Breast Cancer Coalition talk on ONS and Taxol solubility

On May 1, 2011 I presented "Accelerating Discovery by Sharing: a case for Open Notebook Science" at the National Breast Cancer Coalition Annual Advocacy Conference in Arlington, VA. This was the first year where they had a session on an Open Science related theme and the organizers invited me to highlight some of the tools and practices in chemistry which might be applicable to cancer research.

I was really touched by the passion from those in the audience as well as the other speakers and conference participants I met afterward. For many, their deep connection with the cause was strongly rooted in a personal experience as breast cancer survivors themselves or their loved ones. Several expressed a frustration with the current system of sharing results from scientific studies. They felt that knowledge sharing is much slower than it needs to be and that potentially useful "negative" results are generally not disclosed at all.

The NBCC has ambitiously set 2020 as the deadline to end breast cancer (including a countdown clock). It seems reasonable to me that encouraging transparency in research is a good strategy to accelerate progress. Of course, great care must be exercised wherever patient confidentiality is a factor. But health care researchers are already experienced with following protocols to anonymize datasets for publication. Opting to work more openly would not change that but it might affect when and how results are shared. Also there is a great deal of science related to breast cancer that does not directly involve human subjects.

One initiative that particularly impressed me was The Susan G. Komen for the Cure Tissue Bank, presented by Susan Clare from Indiana University and moderated by Virginia Mason from the Inflammatory Breast Cancer Research Foundation. As a result of this effort, thousands of women have donated healthy breast tissue to create a comprehensive database richly annotated with donor genetics and medical history. The idea of trying to tackle a disease state by first understanding normal functioning in great detail was apparently somewhat of a paradigm shift for the cancer research community and it was challenging to implement. According to Dr. Clare, data from the Tissue Bank have shown that the common practice of using apparently unaffected tissue adjacent to a tumor as a control may not be valid.

This example highlights one of the key principles of Open Science: there is value in everyone knowing more - even if it isn't immediately clear how that knowledge will prove to be useful.

In my experience, this is a fundamental point that distinguishes those who are likely to favor Open Science from those who reject its value. If two researchers are discussing Open Science and only one of them views this philosophy as being self-evident the conversation will likely be about why someone would want (or not want) to share more and the focus will fall on extrinsic motivators such as academic credit, intellectual property, etc. If both researchers view this philosophy as self-evident the conversation will probably gravitate towards how and what to share.

I refer to this philosophy as being self-evident because I don't think people can become convinced through argumentation (I've never seen that happen). Within the realm of Open Notebook Science I have been involved in countless discussions about the value of sharing all experimental details - even when errors are discovered. I can think of a few ways in which this is useful - for example telegraphing a research direction to those in the field or providing data for researchers who study how science is actually done (such as Don Pellegrino). But even if I couldn't think of a single application I believe that there is value in sharing all available data.

A good example of this philosophy at work is the Spectral Game. Researchers who uploaded spectral data to ChemSpider as Open Data did not anticipate how their contribution would be used. They didn't do it for extrinsic motives such as traditional academic credit. Assuming that their motivation was similar to our group's, they did it because they believed it was an obviously useful thing to do. It is only much later - after a critical mass of open spectra were collected - that the idea arose to create a game from the dataset.

With this mindset, I explored what contribution we might make to breast cancer research by performing a phrase search strategy. Doing a simple Google search for "breast cancer" solubility generated mainly two types of results.

The first set involve the solubility behavior of biomolecules within the cellular environment. An example would be the observed increased solubility of gamma-tubulin in cancerous cells.
The second type of results address the difficulty in preparing formulations for cancer drugs due to solubility problems. A good example of this is Taxol (paclitaxel), where existing excipients are not completely satisfactory - in the case of Cremophor EL some patients experience a hypersensitivity.
Since our modeling efforts thus far have focused on non-aqueous solubility, there is possibly an opportunity to contribute by exploring the solubility behavior of paclitaxel. By inputting solubility data from a paper by Singla 2002 into our solubility database, Abraham descriptors for paclitaxel are automatically calculated and the solubilities in over 70 solvents are predicted.

In addition, by simply adding the melting point of paclitaxel, we automatically predict its solubility at any temperature where these solvents are liquids (see for example water).

Because of the way we expose our results to the web, a Google search for "paclitaxel solubility acetonitrile" now returns the actual value in the Google summary on the first page of results (currently 7th on the first page). The other hits have all 3 keywords somewhere in the document but one has to click on each link then perform a search within the document to find out if the acetonitrile solubility for paclitaxel is actually reported. (Note that clicking on our link ultimately takes you to the peer-reviewed paper with the original measurement.)

To be clear about what we are doing here - we are not claiming to be the first to predict the solubility of paclitaxel in these solvents using Abraham descriptors or any other method. Nor are we claiming that we have directly made a dent in the formulation problem of paclitaxel. We are not even indicating that we have done a thorough search of the literature - that would take a lot more time than we have had given the enormous amount of work on paclitaxel and its derivatives.

All we are doing is fleshing out the natural interface between the knowledge space of the UsefulChem/ONS Challenge projects and that of breast cancer research - AND - we are exposing the results of that intersection through easily discoverable channels. By design, these results are exposed as self-contained "smallest publishable units" and they are shared as quickly (and as automatically) as possible. The traditional publication system does not have mechanism to disseminate this type of information. (Of course when enough of these are collected and woven into a narrative that fits the criteria for a traditional paper they can and should be submitted for peer-reviewed publication).

Here is a scenario for how this could work in this specific instance. A graduate student (who has never heard of Open Science or UsefulChem, the ONS Challenge, etc.) is asked to look for new formulations for paclitaxel (or other difficult to solubilize anti-cancer agents). They do a search on commercial databases offered by their university for various solubilities of paclitaxel and cannot find a measurement for acetonitrile. They then do a search on Google and find a hit directly answering their query, as I detailed above. This leads them to our prediction services and they start using those numbers in their own models.

That is a good outcome - and that is exactly what has been happening (see the gold nanodot paper and the phenanthrene soil contamination study as examples). But the real paydirt would come from the graduate student recognizing that we've done a lot of work collecting measurements and building models for solubility and melting points, and contact us about a collaboration. As long as they are comfortable with working openly we would be happy actively work together.

I'm using the formulation of paclitaxel as an example but I'm sure that there are many more intersections between solubility and breast cancer research. With a bit of luck I hope we can find a few researchers who are open to this type of collaboration.

As another twist to this story, I will briefly mention here too that Andrew Lang has started to screen our Ugi product virtual library for docking with the site where paclitaxel binds to gamma-tubulin (D-EXP018). This might shed some light on some much cheaper alternatives to the extremely expensive paclitaxel and derivatives. The drug binds through 3 hydrogen bonds, shown below - rendered in 2D and 3D representations (obtained from the PDB ligand viewer)


The slides and recording of my talk are embedded below:

Soft Cover Quilt

Katrin Rodegast quilt

While I like to sew (and refuse to knit), my quilting has never gotten this interesting. I think I’ve been inspired. Artist Katrin Rodegast created this large quilt that was exhibited in Dortmund, Germany. On her site, you can see the details of all the figures she’s incorporated, many of them anatomical. Brains, hearts, skeletons, you name it, have earned their spot.

It is coated with a pattern of 270 illustrations observing the social reality. With my quilt I connect traditional quilt art and modern computer technology.

Something like this would be too pretty to sleep with, and def too large for my apartment. I’m so glad to find this unique piece to gaze at!

Soft Anatomies

Rebecca Ladds ribcage

Rebecca Ladds rabbit anatomy

Rebecca Ladds cat anatomy

Rebecca Ladds has exhaled these wonderful Soft Anatomies. As, according to Ladds, seeing the beauty in all things makes creating as natural a process as breathing. Only in her first year at the Ontario College of Art & Design, her lungs are still pink and ready to breathe new life into the world of anatomical art.

To check out her collection and purchase a print of your own, head to her Etsy!

 

Annals of Eugenics Journal, 1925-1954, Now Available Online


The Annals of Eugenics--now The Annals of Human Genetics--has just made its 1925-1954 journal content available online for researchers in the history of science and medicine. Their current issue also features four specially commissioned articles that contextualizing the content, and highlighting the ways in which Eugenics "embodies the history of human genetics as a scientific enterprise and exemplifies the complex relationship of this discipline with wider society [as well as] the somber role that human genetics played in providing what was taken to be a scientific framework to social prejudice during the period."

This is sure to be some fascinating stuff.

Full details, as told by Advances in the History of Psychology:

The Annals of Human Genetics (AHG), formerly named Annals of Eugenics, has recently made its 1925-1954 journal content available online for researchers. Among the now controversial eugenics research appearing throughout these issues, researchers can also expect to find statistical publications by mathematician Karl Pearson, whose work at University College London concerned the widely used Pearson Product-Moment Correlation Coefficient, the Pearson Chi-Square test, and P-value.

The AHG editorial cites “ongoing use and reference to materials”… “and the somewhat limited availability of the original printed copy” as justification for making the content available online. Furthermore,

"Online access to the Annals of Eugenics archive will also be of interest to historians of science. In many ways, the history of the Annals embodies the history of human genetics as a scientific enterprise and exemplifies the complex relationship of this discipline with wider society. The somber role that human genetics played in providing what was taken to be a scientific framework to social prejudice during the period of “Eugenics” is a well-known case of the complex interaction between science and society. The present issue of the journal includes four specially commissioned articles that attempt to contextualize the online publication of the Annals of Eugenics archive. To exemplify some of the major scientific contributions made during that period, the article by J. Ott highlights key papers on linkage analysis published by the journal. The contributions by K. Weiss, G. Allen, and D. Kevles deal with aspects of the history of eugenics and of human genetics, and explore their relevance to ongoing debates regarding the social implications of human genetics research."

You can read the full article by clicking here.

"Animated Anatomies," Duke University, Durham, North Carolina, Until July 17, 2011




While at the AAHM meeting in Philadelphia a few weeks ago, I met a number of fascinating folks, among them Rachel Ingold, the curator of the History of Medicine Collections at the Duke Medical Center Library & Archives. She was telling me about a wonderful exhibition on flap anatomies (images above) that will be on view there until July of this year; here is what she had to say about it:

Animated Anatomies explores the visually stunning and technically complex genre of printed texts and illustrations known as anatomical flap books. This exhibit traces the flap book genre beginning with early examples from the sixteenth century, to the colorful “golden age” of complex flaps of the nineteenth century, and finally to the common children’s pop-up anatomy books of today. The display—which includes materials from the Rare Book Manuscript and Special Collection Library at Duke University, the Duke Medical Center Library & Archives’ History of Medicine Collections, and from the private collections of the curators of the exhibit—highlights the history of science, medical instruction, and the intricate art of bookmaking.

Through the hands-on process of exposing layer after layer of anatomical illustrations, flap books mimic the act of human dissection, inviting the viewer to participate in a virtual autopsy, so to speak. Whether it’s a sixteenth-century hand-colored treatise on the layers of the eye or a nineteenth-century obstetrical guide in 3-D for performing cesareans, these books draw the viewer in. Over time, as advances in both science and printing promoted more widespread medical knoLinkwledge, anatomical flap books began to appeal to more general audiences eager to learn about their own bodies’ inner workings. Technological developments in machine printing also allowed for more colorful and precise illustrations than the hand-colored treatises of the early modern period.

A symposium was held on April 18 and we hope to have videos posted from this event soon. To learn more about the symposium, exhibit, see photos of anatomical flap books, and watch videos of them in action, visit the exhibit website. For more information, contact Meg Brown at meg.brown@duke.edu or Rachel Ingold at rachel.ingold@duke.edu. The exhibit will be up through July 17, 2011, and is free and open to the public.

This fantastic looking exhibition will be on display in the Perkins Gallery, Perkins Library, at Duke University, Durham, North Carolina, until July 17, 2011, and in the History of Medicine Gallery in the Medical Center and Archives Library from April 13-July 17, 2011. To find out more--or to pay a virtual visit!--check out the exhibition website by clicking here.

Robert Burton’s "The Anatomy of Melancholy" on the BBC


The BBC Radio 4’s In Our Time has just produced an episode about Robert Burton's 17th masterwork The Anatomy of Melancholy; the book is essentially a 17th Century multi-disciplinary investigation of what was then known as melancholy, and, as the BBC describes, brings together "almost two thousand years of scholarship, from Ancient Greek philosophy to seventeenth-century medicine. Melancholy, a condition believed to be caused by an imbalance of the body’s four humours, was characterised by despondency, depression and inactivity. Burton himself suffered from it, and resolved to compile an authoritative work of scholarship on the malady, drawing on all relevant sources."

Can't wait to give this a listen!

You can listen to the episode by clicking here. Found on the Advances in the History of Psychology website; click here to read full post.

Image: Frontspiece to Robert Burton’s The Anatomy of Melancholy, or The Anatomy of Melancholy, What it is: With all the Kinds, Causes, Symptomes, Prognostickes, and Several Cures of it. In Three Maine Partitions with their several Sections, Members, and Subsections. Philosophically, Medicinally, Historically, Opened and Cut Up, 1621

Donate to the Making of a 19th Century Disaster Amuseument! The Cosmorama of the Great Dreamland Fire Needs Your Help!


As many of you know, I have been hard at work on an exhibition called The Great Coney Island Spectacularium, which opened just a few weeks ago at The Coney Island Museum (more on that here).

As part of the exhibition, we are--with the help of scenic painters, lighting designers and prop builders from the theater and opera world--in the midst of building a new component for the exhibition, an 19th Century-style panorama/cosmorama that will allow visitors to experience the 1911 complete destruction of Dreamland by fire in an immersive 360 degree sound, sight, and light spectacular. This component is set to premiere on May 27th, the centenary of the disaster, and is inspired by the immersive disaster spectacles so popular in Coney Island around the turn of the century.

Here's the rub: immersive amusements of this sort, as we are learning the hard way, are quite expensive to produce--probably a large reason that they were put out of business by cinema!--and we are, sadly, seriously under budget.

If 19th Century-style immersive spectacles of this sort are the kind of thing you would like to experience, and you would like to help contribute towards making this project a reality, we would be so pleased to welcome your contribution! Tax-deductable donations to Coney Island USA--our mother institution--can be made by clicking here and then hitting the "Donate" button. No amount too small! All donations appreciated.

Whether you are able to donate or not, please mark your calendar for the cosmorama opening party, which will take place on the centenary of the great disaster on Friday, May 27th, 2011. Or, come experience it later; The Comorama and the rest of The Spectacularium will be on view to the public at the Coney Island Museum until April 29th, 2012.

You can find out more about The Cosmorama by clicking here. You can join our mailing list to get updates about the opening party and other events by entering your email under "events mailing list" on the upper right hand side of the webpage. You can join our Facebook group by clicking here.

Thanks, and see you at Coney!
Joanna

"The Immortalization Commission: Science and the Strange Quest to Cheat Death," John Gray

...“The Immortalization Commission” is a fascinating piece of intellectual history, exploring the intersection of science, religion, mysticism and a kind of philosophical curiosity that made the early 20th century so much more intellectually dynamic, so much more open-minded and eclectic, so much more magical than either philosophy or science is today. If contemporary god-builders — seeking to stave off death with blue-green algae, Bikram yoga and cryogenics — are more crass and materialistic than those in Gray’s story, ultimately they fail to appreciate the same point: that life seems to get much of its meaning from the fact that it ends. --The Scientific Revolt Against Death, review of John Gray's The Immortalization Commission, The New York Times Book Review

You can read the entire review of John Gray's fascinating The Immortalization Commission: Science and the Strange Quest to Cheat Death in today's New York Times by clicking here. You can find out more about the book--and purchase a copy--by clicking here.

Thanks, Aaron, for sending this review my way.

Image: Getty Images, captions reads:The search for eternal life: Even Charles Darwin hedged his bets and attended a seance; found at The Daily Mail.

Morbid Anatomy Library Seeking Volunteer(s)!


The Brooklyn-based Morbid Anatomy Library is currently seeking a volunteer to watch over the library on Saturdays from 12-6, do a bit of book cataloging, and take on assorted odd jobs. The position would begin the weekend of May 21-22; Class credit can be worked out if applicable.

For those who have not yet visited, the Library (see photo above) is an open-to-the-public research library and private collection housing books, photographs, artworks, ephemera, and artifacts relating to medical museums, anatomical art, cabinets of curiosity, death and dying, arcane media, collectors and collecting, and curiosity and curiosities broadly considered. You can find out more information about the library here.

If interested, please email me at morbidanatomy [at] gmail.com.

Thanks!

Above photo of the library by Shannon Taggart.

Low temperature lignocellulose pretreatment: effects and interactions of pretreatment pH are critical for maximizing enzymatic monosaccharide yields from wheat straw

Background:
The recent development of improved enzymes and pentose utilizing yeast for cellulosic ethanol processes calls for new attention to the lignocellulose pretreatment step. This study assessed the influence of pretreatment pH, temperature, and time, and their interactions on the enzymatic glucose and xylose yields from mildly pretreated wheat straw in multivariate experimental designs of acid and alkaline pretreatments.
Results:
The pretreatment pH was the most significant factor affecting both the enzymatic glucose and xylose yields after mild thermal pretreatments at maximum 140 degreesC for 10 min. The maximal enzymatic glucose and xylose yields from the solid, pretreated wheat straw fraction were obtained after pretreatments at the most extreme pH values (pH 1 or pH 13) at the maximum pretreatment temperature of 140 degreesC. Surface response models revealed significantly correlating interactions of the pretreatment pH and temperature on the enzymatic liberation of both glucose and xylose from pretreated, solid wheat straw. The influence of temperature was most pronounced with the acidic pretreatments, but the highest enzymatic monosaccharide yields were obtained after alkaline pretreatments. Alkaline pretreatments also solubilized most of the lignin.
Conclusions:
Pretreatment pH exerted significant effects and factor interactions on the enzymatic glucose and xylose releases. Quite extreme pH values were necessary with mild thermal pretreatment strategies (T < 140 degreesC, time < 10 min.). Alkaline pretreatments generally induced higher enzymatic glucose and xylose release and did so at lower pretreatment temperatures than required with acidic pretreatments.

Effect of mixing on enzymatic hydrolysis of steam-pretreated spruce: a quantitative analysis of conversion and power consumption

Background:
When scaling up lignocellulose-based ethanol production, the desire to increase the final ethanol titer after fermentation can introduce problems. A high concentration of water-insoluble solids (WIS) is needed in the enzymatic hydrolysis step, resulting in increased viscosity, which can cause mass and heat transfer problems because of poor mixing of the material. In the present study, the effects of mixing on the enzymatic hydrolysis of steam-pretreated spruce were investigated using a stirred tank reactor operated with different impeller speeds and enzyme loadings. In addition, the results were related to the power input needed to operate the impeller at different speeds, taking into account the changes in rheology throughout the process.
Results:
A marked difference in hydrolysis rate at different impeller speeds was found. For example, the conversion was twice as high after 48 hours at 500 rpm compared with 25 rpm. This difference remained throughout the 96 hours of hydrolysis. Substantial amounts of energy were required to achieve only minor increases in conversion during the later stages of the process.
Conclusions:
Impeller speed strongly affected both the hydrolysis rate of the pretreated spruce and needed power input. Similar conversions could be obtained at different energy input by altering the mixing (that is, energy input), enzyme load and residence time, an important issue to consider when designing large-scale plants.

Nicotine Raises Blood Sugar Levels in Lab

(HealthDay News) -- Smoking is damaging to everyone's health, but the nicotine in cigarettes may be even more deadly for people who have diabetes.

In lab experiments, researchers discovered that nicotine raised blood sugar levels, and the more nicotine that was present, the higher the blood sugar levels were. Higher blood sugar levels are linked to an increased risk of complications from diabetes, such as eye and kidney disease.

"Smoking is really harmful for diabetics. It's even more harmful to them than to a non-diabetic," said study author Xiao-Chuan Liu, an associate professor in the department of chemistry at California State Polytechnic University in Pomona. "This study should encourage diabetics to quit smoking completely, and to realize that it's the nicotine that's raising [blood sugar levels]."

For that reason, it's also important to limit the use of nicotine replacement products, such as nicotine patches, Liu said.

"If you're using them for a short period of time to quit smoking, that's OK. But, if you still have this addiction to nicotine and are using this product long-term, it will do harm. Don't use electronic cigarettes or nicotine gum for a long time. You need to stop nicotine intake," he advised. Read more...

AyurGold for Healthy Blood

The Seasteading Institute Seeks GIS Specialist

The Seasteading Institute is seeking a GIS Specialist to evaluate potential seasteading locations. We have a GIS data model which we use to evaluate potential seasteading locations. We need somebody proficient with GRASS (preferably) or ArcGIS who is able to fulfill occasional requests to implement changes to the model, run the model, and prepare the outputs.

The ideal candidate should:

read more

Don Pedro Island Beach House

When I stay in a great place on the beach I always like to post a little video of it on YouTube and share it with other people who might be looking for a place to stay. I recently had the good fortune of staying in this beautiful 4 bedroom 3 bath house right on [...]

Dr. Beach Rates Charlotte County Florida Beaches

You know him as “Dr. Beach.” He’s in the news every year around Memorial Day weekend when he announces his list of the Top Ten Beaches in the Nation. His real name is Stephen Leatherman and he’s the Chair Professor and Director of the Laboratory for Coastal Research at Florida International University in Miami, Florida. [...]

Why Did the Gopher Tortoise Cross the Road?

Gopher tortoises are everywhere on Palm Island and Don Pedro Island. They are probably some of the most photographed tortoises in Florida. When someone is building a new house on these islands they have to check for gopher tortoise burrows first. If there are any, they are carefully moved to another lot. Someone joked that [...]

Don Pedro Island: Back to the Good Old Days

Do you ever wonder what it must have been like living on Florida Gulf coast barrier islands back in the 1930′s and 1940′s? Before the development, before the big bridges, before paved roads, life was much slower. People lived without the constant roar of traffic and sirens, slamming of car doors, or the scream of [...]

Luckys Beach Houses Tonga

Budget travelers visiting the Kingdom of Tonga should consider Lucky's Beach Houses on ‘Utungake Island, about 12 kilometers from Vava’u’s main town of Neiafu by road.

Watch your head!

Coming to a head near you...the Arctic's have landed (Graeme Duncan)

Settled and ready to go (Graeme Duncan)

Up close - a female Eider (Graeme Duncan)

Tuesday 10th May comments: Its been another hectic week on the islands although the weather has finally turned and we've had a few closed days - although plenty of summer migrants arrived with the south-easterly weather front.

On the breeding seabird front, the vast number of Arctic Terns which have been roosting nightly with us have finally settled on the islands and it won't be long before they are laying eggs and doing what Arctic's do best - attacking people! The season seems to be rattling along as the first eider chicks have now hatched and more and more Shag chicks are discovered.

On the migrant front, it has been a busy island as both Spotted and Pied Flycatchers have been seen whilst good numbers of common warblers have been noted including our first Grasshopper Warbler of the year.

Exotic Vanuatu: Eratap Island

eratap1Vanuatu is probably one of the most widely sought off locations for island buyers and travelers with demand often outstripping the supply. Fortunately a new island recently came on the market.

Eratap Island (also known as Castaway Island) is located approximately 1350m off the mainland opposite the stunning Eratap Beach Resort. It is 5.6 hectares in size and covered in native coconut trees, native vegetation and fringed with white sandy beaches.

The island is protected by a sheltered breaking reef offshore. On the mainland side there is around 800m of perfect beach to place a resort or home.

It is around 20 minutes drive to Port Vila from the access lot or 6km to Port Vila harbor by boat.

Do not delay as this property will not last.

For more information on this property visit Private Islands Online.