she had a good interaction with the Title IX investigator and felt supported by the faculty in the pharmacy program.

“I could just approach them one-on-one and explain what was going on and they really went out of their way to be helpful,” she said.

To Fasani the administration had a different standpoint.

“One thing that I was asking of the administration was to allow me to take my exams in a different room because I knew that there was already another room that students with disabilities take their exams in,” she said. “I don’t need extra time, I just need to be in a different room so I can focus. It really took a surprising [number] of hoops I had to jump through just to get that.”

Fasani found herself needing to jump through another hoop on the day when the Title IX investigator’s decision was to be made.

“It was 4 p.m. and [there was] still nothing, so I actually went down to the Title IX office myself and I weaseled my way in,” Fasani said. “I stood there and wouldn’t leave until they assured me that it would be done that night.”

After six months of interviewing witnesses and gathering information the Title IX report found that the respondent was in violation of UC policy.

The respondent, however, filed an appeal and the case was contracted to an outside law firm.

The appeal process led to the reversal of the Title IX investigation findings. The respondent was no longer considered in violation of UC policy and thus no punishment was handed down.

“For my case it would have been a mandatory two-year suspension at the least, so that really had a chilling effect on the witnesses,” Fasani said. “The key witness, who actually encouraged me to report the incident, turned around and not only said he didn’t see it, he actually said that he was there at the time and that I was lying, that it did not happen at all.”

Administration Responds

Nyoki Sacramento, who became the Director of the UCSF Office for the Prevention of Harassment and Discrimination in 2017, oversees Title IX investigations.

According to Sacramento, most witnesses are willing to talk with her office. She is, however, aware of instances where witnesses have backed out or are hesitant to talk, and stated this could be considered a strike against a respondent in an indirect way.

When asked about extensions impacting the timeliness of investigations, she highlighted the various complexities that can arise. For instance, sometimes the parties involved remember additional evidence near the end of an investigation. Other times cases may require interviews with 20 plus witnesses. Thus additional time can be necessary to conduct a thorough and fair investigation. When these extensions occur Sacramento said both the complainant and respondent are informed.

The role of Sacramento’s office is to make a policy finding, and it is then the responsibility of UCSF to determine disciplinary actions. This process can also add to the timeline.

Sacramento spoke to the integrity of her staff, stating that every employee in her office takes annual trauma-informed trainings and works to put necessary accommodations in place for complainants.

She also emphasized the hard work and dedication of her staff, and stated they and the UCSF community are on the same side when it comes to prevention of discrimination and harassment.

These issues are also important to the Dean of the Graduate Division Dr. Elizabeth Watkins.

She attended the NASEM briefing and afterward had dinner with the UCSF trainees who organized the event as well as the director of the NASEM study Dr. Frazier Benya. One topic the group discussed was the need for institutional cultural change.

“We should be able to change our practices and frankly have to change our practices,” Watkins said.

Watkins also spoke with senior faculty members following the briefing and they too brought up changing the professional culture.

“We were talking about how it’s really on us to start speaking up in the moment when appropriate or to take the offender off to the side or reach out to them within a day and say, ‘you know what you said is inappropriate and here’s why,’” Watkins said. “The senior faculty are the ones that have the power to make the change. Those who are in positions of power [can] use that in a constructive way to speak for those that are less empowered.”

Task Force on Gender Equality Holds Town Hall

Although unfamiliar with Grace’s case, Fasani said she also wants the administration to be more transparent about perpetrators of sexual harassment.

“Once [a case] is settled if the faculty, or whoever, has been found responsible then we feel it’s really important to let the entire student body know in some way just so that they’re aware,” Fasani said. “Also to encourage others to come forward by showing that the school is taking it seriously and responding to it.”

Now in her fourth-year, Fasani is using her personal experience with the Title IX process in her position on a Student Advisory Board that provides input on sexual violence prevention and response to the UC Office of the President (UCOP).

One change Fasani has pushed for is training for outside law firms that are contracted by the university.

“This really materially affected the outcome of my own case because I had asked repeatedly that the attorney hearing my appeal provide whatever certifications she had in this area and she refused to do so,” Fasani said.

“There’s no way to tell what sort of training [outside lawyers] have received in terms of sexual violence and sexual assault, so we’re working on creating this just-in-time training packet that will help them get a deeper understanding of the process and be more trauma informed.”

Fasani is also advocating for a post investigation survey. Both the complaint and respondent would be asked to fill out the survey to ensure that all parties are being treated fairly and that the investigation is carried out in a trauma informed manner.

UCOP, however, has been pushing back against this idea.

“Their fear, which I understand, is they don’t want their investigators to be pummeled with all this criticism,” Fasani said. “That’s valid, but the way we are envisioning this survey it would be a closed set of answers. Like, ‘on a scale of one to five how respected did you feel by the investigator?’ It’s the kind of thing where you expect people to fill out fives on all of them, and if they’re not, then there is obviously an issue.”

Fasani’s recommendations currently stem from her own experiences, but she hopes to receive feedback from other students.

“I would love to bring up what other people see as a problem because my experience is just one way and I do want to represent the whole student body,” she said.

Fasani, who is graduating, is currently looking for UCSF students to serve on the board for the coming academic year.

A group of UCSF trainees, separate to the UC student advisory board, have also been working to directly address these issues at UCSF.

The UCSF Task Force on Gender Equity and Inclusion formed as a result of a community reflection following the NASEM briefing in October.

The task force will present their NASEM-supported recommendations for changing the culture surrounding gender and sexual harassment to the UCSF administration. The town hall meeting, which will be held Friday March 15th at 1 p.m. in Genentech Hall Auditorium, will also include time to hear from attendees.

If the stories above resonated with you and you want to work to change the climate at UCSF, you are encouraged to attend and contribute to the conversation.

Originally published in Synapse – The UCSF student newspaper on March 12, 2019

Sharing Science

Mon, 01 Mar 2021 09:03:46 -0800

Scientific breakthroughs are occurring at a rate faster than ever before. In 2007, it was estimated that 1.5 million new scientific papers were published.

Despite this exponential growth in scientific discovery, many researchers struggle to access scientific knowledge because a large portion lies just out of reach, trapped behind a paywall.

It is essential for scientists to read primary literature to learn about their area of research and the questions that remain to be answered. However, these financial barriers, instated by publishing companies, prevent researchers from contributing fully to important scientific findings and slows scientific progress.

One solution comes in the form of the open science movement, which believes that scientific knowledge should not be restricted but distributed broadly, free of charge and free of most copyright and licensing restrictions.

The open science movement also promotes increased access to data and research methods as a means of improving reproducibility.

Indeed, the reproducibility crisis we face in the sciences has inspired the creation of several organizations whose purpose is to make protocol searching, sharing and publishing easier.

Two individuals at the forefront of this movement are Editor in Chief of Bio-protocol Marielle Cavrois and CEO and co-founder of protocols.io Lenny Teytelman. They will be at UCSF on June 14 as part of an event hosted by the UCSF Open Science Group.

The current closed science model in which business-minded publishers act as the gate-keepers of scientific knowledge is unsustainable.

Scientific journals were created so scientists could share information and work collectively to push the frontiers of science.

When journals were printed, scientists would submit their research, and the journals would handle the review process as well as typesetting, printing, and distribution of the researchers’ work.

Publishing scientific manuscripts was an expensive process, but it allowed for the broad dissemination of scientific knowledge.

However, journal prices are continuously increasing, and are doing so significantly faster than inflation rates and library budgets.

While publishers do have expenses, the current financial barriers to knowledge seem exorbitant.

Journals don’t fund the discoveries they publish, they don’t employ the researchers or reviewers and, in many cases, they don’t even employ the editors, who are often academic researchers volunteering their valuable time.

Funding for all of these things largely comes from government grants made possible by the tax-paying public.

Publishing companies take this taxpayer-funded research and monetize it by charging high prices to access the resulting research paper.

In addition to price barriers, journals also instate permission barriers.

Before the paper can be published the authors must exclusively assign the journal all rights to their manuscript. Researchers thus lose the control over their own research, including the right to provide copies to colleagues.

When pieces of scientific knowledge are locked behind financial barriers it hurts the researchers by limiting their audience and therefore the impact of their paper. It also harms readers by restricting access to the scientific knowledge on which their careers depend.

Access to scientific manuscripts is just one part of the problem with the current model of scientific communication. Another issue is access to the methods researchers are using to push the frontiers of scientific knowledge.

Troubleshooting and improving scientific methods and techniques are critical to scientific progress. Often these improvements are not considered publishable and thus are difficult to communicate to the broader scientific community.

Additionally, reproducibility is a crucial in science and is necessary to distinguish true findings from artifacts. Methods sections in papers, however, rarely cover the techniques in a manner detailed enough for the procedure to be repeated or offer no details at all, requiring readers to reach out to the authors themselves.

When labs have to individually create or discover improvements for protocols, essentially forcing them to reinvent the wheel, the efficiency of scientific research .

Open science encourages scientists to share protocols they have worked on and allows other researchers to make suggestions and changes that are beneficial for everyone. Open science allows scientists share their published research manuscripts freely without needing to seek permissions. Open science makes it easier for scientific papers to be translated in to different languages and disseminated in developing nations.

Ultimately open science makes scientific research easier to cite, apply, and build upon.

Lightly edited from original publication in Synapse – The UCSF student newspaper on May 23, 2018

Beginners Guide to Science Publishing

Mon, 01 Feb 2021 17:59:21 -0800

It’s been several weeks since you hit the “submit” button, and the manuscript-tracking page has remained permanently open in your web browser. At least once a day you refresh the page, but there is no new status update.

Scientific researchers know how to start the publication process and know the end goal, but for many the path from submission to publication is a mystery.

This path can be a winding one, sometimes your manuscript moves forward and sometimes it moves back.

The rules of the game were recently laid out for me at a Peer Review Workshop at the Public Library of Science (PLoS) and and editor meet-and-greet with PLoS Biology Senior Editor Lauren Richardson.

The first checkpoint for a submitted manuscript is a simple one, the submission is logged and checked to ensure it is complete and has been prepared according to the submission instructions.

Next, the manuscript is read by an editor. At this stage of the game, the editor is assessing if the research presented 1) falls within the scope of the journal, 2) adheres to the journals policies and guidelines, and 3) is original.

From here a paper will either be rejected or it will move on to the peer review process, where the game really begins.

Editors research potential reviewers, collecting clues from the manuscripts cover letter and references. They may also use PubMed to search for additional papers that will lead them to the names of prominent researchers in the field.

Once enough information has been gathered, invitations are sent out to potential participants.

If they are playing by the rules, potential reviewers may decline if they don’t have the time to provide a proper review, don’t feel they have a strong enough background in the research area, or can’t offer objective feedback due to competing interests.

In an attempt to improve their chance of success, editors usually contact more than the traditional three reviewers.

When someone accepts the invitation to review, the editor sets a deadline for review submission.

Reviewers, however, are busy people with labs to run, lectures to give, grants to write, and manuscripts of their own that need finishing. As such, this is often the place where manuscripts get stuck.

In many cases, an editor’s job is to help move the paper through the review process as efficiently as possible. Editors are on your team, but it’s important to remember they are also on at least 30 other teams.

When reviews don’t come back in a timely fashion editors keep the ball rolling and remind reviewers it’s their move.

With the reviews back in their court, the editors must now assess their content.

If Reviewer 1 and Reviewer 2 give contradictory comments or Reviewer 3 offers no expert opinion and only complains about the author’s horrendous syntax then the manuscript may require further review and can be sent back to start.

Once all reviews are in and assessed, an editorial decision is made.

If your paper is accepted, then congratulations you won the game! But if your paper is rejected, your battleship is sunk.

A third option is that your paper is accepted pending revisions.

If the edits are minor, you may just have to get past one gatekeeper, an editor. If major revisions are required, however, the manuscript will be sent back out to external reviewers and the waiting game will begin again.

When the reviews for the revised manuscript trickle in, they will once again be assessed by the editors after which further review or further revision may be needed.

Hopefully, the odds will be forever in your favor and your paper will be accepted, go to production, and finally be published.

Originally published in Synapse – The UCSF student newspaper on May 7, 2018

Advancing Cancer Care

Sun, 03 Jan 2021 16:52:35 -0800

Predicting how cancer patients will respond to treatments has been a major challenge in the field of oncology, but a new preclinical laboratory model may help to more accurately predict treatment outcomes. This new model not only has the potential to create more personalized and more effective treatment plans for patients, but could also improve and accelerate drug screening and development.

Advancements began when scientists discovered that tumor cells taken from a patient and grown under the right conditions can grow, divide, and unite to create a three-dimensional miniature tumor in a dish, a cancer organoid.

In a paper published in the most recent issue of Science, Georgios Vlachogiannis and his colleagues did just that, generating patient-derived organoids (PDOs) from 110 biopsies collected from 71 patients with metastatic gastrointestinal cancers.

These PDOs, which take only six to eight weeks to grow, mimicked the physiology of the patient biopsies from which they were derived, sharing 96 percent of the same protein markers and genetic mutations. Furthermore, these similarities persisted for several months after the organoids were grown.

After establishing the biological similarity between PDOs and their matching patient tumors, the authors tested whether PDOs could be used to predict treatment outcomes in patients.

To accomplish this, Vlachogiannis and colleagues generated PDOs from pre-treatment and post-treatment tumor biopsies from a patient given the anti-cancer drug paclitaxel. Both the pre-treatment and post-treatment organoids were then exposed to paclitaxel.

After this in-lab treatment, the pre-treatment PDO exhibited decreased viability and increased cell death, whereas the post-treatment PDO showed no observable response.

This observation in the lab mirrored what was seen in the clinic. Initially, the patient’s tumor had responded positively to treatment with paclitaxel, but over time the tumor acquired resistance to the drug, leading to disease progression.

Similar findings were observed in PDOs established from other patients as well.

Based on all PDOs analyzed, the authors found that drugs that failed in the PDO failed 100 percent of the time in patients, and drugs that worked in the PDO worked 88 percent of the time in patients.

Although more complex than a layer of cells in a dish, organoids still exist outside a complete biological system. So, to further test the validity of their model, the authors implanted these organoids into mice, this time using PDOs derived from a patient resistant to the drug regorafenib and a patient who is a long-term responder to this drug.

Following implantation, mice were treated with regorafenib and the authors found that their tumor-in-a-dish model held up.

Mice with PDO implants from the regorafenib-sensitive patient responded positively to the drug — marked by damaged microvasculature, decreased blood flow, and increased cell injury of the tissue — whereas mice with PDO implants from the regorafenib-resistant patient showed no improvement.

PDO implants generated from pre- and post-treatment tumor biopsies from a patient who initially responded to regorafenib, but whose disease subsequently progressed, also responded as expected.

Regorafenib-treated mice with the pre-treatment derived PDO showed a significant reduction in microvasculature and increased survival, whereas no significant change was observed in regorafenib-treated mice with the post-treatment PDO implant.

Bench-to-bedside research, in which laboratory discovery is translated into clinical practice, is often a slow going process. Several studies suggest that on average it takes 17 years for research to turn into beneficial patient care.

In this study, PDOs reduce this time from years down to months, making the predictive power of PDOs all the more remarkable.

Still in the early phases, it remains to be seen how thoroughly useful PDO testing will become for drug discovery and personalizing patient care. However for many, this feels like a leap in a promising direction when it comes to cancer treatment.

Originally published in Synapse – The UCSF student newspaper on February 26, 2018

Lab Work During Covid and My First Panic Attack

Fri, 18 Dec 2020 15:21:39 -0800

Do you think lab work is just carrying on as usual during COVID? I’m here to tell you it’s not. COVID adds obstacles that make research much more challenging. Here’s my experience:

Before COVID, I could go to my lab’s supply closet and find all the consumables I needed. Now, gathering supplies for an experiment is like a treasure hunt.

If it’s not in the stock room then I check shelves in the lab, then shared drawers and cabinets, I look on or in my lab mates' benches, and, finally, reach out to other labs.

Sometimes I find what I’m looking for and sometimes I don’t. Sometimes I can MacGyver something together and sometimes I have to cancel my experiment because it’s hard to proceed without pipette tips or microfuge tubes.

Other products are also, understandably, hard to get. I ordered a dendritic cell isolation kit in early December and the company told me the kits were unavailable indefinitely. Do I order a different kit and scrap previous experiments or do I hope indefinitely isn’t as nebulous as it sounds?

Currently, I’m doing experimental techniques I haven’t done in years and am learning some new techniques. With few lab mates around this has been both challenging and isolating.

There also exist smaller stressors like: wearing and breathing into a mask all day; forgetting your water bottle and panicking because the water fountain heads are covered; stopping what you’re doing for EH&S inspections to show you’re cleared for work even though you did that when you arrived on campus; visiting multiple floors in your building to find a restroom where the only stall available isn’t closed off; eating in the break room in 15 minute shifts; dealing with a lack of lab citizenship because no one is around; stressing out because other people on campus are not taking COVID as seriously as you; and being a run down 6th year who just wants to leave it all behind and graduate.

All of this makes long hours in lab longer; makes lengthy protocols that dictate when you can take a break to eat, hydrate, relieve yourself trickier to navigate; makes every task require more thought and prep; makes everything more strenuous.

And at the end of the day all you can do is go home, eat, sleep, wake up, and do it all again. There’s no escape, no social recharge.

For me this all took its toll one Friday this December when I had my first ever panic attack. I was eating dinner with my partner after a 10-hour day and then the room started spinning.

I felt like the world around me was collapsing and there was nothing I could do to stop it, nothing my partner could say to ground me. I felt dread and so overwhelmed that it seemed the only way for this to stop was to detach from my body. I thought I was dying and began repeating to my partner that I loved them.

The mental and physical toll eventually caused me to faint (a result of my vasovagal syncope) and when I came to I vomited.

The week before I was stressed but pushing forward. If you’d asked how I was I would have said “fine.” But “fine” quickly deteriorated into something awful and scary.

This is my story, it’s one of many. I am not alone in precariously teetering between fine and something awful and scary.

Labs may be open and research continues, but it should not and cannot carry on as usual. Check in on people. Show compassion.

Science Meets Journalism

Tue, 01 Dec 2020 19:08:57 -0800

Understanding the complex mechanisms that make us human is a driving force behind much scientific research, but getting at the root of what makes us human is not a purely scientific pursuit.

San Francisco Chronicle science and health writer Erin Allday, who spoke at UCSF on Jan. 26, uses journalism to not only explain science but also to better understand people.

Much like a scientist, Allday starts with questions she wants to answer, works meticulously to gather data, and then presents her results.

Although Allday does not have a background in science, she has worked for over a decade with scientific literature, clinicians and research scientists to learn the language of science.

Ultimately, her work shows that science does not exist in a vacuum. Health issues and scientific discoveries impact people. Part of Allday’s job is to give a voice to these people.

The most vivid example of this is in her 2016 special project entitled “The Last Men Standing,” a long-form narrative profile of survivors of the HIV/AIDS epidemic in San Francisco. The project was the result of interviews with 50 long term survivors of HIV/AIDS.

“And every single one of them had a really compelling story,” Allday said.

“For them having somebody who wanted to hear their stories, being able to share that, was obviously such a relief and [it] meant so much to them that there were people who wanted to listen.

“That was one of the first times that it really hit me the role that we play as journalists just speaking for people who don’t have a voice. To be able to sit in a room and hear somebody’s story, to bear witness to that and then be able to tell their story it’s incredible pressure, but it’s just such an honor and a privilege.”

While Allday works to bring serious, fact-based reporting to issues, not all reporters research as thoroughly as they should or have the training or background to put things into context. And her science-based reporting is a struggle against the myths, conjectures and falsehoods that invariably surround topics such as vaccinations.

“People tend to go hyperbolic on both ends,” Allday said. “Even the people that are very pro-vaccine will make statements or write stories that aren’t backed up by science, and that doesn’t serve anybody.”

For example, in 2008, science-backed reporting shed light on the role unvaccinated communities played in several measle outbreaks in the United States. Subsequently when an outbreak of whooping cough happened some reporters incorrectly jumped to the conclusion that this too was due to unvaccinated individuals.

In actuality, the outbreak was due to a poor whooping cough vaccine and the loss of vaccine-induced immunity.

“It can be this constant battle [to confront the hype] and you have to have confidence in the knowledge that you have to be able to buck up against it,” Allday said. “The role that I can play and presumably the role that [scientists] can play is to get people real news.”

The mistrust and distrust of science, medicine, and the healthcare system, however, can make it difficult to get real news and real science to the people. What makes this issue complex, is that this lack of trust stems from real experiences and emotion-driven beliefs.

People may start out trusting their doctors, but what happens when they try multiple treatments that either don’t work or cause intolerable side effects? What if they follow all the medical advice only to run out of options? What if the doctor says there’s nothing else they can do?

Desperation sets in.

Allday describes one such situation in a special project she is currently working on. A sick child has run out of medical options and a mother is willing to try anything to cure him, including a highly experimental stem cell therapy.

One doctor tells the mother the experimental therapy will do nothing for her child, while another tells her it may save the child’s life.

“She doesn’t know who to trust,” Allday said. “She’s had reason to mistrust medicine and would do anything for her child.”

The doctor recommending the experimental therapy lost his medical license for giving patients that very therapy. While this may set off alarm bells for some, this mother views it differently, it’s reassuring. To her, this doctor is so dedicated to his cause he was willing to sacrifice his medical license to pursue it.

“The best that I can do is write about the facts as I know it, and put it out there that these are experimental treatments and there’s really no evidence that they will help her child at all,” said Allday. “Despite this, people are going to do it anyway.”

In biomedical sciences, we ask questions about mechanisms that contribute to how a body functions, we interrogate genes and cells, we attempt to understand how different perturbations over the course of a lifetime impact a person. We gather data and determine the story it’s telling.

When it comes down to it, science and journalism are not so different: both are about asking questions, both are about telling stories, and both are attempting to get at the root of humanity.

Originally published in Synapse – The UCSF student newspaper on February 9, 2018

The Psychology of Betrayal

Sun, 01 Nov 2020 12:40:22 -0800

Stories of sexual assault are rampant in the news today. From Hollywood producers and radio hosts to politicians and news reporters, it is clear that no field is immune to violations of trust.

The chain of events may seem clear for those who have not experienced emotional, physical, or sexual abuse. A betrayal occurs, a survivor reports that betrayal, and the perpetrator is punished. However, these betrayals and their underlying psychology are far more complex.

On Nov. 6, Dr. Jennifer Freyd, a professor of psychology at the University of Oregon, visited UCSF to present her extensive research aimed at understanding how trauma impacts mental and physical health, behavior, and society.

According to Freyd, the ability to evaluate another person’s level of trustworthiness or tendency for betrayal is a necessary survival mechanism.

When empowered, an individual can more easily recognize these traits and respond by either confronting or withdrawing from the perpetrator.

This situation is made far more complicated when a dependent relationship exists: for example, if a child experiences betrayal by a caregiver.

In addition to the abuse there is a second level of trauma for the survivor as it is a person they depend on for survival who has violated their trust and well-being. Freyd refers to this second level of trauma as “betrayal trauma.”

Because the child depends on this caregiver, confronting or withdrawing from this person threatens this necessary relationship.

In this instance the dependent person may exhibit “betrayal blindness,” which Freyd defines as an unawareness or forgetting of betrayal to ensure that the dependent relationship is preserved.

The impacts of trauma are intricate, creating both moral and psychological conflicts, and are unevenly distributed across the population.

In a 2006 study comparing 433 women and 304 men, Freyd found that women reported higher frequencies of traumatic events (specifically sexual abuse and assaults) perpetrated by someone close to them.

In an independent cohort of 833 individuals, Freyd found that lower socioeconomic status and ethnicity predicted greater exposure to trauma and associated mental health symptoms, such as depression and anxiety.

Moreover, research by Jennifer Berdahl and Celia Moore investigating patterns of harassment at five different organizations found that minority men are harassed at higher rates than white men. Furthermore, women are harassed at higher rates than men and minority women are harassed at higher rates than all other investigated groups.

Thus individuals who are systemically oppressed, and especially those who exist at the intersection of multiple systems of oppression, are at the greatest risk of experiencing betrayal trauma.

Like individuals, institutions, and those who represent them, can also provoke betrayal trauma.

For example, a graduate student is dependent on the Principal Investigator of a lab for mentorship, letters of recommendation, and resources. If the student experiences abuse by their PI, confronting or withdrawing from them may seem impossible. Doing so could hurt the graduate student’s career, so instead they may turn a blind eye to protect themselves and their future.

While this scenario may sound unlikely or shocking to some, Freyd’s research tells a different story.

From a campus-wide sexual violence survey conducted at the University of Oregon, Freyd and colleagues found that while female undergraduates experience more overall sexual harassment and violence, female graduate students experience more sexual or gender-based harassment perpetrated by university faculty or staff members.

Of the approximately 124 female graduate students that reported this type of harassment, only seven informed the university.

Reporting harassment is important for promoting policy changes and awareness, yet non-disclosure is surprisingly common.

While students may disclose a trauma or harassment to family members and close friends, they often don’t feel safe disclosing to the institution where the harassment occurred.

Non-disclosure seems like a more endurable option compared to the risk of reporting and being met with a negative response.

For example, a survivor’s experience may be dismissed (“I doubt that happened”), there may be denial of the perpetrator’s behavior (“Are you sure they meant it that way? It sounds harmless to me”), the survivor may be attacked by the person they are disclosing to (“Based on what you were wearing it seems like you were asking for it”), or the role of victim and offender may be reversed (“You’re horrible for accusing an upstanding member of our society!”).

Freyd refers to these responses collectively as DARVO (which stands for deny, attack, and reverse victim and offender).

DARVO is an effective strategy for perpetrators because it can increase doubt about a survivor’s credibility and is associated with survivor self-blame.

When DARVO occurs at the institutional level, this failure to respond supportively to the survivor can lead to new betrayal and further trauma for the survivor.

Freyd further explained that mandatory reporting policies in place at many institutions are harmful to survivors.

According to Freyd, the first thing you should do to support a survivor of trauma is to help them regain a sense of control. Taking information given to you by a survivor and passing it on to other sources diminishes the survivor’s control, which further promotes non-disclosure.

Instead of required reporting, Freyd asserts that “required supporting” by the institution and survivor-directed reporting better serves survivors.

Individuals and institutions also must become better listeners, and with the proper training Freyd believes this is possible.

Indeed in a 2011 study she found that studying a list of compassionate listening tips for just 10 minutes could enhance supportive listening and help people become better responders to individuals disclosing trauma.

Despite the troubling story much of Freyd’s research told, her talk ended on an optimistic note with 10 ways institutions can better support survivors.

These “10 Principles of institutional Courage” are:

Comply with laws and go beyond mere compliance
Respond well to victim disclosures
Bear witness, be accountable, apologized
Cherish the whistle blower
Engage in self-study
Conduct anonymous surveys
Make sure policy is trauma-informed
Be transparent about data and policy
Research and educate
Commit resources to 1-9

For more information about Freyd and her research visit her website Freyd Dynamics Lab.

Lightly edited from original publication in Synapse – The UCSF student newspaper on December 5, 2017

The Future of Genetics

Thu, 01 Oct 2020 16:24:10 -0800

A couple sits close, intently studying a dossier. On the dossier is a list starting with Embryo #1.

According to the description, Embryo #1 is female, has a high risk of Type II Diabetes, will have blue eyes and blond hair, and has a 20% chance of being in the 90th percentile for math ability.

Alternatively, Embryo #100 is male, will have blue eyes and dark hair, has a 60% chance of being in the top 10% for musical ability, and is at a high risk for depression.

Between Embryo #1 and #100 lie similarly detailed descriptions.

While this may sound like science fiction, according to Hank Greely, Dean F. and Kate Edelman Johnson Professor of Law at Stanford University, this scenario is the soon-to-be future of human reproduction.

“I predict in [my] book [“The End of Sex and the Future of Human Reproduction”] that in 20 to 40 years the majority of babies born to people with good health coverage anywhere in the world will not be conceived in a bed or in the back of a car or under a ‘keep off grass’ sign, but will be conceived in a lab so that parents can then do whole genome sequencing and pick the embryo that they want,” Greely said during his Gladstone GO Graduate Student Organization sponsored bioethics seminar on April 14.

Greely went on to share several stories about advances in human reproduction that will make this future he envisions possible, starting with preimplantation genetic diagnosis (PGD).

“A three day embryo is like eight grapes inside a water balloon that’s filled with jello,” Greely explained. “The grapes really aren’t attached to each other, so what you [do is] make a little hole in the water balloon–the membrane holding the embryo together — and suck out one of those cells. And the other seven cells [do] fine, they [do] not fail at any higher rate than embryos regularly fail, and you take that cell and do genetic testing on it.”

According to Greely, PGD has been clinically available for 25 years, but recently scientists have been using five- or six-day-old embryos from which they can take five, 10, or even 15 cells, thus allowing for more confidence in the genetic testing results.

This procedure, however, is currently limited by the expense of sequencing, the short time frame between taking cells from the embryo for genetic testing and implanting the embryo, and our understanding of genetics.

As sequencing becomes cheaper and allows our knowledge of genetics to grow, Greely predicts that PGD will advance to what he calls enhanced PGD, in which cells taken from embryos will have their entire genome sequenced.

Another huge limitation to PGD is that before you can run genetic tests you first must harvest eggs from the female.

“Normally women ripen one or at most two eggs a month,” Greely said. “If you’re going to go in [for] this invasive procedure you want as many ripe eggs as possible. Very expensive hormones [are used] in order to convince more eggs to ripen than normal. This causes cramping, bloating, mood swings, unpleasantness as well as the fact that [the woman] has to give herself a shot every day for 30 days in a row which people, understandingly, find a little bit disconcerting.”

Furthermore, although a small percentage, some women who go through egg harvesting end up hospitalized or may even die.

“Nobody goes through IVF [in vitro fertilization] just for the heck of it,” Greely said. “They do it because they have to.”

Importantly, Greely also stresses that this unpleasantness and risk all falls on the female.

So what can we do to move away from current methods of egg retrieval? Greely believes the answer is induced pluripotent stem cells (iPSCs).

iPSCs are generated by reprogramming adult cells in a way which induces a loss of their defined cellular identity. In this state the cell now has the the potential to differentiate into any cell type, whether it be an epithelial cell, a cardiomyocyte, or an oocyte.

Greely thus envisions a world in which an individual would give a skin biopsy that would be reprogrammed to become iPSCs which would then be used to make oocyte precursors and finally an oocyte that could be fertilized.

This method, known as in vitro gametogenesis (IVG), could also be used on skin biopsies from males to generate oocytes or skin biopsies from females to generate sperm, thus making it possible for same sex couples to have children who are biologically related to both parents.

Additionally, instead of harvesting only a few eggs, IVG could potentially generate hundreds of eggs non-invasively.

Taking it a step further, whole genome sequencing (WGS) could be performed on all fertilized eggs to generate genetic profiles of each embryo. Parents could know whether the embryo is at high risk for early onset disease or other diseases and medical conditions. They could also learn about the cosmetic make up, behaviors, and sex, and use all this information to help them choose the embryo they want implanted.

One important caveat to this scenario, however, is that rarely do traits adhere to simple Mendelian genetics with one gene coding for one trait.

“It’s all going to be really complicated,” Greely stated. “Probably involving hundreds or thousands of different genetic loci and with a big dollop of environment and chance.”

Another issue is how parents will parse through all this information.

“Even if you’re only looking at 20 different things of significance how do you weigh 50% higher risk of Type II Diabetes versus 50% lower risk of schizophrenia versus 50% chance of being in the top 10% for music ability versus [being] very, very tall?” Greely asks. “It’s going to be a real hard decision.”

Thus, an important aspect of this future Greely envisions will be educating parents to help them make informed decisions that they will ultimately feel comfortable with.

Despite this being a bioethics seminar, Greely only discussed a few ethical quandaries.

For instance, if you can take anyone’s cells and make them into eggs and sperm, then anyone can be a genetic parent. A 50-year-old woman could become a mother, but an eight-month old baby or a woman who died and whose cells were frozen could both also become genetic parents.

While Greely’s point seemed to be that this would change family structures, I think the real issue at the crux of this is legal regulation, which Greely didn’t touch too much on in his talk.

One of the most challenging moral dilemmas associated with this future of human reproduction was, surprisingly, not brought up until the question was posed by an audience member.

As technology like PGD becomes more available and more powerful, will we lose populations of people?

For example, if you knew that an embryo would give rise to a child who was deaf, autistic, or achondroplastic would you chose against that embryo? And if you and others choose against that embryo how will that impact our society?

For one, it will decrease the number of individuals who make up that community thus decreasing research, social, and political support for this community.

Additionally, if parents tend to select against these traits it may send the message that these traits are “bad” and that individuals who do have these traits are leading lives that aren’t worth living.

But how does one determine what is and isn’t a life worth living?

While society as a whole might label certain traits like those listed above as disabilities, members of these communities don’t all hold that view, instead seeing it as a different way of being. For example, autism is sometimes thought of as neurodiversity.

How will beliefs like this affect a parent’s choice? Will an individual who is deaf select to have a deaf child?

This leads to a whole new set of issues Greely also did not cover.

In the future, will parents be discriminated against for choosing certain traits for their children or for choosing to procreate the old fashion way instead of selecting their child based on traits that society sees as favorable? What new power dynamics will these technologies create?

Greely also failed to talk about issues surrounding availability of this technology.

While he hypothesizes that health care programs will fully pay for IVG and WGS–as in the long run it will ultimately reduce healthcare spending–this coverage isn’t going to happen instantly. In the beginning, these processes will still be expensive and likely only available to those with enough money.

If wealthy individuals are screening their embryos to ensure the healthiest embryo is implanted, what will this mean for populations who can’t afford this service? It seems very possible that the burden of health care expenses could fall entirely on them.

Additionally, this could impact the amount of money funneled into biomedical research whether it be because individuals feel they no longer need to donate to a cause that doesn’t affect them or because research in that field no longer seems like a priority due to a shrinking community of affected individuals.

All of this, however, is dependent on how much information we will actually be able to glean from an embryos genetics alone.

Greely believes that “cheap sequencing changes everything” and while it will definitely lead to advancements, it may not be as comprehensive as Greely predicts.

Despite what I believe to be Greely’s slightly over-optimistic vision, his last point rings true.

“If we understand the issues better in advance we are less likely to screw up.”

Originally published in Synapse – The UCSF student newspaper on April 24, 2017

The Maternal Wall Bias

Tue, 01 Sep 2020 13:25:31 -0800

Federal regulations are establishing stronger rights for career women in a variety of industries choosing to have babies, but these protections aren’t taking hold in the world of academia.

PhD-holding women who have children are 35% less likely to enter a tenure track position, and 27% less likely to become tenured – even if they are on a tenure track – than their male counterparts.

Statistics like these suggest that being a woman, especially a woman who wants to have a family, is seen as an undesirable quality for those who want to pursue a permanent post in academia.

“The term that we use for this is ‘maternal wall bias,’ and that’s a negative competence assumption on someone because they are a mother,” explained Jessica Lee a Staff Attorney at the UC Hastings Center for WorkLife Law who gave a seminar on March 6th entitled “Title IX and Babies.”

“The ‘mommy penalty’ actually hurts all women whether or not you have a child or intend to,” said Lee. “Some of your professors, some people in your department may actually think, ‘She’s a liability. She’s a women. We know they leave.’ And that is why it is important for not only mothers, but all women to challenge maternal wall bias.”

Lee went on to paint a grim picture of the role of women in science, technology, engineering and mathematics (STEM).

Female graduate students with children are two times less likely to earn a degree in STEM.

Additionally, twice as many women than men are likely to change their career goal away from being a research professor when they have babies as postdoctoral fellows (postdocs), and the data suggests this isn’t due to a change in priorities.

So, what is leading to the loss of parents, specifically women, in STEM?

To answer this question colleagues of Lee’s Mary Ann Mason, a professor at UC Berkeley, and Joan Williams, from the Center for WorkLife Law, conducted a study in which they surveyed 63 institutions about their leave policies and how they support postdoc parents as well as 741 postdocs about their experience as a postdoc at their institution.

What Mason and Williams found was troubling.

The institutional surveys showed that 50% to 60% of institutions do not provide paid maternity leave for their postdocs. A small number of institutions also did not provide other types of paid leave such as vacation days, sick days, or holidays that new mothers could use to supplement time off for maternity leave.

Institutions were even less likely to grant paternity leave, with 60% to 70% of institutions not providing this benefit for postdoc fathers.

Additionally, some institutions don’t even provide unpaid leave, or as Lee refers to it “job protected leave.”

This means that if an individual opts to take leave to care for a new child, not only will they not be paid, they also won’t be provided job security, meaning they may not be able to come back to work in the same position or at all.

The outcome of the postdoc surveys were just as troubling.

Many surveyed postdocs expressed feeling guilty for taking even the minimal amount of leave a woman requires to recover from giving birth.

One postdoc said she “felt guilty/like I was putting my advisor out” because she requested eight weeks of leave after a difficult childbirth that resulted in partial paralysis.

“This is the sort of pressure that postdocs and grad students end up putting on themselves when there isn’t a policy to tell them what sort of leave to expect or what sort of accommodations can be made in exceptional circumstances,” Lee said. “[The] burden falls on the postdoc to find some way around this discrimination rather than putting the onus on the institution to ensure that this isn’t happening to begin with.”

Another postdoc wrote that her Principal Investigator (PI) came to visit her in the hospital and said, “So what about 2 to 3 weeks and you will be back?” She ended up having to provide a certified note from her doctor stating she needed four weeks to recover before she could go back to work.

According to Lee, a negative response from a PI regarding a request for accommodation or leave can not only lead to tension between a postdoc and a PI, but is also a large contributing factor driving parents, and especially women, out of the STEM pipeline.

Mason and William’s study indicates that institutions must offer more support for parents.

Specifically, it is crucial for institutions to create clear policies surrounding not only maternity leave, but also leave for non-birth parents.

Without policies affording leave to non-birth parents, parental responsibilities fall entirely on women, further fueling the situation in which women are viewed as a leave liability.

In addition to leave policies, Lee suggests institutions also provide support for new parents in the form of flexible schedules or the ability to work from home to alleviate child care insecurity.

While policy changes on the institutional level are essential, it is also crucial that individuals know their rights.

Title IX is a federal law put in place to protect individuals from discrimination on the basis of sex in any educational program or activity.

While it is most commonly associated with sexual harassment, Title IX also requires “reasonable accommodations” for students with disabilities, and this extends to pregnancy.

Under Title IX, students are provided maternity leave for “as long as medically necessary” as determined by a physician. Furthermore, students must be “reinstated to the status which she held” before taking leave.

In the UC system, graduate students are actually entitled to paid leave.

According to the Graduate Divisions benefits page, UCSF graduate students are provided 10 weeks of paid leave in addition to up to two weeks of unpaid leave, pending program approval.

Lee also discussed section 66281.7 of California’s Education Code which entitles graduate students taking maternity leave to a 12-month extension for exams as well as for normative time to getting their degree. Additionally, this section also includes a month extension for non-birth parents.

Parental leave for postdocs, however, is a little less clear.

Certain postdocs that fall under Title IX are entitled to “leave for a reasonable period of time,” although what this period of time is isn’t specified. Additionally, postdocs need not be paid under Title IX, but must be reinstated to the same or equivalent position.

According to the current contract between UC and postdocs posted on the International Union, United Automobile, Aerospace and Agricultural Implement Workers of America (UAW)’s Local 5810 website, postdocs taking Pregnancy Disability Leave are eligible to receive 70% of their weekly earnings if they opt to receive Short-Term Disability coverage during this time. In addition, both birth-parents and non-birth-parents are entitled to four weeks of paid parental leave.

Under the California Family Rights Act, postdocs may also take an additional 12 weeks for new-child bonding.

Lee stressed that when taking leave you do not need to ask permission just provide notification as these are your rights and you are entitled to them.

For more information about Mason, Williams, and Lee’s work and about your rights visit The Pregnant Scholar.

Originally published in Synapse – The UCSF student newspaper on March 27, 2017

The Resurgence of IUDs

Sat, 01 Aug 2020 14:31:42 -0800

“Every time I place an intrauterine device I feel like Margaret Sanger!” Lisa DiGiorgio-Haag exclaimed.

DiGiorgio-Haag has been a nurse practitioner at UCSF Student Health for 24 years and specializes in women’s health.

She completed her Bachelor of Science in Nursing at the University of Pennsylvania, and went on to earn a Master of Science in Nursing and certification eligibility as a Family Nurse Practitioner from UCSF.

It was during her graduate studies that DiGiorgio-Haag decided to focus on women’s health, despite being discouraged to do so.

“I had one professor who really challenged me and insisted that I should not be a women’s health nurse practitioner” DiGiorgio-Haag said. “I really had to take a look at [this and ask] is this really something I want to do if this expert thinks that I shouldn’t be doing it? And [that challenge] motivated me even more to achieve my goals.”

Although she didn’t have strong female role models during her graduate studies, DiGiorgio-Haag says she “grew up really marinating in the power of women,” and feels she was meant to do work in the field of women’s health.

After learning about intrauterine devices (IUD) at a contraceptive technology conference, DiGiorgio-Haag spearheaded an IUD program at UCSF which allows students on the University of California Student Health Insurance Plan (UC SHIP) to get IUD’s inserted at no cost.

IUD’s, which look like a small plastic T, are the most effective form of birth control currently available apart from sterilization. They are long acting, reversible, and the best part is once they’ve been placed you don’t really need to think about them.

“I was so thrilled when I heard about IUDs because for so long in women’s health there were no new options,” DiGiorgio-Haag said. “It was just years and years of this drought of contraception and then the IUD came out and it was just this mindblowing thing for people.”

Education First

One way in which UCSF’s IUD program is unique is that it requires two appointments, one for counseling and one for insertion.

During the counseling session your provider will go over all the options with you, and inform you of the pros/cons of each option.

“What a lot of providers I feel like are doing is they’re not really having that conversation with people,” DiGiorgio-Haag said. “My philosophy is let me educate you. Whatever you decide is fine, but I want you to have the information.”

UCSF Student health offers students a choice between three IUDs: the Skyla, the Mirena, and the ParaGard.

The Skyla and Mirena are made of plastic and contain levonorgestrel, a progestin hormone that induces thickening of the cervical mucus and thinning of the uterine lining to inhibit sperm from reaching and fertilizing an egg.

Although Mirena promotional materials recommend it for women who have had a pregnancy to term, many providers, including DiGiorgio-Haag, have placed Mirenas in women who have never been pregnant.

The reason DiGiorgio-Haag recommends the Mirena is because it lasts longer (5 years versus 3 years for the Skyla), and after one year 70% of patients have amenorrhea, meaning no menstrual period at all.

With the Skyla only 25% of patients have amenorrhea, while the other 75% are likely to have irregular, unpredictable bleeding.

“I think the only reason to choose a Skyla over a Mirena is if the uterus doesn’t measure large enough for the Mirena, which happens rarely,” DiGiorgio-Haag said.

She has been placing IUDs for over 5 years and, to date, has only placed one Skyla.

For individuals who don’t want any hormones, the ParaGard is a hormone free IUD option. It is made from copper, which works to inhibit sperm function, and lasts up to 10 years. The downside to the ParaGard, however, is that it tends to make periods heavier and more crampy.

After laying out all the options and explaining the insertion procedure, your provider will answer any questions you have and schedule an appointment for the insertion. It is important to note that the IUD insertion appointments last one hour and cannot be booked online.

Dispelling myths

You may have heard women from previous generations say IUDs are dangerous and can cause serious infections and infertility. While one version of the IUD released in the 70s, the Dalkon Shield, did cause severe infections in women, today’s iteration of the IUD is safer.

Infections caused by the Dalkon Shield arose due to the use of multifilament strings, but now all IUDs use monofilament strings which have not been associated with a risk of infection.

Monofilament strings are thought to offer protection from infections because the total surface area of the string is exposed to cervical mucus, which blocks bacteria from entering the uterus.

Another common misconception relates to the IUD insertion process.

“If you look on the Internet IUD insertion sounds like the most excruciating thing,” DiGiorgio-Haag said. “The thing I hear a lot is ‘it wasn’t nearly as bad as I thought it was going to be,’ and I think that’s because of the Internet. I feel like we’re always working against that perception that it’s gonna be this horrible, excruciating experience.”

Speaking from personal experience, IUD insertion was definitely not as painful as online accounts made it seem.

Providers at UCSF also do several things to minimize discomfort, such as recommending students schedule their insertion appointment during their menstrual cycle, when the cervix is naturally open, and offering patients a cervical block–something not all providers do.

“I think [the cervical block] makes a big difference,” DiGiorgio-Haag said. “It’s very analogous to having Novocain when you get a filling. You can get a filling without Novocain, but it’s a lot tougher.”

Additionally, providers at UCSF encourage patients to eat and take ibuprofen before their insertion appointment. They will also ask you about your medical history to determine if you are prone to such things as vasovagal syncope (fainting when your body overreacts to stress).

Once the procedure is finished patients can rest in the exam room and enjoy apple juice and hot or cold packs for tender areas.

Individuals who have had a bad reaction to oral contraceptives may think they will have similar problems with the hormonal IUD, but there are some big differences between these two forms of contraception.

“The oral contraceptive is two hormones, we completely eliminate one [estrogen] with the [hormonal] IUD,” DiGiorgio-Haag explains. “And the [hormone in this IUD] is 1/20th the dose of that in the pill and it acts pretty much locally.”

With Trump now officially in the oval office, seeking out long acting birth control should not be delayed.

“We’ve had a huge run on IUDs since the election. Literally since the election our demand has doubled,” DiGiorgio-Haag said. “We’re really trying to meet the demand and so far we’ve been able to do it.”

Students can book an appointment for IUD counseling online through myhealthrecord.ucsf.edu. If you don’t have UC SHIP you can call your local Planned Parenthood health center to find out about getting an IUD placed by providers there.

“Know your rights and be aware of the women who came before you who fought for those rights,” DiGiorgio-Haag advised. “Even though our students have grown up during a time where they have options it’s important to remember that not very long ago women didn’t have many options, and that we could return to that.”

Originally published in Synapse – The UCSF student newspaper on January 20, 2017

Walking the Work-Life Tightrope

Fri, 03 Jul 2020 13:55:17 -0800

Many, if not all, of us are constantly trying to attain work-life balance, but in this day and age we all have so many things to juggle.

In addition to work we have relationships to tend to, side projects to amuse and challenge us, and the extra hours of sleep we wish we were getting.

We think a work-life balance will fix all of our problems, but try as we may, it often seems impossible to attain the balance we desire.

On Tuesday September 27, Dr. Dawna Ballard gave a talk entitled “Talk About Time: Why we Fail at Work-Life Balance,” which offered some insight into how we can take steps to achieve this elusive state. Ballard, an Associate Professor in the Moody College of Communications at the University of Texas, Austin, studies time as it is bound to human communication, otherwise known as chronemics.

“Time [is] part of every culture’s silent language… There [are] rules that people understood, but couldn’t articulate, and it was part of these very deep, hidden assumptions” Ballard told audiences, citing the work of anthropologist Edward Hall.

“The challenge with having hidden assumptions is [that] we confuse what is a hidden assumption [with] truth because we haven’t interrogated it, we haven’t had a conversation about it.”

Achieving work-life balance may thus be difficult because we assume certain things about time, and treat time in a particular way.

“We go through a lot to make time all look the same, but from a chronemic standpoint let’s think about that. If you receive a call from you parent at 2 p.m. versus 2 a.m. [what] is the meaning of that call when you see their name on your caller ID on your phone? That’s not the same, right?” Ballard explained.

“All times literally are not the same in terms of their meaning for us, they might be on a clock, there both times of the day, but in terms of what happens it’s a really big difference.”

While a consistent, objective view of time may have been a good model for management in factories during the industrial revolution, Ballard believes the way we work has changed greatly.

Today our work unfolds more through the events and people around us, again supporting the notion that all times are not the same. Less and less people are on assembly lines. My weeks are defined by the meetings, classes, seminars, and lab work I do as well as the people who are present or absent from these events.

After laying this foundation, Ballard went on to present a study in which she interviewed low wage earners, middle wage earners, and high wage earners of differing genders and ages.

She reported that many low wage workers hadn’t even heard the term work-life balance before, and those who had said it was something “just for managers.”

Middle and high wage earners, on the other hand, said they went through a lot to try to achieve work-life balance, but never felt as though they had fully achieved it.

“The kinds of messages that [the term work-life balance] sends is kind of problematic.

“We know that it’s really from an industrial model and that it’s not this emancipatory discourse that’s helping every one because if it was it would be talked about for everyone.”

Ballard went on to say, “This whole idea I think about balance that’s also challenging is that since no one knew what in the world it was no one knew exactly how to achieve it.”

Instead of thinking about balance, Ballard suggests we think in terms of alignment. To her “balance” represents something that is mechanistic and binary, but the concept of alignment is more dynamic. Instead of balancing work and life on scales and trying to make them completely equal, she suggests we think about being on a tightrope.

As you move across the rope sometimes you are balanced and sometimes you are unsteady, but you’re always moving forward. And what’s important to keeping your balance is listening to your body and aligning it with the rope.

This scenario helps convey the concept that you’re not always in alignment and that’s okay, but in the long term (walking across the whole tightrope) you will need to achieve alignment again otherwise you will fall.

With this image firmly planted in our minds, Ballard came back to her point that all times are not the same, stressing that there are different practices and tools you will need to use to help support or realign you at different times.

Additionally, these tools will be different for different people. When the audience was asked what practices they use to support themselves during a time of commotion, for instance, the answers ranged from just breathing, to drinking coffee, to listening to five minutes of music.

Several parts of Ballard’s talk really resonated with me. It was reassuring to hear that it truly is okay not to be balanced or aligned all the time.

The belief that you can juggle everything going on in your life perfectly is unrealistic, and yet it is a fantasy we are often fed. I now feel more comfortable with the thought that I will wobble on the tightrope sometimes because if I listen to my body, eventually I will become realigned.

In addition to not always being aligned it’s also okay to not always be in control. You can make a to-do list and communicate about what you need to complete these tasks, but ultimately you can’t control the people and events around you.

For me this may mean being kinder to myself when an experiment fails and recognizing that, although not on my to-do list, troubleshooting is part of the process.

Ballard also offered some useful tools for helping you stay aligned or realign. The one that was most useful for me was considering events on different time scales. For example, I’d like to be running three times a week, but when I have a heavy workload I have to re-prioritize.

If I focus on the fact that I am not running as often as I would like, I will just end up feeling frustrated. But if instead I change the time scale to a month and set a number of runs to do in that time — going more often when my workload is lighter and not feeling guilty about not going when my workload is heavy — then I’ve created a more attainable goal.

While Ballard’s talk offered new perspectives and tools I can use personally for in-the-moment relief, the talk lacked solutions for changing the broader institutional culture surrounding work-life balance.

While UCSF appears to support balance amongst students, staff, and faculty through sponsoring talks like this one and emphasizing the existence of work-life balance resources, there are definitely some mixed messages.

“There is no 9 to 5 when it comes to advancing health” proclaims an ad adorning the side of several of UCSF’s shuttles. The picture accompanying the text is a through-the-window shot of a woman working alone in lab at night, giving off the impression that UCSF is surreptitiously spying on her.

While to others this ad may convey UCSF’s great dedication to advancing health, to me it suggests that I should be working “into the wee hours” (as the ad also states) to advance health, although potentially at the detriment of my own.

“When you say your work has work-life friendly policies everyone says, ‘Oh, great!’” said Ballard.

“But if they [the institutions] were really interested they would talk about their time polices, the details. Because work-life policies are never used. Most people don’t take advantage of their vacation time or their leave time or their sick time.

“[So the policies] are there as a message to say we care because we know what this means and everyone loves that term, but if you really were to say let’s just look at the time, how many hours does the average person work here. That would be a better measure. That and do people take vacation time.”

Lightly edited from original publication in Synapse – The UCSF student newspaper on October 4, 2016

Endo-Lysosomes and Antigen Presentation

Fri, 12 Jun 2020 14:19:48 -0800

For phagocytic immune cells, endosomes and lysosomes are critical organelles. Endosomes transport samples of extracellular material into the cell and eventually fuse with lysosomes to create the endo-lysosomal compartment. In this compartment antigens are processed and loaded onto Major Histocompatibility Complex II (MHC-II) molecules for subsequent antigen presentation to T cells. Although classically recognized as waste-management organelles, in pathogen-stimulated dendritic cells (DC) these degradative abilities are dampened to preserve peptides. In addition to functional changes, endo-lysosomes also transform from globular organelles into far-reaching tubular networks. While endo-lysosomes appear to play a key role in antigen presentation, the mechanisms driving these structural and functional changes remain poorly understood.

A recent publication by Hipolito et al. sought to elucidate the molecular underpinnings of this dynamic endo-lysosomal response. In this study, primary murine phagocytes stimulated with the bacterial protein lipopolysaccharide (LPS) showed rapid remodeling of the endo-lysosome, increasing the volume and holding capacity of this compartment after just two hours. This expansion was associated with increased levels of six lysosome-associated proteins, but not their corresponding messenger RNAs (mRNA).

The authors thus examined post-transcriptional mechanisms that may contribute to endo-lysosome expansion, focusing on mammalian target of rapamycin complex 1 (mTORC1). In addition to stimulating mRNA translation, previous literature has shown that mTORC1 is activated in LPS-stimulated macrophages and is necessary for endo-lysosomal tubulation. Hipolito and colleagues found that mTORC1 also plays a role in endo-lysosome expansion and lysosomal-protein translation as these processes were diminished in cells treated with the mTORC1 inhibitor torin1. Additionally, RNA sequencing analysis of an LPS-stimulated macrophage cell line showed activation or inhibition of mTORC1 lead to differences in mRNA translational efficiencies. This suggests mTORC1 may mediate other functional changes within the endo-lysosome.

To understand the impact of mTORC1 on antigen presentation the authors used antibody staining to visualize MHC-II:peptide complexes in torin1-treated DCs stimulated with LPS. Cells with active mTORC1 showed increased MHC-II:peptide complexes as wells as increased MHC-II protein levels compared to cells where mTORC1 activity was inhibited. Additionally, only DCs with active mTORC1 were capable of stimulating IL-2 secretion from T-cells, suggesting that mTORC1 may be important to T-cell activation.

Literature in the innate immunology field largely focuses on changes in cell metabolism, transcription, and cytokine production following pathogen exposure. This study demonstrates that cellular infrastructure is also critical in coordinating appropriate immune responses. mTORC1-modulated endo-lysosome expansion may allow phagocytes to retain more extracellular cargo for antigen processing and tubulation may facilitate delivery of MHC-II:peptide complexes to the cell surface for presentation to T cells. While mTORC1 has been implicated in metabolic reprogramming and managing inflammatory responses in activated innate immune cells, this study points to a role for mTORC1 in endo-lysosome remodeling and potentially antigen secretion. Thus, mTORC1 appears to have multiple interesting and independent functions in immune cell activation. The impact of endo-lysosome restructuring on antigen presentation represents an underappreciated feature of immunity, and additional research in this area may offer novel strategies for harnessing mechanisms of the human immune system to fight infection.

Hello World

Mon, 01 Jun 2020 16:24:10 -0800

I began thinking of myself as a writer when I was ten. I wrote in my diary religiously, submitted poetry to contests, and when asked to submit one or two page stories in English class I submitted ten.

I began thinking of myself as a scientist when I was 12. For one of my elective classes I signed up for Genetics where I extracted DNA for the first time from dog testicles, learned about polydactylism, and bred fruit flies in an attempt to create a new mutant.

I continued to pursue science and writing in parallel. I wrote for my high school newspaper, became a section editor, took creative writing, submitted pieces to my school’s literary journal, and preformed in slam poetry competitions. At the same time, I took science tests for fun as a member of the Science Olympiad team, traveled to Illinois to represent my state in a national competition, and continued taking science electives.

Most of my high school friends knew me as a writer, but few knew me as a scientist.

Then college started and I had to chose.

In my first year I took journalism classes and science classes. While I loved writing I found the interviewing aspect of journalism difficult. It was hard to approach people and coax their stories out. One professor referred to my work as “decently done” but “tame.” And it was true. My classmates who were excelling were taking huge risks and weren’t afraid to push for a story whereas I was anxious about interviewing three elderly women who worked in a hospice shop.

In my genetics lab, however, I wasn’t tame. Any question that popped into my head I asked. When shown a new technique I eagerly volunteered to be the first student to test my skills. On weekends I happily trudged through snow to sit at my lab bench and read my meticulously kept lab notebook, musing over my next experiment. Biology was dynamic, complex, enigmatic. I could ask biology any question and every small answer emboldened me to dig deeper.

Most of my college friends knew me as a scientist, but few knew me as a writer.

Now a PhD student, I recognize there are more similarities between science and writing than there are differences. Scientists and writers are both knowledge gatherers, story tellers, and most importantly truth seekers.

My intent with this blog is to continue my learning, to tell stories of science and scientists, to discover truths, and to let everyone get to know me as a scientist and a writer.