September 29, 2015
University of Washington
Earth-like planets orbiting close to small stars probably have magnetic fields that protect them from stellar radiation and help maintain surface conditions that could be conducive to life, according to research from astronomers.
Earth-like planets orbiting close to small stars probably have magnetic fields that protect them from stellar radiation and help maintain surface conditions that could be conducive to life, according to research from astronomers at the University of Washington.
A planet’s magnetic field emanates from its core and is thought to deflect the charged particles of the stellar wind, protecting the atmosphere from being lost to space. Magnetic fields, born from the cooling of a planet’s interior, could also protect life on the surface from harmful radiation, as Earth’s magnetic field protects us.
Low-mass stars are among the most common in the universe. Planets orbiting near such stars are easier for astronomers to target for study because when they transit, or pass in front of, their host star, they block a larger fraction of the light than if they transited a more massive star. But because such a star is small and dim, its habitable zone — where an orbiting planet gets the heat necessary to maintain life-friendly liquid water on the surface — also lies relatively close in.
And a planet so close to its star is subject to the star’s powerful gravitational pull, which could cause it to become tidally locked, with the same side forever facing its host star, as the moon is with Earth. That same gravitational tug from the star also creates tidally generated heat inside the planet, or tidal heating. Tidal heating is responsible for driving the most volcanically active body in our solar system, Jupiter’s moon Io.
In a paper published Sept. 22 in the journal Astrobiology, lead author Peter Driscoll sought to determine the fate of such worlds across time: “The question I wanted to ask is, around these small stars, where people are going to look for planets, are these planets going to be roasted by gravitational tides?” He was curious, too, about the effect of tidal heating on magnetic fields across long periods of time.
The research combined models of orbital interactions and heating by Rory Barnes, assistant professor of astronomy, with those of thermal evolution of planetary interiors done by Driscoll, who began this work as a UW postdoctoral fellow and is now a geophysicist at the Carnegie Institution for Science in Washington, D.C.
Their simulations ranged from one stellar mass — stars the size of our sun — down to about one-tenth of that size. By merging their models, they were able, Barnes said, “to produce a more realistic picture of what is happening inside these planets.”
Barnes said there has been a general feeling in the astronomical community that tidally locked planets are unlikely to have protective magnetic fields “and therefore are completely at the mercy of their star.” This research suggests that assumption false.
Far from being harmful to a planet’s magnetic field, tidal heating can actually help it along — and in doing so also help the chance for habitability.
This is because of the somewhat counterintuitive fact that the more tidal heating a planetary mantle experiences, the better it is at dissipating its heat, thereby cooling the core, which in turn helps create the magnetic field.
Barnes said that in computer simulations they were able to generate magnetic fields for the lifetimes of these planets, in most cases. “I was excited to see that tidal heating can actually save a planet in the sense that it allows cooling of the core. That’s the dominant way to form magnetic fields.”
And since small or low mass stars are particularly active early in their lives — for the first few billion years or so — “magnetic fields can exist precisely when life needs them the most.”
Driscoll and Barnes also found through orbital calculations that the tidal heating process is more extreme for planets in the habitable zone around very small stars, or those less than half the mass of the sun.
For planets in eccentric, or noncircular orbits around such low mass stars, they found that these orbits tend to become more circular during the time of extreme tidal heating. Once that circularization takes place, the planet stops experiencing any tidal heating at all. The research was done through the Virtual Planetary Laboratory, a UW-based interdisciplinary research group funded through the NASA Astrobiology Institute. “These preliminary results are promising, but we still don’t know how they would change for a planet like Venus, where slow planetary cooling is already hindering magnetic field generation,” Driscoll said. “In the future, exoplanetary magnetic fields could be observable, so we expect there to be a growing interest in this field going forward.”
- P.E. Driscoll, R. Barnes. Tidal Heating of Earth-like Exoplanets around M Stars: Thermal, Magnetic, and Orbital Evolutions. Astrobiology, 2015; 15 (9): 739 DOI:10.1089/ast.2015.1325
Source: University of Washington. “Earth-like planets around small stars likely have protective magnetic fields, aiding chance for life.” ScienceDaily. ScienceDaily, 29 September 2015. <www.sciencedaily.com/releases/2015/09/150929070703.htm>.
Temperature over Antarctica had profound impacts on ocean circulation and carbon uptake
September 28, 2015
University of New South Wales
Changes to overturning circulation in the Southern Ocean as a result of temperatures over Antarctica play key role in carbon uptake by the oceans.
Scientists have struggled for the past few decades to understand why air temperatures around Antarctica over the past one million years were almost perfectly in synch with atmospheric CO2concentrations. Both dipped down during glacial ice ages and back up again during warm interglacials.
By contrast, temperatures in the tropics and Northern Hemisphere were less closely tied to atmospheric CO2concentrations.
“This relationship between Antarctica temperature and CO2suggested that somehow the Southern Ocean was pivotal in controlling natural atmospheric CO2 concentrations,” said Dr Maxim Nikurashin from the ARC Centre of Excellence for Climate System Science.
“The key that unlocked the mystery was the colder atmosphere and extensive sea ice around Antarctica during the glacial period. Together they fundamentally changed top to bottom ocean circulation and enabled more CO2 to be drawn from the atmosphere.”
The researchers found that during glacial periods when the atmosphere was colder and sea ice was far more extensive, deep ocean waters came to the surface much further north of the Antarctic continent than they do today.
This meant that the nutrients brought up from the bottom of the ocean spent more time on the surface of the ocean as the currents moved them southwards before the flow encountered Antarctica and circled back down to the bottom of the ocean.
Because the upwelled waters ran along the surface for a longer period of time, nutrients spent more time near the surface of the ocean where phytoplankton could feed on them for longer.
The biological processes that result from phytoplankton blooms directly take carbon out of the atmosphere. Some of this carbon then sinks to the bottom of the ocean when the phytoplankton die, locking it away in the deep sea for thousands of years.
“The biological processes that take up carbon from the atmosphere even take place in and under the ice — if that ice is not too thick — which is why the biological processes persisted for a lot longer during cooler periods,” the authors said.
“Our results suggest that this change in circulation and the consequent extended biological activity by itself took 30-60ppm of CO2 out of the atmosphere. That’s about one half of the glacial-interglacial change.”
However, when temperatures warm over the Antarctic regions, deep waters rise from the floor of the ocean much closer to the continent. This means nutrients are near the surface for a shorter time before returning to the deep ocean floor.
With less time on the surface there is less time for the biological processes to take place and less carbon is taken out of the atmosphere. This is the situation we see today.
“This finding is a major advance in understanding the natural carbon cycle, gained by applying a new understanding about how the “overturning circulation” of the Southern Ocean works,” said lead author Dr Andrew J Watson from the University of Exeter.
- Andrew J. Watson, Geoffrey K. Vallis, Maxim Nikurashin.Southern Ocean buoyancy forcing of ocean ventilation and glacial atmospheric CO2. Nature Geoscience, 2015; DOI: 10.1038/ngeo2538
Source: University of New South Wales. “How ocean circulation changed atmospheric CO2: Temperature over Antarctica had profound impacts on ocean circulation and carbon uptake.” ScienceDaily. ScienceDaily, 28 September 2015. <www.sciencedaily.com/releases/2015/09/150928123434.htm>.
PharmaVOICE 100 Honors Jules Mitchel as Commander and Chief
For the second year in a row, PharmaVOICE has honored Dr. Jules Mitchel, President of Target Health as a PharmaVOICE 100. Last year he was honored as a leading Entrepreneur and this year as a Commander and Chief. At the DIA meeting this year, Taren Grom, Founding Partner of PharmaVOICE interviewed Dr. Mitchel on his views of the future of the pharmaceutical industry, an industry that he loves.
New York Times Highlights Dr. David Filer – Target Health
From left, Robert E. Woods, James F. Fallon, Andrew Dahl and David Filer at Ali Baba’s Terrace in Manhattan. Credit Nicole Craine for The New York Times
NYT (September 25, 2015) In the seats are four men having a business lunch: James F. Fallon, 53, who runs the New York-based investor relations firm CEOcast; Robert E. Woods, 69, who is with the same firm; David Filer, 67, of Target Health, a New York-based company that runs clinical trials for biotech and pharmaceutical companies; and Andrew Dahl, 59, president and chief executive of the biotech company Zivo Bioscience, in Keego Harbor, Mich. All four ordered the $17.95 lunch special, which included an appetizer and an entree. Among the dishes sampled: a chicken-and-vegetable soup seasoned with lemon juice; spinach tarator, a yogurt dip; lahana dolmasi, cabbage stuffed with a mixture of ground beef and lamb; chicken adana kebabs, made with meat that is minced and flavored with red peppers and paprika; and a gyro kebab. To finish, Ali Riza Dogan, the restaurant’s owner, sent the men a round of Turkish tea and a plate of baklava with his compliments because Dr. Filer is a longtime regular.
WHY THEY CAME: Mr. Dahl had hired Mr. Fallon’s firm to help find potential investors, and the lunch was an opportunity for Mr. Dahl to meet Dr. Filer, who was one. Mr. Dahl had flown in from Detroit that morning, and it was the first of several meetings that Mr. Fallon’s firm had scheduled for him over the course of the week. They chose Ali Baba’s Terrace at Dr. Filer’s suggestion.
ON TARGET is the newsletter of Target Health Inc., a NYC – based, full – service, contract research organization (eCRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services to the pharmaceutical and device industries, including the paperless clinical trial.
For more information about Target Health contact Warren Pearlson (212 – 681 – 2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.
Joyce Hays, Founder and Editor in Chief of On Target
Jules Mitchel, Editor
Now You Can Afford to Map Your Genome
A gene is a locus (or region) of DNA that encodes a functional RNA or protein product, and is the molecular unit of heredity. The transmission of genes to an organism’s offspring is the basis of the inheritance of phenotypic traits.
A company formed by genome pioneer Craig Venter will offer clients of a South Africa – based insurance company whole exome sequencing – sequencing all protein – making genes in the human 1) ___ – at a price that marks yet another dramatic decline in the cost of gene sequencing, the two companies said on Tuesday. Venter’s company, Human Longevity Inc, will provide the tests at a cost of $250 each through a special incentive program offered by Discovery Ltd, an insurer with clients in South Africa and the United Kingdom. Venter, the U.S. scientist who raced the U.S. government to map the human genome 15 years ago for a cost of $100,000, said the $250 price point per whole exome marks a new low in the price of 2) ___ sequencing. It’s our goal to really make this 3) ___ available to broad populations, he said in a telephone interview. The multiyear deal gives Discovery’s clients access to low – cost whole exome sequencing, tests that look only at the protein – making segments of DNA known as exons, which represent 2% of the genome but account for 85% of disease – causing 4) ___. The deal also covers testing for whole genome and cancer genome sequencing services. Financial terms were not disclosed.
Until recently, whole genome sequencing – which 5) ___ all of an individual’s 20,500 genes – was prohibitively expensive, costing about $20,000 just five years ago. As of last year, the average cost of whole genome sequencing fell to $1,500. Whole exome sequencing costs range from $400 to $1,500, plus extra charges for analyzing the results. For insurance company Discovery, exome sequencing will be offered through a behavioral wellness program that provides clients with tools and incentives to make lifestyle changes to help them stay 6) ___. Discovery clients who choose exome screening will receive a comprehensive report detailing their risks for specific 7) ___ and potential strategies to modify those risks. Discovery will provide the reports to clients through a network of physicians and genetic counselors.
Venter’s company, which is based in San Diego, will receive de – identified data from participating Discovery clients, which it will use to build its library of 8) ___ and health information. Such data is becoming highly prized by pharmaceutical companies as a faster means of drug research. Last January, Human Longevity signed a multiyear deal to sequence and analyze tens of thousands of genomes for Roche Holding’s Genentech unit in an effort aimed at identifying new 9) ___ targets and biomarkers.
ANSWERS: genome; 2) gene; 3) sequencing; 4) mutations; 5) maps; 6) healthy; 7) diseases; 8) genetic; 9) drug
Craig Venter, A Force of Nature
J. Craig Venter (1946 to present)
Editor’s note: This history of medicine piece is longer than usual, because like the article on (the great) Oliver Sacks, Craig Venter is another highly unusual person, who spent the first part of his life pursuing interests that no one could have predicted, would lead to global contributions of the first order. Individuals like these two, don’t come along often. For those readers who look forward to history of medicine each week, we guarantee a highly interesting, read:
Genomic entrepreneur, J. Craig Venter, plans to sell genetic workups for as little as $250; however, $25,000 gets you a physical on steroids.
Companies are looking for ways to get consumers interested in their genes.
Fifteen years ago, scientific instigator J. Craig Venter spent $100 million to race the government and sequence a human genome, which turned out to be his own. Now, with a South African health insurer, Venter says he will sequence the medically important genes of its clients for just $250. Human Longevity Inc. (HLI), the startup Venter launched in La Jolla, California, 18 months ago, now operates what’s touted as the world’s largest DNA – sequencing lab. It aims to tackle one million genomes inside of four years, in order to create a giant private database of DNA and medical records. In a step toward building the data trove, Venter’s company says it has formed an agreement with the South African insurer Discovery to partially decode the genomes of its customers, returning the information as part of detailed health reports. The deal is a salvo in the widening battle to try to bring DNA data to consumers through novel avenues and by subsidizing the cost of sequencing. It appears to be the first major deal with an insurer to offer wide access to genetic information on a commercial basis.
Jonathan Broomberg, chief executive of Discovery Health, which insures four million people in South Africa and the United Kingdom, says the genome service will be made available as part of a wellness program and that Discovery will pay half the $250, with individual clients covering the rest. Gene data would be returned to doctors or genetic counselors, not directly to individuals. The data collected, called an exome, is about 2% of the genome, but includes nearly all genes, including major cancer risk factors like the BRCA genes, as well as susceptibility factors for conditions such as colon cancer and heart disease. Typically, the BRCA test on its own costs anywhere from $400 to $4,000. I hope that we get a real breakthrough in the field of personalized wellness, Broomberg says. My fear would be that people are afraid of this and don’t want the information – or that even at this price point, it’s still too expensive. But we’re optimistic. He says he expects as many as 100,000 people to join over several years.
Venter founded Human Longevity with Rob Hariri and Peter Diamandis (see Microbes and Metabolites Fuel an Ambitious Aging Project), primarily to amass the world’s largest database of human genetic and medical information. The hope is to use it to tease out the roles of genes in all diseases, allow accurate predictions about people’s health risks, and suggest ways to avoid those problems. My view is that we know less than 1% of the useful information in the human genome, says Venter. The company this year began accumulating genomes by offering to sequence them for partners including Genentech and the Cleveland Clinic, which need the data for research. Venter said HLI keeps a de – identified copy along with information about patients’ health. HLI will also retain copies of the South Africans’ DNA information and have access to their insurance records. It will bring quite a lot of African genetic material into the global research base, which has been lacking, says Broomberg.
Deals with other insurers could follow. Venter says that only with huge numbers will the exact relationship between genes and traits become clear. For instance, height – largely determined by how tall a person’s parents are – is probably influenced by at least hundreds of genes, each with a small effect. Citing similar objectives, the U.S. government this year said it would assemble a study of one million people under Obama’s precision – medicine initiative (see U.S. to Develop DNA Study of One Million People), but it may not move as fast as Venter’s effort.
A full – body MRI scanner at the health nucleus of Human Longevity, where it offers $25,000 medical workups.
HLI has assembled a team of machine – learning experts in Silicon Valley, led by the creator of Google Translate, to build models that can predict health risks and traits from a person’s genes (see Three Questions for J. Craig Venter). In an initial project, Venter says, volunteers have had their facial features mapped in great detail and the company is trying to show it can predict from genes exactly what people look like. He says the project is unfinished but that just from the genetic code, HLI can already describe the color of your eyes better than you can. Venter also said that this October the company will open a health nucleus at its La Jolla headquarters, with expanded genetic and health services aimed at self – insured executives and athletes. The center, the first of several he hopes to open, will carry out a full analysis of patients’ genomes, sequence their gut bacteria or microbiome, analyze more than two thousand other body chemicals, and put them through a full – body MRI scan. Like an executive physical on steroids, he says. The health nucleus service will be priced at $25,000. These individuals would also become part of the database, Venter said, and would receive constant updates as discoveries are made.
While the quality of Venter’s science is not in much doubt, this is the first time since he was a medic in Vietnam that he’s doled out medicine directly. I think it’s a good concept, says Charis Eng, chair of the Cleveland Clinic’s Genomic Medicine Institute, which collaborates with Venter’s company. But we who practice genomic medicine – we say HLI has absolutely no experience with patient care. I want to inject caution: it needs to be medically sound as well as scientifically sound. Venter has a history of selling big concepts to investors and then using their money to carry out exciting, but not necessarily profitable, science. In 1998 he formed Celera Genomics to privately sequence the human genome, but he was later booted as its president when its business direction changed. The economics of his current plan are also uncertain. Venter’s pitch is that with tens of thousands and ultimately a million genomes, he will uncover the true meaning of each person’s DNA code. But all those discoveries lie in the future. And at a cost of around $1,000 to $1,500 each, a million completely sequenced genomes add up to an expense of more than a billion dollars. HLI has so far raised $80 million, but Venter says he is now meeting with investors in order to raise far larger sums. Venter says he intends to offer several other common kinds of testing, including pre – conception screening for parents (to learn if they carry any heritable genetic risks), sequencing of tumors from cancer clinics, and screening of newborns. Those plans could bring HLI into competition with numerous other startups and labs that offer similar services. It would be just one more off – the – shelf genetic testing company, if the entire motivation weren’t to build this large database, he says. The future game is 100 percent in data interpretation. If we are having this conversation five to 10 years from now, it’s going to be very different. It will be, ?Look how little we knew in 2015.’
John Craig Venter, born October 14, 1946, is an American biotechnologist, biochemist, geneticist, and entrepreneur. He is known for being one of the first to sequence the human genome and the first to transfect a cell with a synthetic genome. Venter founded Celera Genomics, The Institute for Genomic Research (TIGR) and the J. Craig Venter Institute (JCVI), and is now working at JCVI to create synthetic biological organisms. He was listed in Time magazine’s 2007 and 2008 list of the 100 most influential people in the world. In 2010, the British magazine New Statesman listed Craig Venter at 14th in the list of The World’s 50 Most Influential Figures 2010. He is a member of the USA Science and Engineering Festival’s Advisory Board.
Venter was born in Salt Lake City, Utah, the son of Elizabeth and John Venter. In his youth, he did not take his education seriously, preferring to spend his time on the water in boats or surfing. According to his biography, A Life Decoded, he was said to never have been a terribly engaged student, having Cs and Ds on his eighth – grade report cards. He graduated from Mills High School in Millbrae, California. Although he was against the Vietnam War, Venter was drafted and enlisted in the United States Navy where he worked in the intensive – care ward of a field hospital. While in Vietnam, he attempted suicide by swimming out to sea, but as he got closer to the deep blue sea and was approaching the circling of a shark, he changed his mind more than a mile out. Being confronted with wounded, maimed, and dying [marines] on a daily basis instilled in him a desire to study medicine – although he later switched to biomedical research. Venter began his college education at a community college, College of San Mateo in California, and later transferred to the University of California, San Diego, where he studied under biochemist Nathan O. Kaplan. He received a BS in biochemistry in 1972, and a PhD in physiology and pharmacology in 1975, both from UCSD. After working as an associate professor, and later as full professor, at the State University of New York at Buffalo, he joined the National Institutes of Health in 1984.
Venter himself recognized his own ADHD behavior in his adolescence, and later found ADHD – linked genes in his own DNA. While an employee of the NIH, Venter used a technique for rapidly identifying all of the mRNAs present in a cell and began to use it to identify human brain genes. The short cDNA sequence fragments discovered by this method are called expressed sequence tags (ESTs). The NIH Office of Technology Transfer and Venter decided to use these ESTs to attempt to patent the genes they identified, based on the ESTs alone. When Venter disclosed this strategy during a Congressional hearing, a firestorm of controversy erupted. The NIH later stopped the effort and abandoned the patent applications it had filed, following public outcry.
Venter was passionate about the power of genomics to radically transform healthcare. Venter believed that shotgun sequencing was the fastest and most effective way to get useful human genome data. The method was rejected by the Human Genome Project however, since some geneticists felt it would not be accurate enough for a genome as complicated as that of humans, that it would be logistically more difficult, and that it would cost significantly more. Frustrated with what Venter viewed as the slow pace of progress in the Human Genome project, and unable to get funds for his ideas, he sought funding from the private sector to fund Celera Genomics. The goal of the company was to sequence the entire human genome and release it into the public domain for non – commercial use in much less time and for much less cost than the public human genome project. The company planned to profit from their work by creating a value – added database of genomic data to which users could subscribe for a fee. The goal consequently put pressure on the public genome program and spurred several groups to redouble their efforts to produce the full sequence. DNA from five demographically different individuals was used by Celera to generate the sequence of the human genome; one of the individuals was Venter himself.
In 2000, Venter and Francis Collins of the National Institutes of Health and U.S. Public Genome Project jointly made the announcement of the mapping of the human genome, a full three years ahead of the expected end of the Public Genome Program. The announcement was made along with U.S. President Bill Clinton, and UK Prime Minister Tony Blair. Venter and Collins thus shared an award for Biography of the Year from A&E Network. On the 15 February 2001, the Human Genome Project consortium published the first Human Genome in the journal Nature, and was followed, one day later, by a Celera publication in Science. Despite some claims that shotgun sequencing was in some ways less accurate than the clone – by – clone method chosen by the Human Genome Project, the technique became widely accepted by the scientific community. Although Celera was originally set to sequence a composite of DNA samples, partway through the sequencing, Venter switched the samples for his own DNA.
After contributing to the Human Genome, and its release into the public domain, Venter was fired by Celera in early 2002. According to his biography, Venter was ready to leave Celera, and was fired due to conflict with the main investor, Tony White, that had existed since day one of the project. Venter writes that his main goal was always to accelerate science and thereby discovery, and he only sought help from the corporate world when he could not find funding in the public sector. Venter’s Global Ocean Sampling Expedition (GOS) is an ocean exploration genome project with the goal of assessing the genetic diversity in marine microbial communities and to understand their role in nature’s fundamental processes. Begun as a Sargasso Sea pilot sampling project in August 2003, Venter announced the full Expedition on 4 March 2004. The project, which used Venter’s personal yacht, Sorcerer II, started in Halifax, Canada, circumnavigated the globe and returned to the U.S. in January 2006.
Venter is currently the president of the J. Craig Venter Institute, which conducts research in synthetic biology. In June 2005, he co-founded Synthetic Genomics, a firm dedicated to using modified microorganisms to produce clean fuels and biochemicals. In July 2009, ExxonMobil announced a $600 million collaboration with Synthetic Genomics to research and develop next – generation biofuels. Venter is seeking to patent the first partially synthetic species possibly to be named Mycoplasma laboratorium. There is speculation that this line of research could lead to producing bacteria that have been engineered to perform specific reactions, for example, produce fuels, make medicines, combat global warming, and so on. In May 2010, a team of scientists led by Venter became the first to successfully create what was described as synthetic life. This was done by synthesizing a very long DNA molecule containing an entire bacterium genome, and introducing this into another cell, analogous to the accomplishment of Eckard Wimmer’s group, who synthesized and ligated an RNA virus genome and booted it in cell lysate The single – celled organism contains four watermarks written into its DNA to identify it as synthetic and to help trace its descendants. The watermarks include:
1. Code table for entire alphabet with punctuations
2. Names of 46 contributing scientists
3. Three quotations
4. The secret email address for the cell.
On September 4, 2007, a team led by Sam Levy, published the first complete (six – billion – letter) genome of an individual human – Venter’s own DNA sequence. Some of the sequences in Venter’s genome are associated with wet earwax, increased risk of antisocial behavior, Alzheimer’s and cardiovascular diseases. This publication was especially interesting since it contained a diploid instead of a haploid genome and shows promise for personalized medicine via genotyping. This genome, dubbed HuRef by Levy and others, was a landmark accomplishment. The Human Reference Genome Browser is a web application for the navigation and analysis of Venter’s recently published genome. The HuRef database consists of approximately 32 million DNA reads sequenced using microfluidic Sanger sequencing, assembled into 4,528 scaffolds and 4.1 million DNA variations identified by genome analysis. These variants include single – nucleotide polymorphisms (SNPs), block substitutions, short and large indels, and structural variations like insertions, deletions, inversions and copy number changes. The browser enables scientists to navigate the HuRef genome assembly and sequence variations, and to compare it with the NCBI human build 36 assembly in the context of the NCBI and Ensembl annotations. The browser provides a comparative view between NCBI and HuRef consensus sequences, the sequence multi – alignment of the HuRef assembly, Ensembl and dbSNP annotations, HuRef variants, and the underlying variant evidence and functional analysis. The interface also represents the haplotype blocks from which diploid genome sequence can be inferred and the relation of variants to gene annotations. The display of variants and gene annotations are linked to external public resources including dbSNP, Ensembl, Online Mendelian Inheritance in Man (OMIM) and Gene Ontology (GO). Users can search the HuRef genome using HUGO gene names, Ensembl and dbSNP identifiers, HuRef contig or scaffold locations, or NCBI chromosome locations. Users can then easily and quickly browse any genomic region via the simple and intuitive pan and zoom controls; furthermore, data relevant to specific loci can be exported for further analysis.
On March 4, 2014 Venter and co – founders Peter Diamandis and Robert Hariri announced the formation of Human Longevity, Inc., a company focused on extending the healthy, high performance, human lifespan. At the time of the announcement the company had already raised $70 million in venture financing, which was expected to last 18 months. Venter is the chairman and chief executive officer (CEO). The company said that it plans to sequence 40,000 genomes per year, with an initial focus on cancer genomes and the genomes of cancer patients. Human Longevity’s mission is to extend healthy human lifespan by the use of high – resolution big data diagnostics from genomics, metabolomics, microbiomics, and proteomics, and the use of stem cell therapy.
Venter is the author of two books, the first of which was ostensively an autobiography titled A Life Decoded. Venter’s second book was titled Life at the Speed of Light in which he announced his theory that this is the generation in which there appears to be a dovetailing of the two previously diverse fields of science represented by computer programming and the genetic programming of life by DNA sequencing. He was applauded for his position on this by futurist Ray Kurzweil.
Venter has been the subject of several biography books, several scientific documentary books, TV documentaries, numerous magazine articles, and many speeches. Venter has been the subject of articles in several magazines, including Wired, The Economist, Australian science magazine Cosmos, and The Atlantic. Additionally, he was featured on The Colbert Report on both February 27, 2007, and October 30, 2007. Venter appeared in the Evolution episode of the documentary television series Understanding. On May 16, 2004, In a 2007 interview with New Scientist when asked Assuming you can make synthetic bacteria, what will you do with them?, Venter replied: Over the next 20 years, synthetic genomics is going to become the standard for making anything. The chemical industry will depend on it. Hopefully, a large part of the energy industry will depend on it. We really need to find an alternative to taking carbon out of the ground, burning it, and putting it into the atmosphere. That is the single biggest contribution I could make. He was on the 2007 Time 100 most influential people in the world list made by Time magazine. In 2007 he also received the Golden Eurydice Award for contributions to biophilosophy. On December 4, 2007, Venter gave the Dimbleby lecture for the BBC in London. In February 2008, he gave a speech about his current work at the TED conference. Venter was featured in Time magazine’s The Top 10 Everything of 2008 article. Number three in 2008’s Top 10 Scientific Discoveries was a piece outlining his work stitching together the 582,000 base pairs necessary to invent the genetic information for a whole new bacterium. For an episode aired on July 27, 2009, Venter was interviewed on his boat by BBC One for the first episode of TV show Bang Goes the Theory.
On May 20, 2010, Venter announced the creation of first self – replicating semi – synthetic bacterial cell. On November 21, 2010 Steve Kroft profiled Venter and his research on 60 Minutes. In the June 2011 issue of Men’s Journal, Venter was featured as the Survival Skills celebrity of the month. He shared various anecdotes, and advice, including stories of his time in Vietnam, as well as mentioning a bout with melanoma upon his back, which subsequently resulted in giving a pound of flesh to surgery. Venter is mentioned, in the season finale of the first season of the science fiction series Orphan Black, a joint production of Space and BBC America. In the episode, Venter is referenced as patenting an organism and encoding a message in the genome of that organism, an act repeated by the character of Aldous Leekie (played by Matt Frewer). While the clones fear that this renders them as nothing more than property, in reality, in the United States and Canada, where the show primarily takes place, such a patent became unenforceable due to constitutional provisions and laws against owning human beings. Sources: MIT Technology Review; Wikipedia; Wired Magazine
Role of Soft Palate in Adaptation of Transmissible Influenza Viruses
Flu infection in mammals starts when an influenza virus protein called hemagglutinin binds to sialic acid (SA) molecules on the tops of chain-like proteins that thickly line tissue throughout the respiratory tract. Flu viruses adapted to humans and other mammals bind preferentially to a type of SA called alpha 2,6 SA (a2,6 SA), which is the predominant form found in the upper respiratory tract of mammals, while avian flu viruses bind best to a form, a2,3 SA, that predominates in birds.
According to an article published online in the journal Nature (23 September 2015), a previously unappreciated role for the soft palate has been identified to better understand how influenza (flu) viruses acquire the ability to move efficiently between people. In studies using ferrets, the authors collected evidence that this patch of mucous-coated soft tissue separating the mouth from the nasal cavity is a key site for the emergence of flu viruses with a heightened ability to spread through the air. The finding could aid efforts to define the properties governing flu virus transmissibility and predict which viruses are most likely to spark pandemics.
For the study, four mutations were made in the hemagglutinin of the flu strain responsible for the 2009 influenza pandemic. This strain was notoriously good at spreading from person to person. The intent of introducing the mutations was to make the virus preferentially bind to bird-type SA and, presumably, be less transmissible via air than the original virus. The engineered virus was then used to infect a group of ferrets, which are widely used as a model of human influenza infection. The next day, uninfected ferrets were placed in cages separated from infected ferrets by a perforated barrier. Nasal secretions were collected from all of the animals for two weeks.
To the surprise of the authors, the engineered flu virus was transmitted by the airborne route to uninfected ferrets just as well as the original non-mutated virus.
To understand this unexpected result, the authors sequenced viral genetic material obtained from the ferret nasal washes. The sequencing was done by a team at the J. Craig Venter Institute, Rockville, Maryland. It was discovered that airborne transmission was associated with a single genetic change in the engineered virus’s hemagglutinin that gave it the ability to bind to mammalian-type a2,6 SA of a particular class (long chain) without the loss of the other introduced changes that had made it an a2,3 SA binding type. This genetic reversion appears to have occurred within 24 hours of administering the engineered flu virus to the experimentally infected ferrets. Subsequently, they passed it on to uninfected ferrets in the adjacent cages.
Next, the authors looked at tissues from several locations in the ferrets’ upper and lower respiratory tract to more precisely define the location of the reverted, long chain a2,6 SA-binding virus. They infected groups of ferrets with the engineered virus — containing the same four mutations in hemagglutinin as in the first set of experiments — and three, five or seven days later, took tissue samples from various locations, including the soft palate. Results showed that the soft palate, which has surfaces facing both the mouth and nasal cavity, stood out as the prime location for an abundance of virus containing the single genetic reversion that allows it to bind to mammalian-type SA. By three days post-infection, more than 90% of the viral material collected from the soft palate contained the reverted, long chain a2,6-binding form of virus. The other tissue sites examined showed a mix of engineered and reverted virus at all the tested time points after infection. Other parts of the ferret respiratory system do have large amounts of cells bearing a2,6 SA, yet the reverted virus dominated only in the soft palate. Pig and human cadaver soft palate tissue was also studied by the team and revealed density, type and locations of a2,6 SA-bearing proteins similar to those seen in ferrets.
According to the authors, much remains to be explored in this small region of anatomy to better define the characteristics that make it a key spot for rapid virus evolution and selection of airborne transmissible flu viruses. It may be, for example, that flu viruses with superior ability to transmit through the air are those that outcompete other flu virus variants in the soft palate and that inflammation associated with infection there stimulates the sneezing and coughing needed to better propel flu virus onward to new contacts.
Managing Patients with Methylmalonic Acidemia (MMA)
One of Target Health’s expertise is in the area of Orphan Drugs. Dr. Mitchel will be joing FDA and other industry experts on a panel at a NORD meeting in October in Washington.
A medical food, as defined in section 5(b)(3) of the Orphan Drug Act (21 U.S.C. 360ee(b)(3)), is a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.
FDA considers the statutory definition of medical foods to narrowly constrain the types of products that fit within this category of food. Medical foods are distinguished from the broader category of foods for special dietary use and from foods that make health claims by the requirement that medical foods be intended to meet distinctive nutritional requirements of a disease or condition, used under medical supervision, and intended for the specific dietary management of a disease or condition. Medical foods are not those simply recommended by a physician as part of an overall diet to manage the symptoms or reduce the risk of a disease or condition, and all foods fed to sick patients are not medical foods. Instead, medical foods are foods that are specially formulated and processed (as opposed to a naturally occurring foodstuff used in a natural state) for a patient who is seriously ill or who requires use of the product as a major component of a disease or condition’s specific dietary management.
Many medical foods are designed to help manage patients with rare inborn errors of metabolism (IEMs), and can help prevent serious and life-threatening complications. However, according to two studies appearing online in the August issue of Genetics in Medicine such special foods may cause harm in some patients when their use is not carefully monitored and managed, according to a research team led by scientists at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health. The researchers contend that there is a need for more rigorous clinical study of dietary management practices for patients with IEMs, including any associated long-term side effects, which may in turn result in the need to reformulate some medical foods.
According to 2 studies published online Genetics in Medicine (13 August 2015), it was reported that medical foods, including those given to patients with methylmalonic acidemia (MMA), are not subject to the same scrutiny as therapeutic drugs. The authors based their conclusions on more than 10 years of observational studies with large patient groups involving two inborn errors of metabolism. The two IEMs studied are rare genetic disorders in which the body cannot properly turn food into energy. In the first of these, known as isolated methylmalonic acidemia (MMA), mutations in any one of four genes can impede enzyme activity that is necessary for the proper breakdown of amino acids, the building blocks of proteins (specifically the amino acids valine, isoleucine, methionine and threonine). In the other, cobalamin C (cblC) type combined MMA and hyper-homocysteinemia, failure to properly process vitamin B12 results in a different form of MMA that clinically looks different and requires different management.
MMA, one of the most common disorders of organic acid metabolism, results from a deficiency of enzymes involved in amino acid metabolism. About 1 in 50,000 to 150,000 newborns in the United States each year is born with MMA, which is now detected by routine newborn screening. Despite current treatments, the disorder can cause recurrent episodes of metabolic acidosis (when the body produces too much acid, or when the kidneys are not removing enough acid from the body), feeding difficulties, poor growth, enlarged liver, kidney disease, pancreatitis (inflammation of the pancreas), intellectual disability and early death. Many infants and children with the cblC-deficiency form of the disease also experience vision loss, as well as neurological and cognitive problems.
Even today, when a newborn screening test indicates that a baby has MMA it is a medical emergency. According to the authors, if you cannot get in touch with the family, you may need to ask the police to help bring the baby to the emergency room, because the newborns can rapidly become very sick and even perish without immediate treatment.
In the MMA study, 61 patients enrolled from metabolic treatment centers across the United States and abroad were evaluated at the NIH Clinical Center between 2004 and 2014. The authors closely monitored their treatments and responses. Most of the patients received part or all of their nutrition from a special mix of natural protein and MMA medical foods delivered through feeding tubes. Medical foods for MMA did not contain intact protein. They contain free amino acids with the exception of the four toxic amino acids that MMA patients cannot metabolize. These amino acids are essential; the body cannot make them, but people must consume a certain amount to support body and brain growth and function.
As others have observed in patients with MMA, growth outcomes were disappointing. In most patients, height, weight and head circumference were lower than average, while body mass index (BMI) and body fat percentage were higher. Analyzing the patients’ dietary records and lab results, the authors found that when patients on restricted protein diets were given medical foods used to manage MMA, especially in large amounts, the relationships between certain essential amino acids were disturbed. In particular, the patients ended up with four or five times the recommended amounts of leucine. Leucine is a branched chain amino acid essential to liver, muscle and adipose (fat-retaining) tissue but, when given in excess, it causes a depletion of the other branched chain amino acids, valine and isoleucine. This might have untoward effects on growth and brain development.
Further observational studies conducted with a treatment team from the University of Iowa in Iowa City, showed that reducing the intake of medical foods resolved amino acid deficiencies without having to increase the protein intake. However, the authors cautioned that they have not proven a cause-and-effect relationship between the amino acid deficiencies and the poor growth outcomes observed in the patient group. A large prospective clinical trial would be needed for that.
In the cobalamin C (cblC) deficiency study, which is the focus of the second article, the authors made it clear that they believe cblC patients should never be given current-day medical foods designed for patients with isolated MMA. CblC patients — who also have high levels of methymalonic acid and homocysteine in their blood and urine — cannot adequately synthesize the amino acid methionine, a reaction that depends on vitamin B12. As a result, management of cblC includes taking intramuscular vitamin B12 injections and betaine, a substance that among other functions helps the body metabolize the amino acid homocysteine and increases methionine synthesis.
The medical foods designed for patients with isolated MMA contain no methionine and are restricting the exact amino acid that needs to be increased in cblC patients. In addition, these medical foods’ relatively high leucine content may block methionine and other amino acid transport into the brain, where they are needed for growth.
The clinical trial enrolled 28 cblC patients, ranging in age from 2 to 27 years. A subset of nine participants received medical foods while another six followed protein-restricted diets. Both groups had lower growth rates, including decreased head circumference, than other patients who were on natural diets that provided the recommended daily allowance of protein. Another treatment team showed that increasing natural protein intake and discontinuing methionine-restricted medical foods helped improve head growth and blood amino acid concentrations in an infant with cblC.
According to the authors, the new findings highlight the paucity of experimental and clinical trial support underlying dietary management practices commonly used to treat patients with varied forms of methylmalonic acidemia and underscore the community need for a more rigorous clinical study of medical foods in the treatment of patients with IEMs.
Strengthening the Clinical Trial Enterprise for Medical Devices: An FDA/CDRH Strategic Priority Update
The following was extracted from FDA Voice
Every day, millions of Americans rely on FDA approved or cleared medical devices to save, sustain, or improve the quality of their lives. The Center for Devices and Radiological Health (CDRH), is committed to patients having access to high – quality, safe, and effective medical devices, as quickly as possible. Innovation is key to both speed and excellence in that endeavor.
In general, clinical trial data are required in premarket submissions for the highest risk devices to demonstrate that they provide a reasonable assurance of safety and effectiveness. Therefore, the sooner those trials can safely begin, the sooner patients have access to potentially important, innovative technologies. As part of FDA’s 2014 – 2015 Strategic Priorities, CDRH committed to reducing the time and cost of regulatory and non – regulatory aspects of the U.S. clinical trial enterprise, while assuring the protection of human subjects and the generation of robust data.
In 2015, FDA continued to advance clinical trial programs with publication of a new draft guidance document related to FDA considers benefits and risks for Investigational Device Exemptions (IDEs) decisions. These decisions are tailored to the type and intent of the clinical study. FDA also issued a draft guidance that, when final, will encourage the use of adaptive designs for clinical trials and we are considering additional process improvements.
FDA also retrained the review staff on the practical challenges related to conducting a successful trial. As part of this training, more than 100 review staffers visited clinical trial sites to better understand the context and challenges of initiating and conducting clinical trials in the U.S.
Where has all this led? IDE review times, which had already improved in 2014, have continued to progress in 2015. For example:
From 2011 to 2014, the median number of days to full IDE approval decreased from 442 days to 101 days.
During 2015, the median number of days to full IDE approval has decreased to 30 days.
Additionally, full approval entails fewer review cycles. In 2011, only 15% of IDEs were approved within two review cycles. In 2015, 74% of IDEs were approved in two review cycles. This performance meets FDA’s strategic goals and, more importantly, means that important technologies have the potential to reach US patients sooner.
Early Feasibility Studies (EFS) are small clinical studies designed to gain early insights into an innovative technology during the development process before starting a larger clinical trial. EFS often are a critical step in device innovation, but they are frequently conducted in other countries rather than in the U.S. Device developers tend to conduct subsequent feasibility and pivotal clinical studies and then bring their products to market earlier in those countries, where they conducted an EFS to leverage clinicians who have gained experience with their technologies.
As part of our 2014 – 2015 Strategic Priority to Strengthen the Clinical Trials Enterprise, CDRH established a goal of increasing the number of EFS IDEs submitted to each review division in the Center. Interest in the EFS program has grown substantially, with a 50% increase in the number of EFS submissions during the first nine months of 2015, compared with the same period in 2013. In addition, six of our seven Office of Device Evaluation (ODE) review divisions reported an increase in the number of EFS submissions for 2015 compared with 2013. Recently, FDA developed a comprehensive educational module to help industry navigate the EFS process. FDA expects that this is just the beginning and we will continue to see more EFS conducted in the U.S.
To obtain more details regarding FDA’s performance for this important strategic priority, see Clinical Trial Performance Update – September 2015.
Zucchini Gratin with Toasted Pine Nuts
A delicious light, side dish ©Joyce Hays, Target Health Inc.
4 Large or Medium Zucchini
1 and 1/2 teaspoons salt
1/2 cup plain, uncooked Basmati or Jasmine white rice
1 Large onion, chopped
1 cup pine nuts, toasted (you toast them yourself)
5 Tablespoons olive oil, divided
6 large garlic cloves, finely minced (not squeezed)
2 Tablespoons chickpea or almond flour
Almond milk, as needed, or broth
1.5 cup grated Parmesan cheese, divided (save some for topping)
Pinch black pepper
Pinch chili flakes
Do yourself a favor and gather all of the ingredients in one place, before you start to cook. ©Joyce Hays, Target Health Inc.
Toast the pine nuts and set aside
Toasting the pine nuts: Use 1 teaspoon olive oil, or if you’re careful and keep shaking the pan from side to side over the flame, you don’t need any oil. With or without the oil, constantly shake the pan to keep the pine nuts moving, which will toast them evenly and keep them from burning. The minute you get a nice golden brown color, remove immediately, or they will burn. The toasting takes less than one minute. ©Joyce Hays, Target Health Inc.
Wash zucchini and trim ends. Cut in half lengthwise. Remove any large seeds. Coarsely grate and place in a colander set over a bowl. Toss with the salt. Let drain for 30 minutes. The salt helps to pull the liquid out of the zucchini.
Grating the zucchini directly into a flat dish or colander. ©Joyce Hays, Target Health Inc.
Save drained liquid and squeeze a handful of the zucchini and taste. If it’s very salty, rinse and drain it again (don’t save liquid this second time). Squeeze all of the zucchini in handfuls, gently, collecting any juices in the bowl of drained liquid. Blot dry on paper towels. It’s very important that you not only squeeze any excess liquid out of the zucchini, but also dry it with paper towels. If you don’t go through this squeezing and drying process, later when you take the zucchini out of the oven, there will be too much excess liquid to deal with.
Here’s what the drained liquid from the grated zucchini looks like. When you give this liquid back to the casserole, later, the zucchini will not re-absorb it, the rice will absorb it, which is what you want. ©Joyce Hays, Target Health Inc.
Boil rice for exactly 2 to 3 minutes in salted water. You don’t want the rice to cook thoroughly at this point. Drain and set aside.
In a large frying pan, add 3 Tablespoons olive oil and cook the onions slowly, over low flame, for 8 to 10 minutes until tender and translucent. Raise heat slightly and stir several minutes until very lightly browned.
Here the grated zucchini and garlic have been added to the onions. The aroma fills the kitchen. About to add the flour. ©Joyce Hays, Target Health Inc.
Stir in the grated and dried zucchini and garlic; season with salt and pepper. Toss and turn for 2 to 4 minutes until the zucchini is almost tender.
Sprinkle in the flour, stir over moderate heat for 2 minutes, and remove from heat.
Measure the drained, green liquid from the zucchini. If you have less than 2 1/2 cups, add milk or broth, to bring the level up to the 2 1/2 cups.
Stir the 2.5 cups of liquid into the zucchini-onion mixture and return pan to stove over medium-high heat and bring to a simmer, stirring.
Remove from heat again, stir in par-cooked rice and 1 cup of the cheese. Taste and adjust seasoning if needed.
Now, add the pine nuts to the pan and stir for a few seconds.
Finally, add the contents of the pan, into a 2-quart baking dish. Sprinkle with the rest of the parmesan and remaining olive oil.
About to go into the oven. ©Joyce Hays, Target Health Inc.
30 minutes before serving: Heat oven to 425 degrees. Bake in upper third of oven until bubbling and browned on top, about 25 to 30 minutes. (If it begins to brown too quickly, cover it with foil until the last 5 minutes.) The rice should absorb all the liquid. Serve immediately.
Just taken out of the oven. Smells wonderful! ©Joyce Hays, Target Health Inc.
We started dinner with chilled Santa Margherita pinot grigio and a Caesar salad recipe I’m working on. When perfected, I will share, of course. By the way, a few weeks ago, I mentioned an orange/beet salad I’m working on. Some readers wanted that recipe right away. The only reason that you haven’t seen that recipe yet, is that I like to use Cara Cara oranges, and Blood oranges with the beets and these oranges are not at their peak right now. I haven’t forgotten my promise to share this. Meanwhile, my Caesar salad recipe is nearly ready to publish. The next course was the zucchini gratin, which I served with a baked mushroom medley & broccoli. Dessert was our favorite jello cake and Cool whip.
Went to an awful play, not worth discussing, on Saturday. We watched the activities of the Pope with great interest. He’s definitely a man of peace and thoughtfulness and brought beauty into everyone’s home this weekend. Religions should be made of this. We got together with family and generally had a relaxing wonderful weekend.
Saying goodbye to the lazy days of summer. ©Joyce Hays, Target Health Inc.
From Our Table to Yours!
September 24, 2015
You might expect that little happens in the Arctic Ocean during the cold and dark winter. But that just isn’t so, according to researchers who have sampled the activities of many different species during three consecutive winters in Kongsfjorden, Svalbard.
You might expect that little happens in the Arctic Ocean during the cold and dark winter. But that just isn’t so, according to researchers who have sampled the activities of many different species during three consecutive winters in Kongsfjorden, Svalbard. Their findings are published in the Cell Press journalCurrent Biology on September 24.
“This once and for all changes the way we think of marine ecosystems during the polar night,” says Jørgen Berge of UiT The Arctic University of Norway and the University Centre in Svalbard.
“The dark polar night is not a period without any biological activity [as had been assumed]. Concealed behind the curtain of darkness is a world of activity, beauty, and ecosystem importance.”
Berge says the researchers were inspired to look more closely at what happens during the polar night based on a chance encounter they had on a small boat in the middle of a Svalbard fjord.
“Above us was a starry, winter night and below us were countless blue-green ‘stars’ in the deep” produced by bioluminescent organisms, Berge says. “The beauty of it was stunning, and the fact that so many organisms were producing light was a strong indication that the system was not in a resting mode.”
He decided then and there to do a large-scale survey and ecosystem study of the polar night in one of the Svalbard fjords during three consecutive winters. Instead of an ecosystem that had entered a resting state, the researchers say they found a system buzzing with biological activity. In fact, the diversity and reproductive activity of some species was actually greater during the winter than at other times of the year.
The researchers found, for instance, that copepods and other zooplankton were actively reproducing as filter-feeding Iceland scallops kept right on growing. Baited traps with time-lapse cameras revealed an abundant and active community of shallow-water scavengers, including whelks, amphipods, and crabs.
Berge says that he and his colleagues were perhaps most surprised by the seabirds. “Not only are they there, but they are able to find their preferred food in the total darkness,” he says. “We do not know how they are able to do this, and we do not know how common it is for seabirds to overwinter at these latitudes. But we [now] know that they do.”
The findings come at an important moment in time, given a changing climate. They also raise many new questions about how those marine species are able to eke out a living through the winter, the researchers say.
As the melting ice opens up new areas of the Arctic to human activities–from the petroleum industry to fisheries and tourism–Berge says, “we can’t simply assume that the dark polar night is a ‘safe’ period when things are not turned on. Rather, it turns out that the dark polar night is an important period for reproduction in a number of organisms, and, as such, it is probably more sensitive than other parts of the year.”
- Berge et a. Unexpected Levels of Biological Activity during the Polar Night Offer New Perspectives on a Warming Arctic. Current Biology, September 2015 DOI: 10.1016/j.cub.2015.08.024
Source: Cell Press. “In the dark polar winter, the animals aren’t sleeping.” ScienceDaily. ScienceDaily, 24 September 2015. <www.sciencedaily.com/releases/2015/09/150924142523.htm>.