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Rest for the Weary . . . – Thrive Global

January 13th, 2020 3:50 pm

Each night, when I go to sleep, I die. And the next morning, when I wake up, I am reborn.Mahatma Gandhi

Happy New Year! Happy New Decade! Early January and the holidays are over and most of us are getting back into Real Life. For many of us, weve burned the candle at both ends and perhaps are feeling the exhaustion of the culmination of doing too much and not getting enough sleep. Ive heard so many women in the last month or so tiredly grin, (or grimace) and say No rest for the weary. As though we all must blithely accept exhaustion.

But No We cannot accept this lying down . . . or more likely running around! Sleep is essential and has been described by sleep expert Matthew Walker, as our life-support system and Mother Natures best effort yet at immortality.

The decimation of sleep throughout industrialized nationsis having a catastrophic impact on our health, our wellness,even the safety and the education of our children.Its a silent sleep loss epidemic,and its fast becoming one of the greatest public health challengesthat we face in the 21st century.

So why do we needsleep? What difference does a good nights sleep actually make? I think we allknow the obvious answers to that lack of sleep makes us tired, grumpy and notquite able to think properly. But research shows that its much more seriousthan that. Not enough sleep or poor quality sleep impacts our immune system,hormones, heart, learning, memory and even impacts mens testicles and womensreproductive organs. Interestinglyenough, it also impacts our genetic code.

Lack of sleep hugelyimpacts our ability to heal as well. Inour body we have cells that protect us, sometimes called naturalkiller cells.You can think ofnatural killer cells almost like the secret service agentsof your immunesystem.They are very good at identifying dangerous, unwantedelementsand eliminating them.In fact, what theyre doing here isdestroying a cancerous tumor mass.So what you wish for is a virile set ofthese immune assassinsat all times,and tragically, thats what youdont have if youre not sleeping enough.

And as we age, and our memory seems to faderapidly, all of us over 50 can certainly attest to that, sleep is even moreessential. Researchis showing that the disruption of deep sleepis anunderappreciated factorthat is contributing to cognitive decline ormemory declinein aging, and most recently discoveredin Alzheimersdisease as well.

Basically in anutshell there is nothing positive about not getting enough sleep.

A good laugh and a long sleep are the best cures for anything.

Old Irish Proverb

On the other hand,getting enough sleep positively impacts us in almost every way. We have a stronger immune system, betterfocus, better memory, and a more optimistic outlook on life.

Walkerdescribes recent research done at UC Berkeley on sleep and learning:

By placing electrodes all over the head,what weve discovered is that there are big, powerful brainwavesthat happen during the very deepest stages of sleepthat have riding on top of themthese spectacular bursts of electrical activitythat we call sleep spindles.And its the combined quality of these deep-sleep brainwavesthat acts like a file-transfer mechanism at night,shifting memories from a short-term vulnerable reservoirto a more permanent long-term storage site within the brain,and therefore protecting them, making them safe.And it is important that we understandthat during sleep actually transacts these memory benefits,because there are real medical and societal implications.

Sleep provides time for our brains to tidy up and make space; this action is called synapticpruning.

Sleepprovides a time when the brainssynapses theconnections among neuronsshrink back by nearly 20percent.Duringthis time, thesynapsesrest and preparefor the next day, when they will grow stronger while receiving new input tolearn new things.

Without this reset, knownas synaptic homeostasis, synapses could become overloaded andburned out, unable to function at an optimal level. Scientists call this use-dependent corticalreorganization, meaning that we strengthen whichever neural pathways we usemost often, and lose the ones we use the least.

I am totally in favorof pruning those unused pathways. Iusually feel like my brain can use a little Marie Kondo action!

I think we all canagree that getting more and better quality sleep is essential. But what is the best way to do that? Fortunately, Walker does have a fewsuggestions:

The first is regularity.Go to bed at the same time, wake up at the same time,no matter whether its the weekday or the weekend.Regularity is king,and it will anchor your sleepand improve the quantity and the quality of that sleep.The second is keep it cool.Your body needs to drop its core temperatureby about two to three degrees Fahrenheit to initiate sleepand then to stay asleep,and its the reason you will always find it easierto fall asleep in a room thats too coldthan too hot.So aim for a bedroom temperature of around 65 degrees,or about 18 degrees Celsius.Thats going to be optimal for the sleep of most people.

One of my New Years Resolutions this year is to meditate more often, and the Dalai Lama declares that sleep is the best meditation. And who am I to disagree with the Dalai Lama? So I think Ill close here and go take a nap. Happy New Year to all of you, and may you have a restful 2020 filled with wonderful deep healing sleep.

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Forty Seven: Buy The Dip In This CD47 Pioneer Ahead Of ASCO GI – Seeking Alpha

January 13th, 2020 3:49 pm

Shares of CD47 front-runner Forty Seven (FTSV) have risen by 120% over the past year and by 525% over the past three months. Currently, this growing biotech firm sports a market capitalization of around $1.75 billion, with management executing quite efficiently on accessing financing in mid December with 4.86 million common shares priced at $35 per share (plus underwriter option) for gross proceeds of around $170 million.

Biotech Phoenix, a veteran of the industry who graciously offers insights in our Live Chat from time to time, got me interested in this name when he highlighted the significance of promising clinical data for lead product candidate magrolimab in patients with Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML). These are typically indications I'd feel that I don't have an edge in, considering the high amount of competition. However, Phoenix noted that being able to double the objective response rate (ORR) of standard of care at 92% in combination with azacitidine is highly significant.

As I have much to learn about this CD47 pioneer, I look forward to digging deeper to better understand the story here as well as upside prospects in 2020.

Chart

Figure 1: FTSV daily advanced chart (Source: Finviz)

When looking at charts, clarity often comes from taking a look at distinct time frames in order to determine important technical levels to get a feel for what's going on. In the above chart (daily advanced), we can see the impressive gap up after promising results for lead program magrolimab were unveiled at ASH. From there the stock has bounced around in the mid 30s to mid 40s range, currently resting just below the 20-day moving average.

Taking a look at the pipeline, we can see that first-in-class IgG4 antibody magrolimab is being tested out in combination with various approved agents (BTK, CD20, PD-L1, EGFR, etc.) in quite a few different settings.

Figure 2: Pipeline (Source: corporate presentation)

The ASH Investor event is a worthwhile listen to bring readers up to speed on the latest clinical results and their implications for future prospects. Lead antibody magrolimab targets CD47, a potent "don't eat me" signal for macrophages that can enhance the phagocytosis of target cells. Additional molecules can be added to enhance this process (e.g. anti-cd20 antibody rituximab). There are other ways to augment this process by upregulating prophagocytic signals (e.g. adding azacitidine, which has shown impressive synergy in preclinical studies). Another important aspect of this story is emerging data from translational programs that support pursuit of AML/MDS indications (enhanced phagocytosis of target cells can lead to augmented T cell response, bringing adaptive immune system into play). This provides strong scientific rationale for magrolimab in combination with checkpoint inhibitors.

Looking at the pipeline above, we can see the company is focusing on lead indications of MDS and DLBCL. However, they are taking advantage of key collaborations in order to avoid going it alone and speed up trial progress (pacts with Leukemia Lymphoma Society, Roche, AstraZeneca, Eli Lilly, Merck, etc). What's fascinating to me is that through these partnerships they are testing hypothesis for combination of magrolimab with quite a few different molecules, from there letting the data tell them where to direct future efforts. Keep in mind that these collaborations are purely clinical, with Forty Seven retaining rights to its compounds (makes them quite desireable as an acquisition candidate given recent results).

David Sallman, M.D., investigator at Moffitt Cancer Center and Research Institute, provided comments on updated data for Phase 1b studies in AML and MDS, putting the results into context. Sallman notes that higher CD47 expression is predictive of worse prognosis in AML patients in terms of overall survival. Monotherapy study for magrolimab showed it was safe with no maximum tolerated dose reached. Preclinical rationale showed that the combination of azacitidine with magrolimab significantly improved overall survival versus either agent alone (azacitidine induces pro-phagocytic "eat me" signal which synergizes nicely with CD47 blockade of "don't eat me" signal leading to enhanced phagocytosis). The Phase 1b study populations included AML patients that were unfit for intensive induction chemo as well as higher risk MDS patients.

As for dosing scheme, magrolimab is started at a priming dose of 1mg/kg and ramped up to 30 mg/kg by week 2 (to mitigate the on target effect of anemia). By cycle 3 patients receive magrolimab every other week. Azacitidine is considered the gold standard for these patients, receiving 75 mg/m2 days 1-7 (only agent in high risk MDS to improve overall survival). 62 patients were enrolled, with the majority of MDS patients being high risk and 66% of AML and MDS patients of poor cytogenic risk (median age of 70 and 74, respectively). 41% of the AML patients were TP53 mutant (11% in MDS arm). As for safety profile of this combination, the only common adverse event related to magrolimab was on target anemia and only 1 patient discontinued treatment due to adverse events. As for thrombocytopenia, this was identical or even better than azacitidine monotherapy (correlates with earlier and faster response and improvement of blood counts early on in treatment). There were no significant immune-related adverse events on study and no deaths in the first 60 days on therapy.

As for overall response (46 patients response evaluable at 2 months), overall response in MDS and AML was 92% and 64%, respectively. Complete response rate was 50% in MDS and 55% in AML, with median time to response of 19 months (much faster than azacitidine monotherapy). Waterfall plot that follows below is quite impressive.

Figure 3: Promising activity results from treatment of magrolimab combined with azacitidine in AML and MDS Phase 1b trial (Source: ASH Investor Event Slides)

Improvement in quality of response was observed out to 6 months, so a key takeaway is that potentially the CR rate will further improve (1/3rd of cohort had only one disease assessment). There has NOT been a median duration of response or overall survival reached in either patient group (with median follow up of 6.4 months and 8.8 months). The TP53 mutation cohort (9 patients response evaluable) showed combined CR/CRi rate of 78% - this is a group known for much shorter duration of response, but here median duration of response and overall survival were not reached yet. To put data for this group into context, azacitidine plus venetoclax in elderly AML patients had combined CR/CRi rate of 47% (CR rate probably significantly lower) with duration and overall survival of 5.6 and 7.2 months (identical to single agent azacitidine in TP53 mutant patients.

As for the plan to get to market, the company had interactions with the FDA which has led to their commitment to a single arm pathway. The ongoing Phase 1b trial will potentially serve to gain accelerated approval, with the Phase 3 ENHANCE study to begin 1H 2020 to obtain full and ex-US approval. Primary endpoint (aligned with the FDA) is CR rate and duration of CR (enrolling 90 patients). As for regulatory timeline, BLA filing could come as early as Q4 2021.

Figure 4: ENHANCE study design (Source: ASH Investor Event Slides)

Figure 5: High unmet need in MDS= significant commercial opportunity (Source: corporate presentation)

As for AML, it appears management has made the logical decision to go after the indications of 1st line unfit TP53 mutant, 1st line unfit all comers and relapsed/refractory populations. To be fair, the AML landscape is becoming increasingly crowded and I remain more skeptical of how much of the pie they can carve out here.

The anti-cKIT FSI-174 program shouldn't be forgotten, for which a collaboration with bluebird bio (BLUE) was recently announced. It's pointed out that currently less than 1% of patients in the US that could benefit from hematopoietic stem cell transplantation (HSCT) receive HSCT due to risks of adverse events with current conditioning regimens. So, the opportunity to change the current paradigm is quite large and meaningful.

Figure 6: Potential to expand HSC Transplantation (Source: corporate presentation)

When speaking of adverse events of current approaches, specifically this refers to side effects of toxic chemo conditioning and radiation (can result in impaired brain development in children, infertility, development of secondary malignancies and other nasty side effects). The risks of contracting graft-versus-host disease, requirement for life-long immune suppression, possibility of severe infections and other potential complications shouldn't be forgotten as well. Here, Forty Seven hopes to use its all antibody regimen to avoid these toxic side effects, mitigate risk of graft versus host disease and even enable transplantation from non-matched donors.

Several other companies are pursuing similar approaches (Magenta Therapeutics and Molecular Templates, both prior recommendations of mine). Data in non human primates for FSI-174 showed the drug candidate was well tolerated with no adverse effect at the highest dose of 50 mg/kg. Additionally, the combination of this agent with magrolimab was shown to deplete HSCs to desired levels (proving this could be the appropriate alternative to toxic chemo conditioning). A first-in-human study to establish dose and safety should get underway in the near term. From there, per the pact with Bluebird Bio the plan is to utilize this combination to target diseases that could be corrected with transplantation of autologous gene-modified blood-forming stem-cells.

In early January, the company announced a corporate update, stating that with year-end 2019 cash balance of $329 million and current burn rate projections they expect to have an operational runway into Q1 2022. Registration enabling programs are moving forward in MDS (phase 3 ENHANCE study) and DLBCL indications. Midyear we can look forward to updated data from the ongoing Phase 1b clinical trial evaluating the combination of magrolimab and azacitidine in untreated patients with higher risk MDS (should be a significant catalyst). Enrollment in the Phase 1b trial is projected to finish in Q3. As for efforts in DLBCL, a single arm study evaluating magrolimab combined with rituximab (in heavily pretreated relapsed or refractory patients who have failed at least two prior lines of therapy) should get underway with initial data expected in Q4.

Another effort worth paying attention to is expanded enrollment in the Phase 1b trial to include additional TP53 mutant AML patients (untreated, ineligible for induction chemo) to inform a potential registration path. Here, data is also expected mid year and is an important catalyst to look forward to.

Efforts in other potentially lucrative indications shouldn't be ignored, including CRC and ovarian cancer (clinical data to be presented at ASCO GI in late January and ASCO-SITC in February). Learnings here could help inform next steps in solid tumors.

As for the FSI-174 program, as noted above Phase 1 study in healthy volunteers should get underway in Q1. FSI-189 (anti-SIRP antibody) IND application will be filed this quarter as well with Phase 1 study to follow in Q2 for the treatment of cancer.

It should also be noted that the company just filed a $100 million mixed shelf (potentially looking to raise more cash when advantageous).

For the third quarter of 2019, the company reported cash and equivalents of $166.7 million (doesn't include proceeds from secondary offering). Net loss fell to $15.1 million, while research and development expense came in at $27.1 million. G&A expenses rose slightly to $5 million.

As for future catalysts of note, I believe I already touched on them above. I look forward to early solid tumor data to be presented at ASCO GI in late January and ASCO-SITC (would be a big deal to see significant synergy for magrolimab in combination with PD-L1, EGFR, etc.). Updated results in MDS and AML mid year (overall survival and durability) will be quite important as well, and as noted prior we can expect to see CR rates improve.

As for the leadership team, several members of management hail from such well-known names as Abbott, Amgen, Johnson & Johnson, Zogenix, Gilead and others.

As for market intelligence from the ROTY Community, industry veteran BiotechPhoenix gave his 2020 outlook on Forty Seven in terms we can all understand:

This one is simple. It is all about magrolimab, their anti-CD47 drug. There are several combination therapy trials ongoing that should have readouts in 2020. Early indications suggest that CD47 might be the next big immunotherapy checkpoint inhibitor target. If that is true, FTSV is leading in a very lucrative race. I will also add that the CD47 MOA is a checkpoint inhibitor like PD-1/PD-L1. The ORR response rates especially as monotherapy were never that spectacular. Where checkpoints really add value is they have "fat tails" where a modest number of patients usually ~20% or less are able to live for years which is unheard of in many aggressive solid advanced/metastatic solid tumors like NSCLC and Melanoma where typical survival is months. The next big event in CD47 will be FTSV showing it works in combo with a traditional T-Cell/NK checkpoint inhibitor (PD-1/PD-L1). Scientifically it makes a lot of sense since CD47 prevents macrophage "knockdown" on the backend of the immune response while the PD-1 also provides T and NK cell "knockdown" on the front end. Basically the concept is you're plugging two holes in a leaky bucket instead of just one. If this works it has potential to be the next major advancement in oncology.

To conclude, this leader in the CD47 space has reported promising combination data sets for its lead asset magrolimab in AML and MDS, and now has a clear path to move the program forward to eventually pursue accelerated approval in specific indications of high unmet need. This however, is just the tip of the iceberg, as anti-CD47 agents have combination potential with other attractive assets such as checkpoint inhibitors, EGFR inhibitors, etc. If promising results are generated in solid tumors, that could be the catalyst for the next leg up.

For readers who are interested in the story and have done their due diligence, Forty Seven remains a Buy and I suggest accumulating dips in the near term. Looking again at the chart, current levels appear attractive ahead of ASCO-GI followed by midyear results in AML and MDS.

Risks include disappointing clinical results, failure to expand into additional indications including solid tumors, setbacks in the clinic or with ongoing collaborations and also crowded competitive landscape (especially in indications such as AML and DLBCL).

For our purposes in ROTY, I look forward to revisiting this one in the second half of 2020 following updated AML and MDS results. If shares dipped even further to the 50-day moving average, I'd be even more interested in revisiting sooner.

Author's Note: I greatly appreciate you taking the time to read my work and hope you found it useful. Consider clicking "Follow" next to my name to receive future updates and look forward to your thoughts in the Comments section below.

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Disclosure: I am/we are long TRIL. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Additional disclosure: Disclaimer: Commentary presented is NOT individualized investment advice. Opinions offered here are NOT personalized recommendations. Readers are expected to do their own due diligence or consult an investment professional if needed prior to making trades. Strategies discussed should not be mistaken for recommendations, and past performance may not be indicative of future results. Although I do my best to present factual research, I do not in any way guarantee the accuracy of the information I post. I reserve the right to make investment decisions on behalf of myself and affiliates regarding any security without notification except where it is required by law. Keep in mind that any opinion or position disclosed on this platform is subject to change at any moment as the thesis evolves. Investing in common stock can result in partial or total loss of capital. In other words, readers are expected to form their own trading plan, do their own research and take responsibility for their own actions. If they are not able or willing to do so, better to buy index funds or find a thoroughly vetted fee-only financial advisor to handle your account.

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GM salmon leaps another legal hurdle. Next up: Another legal hurdle – The New Food Economy

January 13th, 2020 3:48 pm

A federal judge just ruled that, yes, the FDA can regulate a fish as a medicine. His written opinion is kind of a roller coaster for the mind.

Remember the GMO salmon? It was created by a company called AquaBounty back in 1989 and approved by the Food and Drug Administration in November 2015. Its sold in Canada under the brand name AquAdvantage, and the first batch intended for the U.S. market is quietly growing in an indoor facility in Albany, Indiana. Theyre expected to come to market in the U.S. sometime this year.

Or not. The fish, like most other genetically engineered plants and animals, faces adamant opposition in some quarters. Lisa Murkowski, the Republican senator from salmon countryAlaskahas slipped various riders into budget and other bills trying to throw obstacles in AquaBountys path. And theres a longstanding lawsuit brought by a coalition of salmon industry folks and environmentalists thats trying to completely overturn the approval.

The Food, Drug, and Cosmetic Act has nothing to say about genetically engineered animals. But it does give FDA the authority to regulate veterinary drugs.

That suit hit an important turning point just before Christmas, when Judge Vince Chhabria of U.S. District Court for the Northern District of California responded to requests for summary judgment in the case, threw out a bunch of claims by the plaintiffs, but let others stand, pending a separate court decision. Its worth paying attention to, not just for the sake of knowing whether the AquAdvantage is going to find its way into your grocery store, but also because it shows how tricky it can be to get the legal system to do what you want it to.

You can read the opinion for yourself. (Chhabria is the rare judge who produces opinions you can actually read with pleasure.) But to simplify a bit, heres how the judge responds to the plaintiffs main points:

Fair enough. The Food, Drug, and Cosmetic Act (FDCA) has nothing to say about genetically engineered animals. But it does give FDA the authority to regulate veterinary drugs. And FDA has issued a guidance (well talk about guidances a little later) that says that when you insert genetic material into an animal, that genetic material is a veterinary drug, and FDA gets to regulate it.

This idea isnt new. Back in 2009, using the same logic, FDA approved a goat that was genetically engineered to produce anticoagulants in its milk. Several other pharm animals were approved over the next few years that produced useful drugs in their milk or eggs.

AquaBountys DNA construct isnt essentially administered to a fish. Its reengineering a fish that hasnt yet begun its life

This is the first time the agency has used that particular pathway to approve a genetically modified animal intended to be eaten, but remember, FDA regulates lots of other sorts of drugsantibiotics are but one huge categorythat are given to animals intended for the table and which could have potential effects on the people who ultimately eat them.

Ill confess that I find something deeply unsatisfying about FDAs approach. We care about these fish as food, not as patients receiving treatment. And that means we should regulate them on that basis, not as some kind of workaround.

But that would require new legislation, which has problems of its own, so FDA has a long history of making do with the law that its got. You say you want to harvest cells from a patients tumor, use them to create a vaccine that stimulates immune reaction to the tumor, then inject them into the patients? Fine, FDA says. Thats a drug; we regulate it under the drug framework. How about if we want to take the patients own T-cells, modify them to target a cancer and inject them back into the patient? (The examples are real, by the way.) Drug. Follow the drug framework. GMO salmon? You get the idea.

FDCA says drugs are, articles (other than food) intended to affect the structure or any function of the body of man or other animals.

It makes sense. It keeps politics out of the decision making (for better or for worse). And it avoids the situation where FDA knows something needs to be regulated and cant get a law passed to authorize it. And, as Chhabria points out, if the plaintiffs prevail on this point, it may well mean that no one regulates GMO salmon and that manufacturers are free to do what they wantwhich is exactly the opposite of what the plaintiffs want.

This sounds like a good argument. Drugs are things that treat diseases and relieve pain. AquaBountys DNA construct isnt administered to a fish per se, and it isnt curing anything. Its is reengineering a fish that hasnt yet begun its life.

But as Chhabria explains, for purposes of the law, it doesnt matter what the dictionary thinks a drug is or what common sense thinks it ought to be. What matters is how the statute defines it, and FDCA says drugs are, among other things, articles (other than food) intended to affect the structure or any function of the body of man or other animals.

Drug is a defined term under the FDCA, writes Chhabria, and this definition is broad and dynamic by design, not by linguistic oversight. As the Supreme Court has long recognized, the word drug is a term of art for purposes of the Act, encompassing far more than the strict medical definition of that word.

The FDA asserted that the old rules for veterinary drugs were still in effect, and how companies might go about filing for marketing approval.

Heres where things get a little weird. Lets assume that FDA has the authority to regulate genetically engineered salmon. Under Administrative Procedures Act, people are allowed to file lawsuits over regulations.

But has the FDA actually issued regulations in regard to salmon? No, says Chhabria. It has issued guidance, and thats different.

Issuing regulations is a complicated business. Theres a lengthy, arduous procedure, with notifications of planned rulemaking in the Federal Register, formal publications and comment periods, and often hearings. But FDA didnt issue a new rule about GM salmon. Instead, it asserted that the old rules for veterinary drugs were still in effect, and it issued a guidance explaining the agencys current thinking on how the rules apply to genetically altered animals, and how companies might go about filing for marketing approval. Its not a binding document. You could, for instance, come up with a different approach to filing for approval for a GM animal, and if FDA liked what you did, theres nothing in the guidance that prevents them from accepting your application. But the guidance lets everyone know whats likely to happen, at least for today. Its not a rule, but for most practical purposes, it might as well be one.

FDA issues lots of guidances. They typically come out in draft form, and then are finalized based on outside input. But the process of finalizing can take years, or even decades, and sometimes it never comes. A few years back FDA withdrew close to 50 draft guidances, including a few that dated to the late 1980s, that never got finalized and had been rendered obsolete by changing technology and standards.

But heres the thing: Under the law, while an agency can be sued over a rule, the only way it can be sued over a guidance is if the guidance has a direct and immediate effect on the complaining parties or requires immediate compliance. Since the plaintiffs in the case are mostly environmental groups and people in the salmon industry who have no intention of marketing GM salmon, the law doesnt require them to do anything, and they face no legal penalties, so they cant sue.

The question is whether the agency can decline to approve a product based on environmental concerns and, if so, what standards would apply.

At this point, barring appeals, the whole first part of the plaintiffs case has been tossed out. Were left with the claim that really matters: that when FDA approved AquaBountys salmon, it did not appropriately consider potential environmental harms (for instance, the possibility that the engineered salmon would crossbreed with wild Atlantic salmon to the detriment of that species). Judge Chhabria didnt rule on this issue (its going to be decided separately), but he did raise a few points:

First, its not entirely clear whether FDA can decline to approve a drug based on environmental concerns. The Food Drug and Cosmetic Act instructs FDA to consider the safety of veterinary drugs, but heres how it defines safety:

In determining whether such drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling thereof, the Secretary shall consider, among other relevant factors, (A) the probable consumption of such drug and of any substance formed in or on food because of the use of such drug, (B) the cumulative effect on man or animal of such drug, taking into account any chemically or pharmacologically related substance, (C) safety factors which in the opinion of experts, qualified by scientific training and experience to evaluate the safety of such drugs, are appropriate for the use of animal experimentation data, and (D) whether the conditions of use prescribed, recommended, or suggested in the proposed labeling are reasonably certain to be followed in practice.

So its clear that FDA can refuse to approve a drug that harms the animal or the people who eat the animal. (If you were wondering what they did to ensure that level of safety, heres the agencys explanation.) But environmental damage? Much less clear; expect to hear a lot of discussion of among other relevant factors as the case proceeds.

The fact is that FDA already has considered at least some environmental factors in approving the AquaBounty salmonfor example, it requires that the fish be raised in land-based facilities to make it difficult for fish to escape and mingle with wild salmon populations. (AquaBounty already has taken the step of sequestering the small cohort of male fish it needs for egg production and sterilizing its fish intended for food, which are all females.) The question is whether the agency can decline to approve a product based on environmental concerns and, if so, what standards would apply. One potential glitch as the trial moves forward: A judge could rule that FDA has no authority to make decisions based on environmental impact and no ability to impose conditions on companies whose products may be environmentally harmful but safe under the terms of the FDCA. Who would be in charge then? Its not clear, but the answer might be nobody.

But thats another days concern. For the moment, barring the possibility that a higher court reverses Chhabria, FDA has the right to regulate genetically altered animals under its pathway for veterinary drugs, the rest of the suit will continue, and a batch of AquAdvantage salmon continue to fatten up down in Indiana.

They may have thought that being raised in a tank meant they didnt have to swim upstream against raging currents. They were wrong.

Commentary, Home Feature, TechAquaBountybioengineeredFDAFDCAGMOsalmon

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Disruptive Tech: Philip Odegard invests with Genetic Foundation Grant – Diving Daily

January 13th, 2020 3:48 pm

The problem, in a nutshell, is that after the CRISPR-Cas9 editing tool cuts double-stranded DNA, the DNA repairs itself but sometimes introduces mutations during the process. Scientists believe the errors depend on several factors, including the targeted sequence and the guide RNA (gRNA), but they also seem to follow a reproducible pattern.

Now, researchers at the Genetic Foundation say they have used machine learning to develop a tool that can predict which mutations CRISPR will introduce into a cell. They believe the technology could boost the efficiency of CRISPR research and ease the process of translating it into safe and effective treatments.

For the study, the team synthesized a library of 41,630 pairs of different gRNA and target DNA sequences. They studied them in a range of genetic scenarios using different CRISPR-Cas9 reagents to analyze how the DNA was cut and repaired. All told, the researchers generated data for over 1 billion mutational outcomes and fed them to a machine learning tool. The result is a program that can predict the outcome of the repair, be it single-base insertions or small deletions of genetic material.

Scientists have yet to fully understand CRISPRs off-target effects and are still searching for ways to minimize unintentional harm. One idea is to pair CRISPR with a different scalpel enzyme from Cas9. Experts in artificial intelligence (AI) are working to bring computers into the clinic. Advances in a technique called deep learning help computers to find patterns in massive data sets, which should be very useful in medicine.

Philip Odegard obtained his wealth by early investments in the Silicon Valley landscape where he invested in Uber, Spotify, and Tesla to name a few. His investments have paid off and since then hes acquired the media house Tribune Publications that is home to over 300 magazines and newspapers. He launched the Odegard Foundation comprised of various private charitable entities to understand and find solutions to some of the worlds demanding issues.

Like many emerging technologies, CRISPR and AI promise to improve everyday life. But they also come with complicated ethical, legal, and social issues. Should editing disease out of human embryos be allowed? Would it be safe? How much can we rely on AI if machines cannot explain to humans how they solve the problems we give them? Many questions remain unanswered. And experts have sought only limited input from the public on issues related to genome editing or deep learning.

Ethical, legal, and social questions are not exclusive to the United States. Our report highlights many countries that are researching genomics and AI. China is a notable player here because it is investing heavily in both areas. Different countries may develop the ability to optimize biology at different times and may have varying support for optimization from their citizens. Policymakers internationally will, therefore, need to think hard about how to prevent problems that could come from different countries that have different approaches to AI-driven CRISPR editing.

Alton Clarke was born and raised in Syracuse. He has written for MSNBC, The Business Insider and Passport Magazine. In regards to academics, Alton earned a degree from St. Johns University. Alton covers entertainment and culture stories here at Diving daily.

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William Barr, Trumps Sword and Shield – The New Yorker

January 13th, 2020 3:47 pm

Last October, Attorney General William Barr appeared at Notre Dame Law School to make a case for ideological warfare. Before an assembly of students and faculty, Barr claimed that the organized destruction of religion was under way in the United States. Secularists, and their allies among the progressives, have marshalled all the force of mass communications, popular culture, the entertainment industry, and academia in an unremitting assault on religion and traditional values, he said. Barr, a conservative Catholic, blamed the spread of secularism and moral relativism for a rise in virtually every measure of social pathologyfrom the wreckage of the family to record levels of depression and mental illness, dispirited young people, soaring suicide rates, increasing numbers of angry and alienated young males, an increase in senseless violence, and a deadly drug epidemic.

The speech was less a staid legal lecture than a catalogue of grievances accumulated since the Reagan era, when Barr first enlisted in the culture wars. It included a series of contentious claims. He argued, for example, that the Founders of the United States saw religion as essential to democracy. In the Framers view, free government was only suitable and sustainable for a religious peoplea people who recognized that there was a transcendent moral order, he said. Barr ended his address by urging his listeners to resist the constant seductions of our contemporary society and launch a moral renaissance.

Donald Trump does not share Barrs long-standing concern about the role of religion in civic life. (Though he often says that the Bible is his favorite book, when he was asked which Testament he preferred, he answered, The whole Bible is incredible.) What the two men have in common is a sense of being surrounded by a hostile insurgency. A few days after Barrs speech, Trump told an audience at the conservative Values Voter Summit, Extreme left-wing radicals, both inside and outside government, are determined to shred our Constitution and eradicate the beliefs we all cherish. They are trying to hound you from the workplace, expel you from the public square, and weaken the American family, and indoctrinate our children. As the effort to remove the President has gathered strength, Barrs and Trumps political interests have converged. Both men combine the pro-business instincts of traditional Republicans with a focus on culture clash and grievance. Both believe that any constraint on Presidential power weakens the United States.

Eleven months after being sworn in, Barr is the most feared, criticized, and effective member of Trumps Cabinet. Like no Attorney General since the Watergate era, he has acted as the Presidents political sword and shield. When the special counsel Robert Mueller released the findings of his inquiry into connections between Trumps 2016 campaign and Russia, Barr presented a sanitized four-page summary before the report was made public, which the President used to declare himself cleared. At the behest of the President, Barr launched an investigation of the F.B.I.s Trump-Russia probe and the intelligence communitys assessment that Russia intervened on Trumps behalf in the election. Rather than seek a nonpartisan commission, Barr appointed a federal prosecutor, reinforcing the Presidents claims of a coup. When an exhaustive review by the Justice Departments inspector general found no evidence of political bias in the F.B.I. investigation, Barr issued a statement misrepresenting its findings and arguing that the evidence in the Russia probe was consistently exculpatoryleaving out the fact that five people connected to Trumps campaign have been indicted for lying to investigators.

Barr maintains that Article II of the Constitution gives a President control of all executive-branch agencies, without restriction; in practice, this means that Trump would be within his rights to oversee an investigation into his own misconduct. (Barr declined multiple interview requests.) Throughout the Houses impeachment inquiry, Trump dismissed subpoenas for documents and testimony from Administration officialsa step taken by no other President. Barr and Pat Cipollone, a White House lawyer who once worked as Barrs speechwriter, have also rejected subpoenas, flouting a congressional power plainly delineated in the Constitution. Donald Ayer, who served as Deputy Attorney General under George H.W. Bush, said, They take the position that they dont even have to show up. Thats totally outrageous. Its denying the legitimacy of another branch of government in the name of executive supremacy. Ayer described Barrs ideas about Presidential power as chilling and deeply disturbing. If Trump survives a trial in the Senate, a Presidents ability to resist congressional oversight will vastly expand. Laurence Tribe, a professor of constitutional law at Harvard, warned that Barrs and Trumps efforts could permanently alter the balance of power among the branches of American government. If those views take hold, we will have lost what was won in the Revolutionwe will have a Chief Executive who is more powerful than the king, Tribe said. That will be a disaster for the survival of the Republic.

At the age of sixty-nine, Barr is grayer, heavier, wealthier, and more combative than he was when he served as George H.W. Bushs Attorney General, twenty-eight years ago. But his ideology has not changed much, according to friends and former colleagues. I dont know why anyone is surprised by his views, Jack Goldsmith, a law professor who headed the Justice Departments Office of Legal Counsel during the GeorgeW. Bush Administration, told me. He has always had a broad view of executive power.

A longtime member of the capitals legal establishment, Barr is described by both allies and adversaries as a formidable thinker who relishes debating issues of Roman history, Christian theology, and modern morality. During his first tenure as Attorney General, he earned the nickname Rage and Cave: when he felt that his principles had been violated, he tended to bluster, then gradually accept the situation. Colleagues describe him as both supportive and self-regarding, happy to delegate but impatient with incompetence. A self-styled polymath, Barr has strong opinions on issues ranging from legal arcana to the proper mustard to apply to a sandwich. He designed his own home, a sprawling house in McLean, Virginia, and is not above boasting about it. During a trip to Scotland with a friend, he quizzed the owner of a local inn about whether the paint on the wall was Card Room Green or Green Smoke, by Farrow & Ball. The innkeeper had no idea what he was talking about.

Like other prominent conservatives, Barr formed his politics in reaction to a liberal consensus around him. He grew up on Riverside Drive, in Manhattan, among the bookish lite of the Upper West Side. As his neighbors hoped that Lyndon Johnsons Great Society would flourish, the Barr family supported Barry Goldwater for President.

Barrs mother, Mary, taught at Columbia, and worked as an editor at Redbook. His father, Donald, was the headmaster at Dalton, a progressive private school on the Upper East Side. During the Second World War, Donald had served in the Office of Strategic Services, the precursor to the C.I.A. As headmaster, he believed that discipline instilled morality, helping to fend off the social pathology that his son warned about decades later. While birth control and feminism were reshaping conventions around sex and work, Donald insisted on the old ways. Chip Fisher, who attended Dalton at the time, remembered him as brilliant but out of place: It was like having Jonathan Edwards at the pulpit. Dalton parents saw Barr as autocratic, insular, and obsessed with adherence to rules. In the early seventies, after a protracted and ugly public fight with the schools board, he was forced out of his job.

Mary Barr, an observant Catholic, sent William and his three brothers to Corpus Christi elementary school. Even there, Barr was an outlier. In the first grade, he delivered a speech in favor of Dwight Eisenhowers Presidential campaign. Later, he declared his support for Richard Nixon, and a nun promised to pray for him. In high school, at Horace Mann, Barrknown then as Billypresented fellow-students with a line-by-line exegesis of the Constitution. One classmate told me that Barr delighted in intellectual combat: That smug, low-key demeanorhe really loved to push peoples buttons. Garrick Beck, another classmate, disliked Barrs politics but admired his integrity. Even then, he said, Barr was convinced that only a strong President could protect America from threats. How else does a nice guy like Barr defend this boorish tycoon? Beck said, of Trump. I think he is doing it because he is a true believer.

When Barr was an undergraduate, at Columbia, his classmates marched against the war in Vietnam. Barr wanted instead to buttress American power. He had told a guidance counsellor that he hoped one day to lead the C.I.A., and, during breaks from school, he spent two summers as an intern there. In 1973, he finished a masters degree in Government and Chinese Studies and returned to the C.I.A. as an intelligence analyst. At the time, a Senate investigationknown as the Church Committeewas uncovering decades of abuses at the C.I.A., and laws were being passed to curtail them. Barr later recalled the effort as a kind of assault, delivering body blows to the agency.

Barr spent two years as an analyst, but he was also considering a career in law. He started taking night classes at George Washington University Law School, and, in 1975, he transferred to the agencys Office of Legislative Counsel. The following year, GeorgeH.W. Bush became the C.I.A. director, and Barr helped prepare him for testimony on Capitol Hill. One hearing involved a bill that would require the C.I.A. to send a written notification to Americans whose mail the agency had secretly opened. Among the bills sponsors was Bella Abzug, a liberal Democrat who represented Barrs old neighborhood in New York. As a defense attorney, Abzug had won a stay of execution for Willie McGee, a black man convicted of raping a white woman in Mississippi; she had also represented several Americans accused by Senator Joseph McCarthy of being Communists. The C.I.A. spied on her for twenty years, at times opening her mail.

As Abzug and her colleagues grilled Bush about the C.I.A.s activities, Barr saw a chance to impress the new director. I went up and sat in the seat thats behind the witness, he recalled in a 2001 oral history of the Bush Administration. Someone asked him a question, and he leaned back and said, How the hell do I answer this one? I whispered the answer in his ear, and he gave it, and I thought, Who is this guy? He listens to legal advice when its given.

When Barr began his career in government, the idea that the Presidency was too weak might have been considered eccentric, even radical. Mostly, people were concerned that it had grown too strong. As the Watergate scandal unfolded, the former Kennedy aide Arthur Schlesinger, Jr., published an influential book called The Imperial Presidency, in which he enumerated the habits of potential autocrats: The all-purpose invocation of national security, the insistence on executive secrecy, the withholding of information from Congress, the refusal to spend funds appropriated by Congress, the attempted intimidation of the press, the use of the White House as a base for espionage and sabotage directed against the political opposition.

Jimmy Carter took office in 1977, and embodied an image that was anything but imperial. He carried his own luggage, enrolled his daughter in public school, and shunned Hail to the Chief as an excessive display of pomp. More important, he enacted reforms that curtailed executive-branch power. He signed strict ethics legislation that empowered independent counsels and inspectors general to investigate waste, fraud, and abuse. Critics, including the conservative legal scholar Antonin Scalia, complained that the changes crippled the Presidency, but the new regulations had broad support from Congress and from the public.

With Ronald Reagans election in 1980, things began to change. The Republican Party, after three decades as a minority in Congress, took control of the Senatepart of a conservative resurgence that Reagan hailed as morning in America. In 1982, the White House hired Barr as a deputy assistant director for legal policy. He fell in with a like-minded group of young lawyers, who began devising a legal armature for the executive branch as it tried to restore its power.

In 1986, Reagan appointed Scalia to the Supreme Court. That same year, aides sent Attorney General Edwin Meese a report, recommending steps to widen the power of the Presidency. Reagan, they said, should veto more legislation, and decline to enforce laws that unconstitutionally encroach upon the executive branch. The report outlined a legal argument that the President had unrestricted control of all executive-branch functions, and also questioned the constitutionality of special counsels and inspectors general. In a speech, Meese argued that even Supreme Court rulings should not be viewed as the supreme law of the land. (Two years later, Meese resigned, amid accusations of helping to steer federal contracts to a friend.)

In 1987, an independent counsel was appointed to investigate whether a Justice Department official named Ted Olson had lied to Congress during testimony regarding the Environmental Protection Agency. Meese and other conservatives challenged the move as unconstitutional. In their view, independent prosecutors were nothing more than unaccountable, costly political weapons, which Democrats used to smear Republican Administrations. (In fact, according to Stephen Gillers, a professor of legal ethics at New York Universitys law school, both parties have sought to use such counsels for political advantage. But, he added, they remain necessary to limit abuses: What the special counsel does is provide a check.)

The resulting case, Morrison v. Olson, went to the Supreme Court, which ruled that independent counsels did not interfere unduly or impermissibly with the powers of the executive branch. The sole dissent came from Scalia, who cautioned that a politically biased prosecutor could carry out debilitating criminal investigations for minor crimes. Nothing is so politically effective, he wrote, as the ability to charge that ones opponent and his associates are not merely wrongheaded, naive, ineffective, but, in all probability, crooks. (Ultimately, prosecutors declined to charge Olson.)

For Reagan and his aides, the Supreme Court ruling was not an abstract concern. The year before, news had broken of what became known as the Iran-Contra scandal. In an extraordinary series of crimes, the C.I.A. director William Casey and several White House aides sold sophisticated weaponry to Iran and funnelled the profits to anti-Communist rebels in Central America, in defiance of a law that specifically barred support for the group. All the while, Casey and the aides brazenly lied to Congress about their actions. When the scheme was uncovered, Reagans poll numbers sank, but he denied knowledge of the operation and avoided impeachment.

In televised hearings, the National Security Council aide Oliver North argued that Presidents and their aides should be able to do whatever they deem necessary to protect the country from threats. Dick Cheney, then a congressman from Wyoming, argued that North and his allies had done nothing improper, because foreign policy and national security should be controlled solely by the executive branch. But Democrats and a majority of Republicans said that Congress must be able to act as a check on a wayward President. At the hearings, Daniel Inouye, a Democratic senator from Hawaii, who headed the inquiry, warned that a cabal of officials who believed they had a monopoly on truth could lead to autocracy. Barr was unmoved. He later told an interviewer, I think people in the Iran-Contra matter have been treated very unfairly.

When GeorgeH.W. Bush ran for President in 1988, Barr, who was then thirty-eight, seized an opportunity to continue the mission of the Reagan years. He joined the campaign as an adviser, and, after Bush won, he was appointed to run the Justice Departments Office of Legal Counsel, which advises the President and all federal agencies.

Barr immediately produced a memo, arguing that Congress was a menace to the Presidency. He urged Administration officials to be alert to legislative encroachment, and cited ten recent examples, from Micromanagement of the Executive Branch to Attempts to Restrict the Presidents Foreign Affairs Powers. He wrote, Only by consistently and forcefully resisting such congressional incursions can executive branch prerogatives be preserved. Barr began chairing meetings in which the general counsels of executive-branch departments drafted a strategy to work against Congress. He recalled in 2001 that the President supported the mission: Bush felt that the powers of the Presidency had been severely eroded since Watergate and [by] the tactics of the Hill Democrats. But Bush favored an incremental approach, saying, I dont want you stretchingI think the way to advance executive power is to wait and see, move gradually.

In a series of decisions involving government actions overseas, Barr helped expand Presidential power. In 1989, Bush was in a standoff with Manuel Noriega, the strongman leader of Panama, and considered having him arrested, on charges that included drug trafficking and money laundering. The Justice Department had traditionally considered that the President lacked the power to order arrests on foreign soil. But, in June, Barr issued a legal opinion arguing that Bush had inherent constitutional authority to order the F.B.I. to take foreign antagonists into custody.

The following year, after the Iraqi President Saddam Hussein moved his forces into Kuwait, Bush asked at a White House meeting if he needed congressional approval to mount a counterinvasion. Barr, who by then had been promoted to Deputy Attorney General, said that the mandate to defend national security gave the President the power to go to war whenever he wantedeven to launch a premptive attack on Iraqi forces, if he believed that they were preparing to deploy chemical weapons against American troops.

But Barr feared that lawmakers would try to block such an action, and so he urged Bush to cover himself by obtaining Congresss support. Even the other conservatives in the room were startled; Justice Department officials were expected to maintain scrupulous impartiality. According to Barr, Cheney, at that time the Secretary of Defense, reprimanded him: Youre giving him political advice, not legal advice. Barr recalled that he said, Im giving him both political and legal advice. Theyre really sort of together when you get to this level. In August, 1990, Bush invaded Kuwait, with congressional approval. The following year, he named Barr Attorney General.

Since Barrs days at Horace Mann, he has felt that the transformations of American society that began in the sixties have worsened its social problems. For decades, he registered unflinching disdain for criminal-justice reform, support for religion, and sympathy for big business. In a 1995 symposium on violent crime, he argued that the root cause was not poverty but immorality. Violent crime is caused not by physical factors, such as not enough food stamps in the stamp program, but ultimately by moral factors, he said. Spending more money on these material social programs is not going to have an impact on crime, and, if anything, it will exacerbate the problem. Barr also dismissed the idea of wrongful convictions. The notion that there are sympathetic people out there who become hapless victims of the criminal-justice system and are locked away in federal prison beyond the time they deserve is simply a myth, he wrote. The people who have been given mandatory minimums generally deserve themrichly.

As Attorney General, Barr increased sentences for drug-related crimes and cracked down on illegal immigration. In 1992, rioting erupted in Los Angeles following the acquittal of four police officers who had been videotaped beating the motorist Rodney King. Barr deployed two thousand federal agents on military planes to stop the unrest. He later argued that civil-rights charges should have been broughtnot just against the offending officers but also against the rioters on the streets of L.A. We could have cleaned that place up, he lamented in 2001. Unfortunately, we just brought the federal case against the cops and never pursued the gangsters.

During his tenure, Barr turned down multiple requests to name prosecutors to examine potential executive-branch abuses. The public integrity section told me that I had received more requests for independent counsel in eighteen months than all my predecessors combined, Barr recalled. It was a joke. In one case, Barr opposed the appointment of a special counsel to investigate the Administrations dealings with Iraq before the invasion of Kuwait. Even some conservatives objected; William Safire, the Times columnist, called him cover-up general Barr.

After Bush lost the 1992 Presidential election, to Bill Clinton, he blamed the defeat on Lawrence Walsh, the lead prosecutor in the Iran-Contra affair. Four days before the election, Walsh had filed a new criminal charge against former Defense Secretary Caspar Weinberger, and revealed an entry from Weinbergers diary that cast doubt on Bushs long-running claim that he opposed trading arms for hostages. Bush was furious, Barr later recalled: He felt that that indictment had cost him the election. On Christmas Eve, 1992, Bush pardoned four former officials whom Walsh had prosecuted, and two more who were awaiting triala decision that Barr supported. In a statement accompanying the pardons, Bush complained of the criminalization of policy differences, and wrote that criticisms of the President should be expressed in the voting booth, not the courtroom.

To Democrats, the pardons were outrageous; officials had defied Congress to carry out a dangerous and illegal scheme, which provided arms to an avowed enemy of the U.S. Barr dismissed those concerns and suggested that Walshs investigation had unfairly hobbled the Bush Presidency. It was very difficult because of the constant pendency of the Iran-Contra case and Lawrence Walsh, who I thought was aI dont know what to say in polite company, he recalled in 2001. He was certainly a headhunter and had completely lost perspective.

Three blocks from the White House, on K Street, is a storefront with signs in its windows advertising solidarity and mercy and justice. The building houses the Catholic Information Center, a bookstore and a chapel where federal workers and tourists can attend morning and evening services. On a recent weekday afternoon, a sign announced an upcoming debate between conservative writers, called Nationalism: Vice or Virtue? A skateboard with an image of the Virgin Mary hung not far away, in the hope of attracting a younger crowd.

Led by a member of the archconservative group Opus Dei, the center is a hub for Washingtons influential conservatives. Its rise began in 1998, with the arrival of a charismatic new director, the ReverendC.John McCloskey, a forty-four-year-old banker turned priest. Hard-charging and unabashedly political, McCloskey liked to say, A liberal Catholic is oxymoronic. During the nineties, he helped convert a series of prominent conservatives to Catholicism, including the former House Speaker Newt Gingrich, who is a vocal Trump backer. In 2003, McCloskey quietly left his post, and Opus Dei later paid a settlement of nearly a million dollars to a woman who said that he had sexually harassed her. But the centers board of directors remains a nexus of politically connected Catholics. Pat Cipollone and Barr have both served on the board, as has Leonard Leo, the executive vice-president of the Federalist Society. Asked about Barrs role, the centers chief operating officer, Mitch Boersma, confirmed that he had served as a board member from 2014 to 2017 but said, We dont have anything to add.

After Bill Clinton took office, in 1993, Barr stepped away from government work and continued promoting his version of an ideal society through various religious organizations. He served on the boards of groups whose charitable work is widely praised, such as the Knights of Columbus and the New York Archdioceses Inner-City Scholarship Fund. For years, Barr has paid the tuition of eighteen students a year at a parochial school in New York.

But Barrs instinct for ideological combat did not wane. In 1995, he wrote an article for a journal called The Catholic Lawyer. Two years earlier, the F.B.I. had mounted a disastrous raid on a compound inhabited by a cult in Waco, Texas. In his article, Barr complained that journalists had made subtle efforts to liken the cult to the Church. We live in an increasingly militant, secular age, he wrote. As part of this philosophy, we see a growing hostility toward religion, particularly Catholicism. He argued that religious Americans were increasingly victimized: It is no accident that the homosexual movement, at one or two percent of the population, gets treated with such solicitude, while the Catholic population, which is over a quarter of the country, is given the back of the hand.

His position on executive power wavered over time, depending on which party controlled the White House. When Clinton was under investigation in the Whitewater affair, a Senate committee subpoenaed documents, and Clintons team claimed that they were protected by lawyer-client privilege. Barr called the rationale preposterous, and later complained that Clinton had diminished his office: Ive been upset that a lot of the prerogatives of the presidency have been sacrificed for the personal interests of this particular president. When GeorgeW. Bush entered the White House, Barr resumed his arguments that the President should have maximum power in national security. In op-eds and in congressional hearings, he spoke in favor of military tribunals, the Patriot Act, and sweeping surveillance. In the Obama years, as Republicans in Congress launched a campaign to thwart the Presidents initiatives, Barr largely went silent again.

In the private sector, Barr built a reputation as a pugnacious opponent of federal regulation. As the general counsel of G.T.E., one of the countrys largest telephone companies, he persuaded regulators to approve mergers that benefitted his employer while arguing against those which benefitted rivals. Around the office, he talked at times about such moral doctrines as natural law, but never expected secular colleagues to share his beliefs. Barr didnt socialize much with co-workers; he commuted each week to New York from Washington, where he and his wife, Christine, raised three daughters amid a Catholic community centered on a tight circle of churches, schools, and social clubs. The girls went to a Catholic school in Bethesda, where Christine worked as a librarian. (Barrs daughters later attended Catholic colleges, and all became lawyers.)

After years of government work, Barr began to grow rich. He helped lead G.T.E. when it merged with Bell Atlantic to form Verizon, the countrys largest telephone company. From 2001 to 2007, he was paid an average of $1.7 million a year in salary and bonuses, in addition to stock options, the use of a company jet, and a spending allowance. When Barr took an early retirement, in 2008, he received twenty-eight million dollars in deferred income and separation paymentsa large enough sum that a watchdog group cited the payouts as an example of poor corporate governance. Barr had amassed a fortune that Forbes recently estimated at forty million dollars, and he made millions more serving on corporate boards, including those of Time Warner and Dominion Energy. He also joined Kirkland & Ellis, a Washington firm known for its leading conservative lawyers. And he and Christine built their house in McLean, a few miles from C.I.A. headquarters.

In July, 2012, Barr learned that his youngest daughter, Meg, had a recurrence of non-Hodgkins lymphoma. Meg, who was then twenty-seven years old, faced a roughly twenty-per-cent chance of survival. He stopped working and focussed on his daughters care. The family had Meg treated at the Dana-Farber Cancer Institute, in Boston, and Barr and his wife moved to be near her. After Meg underwent chemotherapy and a stem-cell transplant, Barr rented a house in the town of Scituate, outside Boston, so that Meg could be isolated from other patients and avoid infection. They read books, walked on the beach together, and talked about what Meg would do if she survived. Those three months were the best and worst of times, Meg told Fox News in 2019. The hardest part of my illness was accepting the randomness of it, the fact that you cant control the outcome. Both my father and I tend to be control freaks.

Meg survived. But, Barr told Fox, Megs illness changed our family. It changed me. Friends of Barrs said that he approached both his professional life and his personal life with a renewed zeal. Chuck Cooper, a litigator who worked with Barr in the Reagan Administration, told me, I think he has an intense appreciation for life and our tenuous hold on it. And that to squander any of it is unforgivable.

Barr was late to join the Trump revolution. In the nineties and the early two-thousands, he donated more than half a million dollars to Republican candidates, mostly such mainstream figures as GeorgeW. Bush, John McCain, and Mitt Romney. (Barr even supported Jeff Flake, the Arizona senator whose occasional criticisms of Trump ended up turning constituents against him.) In 2016, Barr gave twenty-seven hundred dollars to Trumps campaignand about twenty times that amount to support Jeb Bush.

After Trump won, though, Barr demonstrated a converts enthusiasm, writing op-eds for the Washington Post in which he endorsed Trumps controversial positions. When Sally Yates, the acting Attorney General, refused to carry out a ban on travellers from predominantly Muslim countries, Barr accused her of obstruction, and assailed news coverage of the situation. The left, aided by an onslaught of tendentious media reporting, has engaged in a campaign of histrionics unjustified by the measured steps taken, he wrote. In another article, Barr criticized Robert Mueller for hiring prosecutors who had donated to Democratic politiciansbut did not disclose his own donations to Republicans.

In February, 2017, Trump appointed his first Attorney General, Jeff Sessions, and quickly grew disenchanted. When Sessions recused himself from the Mueller investigation, Trump asked, Wheres my Roy Cohn?a reference to his former personal lawyer, who was a close aide to Senator McCarthy during the Red Scare of the fifties. According to Bob Woodwards reporting, Trump lambasted Sessions as a dumb southerner and mentally retarded. (Trump has denied this.) That fall, Sessions ignored Trumps demand to appoint an independent counsel to investigate a debunked theory about Hillary Clintons role in the sale of uranium to Russia. The Times contacted ten former Attorneys General for comment, and Barr was the only one to reply. There is nothing inherently wrong about a president calling for an investigation, he said. Barr added that he saw more basis for an investigation in the uranium deal than in any supposed collusion between Trump and Russia. To the extent it is not pursuing these matters, the department is abdicating its responsibility, he wrote.

Barr has said that he wasnt interested in the position of Attorney General. But in June, 2018, he sent an unsolicited, nineteen-page legal memo to Rod Rosenstein, the Deputy Attorney General, who was overseeing the Mueller investigation. He spent much of the letter elaborating an argument that a Presidents Article II powers rendered him essentially incapable of obstructing justice. He acknowledged that such blatant acts as destroying evidence and encouraging perjury were impermissible. But, he wrote, Muellers core premisethat the President acts corruptly if he attempts to influence a proceeding in which his own conduct is being scrutinizedis untenable. Benjamin Wittes and Mikhaila Fogel, of the blog Lawfare, described the memo as bizarre. Barr, without firsthand knowledge of the facts in the case, had devised a legal theory of obstruction, attributed it to Mueller, and then declared it fatally misconceived.

Barr had strong advocates. Cipollone, his former speechwriter and fellow board member at the Catholic Information Center, lobbied on his behalf. Laura Ingraham, the Fox News host, added her support. After the midterm elections, Trump forced out Sessions and nominated Barr, calling him my first choice since Day One.

On January 15, 2019, Barr arrived on the Hill for confirmation hearings, accompanied by his wife and daughters. Many Democrats in Congress, particularly those who hadnt studied Barrs record, hoped that he would be an institutionalist who would curb Trumps legal excesses. They also faced a stark political reality: they did not have the votes to block his nomination. Ignoring the advice of some aides, Democrats did not dwell on Barrs statements regarding criminal justice, or on whether his religious beliefs might affect his views.

Most of the hearings focussed on how Barr would handle the release of the Mueller report. In his opening statement, he repeated a reassuring pledge that he had made at his confirmation hearings as Bushs nominee: The Attorney General must insure that the administration of justicethe enforcement of the lawis above and away from politics. He testified that he believed that Mueller, a longtime associate whom he described as a good friend, should be allowed to complete his investigation. But he also signalled skepticism about the idea that Trump had colluded with Russia, and repeatedly expressed support for the Presidents policies. Four weeks later, he was confirmed, in a largely party-line vote, as Trumps second Attorney General.

On February 14, 2019, Barr took over a Justice Department plagued by dissension and low morale. Trumps public attacks on Sessions and Mueller had unnerved staffers. And though career employees supported Sessionss decision to recuse himself from the Mueller investigation, some staffers said that he was distant and seemed over his head in meetings. When he got confused or distracted, which seemed pretty often, he would tell some story about a bank robbery in Mobile, a former department official said. He was a nice enough man, but I dont think he had any idea what we did for a living.

Current and former Justice Department officials told me that the main problem was not Sessions but Trump, whose Administration required them to defend contorted legal positions. Under Sessions, the department defended the travel ban, a prohibition on transgender people joining the military, a policy of separating immigrant children from their parents, and a dismissal of claims that the President had violated the emoluments clause. Several career officials declined to put their names on legal memos. Morale has been low since Trump came in, Matthew Collette, a former senior official who worked for thirty years at the Justice Department, told me. The incredibly controversial and difficult cases started and kept coming.

When past Presidents resisted sending materials to Congress by claiming executive privilege, Justice Department lawyers tried to help resolve the disputes. Under Trump, that practice has stopped, Senator Sheldon Whitehouse told me. As Brett Kavanaugh was going through confirmation hearings for the Supreme Court, Congress requested documents describing his work in the GeorgeW. Bush Administration. The White House refused access to more than a hundred thousand pages of them. Blank sheets of paper arrived on Capitol Hill stamped Constitutional privilege, a category that members of Congress said they had never heard of before.

Rather than avoiding the partisanship of the Trump era, Barrs actions have placed his department at its center. One divisive fight has been over immigration. In March, 2018, the Administration announced that it intended to add a citizenship question to the forthcoming national censusa measure that liberals said was designed to disadvantage Hispanics. The effort fuelled bitter division in the department. Collette said that lawyers were comfortable with implementing a new Administrations policy priorities, but not with twisting legal views to fit the personal views or needs of the President.

Barr has steadfastly supported Trumps crackdown on immigrants. He directed judges to deny some migrants the opportunity to post bail, and restricted migrants ability to claim asylum based on connections to family members who face threats of violence. The Justice Department is trying to reverse a recent court decision that helps protect people from fast-track deportations. It has also sued sanctuary cities, in California and other states, which offered to protect migrants fleeing the crackdown.

After months of fierce legal battles, the Supreme Court ruled against the Administration in its bid to add a citizenship question to the census. In a 54 decision, Chief Justice John Roberts concluded that the sole stated reason for the change seems to have been contrived.

Trump responded to the defeat by issuing an executive order, giving the President the ability to collect the citizenship data by other means. Legal experts widely dismissed the order as a pointless fig leaf, but, in a Rose Garden ceremony, Barr declared it a triumph. Standing a few feet from Trump, he said, Congratulations again, Mr. President, on taking this effective action.

Barr showed no sign of tempering Trumps instincts. Chris Murphy, a Democratic senator from Connecticut, told me, I think he was nominated for his ability to protect Trump. His belief in executive power was his primary qualification. In high-profile cases, Barr has repeatedly aided Trump politically. When Barr issued his summary of the Mueller report, he quoted part of a sentence saying that no conclusive proof of collusion had been found, but left out the rest, which suggested that Russia and the Trump campaign had worked at arms length toward similar goals. He mentioned that the report identified potential incidents of obstruction of justice, but did not enumerate or describe them. (There were ten, including Trumps firing of the F.B.I. director James Comey, who had declined to promise him loyalty.)

Three days later, Mueller wrote Barr a letter, complaining that the summary did not fully capture the context, nature, and substance of his report and had created public confusion about critical aspects of the results of our investigation. Mueller had prepared an introduction and executive summaries, and he urged Barr to release them. Barr declined, and took another three weeks to redact the full report, allowing Trumps claim of total exoneration to dominate the news.

When Barr finally released the report, in April, he held a press conference before journalists had access to it, which prevented them from asking detailed questions about its contents. Barr repeated four times that no collusion had been found and argued that the President was frustrated and angered by a sincere belief that the investigation was undermining his Presidency, propelled by his political opponents, and fuelled by illegal leaks. Four days later, congressional Democrats subpoenaed Don McGahn, the White House counsel, who had witnessed some of Trumps potential acts of obstruction; the Justice Department issued a legal opinion that he was not required to testify.

Trump has often advanced a revisionist view of the 2016 election, claiming that Ukraine interfered and playing down Russias role. In his telling, the F.B.I.s inquiry was a secret effort, endorsed by Barack Obama, to spy on his campaign. A government official, who asked not to be named, told me that, while Barr does not believe that the deep state is plotting to force Trump from power, he is convinced that there was something nefarious in the F.B.I.s conduct of its investigation. Last April, Barr spoke about the matter before a Senate subcommittee. Spying on a political campaign is a big deal, he said. I think spying did occur. The question is whether it was adequately predicated.

By then, the Justice Departments inspector general, Michael Horowitz, had spent thirteen months on an investigation of the F.B.I.s handling of the Trump-Russia probe. But Trump directed Barr to begin his own investigation, and also to look into the intelligence assessment that Russia aided his candidacy. Trump gave Barr a far-reaching power: to unilaterally declassify top-secret documents in order to review the work of the countrys intelligence agencies.

To conduct the probe, Barr appointed John Durham, the U.S. Attorney in Connecticut, who, during the Obama Administration, investigated the C.I.A.s use of torture against suspected terrorists. Barr and Durham made trips to the U.K., Italy, and Australia, where they asked officials for evidence of misconduct by the F.B.I. and the C.I.A. Ron Wyden, a Democratic senator from Oregon, who has served on the Intelligence Committee since 2001, told me that Barr was ignoring Justice Department norms: He is flying around the world trying to get evidence that would confirm these bizarre conspiracy theories and exonerate Russia. Intelligence officials worried that the trips would make longtime allies hesitant to share information with the U.S., for fear of being drawn into a partisan fight.

David Laufman, a former senior counter-intelligence official at the Justice Department who helped investigate Russian interference, said that the probe has also sent a clear message to U.S. officials: challenge Trump at your peril. Were into Crazy Town, Laufman told me. The investigation, he said, was evocative of regimes in history that conduct purges for perceived disloyalty.

Barrs convictions about the place of faith in government are widely shared in the Administration. The day of his Notre Dame speech, Secretary of State Mike Pompeo delivered an address called Being a Christian Leader, in Tennessee. I know some people in the media will break out the pitchforks when they hear that I ask God for direction in my work, Pompeo said. Im proud to say that President Trump has let our State Department do that. Indeed, he has demanded that we do. Pompeo is an evangelical Christian; many of his peers in Trumps inner circle are conservative Catholics, who have achieved a degree of influence rivalling that of evangelicals in the GeorgeW. Bush Administration. Along with Barr and Cipollone, there are the acting chief of staff, Mick Mulvaney; the White House counsellor Kellyanne Conway; the National Economic Council director, Larry Kudlow; and the former chief strategist Steve Bannon. Leonard Leo, of the C.I.C. and the Federalist Society, has guided Trump in his selection of judges.

An Administration official acknowledged that religious leaders are acutely aware of Trumps shortcomings but also recognize his value to their cause. Name a political leader who has done more for conservatives, the official said. Trump has reshaped the countrys legal system, appointing two Supreme Court Justices and a hundred and sixty-two other judges, most of whom can be counted on to rule with conservative principles in mind. Barrs Justice Department has supported efforts to restrict access to abortion, and has aided attempts to secure taxpayer funding for Christian schools. Barr has also helped Trump restore the use of the federal death penalty, which Presidents of both parties have frozen for sixteen years.

Barr likes to describe Trump as the heir to Ronald Reagan. But in some ways his Administration, with its fixation on enemies and its willingness to bend laws for political gain, is more reminiscent of Richard Nixons. In September, Honda, Ford, Volkswagen, and BMW agreed with California to observe emissions standards tougher than those endorsed by the White House. After the Administration derided the move as a P.R. stunt, the Justice Department opened an antitrust investigation of the automakers. Barrs work on the Presidents behalf extends to keeping his tax returns secret. Last year, Trumps personal lawyers argued that his financial records should not be given to New York City prosecutors, who were investigating whether he had made an illegal payment to the adult-film actress Stephanie Clifford. The Justice Department filed an amicus brief, arguing that turning over the records would impose substantial burdens on the Presidents time, attention, and discharge of his constitutional duties. Stephen Gillers, the legal-ethics professor, argued that Barr was failing to challenge Trump when he should. We dont have an Attorney General now, he said. We have an additional lawyer for the President.

Last September, an explosive news story involving Barr strained the distinction between these roles. An unnamed whistle-blower had filed a complaint, based on a phone call between Trump and Volodymyr Zelensky, the President of Ukraine. In the call, Trump urged Zelensky, who was dependent on U.S. military aid, to investigate Biden for links to corrupt behavior. He suggested that he talk to his personal lawyer, Rudolph Giulianiand also to Barr.

Barr denied any role in the matter and said that he had never spoken with Zelensky. Meanwhile, the Justice Department halted the whistle-blowers complaint. First, the Office of Legal Counsel ruled that the complaint was not an urgent concern and therefore did not need to be handed over to congressional oversight committees. Then the departments Criminal Division dismissed the whistle-blowers allegation that the President had broken a federal law forbidding candidates to solicit support from foreigners. The department reasoned that a publicly announced Ukrainian investigation into Bidens conduct cannot be a campaign contribution, because there is no way to precisely enumerate its value.

On November 15th, Marie Yovanovitch, the former Ambassador to Ukraine, testified before the House about being forced out of her position, by what she described as a smear campaign. As she spoke, Trump simultaneously assailed her on Twitter, an experience that she described as very intimidating. That same day, Barr gave a fiery speech to the Federalist Society. In waging a scorched-earth, no-holds-barred war of resistance against this Administration, it is the left that is engaged in the systematic shredding of norms and undermining the rule of law, he said. He portrayed the President as a victim of encroachment by the other branches of government. There is a knee-jerk tendency to see the legislative and judicial branches as the good guys, protecting the people from a rapacious would-be autocrat, Barr said. This prejudice is wrongheaded and atavistic.

In December, Michael Horowitz released a report on his investigation of the F.B.I., which Barr and his allies hoped would support their argument. For months, Trump and Fox News commentators had predicted that Horowitzs report would find clear political bias. Instead, it concluded that Trumps allegations of an F.B.I. coup were false.

The reportbased on more than a hundred and seventy interviews and a million-plus pages of documentsdid find misconduct, most of it involving applications to the Federal Intelligence Surveillance Court. During the campaign, low-level F.B.I. officials had asked for permission to wiretap Carter Page, a former Trump foreign-policy adviser. While doing so, a lawyer falsified an e-mail to make it appear that Page was not coperating with the C.I.A., when the opposite was true. Agents also withheld concerns about the reliability of allegations against Trump compiled by the former British intelligence officer Christopher Steele.

Horowitzs work showed that the governments secretive surveillance process requires significant reform. But the report found that the opening of the probe was legally justified, and that the officials failures did not induce leaders to commit improper acts. We did not find documentary or testimonial evidence that political bias or improper motivation influenced the decisions, Horowitz wrote. (A separate investigation into Peter Strzok, a senior counter-intelligence agent who had sent scornful text messages about Trump, came to a similar conclusion.) James Baker, the former general counsel of the F.B.I., told me that the Bureau began the investigation before receiving a copy of the Steele dossier and before the Page e-mail was altered. At the time, Democratic Party communications stolen by Russia were circulating online, and Trump had publicly called for Russia to steal and release Hillary Clintons e-mails; several of his campaign officials had been in contact with Russian officials and with suspected intelligence operatives. We have an obligation to protect the United States from Russia, Baker said. Presented with the same facts, I would open the investigation again.

Barr released a response to the report, disputing Horowitzs conclusions. Despite the core finding that the investigation was initiated properly, Barr argued that the report makes clear that the F.B.I. launched an intrusive investigation of a U.S. presidential campaign on the thinnest of suspicions. Durham, the federal prosecutor appointed to carry out a separate investigation, suggested that he and Barr had gathered evidence that contradicted Horowitz. We advised the inspector general that we do not agree with some of the reports conclusions as to predication and how the F.B.I. case was opened, he said. This statement violated a Justice Department practice of not commenting on investigations until they are finished.

Trump went further, suggesting that Horowitz was part of a cabal formed in the previous Administration. Remember that I.G.Horowitz was appointed by Obama, he tweeted. There was tremendous bias and guilt exposed, so obvious, but Horowitz couldnt get himself to say it. Big credibility loss. Obama knew everything!

Christopher Wray, the F.B.I. director, immediately admitted the Bureaus errors and announced forty reforms designed to prevent improper surveillance. But, in a television interview, he pushed back about other false claims. When asked about Trumps calls for an investigation into Ukraines meddling in the election, Wray replied, We have no information that indicates that Ukraine interfered. Wray also urged Americans to vet their sources of information. Theres all kinds of people saying all kinds of things out there, he said. And I think part of us being well protected against malign foreign influence is to build together an American public thats resilient, that has appropriate media literacy, and that takes its information with a grain of salt.

After Wray defended the F.B.I., Trump attacked him as well. I dont know what report current Director of the FBI Christopher Wray was reading, but it sure wasnt the one given to me, he tweeted. With that kind of attitude, he will never be able to fix the FBI, which is badly broken despite having some of the greatest men & women working there!

Wray is still in his job, but others have faced significant consequences. One of these is Dan Coats, the director of National Intelligence, a moderate Republican who publicly questioned some of Trumps claims. Last summer, after months of pressure, Coats resigned, and Trump suggested replacing him with John Ratcliffe, a congressman from Texas who has trafficked in conspiracy theories. (After evidence suggested that Ratcliffe may have exaggerated his rsum, the White House withdrew the nomination; the position remains vacant.) Trump also revoked the security clearance of the former C.I.A. director John Brennan, who has criticized him. Agents recognized the implications; many intelligence officials, after years of low-paying government work, rely on their security clearances to obtain private-sector jobs when they retire. More recently, the President denounced the whistle-blower in the Ukraine case, who has subsequently received many death threats. When the threats spike, armed agents drive him to and from work.

In dozens of interviews, current and former law-enforcement and intelligence officials said that three years of Trumps Twitter attacks, conspiracy theories, and high-profile firings have left their leaders wary of speaking in public, testifying before Congress, or talking to reporters. They know that they will be asked about Trumps false claims. If they respond accurately, they risk being fired for contradicting the President.

The countrys intelligence agencies continue to produce private assessments that counter Trumps specious assertions. They affirm that Russia, not Ukraine, interfered in the 2016 election and predict that it is likely to meddle again in 2020, according to members of the House and the Senate Intelligence Committees. The F.B.I. and the C.I.A. have also assessed that white nationalists and ISIS members represent continued threats, issues that Trump has downplayed. But agency directors believe that they can best protect their institutions by keeping such concerns private. Survival is victory, the government official told me. If you are able to go out on your own terms, or go out last, its a victory for the institution.

If Barrs inquiry results in criminal charges, it would be a radical departure from past practice. When Durham investigated C.I.A. officers for torture, he pressed no criminal charges. Previous investigations into intelligence failures that cost American livessuch as missing warning signs before the 9/11 attacks or wrongly concluding that Saddam Hussein had weapons of mass destructioncarried no possibility of criminal sanction. James Clapper, who was the director of National Intelligence in 2016, cautioned that the election assessment is a work of analysis. If a prosecuting attorney is investigating analysts for their intelligence judgments, thats not good, Clapper said. James Baker worried that Trumps intimidation of investigators would have consequences at the F.B.I. It could reduce the willingness to give frank assessments or to pursue controversial cases, he said, adding, Im nervous about the institution.

In private gatherings, current and former F.B.I. agents and Justice Department officials register exhaustion at Trumps attacks on the F.B.I. Recent retirees told me that they were surprised by how little they missed working at the Bureau.

Some agents have embraced Wrays admonition to do their work and ignore the political brawl around them. After two and a half years on the job, Wray, a low-key former prosecutor and corporate lawyer, has inspired loyalty for handling a difficult situation gracefully. The Bureau, like the country, is deeply divided; even some agents who find Trump personally distasteful say that they support his policies. Comey was a popular director, but agents complain that his calls for people to vote against Trump play into conspiracy theories about the Bureau. The clearest sentiment is disdain for the political class. Last winter, during the longest government shutdown in U.S. history, the Bureaus thirteen thousand agents and twenty thousand support staffers struggled to pay their bills. After employees walked into supervisors offices in tears, agents set up impromptu food banks to help colleagues. Trump caused the shutdown by demanding that Congress fund his border wall with Mexico, but many agents argued that politicians on both sides were responsible. They didnt do their job, Tom OConnor, a retired F.B.I. agent, told me.

The political combat of the Trump era was breeding apathy and disgust. F.B.I. and Justice Department officials said that if Trump was relected there would be an exodus of employees. Some retired agents fear that the institution will not survive another four years.

Stephen Gillers suggested that Trumps attacks were part of a drive for increased power. One way that Trump seeks to maximize control is minimizing the disclosure of information and undermining the credibility of information, he said. The Congress needs information to do its job, and the President has frozen it outespecially in the impeachment investigation. Another check is the media, and the Presidents use of the term fake news can cause people to lose faith in the media. What remains are the courts, which are slow and cumbersome.

Donald Ayer, the former Bush Administration Deputy Attorney General, warned that Barrs interpretations of executive power could be validated. The ultimate question is what happens when these reach the Supreme Court, which has two Trump appointees, he said. There is a real danger that he succeeds. Some legal analysts believe that Barr is overplaying his hand. Benjamin Wittes, of Lawfare, predicted that the Supreme Court would reject Barrs extreme positions, creating precedents that ultimately reduce the power of the Presidency. The idea that the President gets to assert executive privilege over material that has already been made public is laughable, Wittes told me. I think they are very likely to lose a lot of this.

Chuck Cooper, the conservative litigator, disagreed. He said that Barrs tenure represented the achievement of the legal project launched during the Reagan Administration. He is building and extending on a foundation, Cooper said. It was popularized and very robustly advanced by the Meese Justice Department. Last October, in the Oval Office, Trump awarded Meese the Presidential Medal of Freedom, the countrys highest civilian honor. Barr attended, and Meese thanked him for carrying on his legacy: Youve risen to continue the string of great Attorneys General in this country.

As Barr insists on expanded Presidential power, Republican voters are starting to agree. According to the Pew Center, forty-three per cent of Republicans believe that presidents could operate more effectively if they did not have to worry so much about Congress and the courts. That number has increased from fourteen per cent when Trump took office. A House G.O.P. report about Ukraine endorsed his singular authority; slightly misquoting John Marshall, it argued that Trump was, constitutionally, the nations sole organ of foreign affairs, and thus had unlimited latitude in his dealings with Ukraine.

Ayer fears that Barr has combined a Reagan-era drive to dismantle government with a Trump-era drive to politicize it. As the White House succeeds in holding off congressional attempts at removing Trump from office, Barr is winning his long war on the power of the legislative branch. In the 2020 campaign, Trump will argue that he alone can protect the country from the dangers posed by the left, immigrants, and other enemies. And Barrs vision of Presidential power will be the Partys mainstream position. Barr sought out the opportunity to be Donald Trumps Attorney General, Ayer said. This, I believe, was his opportunitythe opportunity of a lifetimeto make major progress on advancing his vision of an all-powerful Chief Executive.

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William Barr, Trumps Sword and Shield - The New Yorker

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What is Cord Blood Stem Cells Market and What Factors will drive the Industry including Leading Players Cord Blood America Inc, Cryo-Cell…

January 13th, 2020 3:47 pm

The Cord Blood Stem Cells Market is predicted to worth +6500 Million USD with a CAGR of +30% over the forecast period 2020 to 2025.

Three sources of stem cells are bone marrow, peripheral blood, and cord blood. The blood in the umbilical cord is called cord blood and is collected at the time of delivery. Cord blood is an abundant source of Red Blood Cells (RBCs), white blood cells (WBCs), platelets and hematopoietic stem cells, and is extracted and stored in a private blood bank for the purpose of treating the disease in the future as needed.

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The global Cord Blood Stem Cells Market analytical report has recently published by Report Consultant to its massive repository. The research report has been summarized with informative and technical details of the dynamics of the market. It has been compiled by using some significant research methodologies such as primary and secondary research techniques. The report also elaborates on the factors which are fueling or hampering the growth of the market. It gives more focus on recent trends and technologies which are boosting the performance of the companies.

Cord Blood Stem Cells Market Key Players:

Cord Blood America Inc, Cryo-Cell International Inc, Cryo-Save AG, Cord Blood Registry Systems Inc, Viacord Inc, China Cord Blood Corporation, Cordlife Group Ltd, Vita 34 AG, Lifecell International Pvt. Ltd, Stemcyte Inc

The Cord Blood Stem Cells Market is segmented by means of storage service, application, and region.

Storage service: Public cord blood bank and Private cord blood bank

Cord blood stem cell market segmentation by application: Blood disease, Cancer, Acute leukemia, Krabbe diseases, and other diseases

Regions: North America (USA, Canada, Mexico), Europe (Germany, France, UK, Italy, Russia), Asia Pacific (China, India, Japan, South Korea, Australia, Indonesia, Malaysia), Middle East and Africa (Bahrain, Egypt, Jordan, Kuwait, Morocco, Oman, Qatar, Saudi Arabia, Syria)

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The report Describes the Cord Blood Stem Cells Market basics like definitions, classifications, applications and industry chain overview, industry policies and plans, product specifications, manufacturing processes, cost structures and so on. Then it analyzed the worlds main region market conditions, including the product price, profit, capacity, production, capacity utilization, supply, demand and industry growth rate, etc. In the end, the report introduced new project SWOT analysis, investment feasibility analysis, and investment return analysis.

Global research Cord Blood Stem Cells Market report highlights:

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What is Cord Blood Stem Cells Market and What Factors will drive the Industry including Leading Players Cord Blood America Inc, Cryo-Cell...

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Global Stem Cell Reconstructive Market 2019 Share, Trend, Segmentation and Forecast to 2025 – Instanews247

January 13th, 2020 3:47 pm

Global Stem Cell Reconstructive Market research Report 2019 may be a comprehensive business study on this state of business that analyses innovative ways for business growth and describes necessary factors like prime manufacturers, production worth, key regions and rate of growth. with growth trends, numerous stakeholders like investors, CEOs, traders, suppliers, analysis & media, international Manager, Director, President, SWOT analysis i.e. Strength, Weakness, Opportunities and Threat to the organization and others. This report focuses on Professional Global Stem Cell Reconstructive Market 2019-2025 volume and value at Global level, regional level and company level.

Global Stem Cell Reconstructive Market 2019 report provides key statistics on the market status of the Stem Cell Reconstructive Manufacturers and is a valuable source of guidance and direction for companies and individuals interested in the Stem Cell Reconstructive Industry. The Stem Cell Reconstructive industry report firstly announced the Stem Cell Reconstructive Market fundamentals: type applications and market overview; product specifications; manufacturing processes; cost structures, raw materials and so on.

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Stem Cell Reconstructive market competition by top manufacturers/ Key player Profiled:Osiris TherapeuticsNuVasiveCytori TherapeuticsTakeda (TiGenix)CynataCelyadMedi-postAnterogenMolmedAnd More

Stem Cell Reconstructive Market is expected to grow at a CAGR of roughly xx% over the next five years, will reach xx million US$ in 2025, from xx million US$ in 2019, according to a new study.

Stem Cell Reconstructive Market Segment by Type covers:Embryonic Stem CellAdult Stem Cell

Stem Cell Reconstructive Market Segment by Applications can be divided into:HospitalsResearch InstitutesOthers

Regional analysis covers:North America (USA, Canada and Mexico)Europe (Germany, France, UK, Russia and Italy)Asia-Pacific (China, Japan, Korea, India and Southeast Asia)South America (Brazil, Argentina, Columbia etc.)Middle East and Africa (Saudi Arabia, UAE, Egypt, Nigeria and South Africa)

This report focuses on the Stem Cell Reconstructive in Global market, especially in North America, Europe and Asia-Pacific, South America, Middle East and Africa. This report categorizes the market based on manufacturers, regions, type and application.

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Key questions answered in the report:What will the market growth rate of Stem Cell Reconstructive market?What are the key factors driving the Global Stem Cell Reconstructive market?Who are the key manufacturers in Stem Cell Reconstructive market space?What are the market opportunities, market risk and market overview of the Stem Cell Reconstructive market?What are sales, revenue, and price analysis of top manufacturers of Stem Cell Reconstructive market?Who are the distributors, traders and dealers of Stem Cell Reconstructive market?What are the Stem Cell Reconstructive market opportunities and threats faced by the vendors in the Global Stem Cell Reconstructive industries?What are sales, revenue, and price analysis by types and applications of Stem Cell Reconstructive market?What are sales, revenue, and price analysis by regions of Stem Cell Reconstructive industries?

Key Benefits Major countries in each region are mapped according to individual market revenue. Comprehensive analysis of factors that drive and restrict the market growth is provided. The report includes an in-depth analysis of current research and clinical developments within the market. Key players and their key developments in the recent years are listed.And More.

The next part also sheds light on the gap between supply and consumption. Apart from the mentioned information, growth rate of Stem Cell Reconstructive market in 2025 is also explained. Additionally, type wise and application wise consumption tables and figures of Stem Cell Reconstructive market are also given.

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Global Stem Cell Reconstructive Market 2019 Share, Trend, Segmentation and Forecast to 2025 - Instanews247

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Connective Tissue Growth Factor Market outlook & growth prediction by players (Genetic Disorders , Liver Fibrosis , Others, BLR Bio LLC ) -…

January 13th, 2020 3:45 pm

A qualitative research study accomplished by HTF MI titled Global Connective Tissue Growth Factor Market covers detailed Product / Industry Scope, current and future market size scenario and elaborates outlook and status to 2025 provides primary data, studies and vendor briefings. The market Study is segmented by key regions along with country level break-up which is accelerating the marketization and by products type, application/end-users. The research study provides estimates for Connective Tissue Growth Factor forecast till 2025. Some of the Major Players Included in the study are BLR-200, IB-DMD, OLX-201, PBI-4050, Others, Demand Coverage (Market Size & Forecast, Consumer Distribution):, Hypertrophic Scars, Opthalmology, Genetic Disorders, Liver Fibrosis, Others, BLR Bio LLC, FibroGen Inc, ProMetic Life Sciences Inc, RXi Pharmaceuticals Corp, North America, Europe, Asia-Pacific, South America & Middle East & Africa.

Get Free Sample Report + All Related Graphs & Charts @:https://www.htfmarketreport.com/sample-report/2214003-global-connective-tissue-growth-factor-market-study-2016-2026-by-segment

1) Can we add or profile new players as per our need?

Yes, we can add or profile new company as per client need in the report. Final confirmation to be provided by research team depending upon the difficulty of survey.

** Data availability will be confirmed by research in case of privately held company. Up to 3 players can be added at no added cost.

2) Can inclusion of additional Segmentation / Market breakdown is possible?Yes, inclusion of additional segmentation / Market breakdown is possible subject to data availability and difficulty of survey. However a detailed requirement needs to be shared with our research before giving final confirmation to client.

** Depending upon the requirement the deliverable time and quote will vary.

3) HowResearch Report is an Interesting One?

This report covers the current scenario and growth prospects of Global Connective Tissue Growth Factor for the period 2019 2025. The study is a professional and in-depth study with around n- no. of tables and figures which provides key statistics on the state of the industry and is a valuable source of guidance and direction for companies and individuals interested in the domain.

The titled segments and sub-section of the market are illuminated below:

The Global Connective Tissue Growth Factor market has been divided into, application, type and region.

On The Basis Of Type, Market is segmented by , by Application it includes

Some of the Key Players Identified are BLR-200, IB-DMD, OLX-201, PBI-4050, Others, Demand Coverage (Market Size & Forecast, Consumer Distribution):, Hypertrophic Scars, Opthalmology, Genetic Disorders, Liver Fibrosis, Others, BLR Bio LLC, FibroGen Inc, ProMetic Life Sciences Inc, RXi Pharmaceuticals Corp, North America, Europe, Asia-Pacific, South America & Middle East & Africa

Geographic Segmentation includes North America, Europe, Asia-Pacific etc

***Sub Regions Included: North America [United States, Canada, Mexico], Asia-Pacific [China, India, Japan, South Korea, Australia, Indonesia, Malaysia, Philippines, Thailand, Vietnam], Europe [Germany, France, UK, Italy, Russia, Rest of Europe], South America [Brazil, Argentina, Rest of South America], Middle East & Africa [GCC Countries, Turkey, Egypt, South Africa, Rest of Middle East & Africa]

*** Unless until specified in Original TOC

To know more about the table of contents, you can click @https://www.htfmarketreport.com/reports/2214003-global-connective-tissue-growth-factor-market-study-2016-2026-by-segment

Furthermore, the years considered for the study are as follows:Historical year 2013-2018Base year 2018Forecast period** 2019 to 2025 [** unless otherwise stated]

**Moreover, it will also include the opportunities available in micro markets for stakeholders to invest, detailed analysis of competitive landscape and product services of key players.

Major Key Features Covered in Global Connective Tissue Growth Factor Market Report:

* To gain insightful analyses of the market and have comprehensive understanding of the Global Connective Tissue Growth Factor and its commercial landscape.* Assess the Connective Tissue Growth Factor production processes, major issues, and solutions to mitigate the development risk.* To understand the most affecting driving and restraining forces in the Connective Tissue Growth Factor and its impact in the global market.* Learn about the market strategies that are being adopted by leading respective organizations.* To understand the future outlook and prospects for Connective Tissue Growth Factor Market.

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Queries we have tried to answered in Global Connective Tissue Growth Factor Market Study:Who are the Leading key players and what are their Key Business strategies in the Global Connective Tissue Growth Factor?What are the key consequences of the five forces analysis of the Connective Tissue Growth Factor?What are different opportunities and threats faced by the dealers in the Global Connective Tissue Growth Factor?What are the strengths and weaknesses and business strategies of the key vendors?

Some Extracts from Table of Contents:Chapter 1. Market OverviewChapter 3. Market DynamicsChapter 4. Research MethodologyChapter 5. Market Factor AnalysisChapter 6. Global Connective Tissue Growth Factor Market, By Delivery ModeChapter 7. Global Connective Tissue Growth Factor Market, By ApplicationChapter 8. Global Connective Tissue Growth Factor Market, By RegionChapter 9. Global Connective Tissue Growth Factor Market, By TypeChapter 10. Company LandscapeChapter 11. Company ProfilesChapter 12. Appendix

Thanks for reading this article; you can also get individual chapter wise section or region wise report version like North America, Europe or Asia.

About Author:HTF Market Report is a wholly owned brand of HTF market Intelligence Consulting Private Limited. HTF Market Report global research and market intelligence consulting organization is uniquely positioned to not only identify growth opportunities but to also empower and inspire you to create visionary growth strategies for futures, enabled by our extraordinary depth and breadth of thought leadership, research, tools, events and experience that assist you for making goals into a reality. Our understanding of the interplay between industry convergence, Mega Trends, technologies and market trends provides our clients with new business models and expansion opportunities. We are focused on identifying the Accurate Forecast in every industry we cover so our clients can reap the benefits of being early market entrants and can accomplish their Goals & Objectives.

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Connective Tissue Growth Factor Market outlook & growth prediction by players (Genetic Disorders , Liver Fibrosis , Others, BLR Bio LLC ) -...

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Pet Talk: Chew on this goats as pets – Marshall News Messenger

January 12th, 2020 2:44 pm

Though goats are often associated with an agricultural lifestyle, these animals are being kept as pets more and more frequently. The owner of a pet goat benefits from companionship, the potential for milk production, land management by grazing, and more.

Dr. Evelyn Mackay, a clinical assistant professor at the Texas A&M College of Veterinary Medicine & Biomedical Sciences, discusses the ins and outs of goat ownership that every potential owner should know.

Goats are fun, social, and playful animals, Mackay said. They make great companions and are often very interactive and bonded to their owners.

This social nature means that potential owners should commit to getting multiple animals, so their goat has a companion.

Although goats can be companions for other animals, such as racehorses, they are happiest when with another member of their species. However, owners of multiple goats must ensure that their goats are treating each other kindly.

Goats have a social structure and sometimes dominant goats may bully and steal food from less dominant goats, Mackay said. This can cause problems in large groups if there are disagreements between goats. Generally, they work out their issues and exist harmoniously, but groups of goats should be similarly sized, and goats with horns should not be housed with goats without horns.

Potential owners living in suburban areas should consider adopting smaller breeds of goats, like Pygmy goats or Nigerian Dwarves, which can be kept in large yards.

Full-sized pet goats, such as dairy goats and Boer goats, need plenty of room for grazing and exercise; therefore, Mackay does not recommend those breeds for potential owners living in suburban environments. In addition, parasites can become an issue if goats are too crowded or housed in an area that is too small.

Ultimately, Mackay recommends consulting with a veterinarian to determine the best type of goat for your family and living situation.

Regardless of goat size and location, it is essential that their environment provides proper nutrition; an improper diet, including human food, treats, or excessive amounts of grain, can cause gastrointestinal issues and make goats very sick.

Pet goats should always have access to some type of forage, like hay or grass, Mackay said. Their diet can be supplemented with a little bit of concentrate (grain or pellets), but the foundation of a healthy diet should always be high-quality hay or grass. They should only be fed grain formulated for goats, since grain for other species, like cattle and horses, can cause toxicities. If they want to feed treats, consider small amounts of fruit or vegetables, but avoid kale and broccoli, which can also be toxic.

Like any animal, a goat requires annual vaccines and wellness exams with a veterinarian.

As outdoor pets, goats must also be protected from predators; Mackay says owners should ensure their pet goats are kept where they cannot be chased by dogs.

One final aspect potential owners should consider is that, as with any pet, a full-grown goat will be considerably larger than the baby they adopt.

Everyone thinks baby goats are very cute but people should be prepared for even the smallest breeds of goats to be a minimum of 60 pounds at maturity, Mackay said.

By The Texas A&M University College of Veterinary Medicine & Biomedical Sciences

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PET TALK: Resolutions for a paw-some New Year – Laredo Morning Times

January 12th, 2020 2:44 pm

The health and well-being of pets should be part of resolution process for their owners.

The health and well-being of pets should be part of resolution process for their owners.

Photo: Texas A&M University

The health and well-being of pets should be part of resolution process for their owners.

The health and well-being of pets should be part of resolution process for their owners.

PET TALK: Resolutions for a paw-some New Year

The new year is an exciting milestone during which we often check in on our wellbeing and set goals for self-improvement. This year, consider using the holiday as an opportunity to evaluate and improve the health of your furry friend, as well, by including them in your new years resolutions.

Dr. Christine Rutter, a clinical assistant professor at the Texas A&M College of Veterinary Medicine & Biomedical Sciences, offers some resolutions owners can set to improve their pets wellness in 2020.

Just as owners may reflect on their physical health every January, the start of the new year is a wonderful time to take stock of your pets health. For example, how are their activity levels and weight? If you are unsure, Rutter advises that owners ask their veterinarian those questions.

I think a resolution to spend more time with your pet is a great one. If your dog can tolerate walking, this is a great way to improve your own mental and physical health, as well as strengthen the bond between pet and owner, Rutter said. For cats, enrichment such as a laser pointer, feather wands, and crinkle toys can really get them moving and they are delightful to watch!

On a similar note, Rutter recommends that pet owners establish a dental care routine for their pet in the new year. A great way to begin this is to bring your pet in for an evaluation and cleaning. Because February is Pet Dental Health Month, Rutter advises that pet owners schedule an appointment early to take advantage of discounts that many veterinarians may offer on their dentistry services.

This can also be a time to check up on your pets check-ups.

Make sure your pet has an annual wellness visit scheduled for routine vaccinations. Knowing which immunizations will be expiring allows owners time to schedule appointments for them to be renewed. Owners should also consider updating their pets heartworm testing and medication, as well as parasite prevention plans with your veterinarian.

There are a lot of new parasite and heartworm prevention products out there, and its a great time to check and see what is right for your pet(s), Rutter said.

Owners may also want to take a second look at the snacks they feed their pets. Many dog treats and rawhides are high in calories, sodium, and fat. Dogs, especially smaller breeds, require far fewer calories than humans do and are easy to overfeed.

Because the little snacks owners feed their pets really add up, Rutter suggests owners consider healthier options.

Dogs typically love baby carrots, apples, green beans, cauliflower, and melon. Just stay away from onions, peppers, grapes, raisins, and garlic, Rutter said. Each dog is different, and if youve been giving them delicious stinky dog treats (or even worse, table food), they may turn their nose at these offerings initially. They will come around once the table food and tasty treats decrease in frequency.

The new year marks the beginning of many commitments to health and personal improvement. In 2020, why not extend your goals to improve the lives of the furry friends who love you the most?

Pet Talk is a service of the College of Veterinary Medicine & Biomedical Sciences, Texas A&M University. Stories can be viewed on the web at vetmed.tamu.edu/news/pet-talk. Suggestions for future topics may be directed to editor@cvm.tamu.edu.

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PET TALK: Resolutions for a paw-some New Year - Laredo Morning Times

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With board creation, Portland biotech startup takes the next step in growth – Mainebiz

January 12th, 2020 2:44 pm

A Portland biotech startup with an unusual line of products for pets has taken a step forward in the companys development with the creation of a 15-member scientific advisory board.

ElleVet Sciences has named prominent veterinary clinicians, researchers and industry experts to the new group, which will oversee scientific development of ElleVets cannabis-based therapeutic products, according to a news release Monday.

"It's an honor to co-chair this groundbreaking advisory board with some of the leading veterinarians of our generation," said Joseph Wakshlag, professor at Cornell University College of Veterinary Medicine and ElleVets chief medical officer. "With so many great minds in the room, it is fantastic to be able to share the science behind the product, which has already fostered great discussions with the group."

Another member of the board, Michael Petty, commented: It is a pleasure to join the ElleVet advisory board. Their unique cannabinoid products seem to have significant potential in managing discomfort in pets and impacting other modalities, a true original in the industry.

Petty is a veterinarian and researcher who has served as lead investigator in 12 U.S. Food and Drug Administration studies of pain management products.

ElleVet was formed in 2017 by Michael J. Williams and Christian Kjaer, both formerly senior executives at Westbrook-based IDEXX Laboratories (Nasdaq: IDXX). The companys products currently include chews and oils that treat arthritis in dogs, using cannabinoids derived from hemp, a form of cannabis.

The formation of a scientific advisory board is a typical step for maturing companies in the biotechnology industry. The creation of the ElleVet board follows the appointment of Wakshlag as chief medical officer in August.

The ElleVet board comprises the following members.

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With board creation, Portland biotech startup takes the next step in growth - Mainebiz

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How wildfire smoke affects pets and other animals – Salon

January 12th, 2020 2:44 pm

Catastrophic fires across the globe are increasing in both frequency and magnitude. The bushfires in Australia, fuelled by heatwaves and drought, have burned more than 10.7 million hectares, an area larger than Iceland.

Over one billion animals are estimated to have died in the Australian bushfires so far. This loss of life is devastating. Horses, dogs and other domestic animals are also being affected by the smoke generated by the wildfires.

As veterinarians who have cared for small animals following the California wildfires and researched the impacts of wildfires on horses in Canada, we have some perspective on how smoke can harm companion animals and what people can do to protect the animals in their care.

What is smoke?

The composition of smoke depends on what is being burned. The smoke from a house fire or a barn fire will contain different compounds than the smoke from wildfires or bushfires.

When an animal inhales smoke, it brings a combination of toxic gases, such as carbon monoxide and hydrogen cyanide, and particulate matter, a mixture of small liquid and solid particles, into its throat, nose and lungs.

Smoke inhalation can damage the respiratory tract in multiple ways; it can cause burns and lead to physical irritation, causing the airway to swell and become blocked.

Toxic gases can impair oxygen delivery and lead to death. Animals with immediate and close exposure to fires, such as barn or house fires, face this risk.

Exposure to bushfires or wildfires results in a sustained, lower-dose exposure to smoke. The major concern here is particulate matter. Very small particulate matter (less than four microns in diametre) can bypass the bodys natural filters and reach the lower airways.

Smoke inhalation in horses

Our relationship with horses is unique in that they bridge the gap between livestock and companion animals. As athletic animals, air quality impacts horses capacity to perform. The financial ramifications of impaired performance is not insignificant, given the economic impact of the horse industry in multiple countries.

Horses have a huge lung capacity. A horse moves more than 2,000 litres of air through its lungs every minute during strenuous exercise. With this air, horses also inhale a large number of pollutants, which is drastically increased during fires.

In 2018, Calgary was smothered in wildfire smoke for more than six weeks, with poor air quality warnings issued daily. During this period, we studied the impact of poor air quality on exercise performance in polo horses that were at a maintenance level of fitness at the end of the competition season. They continued the same training program throughout the trial, so all results are due to the improved conditions and not a conditioning effect.

Every horse involved in the study exhibited coughing at rest and during exercise, with owners complaining of decreased performance.

We performed a procedure called a lung wash on these horses to retrieve cells and particulate matter from their lungs. Every horse in the study showed inflammation of the respiratory tract. We also found large amounts of microscopic pollens and other debris trapped in the cells. These findings are diagnostic of asthma in horses, and were also commonly seen by veterinarians working in the affected area.

We also wanted to know how much the performance of these horses improved after prolonged smoke exposure. The gold standard technique to evaluate athletic performance is the measurement of maximum oxygen consumption, also known as VO2max.

After 2.5 weeks of improved air quality, horses had a 15 per cent increase in speed, as well as a 13.2 per cent increase in VO2max, compared to those measures on the first day of improved air quality. To put this into context, training two-year-old racehorses for eight weeks has been reported to result in a 6.7 per cent improvement in VO2max.

How to keep animals safe

There are many guidelines available for people when air quality is poor, but very little information for pet owners.

The air quality index (AQI) is used in Australia and the United States. The AQI is a single number presented on a scale of 0-500, ranging from excellent air quality to the most hazardous air pollution. Canada uses the Air Quality Health Index (AQHI), using a scale from 1 to 10.

The Australian Broadcasting Corporation reported several regions where AQIs had surpassed 500 in December 2019. Wildfires in northern Alberta in 2018 sent AQHI index past 11 in Calgary in May 2019.

Stay indoors

Where possible, animals should be kept indoors when the AQI is greater than 150 or AQHI is 10+ for multiple days in a row to reduce exposure to small particulate matter. The environment matters, however. For example, a dog in a tightly sealed home will have less exposure to airborne irritants than a horse in a stable.

Like human asthmatics, staying indoors might not prevent symptoms in animals with pre-existing respiratory conditions, especially when smoke persists for greater than five days. In addition, brachycephalic breeds such as pugs and bulldogs are likely to have a reduced tolerance to smoke.

Reduce outdoor physical activity

When animals exercise, they increase the amount of air they inhale, which increases the deposition of particles deep in the lungs.

Based on guidelines from multiple regulatory bodies and associations, we recommend limiting outdoor exercise in animals when smoke is visible. Moderate to intense exercise should be reduced when there is a high or very high risk rating (AQI exceeding 100; AQHI greater than 7). We recommend cancelling events (such as a Thoroughbred race) when there is a very high risk rating (AQI greater than 150 or an AQHI of 10+).

Theres every indication that fire seasons are going to become longer and more frequent. When smoke starts to blanket the land, remember there are simple things you can do to protect the respiratory health of both you and your pets.

This is a corrected version of a story originally published on Jan. 8, 2020. The earlier story included a photo that showed the breakdown of blood components instead of the inflammatory cells, debris and pollens in a horses lungs after exposure to bushfire smoke.

Stephanie Laura Bond, Postdoctoral Associate, Faculty of Veterinary Medicine, University of Calgary; Laura Osborne, Adjunct associate, Faculty of Veterinary Medicine, University of Calgary, and Renaud Leguillette, Professor, Calgary Chair in Equine Sports Medicine, DVM, PhD, Dipl.ACVIM, Dipl. ACVSMR, University of Calgary

This article is republished from The Conversation under a Creative Commons license.

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How wildfire smoke affects pets and other animals - Salon

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New England news in brief – The Boston Globe

January 12th, 2020 2:44 pm

BostonPact will improve care of popular parks

The city and the Friends of the Public Garden entered an agreement to enhance the care of the Public Garden, Boston Common, and the Commonwealth Avenue Mall, Mayor Martin J. Walsh said. Bostons Parks and Recreation Department and the advocacy group signed an agreement Friday that strengthens the 50-year partnership between the Parks Department and the Friends at the strategic and operational level, committing to a shared objective of preserving, restoring, and caring for these historic parks, Walsh said. The pact will allow for more efficient and effective stewardship, and will improve the quality of life for downtown residents while increasing the resilience of these parks. The three spaces draw more than 7 million people each year, and hold Bostons largest collection of public art. They hold our history, they bring people together, and they bring the beauty of nature into our city, Walsh said.

State and local police are investigating the death of a man found stabbed in the parking lot of a housing complex Saturday morning, according to the Bristol district attorneys office. Jorge Vieira, 25, of Fall River died at Rhode Island Hospital in Providence, where he was transferred after first being taken to Saint Annes Hospital in Fall River, prosecutors said. Shortly before 7:30 a.m., emergency crews responded to a 911 call at the housing complex at 2000 Bay Road. Vieiras death is being investigated as a homicide. No further information was available Saturday evening.

Police on Friday arrested the second of two brothers from Clinton suspected of stealing $700 in cash from the Concord Cheese Shop two days before Christmas. Jason Faieta, 36, was apprehended one week after his brother, Brandon Faieta, 33, a former employee of the shop, Concord Police Chief Joseph OConnor said. Both brothers were charged with intent to commit a felony, larceny under $1,200, larceny from a building, and receiving stolen property under $1,200, OConnor said. At his arraignment Friday, Jason Faieta was released on personal recognizance and ordered to stay away from the shop and any witnesses. Brandon Faieta was arraigned last Monday. He was released on $200 bail and ordered to stay away from the business and to have no contact with witnesses, OConnor said. Both are due back in court on March 4.

Fiona, the pet falcon that went missing for two days and whose 78-year-old owner got stuck in a swamp in Westborough looking for her, was found Saturday by an off-duty firefighter. Mark Boyer tracked down the bird by using a GPS device attached to her, according to a Westborough Fire Department Facebook post. The falcon, which is valued at $20,000, was taken to Cummings School of Veterinary Medicine at Tufts University in North Grafton for treatment, the statement said. Boyer was also one of the firefighters who helped rescue Fionas owner, Bill Johnston, who fell through ice at Cedar Swamp while looking for her Thursday, the department said.

Education Commissioner Anglica Infante-Green said Friday that the nonprofit Rhode Island Foundation established the Fund for Rhode Island Public Education to accept donations from individuals, corporations, and foundations interested in improving public education statewide. The foundation will manage and distribute the money according to the education departments priorities and the donors intent. Donors could invest in professional learning opportunities for educators, advanced coursework for students, and upgrades to school facilities, for example, the department said. The fund launched with a $20,000 commitment from the Rhode Island Commodores, a nonprofit. (AP)

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New England news in brief - The Boston Globe

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Enhanced risk for severe weather in Auburn on Saturday – The Auburn Plainsman

January 12th, 2020 2:44 pm

The Auburn area is expected to experience severe weather on Saturday between 2 and 8 p.m., according to the National Weather Service.

Lee County is an "enhanced risk" area, meaning severe thunderstorms, damaging winds up to 70 mph and tornadoes are all possible Saturday, according to the NWS.

The Alabama Emergency Management Agency is expecting storms to enter Alabama around 9 a.m. and leave the state around 9 p.m.

A more exact timing of the storm is expected to become clearer as Saturday approaches.

Forecasters and experts are advising Alabamians to prepare now for severe weather and have a plan in place for taking shelter.

Greene Hall located in the College of Veterinary Medicine and Ralph Draughon Library are opened whenever a tornado watch is issued for Auburn University, day or night, for those who do not have a suitable place to shelter.

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Enhanced risk for severe weather in Auburn on Saturday - The Auburn Plainsman

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Ultragenyx shares jump on ‘better than expected’ gene therapy data – FierceBiotech

January 12th, 2020 2:43 pm

Ultragenyx Pharmaceutical saw its shares jump around 27% in trading Friday after announcing positive top-line data out of its gene therapy trial.

Its a small number, just three patients that form part of a third cohort for the phase 1/2 study, as well as another small test but a longer-term look from the second cohort.

In cohort three testing the biotechs drug DTX301, an adeno-associated virus gene therapy for the treatment of ornithine transcarbamylase (OTC) deficiency, there were two confirmed female responders as well a third potential male responder who requires longer-term follow-up to confirm response status.

The Art of Recognizing Clinical Supply Risk Factors and Applying Proactive Measures to Avoid Study Delays and Disruptions

No two studies are the same and each clinical supply project carries unique risks. But what characteristics are most likely to raise a flag that issues are ahead? Are there certain types of clinical sponsors and studies that are at greater risk of experiencing supply challenges? And how do clinical sponsors know what is important to focus on and what is not? Join us for this webinar as we attempt to answer these questions.

Meanwhile, in cohort two, one female patient saw a new response after a year. The biotech added that the two previously disclosed responders in cohort one and two also remain clinically and metabolically stable at 104 and 78 weeks, respectively. Across all nine patients dosed in the study, up to six patients have demonstrated a response, it said in a statement.

RELATED: BIO: In conversation with Emil Kakkis, Ultragenyx CEO

OTC deficiency is a rare X-linked genetic disorder characterized by complete or partial lack of the enzyme OTC. Excess ammonia, which is a neurotoxin, travels to the central nervous system through the blood,

According to the National Organization for Rare Disorders, the severity and age of onset of OTC deficiency vary from person to person, even within the same family. A severe form of the disorder affects some infants, typically males, shortly after birth (neonatal period). A milder form of the disorder affects some children later in infancy. Both males and females may develop symptoms of OTC deficiency during childhood. Most carrier females are healthy, but may be prone to severe headaches following protein intake.

Analysts at Jefferies said the data looked better than expected and could be a positive spark to help turn the stock heading into 2020 events. It certainly did in the immediate term, with the biotechs shares up by 27% in mid-morning trading Friday.

We are encouraged to see a more uniform response at the higher doses including three female responders. To date, three patients in the study have discontinued alternate pathway medication and liberalized their diets while remaining clinically and metabolically stable, said Eric Crombez, M.D., chief medical officer of the Ultragenyx Gene Therapy development unit.

We are moving to prophylactic steroid use in the next cohort as we believe this could further enhance the level and consistency of expression that we have demonstrated so far.

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Ultragenyx shares jump on 'better than expected' gene therapy data - FierceBiotech

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Gene therapy company begins operations in Longmont – The Denver Channel

January 12th, 2020 2:43 pm

LONGMONT, Colo. A few months ago, 2-year-old Maisie Forest was finally able to sit up on her own for the first time. Her development has been delayed by a rare genetic disorder called Spinal Muscular Atrophy, but last August, she received a groundbreaking treatment for the condition.

"It's a miracle drug," said Maisie's mother, Ciji Green. "It's not the cure, but we're talking about a disease that had no treatments four years ago," she added.

The "miracle drug" Green is referring to Zolgensma, a gene therapy for Spinal Muscular Atrophy made by Novartis-owned AveXis. On Tuesday, AveXis cut the ribbon on a new facility in Longmont where it will soon produce Zolgensma.

"Zolgensma is this first product weve had approved by the FDA for the treatment of kids with Spinal Muscular Atrophy," said AveXis President David Lennon.

The FDA approval came last May, just in time for Maisie to receive the treatment. But her mother still had to fight for the insurance company to pay for it. At $2.1 million per dose, Zolgensma is the most expensive drug or treatment ever made. Lennon said Novartis has invested half a billion dollars in the production of Zolgensma.

For Green, the cost is well worth the changes she's already seen in her daughter. Speaking to employees at the AveXis ribbon cutting, she called them heroes.

"To all of you it may just be a treatment, but to my family and so many others, its so much more," said Green.

AveXis says the same platform they used to produce Zolgensma might be applied to other therapies for other diseases in the future. The company is looking at developing treatments for Rett Syndrome, Friedreichs Ataxia, and an inherited form of Amyotrophic Lateral Sclerosis, or ALS.

"There are actually thousands of these kinds of diseases. Usually they impact a few hundred kids or adults every year, but altogether there are potentially millions of patients who have genetic diseases around the world," said Lennon.

Lennon said AveXis chose Longmont for its production facility in part because of the infrastructure already in place. The building at 4000 Nelson Rd. was previously occupied by pharmaceutical companies AstraZeneca and Amgen. He said the available talent was also a factor.

AveXis retained most of the employees from the previous tenants. With new hires, the Longmont facility currently has a staff of around 300 employees and expects to grow to 400 by the end of 2020.

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Gene therapy company begins operations in Longmont - The Denver Channel

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At 16, Shes a Pioneer in the Fight to Cure Sickle Cell Disease – The New York Times

January 12th, 2020 2:43 pm

In the months after the gene therapy infusion at Boston Childrens, her symptoms disappeared. But doctors had given her blood transfusions while she regrew her own red blood cells, so it was not clear if the absence of symptoms was because of the gene therapy or the transfusions.

As she recovered, Helen returned to her passion: dancing. One day, she came back from her school dance group and told her mother, My legs hurt. It feels funny. Ms. Cintron smiled. Thats soreness, she explained. Helen laughed. She had only known pain from sickle cell.

Helen was scheduled for her six-month checkup on Dec. 16. By then, all the transfused cells were gone, leaving only blood made by stem cells in her own marrow. The doctors would finally tell her whether the therapy was working.

The day before, she and her parents visited the New England Aquarium in Boston. She was able to stay outside on a cold, blustery day, watching one seal bully the others, barking and fighting. When Helen mentioned that her hands were cold, Ms. Cintrons stomach clenched in fear. But it was just a normal thing to feel on a winter day.

The next morning, Dr. Esrick delivered the news. Helens total hemoglobin level was so high it was nearly normal a level she had never before achieved even with blood transfusions. She had no signs of sickle cell disease.

Now you are like me, her father told her. I jump in the pool, I run. Now you can do it, too!

Her family, accustomed to constant vigilance, is only now getting used to normal life.

On Dec. 23, Helen and her mother flew to the familys new home in Arizona.

Helen recently described her transformed outlook on Facebook.

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At 16, Shes a Pioneer in the Fight to Cure Sickle Cell Disease - The New York Times

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Scientists want human trials for gene therapy that could help battle addiction – Digital Trends

January 12th, 2020 2:43 pm

In recent years, new gene editing tools have been used for everything from genetic modification of plants to increase crop yields to, far more controversially, genetic tampering with human embryos. Could a form of gene therapy also be useful in helping treat cocaine addiction, a form of addiction that proves highly resistant to alternative approaches, such as conventional medical treatment and psychotherapy? Thats what researchers from the world-famous Mayo Clinic are hoping to prove.

They are seeking approval for the first-in-human studies of an innovative new single-dose gene therapy. Their approach involves the delivery of a gene coding for an enzyme, called AAV8-hCocH, which metabolizes cocaine in the body into harmless byproducts. In order to progress to this next step in their work, they first have to gain permission from the U.S. Food and Drug Administration (FDA) in the form of an Investigational New Drug Application.

The researchers have already demonstrated the safety of their approach in mice. In a prior experiment, they showed a complete lack of adverse effects in mice which had both been previously exposed to cocaine and those which had not.

Mice given one injection of AAV8-hCocH and regular daily injections of cocaine had far less tissue pathology than cocaine-injected mice with no vector treatment, the researchers wrote in the abstract for their paper describing the work. Biodistribution analysis showed the vector located almost exclusively in the liver. These results indicate that a liver-directed AAV8-hCocH gene transfer at reasonable dosage is safe, well-tolerated, and effective. Thus, gene transfer therapy emerges as a radically new approach to treat compulsive cocaine abuse.

This is not the first time similar work has been carried out. In February 2017, scientists at the University of British Columbia genetically engineered a mouse so as to be incapable of becoming addicted to cocaine. However, one of the researchers on the project told Digital Trends that transferring this work across to humans for possible treatment for addiction was not straightforward. Instead, that work was more focused on exploring the link between drug use and genetics and biochemistry.

Theres still a whole lot more research that needs to be done in this area. Even if the FDA grants the Mayo Clinic researchers permission for their human trials, well most likely be waiting a few years at least before this treatment could be rolled out to the general public. Its an exciting leap forward, nonetheless.

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Scientists want human trials for gene therapy that could help battle addiction - Digital Trends

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Generation Bio grabs a $110M round to ramp up work on next-gen gene therapies – FierceBiotech

January 12th, 2020 2:43 pm

In 2018, Generation Bio broke cover with a $25 million series A, swiftly followed by a meatier $100 million second funding round.

Now, just before the J.P. Morgan Healthcare Conference, it has grabbed its biggest yet, a $110 million series C, as it looks to go all in for IND-enabling studies for its leading programs: liver-targeted therapies for hemophilia A and phenylketonuria.

In addition to the liver, Generation Bio is also working on potential treatments for diseases of skeletal muscle and the eye.

The Art of Recognizing Clinical Supply Risk Factors and Applying Proactive Measures to Avoid Study Delays and Disruptions

No two studies are the same and each clinical supply project carries unique risks. But what characteristics are most likely to raise a flag that issues are ahead? Are there certain types of clinical sponsors and studies that are at greater risk of experiencing supply challenges? And how do clinical sponsors know what is important to focus on and what is not? Join us for this webinar as we attempt to answer these questions.

The early-stage Cambridge, Massachusetts-based biotech saw its major round led by T. Rowe Price with help from Farallon, Wellington Management and existing investors Atlas Venture, Fidelity, Invus, Casdin, Deerfield, Foresite Capital and an entity associated with SVB Leerink.

Generation Bios platform is geared up to be gene therapy 2.0 and is designed to develop re-dosable, long-lasting, scalable gene therapies for severe diseases.

The company is developing gene therapies under the GeneWave banner that use closed-ended DNA rather than viruses to deliver therapeutic proteins, which could sidestep safety issues such as immune reactions

Our vision is to develop re-dosable, long-lasting gene therapies manufactured at a scale that leaves no patient or family behind, said Geoff McDonough, M.D., president and CEO of Generation Bio.

Since our founding we have had the support of high-quality investors who share our excitement about the potential of our platform to lead a new generation of gene therapy and about advancing our lead programs toward the clinic.

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Generation Bio grabs a $110M round to ramp up work on next-gen gene therapies - FierceBiotech

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Solid Bio Restructures to Get Halted Gene Therapy Study Back on Track – Xconomy

January 12th, 2020 2:43 pm

XconomyBoston

Solid Biosciences is slashing its workforce, including two top executives, in order to devote the companys remaining resources to its experimental gene therapy for Duchenne muscular dystrophy.

The corporate restructuring announced Thursday comes two months after the FDA placed a hold on the study after safety problems emerged that were linked to the gene therapy, SGT-001. Cambridge, MA-based Solid Bio (NASDAQ: SLDB) says going forward it will focus on how to address the clinical hold and resume testing. With the corporate changes, Solid Bio says it has enough cash to last into next year. At the end of the third quarter of 2019, the company reported cash and other holdings totaling $105.7 million.

Following the announcement, Solid Bios stock price slid more than 17 percent to $3.66 per share in pre-market trading.

Solid Bio has been developing SGT-001 as a way to potentially address the genetic defect underpinning Duchenne. Patients who have the inherited disease dont make enough of the muscle protein dystrophin. The Solid Bio gene therapy uses an engineered virus to deliver genetic material intended to restore dystrophin production. But the company had also previously disclosed theres a chance that the dosing requirements of the gene therapy could increase the risk of side effects related to the virus used in the treatment.

The complications reported in the November clinical hold included an immune system reaction, a decrease in red blood cells, kidney injury, and blood circulation difficulties. Those problems are similar to ones cited in the FDAs 2018 clinical hold on tests of SGT-001. Months later, the agency allowed the study to resume but with additional safety measures.

Solid Bios board approved the corporate restructuring on Tuesday, according to a securities filing. In the first quarter of this year, the company expects to record a $2.1 million charge related to the layoffs, which will cut about one third of its workforce. Last years annual report states that the company had 111 full-time employees as of Dec. 31, 2018. Those leaving Solid Bio include Alvaro Amorrortu, the companys chief operating officer, and Jorge Quiroz, its chief medical officer. But both will continue to advise Solid Bio under consulting agreements.

Photo by Flickr user reynermedia via a Creative Commons license

Frank Vinluan is an Xconomy editor based in Research Triangle Park. You can reach him at fvinluan [[at]] xconomy.com.

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