Tag Archives: deoxyribonucleic acid

Health technology and the Canadian Broadcasting Corporation’s (CBC) two-tier health system ‘Viewpoint’

There’s a lot of talk and handwringing about Canada’s health care system, which ebbs and flows in almost predictable cycles. Jesse Hirsh in a May 16, 2017 ‘Viewpoints’ segment (an occasional series run as part the of the CBC’s [Canadian Broadcasting Corporation] flagship, daily news programme, The National) dared to reframe the discussion as one about technology and ‘those who get it’ [the technologically literate] and ‘those who don’t’, a state Hirsh described as being illiterate as you can see and hear in the following video.

I don’t know about you but I’m getting tired of being called illiterate when I don’t know something. To be illiterate means you can’t read and write and as it turns out I do both of those things on a daily basis (sometimes even in two languages). Despite my efforts, I’m ignorant about any number of things and those numbers keep increasing day by day. BTW, Is there anyone who isn’t having trouble keeping up?

Moving on from my rhetorical question, Hirsh has a point about the tech divide and about the need for discussion. It’s a point that hadn’t occurred to me (although I think he’s taking it in the wrong direction). In fact, this business of a tech divide already exists if you consider that people who live in rural environments and need the latest lifesaving techniques or complex procedures or access to highly specialized experts have to travel to urban centres. I gather that Hirsh feels that this divide isn’t necessarily going to be an urban/rural split so much as an issue of how technically literate you and your doctor are. That’s intriguing but then his argumentation gets muddled. Confusingly, he seems to be suggesting that the key to the split is your access (not your technical literacy) to artificial intelligence (AI) and algorithms (presumably he’s referring to big data and data analytics). I expect access will come down more to money than technological literacy.

For example, money is likely to be a key issue when you consider his big pitch is for access to IBM’s Watson computer. (My Feb. 28, 2011 posting titled: Engineering, entertainment, IBM’s Watson, and product placement focuses largely on Watson, its winning appearances on the US television game show, Jeopardy, and its subsequent adoption into the University of Maryland’s School of Medicine in a project to bring Watson into the examining room with patients.)

Hirsh’s choice of IBM’s Watson is particularly interesting for a number of reasons. (1) Presumably there are companies other than IBM in this sector. Why do they not rate a mention? (2) Given the current situation with IBM and the Canadian federal government’s introduction of the Phoenix payroll system (a PeopleSoft product customized by IBM), which is a failure of monumental proportions (a Feb. 23, 2017 article by David Reevely for the Ottawa Citizen and a May 25, 2017 article by Jordan Press for the National Post), there may be a little hesitation, if not downright resistance, to a large scale implementation of any IBM product or service, regardless of where the blame lies. (3) Hirsh notes on the home page for his eponymous website,

I’m presently spending time at the IBM Innovation Space in Toronto Canada, investigating the impact of artificial intelligence and cognitive computing on all sectors and industries.

Yes, it would seem he has some sort of relationship with IBM not referenced in his Viewpoints segment on The National. Also, his description of the relationship isn’t especially illuminating but perhaps it.s this? (from the IBM Innovation Space – Toronto Incubator Application webpage),

Our incubator

The IBM Innovation Space is a Toronto-based incubator that provides startups with a collaborative space to innovate and disrupt the market. Our goal is to provide you with the tools needed to take your idea to the next level, introduce you to the right networks and help you acquire new clients. Our unique approach, specifically around client engagement, positions your company for optimal growth and revenue at an accelerated pace.

…

OUR SERVICES

IBM Bluemix
IBM Global Entrepreneur
Softlayer – an IBM Company
Watson

Startups partnered with the IBM Innovation Space can receive up to $120,000 in IBM credits at no charge for up to 12 months through the Global Entrepreneurship Program (GEP). These credits can be used in our products such our IBM Bluemix developer platform, Softlayer cloud services, and our world-renowned IBM Watson ‘cognitive thinking’ APIs. We provide you with enterprise grade technology to meet your clients’ needs, large or small.

Collaborative workspace in the heart of Downtown Toronto
Mentorship opportunities available with leading experts
Access to large clients to scale your startup quickly and effectively
Weekly programming ranging from guest speakers to collaborative activities
Help with funding and access to local VCs and investors

Final comments

While I have some issues with Hirsh’s presentation, I agree that we should be discussing the issues around increased automation of our health care system. A friend of mine’s husband is a doctor and according to him those prescriptions and orders you get when leaving the hospital? They are not made up by a doctor so much as they are spit up by a computer based on the data that the doctors and nurses have supplied.

GIGO, bias, and de-skilling

Leaving aside the wonders that Hirsh describes, there’s an oldish saying in the computer business, garbage in/garbage out (gigo). At its simplest, who’s going to catch a mistake? (There are lots of mistakes made in hospitals and other health care settings.)

There are also issues around the quality of research. Are all the research papers included in the data used by the algorithms going to be considered equal? There’s more than one case where a piece of problematic research has been accepted uncritically, even if it get through peer review, and subsequently cited many times over. One of the ways to measure impact, i.e., importance, is to track the number of citations. There’s also the matter of where the research is published. A ‘high impact’ journal, such as Nature, Science, or Cell, automatically gives a piece of research a boost.

There are other kinds of bias as well. Increasingly, there’s discussion about algorithms being biased and about how machine learning (AI) can become biased. (See my May 24, 2017 posting: Machine learning programs learn bias, which highlights the issues and cites other FrogHeart posts on that and other related topics.)

These problems are to a large extent already present. Doctors have biases and research can be wrong and it can take a long time before there are corrections. However, the advent of an automated health diagnosis and treatment system is likely to exacerbate the problems. For example, if you don’t agree with your doctor’s diagnosis or treatment, you can search other opinions. What happens when your diagnosis and treatment have become data? Will the system give you another opinion? Who will you talk to? The doctor who got an answer from ‘Watson”? Is she or he going to debate Watson? Are you?

This leads to another issue and that’s automated systems getting more credit than they deserve. Futurists such as Hirsh tend to underestimate people and overestimate the positive impact that automation will have. A computer, data analystics, or an AI system are tools not gods. You’ll have as much luck petitioning one of those tools as you would Zeus.

The unasked question is how will your doctor or other health professional gain experience and skills if they never have to practice the basic, boring aspects of health care (asking questions for a history, reading medical journals to keep up with the research, etc.) and leave them to the computers? There had to be a reason for calling it a medical ‘practice’.

There are definitely going to be advantages to these technological innovations but thoughtful adoption of these practices (pun intended) should be our goal.

Who owns your data?

Another issue which is increasingly making itself felt is ownership of data. Jacob Brogan has written a provocative May 23, 2017 piece for slate.com asking that question about the data Ancestry.com gathers for DNA testing (Note: Links have been removed),

AncestryDNA’s pitch to consumers is simple enough. For $99 (US), the company will analyze a sample of your saliva and then send back information about your “ethnic mix.” While that promise may be scientifically dubious, it’s a relatively clear-cut proposal. Some, however, worry that the service might raise significant privacy concerns.

After surveying AncestryDNA’s terms and conditions, consumer protection attorney Joel Winston found a few issues that troubled him. As he noted in a Medium post last week, the agreement asserts that it grants the company “a perpetual, royalty-free, world-wide, transferable license to use your DNA.” (The actual clause is considerably longer.) According to Winston, “With this single contractual provision, customers are granting Ancestry.com the broadest possible rights to own and exploit their genetic information.”

…

Winston also noted a handful of other issues that further complicate the question of ownership. Since we share much of our DNA with our relatives, he warned, “Even if you’ve never used Ancestry.com, but one of your genetic relatives has, the company may already own identifiable portions of your DNA.” [emphasis mine] Theoretically, that means information about your genetic makeup could make its way into the hands of insurers or other interested parties, whether or not you’ve sent the company your spit. (Maryam Zaringhalam explored some related risks in a recent Slate article.) Further, Winston notes that Ancestry’s customers waive their legal rights, meaning that they cannot sue the company if their information gets used against them in some way.

Over the weekend, Eric Heath, Ancestry’s chief privacy officer, responded to these concerns on the company’s own site. He claims that the transferable license is necessary for the company to provide its customers with the service that they’re paying for: “We need that license in order to move your data through our systems, render it around the globe, and to provide you with the results of our analysis work.” In other words, it allows them to send genetic samples to labs (Ancestry uses outside vendors), store the resulting data on servers, and furnish the company’s customers with the results of the study they’ve requested.

Speaking to me over the phone, Heath suggested that this license was akin to the ones that companies such as YouTube employ when users upload original content. It grants them the right to shift that data around and manipulate it in various ways, but isn’t an assertion of ownership. “We have committed to our users that their DNA data is theirs. They own their DNA,” he said.

…

I’m glad to see the company’s representatives are open to discussion and, later in the article, you’ll see there’ve already been some changes made. Still, there is no guarantee that the situation won’t again change, for ill this time.

What data do they have and what can they do with it?

It’s not everybody who thinks data collection and data analytics constitute problems. While some people might balk at the thought of their genetic data being traded around and possibly used against them, e.g., while hunting for a job, or turned into a source of revenue, there tends to be a more laissez-faire attitude to other types of data. Andrew MacLeod’s May 24, 2017 article for thetyee.ca highlights political implications and privacy issues (Note: Links have been removed),

After a small Victoria [British Columbia, Canada] company played an outsized role in the Brexit vote, government information and privacy watchdogs in British Columbia and Britain have been consulting each other about the use of social media to target voters based on their personal data.

The U.K.’s information commissioner, Elizabeth Denham [Note: Denham was formerly B.C.’s Office of the Information and Privacy Commissioner], announced last week [May 17, 2017] that she is launching an investigation into “the use of data analytics for political purposes.”

The investigation will look at whether political parties or advocacy groups are gathering personal information from Facebook and other social media and using it to target individuals with messages, Denham said.

B.C.’s Office of the Information and Privacy Commissioner confirmed it has been contacted by Denham.

Macleod’s March 6, 2017 article for thetyee.ca provides more details about the company’s role (note: Links have been removed),

The “tiny” and “secretive” British Columbia technology company [AggregateIQ; AIQ] that played a key role in the Brexit referendum was until recently listed as the Canadian office of a much larger firm that has 25 years of experience using behavioural research to shape public opinion around the world.

The larger firm, SCL Group, says it has worked to influence election outcomes in 19 countries. Its associated company in the U.S., Cambridge Analytica, has worked on a wide range of campaigns, including Donald Trump’s presidential bid.

In late February [2017], the Telegraph reported that campaign disclosures showed that Vote Leave campaigners had spent £3.5 million — about C$5.75 million [emphasis mine] — with a company called AggregateIQ, run by CEO Zack Massingham in downtown Victoria.

That was more than the Leave side paid any other company or individual during the campaign and about 40 per cent of its spending ahead of the June referendum that saw Britons narrowly vote to exit the European Union.

…

According to media reports, Aggregate develops advertising to be used on sites including Facebook, Twitter and YouTube, then targets messages to audiences who are likely to be receptive.

…

The Telegraph story described Victoria as “provincial” and “picturesque” and AggregateIQ as “secretive” and “low-profile.”

Canadian media also expressed surprise at AggregateIQ’s outsized role in the Brexit vote.

The Globe and Mail’s Paul Waldie wrote “It’s quite a coup for Mr. Massingham, who has only been involved in politics for six years and started AggregateIQ in 2013.”

Victoria Times Colonist columnist Jack Knox wrote “If you have never heard of AIQ, join the club.”

The Victoria company, however, appears to be connected to the much larger SCL Group, which describes itself on its website as “the global leader in data-driven communications.”

In the United States it works through related company Cambridge Analytica and has been involved in elections since 2012. Politico reported in 2015 that the firm was working on Ted Cruz’s presidential primary campaign.

And NBC and other media outlets reported that the Trump campaign paid Cambridge Analytica millions to crunch data on 230 million U.S. adults, using information from loyalty cards, club and gym memberships and charity donations [emphasis mine] to predict how an individual might vote and to shape targeted political messages.

…

That’s quite a chunk of change and I don’t believe that gym memberships, charity donations, etc. were the only sources of information (in the US, there’s voter registration, credit card information, and more) but the list did raise my eyebrows. It would seem we are under surveillance at all times, even in the gym.

In any event, I hope that Hirsh’s call for discussion is successful and that the discussion includes more critical thinking about the implications of Hirsh’s ‘Brave New World’.

Shooting drugs to an infection site with a slingshot

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It seems as if I’ve been writing up nanomedicine research a lot lately, so I would have avoided this piece. However, since I do try to cover Canadian nanotechnology regardless of the topic and this work features researchers from l’Université de Montréal (Québec, Canada), here’s one of the latest innovations in the field of nanomedicine. (I have some additional comments about the nano scene in Canada and one major issue concerning nanomedicine at the end of this posting.) From a May 8, 2017 news item on ScienceDaily,

An international team of researchers from the University of Rome Tor Vergata and the University of Montreal has reported, in a paper published this week in Nature Communications, the design and synthesis of a nanoscale molecular slingshot made of DNA that is 20,000 times smaller than a human hair. This molecular slingshot could “shoot” and deliver drugs at precise locations in the human body once triggered by specific disease markers.

A May 8, 2017 University of Montreal news release (also on EurekAlert), which originated the news item, delves further into the research (Note: A link has been removed),

The molecular slingshot is only a few nanometres long and is composed of a synthetic DNA strand that can load a drug and then effectively act as the rubber band of the slingshot. The two ends of this DNA “rubber band” contain two anchoring moieties that can specifically stick to a target antibody, a Y-shaped protein expressed by the body in response to different pathogens such as bacteria and viruses. When the anchoring moieties of the slingshot recognize and bind to the arms of the target antibody the DNA “rubber band” is stretched and the loaded drug is released.

“One impressive feature about this molecular slingshot,” says Francesco Ricci, Associate Professor of Chemistry at the University of Rome Tor Vergata, “is that it can only be triggered by the specific antibody recognizing the anchoring tags of the DNA ‘rubber band’. By simply changing these tags, one can thus program the slingshot to release a drug in response to a variety of specific antibodies. Since different antibodies are markers of different diseases, this could become a very specific weapon in the clinician’s hands.”

“Another great property of our slingshot,” adds Alexis Vallée-Bélisle, Assistant Professor in the Department of Chemistry at the University of Montreal, “is its high versatility. For example, until now we have demonstrated the working principle of the slingshot using three different trigger antibodies, including an HIV antibody, and employing nucleic acids as model drugs. But thanks to the high programmability of DNA chemistry, one can now design the DNA slingshot to ‘shoot’ a wide range of threrapeutic molecules.”

“Designing this molecular slingshot was a great challenge,” says Simona Ranallo, a postdoctoral researcher in Ricci’s team and principal author of the new study. “It required a long series of experiments to find the optimal design, which keeps the drug loaded in ‘rubber band’ in the absence of the antibody, without affecting too much its shooting efficiency once the antibody triggers the slingshot.”

The group of researchers is now eager to adapt the slingshot for the delivery of clinically relevant drugs, and to demonstrate its clinical efficiency. [emphasis mine] “We envision that similar molecular slingshots may be used in the near future to deliver drugs to specific locations in the body. This would drastically improve the efficiency of drugs as well as decrease their toxic secondary effects,” concludes Ricci.

Here’s a link to and a citation for the paper,

Antibody-powered nucleic acid release using a DNA-based nanomachine by Simona Ranallo, Carl Prévost-Tremblay, Andrea Idili, Alexis Vallée-Bélisle, & Francesco Ricci. Nature Communications 8, Article number: 15150 (2017) doi:10.1038/ncomms15150 Published online: 08 May 2017

This is an open access paper.

A couple of comments

The Canadian nanotechnology scene is pretty much centered in Alberta and Québec. The two provinces have invested a fair amount of money in their efforts. Despite the fact that the province of Alberta also hosts the federal government’s National Institute of Nanotechnology, it seems that the province of Québec is the one making the most progress in its various ‘nano’ fields of endeavour. Another province that should be mentioned with regard to its ‘nano’ efforts is Ontario. As far as I can tell, nanotechnology there doesn’t enjoy the same level of provincial funding support as the other two but there is some important work coming out of Ontario.

My other comment has to do with nanomedicine. While it is an exciting field, there is a tendency toward a certain hyperbole. For anyone who got excited about the ‘slingshot’, don’t forget this hasn’t been tested on any conditions close to the conditions found in a human body nor have they even used, “... clinically relevant drugs, … .” It’s also useful to know that less than 1% of the drugs used in nanoparticle-delivery systems make their way to the affected site (from an April 27, 2016 posting about research investigating the effectiveness of nanoparticle-based drug delivery systems). By the way, it was a researcher at the University of Toronto (Ontario, Canada) who first noted this phenomenon after a meta-analysis of the research,

…

More generally, the authors argue that, in order to increase nanoparticle delivery efficiency, a systematic and coordinated long-term strategy is necessary. To build a strong foundation for the field of cancer nanomedicine, researchers will need to understand a lot more about the interactions between nanoparticles and the body’s various organs than they do today. …

It’s not clear from the news release, the paper, or the May 8, 2017 article by Sherry Noik for the Canadian Broadcasting Corporation’s News Online website, how this proposed solution would be administered but presumably the same factors which affect other nano-based drug deliveries could affect this new one,

Scientists have for many years been working on improving therapies like chemo and radiation on that score, but most efforts have focused on modifying the chemistry rather than altering the delivery of the drug.

“It’s all about tuning the concentration of the drug optimally in the body: high concentration where you want it to be active, and low concentration where you don’t want to affect other healthy parts,” says Prof. Alexis Vallée-Bélisle of the University of Montreal, co-author of the report published this week in Nature Communications.

“If you can increase the concentration of that drug at the specific location, that drug will be more efficient,” he told CBC News in an interview.

‘Like a weapon’

Restricting the movement of the drug also reduces potentially harmful secondary effects on other parts of the body — for instance, the hair loss that can result from toxic cancer treatments, or the loss of so-called good bacteria due to antibiotic use.

The idea of the slingshot is to home in on the target cells at a molecular level.

…

The two ends of the strand anchor themselves to the antibody, stretching the strand taut and catapulting the drug to its target.

“Imagine our slingshot like a weapon, and this weapon is being used by our own antibody,” said Vallée-Bélisle, who heads the Laboratory of Biosensors & Nanomachines at U of M. “We design a specific weapon targeting, for example, HIV. We provide the weapon in the body with the bullet — the drug. If the right solider is there, the soldier can use the weapon and shoot the problem.”

Equally important: if the wrong soldier is present, the weapon won’t be deployed.

So rather than delay treatment for an unidentified infection that could be either viral or bacterial, a patient could receive the medication for both and their body would only use the one it needed.

Getting back to my commentary, how does the drug get to its target? Through the bloodstream? Does it get passed through various organs? How do we increase the amount of medication (in nano-based drug delivery systems) reaching affected areas from less than 1%?

The researchers deserve to be congratulated for this work and given much encouragement and thanks as they grapple with the questions I’ve posed and with all of the questions I don’t know how to ask.

Synthetic genetics and imprinting a sequence of a single DNA (deoxyribonucleic acid) strand

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Caption: A polymer negative of a sequence of the genetic code, chemically active and able to bind complementary nucleobases, has been created by researchers from the Institute of Physical Chemistry of the Polish Academy of Sciences in Warsaw. Credit: IPC PAS, Grzegorz Krzyzewski

Those are very large hands! In any event, I think they left out the word ‘model’ when describing what the researcher is holding.

A Jan. 19, 2017 news item on phys.org announces the research from the Institute of Physical Chemistry of the Polish Academy of Sciences (IPC PAS),

In a carefully designed polymer, researchers at the Polish Academy of Sciences have imprinted a sequence of a single strand of DNA. The resulting negative remained chemically active and was capable of binding the appropriate nucleobases of a genetic code. The polymer matrix—the first of its type—thus functioned exactly like a sequence of real DNA.

A Jan. 18, 2017 IPC PAS press release, which originated the news item, provides more detail about the breakthrough and explains how it could lead to synthetic genetics,

Imprinting of chemical molecules in a polymer, or molecular imprinting, is a well-known method that has been under development for many years. However, no-one has ever before used it to construct a polymer chain complementing a sequence of a single strand of DNA. This feat has just been accomplished by researchers from the Institute of Physical Chemistry of the Polish Academy of Sciences (IPC PAS) in Warsaw in collaboration with the University of North Texas (UNT) in Denton, USA, and the University of Milan in Italy. In an appropriately selected polymer, they reproduced a genetically important DNA sequence, constructed of six nucleobases.

Typically, molecular imprinting is accomplished in several steps. The molecules intended for imprinting are first placed to a solution of monomers (i.e. the basic “building blocks” from which the future polymer is to be formed). The monomers are selected so as to automatically arrange themselves around the molecules being imprinted. Next, the resulting complex is electrochemically polymerized and then the imprinted molecules are extracted from the fixed structure. This process results in a polymer structure with molecular cavities matching the original molecules with their size and shape, and even their local chemical properties.

“Using molecular imprinting, we can produce, e.g. recognition films for chemical sensors, capturing molecules of only a specific chemical compound from the surroundings – since only these molecules fit into the existing molecular cavities. However, there’s no rose without a thorn. Molecular imprinting is perfect for smaller chemical molecules, but the larger the molecule, the more difficult it is to imprint it accurately into the polymer,” explains Prof. Wlodzimierz Kutner (IPC PAS).

Molecules of deoxyribonucleic acid, or DNA, are really large: their lengths are of the order of centimetres. These molecules generally consist of of two long strands, paired up with each other. A single strand is made up of nucleotides with multiple repetitions, each of which contains one of the nucleobases: adenine (A), guanine (G), cytosine (C), or thymine (T). The bases on both strands are not arranged freely: adenine on one strand always corresponds to thymine on the other, and guanine to cytosine. So, when we have one thread, we can always recreate its complement, which is the second strand.

The complementarity of nucleobases in DNA strands is very important for cells. Not only does it increase the permanence of the record of the genetic code (damage in one strand can be repaired based on the construction of the other), but it also makes it possible to transfer it from DNA to RNA in the process known as transcription. Transcription is the first step in the synthesis of proteins.

“Our idea was to try to imprint in the polymer a sequence of a single-stranded DNA. At the same time, we wanted to reproduce not only the shape of the strand, but also the sequential order of the constituent nucleobases,” says Dr. Agnieszka Pietrzyk-Le (IPC PAS).

In the study, financed on the Polish side by grants from the Foundation for Polish Science and the National Centre for Science, researchers from the IPC PAS used sequences of the genetic code known as TATAAA. This sequence plays an important biological role: it participates in deciding on the activation of the gene behind it. TATAAA is found in most eukaryotic cells (those containing a nucleus); in humans it is present in about every fourth gene.

A key step of the research was to design synthetic monomers undergoing electrochemical polymerization. These had to be capable of accurately surrounding the imprinted molecule in such a way that each of the adenines and thymines on the DNA strand were accompanied by their complementary bases. The mechanical requirements were also important, because after polymerization the matrix had to be stable. Suitable monomers were synthesized by the group of Prof. Francis D’Souza (UNT).

“When all the reagents and apparatus have been prepared, the imprinting itself of the TATAAA oligonucleotide is not especially complicated. The most important processes take place automatically in solutions in no more than a few dozen minutes. Finally, on the electrode used for electropolymerization, we obtain a layer of conductive polymer with molecular cavities where the nucleobases are arranged in the TTTATA sequence, that is, complementary to the extracted original”, describes doctoral student Katarzyna Bartold (IPC PAS).

Do polymer matrices prepared in this manner really reconstruct the original sequence of the DNA chain? To answer this question, at the IPC PAS careful measurements were carried out on the properties of the new polymers and a series of experiments was performed that confirmed the interaction of the polymers with various nucleobases in solutions. The results leave no doubt: the polymer DNA negative really is chemically active and selectively binds the TATAAA oligonucleotide, correctly reproducing the sequence of nucleobases.

The possibility of the relatively simple and low-cost production of stable polymer equivalents of DNA sequences is an important step in the development of synthetic genetics, especially in terms of its widespread applications in biotechnology and molecular medicine. If an improvement in the method developed at the IPC PAS is accomplished in the future, it will be possible to reproduce longer sequences of the genetic code in polymer matrices. This opens up inspiring perspectives associated not only with learning about the details of the process of transcription in cells or the construction of chemosensors for applications in nanotechnologies operating on chains of DNA, but also with the permanent archiving and replicating of the genetic code of different organisms.

Here’s a link to and a citation for the paper,

Programmed transfer of sequence information into molecularly imprinted polymer (MIP) for hexa(2,2’-bithien-5-yl) DNA analog formation towards single nucleotide polymorphism (SNP) detection by Katarzyna Bartold, Agnieszka Pietrzyk-Le, Tan-Phat Huynh, Zofia Iskierko, Marta I. Sosnowska, Krzysztof Noworyta, Wojciech Lisowski, Francesco Maria Enrico Sannicolo, Silvia Cauteruccio, Emanuela Licandro, Francis D’Souza, and Wlodzimierz Kutner. ACS Appl. Mater. Interfaces, Just Accepted Manuscript
DOI: 10.1021/acsami.6b14340 Publication Date (Web): January 10, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

DNA-based nanowires in your computer?

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In the quest for smaller and smaller, DNA (deoxyribonucleic acid) is being exploited as never before. From a Nov. 9, 2016 news item on phys.org,

Tinier than the AIDS virus—that is currently the circumference of the smallest transistors. The industry has shrunk the central elements of their computer chips to fourteen nanometers in the last sixty years. Conventional methods, however, are hitting physical boundaries. Researchers around the world are looking for alternatives. One method could be the self-organization of complex components from molecules and atoms. Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and Paderborn University have now made an important advance: the physicists conducted a current through gold-plated nanowires, which independently assembled themselves from single DNA strands. …

A Nov. 9, 2016 HZDR press release (also on EurekAlert), which originated the news item, provides more information,

At first glance, it resembles wormy lines in front of a black background. But what the electron microscope shows up close is that the nanometer-sized structures connect two electrical contacts. Dr. Artur Erbe from the Institute of Ion Beam Physics and Materials Research is pleased about what he sees. “Our measurements have shown that an electrical current is conducted through these tiny wires.” This is not necessarily self-evident, the physicist stresses. We are, after all, dealing with components made of modified DNA. In order to produce the nanowires, the researchers combined a long single strand of genetic material with shorter DNA segments through the base pairs to form a stable double strand. Using this method, the structures independently take on the desired form.

“With the help of this approach, which resembles the Japanese paper folding technique origami and is therefore referred to as DNA-origami, we can create tiny patterns,” explains the HZDR researcher. “Extremely small circuits made of molecules and atoms are also conceivable here.” This strategy, which scientists call the “bottom-up” method, aims to turn conventional production of electronic components on its head. “The industry has thus far been using what is known as the ‘top-down’ method. Large portions are cut away from the base material until the desired structure is achieved. Soon this will no longer be possible due to continual miniaturization.” The new approach is instead oriented on nature: molecules that develop complex structures through self-assembling processes.

Golden Bridges Between Electrodes

The elements that thereby develop would be substantially smaller than today’s tiniest computer chip components. Smaller circuits could theoretically be produced with less effort. There is, however, a problem: “Genetic matter doesn’t conduct a current particularly well,” points out Erbe. He and his colleagues have therefore placed gold-plated nanoparticles on the DNA wires using chemical bonds. Using a “top-down” method – electron beam lithography — they subsequently make contact with the individual wires electronically. “This connection between the substantially larger electrodes and the individual DNA structures have come up against technical difficulties until now. By combining the two methods, we can resolve this issue. We could thus very precisely determine the charge transport through individual wires for the first time,” adds Erbe.

As the tests of the Dresden researchers have shown, a current is actually conducted through the gold-plated wires — it is, however, dependent on the ambient temperature. “The charge transport is simultaneously reduced as the temperature decreases,” describes Erbe. “At normal room temperature, the wires function well, even if the electrons must partially jump from one gold particle to the next because they haven’t completely melded together. The distance, however, is so small that it currently doesn’t even show up using the most advanced microscopes.” In order to improve the conduction, Artur Erbe’s team aims to incorporate conductive polymers between the gold particles. The physicist believes the metallization process could also still be improved.

He is, however, generally pleased with the results: “We could demonstrate that the gold-plated DNA wires conduct energy. We are actually still in the basic research phase, which is why we are using gold rather than a more cost-efficient metal. We have, nevertheless, made an important stride, which could make electronic devices based on DNA possible in the future.”

Here’s a link to and a citation for the paper,

Temperature-Dependent Charge Transport through Individually Contacted DNA Origami-Based Au Nanowires by Bezu Teschome, Stefan Facsko, Tommy Schönherr, Jochen Kerbusch, Adrian Keller, and Artur Erbe. Langmuir, 2016, 32 (40), pp 10159–10165, DOI: 10.1021/acs.langmuir.6b01961, Publication Date (Web): September 14, 2016

Copyright © 2016 American Chemical Society

This paper is behind a paywall.

A DNA origami-based nanoscopic force clamp

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Nanoclamp made of DNA strands. Illustration: Christoph Hohmann

An Oct. 21, 2016 news item on ScienceDaily announces a new nanotool,

Physicists at Ludwig-Maximilians-Universitat (LMU) in Munich have developed a novel nanotool that provides a facile means of characterizing the mechanical properties of biomolecules.

An Oct. 21, 2016 Ludwig-Maximilians-Universitat (LMU) press release (also on EurekAlert), which originated the news item, explains the work in more detail (Note: A link has been removed),

Faced with the thousands of proteins and genes found in virtually every cell in the body, biologists want to know how they all work exactly: How do they interact to carry out their specific functions and how do they respond and adapt to perturbations? One of the crucial factors in all of these processes is the question of how biomolecules react to the minuscule forces that operate at the molecular level. LMU physicists led by Professor Tim Liedl, in collaboration with researchers at the Technical University in Braunschweig and at Regensburg University, have come up with a method that allows them to exert a constant force on a single macromolecule with dimensions of a few nanometers, and to observe the molecule’s response. The researchers can this way test whether or not a protein or a gene is capable of functioning normally when its structure is deformed by forces of the magnitude expected in the interior of cells. This new method of force spectroscopy uses self-assembled nanoscopic power gauges, requires no macroscopic tools and can analyze large numbers of molecules in parallel, which speeds up the process of data acquisition enormously.

With their new approach, the researchers have overcome two fundamental limitations of the most commonly used force spectroscopy instruments. In the case of force microscopy and methodologies based on optical or magnetic tweezers, the molecules under investigation are always directly connected to a macroscopic transducer. They require precise control of the position of an object – a sphere or a sharp metal tip on the order of a micrometer in size – that exerts a force on molecules that are anchored to that object. This strategy is technically extremely demanding and the data obtained is often noisy. Furthermore, these procedures can only be used to probe molecules one at a time. The new method dispenses with all these restrictions. “The structures we use operate completely autonomously“, explains Philipp Nickels, a member of Tim Liedl’s research group. “And we can use them to study countless numbers of molecules simultaneously.”

A feather-light touch

The members of the Munich group, which is affiliated with the Cluster of Excellence NIM (Nanosystems Initiative Munich), are acknowledged masters of “DNA origami”. This methodology exploits the base-pairing properties of DNA for the construction of nanostructures from strands that fold up and pair locally in a manner determined by their nucleotide sequences. In the present case, the DNA sequences are programmed to interact with each other in such a way that the final structure is a molecular clamp that can be programmed to exert a defined force on a test molecule. To this end, a single-stranded DNA that contains a specific sequence capable of recruiting the molecule of interest spans from one arm of the clamp to the other. The applied force can then be tuned by changing the length of the single strand base by base. “That is equivalent to stretching a spring ever so-o-o slightly,” says Nickels. Indeed, by this means it is possible to apply extremely tiny forces between 1 and 15 pN (1 pN = one billionth of a Newton) – comparable in magnitude to those that act on proteins and genes in cells. “In principle, we can capture any type of biomolecule with these clamps and investigate its physical properties,” says Tim Liedl.

The effect of the applied force is read out by taking advantage of the phenomenon of Förster Resonant Energy Transfer (FRET). “FRET involves the transfer of energy between two fluorescent dyes and is strongly dependent on the distance between them.” explains Professor Philip Tinnefeld from TU Braunschweig. When the force applied to the test molecule is sufficient to deform it, the distance between the fluorescent markers changes and the magnitude of energy transfer serves as an exquisitely precise measure of the distortion of the test molecule on the nanometer scale.

Together with Dina Grohmann from Universität Regensburg, the team has used the new technique to investigate the properties of the so-called TATA Binding Protein, an important gene regulator which binds to a specific upstream nucleotide sequence in genes and helps to trigger their expression. They found that the TATA protein can no longer perform its normal function if its target sequence is subjected to a force of more than 6 pN. – The new technology has just made its debut. But since the clamps are minuscule and operate autonomously, it may well be possible in the future to use them to study molecular processes in living cells in real time.

Sometimes reading these news releases, my mind is boggled. What an extraordinary time to live.

Here’s a link to and a citation for the paper,

Molecular force spectroscopy with a DNA origami–based nanoscopic force clamp by Philipp C. Nickels, Bettina Wünsch, Phil Holzmeister, Wooli Bae, Luisa M. Kneer, Dina Grohmann, Philip Tinnefeld, Tim Lied. Science 21 Oct 2016: Vol. 354, Issue 6310, pp. 305-307 DOI: 10.1126/science.aah5974

This paper is behind a paywall.

Doing math in a test tube using analog DNA

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Basically, scientists at Duke University (US) have created an analog computer at the nanoscale, which can perform basic arithmetic. From an Aug. 23, 2016 news item on ScienceDaily,

Often described as the blueprint of life, DNA contains the instructions for making every living thing from a human to a house fly.

But in recent decades, some researchers have been putting the letters of the genetic code to a different use: making tiny nanoscale computers.

In a new study, a Duke University team led by professor John Reif created strands of synthetic DNA that, when mixed together in a test tube in the right concentrations, form an analog circuit that can add, subtract and multiply as they form and break bonds.

Rather than voltage, DNA circuits use the concentrations of specific DNA strands as signals.

An Aug. 23, 2016 Duke University news release (also on EurekAlert), which originated the news item, describes how most DNA-based circuits operate and what makes the one from Duke different,

Other teams have designed DNA-based circuits that can solve problems ranging from calculating square roots to playing tic-tac-toe. But most DNA circuits are digital, where information is encoded as a sequence of zeroes and ones.

Instead, the new Duke device performs calculations in an analog fashion by measuring the varying concentrations of specific DNA molecules directly, without requiring special circuitry to convert them to zeroes and ones first.

…

Unlike the silicon-based circuits used in most modern day electronics, commercial applications of DNA circuits are still a long way off, Reif said.

For one, the test tube calculations are slow. It can take hours to get an answer.

“We can do some limited computing, but we can’t even begin to think of competing with modern-day PCs or other conventional computing devices,” Reif said.

But DNA circuits can be far tinier than those made of silicon. And unlike electronic circuits, DNA circuits work in wet environments, which might make them useful for computing inside the bloodstream or the soupy, cramped quarters of the cell.

The technology takes advantage of DNA’s natural ability to zip and unzip to perform computations. Just like Velcro and magnets have complementary hooks or poles, the nucleotide bases of DNA pair up and bind in a predictable way.

The researchers first create short pieces of synthetic DNA, some single-stranded and some double-stranded with single-stranded ends, and mix them in a test tube.

When a single strand encounters a perfect match at the end of one of the partially double-stranded ones, it latches on and binds, displacing the previously bound strand and causing it to detach, like someone cutting in on a dancing couple.

The newly released strand can in turn pair up with other complementary DNA molecules downstream in the circuit, creating a domino effect.

The researchers solve math problems by measuring the concentrations of specific outgoing strands as the reaction reaches equilibrium.

To see how their circuit would perform over time as the reactions proceeded, Reif and Duke graduate student Tianqi Song used computer software to simulate the reactions over a range of input concentrations. They have also been testing the circuit experimentally in the lab.

Besides addition, subtraction and multiplication, the researchers are also designing more sophisticated analog DNA circuits that can do a wider range of calculations, such as logarithms and exponentials.

Conventional computers went digital decades ago. But for DNA computing, the analog approach has its advantages, the researchers say. For one, analog DNA circuits require fewer strands of DNA than digital ones, Song said.

Analog circuits are also better suited for sensing signals that don’t lend themselves to simple on-off, all-or-none values, such as vital signs and other physiological measurements involved in diagnosing and treating disease.

The hope is that, in the distant future, such devices could be programmed to sense whether particular blood chemicals lie inside or outside the range of values considered normal, and release a specific DNA or RNA — DNA’s chemical cousin — that has a drug-like effect.

Reif’s lab is also beginning to work on DNA-based devices that could detect molecular signatures of particular types of cancer cells, and release substances that spur the immune system to fight back.

“Even very simple DNA computing could still have huge impacts in medicine or science,” Reif said.

Here’s a link to and a citation for the paper,

Analog Computation by DNA Strand Displacement Circuits by Tianqi Song, Sudhanshu Garg, Reem Mokhtar, Hieu Bui, and John Reif. ACS Synth. Biol., 2016, 5 (8), pp 898–912 DOI: 10.1021/acssynbio.6b00144 Publication Date (Web): July 01, 2016

Copyright © 2016 American Chemical Society

This paper is behind a paywall.

Graphene ribbons in solution bending and twisting like DNA

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An Aug. 15, 2016 news item on ScienceDaily announces research into graphene nanoribbons and their DNA (deoxyribonucleic acid)-like properties,

Graphene nanoribbons (GNRs) bend and twist easily in solution, making them adaptable for biological uses like DNA analysis, drug delivery and biomimetic applications, according to scientists at Rice University.

Knowing the details of how GNRs behave in a solution will help make them suitable for wide use in biomimetics, according to Rice physicist Ching-Hwa Kiang, whose lab employed its unique capabilities to probe nanoscale materials like cells and proteins in wet environments. Biomimetic materials are those that imitate the forms and properties of natural materials.

An Aug. 15, 2016 Rice University (Texas, US) news release (also on EurekAlert), which originated the news item, describes the ribbons and the research in more detail,

Graphene nanoribbons can be thousands of times longer than they are wide. They can be produced in bulk by chemically “unzipping” carbon nanotubes, a process invented by Rice chemist and co-author James Tour and his lab.

Their size means they can operate on the scale of biological components like proteins and DNA, Kiang said. “We study the mechanical properties of all different kinds of materials, from proteins to cells, but a little different from the way other people do,” she said. “We like to see how materials behave in solution, because that’s where biological things are.” Kiang is a pioneer in developing methods to probe the energy states of proteins as they fold and unfold.

She said Tour suggested her lab have a look at the mechanical properties of GNRs. “It’s a little extra work to study these things in solution rather than dry, but that’s our specialty,” she said.

Nanoribbons are known for adding strength but not weight to solid-state composites, like bicycle frames and tennis rackets, and forming an electrically active matrix. A recent Rice project infused them into an efficient de-icer coating for aircraft.

But in a squishier environment, their ability to conform to surfaces, carry current and strengthen composites could also be valuable.

“It turns out that graphene behaves reasonably well, somewhat similar to other biological materials. But the interesting part is that it behaves differently in a solution than it does in air,” she said. The researchers found that like DNA and proteins, nanoribbons in solution naturally form folds and loops, but can also form helicoids, wrinkles and spirals.

Kiang, Wijeratne [Sithara Wijeratne, Rice graduate now a postdoctoral researcher at Harvard University] and Jingqiang Li, a co-author and student in the Kiang lab, used atomic force microscopy to test their properties. Atomic force microscopy can not only gather high-resolution images but also take sensitive force measurements of nanomaterials by pulling on them. The researchers probed GNRs and their precursors, graphene oxide nanoribbons.

The researchers discovered that all nanoribbons become rigid under stress, but their rigidity increases as oxide molecules are removed to turn graphene oxide nanoribbons into GNRs. They suggested this ability to tune their rigidity should help with the design and fabrication of GNR-biomimetic interfaces.

“Graphene and graphene oxide materials can be functionalized (or modified) to integrate with various biological systems, such as DNA, protein and even cells,” Kiang said. “These have been realized in biological devices, biomolecule detection and molecular medicine. The sensitivity of graphene bio-devices can be improved by using narrow graphene materials like nanoribbons.”

Wijeratne noted graphene nanoribbons are already being tested for use in DNA sequencing, in which strands of DNA are pulled through a nanopore in an electrified material. The base components of DNA affect the electric field, which can be read to identify the bases.

The researchers saw nanoribbons’ biocompatibility as potentially useful for sensors that could travel through the body and report on what they find, not unlike the Tour lab’s nanoreporters that retrieve information from oil wells.

Further studies will focus on the effect of the nanoribbons’ width, which range from 10 to 100 nanometers, on their properties.

Here’s a link to and a citation for the paper,

Detecting the Biopolymer Behavior of Graphene Nanoribbons in Aqueous Solution by Sithara S. Wijeratne, Evgeni S. Penev, Wei Lu, Jingqiang Li, Amanda L. Duque, Boris I. Yakobson, James M. Tour, & Ching-Hwa Kiang. Scientific Reports 6, Article number: 31174 (2016) doi:10.1038/srep31174 Published online: 09 August 2016

This paper is open access.

Movies and science, science, science (Part 1 of 2)

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In the last few years, there’s been a veritable plethora of movies (and television shows in Canada and the US) that are about science and technology or have a significant component or investigate the social impact. The trend does not seem to be slowing.

This first of two parts features the film, *Hidden* Figures, and a play being turned into a film, Photograph 51. The second part features the evolving Theranos story and plans to turn it into a film, The Man Who Knew Infinity, a film about an Indian mathematician, the science of the recent all woman Ghostbusters, and an ezine devoted to science films.

For the following movie tidbits, I have David Bruggeman to thank.

Hidden Figures

From David’s June 21, 2016 post on his Pasco Phronesis blog (Note: A link has been removed),

Hidden Figures is a fictionalized treatment of the book of the same name written by Margot Lee Shetterly (and underwritten by the Sloan Foundation). Neither the book nor the film are released yet. The book is scheduled for a September release, and the film currently has a January release date in the U.S.

Both the film and the book focus on the story of African American women who worked as computers for the government at the Langley National Aeronautic Laboratory in Hampton, Virginia. The women served as human computers, making the calculations NASA needed during the Space Race. While the book features four women, the film is focused on three: Katherine Johnson (recipient of the Presidential Medal of Freedom), Dorothy Vaughan, and Mary Jackson. They are played by, respectively, Taraji P. Henson, Octavia Spencer, and Janelle Monae. Other actors in the film include Kevin Costner, Kirsten Dunst, Aldis Hodge, and Jim Parsons. The film is directed by Theodore Melfi, and the script is by Allison Schroeder.

*ETA Oct. 6, 2016: The book ‘Hidden Figures’ is nonfiction while the movie is a fictionalized adaptation based on a true story.*

According to imdb.com, the movie’s release date is Dec. 25, 2016 (this could change again).

The history for ‘human computers’ stretches back to the 17th century, at least. From the Human Computer entry in Wikipedia (Note: Links have been removed),

The term “computer”, in use from the early 17th century (the first known written reference dates from 1613),[1] meant “one who computes”: a person performing mathematical calculations, before electronic computers became commercially available. “The human computer is supposed to be following fixed rules; he has no authority to deviate from them in any detail.” (Turing, 1950) Teams of people were frequently used to undertake long and often tedious calculations; the work was divided so that this could be done in parallel.

Prior to NASA, a team of women in the 19th century in the US were known as Harvard Computers (from the Wikipedia entry; Note: Links have been removed),

Edward Charles Pickering (director of the Harvard Observatory from 1877 to 1919) decided to hire women as skilled workers to process astronomical data. Among these women were Williamina Fleming, Annie Jump Cannon, Henrietta Swan Leavitt and Antonia Maury. This staff came to be known as “Pickering’s Harem” or, more respectfully, as the Harvard Computers.[1] This was an example of what has been identified as the “harem effect” in the history and sociology of science.

It seems that several factors contributed to Pickering’s decision to hire women instead of men. Among them was the fact that men were paid much more than women, so he could employ more staff with the same budget. This was relevant in a time when the amount of astronomical data was surpassing the capacity of the Observatories to process it.[2]

The first woman hired was Williamina Fleming, who was working as a maid for Pickering. It seems that Pickering was increasingly frustrated with his male assistants and declared that even his maid could do a better job. Apparently he was not mistaken, as Fleming undertook her assigned chores efficiently. When the Harvard Observatory received in 1886 a generous donation from the widow of Henry Draper, Pickering decided to hire more female staff and put Fleming in charge of them.[3]

While it’s not thrilling to find out that Pickering was content to exploit the women he was hiring, he deserves kudos for recognizing that women could do excellent work and acting on that recognition. When you consider the times, Pickering’s was an extraordinary act.

Getting back to Hidden Figures, an Aug.15, 2016 posting by Kathleen for Lainey Gossip celebrates the then newly released trailer for the movie,

If you’ve been watching the Olympics [Rio 2016], you know how much the past 10 days have been an epic display of #BlackGirlMagic. Fittingly, the trailer for Hidden Figures was released last night during Sunday’s Olympic coverage. It’s the story of three brilliant African American women, played by Taraji P Henson, Octavia Spencer and Janelle Monae, who made history by serving as the brains behind the NASA launch of astronaut John Glenn into orbit in 1962.

Three black women helped launch a dude into space in the 60s. AT NASA. Think about how America treated black women in the 60s. As Katherine Johnson, played by Taraji P Henson, jokes in the trailer, they were still sitting at the back of the bus. In 1962 Malcolm X said, “The most disrespected person in America is the Black woman, the most unprotected person in America is the Black woman. The most neglected person in America is the Black woman.” These women had to face that truth every day and they still rose to greatness. I’m obsessed with this story.

Overall, the trailer is good. I like the pace and the performances look strong. …

…

I’m most excited for Hidden Figures (as Lainey pointed out, this title is THE WORST) because black girls are being celebrated for their brains on screen. That is rare. When the trailer aired, my brother Sam texted me, “WHOA, a smart black girl movie!”

*ETA Sept. 5, 2016: Aran Shetterly contacted me to say this:

What you may not know is that the term “Hidden Figures” is a specific reference to flight science. It tested a pilot’s ability to pick out a simple figure from a set of more complex, difficult to see images. http://www.militaryaptitudetests.com/afoqt/

Thank you Mr. Shetterly!

Photograph 51 (the Rosalind Franklin story)

Also in David’s June 21, 2016 post is a mention of Photograph 51, a play and soon-to-be film about Rosalind Franklin, the discovery of the double helix, and a science controversy. I first wrote about Photograph 51 in a Jan. 16, 2012 posting (scroll down about 50% of the way) regarding an international script writing competition being held in Dublin, Ireland. At the time, I noted that Anna Ziegler’s play, Photograph 51 had won a previous competition cycle of the screenwriting competition. I wrote again about the play in a Sept. 2, 2015 posting about its London production (Sept. 5 – Nov. 21, 2015) featuring actress Nicole Kidman.

The versions of the Franklin story with which I’m familiar paint her as the wronged party, ignored and unacknowledged by the scientists (Francis, Crick, James Watson, and Maurice Wilkins) who got all the glory and the Nobel Prize. Stephen Curry in a Sept. 16, 2015 posting on the Guardian science blogs suggests the story may not be quite as simple as that (Note: A link has been removed),

Ziegler [Anna Ziegler, playwright] is up front in admitting that she has rearranged facts to suit the drama. This creates some oddities of chronology and motive for those familiar with the history. I know of no suggestion of romantic interest in Franklin from Wilkins, or of a separation of Crick from his wife in the aftermath of his triumph with Watson in solving the DNA structure. There is no mention in the play of the fact that Franklin published her work (and the famous photograph 51) in the journal Nature alongside Watson and Crick’s paper and one by Wilkins. Nor does the audience hear of the international recognition that Franklin enjoyed in her own right between 1953 and her untimely death in 1958, not just for her involvement in DNA, but also for her work on the structure of coal and of viruses.

Published long after her death, The Double Helix is widely thought to treat Franklin unfairly. In the minds of many she remains the wronged woman whose pioneering results were taken by others to solve DNA and win the Nobel prize. But the real story – many elements of which come across strongly in the play – is more complex*.

…

Franklin is a gifted experimentalist. Her key contributions to the discovery were in improving methods for taking X-ray pictures of and discovering the distinct A and B conformations of DNA. But it becomes clear that her methodical, meticulous approach to data analysis – much to Wilkins’ impotent frustration – eventually allows the Kings ‘team’ to be overtaken by the bolder, intuitive stratagem of Watson and Crick.

…

Curry’s piece is a good read and provides insight into the ways temperament affects how science is practiced.

Interestingly, there was a 1987 dramatization of the ‘double helix or life story’ (from the Life Story entry on Wikipedia; Note: Links have been removed),

The film tells the story of the rivalries of the two teams of scientists attempting to discover the structure of DNA. Francis Crick and James D. Watson at Cambridge University and Maurice Wilkins and Rosalind Franklin at King’s College London.

The film manages to convey the loneliness and competitiveness of scientific research but also educates the viewer as to how the structure of DNA was discovered. In particular, it explores the tension between the patient, dedicated laboratory work of Franklin and the sometimes uninformed intuitive leaps of Watson and Crick, all played against a background of institutional turf wars, personality conflicts and sexism. In the film Watson jokes, plugging the path of intuition: “Blessed are they who believed before there was any evidence.” The film also shows why Watson and Crick made their discovery, overtaking their competitors in part by reasoning from genetic function to predict chemical structure, thus helping to establish the then still-nascent field of molecular biology.

You can find out more about the stars, crew, and cast here on imdb.com

In addition to Life Story, the dramatization is also sometimes titled as ‘The Race for the Double Helix’ or the ‘Double Helix’.

Getting back to Photograph 51 (the film), Michael Grandage who directed the stage play will also direct the film. Grandage just made his debut as a film director with ‘Genius’ starring Colin Firth and Jude Law. According to this June 23, 2016 review by Sarah on Laineygossip.com, he stumbled a bit by casting British and Australian actors as Americans,

The first hurdle to clear with Genius, the feature film debut of English theater director Michael Grandage, is that everyone is played by Brits and Aussies, and by “everyone” I mean some of the most towering figures of American literature. You cast the best actor for the role and a good actor can convince you they’re anyone, so it shouldn’t really matter, but there is something profoundly odd about watching a parade of Lit 101 All Stars appear on screen and struggle with American accents. …

That kind of casting should not be a problem with Photograph 51 where the action takes place with British personalities.

Part 2 is here.

*’Human’ corrected to ‘Hidden’ on Sept. 5, 2016.

DNA origami as Van Gogh’s Starry Night

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This glowing reproduction of “The Starry Night” contains 65,536 pixels and is the width of a dime across.
Credit: Ashwin Gopinath/Caltech

It may take you a few seconds (it did me) but it’s possible to see Van Gogh’s Starry Night in this image. A July 12, 2016 news item on ScienceDaily reveals more,

Using folded DNA [deoxyribonucleic acid] to precisely place glowing molecules within microscopic light resonators, researchers at Caltech have created one of the world’s smallest reproductions of Vincent van Gogh’s The Starry Night.

A July 12, 2016 Caltech news release (also on EurekAlert) by Richard Perkins, which originated the news item, provides more information about the image, DNA origami, and this latest research on coupling light emitters to photonic crystal cavities (Note: Links have been removed),

The monochrome image—just the width of a dime across—was a proof-of-concept project that demonstrated, for the first time, how the precision placement of DNA origami can be used to build chip-based devices like computer circuits at smaller scales than ever before.

DNA origami, developed 10 years ago by Caltech’s Paul Rothemund (BS ’94), is a technique that allows researchers to fold a long strand of DNA into any desired shape. The folded DNA then acts as a scaffold onto which researchers can attach and organize all kinds of nanometer-scale components, from fluorescent molecules to electrically conductive carbon nanotubes to drugs.

“Think of it a bit like the pegboards people use to organize tools in their garages, only in this case, the pegboard assembles itself from DNA strands and the tools likewise find their own positions,” says Rothemund, research professor of bioengineering, computing and mathematical sciences, and computation and neural systems. “It all happens in a test tube without human intervention, which is important because all of the parts are too small to manipulate efficiently, and we want to make billions of devices.”

The process has the potential to influence a variety of applications from drug delivery to the construction of nanoscale computers. But for many applications, organizing nanoscale components to create devices on DNA pegboards is not enough; the devices have to be wired together into larger circuits and need to have a way of communicating with larger-scale devices.

One early approach was to make electrodes first, and then scatter devices randomly on a surface, with the expectation that at least a few would land where desired, a method Rothemund describes as “spray and pray.”

In 2009, Rothemund and colleagues at IBM Research first described a technique through which DNA origami can be positioned at precise locations on surfaces using electron-beam lithography to etch sticky binding sites that have the same shape as the origami. For example, triangular sticky patches bind triangularly folded DNA.

Over the last seven years, Rothemund and Ashwin Gopinath, senior postdoctoral scholar in bioengineering at Caltech, have refined and extended this technique so that DNA shapes can be precisely positioned on almost any surface used in the manufacture of computer chips. In the Nature paper, they report the first application of the technique—using DNA origami to install fluorescent molecules into microscopic light sources.

“It’s like using DNA origami to screw molecular light bulbs into microscopic lamps,” Rothemund says.

In this case, the lamps are microfabricated structures called photonic crystal cavities (PCCs), which are tuned to resonate at a particular wavelength of light, much like a tuning fork vibrates with a particular pitch. Created within a thin glass-like membrane, a PCC takes the form of a bacterium-shaped defect within an otherwise perfect honeycomb of holes.

“Depending on the exact size and spacing of the holes, a particular wavelength of light reflects off the edge of the cavity and gets trapped inside,” says Gopinath, the lead author of the study. He built PCCs that are tuned to resonate at around 660 nanometers, the wavelength corresponding to a deep shade of the color red. Fluorescent molecules tuned to glow at a similar wavelength light up the lamps—provided they stick to exactly the right place within the PCC.

“A fluorescent molecule tuned to the same color as a PCC actually glows more brightly inside the cavity, but the strength of this coupling effect depends strongly on the molecule’s position within the cavity. A few tens of nanometers is the difference between the molecule glowing brightly, or not at all,” Gopinath says.

By moving DNA origami through the PCCs in 20-nanometer steps, the researchers found that they could map out a checkerboard pattern of hot and cold spots, where the molecular light bulbs either glowed weakly or strongly. As a result, they were able to use DNA origami to position fluorescent molecules to make lamps of varying intensity. Similar structures have been proposed to power quantum computers and for use in other optical applications that require many tiny light sources integrated together on a single chip.

“All previous work coupling light emitters to PCCs only successfully created a handful of working lamps, owing to the extraordinary difficulty of reproducibly controlling the number and position of emitters in a cavity,” Gopinath says. To prove their new technology, the researchers decided to scale-up and provide a visually compelling demonstration. By creating PCCs with different numbers of binding sites, Gopinath was able to reliably install any number from zero to seven DNA origami, allowing him to digitally control the brightness of each lamp. He treated each lamp as a pixel with one of eight different intensities, and produced an array of 65,536 of the PCC pixels (a 256 x 256 pixel grid) to create a reproduction of Van Gogh’s “The Starry Night.”

Now that the team can reliably combine molecules with PCCs, they are working to improve the light emitters. Currently, the fluorescent molecules last about 45 seconds before reacting with oxygen and “burning out,” and they emit a few shades of red rather than a single pure color. Solving both these problems will help with applications such as quantum computers.

“Aside from applications, there’s a lot of fundamental science to be done,” Gopinath says.

Here’s a link to and a citation for the paper,

Engineering and mapping nanocavity emission via precision placement of DNA origami by Ashwin Gopinath, Evan Miyazono, Andrei Faraon, & Paul W. K. Rothemund. Nature (2016) doi:10.1038/nature18287 Published online 11 July 2016

This paper is behind a paywall.

DNA as a sensor

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McMaster University (Ontario, Canada) researchers have developed a technique for using DNA (deoxyribonucleic acid) as a sensor according to a July 7, 2016 news item on ScienceDaily,

Researchers at McMaster University have established a way to harness DNA as the engine of a microscopic “machine” they can turn on to detect trace amounts of substances that range from viruses and bacteria to cocaine and metals.

“It’s a completely new platform that can be adapted to many kinds of uses,” says John Brennan, director of McMaster’s Biointerfaces Insitute and co-author of a paper in the journal Nature Communications that describes the technology. “These DNA nano-architectures are adaptable, so that any target should be detectable.”

A July 7, 2016 McMaster University news release (also on EurekAlert), which originated the news item, expands on the theme,

DNA is best known as a genetic material, but is also a very programmable molecule that lends itself to engineering for synthetic applications.

The new method shapes separately programmed pieces of DNA material into pairs of interlocking circles.

The first remains inactive until it is released by the second, like a bicycle wheel in a lock. When the second circle, acting as the lock, is exposed to even a trace of the target substance, it opens, freeing the first circle of DNA, which replicates quickly and creates a signal, such as a colour change.

“The key is that it’s selectively triggered by whatever we want to detect,” says Brennan, who holds the Canada Research Chair in Bioanalytical Chemistry and Biointerfaces. “We have essentially taken a piece of DNA and forced it to do something it was never designed to do. We can design the lock to be specific to a certain key. All the parts are made of DNA, and ultimately that key is defined by how we build it.”

The idea for the “DNA nanomachine” comes from nature itself, explains co-author Yingfu Li, who holds the Canada Research Chair in Nucleic Acids Research.

“Biology uses all kinds of nanoscale molecular machines to achieve important functions in cells,” Li says. “For the first time, we have designed a DNA-based nano-machine that is capable of achieving ultra-sensitive detection of a bacterial pathogen.”

The DNA-based nanomachine is being further developed into a user-friendly detection kit that will enable rapid testing of a variety of substances, and could move to clinical testing within a year.

Here’s a link to and a citation for the paper,

Programming a topologically constrained DNA nanostructure into a sensor by Meng Liu, Qiang Zhang, Zhongping Li, Jimmy Gu, John D. Brennan, & Yingfu Li. Nature Communications 7, Article number: 12074 doi:10.1038/ncomms12074 Published 23 June 2016

This paper is open access.