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Study Demonstrates Impact of Both Inherited and Acquired Mutations on Cancer – Newswise

Posted: May 16, 2020 at 11:45 am

Newswise New Haven, Conn. The common belief that tumors arise via activation of a few genes that drive cancer development is unsupported by a widespread investigation into those genes and others in three large patient genetic databases, according to a study led by Yale Cancer Center (YCC) researchers. The findings were published online today in the Journal Nature Communications.

The pattern the Yale team uncovered shows that cancer develops due to combined effects of many gene variants originating both as the germline mutations, or inherited alterations in genes, and somatic mutations, changes that genes acquire after birth and over a lifespan. Some inherited germline variants do increase the risk of developing cancer, but additional somatic mutations are required for cancer to develop, usually in the third or fourth decade of life. Somatic mutations are random mutations that build up in cells as a person ages, and can substantially increase due to environmental effects, such as sunlight, cigarette smoking, diet, and exposure to various carcinogens.

In the new study, scientists found the proportion of germline variants to somatic mutations is linked to the age of cancer onset. Cancers that occur before age 50 which account for half of all cases have a greater degree of germline variations relative to somatic mutations. Likewise, investigators report that as people 50 and older age, their cancer is characterized by increasing levels of somatic mutations compared to germline variants. Thus, in younger people, a diagnosis of cancer is caused by a greater contribution of germline alterations, and late-onset cancer cancers are more dependent on acquired somatic mutations, said the researchers.

The strange thing about cancer driver genes, which had long been thought to be necessary and sufficient for cancer development, is that they do not seem to exist, said Lajos Pusztai, M.D., D.Phil., professor of medicine (medical oncology), co-director of the Genetics and Genomics Research Program at YCC, and senior author of the study. There is always some additional genetic abnormality that is also required for a cancer driver to manifest its transforming effect.

He added: Our work suggests to us that genes commonly considered cancer drivers may be more appropriately called cancer enablers because, under the right constellation of other genomic events, they enable transformation of a normal cell into cancer. In short, we hypothesize that the combined effect of other co-occurring somatic mutations and inherited germline variants together conspire to bring about cancer development.

This new understanding of cancer could have profound implications for prevention and treatment, according to the researchers. Instead of targeting just one or several cancer drivers in a given cancer type, effective cancer control may require a broader analysis of individual patient genomes and treatment that is specifically aligned with both germline and somatic mutations.

In this study, including postdoctoral fellow Tao Qing, Ph.D., the investigators analyzed three different large data sets The Cancer Genome Atlas (TCGA), the Pancancer Analysis of Whole Genomes (PCAWG) and the United Kingdoms Biobank (UKBB). The team is currently working on a cancer gene affectedness score that could be calculated for an individual and would sum up the combined effect of all deleterious germline variants. the researchers said this score could be used as new personalized cancer risk measure.

Funding for the study was provided by the Breast Cancer Research Foundation and the Susan G. Komen Foundation.

About Yale Cancer Center and Smilow Cancer Hospital Yale Cancer Center (YCC) is one of only 51 National Cancer Institute (NCI-designated comprehensive cancer) centers in the nation and the only such center in Connecticut. Cancer treatment for patients is available at Smilow Cancer Hospital through 13 multidisciplinary teams and at 15 Smilow Cancer Hospital Care Centers in Connecticut and Rhode Island. Smilow Cancer Hospital is accredited by the Commission on Cancer, a Quality program of the American College of Surgeons. Comprehensive cancer centers play a vital role in the advancement of the NCIs goal of reducing morbidity and mortality from cancer through scientific research, cancer prevention, and innovative cancer treatment.

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Study Demonstrates Impact of Both Inherited and Acquired Mutations on Cancer - Newswise

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Genomic Stocks Are in the First Inning of a Multi-Year Megatrend – ETF Trends

Posted: May 16, 2020 at 11:45 am

By Justin Spittler

Its easily the most overlooked megatrend Ive ever written about. Folks ignore this opportunity because its tough to wrap your head around. But its absolutely worth understanding.

The companies in this space are revolutionizing healthcare. Trillions of dollars are on the line. So, I dont expect this megatrend to fly under investors radars much longer.

In fact, the stocks at the forefront of this megatrend are waking up before our eyes. This tells me huge gains are on the horizon.

In a minute, Ill sharefour ways serious investors can profit off this revolution.But first, lets cover the basics.

Genomics is the study of all of a persons genes, and how those genes interact with each other and our own environments. By understanding all of our genes (our genome), scientists can discover secrets embedded in our DNA.

That is a gamechanger. With genetics, scientists only look at a single gene. With genomics, they examine all the genes that make up an organism. And that helps us understand human biology at a much deeper level.

Thanks to genomics, scientists can now determine at an early age what diseases a person might contract later in life. It can also help doctors detect problems earlier and more accurately treat them.

Its also helping us understand why some people who smoke, never exercise, and eat unhealthy foods live to be 100 years old. Armed with this information, scientists and doctors can better understand how someone will react to a particular drug or treatment. That opens the door for personalized or precise medicine.

People with vastly different genetic makeups receive the same treatment and the same drugs. Understanding a persons genetic makeup eliminates much of the guesswork. It will help doctors develop tailor-made solutions for every patient.

Genomics is also revolutionizing how pharmaceutical companies develop drugs. It even makes gene editing possible. Gene editing is exactly what it sounds like. Its the ability to manipulate a persons genes.

It sounds like science fiction. But scientists are already able to cut and paste mutations that cause cancer out of our DNA. I know this is all very technical. But the key takeaway here is that genomics is going to completely transform healthcare.

Breakthroughs in this field will ultimately allowbillionsof people to live longer and healthier lives. And the companies that make this happen will reap fortunes. Investors who understand this stand to make a fortune in the coming years. Of course, none of this was possible until recently.

The Human Genome Project took more than 10 years and about $3 billion to map the first human genome. Today, we can map a persons DNA in only a few hours for about $1,000.

Three years from now, the cost will fall to just $100. Thats one-millionth of what it cost two decades ago! When that happens, DNA sequencing will officially go mainstream.

By 2025, its projected that 100 million genomes will be sequenced. Thats up from 2.4 million genomes two years ago!

This will open a whole new world of understanding. Well truly be able to understand diseases on a personal level. Scientists could even use this tidal wave of information to cure cancer, HIV, pediatric blindness, and many other diseases!

And yet, the genomics revolution is completely ignored by the masses. Again, this is partly because the science of genomics will make most peoples heads spin.

The worlds biggest pharmaceutical and life sciences companies are at the forefront of this megatrend. Much smaller companies are also leading this revolution. But thats no excuse to ignore this opportunity.

Illumina (ILMN)the worldwide leader in genetic sequencinghas surged more than 188% since 2017.CRISPR Therapeutics (CRSP)a gene editing pioneersurged more than 400% in its first two years after its IPO.Editas Medicine (EDIT)another major player in the gene editing spacespiked 131% in its first two months as a publicly traded company!NeoGenomics (NEO), which specializes in cancer diagnostics, has rallied more than 5,000% since 2016!

Of course, anyone could cherry pick examples to prove their point. But this isnt the case of just a few stocks doing well.

Look at this chart. It shows the performance of theARK Genomic Revolution ETF (ARKG)since the start of 2017. This fund invests in companies at the forefront of genetic editing. Its actively managed by ARK Invest, an investment manager laser-focused on disruptive innovation.

ARKG has been on an absolute tear since the start of 2017. During that stretch, ARKG outperformed the biotech stocks by 3-to-1. It also crushed healthcare stocks by more than two-fold!

Dont worry if you missed out on this initial surge. Genomic stocks are just getting warmed up.

ARKG broke out to record highs recently. That puts the fund in the top 1% of stocks. In other words, genomics stocks are leading the market.

At RiskHedge,we focus on leaders because they deliver the biggest gains during bull markets. They also shine during bear markets. They either fall much less than most stocks or surge when most stocks are plunging. In todays uncertain environment, these are theonlystocks you should own.

Cathie Wood, ARKs CEO and founder, recently called the genomic revolution one of the most exciting investment ideas we have ever experienced.

Thats a bold statement. But its understandable. Genetic factors play a role in nine of the 10 leading causes of death in the United Statesoutside of car crashes and other accidents. In many cases, theyre the reason people get heart disease, cancer, and diabetes.

Its also estimated 1 in 5 adults may carry disease-related genetic mutations. And yet, only 5% of the diseases caused by one gene are treatable today. With gene editing that number could eventually reach 100%. According to Cathie Wood, those diseases alone represent a $2 trillion opportunity. The market for diseases caused by multiple genes issignificantlylarger!

And yet, CRISPR Therapeutics, Editas Medicine, andInvitae Corporation (NVTA)three companies pioneering gene editingaretogetherworth less than $8 billion!

The easiest way to capitalize on this megatrend is to invest in ARKG. You may also want consider investing in EDIT, NVTA, and CRSP. These three companies are at the forefront of the genetic editing revolution. Theyre also all top-ten holdings in ARKG.

By investing in these companies, youre making concentrated bets on companies turning the entire healthcare model on its head! Youll also be investing in companies that will likely save countless lives. Its a true win-win!

Just understand that the genomics revolution will unfold over the next 20 to 30 years. So, treat these stocks like long-term speculations.

The Great Disruptors:3 Breakthrough Stocks Set to Double Your Money

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What Tests for COVID-19 Antibodies Can and Can’t Tell Us About the Disease – Healthline

Posted: May 16, 2020 at 11:45 am

Antigen tests are the latest tool thats been given emergency use authorization by the Food and Drug Administration (FDA) in our fight against the new coronavirus.

The tests, which function similarly to rapid flu or strep tests, are designed to quickly detect tiny pieces of protein from the novel coronavirus that causes COVID-19. The test is done by swabbing a persons nasal cavity.

So far, only one antigen test has been permitted a rapid test kit created by the Quidel Corporation in San Diego that can show results within 15 minutes.

The FDA hopes to evaluate and authorize more antigen tests in the coming weeks.

The main advantage of these tests is their speed, according to the FDA. Being able to immediately know whether or not someones been exposed to the virus could, in theory, help reopen the economy and allow people to get back to work safely.

Antigen tests are also cheaper than other diagnostic tests available, and could easily be scaled up and distributed widely.

But there are some drawbacks to consider when administering these types of tests, health experts say.

The current diagnostic tests available are polymerase chain reaction (PCR) tests.

By swabbing a persons nasal cavity, PCR tests can detect the viruss genetic material and diagnose if a person is actively sick with COVID-19.

PCR tests are thought to be very accurate because of how sensitive they are to picking up genetic material. Theyre able to detect small amounts of genetic material, but it takes time to process and interpret the results in a lab.

Antigen tests, on the other hand, swab for antigens, or protein fragments on the surface of a virus that triggers an immune response.

This test looks for parts of the virus in tissue as a way of detecting infection, said Dr. James Zehnder, director of clinical pathology at Stanford Medicine.

Theyre lightning fast, providing results within minutes. But theres a lot of room for error.

Theyre faster but less sensitive [than PCR tests]. They miss many cases; very much limiting their value, said Dr. Sheldon Campbell, a Yale Medicine pathologist and professor of laboratory medicine at the medical school.

If a person tests positive on an antigen test, theres a high chance they do in fact have COVID-19.

That said, the FDA states that antigen tests miss a lot of active infections, and lead to a lot of false negatives. (Quidels test allegedly only catches 85 percent of positive cases.)

Its very concerning, said Campbell. They need 1,000 or more times as many virus particles to detect as the RNA tests do.

False negatives from an antigen test should be confirmed with a PCR test, the FDA advised.

Experts dont want a lot of people walking around thinking they dont have COVID-19, when in actuality they do.

Zehnder said that PCR tests remain the most sensitive and specific test to determine if someone is infected.

Antigen tests are limited, considering the whole purpose of diagnostic testing is to accurately detect cases and prevent transmission.

If your test results are crucial i.e. someone needs to know if theyre able to go to work or return to a long-term care facility its probably best to take a PCR diagnostic test.

If your results are less urgent perhaps you just want confirmation whether or not you have COVID-19 and will continue quarantining regardless then an antigen test alone may be useful, Campbell noted.

The tests arent as accurate as health experts would like them to be, but theyre another resource that can better help us manage the ongoing pandemic.

Antigen tests are the latest tool thats been given emergency use authorization by the FDA in our fight against the new coronavirus.

The tests, which function similarly to rapid flu or strep tests, are designed to rapidly detect tiny pieces of protein from the virus by swabbing a persons nasal cavity.

Though they provide rapid results and are cheap to produce, the tests are known to produce many false negatives and the results often need to be validated via a polymerase chain reaction test, or PCR test.

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Stoke Therapeutics Reports First Quarter Financial Results and Provides Business Updates – BioSpace

Posted: May 16, 2020 at 11:45 am

Company on track to begin enrollment and dosing of STK-001 in Part A of Phase 1/2a Monarch clinical trial in children and adolescents with Dravet syndrome in 2H 2020

Research activities ongoing to identify an additional preclinical candidate derived from the companys TANGO technology platform for the treatment of an additional genetic disease in 2H 2020

As of March 31, 2020, company has $211.5 million in cash, cash equivalents and restricted cash, anticipated to fund operations into 2023

BEDFORD, Mass.--(BUSINESS WIRE)-- Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company pioneering a new way to treat the underlying cause of genetic diseases by precisely upregulating protein expression, today reported financial results for the first quarter of 2020 and provided business updates.

I am incredibly gratified by the focus and determination of our employees during these challenging times. Thanks to their unwavering commitment to patients, we are continuing to make progress with STK-001 and are on track to enroll and dose the first children and adolescents with Dravet syndrome in the Phase 1/2a Monarch study later this year, said Edward M. Kaye, M.D., Chief Executive Officer of Stoke Therapeutics. Our understanding of the potential for our TANGO technology in additional genetic diseases has continued to advance and we are generating data that we believe will support the nomination of a second preclinical candidate in the second half of 2020.

First Quarter 2020 Business Highlights and Recent Developments

Upcoming Anticipated Milestones

First Quarter and Year-to-Date Results

About STK-001

STK-001 is an investigational new medicine for the treatment of Dravet syndrome. Stoke believes that STK-001, a proprietary antisense oligonucleotide (ASO), has the potential to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome. STK-001 is designed to upregulate NaV1.1 protein expression by leveraging the non-mutant (wild-type) copy of the SCN1A gene to restore physiological NaV1.1 levels, thereby reducing both occurrence of seizures and significant non-seizure comorbidities. Stoke has generated preclinical data demonstrating proof-of-mechanism and proof-of-concept for STK-001. STK-001 has been granted orphan drug designation by the FDA as a potential new treatment for Dravet syndrome.

About Phase 1/2a Clinical Study (Monarch)

The Monarch study is a Phase 1/2a open-label study of children and adolescents ages 2 to 18 who have an established diagnosis of Dravet syndrome and have evidence of a pathogenic genetic mutation in the SCN1A gene. The primary objectives for the study will be to assess the safety and tolerability of STK-001, as well as to characterize human pharmacokinetics. A secondary objective will be to assess the efficacy as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in convulsive seizure frequency over a 12-week treatment period. Stoke also intends to measure non-seizure aspects of the disease, such as quality of life as secondary endpoints. Stoke plans to enroll approximately 40 patients at 20 sites in the United States. Enrollment and dosing are expected to begin in the second half of 2020.

About Dravet Syndrome

Dravet syndrome is a severe and progressive genetic epilepsy characterized by frequent, prolonged and refractory seizures, beginning within the first year of life. Dravet syndrome is difficult to treat and has a poor long-term prognosis. Complications of the disease often contribute to a poor quality of life for patients and their caregivers. The effects of the disease go beyond seizures and often include severe intellectual disabilities, severe developmental disabilities, motor impairment, speech impairment, autism, behavioral difficulties and sleep abnormalities. Compared with the general epilepsy population, people living with Dravet syndrome have a higher risk of sudden unexpected death in epilepsy, or SUDEP. Dravet syndrome affects approximately 35,000 people in the United States, Canada, Japan, Germany, France and the United Kingdom, and it is not concentrated in a particular geographic area or ethnic group.

About Stoke Therapeutics

Stoke Therapeutics (Nasdaq: STOK) is a biotechnology company pioneering a new way to treat the underlying causes of severe genetic diseases by precisely upregulating protein expression to restore target proteins to near normal levels. Stoke aims to develop the first precision medicine platform to target the underlying cause of a broad spectrum of genetic diseases in which the patient has one healthy copy of a gene and one mutated copy that fails to produce a protein essential to health. These diseases, in which loss of approximately 50% of normal protein expression causes disease, are called autosomal dominant haploinsufficiencies. Stoke is headquartered in Bedford, Massachusetts with offices in Cambridge, Massachusetts. For more information, visit https://www.stoketherapeutics.com/ or follow the company on Twitter at @StokeTx.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: our first quarter results; the direct and indirect impact of COVID-19 on our business, financial condition and operations, including on our, expenses, supply chain, strategic partners, research and development costs, clinical trials and employees; our expectation about timing and execution of anticipated milestones, including enrollment in Part A of our Phase 1/2a Monarch clinical trial in Dravet syndrome, and our ability to use study data to advance the development of STK-001; the ability of STK-001 to treat the underlying causes of Dravet syndrome; and the ability of TANGO to design medicines to increase protein production. These forward-looking statements may be accompanied by such words as aim, anticipate, believe, could, estimate, expect, forecast, goal, intend, may, might, plan, potential, possible, will, would, and other words and terms of similar meaning. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop, obtain regulatory approval for and commercialize STK-001 and future product candidates; the timing and results of preclinical studies and clinical trials; the risk that positive results in a clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; failure to protect and enforce our intellectual property, and other proprietary rights; failure to successfully execute or realize the anticipated benefits of our strategic and growth initiatives; risks relating to technology failures or breaches; our dependence on collaborators and other third parties for the development, regulatory approval, and commercialization of products and other aspects of our business, which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; risks associated with current and potential future healthcare reforms; risks relating to attracting and retaining key personnel; failure to comply with legal and regulatory requirements; risks relating to access to capital and credit markets; environmental risks; risks relating to the use of social media for our business; and the other risks and uncertainties that are described in the Risk Factors section of our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this press release. We do not undertake any obligation to publicly update any forward-looking statements.

Financial Tables Follow

Stoke Therapeutics, Inc.Condensed consolidated balance sheets(in thousands, except share and per share amounts)(unaudited)

March 31,

December 31,

2020

2019

Assets

Current assets:

Cash and cash equivalents

$

211,288

$

222,471

Prepaid expenses and other current assets

4,342

3,281

Interest receivable

144

281

Total current assets

$

215,774

$

226,033

Restricted cash

205

205

Operating lease right-of-use assets

1,900

Property and equipment, net

2,962

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SEngine Precision Medicine to Present Data Related to the Predictive Value of PARIS Test, an Organoid-based Drug Response Assay, for…

Posted: May 16, 2020 at 11:45 am

SEATTLE, May 15, 2020 (GLOBE NEWSWIRE) -- SEngine Precision Medicine, a precision oncology company revolutionizing cancer diagnostics and therapies by pre-testing drugs on patient-derivedtumor-based organoids, today announced that data from a retrospective study summarizing the predictive value of the PARIS Test for cholangiocarcinoma will be presented virtually as a poster session (abstract number 8026) at the 2020 AACR Virtual Meeting Session II, to be held June 22-24, 2020.

The PARIS Test is CLIA certified to provide an actionable report to oncologists as a tool for therapeutic decisions, ranking sensitivity to targeted, endocrine and chemotherapy agents. The AACR poster presentation summarizes the strong correlation between genomics,retrospective treatment outcomes and PARIS Test drug sensitivity results based on a retrospective analysis of 17 cholangiocarcinoma patients.

This study shows the feasibility of functional testing of organoids derived from cholangiocarcinoma patients tissue in a CLIA-certified diagnostic test. These results correlate well with genomically predicted drug sensitivities for all patients, as well as showed additional drug sensitivities beyond those predicted by genomics offering patients additional potential treatment options. For patients whose cancer progressed on previous treatments (n=3), 100% retrospective concordance was shown between organoid drug resistance and prior treatment outcomes. Each patient represents a mosaic of drug sensitivities, reflecting unique combinations of genetic and epigenetic alterations, and the PARIS Test can identify the best personalized drug for them.

Details related to the poster presentation are as follows:Title:Organoid based functional test to predict personalized treatment in cholangiocarcinomaLead Author:Astrid Margossian, MD, PhDSenior Author: Carla Grandori, MD, PhDAbstract Number: 8026Poster Session: Translational Research with Targeted Therapies

About PARIS TestThe PARIS Test is based on the capability to propagate patient-specific cancer tissue as organoids ex vivo and is applicable to all solid tumors including colon, breast, lung, ovarian and pancreatic cancer. Organoids are cancer-derived cells grown in 3D outside the body, which maintain the functionality of the original tumor as well as its genomic characteristics. For cancers with no clear standard-of-care treatments, such as cholangiocarcinoma, personalized patient-derived tumor organoid testing lets treating physicians match the right drug to the right patient by providing organoid drug response data on candidate therapies.

About SEngine Precision Medicine SEngine Precision Medicine Inc. is a precision oncology company revolutionizing cancer diagnostics and therapies by pre-testing drugs on patient-derived organoids grown ex-vivo utilizing patient specific tumor cells.As a spin-out from the world-renowned Fred Hutchinson Cancer Research Center, SEngine is leveraging over two decades of R&D in diagnostics and drug discovery. The Company is commercializing the PARIS Test, a next generation diagnostic test that predicts drug responses integrating knowledge of cancer genomics with organoids, robotics, and AI-driven computational tools. SEngines CLIA certified PARIS Test generates predictive drug sensitivity reports for patients with solid tumors. SEngine is also pursuing drug discovery via strategic collaborations with biopharmaceutical / pharma companies leveraging its precision oncology platform.

Discover more at SengineMedicine.com and follow the latest news from SEngine on Twitter at @SEngineMedicine and on LinkedIn.

Contact:Stephanie Carringtonstephanie.carrington@westwicke.com646-277-1282

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What the SARS-CoV-2 Genome Reveals – Michigan Medicine

Posted: May 16, 2020 at 11:45 am

Viruses may seem like cunning villains, purposefully mutating to increasingly deadlier forms to outwit their human hosts. In reality, a lot of what happens with a virus is completely random. This randomness can make figuring out where a virus came from, how it spreads and what makes it tick especially tricky. For SARS-CoV-2, the new virus that causes COVID-19, scientists are looking to its genome for answers to some of these questions.

Researchers were recently able to determine that New York City may have been the original epicenter of the U.S. epidemic and that those initial cases were likely imported from Europe. They can tell this by looking at the genome and its sequence and seeing how they are similar or different, explains Adam Lauring, M.D., Ph.D., associate professor of microbiology and immunology and infectious disease.

Armed with virus samples taken from people with COVID-19, virologists and epidemiologists create what is known as a phylogenetic tree. This viral family tree lines up the genetic codes from each sample of virus to see whos related to whom.

Based on the genetic sequences and time of collection, you can start to paint a picture of how the virus moves through a population. The earliest [virus samples] in New York were more similar to the ones from people in Europe who were infected. You start with the dates, then look at the sequences and figure thats the most likely scenario, says Lauring. Its not foolproof, though. Theres always uncertainty.

A real world example of this uncertainty came to light with a study posted online in April, which described the deaths of two people from COVID-19 in Santa Clara, California weeks earlier than the virus was thought to be in California. What this tells us is that theres definitely missing data, says Lauring. This begs the question, he says, of where did those cases came from and how long the virus was spreading before the outbreak was recognized.

SEE ALSO: Seeking Medical Care During COVID-19

Researchers are also looking at the SARS-CoV-2 genome for clues about its true origin: the animal that infected the first person. So far, bats appear to be the most likely suspect. Looking at the phylogenetic tree, we see that a bat coronavirus is the closest relative to SARS-CoV-2, sharing around 96% of their genomes, says Lauring. But that too, is not the full story. Another animal, a small, scaly-skinned mammal called a pangolin, has been implicated as well.

The spike protein in SARS-CoV-2, the main protein on the surface that binds to the cells receptor and how the virus gets into the cell, is similar to a pangolin coronavirus spike protein, says Lauring. Its almost like, when you tell a person he has his fathers nose. That feature is similar, but across features the father and child may not look very similar. Coronaviruses, like a lot of other viruses, swap genes around.

These swaps are examples of mutations, which are common in RNA viruses like SARS-CoV-2. Laurings lab focuses on mutations in influenza, the RNA virus behind the infamous 1918 Spanish flu pandemic. Understanding how influenza mutates is critical for making decisions about the annual influenza vaccine. RNA viruses mutate relatively quickly because they lack a proofreading mechanism to look for and repair errors during replication.

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However, SARS-CoV-2 and its coronavirus cousins are unique among RNA viruses, because they have a proofreading enzyme. The coronavirus genomes are three times longer than youd expect them to be, and the presence of the proofreading enzyme explains that nicely, says Katherine Spindler, Ph.D., professor in the department of microbiology and immunology. Spindler is a host for the podcast This Week in Virology, which examines the latest science around SARS-CoV-2 and other viruses.

With this enzyme, the virus can make a few more errors and not have it be lethal for the virus. As a result, SARS-CoV-2 mutates more slowly than other RNA viruses. Spindler notes that only about 20 mutations have been retained in the genome so far since the beginning of 2020, despite the billions of times the virus has replicated.

SEE ALSO: Keeping Our Patients Safe During COVID-19

Even with its relatively slow mutation rate, mutations present in each persons SARS-CoV-2 genome allows researchers to do genetic tracing in real time, says Lauring. His lab hopes to study the virus genome more closely to look at how the virus is transmitted in healthcare settings and communities.

He stresses that just because a virus mutates doesnt mean the mutations are making it stronger, more likely to be transmitted, or that it will be tougher to develop a vaccine. My hunch is evolution wont be the biggest challenge in developing a vaccine. There are viruses that evolve relatively quickly for which we do have vaccines, for example polio, measles, mumps, Ebola, hepatitis A, notes Lauring.

Spindler adds that the fact that were seeing a variety of COVID-19 symptoms doesnt mean there are different mutant strains. Every new symptom that comes along, from COVID toes and skin rashes to blood clots, are likely just additional manifestations of the virus as it infects so many different people, she says. Figuring out the mysteries of SARS-CoV-2 will take years of experimental work, she says.

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WHITEHALL ANALYTICA THE AI SUPERSTATE: Part 2 Is COVID-19 Fast-Tracking a Eugenics-Inspired Genomics Programme in the NHS? – Byline Times

Posted: May 16, 2020 at 11:45 am

Nafeez Ahmed explores the troubling implications and assumptions of the Governments AI-driven gene programme.

In Part 1 of this investigation, I looked at how the convergence of an AI Superstate and corporate interests with health data lies at the heart of a new frontier for profit and surveillance. But the Governments response during the COVID-19 pandemic has revealed something even more profoundly disturbing: a fascination with genomics which moves from a merely descriptive tool to something so prescriptive it verges on eugenics.

The NHSX app is simply one project with a questionable design which appears to result from the Governments much wider project to remake the NHS.

At the core of the new NHSX AI drive is the goal of predictive, preventive, personalised and participatory medicine, according to an NHSX document published in October 2019. Pivotal to this AI-driven transformation is genetics:

Key to unlocking the benefits of precision medicine with AI is the use of genomic data generated by genome sequencing. Machine learning is already being used to automate genome quality control. AI has improved the ability to process genomes rapidly and to high standards and can also now help improve genome interpretation.

The NHS Genomic Medicine Service is starting with a focus on cancer, rare and inherited diseases,but its broader goal is far more comprehensive. Initially, the hope is that genomics will expand to cover other areas, such as pharmacogenomics, which looks at how an individuals genes influence a particular biological process that mediates the effects of a medicine, according to The Pharmaceutical Journal.

But the end-goal is to convert the NHS into a health service oriented fundamentally around the role of genetics in disease. The aspiration is that from 2020, and by 2025, genomic medicine will be an embedded part of routine care to enable better prediction and prevention of disease and fewer adverse drug reactions. The GMS aims to complete five million genomic analyses and five million early disease cohorts over the next five years.

By 2025, genomic technologies will be embedded through multiple clinical pathways and included as a fundamental part of clinical training. As a result, it is hoped that there will be a new taxonomy of medicine based on the underlying drivers of disease.

But, this entire premise is deeply questionable. There is little evidence that the underlying drivers of disease are primarily genetic.

Last December, a study in the journal PLOS One found that genetics usually explains no more than 5-10% of the risk for several common diseases. The study examined data from nearly 600 earlier studies identifying associations between common variations in the DNA sequence and more than 200 medical conditions. But its conclusion was stark: more than 95% of diseases or disease risks including Alzheimers, autism, asthma, juvenile diabetes, psoriasis, and so on could not be predicted accurately from the DNA sequence. A separate meta-analysis of two decades of DNA science corroborated this finding.

The implication is startling: that the entire premise for the billions of pounds this Government is investing in building a new privatised NHS infrastructure for AI-driven genomic medicine is scientifically unfounded.

The obsession with genetics can be traced directly back to the Prime Ministers chief advisor, Dominic Cummings.

Cummings set out his vision for the NHS in a February 2019 blog, which although previously reported on has not been fully appreciated for its astonishingly direct implications. While focusing on disease risk, the blog flagged-up Cummings hopes that a new NHS genomics prediction programme would ultimately allow the UK to, not just prevent diseases, but to do so before birth in effect a nod toward the selective breeding techniques at the core of eugenics.

They are using the COVID-19 crisis to erect a corporate superstate powered by mass surveillance and AI. Their grim ambition is to reach into the very DNA of every British citizen.

His vision for what a genomics-focused NHS would look like bears startling resemblance to the core ideas of eugenics the discredited pseudoscience aiming to improve the genetic quality of a human population by selecting for superior groups and excluding those with inferior genes. Its worst manifestations were exemplified by the Nazis.

In the blog, Cummings wrote:

Britain could contribute huge value to the world by leveraging existing assets, including scientific talent and how the NHS is structured, to push the frontiers of a rapidly evolving scientific field genomic prediction. He called for free universal SNP [single-nucleotide polymorphis] genetic sequencing as part of a shift to genuinely preventive medicine, to be rolled-out across the UK. This approach holds the promise of revolutionising healthcare in ways that give Britain some natural advantages over Europe and America.

Later in the post, Cummings allowed himself to speak more directly to what natural advantages could actually entail. He claimed that a combination of AI-driven machine learning with very large genetic sampling could enable the precise prediction of complex traits such as general intelligence and most diseases.

The two scientists Cummings cited as the primary sources for his vision were educational psychologist Robert Plomin and physicist Steven Hsu.

Plomin, described by Cummings as the worlds leading expert on the subject, is a renowned scientist. But he also has a history of association with the eugenics movement, according to Dr David King, founder of Human Genetics Alert and previously a molecular biologist. (Sir David King, the former chief scientific adviser to the UK Government, has also criticised the genome sequencing goldrush).*

When The Bell Curve a book advocating the genetic inferiority of African Americans was published, Plomin was a key signatory to a statement defending the science behind the book, explained Dr David King in a paper for the non-profit watchdog Human Genetics Alert. The statement carefully avoided explicitly endorsing The Bell Curves racist conclusions (aptly summarised by Francis Wheen as black people are more stupid than white people: always have been, always will be. This is why they have less economic and social success), while failing to repudiate them. Plomins fellow co-signatories included several self-proclaimed scientific racists, Philippe Rushton and Richard Lynn. Plomin has also published papers with the American Eugenics Society and spoken at several meetings of the British Eugenics Society (the latter rebranded itself as the Galton Institute in 1989) both of which advocated racial science.

In December 2013, Plomin was called as an expert witness to the House of Commons Education Select Committee, where he called for the Government to focus on the heritability of educational attainment. Twenty-five minutes into the session, Dominic Raab who as Foreign Secretary and First Secretary has stood in for Boris Johnson during his period of absence due to COVID-19 prompted Plomin to focus more specifically on explaining his views about genetics, intelligence and socio-economic status.

Just two months before Plomins parliamentary testimony, a 237-page dossier by Cummings then a top advisor to Education Secretary Michael Gove was leaked to the press. The paper claimed that genetics plays a bigger role in a childs IQ than teaching and called for giving specialist education as per Eton to the top 2% in IQ. Pete Shanks of the Centre for Genetics and Society described Cummings policy proposal as a blatantly eugenic association of genes with intelligence, intelligence with worth, and worth with the right to rule.

The Cummings dossier which cites Plomin extensively further reveals that, according to Cummings, he had invited Plomin into the DfE [Department for Education] to explain the science of IQ and genetics to officials and ministers.

The Education Select Committees report shows that, at the time of Plomins testimony, the Government was resistant to these views. But, the position appears to have changed since then, with figures such as Cummings, Raab and Gove now at the seat of power under Prime Minister Boris Johnson.

Plomin would go on to work with Steven Hsu, who was involved in a major Chinese genome sequencing project based on thousands of samples from very high-IQ people around the world. The goal was to identify genes that can predict intelligence. Hsu went on to launch his own company, Genomic Prediction. In slide presentations about his work from 2012, Hsu approvingly quoted British eugenicist Ronald Fisher, closing his slides with the following quotation: but such a race will inevitably arise in whatever country first sees the inheritance of mental characters elucidated. Hsus slides, wrote David King, include plans for a eugenic breeding scheme using embryo selection to improve the overall IQ of the population.

Yet, on his blog, Cummings confirmed that Hsu has recently attended a conference in the UK where he presented some of these ideas to UK policy-makers. Among the ideas Hsu presented to Cummings colleagues in Government was that the UK could become the world leader in genomic research by combining population-level genotyping with NHS health records. Hsu further claimed that risk prediction for common diseases was already available to guide early interventions that save lives and money.

Hopefully the NHS and Department for Health will play the Gretzky game, take expert advice from the likes of Plomin and Hsu and take this opportunity to make the UK a world leader in one of the most important frontiers in science, enthused Cummings.

Plomins claim that intelligence is determined primarily by genes contradicts a vast body of scientific literature, and is largely overblown. One of the latest studies debunking Cummings hopes was led by the University of Bristol and published in March. Based on a sample size of 3,500 children, the study found that polygenic scores (which combine information from all genetic material across the entire genome) have limited use for accurately predicting individual educational performance or for personalised education.

The study did not dismiss a role for genes outright, noting genetic scores modestly predictededucational achievement. The problem was that these predictions were less accurate than using standard information known to predicteducational outcomes, such as achievement at younger ages, parents educational attainment or family socio-economic position.

Last November, Hsus Genomic Prediction began touting new report cards to its customers. The cards displayed alleged results of genetic tests containing warnings that embryos might have low intelligence, grow up to be short, or have other conditions such as diabetes. But, according to the MIT Technology Review, the company has struggled both to validate its predictions and to interest fertility centres in them. In the month prior to Hsus grand announcement, the first major study to test the empirical viability of screening embryos, led by statistical geneticist Shai Carmi of the Hebrew University of Jerusalem, concluded that the technology is not plausible.

The lack of scientific substantiation has not stopped Cummings from suggesting a more interventionist vision for the NHS, which could be accused of paving the way for a new form of eugenics. In his February 2019 blog, he wrote: We can imagine everybody in the UK being given valuable information about their health for free,truly preventive medicinewhere we target resources at those most at risk, and early (evenin utero) identification of risks. This passage appears to nod to the core eugenics notion of selective breeding using embryo selection. Cummings even went further to endorse the goal of editing genes to fix problems.

In a further telling but slightly more well-known passage, Cummings characterised the genomics programme as a precursor to more realistic views about IQ and social mobility: It ought to go without saying that turning this idea into a political/government success requires focus on A) the NHS, health, science, NOT getting sidetracked into B) arguments about things like IQ and social mobility. Over time, the educated classes will continue to be dragged to more realistic views on (B) but this will be a complex process entangled with many hysterical episodes. (A) requires ruthless focus.

This passage affirms that Cummings approach is deliberately deceptive. The focus on health and the NHS is revealed as a cover for a longer-term vision to usher in more realistic views about things like IQ and social mobility. The passage also lifts the rock on Cummings weakest point that he fears that public attention on these more realistic views could sidetrack the broader strategy before it reaches fruition.

In the words of Dr David King, Cummings deference to Hsu, who openly advocated eugenics breeding programmes, suggests that the Prime Ministers chief advisor clearly favours this strategy for Britain; of course, this is precisely what all the European countries were trying to achieve in the heyday of eugenics to overcome their imperialist competitors by improving the national stock.

This, it seems, is the essence of Cummings ambition to use the NHS genomics prediction programme as a mechanism to provide Britain natural advantages over Europe and America.

And in this context, it is impossible to ignore the implications of Cummings appointment of Andrew Sabisky to a senior role advising Boris Johnson. When Johnsons spokespeople were asked repeatedly whether the Prime Minister would condemn Sabiskys sympathies for racist eugenics, he repeatedly refused. Sabisky later stepped away from the role.

The COVID-19 pandemic has now provided the Government with the opportunity to double down on its goals of extending genome sequencing across the UK population.

While genomic sequencing of the Coronavirus is undoubtedly an important scientific task to map and understand it, the crisis fits neatly into Cummings call for a ruthless focus on the NHS as a vehicle for Britains genetic enhancement.

On 23 March, when the UK finally instituted a lockdown at least three weeks after being informed that hundreds of thousands of people (and potentially up to a million) people were at risk of death from its previous policy of herd immunity, the Government launched a new scientific research consortium coordinated by Cambridge University along with the Wellcome Sanger Institute, the NHS and Public Health England.

The consortium would gather samples from patients confirmed with COVID-19 and send them to genetic sequencing centres across the country to analyse the whole genetic code of the samples. The project was billed breathlessly as an essential step in being able to control the pandemic and prevent further spread.

Unsurprisingly, it has done no such thing. Instead, six weeks later, the UK has ended up with the highest COVID-19 fatality rate in Europe.

As the death toll approaches the same level of British civilian casualties during the Second World War, the Governments strategy has privileged ambiguous, extortionate high technology solutions, pouring hundreds of millions of pounds into powerful private sector players with no transparency or due process. Meanwhile, traditional, proven, public health strategies such as better border controls, or extensive contact tracing and testing by scaling up local capacity, were inexplicably delayed for months.

On 13 March, the Government launched a new partnership between the NHS, Genomics England, the GenOMICC consortium, and US biotech giant Illumina, to conduct a nationwide human whole genome sequencing study targeting COVID-19 patients in 170 intensive care units.

The Governments new genome sequencing partner, Illumina, has previously produced genetic sequencing systems marketed to police agencies in China to facilitate its genetic profiling of the minority Uyghur population in Xinjang the largest system of discriminatory, ethnically-targeted biometric surveillance using DNA ever created.

It is difficult to avoid the conclusion that Dominic Cummings and his fellow ideologues in Government are hell-bent on pursuing a pseudo-scientific vision that has been years in the making.They are using the COVID-19 crisis to erect a corporate superstate powered by mass surveillance and AI. Their grim ambition is to reach into the very DNA of every British citizen.

Dominic Cummings was contacted for this article, but is yet to reply.

*This article was corrected to remove a confusion between Sir David King, the former government chief scientific adviser, and Dr David King, the molecular biologist who isthefounder and Director of Human Genetics Alert.

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WHITEHALL ANALYTICA THE AI SUPERSTATE: Part 2 Is COVID-19 Fast-Tracking a Eugenics-Inspired Genomics Programme in the NHS? - Byline Times

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Researchers: Disease affecting kids could be in the genes – Newsday

Posted: May 16, 2020 at 11:45 am

The key to understanding and fighting the mysterious COVID-19-related inflammatory illness that is targeting children across the state could be in their genes.

The New York Genome Center is analyzingblood samples from the young patients with the hopes of finding genetic markers specific to the disease known as "pediatric multi-system inflammatory syndrome associated with COVID-19."

The state is investigating 102 cases of children who have the illness, which shows symptoms similar to Kawasaki disease or toxic shock syndrome. Three people, including an 18-year-old girl from Suffolk County, have died from the syndrome.

"This approach is widely used to study the genetic basis of all diseases, said Tom Maniatis, Evnin Family scientific director and chief executive officer of the New York Genome Center. We are trying to see if there are anygenetic clues to what might be causing this syndromein children.

If we can detect and understand thegenetic basis for predisposition, and how the immune system is affected in the disease, it might be possible to develop strategies for the clinical care of these children, he added.

Gov.Andrew M. Cuomo announced last week the state Department of Health was partnering with the Genome Center and The Rockefeller University to conduct a genome and RNA sequencing study of the illness, which hasbeen identified in 14 other states, including neighboring New Jersey and Connecticut, as well as five European countries.

Cuomo said Wednesday that60% of children with the illness have tested positive for COVID-19 and 40% had the antibody, meaning they may have been exposed to the coronavirus weeks before. Of those affected, 71% became seriously ill and were placed in intensive care units. He said 43% of those minors remain hospitalized and 19% had to be intubated.

According to a racial and ethnic breakdown of cases on thestate health department's website, 25% were white, 23% black, 20% other, 3% Asian and 31% unknown. In addition, 35% were Hispanic/Latino, 40% non Hispanic and 25% unknown.

Officials at Cohen Childrens Medical Center in New Hyde Park said they are seeing as many as two or three children a day with symptoms of the syndrome: fever and severe abdominal pain, rashes and red lips, eyes and tongue.

Experts believethe patients bodies might be having an extreme reaction to COVID-19, the disease caused by the novel coronavirus.

Whats so striking about this phenomena is that we all thought that most children were relatively safe, considering that they have the lowest mortality rate of any of the categories of COVID patients, Maniatis said.

A genome is an organisms complete set of DNA, including its genes, with all of the information needed to build and maintain that organism, according to the Bethesda, Maryland-based National Institutes of Health.

Researchers will look through the genome of patients in an effort to find DNA sequences that vary from the standard.

By comparing the childrens DNA sequence to the standard, we might be able to identify a variant that is not seen normally in most individuals, Maniatis said. And if you can show that it happens enough, you can begin to conclude that statistically its likely the DNA sequence change is associated with the disease."

The next step is RNA sequencing, which could provide insights into identification of altered immune pathways that are known to operate during virus infections.

Similar sequencing research conducted in the past led scientists to discover a gene mutation in people with blood cancer that impacted their immune system. A drug calledGleevec was developed to correct that mutation.

The Feinstein Institutes for Medical Research in Manhasset plans to participate in the study, said Dr. Peter Gregersen, professor of molecular medicine at Feinstein, the research arm of Northwell Health.

He said understanding the genetic variations of COVID-19 and the related illness thats attacking children is key to finding effective treatment.

We know age, sex and certain underlying conditions play a role, but genetic variations have something to do with this as well, Gregersen said. A lot of variations are unexplained. We know there is a huge variation, and some people dont get sick at all, while others have a devastating illness.

Maniatis said a vital part of the investigation is the collaboration with Jean-Laurent Casanova, head of the St. Giles Laboratory of Human Genetics of Infectious Diseases at The Rockefeller University.

He is one of the worlds experts in this field, and he established an international consortium directed toward understanding exceptional cases of clinical manifestations, Maniatis said. With Jean-Laurents participation, the search would extend from our efforts in New York and New Jersey to include researchers around the world and that will increase the statistical significance of any finding.

Lisa joined Newsday as a staff writer in 2019. She previously worked at amNewYork, the New York Daily News and the Asbury Park Press covering politics, government and general assignment.

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Doctor believes Dominican Republic’s economy could open in two weeks – Dominican Today

Posted: May 16, 2020 at 11:45 am

Dr. Jos Rafael Yunn, an infectologist, and intensivist, considered yesterday that if the behavior of covid-19 continues on the same trajectory in the country, the gradual opening of the economy can begin in two weeks. He assured that the low mortality from covid-19, less than 1%, could be due to multiple explanations, genetic or of treatments that have been applied.

If the behavior of the epidemic in the country does not change in the next two weeks, we could gradually open the confinement, always protecting vulnerable people, he said. He believes that the opening of the economy should be started using intelligent measures of social distancing, and penalizing if they are not carried out through the use of continuous surveillance.

The critical medicine expert assures that the case fatality rate in the Dominican Republic has not increased, even with a high positivity rate.When analyzing the number of patients in intensive care units, based on real-time, it is 1.8%. The expert and member of the high-level commission that manages the issue said that the opening process should be carried out, protecting vulnerable people.

Yunn considers that everything must be done evaluating the number of cases, the percentage of occupancy of beds, and the percentage of lethality, in a systematic and constant way.

The main hypothesis is that the behavior of covid-19 could be related to issues such as climate, previous vaccination against tuberculosis with BCG, cross-reaction with other viruses such as zika, dengue, and chikungunya. It could also be explained in the use of such criticized treatments as Hydroxychloroquine or Ivermectin.

Could the disease and lethality behavior of covid-19 be due to vitamin D levels? asks the specialist.Is it also the genetic factors, is the stability the result of appropriate early quarantine or the sum of all? He asks.

Yesterdays report from the General Directorate of Epidemiology reported that the country already registers 11,739 positive cases (419 new ones), of which 1,885 people are in hospital isolation and 5,873 in-home isolation; visits are made to the latter for face-to-face monitoring, as well as telephone assistance and delivery of the indicated medications.

Only 127 of hospitalized patients are in intensive care units (ICU). The positivity rate in the samples processed during the last four weeks is 21.30%. Measures the specialists and authorities keep in place are the recommendations to the population to maintain a distance of at least one meter between two people. Also, the use of masks in work and public spaces. Care and isolation at the home of people with mild signs and symptoms.

It is recommended to seek care in health centers if you have a fever, headache, sore throat, diarrhea, loss of smell, malaise, cough, and respiratory distress.

To doctors, Yunn warned they refrain from doing ego-based medicine, and instead employ an evidence-based medicine.He assured that the low mortality, less than 1% by covid-19, could be due to multiple explanations, genetic, environmental, measures, or treatment regimes, in Dominicans.

The critical medicine expert referred to the warning made by his infectious colleagues about the use of treatments such as Ivermectin and other therapeutic options to treat covid-19. There is no justification right now for sending letters between medical societies without a proposal that offers solutions, he said.

In his opinion, what should be done in the medical community is to evaluate the protocols that are currently being applied and then, according to the lessons learned, carry out clinical trials to guide their effectiveness. Otherwise we would be promoting an ego-based medicine and not evidence-based collaborative medicine, said the expert.

It was asked what use is the state of confinement to which the countrys regulatory bodies have subjected the population if medical practice is frequently reversed.The lethality has not been so excessive.

The Society Infectious Diseases group expressed concern about the possibility that Ivermectin could be used as one of the therapeutic options to treat covid-19. MostSociety of Infectology members state that the use of parenteral Ivermectin should not even be weighted for the regular treatment of covid-19.

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Doctor believes Dominican Republic's economy could open in two weeks - Dominican Today

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Genetic Analysis Reveals the Fascinating Evolutionary Origins of Catmint AKA Catnip – SciTechDaily

Posted: May 16, 2020 at 11:45 am

Catmint emits the odor nepetalactone which triggers a kind of ecstasy in sexually mature cats: They get high on sniffing at catmint plants, roll on the floor and exhibit an unusually playful behavior. Credit: Phil Robinson, John Innes Centre, Norwich, UK

Researchers discover the evolutionary origins of the cat attractant nepetalactone.

Catmint, also known as catnip, is well-known for its intoxicating effect on cats. The odor responsible for the cats strange behavior is nepetalactone, a volatile iridoid produced by catmint.

An international team of researchers has now found through genome analysis that the ability to produce iridoids had already been lost in ancestors of catmint in the course of evolution. Hence, nepetalactone biosynthesis is the result of repeated evolution. Nevertheless, this particular iridoid differs considerably from other compounds in this group of natural products with regards to its chemical structure and properties, and most likely its ecological functions (Science Advances).

Iridoids are plant secondary metabolites from the group of terpenes. Many plants produce these substances to defend themselves against herbivores or to protect themselves from pathogens, among these plants many species from the mint family (Lamiaceae). The ancestors of a particularly species-rich subfamily of the Lamiaceae, the Nepetoideae, which includes many well-known herbs, such as basil, oregano, rosemary, lemon balm, and mint, had lost the ability to produce iridoids in the course of evolution.

However, there is an important exception: the genus Nepeta, called catmint or catnip. Catmint plants produce iridoids including a very special form: nepetalactone, a volatile substance known to excite cats. Presumably, its actual function is to deter herbivores from trying to feed on catmint.

Catmint (Nepeta cataria), also called catnip, from the genus Nepeta belongs to the Lamiaceae family. It is well-known for its effect on cats. However, it is not clear why cats respond to the odor nepetalactone. Credit: Phil Robinson, John Innes Centre, Norwich, UK

An international team of researchers led by Sarah OConnor, director of the Department of Natural Product Biosynthesis at the Max Planck Institute for Chemical Ecology in Jena, Germany, has now investigated how and why catmint makes nepetalactone and how the biosynthetic pathways for the formation of this unique chemical molecule have evolved.

To answer this question, they sequenced the genome of catmint. We discovered a suite of unusual enzymes that generate nepetalactone molecules. These enzymes are not found in any related plant species and have evolved uniquely in catmint. When we first saw the genome sequence of catmint we realized that the important genes that we hypothesized were active in the formation of nepetalactone were next to each other in the genome. This allowed us to solve the problem more easily, explains Benjamin Lichman from the University of York, who is the first author of the study.

The scientists compared the genome of two catmint species which are both able to produce nepetalactone to the closely related medicinal plant hyssop (Hyssopus officinalis) which is neither able to produce nepetalactone nor any other iridoids. This comparative approach, the reconstruction of ancient genes, as well as comprehensive phylogenetic analyses enabled the researchers to understand the chronology of events that led to the emergence of nepetalactone biosynthesis. They were able to determine the mechanisms for the loss and subsequent re-evolution of iridoid biosynthesis in catmint. These new discoveries provide broader lessons in the evolution of plant metabolic novelty and diversity.

In particular, the nepetalactone pathway is found as a gene cluster, a group of similar genes located in the immediate vicinity in the genome. By looking at this cluster, together with gene fossils and resurrected ancient enzymes the scientists elucidated important steps that led to the formation of this cluster. Similar steps lead to the evolution of the impressive plant metabolic diversity in many plant lineages.

Catmint provides a great model example for studying these processes. We are now trying to modify the chemicals present in the catmint plants. This will help us know if we completely understand all aspects of the pathway as well as understand the ecological functions of nepetalactone. This can in turn help us to uncover the selective pressures that led to loss and regain of this pathway. We are also looking at other Nepeta species that produce unusual iridoids, says Sarah OConnor summarizing her future research plans.

The leader of the study has been the new director and head of the Department of Natural Product Biosynthesis at the Max Planck Institute for Chemical Ecology in Jena, Germany, since last year. The focus of her research is on the biosynthesis of plant metabolic products which do not only have multiple ecological roles in mediating a plants interactions with its environment, but also hold promising potential in medicine. She wants to understand how and why plants apply such complex chemical reactions to produce this fascinating diversity of molecules: Plants are constantly evolving new chemistry. With our research, we would like to get snapshots of this evolution in action.

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Reference: The evolutionary origins of the cat attractant nepetalactone in catnip by Benjamin R. Lichman, Grant T. Godden, John P. Hamilton, Lira Palmer, Mohamed O. Kamileen, Dongyan Zhao, Brieanne Vaillancourt, Joshua C. Wood, Miao Sun, Taliesin J. Kinser, Laura K. Henry, Carlos Rodriguez-Lopez, Natalia Dudareva, Douglas E. Soltis, Pamela S. Soltis, C. Robin Buell and Sarah E. OConnor, 13 May 2020, Science Advances.DOI: 10.1126/sciadv.aba0721

This research was funded by the Mint Genome Project (National Science Foundation) led by C. Robin Buell at Michigan State University.

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