Meditations of an oncology geek

Chemistry in Context: AR-V7 in Metastatic Prostate Cancer

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23 December 2016

Hi Everyone,

I have some great news to share:

Recently, the work of my colleagues and collaborators was accepted and published in the prestigious journal European Urology. A retrospective analysis of the cohort presented in Scher et al. JAMA Oncology, this study investigated the scoring criteria of the AR-V7 biomarker in circulating tumor cells. We found that the AR-V7 is predictive of drug class-specific survival when the AR-V7 protein is localized to the nucleus of circulating tumor cells in metastatic prostate cancer patients: that patients who had these types of CTCs survived longer on taxane chemotherapy instead of androgen receptor signaling inhibitors like abiraterone, enzalutamide and apalutamide.

My individual contributions were lead biostatistician and drafting the manuscript. The open access article is available here: Nuclear-specific AR-V7 Protein Localization is Necessary to Guide Treatment Selection in Metastatic Castration-resistant Prostate Cancer


Written by Ryon

December 24th, 2016 at 9:51 am

Posted in Science Blog

Nerd Nite, Liquid Biopsies, and the Future of Cancer Diagnostics

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14 December 2016

Hi Everyone,

Last week I had the privilege of being an invited speaker at Nerd Nite. From Wikipedia:

Nerd Nite is an event usually held at a bar or other public venue where 2-3 presenters share about a topic of personal interest or expertise in a fun-yet-intellectual format while the audience shares a drink. It was started in 2003 by then graduate student (now East Carolina University professor) Chris Balakrishan at the Midway Cafe in the Jamaica Plain neighborhood of Boston and spread to New York City in 2006, where Matt Wasowski was tasked with expanding Nerd Nite globally. Nerd Nite is held at more than 80 cities worldwide.

One of those cities is San Diego, where the venue started up a few months back, held just outside the Liberty Public Market, right next to Stone Brewery. The Wikipedia description is apt, as most of the audience has a beer in hand. While the outdoor venue and proximity to Lindberg Field lead to some noisy interruptions, it seems to be a custom to raise one’s drink and take a swig when the speaker is momentarily drowned out by jet noise.

All in all, there were about 40 people present of diverse intellectual curiosities and backgrounds, and when mixed with beer, lead to some really fun public discussions about the intersection of science and science fiction.

I gave a talk titled “The Future of Cancer Diagnostics: The Liquid Biopsy” where I outlined three main areas of cancer diagnostics (see photo) that can be revolutionized by emerging rare blood analyte technologies, especially those that can detect and characterize circulating tumor cells. In particular, I discussed our recent work on CTC-based AR-V7 protein as an emerging treatment selection biomarker in advanced prostate cancer. The next step will be clinical studies to investigate the clinical utility of monitoring resistance (i.e. once a patient gets a drug, not just before a patient gets a drug) using the same or similar types of tests.

The key advantages of liquid biopsy are accessibility, repeatability, and fewer side effects; no one will get a collapsed lung from observing circulating lung tumor cells, and there is no drill required to see circulating tumor cells from a bone metastasis in prostate cancer. Blood draws also do not require trips to hospitals, and can be repeated with much, much higher frequency than tissue biopsies, enabling the potential for sequential monitoring of cancer, which is a disease that evolves over time in cancer patients.

The challenges facing the use of circulating tumor cells lie in the sensitivity of detection, for which I discussed emerging technologies in tandem with established literature suggesting that there is biological feasibility for early detection of cancer using CTCs, and that the main hurdles right now are organizational (i.e. funding and time) required to run the clinical studies and clinical trials to expand clinical utility into the “early detection” area of cancer diagnostics. While treatment selection and recurrence monitoring are very important unmet needs in oncology, and are in late phases of clinical development, it is the early detection of cancer that could extend patient lives by decades, not just years.

It’s a tantalizing vision of the future of oncology, but it is important to underscore that oncology is not changed by technology alone, but by the application and testing (i.e. clinical trials) of technology: do the benefits outweigh the potential harms and costs? What patients benefit, and how much? Emerging technology and studies have clearly demonstrated that the scales can be tipped well into the patients’ favor, at least in the treatment selection area of advanced prostate cancer. It’s a great proof of concept, and this rigor of clinical studies will need to be applied to the recurrence monitoring and early detection areas of oncology diagnostics as well.

…and this is where I got of my soapbox and had a sip of my beer! I really enjoyed the vibe, and will be a regular at Nerd Nite, and it’s so incredibly important to have these types of public discourses about science and technology. Already looking forward to next month!

Written by Ryon

December 14th, 2016 at 9:29 am

Posted in Science Blog

The Epic Journey Continues: A First-In-Class Test Will Change Advanced Prostate Cancer Care

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6 July 2016

Hi Everyone,

I have some great news to share:

1) Recently, the work of my colleagues and collaborators was accepted and published in the prestigious journal JAMA Oncology. We developed a test to predict standard of care drug responses in advanced prostate cancer patients using only a blood draw. The clinical study suggests that use of our test could allow patients with the most aggressive subtype of prostate cancer could live about 4X as long. I was one of the authors on the study, drafting the manuscript and performing bio-statistical analyses. This represents the first “liquid biopsy” test to demonstrate clinical utility at a key medical decision point in cancer patient care.

Association of AR-V7 on Circulating Tumor Cells as a Treatment-Specific Biomarker With Outcomes and Survival in Castration-Resistant Prostate Cancer

2) Today I can publicly share: Genomic Health, arguably the most successful oncology diagnostics company in the world, has partnered with us to distribute and scale the test into clinics across the U.S. The announcement was covered by the Wall Street Journal.

Not too far into the future this test will be extending the lives of tens of thousands of men with very aggressive prostate cancer. Men who just want a fighting chance, and it’s an honor to give them that fighting chance. 10 years ago (summer of 2006) I made a conscious decision that I wanted to devote the most formative years of my life to using science to make tangible improvements in the lives of cancer patients. I’m living the dream. This is the first test of many. My team and I are just getting started.

Thank you all for your support.


Written by Ryon

July 6th, 2016 at 10:47 pm

Posted in Science Blog

Re-directing Ingroup Psychology to Mass Human Identity through Scientific Futurism

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18 December 2015

Could a change in perspective, solidified by large works of science and engineering, creatively re-direct humanity toward a peaceful co-existence with our planet and ourselves, via creatively commandeering our evolutionarily-engrained psychological tendencies?

Today’s piece admittedly reflects a bit of the dreamer in me. I have taken a few ideas that have been floating around my head for a while and organized them into this essay that I would like to share, dear reader. I usually don’t try to condense this level of abstraction to words, but I figure there is no harm in trying. Today I ask the question: from a strictly non-utilitarian perspective (i.e. not making new things for the sake of making new things) could the large-scale cultural practice of science ignite the best angels of humanity’s nature?

I’d like to start off with the psychological concept of in-group vs. outgroup (wording from wikipedia):

In sociology and social psychology, an ingroup is a social group to which a person psychologically identifies as being a member. By contrast, an outgroup is a social group with which an individual does not identify. For example, people may find it psychologically meaningful to view themselves according to their race, culture, gender, age, or religion. It has been found that the psychological membership of social groups and categories is associated with a wide variety of phenomena.

It has been eloquently proposed elsewhere that this psychological phenomenon might be at the core of human cooperation. The evolution of the capacity for empathy has fostered cooperation in a way that few animals have, humans have cooperatively birthed civilization, becoming a dominant species on Earth. It was “us” against “nature” or “us” against megafauna or “us” against the rest of the world. Humans are very good at working as teams when the opposition is implicitly or explicitly defined. Unfortunately, this also expands into “us” against “other group of humans” as well, as recently expanded upon by Adam Piore in Nautilus Magazine:

This takes on real-world consequences when you consider the lasting legacy of competition and warfare between Serbs and Croats, for instance, or Sunni and Shia in the Middle East. Or Tutsi and Hutus in Rwanda. Solidarity with an ingroup and hatred of an outgroup, molded by history, culture, and perceptions rooted in subconscious forces, can explain the horrific actions of terrorists.

While terrorism is outside the scope of this essay, a topic of late that has firmly caught my attention is the perception and concept of a joint human identity. Short of contact with some extra-terrestrial competition to unite us against a common “other”, what sort of joint identity mantle could Earthlings assume to ignite the better angles of our in-group psychological tendencies for the betterment of all humans? If we were able to look beyond our cities, countries, and continents, collectively “zoom out” and adopt a more cosmic perspective, we might collectively be able to appreciate how small humanity, Earth, and out solar system neighborhood is compared to the scope of what is out there. We (humanity) might realize that there is a lot of “other” out there, and solidify a joint human identity by contrast.

While I propose that this perspective would be a very healthy mantle for humanity to adopt, most individual humans learn best not by pondering, but by doing. Is there some activity or challenge that we (humanity) can collectively take on as a vehicle to galvanize our psychological tendencies for cooperation?

On a smaller scale, I wrote briefly about the possibility of biotechnology as the auto shop of the 21st century, where I referenced a talk by Neil Degrasse Tyson:

Meanwhile, however, that entire era galvanized the nation. Forget the war driver, it galvanized us all to dream about tomorrow. To think about the homes of tomorrow. The cities of tomorrow. The food of tomorrow. Everything was future world – future land.

Throughout his talk, Dr. Tyson paints a portrait of a united humanity working toward a common goal. In this instance, it was the NASA Space Program of the 1960s. The scientific and engineering advances are an undeniable tangible benefit. However, Tyson argues that while significant, the greatest value is the cultural practice of progress, of building a better world for tomorrow. It is a tantalizing dream to galvanize our nation, if not humanity, under a common banner of progress: scientific, humanitarian, philosophical. I find this to be a curiously optimistic mindset, with a rough framework for action.

A question I am left to ponder is how the well-studied ingroup vs. outgroup psychological phenomena could be craftily re-directed for the betterment of humanity as a whole? Could we somehow ignite humanity under not a common flag, but a common goal? A mission to Mars? The building of a space elevator? The vision of harmonious co-existence of Earth and humans? If we (humanity) do need an “other” to define ourselves by contrast, could it be the cosmos as our wilderness? To get to that contrast, could we adjust our perspective? And to reinforce that contrast and perspective, could we use large works of science and engineering to do it?

Expanding every human’s ingroup to encompass all humans would be very powerful. Imagine if we did not identify as “Californians” or “Americans” or “Jews” or “Christians”, but instead as “Humans” or “Earthlings.” We would expand our spheres of empathy, be not merely tolerant, but accepting of our differences, in part because the differences seem trite by contrast. We might even strive to harmonious co-existence with our planet, and our collective human family, galvanized by the cultural practice of large-scale science and engineering to reach common goals that concurrently re-directs our psychological tendencies toward mass human identity.

…and with that, I’ll get off my soapbox and go crunch some organic granola. If you have made it this far, dear reader, I would like to thank you for dropping by!


p.s. recommended further reading by Neil Degrasse Tyson:

Written by Ryon

December 17th, 2015 at 10:41 pm

Posted in Science Blog

From PhD to Biotech: Key Lessons and Insights

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15 November 2015

Dear Reader,

This post has been a long time in the making. I apologize in advance for the length and degree of philosophical waxing, but I nonetheless feel compelled to share. I have chosen five key areas and insights that were of great value to me, and continue to hold water:

1) The clinic is queen
2) Twitter is a wonderful gateway to understand biotech and pharmaceutical trends
3) LinkedIn is the de facto e-business card
4) Writing and communication skills are immensely valuable and should be practiced
5) Networking matters (an understatement)

Intro (i.e. philosophical waxing)

Academic research and the biotech industry intersect not merely where medicine is practiced, but how medicine changes and progresses. Without medicine, science loses much application. Without science, medicine loses its eyesight. Modern medicine is based on what we can repeatedly observe and test, and the results have unequivocally transformed the physical well-being of humanity. The manner in which scientific knowledge turns into action requires physical vectors: drugs, tools, devices. Venerable academic traditions and contemporary scientific and technological evolution mix into a kaleidoscopic dance of research, development, and business that is biotechnology. It is this broad swath of industry from which the vectors emerge that literally change medicine. It is immensely exciting, and many young scientists seek to make the transition from academic science to the burgeoning biotechnology industry.

Freshly minted PhDs can often struggle to make the transition from the yin of academic research to the yang of biotechnology. The reasons for this phenomenon are many, and have been described eloquently elsewhere.* I defended my PhD 18 months ago, and have since made that jump, and I would like to share some of the lessons I’ve learned along the way, in hopes that this might be of use to my scientific siblings. I realize that my experience/advice is far from all-encompassing, and that it is highly biased by my personal experiences, and I do not in any way expect my experiences to completely mirror those of anyone else. However, there is a good possibility that at least some of my experiences will rhyme with those of others in similar situations. To this tune, I am sharing some of the lessons I have observed and insights gained along the way.

1) The clinic is queen

In my view, all PhD Candidates should spend some time in the clinic. If one wants to improve patient lives, one has to change clinical practice. If one wants to change clinical practice, one really needs to understand clinical practice. The nuances of the clinical cannot be learned didactically.

I was very fortunate in this regard, as my PhD program was open to me taking part in the HHMI-sponsored program Med-Into-Grad. For three months I spent a large portion of my time away from the bench and in the clinic, learning the basics of pathology, attending tumor boards, shadowing oncologists, and getting to know residents and fellows.

Coming away from this experience, I am still amazed at how much effort is wasted in basic research, and even highly invested biotech companies, on ideas and projects that seem laughably implausible to impact patient care for reasons that become painfully obvious in the clinic.

2) Twitter is a wonderful gateway to understand biotech and pharmaceutical trends

Twitter is a fantastic platform to follow trends in research, regulation, clinical trials, and investment in biotech and pharma. It’s also a platform to create a professional, personal online footprint. A fantastic recent post on Quora by a top engineering recruiter for the likes of Facebook, Google, and Expedia listed a few things that can be done to make a candidate stand out, among them:

Include URLs for online footprints — Nuff said. And within your comfortability of course. I get it. We’ve overshared our way to a more private society, but if you’re looking to stand out, write some stuff on the Internet. Contribute to open source repositories. Demonstrate some level of domain expertise/interest outside of your 9-5.

It is best to use twitter to follow key people and organizations in the field while it is wise to post to twitter sparingly. When posting, anything other than a re-tweet should be well thought out and provide some element of originality in idea or perspective. I include my twitter handle (@RyonGraf) on my resume.

Influential scientific papers get shared frequently and ricocheted around the twittersphere. Many times I have come across said articles within my areas of discipline before pubmed! it is also a wonderful exercise to see what influential people within the field find interesting, and why. When researching or investigating something entirely new (biomarker, drug, etc) I typically do both pubmed and twitter searches as my first steps. While pubmed will have peer-reviewed research and published commentaries, twitter offers a much wider net to how people *receive* or *interpret* available research, especially in realms peripheral to the research realm. Additionally, it offers near real-time trends and developments at major scientific conferences.

The Beaker has a list of great Twitter accounts to follow

Some of my personal favorites include:

General science:
Matthew Herper
Virginia Hughes
Carl Zimmer
Nature News and Comment

Specific to my field:
Nature Reviews Clinical Oncology

The Economist
The Atlantic
Nautilus Magazine

3) LinkedIn is the de facto e-business card

Rule #1 about LinkedIn: Have a nice photo (this applies to Twitter too). I know this sounds trite and shallow, but I have found this to be extremely valuable. LinkedIn is not a dating website, but many of the same rules about first e-impressions apply. A photo is worth more than 1000 words, and is a first impression for many. People DO judge others by their photo. A poor photo is even worse than no photo.

Descriptions of previous work, awards, projects, publications, should be as succinct as possible. Potential employers and co-workers will be the main viewers of a profile, and they are not looking for an essay. Like a resume, it is best to leave the viewer curious for more. It is best to spend LinkedIn development time at making things succinct and getting a decent profile photo.

4) Writing and communication skills are immensely valuable and should be practiced

I went off the deep end in this regard, creating my science blog in February 2011. Writing about scientific topics both within and peripheral to my realm of expertise gave me an opportunity to turn esoteric into succinct, to make science relatable to a wide audience. Writing for my science blog also forced me to become more aware of societal, historical, and ethical contexts for current science topics. I found that this exercise helped me become much more fluent in conversations at social gatherings, and fed back into networking.

Crafting the occasional science tweet on Twitter forced me to practice extremely succinct communication, which is a very important skill in the biotech realm. I also enjoy writing haikus. There, I said it. I don’t write them about science, mind you, and I don’t post them online, but writing haikus is a similar exercise in describing a sensation, scene, or act in 17 syllables.

Higher level (responsibilities and compensation) positions require a greater breadth of knowledge scientific and peripheral. Following trends (*cough* *Twitter* *cough*) and engaging in conversations on these topics lay the foundation for upward advancement.

5) Networking matters

Networking is an overtly extroverted activity. Many scientists are not extroverted. There are two primary, practical benefits to networking as I see it:

a) Expanding the group of people one knows in similar or peripheral fields
b) Improving social skills

Compared to the academic realm, projects in the biotech realm are generally larger in scope and work, and require more diverse skill sets that are best accomplished by many people at once. In other words, it is much more collaborative, and with that comes a necessity for social skills and a level of extroversion. Time spent among diverse people in diverse situations will help build the social skills not merely to help get a job, but to do a job well.

In biotech, who one knows rivals or even exceeds the importance of what one knows. From my experience, the vast majority of people at my company either found out about the job opening through someone they knew, and / or it was also the recommendation of people they knew that helped land them the job once applying. Social currency goes a long way, and it’s very hard to vet someone in an interview process. It’s much more comprehensive to additionally survey the people for whom have built up social currency with a candidate through a history of in-real-life interactions.

I want to drive the point home that networking is far more than looking for a job. At a not-so-infrequent cadence, people I peripherally know (with whom I have had very little interaction and had not built rapport) enter the job market suddenly take up an interest in building rapport with me for recommendations. Depending on the situations, I find this anything from unappealing to utterly disingenuous and fake, and sometimes leads to worse impressions than not interacting at all. I would be a lot more comfortable recommending someone for a position if I had known and worked with for years and developed a history of rapport, someone whom I had observed and could vouch for in many situations. After all, I want good people at my company, and when we open position it’s not out of charity; we need that position filled and the job conducted. To that end, I want to not only help good people I know find a good fit, but I also want my company to succeed, and I want my work environment and company culture to thrive as well. Building that social currency is very difficult to do when one *needs* a job. One can’t grow a garden when hungry, and growing a garden takes many small, constant, efforts. The same rules apply to networking; it is something to be practiced all the time. (with that, I just got up to water my indoor plants)

Networking is not going to networking events, especially not “postdoc” or “grad student” networking events filled with academics. It’s best to go to events pertaining to the interests one has outside of lab. Some of the best networking I have done was at charity events, art gallery happy hours, and while cycling. In truth, any social activity shared by intelligent, successful people is where you want to be.

As I alluded to above, this requires a level of extroversion that many young scientists are not used to, and although I am very much an introvert at heart, I came to learn to be somewhat of an extroverted introvert, and learned to actually enjoy being in social situations surrounded by people I do not know. I learned to become curious about others’ stories and careers, and how they got to their current walk in life. This also allowed me to spend time with people who were in successful careers elsewhere (IT, finance, defense) and become aware of the norms of professionals in fields outside of academia.

In closing

If you’ve made it this far, read reader, it is my hope that this blog post might provide some bit of illumination. As I mentioned before, I am a far cry from a seasoned veteran of the biotech realm. That said, I will risk going out on a limb to share some of my insights thus far in hopes that they will be of use to my scientific siblings. It’s been an absolutely wild 18 months since defending my PhD. The pace is unrelenting, the innovation is inspiring, and I jump out of bed every day excited to go to work. It is my hope that you will find the same :)


*I offer a few commentaries on the current career prospects for young PhDs in academic science:
Boston Globe: Glut of postdoc researchers stirs quiet crisis in science
Science Commentary: The Postdoc: A Special Kind of Hell
Times of Higher Education: Too many postdocs, not enough research jobs

**also, a useful article for introverts learning extroversion:
Forbes: 5 Qualities of Charismatic People

Written by Ryon

November 14th, 2015 at 8:33 pm

Posted in Science Blog

New Publication

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10 May 2015

I am pleased to announce that my company’s first peer-reviewed scientific publication is now available online and open access:

Analytical Validation and Capabilities of the Epic CTC Platform: Enrichment-Free Circulating Tumour Cell Detection and Characterization

It’s been immensely rewarding (and quite fun!) to work with such an innovative team. The platform has allowed us an unparalleled view into the basic nature of circulating tumor cells, and we will be following this up with forthcoming publications.

As the title implies, it includes an analytical validation for detection of CTC surrogates (cancer cell line cells spiked into healthy donor blood) as well as an overview of the dimensions of molecular characterization enabled on our platform.

The liquid biopsy is not-so-slowly becoming a reality, and I could not be more thrilled. Optimal therapy guidance in oncology, especially for targeted therapies, frequently require a tissue biopsy. I yearn for the day that cutting and prodding patients prior to systemic therapy will be seen as blunt at best and draconian at worst. We can and will guide therapy without invasive biopsies, or even trips to a hospital.

Siddhartha Mukherjee has many eloquent lines to describe the nuances and struggles of oncology, of which this one particularly comes to mind:

Cancer’s life is a recapitulation of the body’s life, its existence a pathological mirror of our own.

To this, I would like to add that cancer is a recapitulation of basic tenants of population biology as well, namely the ability to evolve in response to selective pressures. What is truly needed is not a high-resolution snapshot of disease at one time point, but a movie of clonal evolution to expose shifting kinks in cancer’s armor. Solid tissue biopsies largely preclude repeat sampling, but single-cell protein and genomic analyses on circulating tumor cells might provide such a movie. Stay tuned!


Written by Ryon

May 10th, 2015 at 4:01 pm

Posted in Science Blog

STEAM day at Muirlands Middle School

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29 March 2015

About a week ago I had the honor and privilege to attend Muirlands Middle School’s STEAM career day as an invited speaker. The last time I set foot on the Muirlands campus I was a student. As I walked by the front gate I had the distinct recollection of the sound of the principal’s voice telling me and my friends to get off our skateboards! (the kids thought that was pretty funny)

Muirlands has a big emphasis on STEAM (Science, Technology, Engineering, Arts and Math) and organized a career day lineup of about 35 speakers to attend and meet with students. The lineup of speakers was nothing short of impressive; they ranged from professors of medicine to large tech company CEO’s to accomplished artists and oceanographic explorers. It was both quite surreal and fun to be in the company of so many interesting people. After a short meet and greet with other speakers I was whisked away to the first of three classes by one of the student ambassadors.

For each class I had about 15 minutes to give a talk about my career and how I get there, followed by 10 minutes of what must be some of the most entertaining questions I’ve heard in a long time. I was asked questions like: “What would happen in the lab if someone mistook a tube of blood for fruit punch? Would you get cancer?” “Why do cancers come back and why can’t you give the same medicine again?” “What if the computers get so smart that you won’t have a job anymore?” (the last was in response to an overview on machine learning)

It never ceases to amaze me how amazingly curious and creative these young minds are. I am in awe at their collective potential and I am so thrilled to have been able to attend STEAM day at Muirlands.

Key messages from my talk:

1) There are a lot of different careers in science, it’s not just “scientists.”
2) Lots of different people practice the tools and methods of science.
3) Science and art have much in common; practicing science (as opposed to science taught from a book) is a very creative endeavor and shares a very similar tune to the artistic process.
4) Science and technology can make the world better. Going to work every day with that impetus is inspiring and fulfilling and I am very happy with my career trajectory.

I would like to give a huge thank-you to Lisa Bonebrake and all the volunteers for organizing such a wonderful event. The La Jolla Light had a great writeup on the event as well:


Photo: I got a large envelope in the mail with a thank-you note from every student in the three classes I met. Aside from completely melting my heart, it never ceases to amaze me how much curiosity, optimism, and potential middle schoolers have.

Written by Ryon

March 29th, 2015 at 2:27 pm

Posted in Science Blog

Biotechnology as the Auto Shop of the 21st Century?

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23 November 2014

A few weeks back I found out about the following:
1) My old high school is trying to raise funds for upgraded biotechnology labs
2) The La Jolla Community Foundation was to host a kickoff fundraiser for the event at LJHS
3) Craig Venter was going to speak at the fundraiser

Simply put, I was pretty excited to attend. Once there I had the pleasure of meeting current teachers, parents, and curious community members in the mixer before moving into the main auditorium to see a fantastic presentation by Timothy Scott of Pharmatek, and the somewhat surreal experience of seeing Craig Venter interviewed by basketball hall of famer Bill Walton.

Venter started off the night with the quip “the last time was at a high school and met the principal, it was not on the best of terms.” After a few laughs and anecdotes, he and Walton slowly moved to discuss a vision for the future of biotechnology and medicine, the cornerstone of which will be individuals who have hands-on experience with with the fundamentals of biotechnology. And here’s the kicker: that this education can happen in high school.

Equally important to hands-on technological experience is practicing science as problem solving as opposed to the current high school science educational model dominated by rote memorization.

While a few of the speakers portrayed a sentiment that we might produce the next Craig Venter through this project, a more subtle, and to me more practical vision emerged: the La Jolla High School Biological Science and Technology Center is also meant to teach marketable, vocational skills. A portrait emerged of what could be the “auto shop” style classes of the 21st century: Biotechnology.

At Epic Sciences I work in a highly dynamic, collaborative environment with those in business development, quality assurance, competitive intelligence, assay development, product development, and project coordination. Working at a small biotech company has especially driven the point home that there are many career paths and areas of expertise within biotech, but a common thread woven into all of them is the fundamental understanding of the biology and the technology. Most that work at my company have some hands-on experience in the lab. In fact, we value this so much that we have a hands-on training program in the lab at Epic that every new employee, from intern to VP, has to pass.

So, Could biotechnology be the auto shop of the 21st century?

Auto shop taught hands-on skills working with machinery, offering both the practical knowledge to work on one’s automobile, but also the type of primer for a career working in mechanistic industry. Auto shop was a course that offered vocational skills that might be especially valuable to one looking to go directly into the workforce from high school; the norm in generations past when ample jobs existed in that industry.

Large-scale mechanistic industry has been on the decline in the U.S. for more than a generation, outsourced overseas and replaced by other industries. The biotech industry, in contrast, is rapidly growing here in the U.S. and especially San Diego County. Biotechnology can be used to tackle many of the issues of our time, from medicine to energy to climate preservation. Craig Venter went so far as to argue that biotechnology is essential for our survival as a species.

Taking a step back, the possibility of having marketable, vocational skills taught at the high school level is especially attractive to my generation: the tandem increase in tuition rates and decrease in degree worth has made the college route more tenuous than generations past.

College route or not, I would argue that hands-on training in biotechnology and the practice of problem-solving science at the high school level is a very good investment of student time, and our public and private resources. The potential windfalls are great for both the individual and the whole.

Biotechnology Innovation as Positive Cultural Phenomena?

At this point in my blog post I realize that I might be in danger of rambling on about spurring jobs and development and helping produce a more scientifically literate generation. Perhaps we might even be able to start “dreaming of tomorrow” again as posited by Neil DeGrasse Tyson, who has eloquently spoken about the cultural value of optimism and progress that science and technology impart:

Meanwhile, however, that entire era galvanized the nation. Forget the war driver, it galvanized us all to dream about tomorrow. To think about the homes of tomorrow. The cities of tomorrow. The food of tomorrow. Everything was future world – future land.

The World’s Fair? – all of this was focused on enabling people to make tomorrow come. That was a – that was a cultural mindset the space program brought upon us. And we reaped the benefits of economic growth because you had people wanting to become scientists and engineers – who are the people who enable tomorrow to exist today.

And even if you’re not a scientist or technologist, you will value that activity. And that, in the 21st Century, are the foundation of tomorrow’s economies and without it, we might as well just slide back to the cave because that’s where we’re heading right now – broke.

(skip to 1:07 in the embedded video below for the above quote)

I encourage you, dear reader, to watch the first two minutes of this video and perhaps insert “biotechnology” in place of “space exploration”; many of the same messages hold true:

Perhaps the applications of biotechnology could be a source of optimism that we need as a culture? Could we start a trend here? I certainly hope so. The dreamer in me sees basic biotechnology labs in high schools everywhere, a generation from now a greatly expanded biotechnology industry producing wonderful medical advances and living much more harmoniously with our planet.

Alas, a goal without a plan is fantasy. While these visions are admittedly grandiose, the common thread is transforming the basics of science education and biotechnology training at the high school level. The La Jolla Community Foundation is embarking on an ambitious fundraising campaign to do this at La Jolla High School. While LJHS is located in a posh neighborhood, roughly 40% of the student body is bussed in daily from other (less posh) regions of San Diego County. The geographic proximity of LJHS to the heart of the biotech industry lends potential internships and collaborations. After this bioscience center is established, the lessons from implementation can be translated to other high schools in the region, and beyond. I am following this with great interest.


Written by Ryon

November 23rd, 2014 at 11:37 am

Posted in Science Blog

Impressions: 2nd annual Pedal the Cause

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29 September 2014

One week ago concluded the second annual Pedal the Cause. In lieu of a lengthy piece, I would like to present ideas / impressions that constitute small pictures of a larger portrait. And photos.

Temporary Pain
Let’s face it, riding 170 miles through mountainous territory is pretty hard regardless of the pace. There *will* be some pain and discomfort along the way. But, that’s sort of the point. Cancer patients go through tremendous pain and discomfort through the process of their disease and treatment, and a little bit of athletic-induced physical hardship is a great means to both empathize with cancer patients and to learn to appreciate our good health.

Image: at the finish line at UCSD on Day 2, 170 miles in our legs and smiles on our faces. I’m on the left.

Everyone at the Athletes’ Village in Temecula made the distance. Everyone had a story about their ride, about their life, and about cancer. Pedal the Cause brings together a truly impressive caliber of people that would be worth riding 170 miles and raising thousands of dollars to be able to spend an evening in the company of.

Image: The evening in Temecula brought together cancer survivors, patients, caretakers, and well wishers. And jokes by Bob Roll. Photo:A.Czapracki

Health Promotion
Even if every research project funded by Pedal falls flat and fails to produce anything that will be of great value to cancer patients (a highly unlikely scenario), Pedal does one thing that is so essential: health promotion. There is one thing that we can never get back: time. None of us know with certainty how much time we have remaining in our lives. There are many things that are out of our control, but one thing that remains within our control is the QUALITY of that time, and aerobic exercise, specifically the promotion of a healthy-addictive habit like cycling, is a fantastic way to enhance the quality of anyone’s life, especially here in Southern California. (But keep that sunscreen close!) Cycling is a means for many people to make lasting, impactful habitual changes in their lives, and I am always so thrilled to hear of people who got back into, or started cycling just to partake in Pedal the Cause.

Quality and Speed of Research Funding
A lot of cancer charities give money to research, though some give only a fraction, and some give none at all, benefitting from the illusion of giving to research. Pedal the Cause gives all proceeds to cancer research in San Diego. It funds the type of collaborative, high-risk, high-reward research that is needed to make a dent in cancer. There is also the aspect of time: Federal funding usually requires years of preliminary research to even get within a country mile of any grant money, making it nearly impossible for innovative research to get funded. As the federal science budget continues to fall, this trend is expected to continue, undermining scientific innovation and discovery. Pedal the Cause completely sidesteps this process and directly funds very promising projects.

Pedal the Cause forces one to walk outside their comfort bubble and engage new people. I had the incredible fortune of being able to use Pedal the Cause fundraising as a bit of an icebreaker to get to know people at my new company, Epic Sciences. To make a long story short, I embarked on a fundraising campaign that involved getting many of my friends, old and new, to donate between $1 and $5 for every time I managed to go up and down Torrey Pines Grade in 5 hours. It was a LOT of fun and a great challenge. More here. I would like to give a huge thank you to my colleagues at Epic Sciences, who provided the lion’s share of donations for fundraising. There really is no shortage of generous, driven, empathetic, genuine people in the cancer / oncology community here in San Diego. It is my hope that Pedal the Cause will continue to grow, and attract more wonderful people to this burgeoning regional cultural event.

Image: The start line, day one. Cancer researchers and caretakers have green armband, cancer survivors have the bright orange helmets. Photo: A.Czapracki

Written by Ryon

September 28th, 2014 at 8:53 pm

Posted in Science Blog

The Epic Window: Circulating Tumor Cells and the Liquid Biopsy

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14 July 2014

Dear Friends and Family,

I’d like to offer a life-update style post (I’ve been a bit off the radar, sorry!). In the span of the last 90 days the following events happened:

1) I defended my PhD
2) Job applications and interviews
3) I began work at Epic Sciences

The short version is that, after a tumultuous last several months (years?) of my PhD, and the job interview process, I have found myself in a high-energy environment surrounded by diversely talented, innovative, genuinely cool, down to earth people all working together to change the face of oncology. I guess you could say I’m a little excited.

Image: a circulating tumor cell (red) from a profile on Epic Sciences in Discover Blogs

To illustrate challenges in oncology, a quote came to mind from the Emperor of All Maladies:

Specificity refers to the ability of any medicine to discriminate between its intended target and its host. Killing a cancer cell in a test tube is not a particularly difficult task: the chemical world is packed with malevolent poisons that, even in infinitesimal quantities, can dispatch a cancer cell within minutes. The trouble lies in finding a selective poison—a drug that will kill cancer without annihilating the patient. Systemic therapy without specificity is an indiscriminate bomb. For an anticancer poison to become a useful drug, Meyer knew, it needed to be a fantastically nimble knife: sharp enough to kill cancer yet selective enough to spare the patient. – Siddhartha Mukherjee

There has been a wave of new anti-cancer therapies approved by the FDA in the last 5 years, many of which have been touted as ushering in the era of precision medicine. These therapies exploit small molecular discrepancies between cancer cells and healthy cells. The problem is, not all cancers have all the same vulnerabilities and the landscape is incredibly diverse, so much so that leading personalized oncology proponents like Dr. Razelle Kurzrock of UCSD refer to use the metaphor of an individual patient’s cancer molecular profile being as unique as snowflakes, and the correct combination of therapies for every patient might be equally unique.

These precision therapies need informed molecular roadmaps, so patients can receive therap(ies) most suited to them. Currently, this requires tissue samples for requisite molecular analyses. However, tissue biopsies are highly invasive to patients, and longitudinal sampling of how an individual patient’s cancer evolves resistance is nearly impossible with current technology.

The process by which the seeds of tumors establish into metastatic niches (i.e. what causes 90% of mortality from solid tumors) involves transit through the blood, which offers an opportunity for molecular characterization of these cells through a routine blood draw. For years I’ve been very interested in this process, so much so that I did a PhD in this area of research!

The last few years have seen an expanded interest in these circulating tumor cells (CTC’s), as new technologies have emerged to capture and analyze them. This is no easy task; it is literally akin to finding one in one *billion* cells in the blood. About a year ago I became aware of the CTC detecting technology of Epic Sciences. To make a long story short, I recently started working to apply circulating tumor cell (CTC) detection and characterization technology for use in guiding oncology clinical trials.

Image: The Scientist recently produced an overview of CTC detection technologies featuring Epic Sciences

As I alluded to before, tissue sampling of tumors in a cancer patient is highly invasive. No one likes being cut up or prodded, probably just slightly less so than having to get an MRI or PET scan. All of the aforementioned require a trip to a hospital, and a lot of the patient’s and health professionals’ valuable time. Advanced cancer patients might also be too sick for these means of examining their cancer, hindering decisions about what therapies to give (or not to give) or what other measures would be most ethical and humane for the patient and their family.

Blood draws, on the other hand, are minimally invasive, and can be performed even at a local clinic. Blood draws can also be performed frequently; it would be unthinkable to perform a tissue biopsy or a PET scan on a cancer patient twice a month!

While the mere presence of circulating tumor cells gives clues to the stage and progression of a patient’s cancer, the real value is in the molecular and genetic characterization of CTC’s. An immensely unmet need in oncology diagnostics and therapy is a means to confront the intratumor heterogeneity that exists within an individual patient’s disease. A patient’s tumor(s) can be very genetically diverse in both location and time and it’s powerful (and in my opinion pragmatic) to have clues about the cancer cells that can cause the most harm to the patient: the ones that make their way into the blood.

Molecular characterization of CTC’s is a fantastic companion to targeted anti-cancer therapies, and I am thrilled to work as part of a team developing the “Liquid Biopsy” for oncology. I have no reservations saying that I am genuinely excited to get out of bed every morning, and I consider myself a very fortunate man to be able to pursue my passions.

If you have read this far I thank you, dear reader. More (meditations) to come!


Written by Ryon

July 14th, 2014 at 6:51 am

Posted in Science Blog