A November 21, 2017 news item on Nanowerk describes a rather extraordinary (to me, anyway) approach to using CRRISP ( Clustered Regularly Interspaced Short Palindromic Repeats)-CAS9 (Note: A link has been removed),
A team of scientists led by Virginia Commonwealth University physicist Jason Reed, Ph.D., have developed new nanomapping technology that could transform the way disease-causing genetic mutations are diagnosed and discovered. Described in a study published today [November 21, 2017] in the journal Nature Communications (“DNA nanomapping using CRISPR-Cas9 as a programmable nanoparticle”), this novel approach uses high-speed atomic force microscopy (AFM) combined with a CRISPR-based chemical barcoding technique to map DNA nearly as accurately as DNA sequencing while processing large sections of the genome at a much faster rate. What’s more–the technology can be powered by parts found in your run-of-the-mill DVD player.
The human genome is made up of billions of DNA base pairs. Unraveled, it stretches to a length of nearly six feet long. When cells divide, they must make a copy of their DNA for the new cell. However, sometimes various sections of the DNA are copied incorrectly or pasted together at the wrong location, leading to genetic mutations that cause diseases such as cancer. DNA sequencing is so precise that it can analyze individual base pairs of DNA. But in order to analyze large sections of the genome to find genetic mutations, technicians must determine millions of tiny sequences and then piece them together with computer software. In contrast, biomedical imaging techniques such as fluorescence in situ hybridization, known as FISH, can only analyze DNA at a resolution of several hundred thousand base pairs.
Reed’s new high-speed AFM method can map DNA to a resolution of tens of base pairs while creating images up to a million base pairs in size. And it does it using a fraction of the amount of specimen required for DNA sequencing.
“DNA sequencing is a powerful tool, but it is still quite expensive and has several technological and functional limitations that make it difficult to map large areas of the genome efficiently and accurately,” said Reed, principal investigator on the study. Reed is a member of the Cancer Molecular Genetics research program at VCU Massey Cancer Center and an associate professor in the Department of Physics in the College of Humanities and Sciences.
“Our approach bridges the gap between DNA sequencing and other physical mapping techniques that lack resolution,” he said. “It can be used as a stand-alone method or it can complement DNA sequencing by reducing complexity and error when piecing together the small bits of genome analyzed during the sequencing process.”
IBM scientists made headlines in 1989 when they developed AFM technology and used a related technique to rearrange molecules at the atomic level to spell out “IBM.” AFM achieves this level of detail by using a microscopic stylus — similar to a needle on a record player — that barely makes contact with the surface of the material being studied. The interaction between the stylus and the molecules creates the image. However, traditional AFM is too slow for medical applications and so it is primarily used by engineers in materials science.
“Our device works in the same fashion as AFM but we move the sample past the stylus at a much greater velocity and use optical instruments to detect the interaction between the stylus and the molecules. We can achieve the same level of detail as traditional AFM but can process material more than a thousand times faster,” said Reed, whose team proved the technology can be mainstreamed by using optical equipment found in DVD players. “High-speed AFM is ideally suited for some medical applications as it can process materials quickly and provide hundreds of times more resolution than comparable imaging methods.”
Increasing the speed of AFM was just one hurdle Reed and his colleagues had to overcome. In order to actually identify genetic mutations in DNA, they had to develop a way to place markers or labels on the surface of the DNA molecules so they could recognize patterns and irregularities. An ingenious chemical barcoding solution was developed using a form of CRISPR technology.
CRISPR has made a lot of headlines recently in regard to gene editing. CRISPR is an enzyme that scientists have been able to “program” using targeting RNA in order to cut DNA at precise locations that the cell then repairs on its own. Reed’s team altered the chemical reaction conditions of the CRISPR enzyme so that it only sticks to the DNA and does not actually cut it.
“Because the CRISPR enzyme is a protein that’s physically bigger than the DNA molecule, it’s perfect for this barcoding application,” Reed said. “We were amazed to discover this method is nearly 90 percent efficient at bonding to the DNA molecules. And because it’s easy to see the CRISPR proteins, you can spot genetic mutations among the patterns in DNA.”
To demonstrate the technique’s effectiveness, the researchers mapped genetic translocations present in lymph node biopsies of lymphoma patients. Translocations occur when one section of the DNA gets copied and pasted to the wrong place in the genome. They are especially prevalent in blood cancers such as lymphoma but occur in other cancers as well.
While there are many potential uses for this technology, Reed and his team are focusing on medical applications. They are currently developing software based on existing algorithms that can analyze patterns in sections of DNA up to and over a million base pairs in size. Once completed, it would not be hard to imagine this shoebox-sized instrument in pathology labs assisting in the diagnosis and treatment of diseases linked to genetic mutations.
Here’s a link to and a citation for the paper,
DNA nanomapping using CRISPR-Cas9 as a programmable nanoparticle by Andrey Mikheikin, Anita Olsen, Kevin Leslie, Freddie Russell-Pavier, Andrew Yacoot, Loren Picco, Oliver Payton, Amir Toor, Alden Chesney, James K. Gimzewski, Bud Mishra, & Jason Reed. Nature Communications 8, Article number: 1665 (2017) doi:10.1038/s41467-017-01891-9 Published online: 21 November 2017
As so often happens in the sciences, now that the initial euphoria has expended itself problems (and solutions) with CRISPR ((clustered regularly interspaced short palindromic repeats))-CAAS9 are being disclosed to those of us who are not experts. From an Oct. 3, 2017 article by Bob Yirka for phys.org,
A team of researchers from the University of California and the University of Tokyo has found a way to use the CRISPR gene editing technique that does not rely on a virus for delivery. In their paper published in the journal Nature Biomedical Engineering, the group describes the new technique, how well it works and improvements that need to be made to make it a viable gene editing tool.
CRISPR-Cas9 has been in the news a lot lately because it allows researchers to directly edit genes—either disabling unwanted parts or replacing them altogether. But despite many success stories, the technique still suffers from a major deficit that prevents it from being used as a true medical tool—it sometimes makes mistakes. Those mistakes can cause small or big problems for a host depending on what goes wrong. Prior research has suggested that the majority of mistakes are due to delivery problems, which means that a replacement for the virus part of the technique is required. In this new effort, the researchers report that they have discovered just a such a replacement, and it worked so well that it was able to repair a gene mutation in a Duchenne muscular dystrophy mouse model. The team has named the new technique CRISPR-Gold, because a gold nanoparticle was used to deliver the gene editing molecules instead of a virus.
An Oct. 2, 2017 article by Abby Olena for The Scientist lays out the CRISPR-CAS9 problems the scientists are trying to solve (Note: Links have been removed),
While promising, applications of CRISPR-Cas9 gene editing have so far been limited by the challenges of delivery—namely, how to get all the CRISPR parts to every cell that needs them. In a study published today (October 2) in Nature Biomedical Engineering, researchers have successfully repaired a mutation in the gene for dystrophin in a mouse model of Duchenne muscular dystrophy by injecting a vehicle they call CRISPR-Gold, which contains the Cas9 protein, guide RNA, and donor DNA, all wrapped around a tiny gold ball.
The authors have made “great progress in the gene editing area,” says Tufts University biomedical engineer Qiaobing Xu, who did not participate in the work but penned an accompanying commentary. Because their approach is nonviral, Xu explains, it will minimize the potential off-target effects that result from constant Cas9 activity, which occurs when users deliver the Cas9 template with a viral vector.
Duchenne muscular dystrophy is a degenerative disease of the muscles caused by a lack of the protein dystrophin. In about a third of patients, the gene for dystrophin has small deletions or single base mutations that render it nonfunctional, which makes this gene an excellent candidate for gene editing. Researchers have previously used viral delivery of CRISPR-Cas9 components to delete the mutated exon and achieve clinical improvements in mouse models of the disease.
“In this paper, we were actually able to correct [the gene for] dystrophin back to the wild-type sequence” via homology-directed repair (HDR), coauthor Niren Murthy, a drug delivery researcher at the University of California, Berkeley, tells The Scientist. “The other way of treating this is to do something called exon skipping, which is where you delete some of the exons and you can get dystrophin to be produced, but it’s not [as functional as] the wild-type protein.”
The research team created CRISPR-Gold by covering a central gold nanoparticle with DNA that they modified so it would stick to the particle. This gold-conjugated DNA bound the donor DNA needed for HDR, which the Cas9 protein and guide RNA bound to in turn. They coated the entire complex with a polymer that seems to trigger endocytosis and then facilitate escape of the Cas9 protein, guide RNA, and template DNA from endosomes within cells.
In order to do HDR, “you have to provide the cell [with] the Cas9 enzyme, guide RNA by which you target Cas9 to a particular part of the genome, and a big chunk of DNA, which will be used as a template to edit the mutant sequence to wild-type,” explains coauthor Irina Conboy, who studies tissue repair at the University of California, Berkeley. “They all have to be present at the same time and at the same place, so in our system you have a nanoparticle which simultaneously delivers all of those three key components in their active state.”
Olena’s article carries on to describe how the team created CRISPR-Gold and more.
Scientists at the University of California, Berkeley, have engineered a new way to deliver CRISPR-Cas9 gene-editing technology inside cells and have demonstrated in mice that the technology can repair the mutation that causes Duchenne muscular dystrophy, a severe muscle-wasting disease. A new study shows that a single injection of CRISPR-Gold, as the new delivery system is called, into mice with Duchenne muscular dystrophy led to an 18-times-higher correction rate and a two-fold increase in a strength and agility test compared to control groups.
CRISPR–Gold is composed of 15 nanometer gold nanoparticles that are conjugated to thiol-modified oligonucleotides (DNA-Thiol), which are hybridized with single-stranded donor DNA and subsequently complexed with Cas9 and encapsulated by a polymer that disrupts the endosome of the cell.
Since 2012, when study co-author Jennifer Doudna, a professor of molecular and cell biology and of chemistry at UC Berkeley, and colleague Emmanuelle Charpentier, of the Max Planck Institute for Infection Biology, repurposed the Cas9 protein to create a cheap, precise and easy-to-use gene editor, researchers have hoped that therapies based on CRISPR-Cas9 would one day revolutionize the treatment of genetic diseases. Yet developing treatments for genetic diseases remains a big challenge in medicine. This is because most genetic diseases can be cured only if the disease-causing gene mutation is corrected back to the normal sequence, and this is impossible to do with conventional therapeutics.
CRISPR/Cas9, however, can correct gene mutations by cutting the mutated DNA and triggering homology-directed DNA repair. However, strategies for safely delivering the necessary components (Cas9, guide RNA that directs Cas9 to a specific gene, and donor DNA) into cells need to be developed before the potential of CRISPR-Cas9-based therapeutics can be realized. A common technique to deliver CRISPR-Cas9 into cells employs viruses, but that technique has a number of complications. CRISPR-Gold does not need viruses.
In the new study, research lead by the laboratories of Berkeley bioengineering professors Niren Murthy and Irina Conboy demonstrated that their novel approach, called CRISPR-Gold because gold nanoparticles are a key component, can deliver Cas9 – the protein that binds and cuts DNA – along with guide RNA and donor DNA into the cells of a living organism to fix a gene mutation.
“CRISPR-Gold is the first example of a delivery vehicle that can deliver all of the CRISPR components needed to correct gene mutations, without the use of viruses,” Murthy said.
The study was published October 2  in the journal Nature Biomedical Engineering.
CRISPR-Gold repairs DNA mutations through a process called homology-directed repair. Scientists have struggled to develop homology-directed repair-based therapeutics because they require activity at the same place and time as Cas9 protein, an RNA guide that recognizes the mutation and donor DNA to correct the mutation.
To overcome these challenges, the Berkeley scientists invented a delivery vessel that binds all of these components together, and then releases them when the vessel is inside a wide variety of cell types, triggering homology directed repair. CRISPR-Gold’s gold nanoparticles coat the donor DNA and also bind Cas9. When injected into mice, their cells recognize a marker in CRISPR-Gold and then import the delivery vessel. Then, through a series of cellular mechanisms, CRISPR-Gold is released into the cells’ cytoplasm and breaks apart, rapidly releasing Cas9 and donor DNA.
CRISPR-Gold’s method of action (Click to enlarge).
A single injection of CRISPR-Gold into muscle tissue of mice that model Duchenne muscular dystrophy restored 5.4 percent of the dystrophin gene, which causes the disease, to the wild- type, or normal, sequence. This correction rate was approximately 18 times higher than in mice treated with Cas9 and donor DNA by themselves, which experienced only a 0.3 percent correction rate.
Importantly, the study authors note, CRISPR-Gold faithfully restored the normal sequence of dystrophin, which is a significant improvement over previously published approaches that only removed the faulty part of the gene, making it shorter and converting one disease into another, milder disease.
CRISPR-Gold was also able to reduce tissue fibrosis – the hallmark of diseases where muscles do not function properly – and enhanced strength and agility in mice with Duchenne muscular dystrophy. CRISPR-Gold-treated mice showed a two-fold increase in hanging time in a common test for mouse strength and agility, compared to mice injected with a control.
“These experiments suggest that it will be possible to develop non-viral CRISPR therapeutics that can safely correct gene mutations, via the process of homology-directed repair, by simply developing nanoparticles that can simultaneously encapsulate all of the CRISPR components,” Murthy said.
CRISPR in action: A model of the Cas9 protein cutting a double-stranded piece of DNA
The study found that CRISPR-Gold’s approach to Cas9 protein delivery is safer than viral delivery of CRISPR, which, in addition to toxicity, amplifies the side effects of Cas9 through continuous expression of this DNA-cutting enzyme. When the research team tested CRISPR-Gold’s gene-editing capability in mice, they found that CRISPR-Gold efficiently corrected the DNA mutation that causes Duchenne muscular dystrophy, with minimal collateral DNA damage.
The researchers quantified CRISPR-Gold’s off-target DNA damage and found damage levels similar to the that of a typical DNA sequencing error in a typical cell that was not exposed to CRISPR (0.005 – 0.2 percent). To test for possible immunogenicity, the blood stream cytokine profiles of mice were analyzed at 24 hours and two weeks after the CRISPR-Gold injection. CRISPR-Gold did not cause an acute up-regulation of inflammatory cytokines in plasma, after multiple injections, or weight loss, suggesting that CRISPR-Gold can be used multiple times safely, and that it has a high therapeutic window for gene editing in muscle tissue.
“CRISPR-Gold and, more broadly, CRISPR-nanoparticles open a new way for safer, accurately controlled delivery of gene-editing tools,” Conboy said. “Ultimately, these techniques could be developed into a new medicine for Duchenne muscular dystrophy and a number of other genetic diseases.”
A clinical trial will be needed to discern whether CRISPR-Gold is an effective treatment for genetic diseases in humans. Study co-authors Kunwoo Lee and Hyo Min Park have formed a start-up company, GenEdit (Murthy has an ownership stake in GenEdit), which is focused on translating the CRISPR-Gold technology into humans. The labs of Murthy and Conboy are also working on the next generation of particles that can deliver CRISPR into tissues from the blood stream and would preferentially target adult stem cells, which are considered the best targets for gene correction because stem and progenitor cells are capable of gene editing, self-renewal and differentiation.
“Genetic diseases cause devastating levels of mortality and morbidity, and new strategies for treating them are greatly needed,” Murthy said. “CRISPR-Gold was able to correct disease-causing gene mutations in vivo, via the non-viral delivery of Cas9 protein, guide RNA and donor DNA, and therefore has the potential to develop into a therapeutic for treating genetic diseases.”
The study was funded by the National Institutes of Health, the W.M. Keck Foundation, the Moore Foundation, the Li Ka Shing Foundation, Calico, Packer, Roger’s and SENS, and the Center of Innovation (COI) Program of the Japan Science and Technology Agency.
Here’s a link to and a citation for the paper,
Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homology-directed DNA repair by Kunwoo Lee, Michael Conboy, Hyo Min Park, Fuguo Jiang, Hyun Jin Kim, Mark A. Dewitt, Vanessa A. Mackley, Kevin Chang, Anirudh Rao, Colin Skinner, Tamanna Shobha, Melod Mehdipour, Hui Liu, Wen-chin Huang, Freeman Lan, Nicolas L. Bray, Song Li, Jacob E. Corn, Kazunori Kataoka, Jennifer A. Doudna, Irina Conboy, & Niren Murthy. Nature Biomedical Engineering (2017) doi:10.1038/s41551-017-0137-2 Published online: 02 October 2017
It seems a Swiss team from the École Polytechnique de Lausanne (EPFL) have collaborated with American companies Twist Bioscience and Microsoft, as well as, the University of Washington (state) to preserve two iconic jazz pieces on DNA (deoxyribonucleic acid) according to a Sept. 29, 2017 news item on phys.org,,
Thanks to an innovative technology for encoding data in DNA strands, two items of world heritage – songs recorded at the Montreux Jazz Festival [held in Switzerland] and digitized by EPFL – have been safeguarded for eternity. This marks the first time that cultural artifacts granted UNESCO heritage status have been saved in such a manner, ensuring they are preserved for thousands of years. The method was developed by US company Twist Bioscience and is being unveiled today in a demonstrator created at the EPFL+ECAL Lab.
“Tutu” by Miles Davis and “Smoke on the Water” by Deep Purple have already made their mark on music history. Now they have entered the annals of science, for eternity. Recordings of these two legendary songs were digitized by the Ecole Polytechnique Fédérale de Lausanne (EPFL) as part of the Montreux Jazz Digital Project, and they are the first to be stored in the form of a DNA sequence that can be subsequently decoded and listened to without any reduction in quality.
This feat was achieved by US company Twist Bioscience working in association with Microsoft Research and the University of Washington. The pioneering technology is actually based on a mechanism that has been at work on Earth for billions of years: storing information in the form of DNA strands. This fundamental process is what has allowed all living species, plants and animals alike, to live on from generation to generation.
The entire world wide web in a shoe box
All electronic data storage involves encoding data in binary format – a series of zeros and ones – and then recording it on a physical medium. DNA works in a similar way, but is composed of long strands of series of four nucleotides (A, T, C and G) that make up a “code.” While the basic principle may be the same, the two methods differ greatly in terms of efficiency: if all the information currently on the internet was stored in the form of DNA, it would fit in a shoe box!
Recent advances in biotechnology now make it possible for humans to do what Mother Nature has always done. Today’s scientists can create artificial DNA strands, “record” any kind of genetic code on them and then analyze them using a sequencer to reconstruct the original data. What’s more, DNA is extraordinarily stable, as evidenced by prehistoric fragments that have been preserved in amber. Artificial strands created by scientists and carefully encapsulated should likewise last for millennia.
To help demonstrate the feasibility of this new method, EPFL’s Metamedia Center provided recordings of two famous songs played at the Montreux Jazz Festival: “Tutu” by Miles Davis, and “Smoke on the Water” by Deep Purple. Twist Bioscience and its research partners encoded the recordings, transformed them into DNA strands and then sequenced and decoded them and played them again – without any reduction in quality.
The amount of artificial DNA strands needed to record the two songs is invisible to the naked eye, and the amount needed to record all 50 years of the Festival’s archives, which have been included in UNESCO’s [United Nations Educational, Scientific and Cultural Organization] Memory of the World Register, would be equal in size to a grain of sand. “Our partnership with EPFL in digitizing our archives aims not only at their positive exploration, but also at their preservation for the next generations,” says Thierry Amsallem, president of the Claude Nobs Foundation. “By taking part in this pioneering experiment which writes the songs into DNA strands, we can be certain that they will be saved on a medium that will never become obsolete!”
A new concept of time
At EPFL’s first-ever ArtTech forum, attendees got to hear the two songs played after being stored in DNA, using a demonstrator developed at the EPFL+ECAL Lab. The system shows that being able to store data for thousands of years is a revolutionary breakthrough that can completely change our relationship with data, memory and time. “For us, it means looking into radically new ways of interacting with cultural heritage that can potentially cut across civilizations,” says Nicolas Henchoz, head of the EPFL+ECAL Lab.
Quincy Jones, a longstanding Festival supporter, is particularly enthusiastic about this technological breakthrough: “With advancements in nanotechnology, I believe we can expect to see people living prolonged lives, and with that, we can also expect to see more developments in the enhancement of how we live. For me, life is all about learning where you came from in order to get where you want to go, but in order to do so, you need access to history! And with the unreliability of how archives are often stored, I sometimes worry that our future generations will be left without such access… So, it absolutely makes my soul smile to know that EPFL, Twist Bioscience and their partners are coming together to preserve the beauty and history of the Montreux Jazz Festival for our future generations, on DNA! I’ve been a part of this festival for decades and it truly is a magnificent representation of what happens when different cultures unite for the sake of music. Absolute magic. And I’m proud to know that the memory of this special place will never be lost.
Twist Bioscience, a company accelerating science and innovation through rapid, high-quality DNA synthesis, today announced that, working with Microsoft and University of Washington researchers, they have successfully stored archival-quality audio recordings of two important music performances from the archives of the world-renowned Montreux Jazz Festival.
These selections are encoded and stored in nature’s preferred storage medium, DNA, for the first time. These tiny specks of DNA will preserve a part of UNESCO’s Memory of the World Archive, where valuable cultural heritage collections are recorded. This is the first time DNA has been used as a long-term archival-quality storage medium.
Quincy Jones, world-renowned Entertainment Executive, Music Composer and Arranger, Musician and Music Producer said, “With advancements in nanotechnology, I believe we can expect to see people living prolonged lives, and with that, we can also expect to see more developments in the enhancement of how we live. For me, life is all about learning where you came from in order to get where you want to go, but in order to do so, you need access to history! And with the unreliability of how archives are often stored, I sometimes worry that our future generations will be left without such access…So, it absolutely makes my soul smile to know that EPFL, Twist Bioscience and others are coming together to preserve the beauty and history of the Montreux Jazz Festival for our future generations, on DNA!…I’ve been a part of this festival for decades and it truly is a magnificent representation of what happens when different cultures unite for the sake of music. Absolute magic. And I’m proud to know that the memory of this special place will never be lost.”
“Our partnership with EPFL in digitizing our archives aims not only at their positive exploration, but also at their preservation for the next generations,” says Thierry Amsallem, president of the Claude Nobs Foundation. “By taking part in this pioneering experiment which writes the songs into DNA strands, we can be certain that they will be saved on a medium that will never become obsolete!”
The Montreux Jazz Digital Project is a collaboration between the Claude Nobs Foundation, curator of the Montreux Jazz Festival audio-visual collection and the École Polytechnique Fédérale de Lausanne (EPFL) to digitize, enrich, store, show, and preserve this notable legacy created by Claude Nobs, the Festival’s founder.
In this proof-of-principle project, two quintessential music performances from the Montreux Jazz Festival – Smoke on the Water, performed by Deep Purple and Tutu, performed by Miles Davis – have been encoded onto DNA and read back with 100 percent accuracy. After being decoded, the songs were played on September 29th  at the ArtTech Forum (see below) in Lausanne, Switzerland. Smoke on the Water was selected as a tribute to Claude Nobs, the Montreux Jazz Festival’s founder. The song memorializes a fire and Funky Claude’srescue efforts at the Casino Barrière de Montreux during a Frank Zappa concert promoted by Claude Nobs. Miles Davis’ Tutu was selected for the role he played in music history and the Montreux Jazz Festival’s success. Miles Davis died in 1991.
“We archived two magical musical pieces on DNA of this historic collection, equating to 140MB of stored data in DNA,” said Karin Strauss, Ph.D., a Senior Researcher at Microsoft, and one of the project’s leaders. “The amount of DNA used to store these songs is much smaller than one grain of sand. Amazingly, storing the entire six petabyte Montreux Jazz Festival’s collection would result in DNA smaller than one grain of rice.”
Luis Ceze, Ph.D., a professor in the Paul G. Allen School of Computer Science & Engineering at the University of Washington, said, “DNA, nature’s preferred information storage medium, is an ideal fit for digital archives because of its durability, density and eternal relevance. Storing items from the Montreux Jazz Festival is a perfect way to show how fast DNA digital data storage is becoming real.”
Nature’s Preferred Storage Medium
Nature selected DNA as its hard drive billions of years ago to encode all the genetic instructions necessary for life. These instructions include all the information necessary for survival. DNA molecules encode information with sequences of discrete units. In computers, these discrete units are the 0s and 1s of “binary code,” whereas in DNA molecules, the units are the four distinct nucleotide bases: adenine (A), cytosine (C), guanine (G) and thymine (T).
“DNA is a remarkably efficient molecule that can remain stable for millennia,” said Bill Peck, Ph.D., chief technology officer of Twist Bioscience. “This is a very exciting project: we are now in an age where we can use the remarkable efficiencies of nature to archive master copies of our cultural heritage in DNA. As we develop the economies of this process new performances can be added any time. Unlike current storage technologies, nature’s media will not change and will remain readable through time. There will be no new technology to replace DNA, nature has already optimized the format.”
DNA: Far More Efficient Than a Computer
Each cell within the human body contains approximately three billion base pairs of DNA. With 75 trillion cells in the human body, this equates to the storage of 150 zettabytes (1021) of information within each body. By comparison, the largest data centers can be hundreds of thousands to even millions of square feet to hold a comparable amount of stored data.
The Elegance of DNA as a Storage Medium
Like music, which can be widely varied with a finite number of notes, DNA encodes individuality with only four different letters in varied combinations. When using DNA as a storage medium, there are several advantages in addition to the universality of the format and incredible storage density. DNA can be stable for thousands of years when stored in a cool dry place and is easy to copy using polymerase chain reaction to create back-up copies of archived material. In addition, because of PCR, small data sets can be targeted and recovered quickly from a large dataset without needing to read the entire file.
How to Store Digital Data in DNA
To encode the music performances into archival storage copies in DNA, Twist Bioscience worked with Microsoft and University of Washington researchers to complete four steps: Coding, synthesis/storage, retrieval and decoding. First, the digital files were converted from the binary code using 0s and 1s into sequences of A, C, T and G. For purposes of the example, 00 represents A, 10 represents C, 01 represents G and 11 represents T. Twist Bioscience then synthesizes the DNA in short segments in the sequence order provided. The short DNA segments each contain about 12 bytes of data as well as a sequence number to indicate their place within the overall sequence. This is the process of storage. And finally, to ensure that the file is stored accurately, the sequence is read back to ensure 100 percent accuracy, and then decoded from A, C, T or G into a two-digit binary representation.
Importantly, to encapsulate and preserve encoded DNA, the collaborators are working with Professor Dr. Robert Grass of ETH Zurich. Grass has developed an innovative technology inspired by preservation of DNA within prehistoric fossils. With this technology, digital data encoded in DNA remains preserved for millennia.
About UNESCO’s Memory of the World Register
UNESCO established the Memory of the World Register in 1992 in response to a growing awareness of the perilous state of preservation of, and access to, documentary heritage in various parts of the world. Through its National Commissions, UNESCO prepared a list of endangered library and archive holdings and a world list of national cinematic heritage.
A range of pilot projects employing contemporary technology to reproduce original documentary heritage on other media began. These included, for example, a CD-ROM of the 13th Century Radzivill Chronicle, tracing the origins of the peoples of Europe, and Memoria de Iberoamerica, a joint newspaper microfilming project involving seven Latin American countries. These projects enhanced access to this documentary heritage and contributed to its preservation.
“We are incredibly proud to be a part of this momentous event, with the first archived songs placed into the UNESCO Memory of the World Register,” said Emily Leproust, Ph.D., CEO of Twist Bioscience.
The ArtTech Foundation, created by renowned scientists and dignitaries from Crans-Montana, Switzerland, wishes to stimulate reflection and support pioneering and innovative projects beyond the known boundaries of culture and science.
Benefitting from the establishment of a favorable environment for the creation of technology companies, the Foundation aims to position itself as key promoter of ideas and innovative endeavors within a landscape of “Culture and Science” that is still being shaped.
Several initiatives, including our annual global platform launched in the spring of 2017, are helping to create a community that brings together researchers, celebrities in the world of culture and the arts, as well as investors and entrepreneurs from Switzerland and across the globe.
EPFL, one of the two Swiss Federal Institutes of Technology, based in Lausanne, is Europe’s most cosmopolitan technical university with students, professors and staff from over 120 nations. A dynamic environment, open to Switzerland and the world, EPFL is centered on its three missions: teaching, research and technology transfer. EPFL works together with an extensive network of partners including other universities and institutes of technology, developing and emerging countries, secondary schools and colleges, industry and economy, political circles and the general public, to bring about real impact for society.
About Twist Bioscience
At Twist Bioscience, our expertise is accelerating science and innovation by leveraging the power of scale. We have developed a proprietary semiconductor-based synthetic DNA manufacturing process featuring a high throughput silicon platform capable of producing synthetic biology tools, including genes, oligonucleotide pools and variant libraries. By synthesizing DNA on silicon instead of on traditional 96-well plastic plates, our platform overcomes the current inefficiencies of synthetic DNA production, and enables cost-effective, rapid, high-quality and high throughput synthetic gene production, which in turn, expedites the design, build and test cycle to enable personalized medicines, pharmaceuticals, sustainable chemical production, improved agriculture production, diagnostics and biodetection. We are also developing new technologies to address large scale data storage. For more information, please visit www.twistbioscience.com. Twist Bioscience is on Twitter. Sign up to follow our Twitter feed @TwistBioscience at https://twitter.com/TwistBioscience.
If you hadn’t read the EPFL press release first, it might have taken a minute to figure out why EPFL is being mentioned in the Twist Bioscience news release. Presumably someone was rushing to make a deadline. Ah well, I’ve seen and written worse.
I haven’t been able to find any video or audio recordings of the DNA-preserved performances but there is an informational video (originally published July 7, 2016) from Microsoft and the University of Washington describing the DNA-based technology,
I also found this description of listening to the DNA-preserved music in an Oct. 6, 2017 blog posting for the Canadian Broadcasting Corporation’s (CBC) Day 6 radio programme,
To listen to them, one must first suspend the DNA holding the songs in a solution. Next, one can use a DNA sequencer to read the letters of the bases forming the molecules. Then, algorithms can determine the digital code those letters form. From that code, comes the music.
It’s complicated but Ceze says his team performed this process without error.
After giving a basic explanation of the technology and some of the controversies in part 1 and offering more detail about the technology and about the possibility of designer babies in part 2; this part covers public discussion, a call for one and the suggestion that one is taking place in popular culture.
In early August 2017, an international team of scientists announced they had successfully edited the DNA of human embryos. As people process the political, moral and regulatory issues of the technology — which nudges us closer to nonfiction than science fiction — researchers at the University of Wisconsin-Madison and Temple University show the time is now to involve the American public in discussions about human genome editing.
In a study published Aug. 11 in the journal Science, the researchers assessed what people in the United States think about the uses of human genome editing and how their attitudes may drive public discussion. They found a public divided on its uses but united in the importance of moving conversations forward.
“There are several pathways we can go down with gene editing,” says UW-Madison’s Dietram Scheufele, lead author of the study and member of a National Academy of Sciences committee that compiled a report focused on human gene editing earlier this year. “Our study takes an exhaustive look at all of those possible pathways forward and asks where the public stands on each one of them.”
Compared to previous studies on public attitudes about the technology, the new study takes a more nuanced approach, examining public opinion about the use of gene editing for disease therapy versus for human enhancement, and about editing that becomes hereditary versus editing that does not.
The research team, which included Scheufele and Dominique Brossard — both professors of life sciences communication — along with Michael Xenos, professor of communication arts, first surveyed study participants about the use of editing to treat disease (therapy) versus for enhancement (creating so-called “designer babies”). While about two-thirds of respondents expressed at least some support for therapeutic editing, only one-third expressed support for using the technology for enhancement.
Diving even deeper, researchers looked into public attitudes about gene editing on specific cell types — somatic or germline — either for therapy or enhancement. Somatic cells are non-reproductive, so edits made in those cells do not affect future generations. Germline cells, however, are heritable, and changes made in these cells would be passed on to children.
Public support of therapeutic editing was high both in cells that would be inherited and those that would not, with 65 percent of respondents supporting therapy in germline cells and 64 percent supporting therapy in somatic cells. When considering enhancement editing, however, support depended more upon whether the changes would affect future generations. Only 26 percent of people surveyed supported enhancement editing in heritable germline cells and 39 percent supported enhancement of somatic cells that would not be passed on to children.
“A majority of people are saying that germline enhancement is where the technology crosses that invisible line and becomes unacceptable,” says Scheufele. “When it comes to therapy, the public is more open, and that may partly be reflective of how severe some of those genetically inherited diseases are. The potential treatments for those diseases are something the public at least is willing to consider.”
Beyond questions of support, researchers also wanted to understand what was driving public opinions. They found that two factors were related to respondents’ attitudes toward gene editing as well as their attitudes toward the public’s role in its emergence: the level of religious guidance in their lives, and factual knowledge about the technology.
Those with a high level of religious guidance in their daily lives had lower support for human genome editing than those with low religious guidance. Additionally, those with high knowledge of the technology were more supportive of it than those with less knowledge.
While respondents with high religious guidance and those with high knowledge differed on their support for the technology, both groups highly supported public engagement in its development and use. These results suggest broad agreement that the public should be involved in questions of political, regulatory and moral aspects of human genome editing.
“The public may be split along lines of religiosity or knowledge with regard to what they think about the technology and scientific community, but they are united in the idea that this is an issue that requires public involvement,” says Scheufele. “Our findings show very nicely that the public is ready for these discussions and that the time to have the discussions is now, before the science is fully ready and while we have time to carefully think through different options regarding how we want to move forward.”
Here’s a link to and a citation for the paper,
U.S. attitudes on human genome editing by Dietram A. Scheufele, Michael A. Xenos, Emily L. Howell, Kathleen M. Rose, Dominique Brossard1, and Bruce W. Hardy. Science 11 Aug 2017: Vol. 357, Issue 6351, pp. 553-554 DOI: 10.1126/science.aan3708
This paper is behind a paywall.
A couple of final comments
Briefly, I notice that there’s no mention of the ethics of patenting this technology in the news release about the study.
Moving on, it seems surprising that the first team to engage in germline editing in the US is in Oregon; I would have expected the work to come from Massachusetts, California, or Illinois where a lot of bleeding edge medical research is performed. However, given the dearth of financial support from federal funding institutions, it seems likely that only an outsider would dare to engage i the research. Given the timing, Mitalipov’s work was already well underway before the recent about-face from the US National Academy of Sciences (Note: Kaiser’s Feb. 14, 2017 article does note that for some the recent recommendations do not represent any change).
As for discussion on issues such as editing of the germline, I’ve often noted here that popular culture (including advertising with the science fiction and other dramas laid in various media) often provides an informal forum for discussion. Joelle Renstrom in an Aug. 13, 2017 article for slate.com writes that Orphan Black (a BBC America series featuring clones) opened up a series of questions about science and ethics in the guise of a thriller about clones. She offers a précis of the first four seasons (Note: A link has been removed),
If you stopped watching a few seasons back, here’s a brief synopsis of how the mysteries wrap up. Neolution, an organization that seeks to control human evolution through genetic modification, began Project Leda, the cloning program, for two primary reasons: to see whether they could and to experiment with mutations that might allow people (i.e., themselves) to live longer. Neolution partnered with biotech companies such as Dyad, using its big pharma reach and deep pockets to harvest people’s genetic information and to conduct individual and germline (that is, genetic alterations passed down through generations) experiments, including infertility treatments that result in horrifying birth defects and body modification, such as tail-growing.
She then provides the article’s thesis (Note: Links have been removed),
Orphan Black demonstrates Carl Sagan’s warning of a time when “awesome technological powers are in the hands of a very few.” Neolutionists do whatever they want, pausing only to consider whether they’re missing an opportunity to exploit. Their hubris is straight out of Victor Frankenstein’s playbook. Frankenstein wonders whether he ought to first reanimate something “of simpler organisation” than a human, but starting small means waiting for glory. Orphan Black’s evil scientists embody this belief: if they’re going to play God, then they’ll control not just their own destinies, but the clones’ and, ultimately, all of humanity’s. Any sacrifices along the way are for the greater good—reasoning that culminates in Westmoreland’s eugenics fantasy to genetically sterilize 99 percent of the population he doesn’t enhance.
Orphan Black uses sci-fi tropes to explore real-world plausibility. Neolution shares similarities with transhumanism, the belief that humans should use science and technology to take control of their own evolution. While some transhumanists dabble in body modifications, such as microchip implants or night-vision eye drops, others seek to end suffering by curing human illness and aging. But even these goals can be seen as selfish, as access to disease-eradicating or life-extending technologies would be limited to the wealthy. Westmoreland’s goal to “sell Neolution to the 1 percent” seems frighteningly plausible—transhumanists, who statistically tend to be white, well-educated, and male, and their associated organizations raise and spend massive sums of money to help fulfill their goals. …
On Orphan Black, denial of choice is tantamount to imprisonment. That the clones have to earn autonomy underscores the need for ethics in science, especially when it comes to genetics. The show’s message here is timely given the rise of gene-editing techniques such as CRISPR. Recently, the National Academy of Sciences gave germline gene editing the green light, just one year after academy scientists from around the world argued it would be “irresponsible to proceed” without further exploring the implications. Scientists in the United Kingdom and China have already begun human genetic engineering and American scientists recently genetically engineered a human embryo for the first time. The possibility of Project Leda isn’t farfetched. Orphan Black warns us that money, power, and fear of death can corrupt both people and science. Once that happens, loss of humanity—of both the scientists and the subjects—is inevitable.
In Carl Sagan’s dark vision of the future, “people have lost the ability to set their own agendas or knowledgeably question those in authority.” This describes the plight of the clones at the outset of Orphan Black, but as the series continues, they challenge this paradigm by approaching science and scientists with skepticism, ingenuity, and grit. …
I hope there are discussions such as those Scheufele and Brossard are advocating but it might be worth considering that there is already some discussion underway, as informal as it is.
Having included an explanation of CRISPR-CAS9 technology along with the news about the first US team to edit the germline and bits and pieces about ethics and a patent fight (part 1), this part hones in on the details of the work and worries about ‘designer babies’.
The interest flurry
I found three articles addressing the research and all three concur that despite some of the early reporting, this is not the beginning of a ‘designer baby’ generation.
MIT Technology Review reported Thursday that a team of researchers from Portland, Oregon were the first team of U.S.-based scientists to successfully create a genetically modified human embryo. The researchers, led by Shoukhrat Mitalipov of Oregon Health and Science University, changed the DNA of—in MIT Technology Review’s words—“many tens” of genetically-diseased embryos by injecting the host egg with CRISPR, a DNA-based gene editing tool first discovered in bacteria, at the time of fertilization. CRISPR-Cas9, as the full editing system is called, allows scientists to change genes accurately and efficiently. As has happened with research elsewhere, the CRISPR-edited embryos weren’t implanted—they were kept sustained for only a couple of days.
In addition to being the first American team to complete this feat, the researchers also improved upon the work of the three Chinese research teams that beat them to editing embryos with CRISPR: Mitalipov’s team increased the proportion of embryonic cells that received the intended genetic changes, addressing an issue called “mosaicism,” which is when an embryo is comprised of cells with different genetic makeups. Increasing that proportion is essential to CRISPR work in eliminating inherited diseases, to ensure that the CRISPR therapy has the intended result. The Oregon team also reduced the number of genetic errors introduced by CRISPR, reducing the likelihood that a patient would develop cancer elsewhere in the body.
Separate from the scientific advancements, it’s a big deal that this work happened in a country with such intense politicization of embryo research. …
But there are a great number of obstacles between the current research and the future of genetically editing all children to be 12-foot-tall Einsteins.
Ed Yong in an Aug. 2, 2017 article for The Atlantic offered a comprehensive overview of the research and its implications (unusually for Yong, there seems to be mildly condescending note but it’s worth ignoring for the wealth of information in the article; Note: Links have been removed),
… the full details of the experiment, which are released today, show that the study is scientifically important but much less of a social inflection point than has been suggested. “This has been widely reported as the dawn of the era of the designer baby, making it probably the fifth or sixth time people have reported that dawn,” says Alta Charo, an expert on law and bioethics at the University of Wisconsin-Madison. “And it’s not.”
Given the persistent confusion around CRISPR and its implications, I’ve laid out exactly what the team did, and what it means.
Who did the experiments?
Shoukhrat Mitalipov is a Kazakhstani-born cell biologist with a history of breakthroughs—and controversy—in the stem cell field. He was the scientist to clone monkeys. He was the first to create human embryos by cloning adult cells—a move that could provide patients with an easy supply of personalized stem cells. He also pioneered a technique for creating embryos with genetic material from three biological parents, as a way of preventing a group of debilitating inherited diseases.
Although MIT Tech Review name-checked Mitalipov alone, the paper splits credit for the research between five collaborating teams—four based in the United States, and one in South Korea.
What did they actually do?
The project effectively began with an elevator conversation between Mitalipov and his colleague Sanjiv Kaul. Mitalipov explained that he wanted to use CRISPR to correct a disease-causing gene in human embryos, and was trying to figure out which disease to focus on. Kaul, a cardiologist, told him about hypertrophic cardiomyopathy (HCM)—an inherited heart disease that’s commonly caused by mutations in a gene called MYBPC3. HCM is surprisingly common, affecting 1 in 500 adults. Many of them lead normal lives, but in some, the walls of their hearts can thicken and suddenly fail. For that reason, HCM is the commonest cause of sudden death in athletes. “There really is no treatment,” says Kaul. “A number of drugs are being evaluated but they are all experimental,” and they merely treat the symptoms. The team wanted to prevent HCM entirely by removing the underlying mutation.
They collected sperm from a man with HCM and used CRISPR to change his mutant gene into its normal healthy version, while simultaneously using the sperm to fertilize eggs that had been donated by female volunteers. In this way, they created embryos that were completely free of the mutation. The procedure was effective, and avoided some of the critical problems that have plagued past attempts to use CRISPR in human embryos.
Wait, other human embryos have been edited before?
There have been three attempts in China. The first two—in 2015 and 2016—used non-viable embryos that could never have resulted in a live birth. The third—announced this March—was the first to use viable embryos that could theoretically have been implanted in a womb. All of these studies showed that CRISPR gene-editing, for all its hype, is still in its infancy.
The editing was imprecise. CRISPR is heralded for its precision, allowing scientists to edit particular genes of choice. But in practice, some of the Chinese researchers found worrying levels of off-target mutations, where CRISPR mistakenly cut other parts of the genome.
The editing was inefficient. The first Chinese team only managed to successfully edit a disease gene in 4 out of 86 embryos, and the second team fared even worse.
The editing was incomplete. Even in the successful cases, each embryo had a mix of modified and unmodified cells. This pattern, known as mosaicism, poses serious safety problems if gene-editing were ever to be used in practice. Doctors could end up implanting women with embryos that they thought were free of a disease-causing mutation, but were only partially free. The resulting person would still have many tissues and organs that carry those mutations, and might go on to develop symptoms.
What did the American team do differently?
The Chinese teams all used CRISPR to edit embryos at early stages of their development. By contrast, the Oregon researchers delivered the CRISPR components at the earliest possible point—minutes before fertilization. That neatly avoids the problem of mosaicism by ensuring that an embryo is edited from the very moment it is created. The team did this with 54 embryos and successfully edited the mutant MYBPC3 gene in 72 percent of them. In the other 28 percent, the editing didn’t work—a high failure rate, but far lower than in previous attempts. Better still, the team found no evidence of off-target mutations.
This is a big deal. Many scientists assumed that they’d have to do something more convoluted to avoid mosaicism. They’d have to collect a patient’s cells, which they’d revert into stem cells, which they’d use to make sperm or eggs, which they’d edit using CRISPR. “That’s a lot of extra steps, with more risks,” says Alta Charo. “If it’s possible to edit the embryo itself, that’s a real advance.” Perhaps for that reason, this is the first study to edit human embryos that was published in a top-tier scientific journal—Nature, which rejected some of the earlier Chinese papers.
Is this kind of research even legal?
Yes. In Western Europe, 15 countries out of 22 ban any attempts to change the human germ line—a term referring to sperm, eggs, and other cells that can transmit genetic information to future generations. No such stance exists in the United States but Congress has banned the Food and Drug Administration from considering research applications that make such modifications. Separately, federal agencies like the National Institutes of Health are banned from funding research that ultimately destroys human embryos. But the Oregon team used non-federal money from their institutions, and donations from several small non-profits. No taxpayer money went into their work. [emphasis mine]
Why would you want to edit embryos at all?
Partly to learn more about ourselves. By using CRISPR to manipulate the genes of embryos, scientists can learn more about the earliest stages of human development, and about problems like infertility and miscarriages. That’s why biologist Kathy Niakan from the Crick Institute in London recently secured a license from a British regulator to use CRISPR on human embryos.
Isn’t this a slippery slope toward making designer babies?
In terms of avoiding genetic diseases, it’s not conceptually different from PGD, which is already widely used. The bigger worry is that gene-editing could be used to make people stronger, smarter, or taller, paving the way for a new eugenics, and widening the already substantial gaps between the wealthy and poor. But many geneticists believe that such a future is fundamentally unlikely because complex traits like height and intelligence are the work of hundreds or thousands of genes, each of which have a tiny effect. The prospect of editing them all is implausible. And since genes are so thoroughly interconnected, it may be impossible to edit one particular trait without also affecting many others.
“There’s the worry that this could be used for enhancement, so society has to draw a line,” says Mitalipov. “But this is pretty complex technology and it wouldn’t be hard to regulate it.”
Does this discovery have any social importance at all?
“It’s not so much about designer babies as it is about geographical location,” says Charo. “It’s happening in the United States, and everything here around embryo research has high sensitivity.” She and others worry that the early report about the study, before the actual details were available for scrutiny, could lead to unnecessary panic. “Panic reactions often lead to panic-driven policy … which is usually bad policy,” wrote Greely [bioethicist Hank Greely].
As I understand it, despite the change in stance, there is no federal funding available for the research performed by Mitalipov and his team.
Finally, University College London (UCL) scientists Joyce Harper and Helen O’Neill wrote about CRISPR, the Oregon team’s work, and the possibilities in an Aug. 3, 2017 essay for The Conversation (Note: Links have been removed),
The genome editing tool used, CRISPR-Cas9, has transformed the field of biology in the short time since its discovery in that it not only promises, but delivers. CRISPR has surpassed all previous efforts to engineer cells and alter genomes at a fraction of the time and cost.
The technology, which works like molecular scissors to cut and paste DNA, is a natural defence system that bacteria use to fend off harmful infections. This system has the ability to recognise invading virus DNA, cut it and integrate this cut sequence into its own genome – allowing the bacterium to render itself immune to future infections of viruses with similar DNA. It is this ability to recognise and cut DNA that has allowed scientists to use it to target and edit specific DNA regions.
When this technology is applied to “germ cells” – the sperm and eggs – or embryos, it changes the germline. That means that any alterations made would be permanent and passed down to future generations. This makes it more ethically complex, but there are strict regulations around human germline genome editing, which is predominantly illegal. The UK received a licence in 2016 to carry out CRISPR on human embryos for research into early development. But edited embryos are not allowed to be inserted into the uterus and develop into a fetus in any country.
Germline genome editing came into the global spotlight when Chinese scientists announced in 2015 that they had used CRISPR to edit non-viable human embryos – cells that could never result in a live birth. They did this to modify the gene responsible for the blood disorder β-thalassaemia. While it was met with some success, it received a lot of criticism because of the premature use of this technology in human embryos. The results showed a high number of potentially dangerous, off-target mutations created in the procedure.
The new study, published in Nature, is different because it deals with viable human embryos and shows that the genome editing can be carried out safely – without creating harmful mutations. The team used CRISPR to correct a mutation in the gene MYBPC3, which accounts for approximately 40% of the myocardial disease hypertrophic cardiomyopathy. This is a dominant disease, so an affected individual only needs one abnormal copy of the gene to be affected.
The researchers used sperm from a patient carrying one copy of the MYBPC3 mutation to create 54 embryos. They edited them using CRISPR-Cas9 to correct the mutation. Without genome editing, approximately 50% of the embryos would carry the patients’ normal gene and 50% would carry his abnormal gene.
After genome editing, the aim would be for 100% of embryos to be normal. In the first round of the experiments, they found that 66.7% of embryos – 36 out of 54 – were normal after being injected with CRIPSR. Of the remaining 18 embryos, five had remained unchanged, suggesting editing had not worked. In 13 embryos, only a portion of cells had been edited.
The level of efficiency is affected by the type of CRISPR machinery used and, critically, the timing in which it is put into the embryo. The researchers therefore also tried injecting the sperm and the CRISPR-Cas9 complex into the egg at the same time, which resulted in more promising results. This was done for 75 mature donated human eggs using a common IVF technique called intracytoplasmic sperm injection. This time, impressively, 72.4% of embryos were normal as a result. The approach also lowered the number of embryos containing a mixture of edited and unedited cells (these embryos are called mosaics).
Finally, the team injected a further 22 embryos which were grown into blastocyst – a later stage of embryo development. These were sequenced and the researchers found that the editing had indeed worked. Importantly, they could show that the level of off-target mutations was low.
A brave new world?
So does this mean we finally have a cure for debilitating, heritable diseases? It’s important to remember that the study did not achieve a 100% success rate. Even the researchers themselves stress that further research is needed in order to fully understand the potential and limitations of the technique.
In our view, it is unlikely that genome editing would be used to treat the majority of inherited conditions anytime soon. We still can’t be sure how a child with a genetically altered genome will develop over a lifetime, so it seems unlikely that couples carrying a genetic disease would embark on gene editing rather than undergoing already available tests – such as preimplantation genetic diagnosis or prenatal diagnosis – where the embryos or fetus are tested for genetic faults.
As might be expected there is now a call for public discussion about the ethics about this kind of work. See Part 3.
For anyone who started in the middle of this series, here’s Part 1 featuring an introduction to the technology and some of the issues.
There’s been a minor flurry of interest in CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats; also known as CRISPR-CAS9), a gene-editing technique, since a team in Oregon announced a paper describing their work editing the germline. Since I’ve been following the CRISPR-CAS9 story for a while this seems like a good juncture for a more in-depth look at the topic. In this first part I’m including an introduction to CRISPR, some information about the latest US work, and some previous writing about ethics issues raised when Chinese scientists first announced their work editing germlines in 2015 and during the patent dispute between the University of California at Berkeley and Harvard University’s Broad Institute.
Introduction to CRISPR
I’ve been searching for a good description of CRISPR and this helped to clear up some questions for me (Thank you to MIT Review),
For anyone who’s been reading about science for a while, this upbeat approach to explaining how a particular technology will solve all sorts of problems will seem quite familiar. It’s not the most hyperbolic piece I’ve seen but it barely mentions any problems associated with research (for some of the problems see: ‘The interest flurry’ later in part 2).
Steve Connor’s July 26, 2017 article for the MIT (Massachusetts Institute of Technology) Technology Review breaks the news (Note: Links have been removed),
The first known attempt at creating genetically modified human embryos in the United States has been carried out by a team of researchers in Portland, Oregon, MIT Technology Review has learned.
The effort, led by Shoukhrat Mitalipov of Oregon Health and Science University, involved changing the DNA of a large number of one-cell embryos with the gene-editing technique CRISPR, according to people familiar with the scientific results.
Until now, American scientists have watched with a combination of awe, envy, and some alarm as scientists elsewhere were first to explore the controversial practice. To date, three previous reports of editing human embryos were all published by scientists in China.
Now Mitalipov is believed to have broken new ground both in the number of embryos experimented upon and by demonstrating that it is possible to safely and efficiently correct defective genes that cause inherited diseases.
Although none of the embryos were allowed to develop for more than a few days—and there was never any intention of implanting them into a womb—the experiments are a milestone on what may prove to be an inevitable journey toward the birth of the first genetically modified humans.
In altering the DNA code of human embryos, the objective of scientists is to show that they can eradicate or correct genes that cause inherited disease, like the blood condition beta-thalassemia. The process is termed “germline engineering” because any genetically modified child would then pass the changes on to subsequent generations via their own germ cells—the egg and sperm.
Some critics say germline experiments could open the floodgates to a brave new world of “designer babies” engineered with genetic enhancements—a prospect bitterly opposed by a range of religious organizations, civil society groups, and biotech companies.
The U.S. intelligence community last year called CRISPR a potential “weapon of mass destruction.”
Here’s a link to a citation for the groundbreaking paper,
Correction of a pathogenic gene mutation in human embryos by Hong Ma, Nuria Marti-Gutierrez, Sang-Wook Park, Jun Wu, Yeonmi Lee, Keiichiro Suzuki, Amy Koski, Dongmei Ji, Tomonari Hayama, Riffat Ahmed, Hayley Darby, Crystal Van Dyken, Ying Li, Eunju Kang, A.-Reum Park, Daesik Kim, Sang-Tae Kim, Jianhui Gong, Ying Gu, Xun Xu, David Battaglia, Sacha A. Krieg, David M. Lee, Diana H. Wu, Don P. Wolf, Stephen B. Heitner, Juan Carlos Izpisua Belmonte, Paula Amato, Jin-Soo Kim, Sanjiv Kaul, & Shoukhrat Mitalipov. Nature (2017) doi:10.1038/nature23305 Published online 02 August 2017
This paper appears to be open access.
CRISPR Issues: ethics and patents
In my May 14, 2015 posting I mentioned a ‘moratorium’ on germline research, the Chinese research paper, and the stance taken by the US National Institutes of Health (NIH),
The CRISPR technology has reignited a discussion about ethical and moral issues of human genetic engineering some of which is reviewed in an April 7, 2015 posting about a moratorium by Sheila Jasanoff, J. Benjamin Hurlbut and Krishanu Saha for the Guardian science blogs (Note: A link has been removed),
On April 3, 2015, a group of prominent biologists and ethicists writing in Science called for a moratorium on germline gene engineering; modifications to the human genome that will be passed on to future generations. The moratorium would apply to a technology called CRISPR/Cas9, which enables the removal of undesirable genes, insertion of desirable ones, and the broad recoding of nearly any DNA sequence.
Such modifications could affect every cell in an adult human being, including germ cells, and therefore be passed down through the generations. Many organisms across the range of biological complexity have already been edited in this way to generate designer bacteria, plants and primates. There is little reason to believe the same could not be done with human eggs, sperm and embryos. Now that the technology to engineer human germlines is here, the advocates for a moratorium declared, it is time to chart a prudent path forward. They recommend four actions: a hold on clinical applications; creation of expert forums; transparent research; and a globally representative group to recommend policy approaches.
The authors go on to review precedents and reasons for the moratorium while suggesting we need better ways for citizens to engage with and debate these issues,
An effective moratorium must be grounded in the principle that the power to modify the human genome demands serious engagement not only from scientists and ethicists but from all citizens. We need a more complex architecture for public deliberation, built on the recognition that we, as citizens, have a duty to participate in shaping our biotechnological futures, just as governments have a duty to empower us to participate in that process. Decisions such as whether or not to edit human genes should not be left to elite and invisible experts, whether in universities, ad hoc commissions, or parliamentary advisory committees. Nor should public deliberation be temporally limited by the span of a moratorium or narrowed to topics that experts deem reasonable to debate.
I recommend reading the post in its entirety as there are nuances that are best appreciated in the entirety of the piece.
Shortly after this essay was published, Chinese scientists announced they had genetically modified (nonviable) human embryos. From an April 22, 2015 article by David Cyranoski and Sara Reardon in Nature where the research and some of the ethical issues discussed,
In a world first, Chinese scientists have reported editing the genomes of human embryos. The results are published1 in the online journal Protein & Cell and confirm widespread rumours that such experiments had been conducted — rumours that sparked a high-profile debate last month2, 3 about the ethical implications of such work.
In the paper, researchers led by Junjiu Huang, a gene-function researcher at Sun Yat-sen University in Guangzhou, tried to head off such concerns by using ‘non-viable’ embryos, which cannot result in a live birth, that were obtained from local fertility clinics. The team attempted to modify the gene responsible for β-thalassaemia, a potentially fatal blood disorder, using a gene-editing technique known as CRISPR/Cas9. The researchers say that their results reveal serious obstacles to using the method in medical applications.
“I believe this is the first report of CRISPR/Cas9 applied to human pre-implantation embryos and as such the study is a landmark, as well as a cautionary tale,” says George Daley, a stem-cell biologist at Harvard Medical School in Boston, Massachusetts. “Their study should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes.”
Huang says that the paper was rejected by Nature and Science, in part because of ethical objections; both journals declined to comment on the claim. (Nature’s news team is editorially independent of its research editorial team.)
He adds that critics of the paper have noted that the low efficiencies and high number of off-target mutations could be specific to the abnormal embryos used in the study. Huang acknowledges the critique, but because there are no examples of gene editing in normal embryos he says that there is no way to know if the technique operates differently in them.
Still, he maintains that the embryos allow for a more meaningful model — and one closer to a normal human embryo — than an animal model or one using adult human cells. “We wanted to show our data to the world so people know what really happened with this model, rather than just talking about what would happen without data,” he says.
This, too, is a good and thoughtful read.
There was an official response in the US to the publication of this research, from an April 29, 2015 post by David Bruggeman on his Pasco Phronesis blog (Note: Links have been removed),
In light of Chinese researchers reporting their efforts to edit the genes of ‘non-viable’ human embryos, the National Institutes of Health (NIH) Director Francis Collins issued a statement (H/T Carl Zimmer).
“NIH will not fund any use of gene-editing technologies in human embryos. The concept of altering the human germline in embryos for clinical purposes has been debated over many years from many different perspectives, and has been viewed almost universally as a line that should not be crossed. Advances in technology have given us an elegant new way of carrying out genome editing, but the strong arguments against engaging in this activity remain. These include the serious and unquantifiable safety issues, ethical issues presented by altering the germline in a way that affects the next generation without their consent, and a current lack of compelling medical applications justifying the use of CRISPR/Cas9 in embryos.” …
The US has modified its stance according to a February 14, 2017 article by Jocelyn Kaiser for Science Magazine (Note: Links have been removed),
Editing the DNA of a human embryo to prevent a disease in a baby could be ethically allowable one day—but only in rare circumstances and with safeguards in place, says a widely anticipated report released today.
The report from an international committee convened by the U.S. National Academy of Sciences (NAS) and the National Academy of Medicine in Washington, D.C., concludes that such a clinical trial “might be permitted, but only following much more research” on risks and benefits, and “only for compelling reasons and under strict oversight.” Those situations could be limited to couples who both have a serious genetic disease and for whom embryo editing is “really the last reasonable option” if they want to have a healthy biological child, says committee co-chair Alta Charo, a bioethicist at the University of Wisconsin in Madison.
Some researchers are pleased with the report, saying it is consistent with previous conclusions that safely altering the DNA of human eggs, sperm, or early embryos—known as germline editing—to create a baby could be possible eventually. “They have closed the door to the vast majority of germline applications and left it open for a very small, well-defined subset. That’s not unreasonable in my opinion,” says genome researcher Eric Lander of the Broad Institute in Cambridge, Massachusetts. Lander was among the organizers of an international summit at NAS in December 2015 who called for more discussion before proceeding with embryo editing.
But others see the report as lowering the bar for such experiments because it does not explicitly say they should be prohibited for now. “It changes the tone to an affirmative position in the absence of the broad public debate this report calls for,” says Edward Lanphier, chairman of the DNA editing company Sangamo Therapeutics in Richmond, California. Two years ago, he co-authored a Nature commentary calling for a moratorium on clinical embryo editing.
One advocacy group opposed to embryo editing goes further. “We’re very disappointed with the report. It’s really a pretty dramatic shift from the existing and widespread agreement globally that human germline editing should be prohibited,” says Marcy Darnovsky, executive director of the Center for Genetics and Society in Berkeley, California.
Interestingly, this change of stance occurred just prior to a CRISPR patent decision (from my March 15, 2017 posting),
I have written about the CRISPR patent tussle (Harvard & MIT’s [Massachusetts Institute of Technology] Broad Institute vs the University of California at Berkeley) previously in a Jan. 6, 2015 posting and in a more detailed May 14, 2015 posting. I also mentioned (in a Jan. 17, 2017 posting) CRISPR and its patent issues in the context of a posting about a Slate.com series on Frankenstein and the novel’s applicability to our own time. This patent fight is being bitterly fought as fortunes are at stake.
It seems a decision has been made regarding the CRISPR patent claims. From a Feb. 17, 2017 article by Charmaine Distor for The Science Times,
After an intense court battle, the US Patent and Trademark Office (USPTO) released its ruling on February 15 . The rights for the CRISPR-Cas9 gene editing technology was handed over to the Broad Institute of Harvard University and the Massachusetts Institute of Technology (MIT).
According to an article in Nature, the said court battle was between the Broad Institute and the University of California. The two institutions are fighting over the intellectual property right for the CRISPR patent. The case between the two started when the patent was first awarded to the Broad Institute despite having the University of California apply first for the CRISPR patent.
Heidi Ledford’s Feb. 17, 2017 article for Nature provides more insight into the situation (Note: Links have been removed),
It [USPTO] ruled that the Broad Institute of Harvard and MIT in Cambridge could keep its patents on using CRISPR–Cas9 in eukaryotic cells. That was a blow to the University of California in Berkeley, which had filed its own patents and had hoped to have the Broad’s thrown out.
The fight goes back to 2012, when Jennifer Doudna at Berkeley, Emmanuelle Charpentier, then at the University of Vienna, and their colleagues outlined how CRISPR–Cas9 could be used to precisely cut isolated DNA1. In 2013, Feng Zhang at the Broad and his colleagues — and other teams — showed2 how it could be adapted to edit DNA in eukaryotic cells such as plants, livestock and humans.
Berkeley filed for a patent earlier, but the USPTO granted the Broad’s patents first — and this week upheld them. There are high stakes involved in the ruling. The holder of key patents could make millions of dollars from CRISPR–Cas9’s applications in industry: already, the technique has sped up genetic research, and scientists are using it to develop disease-resistant livestock and treatments for human diseases.
I also noted this eyebrow-lifting statistic, “As for Ledford’s 3rd point, there are an estimated 763 patent families (groups of related patents) claiming CAS9 leading to the distinct possibility that the Broad Institute will be fighting many patent claims in the future.)
Using this new sunscreen does mean slathering on salmon sperm, more or lees, (read the Methods section of the academic paper cited later in this post). Considering that you’ve likely eaten (insect parts in chocolate) and slathered on more discomfiting stuff already and this development gives you access to an all natural, highly effective sunscreen, if it ever makes its way out of the laboratory, it might not be so bad. From a July 26, 2017 article by Sarah Knapton for The Telegraph,
Sunscreen made from DNA [deoxyribonucleic acid] which acts like a second skin to prevent sun damage is on the horizon.
Scientists in the US have developed a film from the DNA of salmon which gets better at protecting the skin from ultraviolet light the more it is exposed to the Sun.
It also helps lock in moisture beneath the surface which is usually lost during tanning.
“Ultraviolet (UV) light can actually damage DNA, and that’s not good for the skin,” said Guy German, assistant professor of biomedical engineering at Binghamton University. “We thought, let’s flip it. What happens instead if we actually used DNA as a sacrificial layer? So instead of damaging DNA within the skin, we damage a layer on top of the skin.”
German and a team of researchers developed thin and optically transparent crystalline DNA films and irradiated them with UV light. They found that the more they exposed the film to UV light, the better the film got at absorbing it.
“If you translate that, it means to me that if you use this as a topical cream or sunscreen, the longer that you stay out on the beach, the better it gets at being a sunscreen,” said German.
As an added bonus, the DNA coatings are also hygroscopic, meaning that skin coated with the DNA films can store and hold water much more than uncoated skin. When applied to human skin, they are capable of slowing water evaporation and keeping the tissue hydrated for extended periods of time.
German intends to see next if these materials might be good as a wound covering for hostile environments where 1) you want to be able to see the wound healing without removing the dressing, 2) you want to protect the wound from the sun and 3) you want to keep the wound in a moist environment, known to promote faster wound healing rates.
“Not only do we think this might have applications for sunscreen and moisturizers directly, but if it’s optically transparent and prevents tissue damage from the sun and it’s good at keeping the skin hydrated, we think this might be potentially exploitable as a wound covering for extreme environments,” he said.
Years ago I worked as a publicist for the BC (British Columbia) Motorcycle Federation’s Ride for Sight; they were raising funds for research into retinitis pigmentosa (RP). I hadn’t thought about that in years but it all came back when I saw this April 21, 2017 news item on ScienceDaily,
Using the gene-editing tool CRISPR/Cas9, researchers at University of California San Diego [UCSD] School of Medicine and Shiley Eye Institute at UC San Diego Health, with colleagues in China, have reprogrammed mutated rod photoreceptors to become functioning cone photoreceptors, reversing cellular degeneration and restoring visual function in two mouse models of retinitis pigmentosa.
Caption: This is a confocal micrograph of mouse retina depicting optic fiber layer. Credit: Image courtesy of National Center for Microscopy and Imaging Research, UC San Diego.
Retinitis pigmentosa (RP) is a group of inherited vision disorders caused by numerous mutations in more than 60 genes. The mutations affect the eyes’ photoreceptors, specialized cells in the retina that sense and convert light images into electrical signals sent to the brain. There are two types: rod cells that function for night vision and peripheral vision, and cone cells that provide central vision (visual acuity) and discern color. The human retina typically contains 120 million rod cells and 6 million cone cells.
In RP, which affects approximately 100,000 Americans and 1 in 4,000 persons worldwide, rod-specific genetic mutations cause rod photoreceptor cells to dysfunction and degenerate over time. Initial symptoms are loss of peripheral and night vision, followed by diminished visual acuity and color perception as cone cells also begin to fail and die. There is no treatment for RP. The eventual result may be legal blindness.
In their published research, a team led by senior author Kang Zhang, MD, PhD, chief of ophthalmic genetics, founding director of the Institute for Genomic Medicine and co-director of biomaterials and tissue engineering at the Institute of Engineering in Medicine, both at UC San Diego School of Medicine, used CRISPR/Cas9 to deactivate a master switch gene called Nrl and a downstream transcription factor called Nr2e3.
CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, allows researchers to target specific stretches of genetic code and edit DNA at precise locations, modifying select gene functions. Deactivating either Nrl or Nr2e3 reprogrammed rod cells to become cone cells.
“Cone cells are less vulnerable to the genetic mutations that cause RP,” said Zhang. “Our strategy was to use gene therapy to make the underlying mutations irrelevant, resulting in the preservation of tissue and vision.”
The scientists tested their approach in two different mouse models of RP. In both cases, they found an abundance of reprogrammed cone cells and preserved cellular architecture in the retinas. Electroretinography testing of rod and cone receptors in live mice show improved function.
Zhang said a recent independent study led by Zhijian Wu, PhD, at National Eye Institute, part of the National Institutes of Health, also reached similar conclusions.
The researchers used adeno-associated virus (AAV) to perform the gene therapy, which they said should help advance their work to human clinical trials quicker. “AAV is a common cold virus and has been used in many successful gene therapy treatments with a relatively good safely profile,” said Zhang. “Human clinical trials could be planned soon after completion of preclinical study. There is no treatment for RP so the need is great and pressing. In addition, our approach of reprogramming mutation-sensitive cells to mutation-resistant cells may have broader application to other human diseases, including cancer.”
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,
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.
IBM Global Entrepreneur
Softlayer – an IBM Company
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
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 , 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’.
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.
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.
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.