Wednesday, September 26, 2018
Sunday, September 16, 2018
An international consortium involving over 50 institutions has announced an ambitious project to assemble high-quality genome sequences of all 66,000 vertebrate species on Earth, including all mammals, birds, reptiles, amphibians, and fish. With an estimated total cost of $600 million dollars, it’s a project of biblical proportions.
It’s called the Vertebrate Genomes Project (VGP), and it’s being organized by a consortium called Genome 10K, or G10K. As its name implies, this group had initially planned to sequence the genomes of at least 10,000 vertebrate species, but now, owing to tremendous advances and cost reductions in gene sequencing technologies, G10K has decided to up the ante, aiming to sequence both a male and female individual from each of the approximately 66,000 vertebrate species on Earth.
Cofounders of the project announced the new goal yesterday at a press briefing held during the opening session of the 2018 Genome 10K conference, currently being held at Rockefeller University in New York City. The project will involve over 150 experts from 50 institutions in 12 countries.
The announcement comes in tandem with the release of 14 new high-quality genomes for species representing all five vertebrate classes, including genomes of the greater horseshoe bat, Canadian lynx, platypus, Anna’s hummingbird, the kakapo parrot (of which there are only 150 surviving individuals), Goode’s desert tortoise, two-lined caecilian (a strange limbless amphibian that looks like a snake), and climbing perch. These 14 genomes, and those compiled over the course of the project, will be made available to scientists for the purposes of research.
Indeed, there’s more to VGP than just sequencing animal genomes. Like the Human Genome Project, this endeavor will undoubtedly produce breakthroughs in high-resolution sequencing and genome-assembly methods, while resulting in lower costs and fewer errors. The project will also address important questions in biology and disease, and make immediate impacts on the fields of evolution, genomics, and conservation biology. On that last point, a complete catalogue of Earth’s vertebrate species could serve as a safeguard against extinction—both in terms of preventing extinction, and possibly reviving extinct species in the future.
Speaking at the press conference yesterday, Oliver Ryer, a cofounder of G10K and a director at the San Diego Zoo Institute for Conservation Research, said VGP has the potential to “transform all realms of biology.” He said it will allow scientists to understand the reasons for extinction, including the presence of deleterious mutations, inbreeding, and genetic bottlenecks. As an example, Ryer described the discovery of a deleterious recessive gene among California condors, saying “we can now identify birds that are carriers of this lethal trait.” Ultimately, he believes the project will make us “better stewards of life on Earth” and enable us to “preserve our biological heritage.”
When G10K was launched 10 years ago, its members had no idea how long it would take to sequence genomes of sufficient quality to do good science and to do so affordably.
“I am incredibly excited that now we’re now in a position to get it right,” David Haussler, a G10K cofounder and the director of the UC Santa Cruz Genomics Institute, said at yesterday’s meeting. “Now is really the time to get started,” adding, “we have no excuse to not do this.”
To generate high-quality genome assemblies, the VGP team is emphasizing “long-reads” over “short-reads,” which means sequencing technologies that produce longer chunks of contiguous genetic data will be favored over those that produce shorter ones. This will make it considerably easier to assemble the DNA sequences into whole chromosomes. So instead of having to work with a jigsaw puzzle containing millions of pieces, the long-reads will result in a puzzle consisting of thousands of pieces.
Also, the researchers will refrain from combining male and female chromosomes into a single genome—a common practice that was resulting in far too many errors. Instead, the team will assemble both the paternal and maternal DNA of individuals in a process known as phasing. As Gene Myers, a VGP team member and a lead researcher at the Max Planck Institute of Molecular Cell Biology and Genetics, said yesterday, each species will be a “one and done” deal, meaning that the quality of the sequences will be so good that the work shouldn’t have to be repeated in the future. That way, “we can get on with the science,” he said.
In terms of process, the researchers will build long-read sequences with an initial assembly of chromosome chunks called “contigs.” These chunks will be joined together to create even bigger pieces, called scaffolds, which will in turn be linked to others to create even larger assemblies, all the way to full-sized chromosomes. Optical DNA maps and computer algorithms will assist in the process, ensuring the proper sequential order and flagging any structural errors.
“The advances in long-read sequencing and long-range scaffolding technologies is revolutionizing de novo [starting from scratch] DNA sequencing,” said Myers. “After a 10-year hiatus, this trend inspired me to return to genome assembly as I believe we will ultimately be able to produce near-perfect, telomere-to-telomere genome reconstructions, and if current cost trends continue, for less than $1,000 on average per vertebrate species, thus dramatically altering the landscape of genomics.”
Indeed, it wasn’t too long ago that it cost millions of dollars and years of effort to complete the genome of a single animal. New sequencing technologies could soon make it possible to create an entire genome in a single week, said Adam Phillippy, G10K assembly chair and lead at the NIH’s National Human Genome Research Institute. It now costs about $30,000 to to sequence the DNA of a new species for the first time.
The new sequences will be stored and made publically available at the Genome Ark database, a digital open-access library of genomes. Corporate sponsors DNAnexus and Amazon Web “have been instrumental in getting this project off the ground,” said Phillippy.
“This project is outlandish and outrageous—but it’s feasible, and it’s inevitable,” Harris Lewin, a VGP team member from UC Davis, said at the press briefing.
Around $600 million will be needed to complete all phases of VGP, according to a G10K press release. To fund the project, G10K is acquiring money from private institutions and corporate sponsors. But the consortium is also doing some crowdsourcing, having already collected $2.5 million out of the $6 million required for the first phase of the project (the first phase will involve the sequencing of at least one individual from all 260 orders of living vertebrates).
All hyperbole aside, this is one of the most ambitious projects we’ve seen in a while, rivaling the Human Genome Project (HGP), the Human Connectome Project (an ongoing effort to map all the connections of the human brain), and the VGP’s sister project, the Earth BioGenome Project (EGP), which was announced earlier this year. The goal of the EGP is to sequence all eukaryotes (there are around 8.7 million species on the planet), at an estimated cost of $4.7 billion dollars. In an email to Gizmodo, a spokesperson for G10K said EGP will be functioning as the coordinating body, and VGP vertebrate genomes will be contributed to the overall effort to eliminate replication of work.
No timeline was given for the VGP project, but as the HGP demonstrated, a slow start is not necessarily reflective of a project’s overall pace. As time passes, and as technologies and techniques improve, the VGP researchers should start to see accelerating returns, both in terms of speed and reductions in cost. Once complete, we’ll have a remarkable repository at our disposal, one even Noah would be proud of.
Mr. Smith Went to Washington in a “Ford”
It was some time ago when Frank Capra directed Jimmy Stewart in a wonderful display of political persistence. Modern day Toronto presents us with the drama of Premier Doug Ford going up against a washed-up Toronto council intent on maintaining their jobs, rather than seceding to the political will of 2.3 million Ontarions.
This same council is attempting to safeguard the influence of 3,338 registered Lobbyists, 47 Councillors and one mayor. I have talked to so many people and I have yet to come across anyone who disagrees with what Premier Ford is doing. The bias media, Andrea Horwath and the sordid remains of the Liberal party are engaged in a battle of self-preservation.
When the dust settles, the political and media propaganda will find itself scattered in the box of a Mack dump truck.
Torontonians are missing the obvious. Municipal councillors will soon have more power and influence than anyone ever imagined. The competing candidates are keeping this new found entitlement of political power extremely quiet. My suspicion is that the winning councillors will be compelled to make council a more effective decision making centre. Ultimately, their influence will be subjected to much more scrutiny.
After waiting two decades, “Toronto’s Amalgamation” may actually come to pass. The reduction of City Council is but one small step for Torontonians and one giant leap for Ontarions.
I suggest someone order the pizza for the midnight sitting of Ontario’s legislature, accompanied by some extremely strong laxative. We want to make sure all the b*ll-sh*t is flushed after this session of parliament.
Saturday, September 15, 2018
Friday, September 14, 2018
"Crickets," Belobaba adds, describing the government's response.
As an Ontarion, I’m concerned about the provincial judicial system. A judge’s appointment is a means by which a political party’s agenda can be preserved beyond the ballot box. We witness the same turmoil in the USA with President Trump attempting to bring back sanity to the U.S. Supreme Court.
Special Interest Groups and in many cases the media have made it their mandate to present Conservatism as an evil ideology. Political parties know they may lose an election and by appointing party loyalists to any superior Court, they preserve an existing, covert or planned political party agenda. The sex curriculum, cap and trade, and climate change are but a few issues being pushed hard by the leftist Liberal agenda. These issues are in fact a globalist manifesto, so we must ask who is influencing and governing our liberal and socialist parliamentarians.
I would very seldom agree with rambling John Tory, but in this matter I would agree. Other than the completely legal deployment of the notwithstanding clause, a public referendum would have been the only logical method of reaching a compromise solution.
What is ABSOLUTELY justifiable is Premier Ford’s decision, in that you cannot have the position of a majority government, who has garnered overwhelming public support, be overridden by a judge who uses the word crickets to explain his position.
One can only conclude this judge rendered his decision late at night, rocking on his back porch chair, listening to crickets, while sipping on a glass of red wine, perhaps smoking a joint, and very likely speaking to ex-premieres McGuinty and Wynne. The latter two individuals raped and pillaged this economy and continue to exist amongst the army of liberalized Ontario Public Service Employees. A "service" who were likely indoctrinated via nepotism and fraternity.
A logical person would conclude that another judge would have rendered a completely different opinion on the Better Local Government Act. Leaving justice to the throws of chance and statistics is completely wrong. Leaving it to a covert loyalty is criminal.
Let’s face it, the use of marijuana has not yet been legalized, so we will assume Judge Belobaba had less than a gram before he rendered his decision.
I wish to conclude the following, a) judges should not be appointed, they should be elected, b) the term of any appointment/election would be limited to 5 years and c) in any important decision, at least five judges would have to provide a decision - not one.
Thank you and Crickets
I hope the judge was not horny as well
I hope the judge was not horny as well
A cricket's chirp isn't just for fun: it's actually a mating call. Because crickets are nocturnal, they use sound to navigate the nighttime dating scene. When you hear a cricket chirping, it is always a male, calling for a female cricket by rubbing his wings together briskly.
Friday, September 7, 2018
Over 100 years ago, an American bone surgeon by the name of William Coley, was one of the first researchers to pioneer methods of stimulating the immune system as a core methodology in the treatment of cancer. He developed a naturally derived bacterial-based therapy that he investigated for the treatment of multiple types of cancer, that was later named “Coley’s Fluid.”
Years later, after a thorough review can be made of his preliminary clinical studies, it is no longer a question “if Coley’s Fluid worked on many cancers?” The results of his early trials at Memorial Sloan Kettering had phenomenal results rivaling the standard of care we have today for indications such as melanoma and sarcoma tumors. However the question remains, what happened to his research, and why are these treatments not available today in the United States?
William Coley: Man On A Mission
Coley became a man on a mission after an upsetting death of a Sarcoma patient that he thought would be cured after surgery.1 After this patient’s death, Coley went through the files of Memorial Hospital (now Sloan Kettering) to find if anyone had ever survived a Sarcoma. He only found one patient who had survived and 7 years later brought this patient back in to figure out how he was alive. It turned out this patient contracted an erysipelas infection while he had the sarcoma. When the patient survived the infection the cancer was gone.2,3
Coley thought that if an accidental infection could cause the spontaneous remission of cancer then so should an intentional infection. Coley treated patients with this live bacteria reporting dramatic tumor regression but also some fatalities.4 Coley’s rationale was to change to a dead bacteria, making it safe so the immune response wouldn’t keep repeating itself. Remarkably, from 1891-1936, Dr. Coley had a higher success rate treating many cancers than we do today! 5
His daughter, Helen Coley Nauts, carried on his work and spent 16 years researching her father’s files. She made history by publishing his monographs at Memorial Hospital showing that he did in fact have a treatment that produced many complete and durable remissions. In 1953 she founded the Cancer Research Institute which carried on the work of Immunotherapy for Cancer for the last 66 years.6
MD Anderson Scientist Claim Coley CURE Unrivaled!
“This fortuitous combination of gram negative and gram positive bacteria possessed a wide array of immune-stimulatory properties allowing Dr. Coley to achieve long term cure rates unrivaled by medical science 73 years past his death.” 7
- Dr. William Dekkar and Dr. Amar Safdar MD Anderson Scientists
Helen Coley Nauts
So why wasn’t Coley’s Fluid given more credit for treating cancer even with remarkable documented complete responses?
Ewing Was The Establishment
Looking back 100 years, a brilliant pathologist named James Ewing didn’t believe in Dr. Coley’s work and became his number 1 opponent.8 Ewing was the co-founder of The American Society of Control of Cancer which is now the American Cancer Society,9 and unlike William Coley, he had the backing of the conventional oncology community.10
“Fanatical Supporter of Radiation Outlaws Coleys Fluid”
In 1910, James Ewing was given $100,000 (Approximately $2.4 million today) to endow 20 beds and purchase radiation equipment.11 This was in collaboration with Memorial Hospital and it inspired Ewing to be a “fanatical supporter of radiation therapy.”12 While he was doing these studies, Coley was showing his results which proved to be more successful for overall survival than radiation. Ewing and his powerful group criticized Coley for not doing the treatment the same every time, injecting the fluid in different places and not keeping records the way they wanted.13 Ewing, known as The Chief of Cancer Pathology,14 also questioned if Coley’s patients had cancer at all. Later Ewing became Coley’s boss and outlawed the use of the fluids at memorial hospital.15
IN A PAPER CALLED
“THE TOXINS OF WILLIAM B. COLEY AND THE TREATMENT OF BONE AND SOFT-TISSUE SARCOMAS”
THE AUTHOR DR. EDWARD MCCARTHY WRITES:
“James Ewing, perhaps the most famous cancer pathologist in the country, was a leading opponent of Coley's work. This was a particular problem for Coley because Ewing was Medical Director of Memorial Hospital, and for many years was Coley's boss. Their memos to one another reflect constant interpersonal animosity. Ewing himself had become a fanatical supporter of radiation therapy for the treatment of all bone tumors and repudiated any other theories for the treatment of cancer. Ewing therefore refused Coley permission to use his toxins at Memorial Hospital. This was ironic, because Coley had more experience than any other surgeon in the country in treating the small round blue cell sarcoma that still carries Ewing's name.” 16 (Ewing Sarcoma)
Coley Causes Immune System To Wake Up With Fever
The banning of Coley’s fluid by Dr. Ewing came at a time when Coley was getting many complete responses without surgery. Coley would inject his fluid which would cause flu like symptoms and a fever. If his injection didn’t cause a fever he would raise the dose the next day. This was administered repeatedly without accumulated toxicity. Coley had many durable remissions even with cancers that are very complicated today.17
Coley’s Patients Did Better Than Many Today
Take for instance that according to John Hopkins “Ewing sarcoma patients have a 5 year survival rate of between 15% to 30%.18 The treatment today includes radiation therapy. Coley had 11 of 52 non operable Ewing Sarcoma patients (21%) that lived 5 years.19 Ewings Sarcoma is known not to respond well to chemotherapy or checkpoint inhibitors.
Or take Inoperable Melanoma. Dr. Coley showed a 60% 5 year survival.20 The latest SEER government data from 2008-2014 showed a 23% 5 year survival for stage 4 melanoma.21 With the new checkpoint inhibitors the Melanoma 5 year survival is likely to go up but the fact is Dr. Coley had a better success rate treating this disease than the numbers posted from the latest numbers in the SEER database from 2008-2014.22
Coley's Toxin Treatment Data from Helen Coley Nauts
Lessons to be learned
“Their memos to one another reflect constant interpersonal animosity”
Imagine what it would look like now if 100 years ago Dr. Coley and Dr. Ewing were able to get along. Two brilliant doctors who are today regarded as some of the biggest influences in cancer research. The problem was both men wanted to be right and the quest for being right led to the world not choosing to use immunotherapy in conjunction with radiation.
Times Are Changing!!
We are in a paradigm shift in cancer therapy. Although there are those that are still very righteous, many scientists and doctors are starting to realize that there can be something taken from all areas. Working together is a lot easier than working against each other. Being stuck to one ideology ( i.e. Only chemo, radiation and surgery) doesn’t serve anyone except the ones that MUST be “right”. (Or those who profit from it)
Immunotherapy as a cancer treatment was laughed at until the last few years by the establishment oncologists…but the results have been astounding! In the last 5 years, multiple trials have launched mixing things like radiation and immunotherapy.
ONE REALLY INTERESTING PROOF OF CONCEPT STUDY BY DR. SYLVIA FORMENTI AND DR. SANDRA DEMARIA TITLED
“COMBINING RADIOTHERAPY AND CANCER IMMUNOTHERAPY: A PARADIGM SHIFT”23, CONCLUDED:
“A new role for radiotherapy as a valuable partner of cancer immunotherapy is emerging. Preclinical evidence was recently confirmed by clinical objective responses reported in patients with different types of cancers at advanced stage of disease. The optimal immunotherapy to combine with radiotherapy remains to be defined. However, initial responses in the clinic have occurred with diverse immunotherapy approaches, which supports a general role of radiotherapy as a valid adjuvant.
Dose and fractionation are likely to be key variables in determining the effects of ionizing radiation on the immune system of the patients and/or in determining the success of radiotherapy when combined with different forms of immunotherapy. Similarly, the correct sequencing of radiotherapy and immunotherapy depends on the type of immunotherapy chosen.
In any event, radiation effects on the immune system have uncovered a novel application of this modality beyond that of a therapy that merely aims to accomplish local control of tumors, a paradigm shift from its current use in cancer. More than a century after the discovery of radium, ionizing radiation continues to surprise by revealing additional clinical effects and consequences.”
Lower Doses of Radiation?
This paper talks about using different doses of radiation, at different times with immunotherapy. The methodology of how and when to use it with immunotherapy still needs to be figured out, but it’s great to see a top radiation oncologist and immunologist looking at this. It can also possibly mean less radiation and less immunotherapy which means less side effects.
What Did We Learn?
So the lesson learned from Dr. James Ewing vs Dr. William Coley is that no person “won”. And in reality the world lost out. Just think if these two brilliant minds could have aligned realizing that their shared vision was to cure cancer. 100 years later we are finally studying the effects of immunotherapy and radiation combined. Pride and ego can get in the way of some amazing people. People that are still revered today but couldn’t get along 100 years ago while working at the same institution. An institution that has pioneered both of their work but wasn’t able to overcome the damage the battle caused until now.
We now know the lesson. It’s up to us as a society to learn from it.
How CHIPSA Uses Immunotherapy
CHIPSA has used immunotherapy for nearly 40 years. In 1996, the famed German physician Dr. Josef Issels came to Tijuana Mexico from Germany. Dr. Issels used Coley’s fluid and different immunotherapy treatments in Germany since the 1950’s. He would also use Coley’s fluid in conjunction with chemotherapy.
Issels brought the Coley’s treatment to Mexico. He had an interest in the effects of diet on cancer. In previous manuscripts Dr. Max Gerson mentioned that he was interested in working with Dr. Coley. This is something that Dr. Issels was open to. Issels was a doctor and scientist with an open mind; he spent the last two years of his life working at CHIPSA and sharing his knowledge. His family has also carries on his work today.
Now, 22 years later, Coley’s fluid is still an integral part of our treatment protocol. We see it as a “super adjuvant” as it works on multiple pathways that have now been discovered by mainstream science. In 2011, Bruce Buetler won a Nobel prize for discovering the TLR-4 pathway.24 In 2007 CPG was popularized when Coley’s Pharmaceutical sold 27% of their company to Pfizer for $164,000,000. CPG is a TLR 7, 8 and 9 therapeutic and was discovered as one of the drivers of Coley’s fluid.25 Basically, Coley’s fluid drives the innate immune system hard and allows the immune system to “wake up”. This increases the potential positive effects of treatments like IPT, Gerson Therapy, Apatone, and conventional approaches like chemotherapy and radiation.