#Joe Haworth

[nerds-yearbook]

In 1880, murderer Joe Caswell was prepared to be hung for his crimes. The witnesses to the event were shocked as when Caswell dropped with the noose he suddenly vanished. They are further mystified, when the body of a murderer from the year 1960 suddenly appeared and took his place in the noose. ("Execution", Twilight Zone, TV)

[babadork]

[unwelcome-ephestion]

There's an almost Mandela Effect to suggest that Liza Minnelli was the original Sally Bowles in Cabaret in 1966 - this isn't true. The original Sally on Broadway was Jill Haworth, mainly known for films in that era. But this was not from lack of interest on Minnelli's part. She fought for the role, but producer/director Hal Prince decided that she was too American - Sally needed to be British. (Eagle eared listeners will notice that Sally as played by Minnelli in the film is American - presumably a question of authenticity.) Jill Haworth was asked by Hal Prince if she could sing, and allegedly responded "louder than Merman", an impressive claim given that Ethel Merman is still noted for her volume long after her death.

Minnelli had been associated with composer and lyricist John Kander and Fred Ebb before, having won a Tony for starring in their show Flora, the Red Menace, and whilst this role wasn't initially to be, her longstanding collaboration with them and role as muse of a sort continued past the Cabaret film to New York, New York, which is coming to Broadway (sans Liza, obviously) this year.

Who was the first Sally in the West End, however? This is a great piece of trivia - none other than Judi Dench. Her pipes are not Minnelli's, but anyone who has seen recent revivals will know that Sally is not meant to be a great singer, she is meant to be brash and deluded and heartbreaking, which Dench carries off with expected aplomb. One of a few forays into musicals for Dame Judi that we may explore later!

Take a listen and see who you prefer - this is Cabaret.

(Jill Haworth)

(Liza Minnelli)

(Judi Dench)

[ljblueteak]

Paul McCartney on Sgt. Pepper. Photos by Michael Cooper

(transcribed below)

I came up with the title and went to Robert with some drawings for the idea of the cover. I had come to the conclusion that The Beatles were getting a little bit safe, and we were a little intimidated by the idea of making 'the new Beatles album.' It was quite a big thing: "Wow, follow that!" So to relieve the pressure I got the idea, maybe from some from friends or something I'd read, that we shouldn't record it as The Beatles.

Mentally we should approach it as another group of people and totally give ourselves alter egos. So I came up with the idea of Sgt. Pepper's Lonely Hearts Club Band and the song 'It was Twenty Years Ago Today', and I started mentioning this to Robert in our late-night talks.

The original concept was actually a little bit different from how it turned out. I'd always liked those floral clocks that they have at seaside towns; they have a little green bank and put flowers in the shape of a clock. The original idea was that it was going to be a presentation from the Mayor of Middlesbrough or somewhere. There'd be this floral bank and there'd be us there and then at other parts of the cover we were going to have all the band's heroes--they were going to be on a photo, maybe behind the wall or something.

So there were these two ideas that eventually got pushed into one and then I said to everyone, 'OK, who are your favourites?" Marlon Brando was one of the first choices, and James Dean, Monroe--all those obvious ones and then other suggestions started to come in. George came up with all the Hindus, Babaji was his, and then there were things like footballers from our youth, you know, we had little joke things--Albert Stubbins--he's a footballer and so he was in and then it kind of snowballed.

I took all these ideas, the floral clock, the kind of presentation by a mayor, these heroes of ours, and Robert and I went with them to Peter Blake. Peter had all these sculptures of little people around, because he was married to Jann Haworth at the time and Jann was doing all those surfers and things like John Betjeman as a teddy bear and all that, so they crept in there.

The famous flowers that started off as the floral clock then became a guitar and the word 'Beatles'--they weren't marijuana leaves, they just looked like them--and so the Americans thought "Wow, well, this is it, it's all happening." We started shooting the cover and people would say, "Oh, can I come, can I come?" and we let more or less everyone come along, but eventually it got to the point where we had to say, "That's enough!"

So Robert would get all this and he'd show all the Indian stuff to George; and there'd be H.G. Wells and Johnny Weissmuller, Issy Bonn and all those people, and Burroughs would have been a suggestion probably from Robert, and there were a few kind of LA guys that Robert had slipped in. He'd slip in people that we didn't even know but we didn't mind, it was the spirit of the thing.

I don't know how many nights Michael spent on it but we were only there for that one night, the last night. They did all this without us. It was very nice when we turned up and it was all done, but not as impressive as when I saw the cover; just actually looking at the set wasn't as impressive as seeing the finished cover.

Jesus and Hitler were on John's favourites list but they had to be taken off. John was that kind of guy but you couldn't very well have Hitler and so he had to go. Gandhi also had to go because the head of EMI, Sir Joe Lockwood, said that in India they wouldn't allow the record to be printed. We said "You're kidding, they'll love it," but he said no, so that was something the lawyers made us take off. There were a few people who just went by the wayside.

We went to Burman's, the theatrical costumiers, to have all our outfits made up and the Stones did the same for the Satanic Majesties album.

It was great. The main centrefold was originally going to be a drawing by The Fool--Simon Posthuma and Marijke Koger, Dutch artists who'd produced some surrealistic work. They depicted us all up in the clouds and it was all very very acid, everything everywhere, lots of colours--but Robert didn't like it as art and so he vetoed it. We said "No man, it's really good. We love it, we love it."

The shoes were made by Anello and David, which was the first place we came into contact with, and we got our lovely handmade Beatle boots there.

Robert and I went down to Peter's house and Peter developed it all from there. The lists were his idea, and all the cut-outs instead of using real people, and then the floral clock got changed around; but basically it was the original theme.

The 'Welcome The Rolling Stones' was something they put in. They sort of asked us if we minded and we said, "No, no, not at all." Peter organized a fairground painter to paint the drum as that was someone that he used to hang out with.

From Blinds & Shutters

[byneddiedingo]

Jack Lemmon and Marilyn Monroe in Some Like It Hot (Billy Wilder, 1959)

Cast: Marilyn Monroe, Tony Curtis, Jack Lemmon, Joe E. Brown, George Raft, Pat O'Brien, Nehemiah Persoff, Joan Shawlee. Screenplay: Billy Wilder, I.A.L. Diamond, suggested by a story by Robert Thoeren and Michael Logan. Cinematography: Charles Lang. Art direction: Ted Haworth. Film editing: Arthur P. Schmidt. Music: Adolph Deutsch.

Some Like It Hot is a hilarious farce and one of the sweetest natured of Billy Wilder's usually acerbic comedies, thanks to skillful performances by Jack Lemmon and Tony Curtis and Marilyn Monroe's breath-taking luminosity. And it would be easy enough to leave it at that. But after all we've learned about sexual orientation and identity, after many feminist critiques of Hollywood's depiction of women, and after many explorations of Monroe's tragic history, it's a little naive to do so. Plumb beneath the surface of what seems to be blithe entertainment and you'll find disturbance in the depths. Take the celebrated ending of the film, for example. Sugar (Monroe) gets Jerry (Curtis), but at what price? As he warns her, he's exactly the kind of guy she knows is bad for her. And Osgood's (Joe E. Brown) shrugging off the fact that Daphne (Lemmon) is a man is one of the funniest moments on film, but in fact, the two men have the kind of chemistry together (as in the tango scene) that works, whereas Curtis and Monroe have no real chemistry. Is the film making a case, well in advance of its time, for same-sex attraction? Probably not Wilder's conscious intention, but what does that matter? As for the difficulties of working with Monroe that Wilder and her co-stars later complained about -- though Curtis eventually retracted the much-quoted statement that kissing her was "like kissing Hitler" -- this remains perhaps her best film and best performance. Imagine the movie with Mitzi Gaynor (originally considered for the part and on standby in case Monroe bailed on it) and you have nothing like the one we now know. In lesser hands than Wilder's the clichés (men in drag on run from gangsters) would have resulted in a second-rate comedy. The real marvel is that Wilder produced something enduring out of clichéd material. Curtis and Lemmon are great, even though their roles are the traditional comic teaming of a bully (Curtis) and a patsy (Lemmon), the formula already worked over by Laurel and Hardy, Abbott and Costello, Bing Crosby and Bob Hope, and Dean Martin and Jerry Lewis. Sometimes what you have to do is take the formula and transcend it.

[kwebtv]

Burke’s Law -  List of Guest Stars

The Special Guest Stars of “Burke’s Law” read like a Who’s Who list of Hollywood of the era.  Many of the appearances, however, were no more than one scene cameos.  This is as complete a list ever compiled of all those who even made the briefest of appearances on the series.  

Beverly Adams, Nick Adams, Stanley Adams, Eddie Albert, Mabel Albertson, Lola Albright, Elizabeth Allen, June Allyson, Don Ameche, Michael Ansara, Army Archerd, Phil Arnold, Mary Astor, Frankie Avalon, Hy Averback, Jim Backus, Betty Barry, Susan Bay, Ed Begley, William Bendix, Joan Bennett, Edgar Bergen, Shelley Berman, Herschel Bernardi, Ken Berry, Lyle Bettger, Robert Bice, Theodore Bikel, Janet Blair, Madge Blake, Joan Blondell, Ann Blyth, Carl Boehm, Peter Bourne, Rosemarie Bowe, Eddie Bracken, Steve Brodie, Jan Brooks, Dorian Brown, Bobby Buntrock, Edd Byrnes, Corinne Calvet, Rory Calhoun, Pepe Callahan, Rod Cameron, Macdonald Carey, Hoagy Carmichael, Richard Carlson, Jack Carter, Steve Carruthers, Marianna Case, Seymour Cassel, John Cassavetes, Tom Cassidy, Joan Caulfield, Barrie Chase, Eduardo Ciannelli, Dane Clark, Dick Clark, Steve Cochran, Hans Conried, Jackie Coogan, Gladys Cooper, Henry Corden, Wendell Corey, Hazel Court, Wally Cox, Jeanne Crain, Susanne Cramer, Les Crane, Broderick Crawford, Suzanne Cupito, Arlene Dahl, Vic Dana, Jane Darwell, Sammy Davis Jr., Linda Darnell, Dennis Day, Laraine Day, Yvonne DeCarlo, Gloria De Haven, William Demarest, Andy Devine, Richard Devon, Billy De Wolfe, Don Diamond, Diana Dors, Joanne Dru, Paul Dubov, Howard Duff, Dan Duryea, Robert Easton, Barbara Eden, John Ericson, Leif Erickson, Tom Ewell, Nanette Fabray, Felicia Farr, Sharon Farrell, Herbie Faye, Fritz Feld, Susan Flannery, James Flavin, Rhonda Fleming, Nina Foch, Steve Forrest, Linda Foster, Byron Foulger, Eddie Foy Jr., Anne Francis, David Fresco, Annette Funicello, Eva Gabor, Zsa Zsa Gabor, Reginald Gardiner, Nancy Gates, Lisa Gaye, Sandra Giles, Mark Goddard, Thomas Gomez, Pedro Gonzalez Gonzalez, Sandra Gould, Wilton Graff, Gloria Grahame, Shelby Grant, Jane Greer, Virginia Grey, Tammy Grimes, Richard Hale, Jack Haley, George Hamilton, Ann Harding, Joy Harmon, Phil Harris, Stacy Harris, Dee Hartford, June Havoc, Jill Haworth, Richard Haydn, Louis Hayward, Hugh Hefner, Anne Helm, Percy Helton, Irene Hervey, Joe Higgins, Marianna Hill, Bern Hoffman, Jonathan Hole, Celeste Holm, Charlene Holt, Oscar Homolka, Barbara Horne, Edward Everett Horton, Breena Howard, Rodolfo Hoyos Jr., Arthur Hunnicutt, Tab Hunter, Joan Huntington, Josephine Hutchinson, Betty Hutton, Gunilla Hutton, Martha Hyer, Diana Hyland, Marty Ingels, John Ireland, Mako Iwamatsu, Joyce Jameson, Glynis Johns, I. Stanford Jolley, Carolyn Jones, Dean Jones, Spike Jones, Victor Jory, Jackie Joseph, Stubby Kaye, Monica Keating, Buster Keaton, Cecil Kellaway, Claire Kelly, Patsy Kelly, Kathy Kersh, Eartha Kitt, Nancy Kovack, Fred Krone, Lou Krugman, Frankie Laine, Fernando Lamas, Dorothy Lamour, Elsa Lanchester, Abbe Lane, Charles Lane, Lauren Lane, Harry Lauter, Norman Leavitt, Gypsy Rose Lee, Ruta Lee, Teri Lee, Peter Leeds, Margaret Leighton, Sheldon Leonard, Art Lewis, Buddy Lewis, Dave Loring, Joanne Ludden,  Ida Lupino, Tina Louise, Paul Lynde, Diana Lynn, James MacArthur, Gisele MacKenzie, Diane McBain, Kevin McCarthy, Bill McClean, Stephen McNally, Elizabeth MacRae, Jayne Mansfield, Hal March, Shary Marshall, Dewey Martin, Marlyn Mason, Hedley Mattingly, Marilyn Maxwell, Virginia Mayo, Patricia Medina, Troy Melton, Burgess Meredith, Una Merkel, Dina Merrill, Torben Meyer, Barbara Michaels, Robert Middleton, Vera Miles, Sal Mineo, Mary Ann Mobley, Alan Mowbray, Ricardo Montalbán, Elizabeth Montgomery, Ralph Moody, Alvy Moore, Terry Moore, Agnes Moorehead, Anne Morell, Rita Moreno, Byron Morrow, Jan Murray, Ken Murray, George Nader, J. Carrol Naish, Bek Nelson, Gene Nelson, David Niven, Chris Noel, Kathleen Nolan, Sheree North, Louis Nye, Arthur O'Connell, Quinn O'Hara, Susan Oliver, Debra Paget, Janis Paige, Nestor Paiva, Luciana Paluzzi, Julie Parrish, Fess Parker, Suzy Parker, Bert Parks, Harvey Parry, Hank Patterson, Joan Patrick, Nehemiah Persoff, Walter Pidgeon, Zasu Pitts, Edward Platt, Juliet Prowse, Eddie Quillan, Louis Quinn, Basil Rathbone, Aldo Ray, Martha Raye, Gene Raymond, Peggy Rea, Philip Reed, Carl Reiner, Stafford Repp, Paul Rhone, Paul Richards, Don Rickles, Will Rogers Jr., Ruth Roman, Cesar Romero, Mickey Rooney, Gena Rowlands, Charlie Ruggles, Janice Rule, Soupy Sales, Hugh Sanders, Tura Satana, Telly Savalas, John Saxon, Lizabeth Scott, Lisa Seagram, Pilar Seurat, William Shatner, Karen Sharpe, James Shigeta, Nina Shipman, Susan Silo, Johnny Silver, Nancy Sinatra, The Smothers Brothers, Joanie Sommers, Joan Staley, Jan Sterling, Elaine Stewart, Jill St. John, Dean Stockwell, Gale Storm, Susan Strasberg, Inger Stratton, Amzie Strickland, Gil Stuart, Grady Sutton, Kay Sutton, Gloria Swanson, Russ Tamblyn. Don Taylor, Dub Taylor, Vaughn Taylor, Irene Tedrow, Terry-Thomas, Ginny Tiu, Dan Tobin, Forrest Tucker, Tom Tully, Jim Turley, Lurene Tuttle, Ann Tyrrell, Miyoshi Umeki, Mamie van Doren, Deborah Walley, Sandra Warner, David Wayne, Ray Weaver, Lennie Weinrib, Dawn Wells, Delores Wells, Rebecca Welles, Jack Weston, David White, James Whitmore, Michael Wilding, Annazette Williams, Dave Willock, Chill Wills, Marie Wilson, Nancy Wilson, Sandra Wirth, Ed Wynn, Keenan Wynn, Dana Wynter, Celeste Yarnall, Francine York.

[screamingeyepress]

Ever wanted to read interviews with your favorite underground comics from three of your favorite underground publishers? Well, you can do that now in Outsider Comics! Featuring in-depth conversations with icons such as Melinda Gebbie, Jeff Smith, and Steve Rude, and more, each interview is a revealing look at the passion and dedication these creators bring to their craft.

Pick up a copy: https://www.amazon.com/dp/B0DM6JGXN9/

[sa7abnews]

Kamala Harris panned for requiring ID to enter Arizona rally after previously painting voter ID laws as racist

New Post has been published on https://sa7ab.info/2024/08/12/kamala-harris-panned-for-requiring-id-to-enter-arizona-rally-after-previously-painting-voter-id-laws-as-racist/

Kamala Harris panned for requiring ID to enter Arizona rally after previously painting voter ID laws as racist

Vice President Harris was mocked online for requiring campaign rallygoers to present a government-issued ID upon entry, despite the Democratic presidential nominee opposing voter ID laws. Ahead of Harris’ rally alongside vice presidential running mate Minnesota Gov. Tim Walz in Arizona on Friday, her campaign sent out an email advising that only confirmed RSVPs will be admitted. The email said those on the RSVP list must present a matching government-issued photo ID in order to be admitted to the venue, KTAR reported. The exact site of the Phoenix-area campaign event, first announced on July 30, was not revealed until Thursday. The email specified the event would take place at Desert Diamond Arena, located 15 miles northwest of downtown Phoenix, with attendees being admitted Friday between 1:30 p.m. and 3:30 p.m., according to KTAR. The campaign reportedly said the Arizona Democratic Party would send out “non-transferrable invitations” by email on Thursday afternoon to attend Friday’s event. MINNESOTA GOP DEMANDS PROBE AFTER NONCITIZEN CLAIMS RECEIVING PRIMARY BALLOT WITHOUT REGISTERING TO VOTEX users began sharing screenshots of the email and lambasted Harris for perceived hypocrisy. “Voter ID is racist, but you can’t get into a Kamala rally without ID,” actor Kevin Sorbo wrote to his 2 million followers. “So let me get this straight: Requiring ID to vote is racist… But requiring ID to attend a Kamala Harris ‘rally�� is NOT racist?” Nick Sortor wrote to his more than 448,000 followers. “You need photo ID to get into an invite-only Kamala Harris event, but not to vote?” another user, Ian Haworth, echoed. “Kamala Harris requires photo ID to enter a private campaign event. Kamala Harris doesn’t want to require photo ID to vote. Kamala Harris doesn’t want to require ID before crossing our border. Weird,” political commentator Gunther Eagleman also wrote on X.  Fox News Digital reached out to the Harris campaign for comment, but they did not immediately respond.In 2021, Harris gave her first interview as vice president on the topic of changes to voting laws with Soledad O’Brien on BET.”I don’t think that we should underestimate what that could mean,” Harris said about allowing voter ID laws. “Because in some people’s mind that means, well, you’re going to have to Xerox or photocopy your ID to send it in to prove you are who you are. Well, there are a whole lot of people, especially people who live in rural communities, who don’t – there’s no Kinko’s, there’s no Office Max near them. People have to understand that when we’re talking about voter ID laws, be clear about who you have in mind and what would be required of them to prove who they are.” “Of course, people have to prove who they are. But not in a way that makes it almost impossible for them to prove who they are,” Harris added. AG GARLAND PLEDGES TO FIGHT VOTER ID LAWS, ELECTION INTEGRITY MEASURESNot long after then-candidate Joe Biden named Kamala Harris his vice-presidential running mate in August 2020, Harris penned an op-ed in The Washington Post on the 100th anniversary of the adoption of the 19th Amendment, which gave women the constitutional right to vote. “That is, unless you were Black. Or Latina. Or Asian. Or Indigenous,” Harris wrote. “And when the 19th Amendment was ratified at last, Black women were again left behind: Poll taxes, literacy tests and other Jim Crow voter suppression tactics effectively prohibited most people of color from voting.” The vice presidential candidate at the time then tried to make a comparison to modern times. Harris accused Republicans of “once again doing everything in their power to suppress and attack the voting rights of people of color.” “They are deploying suppressive voter ID laws, racial gerrymandering, voter roll purges, precinct closures and reduced early-voting days – all of which have been laser-targeted toward communities of color since the Supreme Court gutted the Voting Rights Act in 2013,” she wrote. 

[nofatclips]

Blackwind by Patrick Watson from the album Adventures In Your Own Backyard - Video by Chloé Poirier Sauvé

[nerds-yearbook]

In 1960, Professor Manion had invented the first time transporter. On his first attempt he brought to his present, a man from 80 years past. He slowly learned and was upset to find that he teleported the murderer Joe Caswell just as he was being hung for his crimes. Manion paid for his mistake by being the next victim murdered by Caswell. The modern world turned out to be too much for Caswell who returned to the lab. He encountered a thief from the present who killed Caswell and then accidentally activated the time traveling device… to send him back to 1880 to take Caswell’s place in the noose. ("Execution", Twilight Zone, TV)

[niallodonohoe]

C's Recap - 18 Hits on 18th of May Help Canadians Pop the Hops in Hillsboro

C's Recap - 18 Hits on 18th of May Help Canadians Pop the Hops in Hillsboro. #VanCanadians #MontysMounties #WeAreBlueJays

The Vancouver Canadians won the first “Battle of the Boro” as they jumped all over the Hillsboro Hops 13-4 to open up their six-game series at Ron Tonkin Field. The win extends Vancouver’s winning streak to six. The C’s—playing the role of visitor for the first time in Hillsboro—took the early lead in the first. Tanner Kirwer singled to left, was bunted over to second by Philip Clarke and scored…

[mednerds]

New generation of cancer-preventing vaccines could wipe out tumors before they form

By Jocelyn Kaiser (Science). doi: 10.1126/science.abq3411.

When Dave Dubin learned at age 29 that he had colon cancer, it wasnt a big surprise. His grandfather and father had both survived the disease. “It was almost the Dubin way, and we just went on,” Dubin says. He had surgery and chemotherapy, but his cancer came back 10 years later. Genetic testing finally found an explanation for his family’s trials: a mutation in a DNA repair gene that lets genetic errors pile up in dividing cells. The disease, Lynch syndrome, comes with up to a 70% lifetime risk of cancer.

Dubin, 55, gets annual colonoscopies, endoscopies, and imaging scans, which caught a third cancer, in his kidney. His eldest son, Zach Dubin, 26, inherited the DNA repair mutation and also regularly gets checked for cancer. “It’s no fun. Nobody enjoys it,” Dave Dubin says—not the 2-day colonoscopy prep and procedure, nor the worrying about possible tumors. The disease also turned him into an activist. He and his family in Haworth, New Jersey, launched a nonprofit, AliveAndKickn, to promote research and awareness of Lynch syndrome, which affects an estimated 1.1 million people in the United States.

“There is a lot of anxiety in this patient population,” says oncologist and geneticist Eduardo Vilar-Sanchez of the MD Anderson Cancer Center. “It is a big psychological burden.” In hopes of easing that strain, Vilar-Sanchez will soon lead a clinical trial of a vaccine to prevent or at least delay Lynch-related cancers. If it works, Dave Dubin says, “it could be huge.”

Vaccines to prevent certain types of cancer already exist. They target viruses: hepatitis B virus, which can trigger liver cancer, and human papillomavirus, which causes cervical and some other cancers. But most cancers are not caused by viruses. The Lynch vaccine trial will be one of the first clinical tests of a vaccine to prevent nonviral cancers.

The idea is to deliver into the body bits of proteins, or antigens, from cancer cells to stimulate the immune system to attack any incipient tumors. The concept isn’t new, and it has faced skepticism. A decade ago, a Nature editorial dismissed a prominent breast cancer advocacy group’s goal of developing a preventive vaccine by 2020 as “misguided,” in part because of the genetic complexity of tumors. The editorial called the goal an “objective that science cannot yet deliver.” But now, a few teams—including one funded by the same advocacy group, the National Breast Cancer Coalition (NBCC)—are poised to test preventive vaccines, in some cases in healthy people at high genetic risk for breast and other cancers. Their efforts have been propelled by new insights into the genetic changes in early cancers, along with the recognition that because even nascent tumors can suppress the immune system, the vaccines should work best in healthy people who have never had cancer.

Researchers are trying out several vaccine strategies. Some use so-called tumor antigens, molecular markers that are scarce on healthy cells but plentiful on cancer cells. The Lynch vaccine instead targets “neoantigens,” a potent type of antigen only found on tumor cells. Some deploy just a single antigen whereas others use a large number, in a bid to broadly shield against cancer. The best approach is unclear, and developers also face the difficult challenge of measuring success without waiting decades for healthy people to develop cancers.

Early trials are yielding glimmers of promise. If the idea works to prevent one or a few cancers, it could be extended to meet an ambitious goal suggested by President Joe Biden: developing a vaccine that could prevent many types of cancer, modeled on the messenger RNA (mRNA) vaccines that have helped fight the COVID-19 pandemic. “We are a long way from a general vaccine” to prevent cancer, says medical oncologist Shizuko Sei of the National Cancer Institute’s Division of Cancer Prevention. “But it could be in the distant future. It’s a stepwise approach.”

EFFORTS TO HARNESS the immune system to fight cancer have a long history. In the 1890s, physician William Coley reported that injections of bacterial toxins—a vaccine of sorts—sometimes shrank patients’ tumors, apparently by stimulating the immune system. Decades later, researchers discovered that immune cells called T cells could recognize tumor antigens as foreign and attack cancers. This finding led to two classes of approved therapies: drugs that lift molecular brakes on T cells so they can intensify their anticancer attack, and T cells engineered to home in on cancer cells. Both kinds of treatment have had striking success against certain cancers.

A third type of immunotherapy, vaccines to treat cancer, has lagged. Efforts took off in the early 1990s, when researchers began to tally dozens of tumor antigens that might rouse a patient’s immune defenses. Often these antigens are proteins that cancer cells use to grow or spread, so the antigens are good markers of cancer cells.

But despite promising data from animal experiments, most treatment vaccines failed to halt tumor growth in people. Because tumor-associated antigens can also be present in scant quantities on normal cells, the immune system tends to ignore them. The chemotherapy or other harsh treatments cancer patients receive also weaken their immune response, and tumors are protected by their “microenvironment”—surrounding cells and molecules that suppress killer T cells and block them from entering tumors. The only approved treatment vaccine, for advanced prostate cancer, extends life by just 4 months.

Some scientists thought cancer vaccines might work better to prevent rather than treat the disease. One proponent was University of Pittsburgh cancer immunologist Olivera Finn, whose team in 1989 discovered the first tumor-associated antigen: a version of MUC1, a sugar-laden cell-surface protein. The altered version dots many types of cancer cells.

Finn developed a vaccine consisting of short stretches of MUC1. In the first study of a preventive vaccine in healthy people, she tested safety in 39 people who had previously had precancerous colon polyps, which put them at elevated risk for colon cancer. In 2013, her team reported 17 had a strong immune response, with much higher levels of antibodies to the tumor version of MUC1 than previously seen in cancer patients who got the vaccine as treatment. The other 22 people, who didn’t make antibodies, had immune-suppressing cells in their blood, apparently lingering from their removed polyps, Finn says.

The trial’s modest success led to a larger, placebo-controlled trial to see whether the vaccine prevented new polyps in people who had had them removed. This time, just 11 of 53 participants who received the vaccine produced plentiful antibodies, possibly because the patients’ immune-suppressing polyps had been removed only recently. But among the 11 responders, only three had polyps recur within 1 year of receiving the vaccine, compared with 31 of 47 participants in a placebo group, Finn’s team reports in a paper submitted to a journal.

“It was very encouraging,” Finn says. “When you have no recurrence in responders, you know the vaccine is working.” Adding a treatment that blocks immune-suppressing cells may boost response rates, she says. Her team now plans MUC1 vaccine trials for several precancerous conditions.

ONE DRAWBACK of Finn’s vaccine strategy is that the short proteins, or peptides, it contains mainly trigger one arm of the immune system: the B cells that make antibodies. “For immunity against cancer we really need to mobilize T cells,” says cancer immunologist Robert Vonderheide, director of Penn Medicine’s Abramson Cancer Center. That’s best done by injecting the genetic instructions for the antigen rather than the antigen itself. Special immune cells then take up the DNA or RNA, manufacture the antigen, chop it up, and display bits tailored to that person’s immune system on their cell surfaces. These antigen-presenting cells then teach T cells to recognize and kill tumor cells.

Vonderheide’s team is testing a DNA-based vaccine targeting a different antigen that marks many tumors: hTERT, a small chunk of telomerase, an enzyme that protects chromosomes as cancer cells proliferate.

Results of a trial testing the vaccine’s safety in 93 patients in remission after treatment for various cancers were encouraging. All but four people made T cells that home in on hTERT, the team reported in the Journal for ImmunoTherapy of Cancer in July 2021. And there was a hint the vaccine was warding off cancer. Among the 34 people who had had pancreatic cancer, 41% were still cancer free after 18 months. In other pancreatic cancer patients in remission, their tumor reappears within an average of 12 months.

The Penn team is now studying safety and immune responses to the vaccine in 16 people in remission from previous cancers who have inherited mutations in BRCA1 or BRCA2, relatively common cancer genes that raise risk for breast and some other cancers. Next year, the researchers expect to give the vaccine to 28 people with BRCA mutations who have never had cancer.

But because hTERT is found on some normal cells as well as cancerous ones, a vaccine could trigger an autoimmune attack on healthy cells, suggests immunologist Vincent Tuohy of the Cleveland Clinic. He has devised a breast cancer prevention vaccine that may be safer because it contains a breast cell protein called alpha-lactalbumin that people only make during late pregnancy and breastfeeding. Production of the protein also occurs in triple negative breast cancer, an aggressive form of the disease. Tuohy’s team is testing whether his protein vaccine can stimulate an immune response in 24 women who have been treated for triple negative breast cancer and have no plans to get pregnant. The next step, he says, will be a trial in healthy women with BRCA1 mutations, who are prone to this cancer type.

Other teams hope to offer broader protection against breast cancer. Undeterred by being called “misguided” in 2012, NBCC is close to testing a breast cancer vaccine, initially in healthy breast cancer survivors. The advocacy group’s president, Fran Visco, says it set the ambitious goal because it was “frustrated with the lack of innovation in breast cancer.” With scientist partners, it has settled on a vaccine that combines six tumor antigens, including hTERT and MUC1. “We don’t know what type of breast cancer a woman is going to get,” explains trial leader Keith Knutson, an immunologist at the Mayo Clinic. Multipronged vaccines “are probably going to be more effective than vaccines targeting one individual protein,” says cancer immunologist Nora Disis of the University of Washington, Seattle, who is developing such a vaccine to prevent colon cancer.

AS SOME TEAMS are trying to broaden the immune response triggered by cancer vaccines, others want to make it safer and more precise by targeting neoantigens, only found on cancer cells. Those efforts have accelerated over the past decade thanks to a surge in tumor genome sequencing, which has revealed a flood of neoantigens. Some drive cancer growth, whereas others have no apparent function. Most are unique to an individual cancer—an obstacle for developing preventive vaccines, which have to target markers that can be predicted in advance.

Some neoantigens reliably appear on many people’s tumors, however. For instance, pancreatic cancer is almost always triggered by mutations in a growth protein called KRAS, which give rise to a predictable set of neoantigens. This spring, Johns Hopkins University immunologist Elizabeth Jaffee and colleague Neeha Zaidi will begin to safety test a vaccine containing mutated KRAS peptides in 25 men and women who haven’t had cancer but are at high risk because of an inherited mutation or family history. KRAS is like pancreatic cancer’s Achilles’ heel, Jaffee says: It’s the first of several genes to get mutated. As a result, the team hopes early tumor cells won’t be able to evade the vaccine by ditching KRAS and finding another way to grow.

Lynch syndrome cancers also sport a predictable set of neoantigens. That’s because patients’ DNA repair problem leads to “frameshift” mutations, which shift how a cell’s proteinmaking machinery reads a gene, scrambling the resulting protein in a consistent way. A peptide vaccine containing a few of these neoantigens, which was developed by a German team, caused no serious side effects when tested in people with cancer. A similar vaccine designed for mice with Lynch syndrome reduced tumor growth, researchers reported in July 2021 in Gastroenterology.

The vaccine Vilar-Sanchez’s team will test is more ambitious: It consists of viruses modified to carry DNA for a whopping 209 frameshift neoantigens found in Lynch tumors. People’s immune systems vary in how they respond to specific neoantigens, and different individuals’ tumors won’t all make the same set. “Therefore, the best [approach] is to have many,” says Elisa Scarselli, chief scientific officer of Nouscom, an Italian company developing the vaccine.

The vaccine is also being developed as treatment, and in an early test Nouscom is giving it along with an immunotherapy drug to patients who have metastatic cancers with frameshift mutations like those in Lynch syndrome. At a meeting in fall 2021, the company reported the treatment shrank tumors in seven of the first 12 patients. “We really believe we will see even more immunogenicity in healthy carriers of Lynch disease” because they should have stronger immune systems, Scarselli says.

Vilar-Sanchez’s trial, beginning within a few months, will give the vaccine to 45 volunteers with Lynch syndrome—both people in remission after cancer treatment and others who have never had tumors. Investigators will assess whether the vaccine stimulates an immune response and has any apparent effect on polyps or tumor formation.

If the results look good, the next step will be a randomized study of hundreds of patients over perhaps 5 to 10 years. “There’s a lot to be gained” if the vaccine works, Vilar-Sanchez says. “A cancer vaccine is not going to reduce the risk to zero, but it could impact how often we perform screening.” It could also help patients decide whether to have a hysterectomy to prevent endometrial cancers, which are common in people with Lynch syndrome.

All prevention vaccines would face a long road to regulatory approval if researchers must wait for tumors to appear to judge the vaccine’s efficacy. So they will also look for surrogate measures of protection, such as reduced growth of polyps in people prone to colon cancer. For breast cancer, researchers don’t have biomarkers yet but hope to find them, perhaps a change in blood-borne immune cells or breast tissue, Vonderheide says.

“We have to be smart enough to present to the FDA [U.S. Food and Drug Administration] a biomarker of success,” Vonderheide says. “This is formidable. But we’re inspired because the impact will be massive.”

WHATEVER THEIR PREFERRED antigens, many scientists expect to model their next preventive vaccines on the leading COVID-19 vaccines, which use a lipid particle to ferry mRNA for antigens into cells. mRNA vaccines are easier to make and deliver than DNA or viral vaccines, and the pandemic has shown they’re generally safe and stimulate a strong response. “The fact that mRNA vaccines have shown safety in billions of healthy people of all ages makes [mRNA] a very good platform” for preventive cancer vaccines, Jaffee says.

The White House is gunning for mRNA vaccines to prevent cancer, too. They are on the list of potential projects for a reignited Cancer Moonshot and the new high-risk, high-reward research agency, the Advanced Research Projects Agency for Health (ARPA-H). A concept paper for ARPA-H puts the goal this way: “Use mRNA vaccines to teach the immune system to recognize 50 common genetic mutations that drive cancers, so that the body will wipe out cancer cells when they first arise.”

That description raises some eyebrows. “That would be heroic,” Finn says, because the vaccine antigens would have to cover not only a huge number of cancer mutations, but also “the incredible genetic diversity” in individuals’ immune responses. “Not impossible but not simple,” she says.

Clinical geneticist Steven Lipkin of Weill Cornell Medicine, who works on Lynch syndrome vaccines, is cautiously optimistic, noting that a vaccine that cut the rates of the most common cancers “by say one-third or one-half in a large number of people would be a tremendous benefit.”

One team is already testing a multicancer prevention vaccine—not yet in people, but in dogs. In a 5-year trial, a team is giving 400 middle-age dogs a vaccine that contains 31 antigens from eight common dog cancers. (Another 400 dogs are getting a placebo vaccine.) It relies on RNA neoantigens, little-studied molecules that result from RNA processing errors rather than mutations in DNA. They are far more abundant than DNA neoantigens in dogs and people, and are “highly immunogenic,” says developer and biochemist Stephen Johnston of the Biodesign Institute at Arizona State University, Tempe. If they prove effective, they might make it easier to reach the White House’s goal of developing a pancancer human vaccine, he says.

Another proponent of a universal cancer prevention vaccine is Johns Hopkins cancer geneticist Bert Vogelstein. He notes that sequencing has shown “a relatively small number of genes are involved in most cancers,” suggesting a limited number of antigens could lead to broad protection. Such a vaccine “seems like science fiction,” Vogelstein says, but “a concerted effort by many labs” might succeed. Sei agrees: “That’s not crazy. That’s possible.”

For Dave Dubin, even a narrower success—a Lynch syndrome vaccine—“could be game-changing,” he says, if it meant fewer cancer screenings and no more major surgeries. “The goal would be almost to live a normal life.”

[emisirrelevant]

THOUGHTS ON THE FINALE OF PRETTY LITTLE LIARS ORIGINAL SIN!!!!

*SPOILERS* if you haven't watched the last few episodes yet you've been warned

*TW/CW- mature/sensitive content in this post

I am literally still processing everything but:

Was I the only one who thought the Liars' plan with the blood drive was actually kind of creative?

Ohhh the principal rejecting Tabby's film had me SEETHING. I should have known from that scene he'd be the one behind it all/pulling the strings.

Going back and rewatching the scene where Chip tries to ask Imogen if she wants to go to his place for Thanksgiving is now very uncomfortable. Thank god she had Tabby and her mom!! And that's on the tabogen agenda.

I honestly thought Shawn was going to be a part of the A stuff or the guy who assaulted Tabby and Imogen but he was not. If we get a season 2 though, I'm keeping an eye on him. No offense Noa- but he lied about the pills/drugs. Like I wonder if he really was telling the truth when he said later that he threw them out.

The club scene!! Iconic, but the rational part of my brain also was like "Yes Faran good suggestion- WAIT THEY'RE MINORS THEY SHOULD NOT BE OUT CLUBBING"

When Kelly(?) "said call me Karen" to Greg- HUHHH?

I knew Crazy Joe wasn't A

It felt too much like a red herring to me- too obvious

The Waters' house did give me AHS Murder House vibes- they really nailed the creepy vibe with the set

Yess finally I’m so glad they got the moms to talk about Angela- also the fact that each mom's situation with Angela paralleled the daughters in the present

Noa saying "I can't handle juggling two addicts in my life" SWEETIE no :(((((

FARAN LETTING HER HAIR DOWN!!

I'm glad Henry told Faran about Kelly kissing him and didn't keep it a secret. Maybe there is one decent man on this show??

Also Ben Cook heyyy good for him getting those roles!

Ash just eating the pizza instead of directly answering Mouse's mom HAHA

Tabby's mom going OFF on Wes like that!!!

Faran going off on Sheriff Beasley!! QUEEN!

We got to see Imogen’s dad, interesting.

**The fact that he mentioned that Imogen’s mom stated in her will for Imogen to live with the Haworthes if anything bad happened though- TABOGEN WAS FATED! 

Honestly the whole Beasley family situation was really sad- and like the fact that there are some families like this in real life- it was really giving me Melanie Martinez Dollhouse vibes for sure.

Oh I see Kelly x Faran as a potential headcanon.

Oh damn. It was Chip. 

The whole scene when Imogen and Tabby confronted Chip though?Wow. Top tier acting from Bailee and Chandler. Powerful.

"This year has made us very, very good liars" ICONIC!

OMG THE FINAL EPISODE THOUGH HHHHHH

So much went DOWN!!

I'm still in shock with A doing that to Davie's body though- Tabby asking if Imogen was okay "Nope. Definitely not"

IMOGEN ADAMS DESERVES THE ENTIRE WORLD!! Fuck A for giving her life long trauma!

Not Angela's brother being named Archie- STOP WITH THE R*VERD*LE REFERENCES

IT WAS THE PRINCIPAL!!!! That was a good twist, I appreciate it.

Omg Kelly's mom stabbing Sheriff Beasley though was another twist I did not see coming.

1000000000+ points for adding a Motley Crue song in there!!

I absolutely LOVED the moment when the rest of the girls immediately stood up when the principal threatened to shoot Imogen and her baby- RIDE OR DIES FOR EACH OTHER YES

**THE FIGHT SCENE WITH IMOGEN AND A!!

MAKING CINEMATIC HISTORY

The camera angles in this show- absolutely DELICIOUS

Tabby being there when Imogen woke up in the hospital GO TABOGEN GO

The scene where everyone was celebrating Christmas together 🥺🥺 (every other ship kissing and then TABOGEN pls SEASON 2 SO WE CAN MAKE IT HAPPEN!!!)

Also why did I know someone was going to say Die Hard when Tabby asked about favorite Christmas movies and why did it fit Shawn perfectly-

Aww Elodie and Shirley saying they're going to couples therapy GOOD FOR THEM!! (technically they ALL need it lol)

Interesting way to bring back some original PLL with that Aria and Ezra mention.. but when that baby finds out that her parents were in a student teacher relationship-

Overall glad that all those nasty men were EXPOSED. Especially the principal and Sheriff Beasley. Still wondering about Wes though. If there's a season 2 I'm keeping an eye on him too.

So Kelly was Kelly the whole time- I like that there’s a possibility that she stays friends with the Liars in the future- but like what if it’s still Karen? I wanna believe it’s Kelly and that Kelly is good but still.

And finally, Imogen saying she thinks it’s over

But A killed Sheriff Beasley AND came back for Chip-

When I first heard about this show, I was skeptical at first and didn't have many expectations going into it. I never watched the very first Pretty Little Liars series in its entirety, but this spinoff somehow managed to pull me in. Thank you PLLOS Original Sin for everything! What an amazing cast and show. I would definitely recommend this show to others.

SEASON 2, SEASON 2, SEASON 2

[byneddiedingo]

Betsy Blair and Ernest Borgnine in Marty (Delbert Mann, 1955)

Cast: Ernest Borgnine, Betsy Blair, Esther Minciotti, Augusta Ciolli, Joe Mantell, Karen Steele, Jerry Paris, Frank Sutton. Screenplay: Paddy Chayefsky. Cinematography: Joseph LaShelle. Art direction: Ted Haworth, Walter M. Simonds. Music: Roy Webb.  

That Marty is such an engaging little movie is largely because Ernest Borgnine and Betsy Blair have such remarkable low-key chemistry together and Paddy Chayefsky's screenplay brings them together convincingly and keeps them apart smartly. Chayefsky does overdo the "what do you wanna do tonight" shtick, which kept contemporary comedians busy far too long, and the self-pitying Italian mama stereotypes of Marty's mother, Mrs. Piletti (Esther Minciotti), and Aunt Catherine (Augusta Ciolli), but it's on the whole a well-made script. Some credit is obviously due to the director, Delbert Mann, who also directed Chayefsky's 1953 teleplay on which the movie is based. It was his big-screen debut and won him an Oscar, but he never followed up with another comparable film -- his best later work was probably on two Doris Day comedies, Lover Come Back (1961) and That Touch of Mink (1962). Oscars also went to Borgnine, Chayefsky, and the film itself, and nominations to Blair, Joe Mantell as Marty's pal Angie, Joseph LaShelle's wonderfully atmospheric cinematography, and to the art directors. In fact, if Marty has any lasting claim to fame other than being a satisfying romantic drama, it's in the Academy's uncharacteristic recognition of a "little" film -- especially noticeable in the mid-50s when the prevailing Hollywood trend was to "give 'em something they can't get on television." Since they had already gotten Marty on TV two years earlier, the Oscar attention was especially surprising. It didn't signal any sort of trend, however: The following year, the best picture winner was Around the World in 80 Days (Michael Anderson), a typically bloated extravaganza loaded with movie-star cameos, and for the first time, all of the best picture nominees for 1956 were filmed in color. It was as if the Academy had said, "Fine, we did our duty, now let's get back to business."

[batmanonthecover]

BATMAN #177 - December 1965

Cover Art: Carmine Infantino

TWO BATMEN TOO MANY

Script: Bill Finger

Art: Sheldon Moldoff as “Bob Kane” (Pencils), Joe Giella (Inks), Gasper Saladino (Letters)

Characters:  Batman [Bruce Wayne]; Robin [Dick Grayson]; Elongated Man [Ralph Dibny; aka Big Batman]; The Atom [Ray Palmer; aka Little Batman]; The Bangle Brothers (carnival owners); Ed "Numbers" Garvey (villain); Garvey's gang (villains)

Synopsis: Batman concocts a scheme against numbers racketeer Ed Garvey to prove conclusively that the crook planned and carried out the Kimber Gem job.

Batman story #1,110

THE ART GALLERY OF ROGUES

Script: John Broome

Art: Sheldon Moldoff as “Bob Kane” (Pencils), Sid Greene (Inks), Gasper Saladino (Letters)

Characters: Batman [Bruce Wayne]; Robin [Dick Grayson]; Commissioner James Gordon; Roy Rennie (publicity agent); Marylene Haworth (actress); Lathrop (villain, art dealer); Lathrop's henchmen [Yawkie; Slats] (villains)

Synopsis: Batman deduces that a man named Lathrop has stolen some artwork from a gallery and passed it off to one of his henchmen in order to get a grant from the Alfred Foundation.

Batman story #1,111