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(DD-59: dp. 1,205; 1. 315'3"; b. 29'11"; dr. 9'4", s. 29 k.
cpl. 133; a. 4 4", 4 21" tt.; cl. Tuckee)
The second Porter (DD-59) was laid down by William Cramp and Sons, Philadelphia, Penn., 24 February 1914 Iaunched 26 August 1915, sponsored bv Miss Georgiana Porter Cusachs; and commissioned 17 April 1916, Lt. Comdr. Ward K. Wortman in command.
After shakedown in the Caribbean, Porter sailed in convoy 24 April 1917 escorting the first U.S. troops to Europe. She arrived at Queenstown, Ireland, 4 May, where she was based during World War I, meeting and escorting convoys from the U.S. as they entered the war zone. Kept busy as a convoy escort, she severely damaged U-108, 28 April 1918, while the German submarine was steaming to intercept a convoy. Operating from Brest after 14 June, she returned to the United States at the end of the war.
After World War I Porter operated off the East Coast and was decommissioned 23 June 1922. Transferred to the Coast Guard, 7 June 1924, she was returned to the Navy 30 June 1933, and disposed of by scrapping under the terms of the 1930 London Treaty for Limitation of Armament the following year. Her name was struck from the Navy List 5 July 1934 and her materials were sold 22 August 1934.
USS Porter (DD-800)
USS Porter (DD-800) was a Fletcher-class destroyer of the United States Navy, the fourth Navy ship named for Commodore David Porter (1780–1843), and his son Admiral David Dixon Porter (1813–1891).
- 60,000 shp (45 MW)
- geared turbines
- 2 propellers
- 6,500 nautical miles at 15 kt
- (12,000 km at 30 km/h)
- 5 × 5 in (127 mm)DP guns,
- 10 × 40 mmAA guns,
- 7 × 20 mm AA guns,
- 10 × 21 in (53 cm)torpedo tubes,
- 6 × depth charge projectors,
- 2 × depth charge tracks
Porter was laid down by the Todd Pacific Shipyards, Inc., Seattle, Wash., 6 July 1943 launched 13 March 1944 sponsored by Miss Georgiana Porter Cusachs and commissioned 24 June 1944 Commander H . R. Prince in command.
The World War II Army Enlistment Records File and Access to Archival DatabasesNine young men who have enlisted in the Regular Army wait outside the Fair Park recruiting station in Dallas, Texas, in January 1946. The AAD resource has 9.2 million records for enlistments in the Army, Enlisted Reserve Corps, and Women s Army Auxiliary Corps for the period 1938—1946. (111-SC-235858)
World War II Army Enlistment Records provide a rich source of information for genealogists and other researchers at the National Archives and Records Adminstration interested in Army enlistees in World War II. Since their release through NARA's Access to Archival Databases (AAD) resource in May 2004, they have quickly become the most popular series of electronic records accessible through that resource.
AAD, as the first installment of NARA's Electronic Records Archives (ERA) program, is leading the way to providing improved access to NARA's rich holdings of electronic records. In the first year, thousands of AAD users performed more than 700,000 queries against the enlistment records file alone. With 9.2 million records for enlistments in the Army, Enlisted Reserve Corps, and Women's Army Auxiliary Corps, this should come as little surprise.
In addition to genealogists, individuals who served in the war (and their children and grandchildren) are using the records to document military service.
The enlistment records are one of 45 series of electronic records currently available on AAD. Those series contain more than 85 million historic electronic records created by more than 20 federal agencies on a wide range of topics. The enlistment records complement other World War II–era electronic records in AAD, including the Records of Duty Locations for Naval Intelligence Personnel, Records About Japanese Americans Relocated During World War II, and Records of World War II Prisoners of War.
This article provides information about how the enlistment file came to be in AAD, along with some tips and pointers for finding records in the file.
Preparing the Records for Access in AAD
The story of the electronic World War II Army Enlistment Record file begins with the disastrous July 12, 1973, fire at NARA's National Personnel Records Center for Military Personnel Records (NPRC). The fire destroyed approximately 16–18 million Official Military Personnel Files, including the records of approximately 80 percent of U.S. Army personnel discharged between November 1, 1912, and January 1, 1960. Following the fire, NPRC staff began identifying various series of records in NARA's custody that could assist them in reconstructing the lost basic service data. With these alternative sources, they could verify military service and provide a Certification of Military Service.
Among the sources identified was a series of 16mm microfilm of computer punch cards titled "Microfilm Copy of the Army Serial Number File, 1938–1946." The Personnel Services Support Division of the Adjutant General's Office had created the microfilm in 1947, and NARA accessioned it in 1959. The original punch cards, which contained basic information about enlistees at the time they entered Army service, were destroyed after microfilming, a common practice at that time. The NPRC began using a copy of the microfilm, but it presented some challenges. First, there were 1,586 rolls of microfilm, making manual review very difficult. Second, the punch cards were microfilmed in serial number order, making a search by name impossible. Third, a variety of punch card formats were used to record the enlistment data over time, and documentation of the various recording formats was hard to identify.
A goal of the NPRC was to have as many of the reconstructed records available to its staff electronically to speed response time to its over one million annual requestors. In 1992, NPRC contacted NARA's Center for Electronic Records seeking some assistance with these challenges.
The Center's director was familiar with the Bureau of the Census's Film Optical Sensing Device for Input to Computers (FOSDIC) system and its successful use in processing the 1960 through 1990 decennial censuses. Census returns, which were essentially "bubble" forms where answers were supplied by blacking out the appropriate circle, were microfilmed, and then FOSDIC extracted the answers from the image. Since the Bureau of the Census had already modified the original FOSDIC to process a series of 300 million microfilmed punch cards containing weather data, it responded affirmatively to the challenge presented by NARA.
The Bureau of the Census completed the project during federal fiscal year 1994 on time and below budget. They successfully converted 1,374 of the 1,586 rolls, or 87 percent of the rolls of microfilm. The 212 remaining rolls containing approximately 1.5 million punch cards could not be converted because the card images were so dark that the scanner produced few, or no, usable records. In July 1994, the Bureau of the Census provided NARA with 1,374 data files (one per converted roll) on twelve 3480-class tape cartridges. NPRC received copies of the files, and they worked with Center for Electronic Records staff to identify the relevant War Department Technical Manuals containing technical documentation for the punch cards. Additional code tables and documentation continue to be identified among NARA's vast textual records holdings from World War II.
The unique characteristic of the files created by the Bureau of the Census was that FOSDIC read each punch card image up to 10 times in an attempt to create a clean record and extract all characters from the original punch card. Usually, the first read would contain the majority of data extracted from the card image. If all data could not be extracted, subsequent reads of the card image would result in additional records containing periods for characters successfully read on previous reads and alphanumeric characters for those interpreted on the current read. Varying interpretations of the same character may have occurred across the multiple reads. A blank record separates records or groups of records pertaining to an individual punch card image. Each file also contained a header record indicating the box and microfilm roll number and an end of file record. In cases where FOSDIC could not interpret any information from a punch card or series of punch cards within a file, FOSDIC inserted a record indicating "ONE OR MORE RECORDS WERE UNREADABLE AT THIS LOCATION."
These features presented challenges to the NPRC because the alphanumeric data were spread over multiple records, making it hard to use and interpret. The large number of files still presented a logistical problem for identifying and searching for individuals, especially given the computer technology of that time. During the 1990s, NPRC collected code books and began an analysis of the records while NARA's St. Louis Data Systems Center created early edit programs in an attempt to merge best guesses into one record. Given the complexities of the files, however, and the limited ability to search and locate individual records, NARA undertook no additional processing of the electronic version of the "Microfilm Copy of the Army Serial Number File, 1938–1946."
That is, until 2002. In that year, staff took another look at the languished project, primarily because of the newly developed Access to Archival Databases (AAD) resource. They determined that to get the records ready for AAD, the project should be approached in two phases. The first phase involved "merging" the 1,374 files into 12 files, corresponding to the number of computer tape cartridges provided by the Bureau of the Census. The purpose was to reduce the number of files to a manageable number and allow for an overall evaluation of the scope, content, and quality of the electronic files. This first phase was completed in May 2002 and resulted in the series "Electronic Army Serial Number Raw Files, 1994–2002," which contains 23,446,462 records.
The objective of phase two was to get a single data file with a single "best guess" record for each serial number so that it could be made available through the AAD resource. First, the 12 files were merged again into a single file. A NARA programmer then wrote a computer program to "collapse" the multiple FOSDIC reads of the punch card images into a single "best guess" record. When we collapsed the multiple records, we were able to collapse only the data appearing in the FOSDIC second read of the punch card into the first read. FOSDIC may have correctly interpreted any specific character correctly on the third or later reads of the punch card, but we were unable to apply a more complicated algorithm to the processing to provide a better "guess" than what appears in the resultant file. We therefore have retained the Electronic Army Serial Number Raw Files, should researchers wish to reprocess the raw data and create a better "best guess" file.
The program also matched the associated box and roll data to the end of each cleaned up record. The records with the value "ONE OR MORE CARDS WERE UNREADABLE AT THIS LOCATION" are retained in the file in their original positions. The resultant file, known as the "World War II Enlistment Records: Electronic Army Serial Number Merged File, 2002," has a total of 9,200,232 "best guess" records, including 160,390 records indicating the punch cards that FOSDIC was unable to interpret. It is this file that NARA makes available in the AAD resource.
Army Enlistment Records File Characteristics and AAD
It is important for users of the AAD file to understand how far removed the enlistment records are from the microfilm images of the original computer punch cards. Each successive processing stage invariably introduced the chance of errors.
As with most archival records now used for genealogical research, the records were originally created for a very different purpose than identifying specific individuals. In the case of the enlistment cards, they were designed to reflect, at the time of entrance into service, basic characteristics of each enlistee in the Army, Enlisted Reserve Corps, and the Women's Army Auxiliary Corps. The Adjutant General's Office used the punch cards to prepare tables analyzing occurrence of the various characteristics among individuals, enlisted or inducted, and to provide information for policies of demobilization. Therefore, given that the original intent of the program was to prepare statistical tables, less attention may have been paid to the proper spelling of names and accurate keypunching of personal data fields.
Most important, the many migrations of these records—from original recording on punch cards, to copying them to microfilm, to FOSDIC processing, to "merging" and "collapsing"—means that error could have been introduced at any phase. The poor quality of the original microfilm caused most of the errors. To determine the level of error in the resultant file, NARA staff compared a random sample of the World War II Enlistment Records to the microfilmed punch cards. Of the sample records examined, 35 percent of them were found to have a scanning error. However, only 4.7 percent of the records had any character error in the name column, and only 1.3 percent had character errors in the serial number column. While a large number of records had other errors, they were minor. For example, the term of enlistment column frequently has the value of "0" in the electronic file where no punch appears on the original card. Other errors can be intuitively corrected by the users, such as understanding "POT" or "PVO" to mean PVT in the grade column. To help minimize these problems, NARA staff outlined some of the common errors in a set of Frequently Asked Questions for AAD.
The bulk of the records are for the period 1941 through 1946. About 4 percent of the records contain data originally recorded on Enlisted Reserve Corps Statistical cards, and the bulk of those records are from 1942 and 1943.
Number of Enlistment Records by Year
|Year||Number of Enlistment Cards|
|Other Years or Miscoded||41,756|
In general, the records contain the serial number, name, state and county of residence, place of enlistment, date of enlistment, grade, Army branch, term of enlistment, longevity, nativity (place of birth), year of birth, race, education, civilian occupation, marital status, height and weight (before 1943), military occupational specialty (1945 and later), and component of the Army. As noted earlier, at the end of each "best guess" record appear the box and roll number of the microfilmed punch cards.
To facilitate search and retrieval in the AAD resource, the file is split into two tables: a large file containing general Army enlistment records, including enlistees in the Women's Army Auxiliary Corps, and a second with records of enlistees in the reserve corps. Over time the enlistment card format changed, and the height and weight or military occupational specialty categories were recorded in the same columns on the original punch cards. Because there is no easy way to distinguish original data recorded on the two
forms, NARA chose to drop that data from the AAD version of the file.
Finding Records in AAD
Users can search and retrieve the enlistment records through the Access to Archival Database (AAD) resource. Before using AAD, we recommend that the user read the "Getting Started Guide" on the AAD home page. The Frequently Asked Questions developed especially for the World War II Army Enlistment Records File also provide a number of helpful tips and hints about technical data characteristics of various fields.Recruits receive applications from Staff Sgt. N. R. Kelly at the New York Recruiting Office at 39 Whitehall street in June 1940. (111-SC-115556)
From the AAD home page, the user can execute a search across all series in AAD by entering a name or other search term in the "Search AAD" box. Results will be returned from the Army serial number file and from all other series in AAD where appropriate. Alternatively, the user may go straight to the enlistment records by using the link under "Most Popular" or by choosing the categories for Military Personnel, World War II, or 1940–1955. The user next clicks on "search" to access either the Enlistment Records or the Reserve Corps Records. This will bring up a page where the user may search these records.
Using an individual's Army serial number may be the most efficient way to find a record. Type the serial number in the search box without hyphens, submit the search, and a summary of the record with that serial number will appear. Clicking the icon in the column titled "View Record" will display the full record, which will contain meanings for the coded data. To print a copy of any record, click "Print" at the top of the screen, and this will display the full record again in a format suitable for printing.
A common way to search for individual records is by name. Users should note that searches are not case sensitive even though entries are uppercase in the file. In making the records available in AAD, staff inserted "#" for blanks that would normally appear between the last and first names and in other instances. The name column includes all possible parts of a name: surname, space, first name, space, middle initial, and SR, JR, 3rd, etc. Names with "Mac," "Mc," "de," "Van," etc., have a space between the prefix and the rest of the surname when both the prefix and following letter are capitalized. For example: McAffee was recorded as MC AFFEE, but Mcaffee was recorded as MCAFFEE. Names with apostrophes, like O'Brien, usually do not have a space between the prefix and the rest of the name, i.e., OBRIEN. Van Heusen is recorded as VAN HEUSEN. When the full name was longer than the number of characters available in the name column, as much of the surname as possible is in the column, and initials were used for the first name. AAD also allows for using wildcards in searches so that users can identify records even when unsure of name spelling or format.
For example, to find my grandfather's record, I entered "James N Tronolone" into the name search box. Alternatively, I could have simply entered "Tronolone" and selected his record from among the 23 records for persons with that last name in the enlistment table. If the user is searching for a common name, the name can be combined with other fields, such as state or state and county, to narrow the search for an individual record. Users will often use the information retrieved in the AAD search, such as the serial number when not otherwise known, to request further information about their relative from the National Personnel Records Center.
Because this file was originally designed for computer processing, data fields such as the state and county of residence, place of enlistment, civilian occupation, and marital status were represented by numeric codes rather than being spelled out. These codes allowed for the uniform recording of repetitive data in a keypunch operation and for the efficient sorting and tabulation of the computer punch cards. AAD reinterprets the coded fields "in English" so that users can understand the information. The full record also links to notes on specific fields that more fully explain the meanings of codes.
Another common search strategy is to find records of individuals who enlisted at a specific place or came from a specific county. This requires searching AAD using one or more coded fields. The fields Residence: State Residence: County and Place of Enlistment are options on the main database search screen. To search these fields, click on the "Select from Code List" link to bring up a window with a list of all the coded values. Select a value, and then click the "Submit" button. This will paste the code into the search box, and then the user can execute the search.
For example, to get a list of enlistees from Centre County, Pennsylvania, first select the primary code for Pennsylvania (code 32). Then select the appropriate county code (Centre County's code is 027). Once these codes are pasted into the search boxes and the search is submitted, AAD will return 3,170 records. All search results will be returned, but because this number exceeds the download limitation of 1,000 records, no records can be downloaded for additional processing. To get a complete list, a user could execute multiple queries, such as by running a series of searches by year of enlistment. Multiple records retrieved in this way can be downloaded to the user's computer in the form of an ASCII spreadsheet file with comma-separated values, with or without the code meanings. The file can then be directly imported into spreadsheet software, such as Microsoft Excel, for further manipulation.
The story of the World War II Army Enlistment Records File is unique, but it illustrates the lengths to which NARA will go to provide researchers with ready access to the documentary heritage of the United States Government.
As NARA develops its Electronic Records Archives, AAD will continue to be an integral part of that program and will grow to provide access to the expanding number and variety of electronic records being deposited in the National Archives.
Theodore J. Hull is an archivist in the Electronic and Special Media Records Services Division of the National Archives and Records Administration, College Park, Maryland. His primary responsibility is the archival processing of NARA's electronic records holdings of the Bureau of the Census.
USS William D. Porter: The U.S. Navy Destroyer’s Service in World War II
Sometimes the things that almost happened are as interesting as the things that did. Nearly every photo history book of World War II shows the famous picture of President Franklin Delano Roosevelt meeting with Winston Churchill and Josef Stalin at Tehran in November 1943. The accompanying caption usually mentions something about the meeting solidifying the alliance that would go on to win World War II. Rarely mentioned, however, is that the historic moment might never have occurred — because the president, the entire Joint Chiefs of Staff and numerous other top American leaders on board USS Iowa were nearly victims of a torpedo attack on the way to the summit. This important fact is overlooked because it was not an enemy attack that could have killed the president but a torpedo fired from an American destroyer in a torpedo drill gone awry.
The shot that almost changed history was fired by William D. Porter, known to those who sailed on it or found themselves in its sights as the ‘Willie Dee,’ one of hundreds of destroyers the United States built in a hurry as it became obvious that much of the country’s participation in the expanding global war would be at sea. The destroyer was put into service in July 1943, with a crew of 125 young men who, but for just a few experienced hands scattered here and there, were all in high school or working on a farm while the ship was being built. They were as fresh as the ship on which they served.
But that was the military in 1943 — lots of eager young men hoping to learn their jobs before someone started shooting at them. Time for training was short, so barely four months after Willie Dee hit the water, it was assigned to one of the most critical and super secret missions the Navy had yet undertaken. President Roosevelt was traveling to French North Africa to meet with Churchill, Stalin and Chinese Generalissimo Chiang Kai-shek. No one was to know about the trip until the commander in chief arrived safely.
Roosevelt boarded the massive battleship Iowa on November 12, 1943, along with Secretary of State Cordell Hull, the Joint Chiefs of Staff and enough VIPs and top aides to awe even the most imperturbable sailor. The president’s party, numbering about 80 souls, had all slipped out of Washington as quietly and discreetly as possible aboard Roosevelt’s presidential yacht Potomac, and had cruised down the Potomac River to rendezvous with Iowa at the river’s mouth in Chesapeake Bay. The 45,000-ton battleship, traveling up the bay from its berth in Norfolk, Va., to meet Potomac, had to discharge nearly all of its fuel just to keep from running aground in the river.
‘We didn’t know what we were doing in Chesapeake Bay until we saw the president’s yacht come alongside,’ recalls Grier Sims, a crew member on board Iowa. ‘They had installed a bathtub when we were in Norfolk, and we were all asking what the hell a bathtub is doing on a battleship. Then it made sense when the president came on board.’
The president was taken aboard in his wheelchair with no fanfare, then Iowa slipped silently out to sea with strict orders to lie low and make no radio contact. The battleship was joined by two escort aircraft carriers, which would provide air cover, and three destroyers to provide protection from the German submarines that were still wreaking havoc on ships in the Atlantic. One of those destroyers was Willie Dee.
The mission was simple but critical: Get Roosevelt and his entourage to Mers-el-Kebir in French North Africa for the first of the high level summits between the Allied leaders. The ships traveled at high speed all the way across the Atlantic, with the smaller destroyers struggling to keep up. Most of the sailors in the convoy did not know the purpose of their secret mission, or that the president was on board Iowa, but the tension among the officers signaled that they were involved in some sort of high stakes operation.
‘On the Iowa we knew he was on board but most of us didn’t really see him much,’ Sims says. ‘We didn’t know where we were going, but we were at flank speed all the time, so that thing was shaking. We were really moving.’
Even at maximum speed, the trip would take eight days, so during the voyage the ships and their crews continued with the training and drills that they normally conducted when at sea. Such activity was important to keep the men busy, and in the case of Willie Dee, to better prepare its relatively green crew for life at sea.
The destroyer’s trip got off to a rough start. As Captain Wilfred Walter backed Willie Dee out of its berth next to another ship in Norfolk, there was a god-awful racket. As Walter and the other officers looked off the bridge, they saw that their ship wasn’t coming apart — Willie Dee’s anchor had snagged the Navy ship beside it and ripped off its railing, life rafts, a small boat and various other pieces of equipment. Although it wreaked havoc on its neighbor, Willie Dee’s damage was limited to scratches on its anchor. Rushing to meet his rendezvous with Iowa, Walter only had time to make a quick apology before his destroyer continued on to its way.
Within the first 48 hours of the secret mission, Willie Dee continued drawing uncomplimentary attention to itself. At one point after joining the rest of the convoy, the ships were making their way through an area known to be infested with U-boats when a large explosion suddenly rocked the water. All the ships immediately initiated antisubmarine maneuvers and went on high alert, until Willie Dee signaled that there was no submarine. The explosion was just one of its own depth charges that had accidentally fallen off the ship because the trigger was not set on’safe’ as it should have been.
Soon after that embarrassment, Willie Dee was hit by a freak wave that washed a man overboard, never to be found. Quick on the heels of that mishap the engine room lost power for a while, causing the destroyer to fall far behind the rest of the convoy. By then, Chief of Naval Operations Admiral Ernest J. King, who was on board Iowa, had become aware of Willie Dee’s difficulties and, with so many personages looking over his shoulder, the head of the Navy was becoming increasingly embarrassed and frustrated. He made his displeasure known to Captain Walter, who knew that he was fumbling a career opportunity on this high profile mission. Duly admonished, Willie Dee’s skipper vowed to improve his ship’s performance for the rest of the trip and ensured that his crew trained hard while at sea.
The other crews were hard at work also, and on November 14, when the convoy was just east of Bermuda, Iowa‘s captain offered to show Roosevelt and his aides how the battleship could defend itself against an air attack. As Iowa fired its defensive guns at weather balloons sent aloft as targets, and the president sat on deck enjoying the show, Walter and his crew watched from 6,000 yards away and grew eager to join in the fun. They got their chance when the battleship missed a few of the target balloons, which drifted into range of Willie Dee’s guns. Seeing an opportunity to redeem himself, Walter quickly sent his crew to battle stations, and the gunners commenced firing on the balloons. At the same time, he ordered the crew to conduct a drill in which they would practice launching torpedoes at another ship.
So down belowdecks in the torpedo rooms, crewmen Lawton Dawson and Tony Fazio started simulating a real combat situation. The only difference between a drill and the real thing was that in a drill, Dawson and Fazio first removed all the primers that launched the torpedoes out of Willie Dee’s four tubes. Without the primers, the firing signal could not cause the explosion needed to expel the torpedos from the tubes into the water. To carry out the simulated attack, the torpedo crew needed a target. As was common in drills, they used any nearby ship. The biggest and easiest target they could see was Iowa.
When Dawson and Fazio were ready, the bridge officer sent the commands for the simulated firing and the torpedo crew below ‘fired’ a torpedo. After a pause in which he normally would have confirmed that the torpedo was on its way, the bridge officer continued the drill with ‘Fire 2!’ As expected, there was another pause and then he commanded ‘Fire 3!’
This time, his command was confirmed with a ‘whooooooosh’ as the torpedo flew out of its tube and into the water — to the astonishment and horror of the officers on the bridge. A live torpedo was in the water and headed straight for Iowa.
Officers on Willie Dee’s bridge started racing around, barking orders and calling for confirmation that what they feared was happening was in fact happening. At most, the torpedo might take two minutes to reach Iowa, and battleships can’t turn on a dime, so there was no time to waste.
Walter ordered a warning immediately sent to Iowa. But the secret convoy was under strict orders not to use the radio. Instead, a signalman was to signal the battleship by flashing light. Unfortunately, in his haste and inexperience, the young sailor first flashed that a torpedo was in the water but moving away from Iowa. Becoming more flustered as he watched the torpedo swim toward the battleship, he tried again and somehow signaled that Willie Dee was going in reverse at full speed.
Walter realized the flash signals weren’t going to work, and he was running out of time, so he decided to break radio silence. Willie Dee’s radioman quickly called to Iowa using its code name: ‘Lion, Lion, come right!’
The radioman on Iowa, surprised to hear anyone on the air, responded by calmly asking who was calling and why: ‘Identify and say again. Where is submarine?’Willie Dee’s operator responded with ‘Torpedo in the water! Lion, come right! Emergency! Come right, Lion! Come right!’
And then there was no more response from Iowa, because at about the same moment the lookout on the battleship had spotted the fish and was screaming: ‘Torpedo on our starboard quarter! This is not a drill! Torpedo on our starboard quarter!’
Iowa turned sharply right and increased speed as its guns began firing on the incoming torpedo. Walter and his crew on Willie Dee could only watch and hope the big ship made the turn in time.
The battleship sounded its General Quarters alarm, and the crew began racing to emergency stations. Those on deck soon saw the incoming torpedo as the ship leaned heavily to the left in a desperate maneuver. The list was so pronounced that Roosevelt’s bodyguards had to steady his wheelchair. One of the guards even reached for his pistol with the intent of shooting the torpedo as it came closer.
As the crew of Willie Dee held their breath and watched, the battleship made the turn in time, and the torpedo exploded in the big ship’s wake. Roosevelt later made a note in his diary about the trip that said: ‘On Monday last a gun drill. Porter fired a torpedo at us by mistake. We saw it — missed it by 1,000 feet.’
Walter and the Willie Dee crew could breathe again, but for them the incident was far from over. Once Iowa came back into formation, Walter could see that the battleship’s guns were trained on the destroyer that had just fired on the president. Soon Iowa radioed to ask what in the world had happened. ‘We did it,’ was Walter’s reply.
After quickly conferring with his own crew, who had no immediate explanation for how the torpedo ended up in the water, a red-faced Walter tried to assure Iowa that the whole thing was just an accident. Under the circumstances, however, suspicions ran high, and the hard luck Willie Dee was ordered out of the convoy. Iowa continued on to North Africa and delivered the president for his history-making summit, but Willie Dee was sent to a U.S. naval station in Bermuda. Fully armed U.S. Marines greeted the ship as it docked and placed the entire crew under arrest — the first time ever that a U.S. Navy crew was arrested en masse.
Willie Dee’s crew was grilled in a secret inquiry whose first purpose was to determine whether the ship had been infiltrated by a saboteur. Was firing the torpedo a simple boneheaded mistake or part of a larger conspiracy to assassinate Roosevelt and derail the Allies’ summit?
It took several days of testimony for the board of inquiry to determine that the live primer had been left in torpedo tube 3 by accident, rather than by someone using it deliberately during a drill, which meant that there was no conspiracy. Willie Dee’s crew had just screwed up in a big way. Exactly how remained a mystery until crewman Dawson finally confessed that he had lied in his first testimony, in which he claimed to have no idea how the live primer was left in place. Coming clean, he told the board that, in fact, he had accidentally left the primer in place when he removed the other three from the torpedo tubes. When the torpedo fired unexpectedly, he panicked and threw the used primer overboard.
One officer, Lieutenant William Poindexter, explained to the board of inquiry that ‘the inexperience of the personnel of the William D. Porter, men as well as officers,’ must be considered as a partial explanation for the accident. Of 16 officers junior to Poindexter, only four had any experience on a ship before coming to Willie Dee.
Nevertheless, Willie Dee had nearly killed the president, so someone had to be punished. For the initial mistake and his subsequent cover-up, the 22-year-old Dawson was sentenced to 14 years of hard labor. But when Roosevelt heard of the sentence, he ordered the Navy not to punish Dawson since the incident was clearly a mistake and no harm had been done. Maybe not, but in almost sinking Iowa, Willie Dee became known in the Navy as a screw-up ship to watch out for.
After 1943 the ship was commonly hailed by other ships with the greeting: ‘Don’t shoot! We’re Republicans!’ Willie Dee became a black sheep, and sailors like Bill Glover, a 17-year-old from Montgomery, Ala., when he joined the destroyer in 1944, were not happy about being assigned to it. ‘In less than a year after launching, it had done several things we heard about, so I didn’t want to go to the Porter,’ he said. ‘They acknowledged it when I got on board, laughed about it some. Nobody had gotten hurt, so you could joke about it some. And plus, there was a war on so we had other things to do.’ Besides, Glover said, Willie Dee didn’t screw up any more than the typical Navy ship run with inexperienced crews who had never been to sea. Willie Dee drew attention with a particularly dramatic error involving the president, but similar mistakes happened all the time as young crews learned on the job, he remembered.
‘Once you’ve fired a torpedo at Roosevelt, then everyone is looking at you and you get noticed for all the little things that everyone else is doing too,’ Glover said. ‘There were a lot of rookies in the service in 1943. Mistakes were made because 17-year-olds don’t know how not to make mistakes.’ Glover pointed out a fact largely forgotten in the victory of World War II: In the scramble to gear up in the early days of the war, the nation was sending brand new ships to sea with crews so young and inexperienced that they were quite literally learning everything as they went.
Still, the shadow of that ill-timed shot continued to haunt Willie Dee. Seeing how the destroyer had performed in a high profile task such as guarding the president’s secret convoy, the Navy thought the ship might be better off in an assignment where it could do little harm. The destroyer was sent to the Aleutian Islands for a year, and while serving in the frigid waters off Alaska the crew worked hard to vindicate their ship’s reputation.
Although they performed well, their ship seemed to be haunted by a Jonah and unable to entirely shake its embarrassing past. During a break in exercises in the Aleutians a sailor came back to the ship drunk after leave and decided he wanted to fire one of Willie Dee’s big guns. He fired the weapon before anyone could stop him, having no idea where the 5-inch shell would land. Unfortunately, it just happened to land in the front yard of the base commandant’s home while he was having a little party for fellow officers and their wives. Fortunately, the only damage was to the destroyer’s already unenviable reputation.
With the naval war in the Pacific reaching its climax, however, the Navy concluded that even Willie Dee was needed for the final campaigns. With a more seasoned crew, Willie Dee left the Aleutian Islands for the western Pacific performing escort duty to the Philippines and taking part in the operations at Mindoro and Lingayen Gulf. In late March 1945, Porter was sent to Okinawa, where it patrolled far out in the ocean to intercept Japanese aircraft before they got in close to the bigger ships. On one patrol, Willie Dee was fighting off kamikazes, each loaded with enough explosives to easily sink a destroyer. As one of the suicide planes came in low and aimed straight for the ship, Willie Dee’s gunners fired furiously, trying to down the plane before it struck them.
This time their training paid off and the crew rejoiced when the plane went down well short of the ship and didn’t explode. Maybe, some thought, Willie Dee’s luck was finally beginning to change. They were wrong.
The Japanese plane had been moving so fast that even after it went into the water it continued to move toward the ship. It kept moving until it was right under William D. Porter and exploded with enough force to lift the destroyer right out of the water.
The ship with the short, troubled history held on for three hours, long enough for every man on board to be rescued. Willie Dee then slipped beneath the waves, hardly to be mentioned again, its niche in history kept secret until the Iowa incident was officially reported in 1958.
This article was written by Gregory A. Freeman and originally appeared in the December 2005 issue of World War II magazine. For more great articles subscribe to World War II magazine today!
Recent advances in mRNA vaccine technology
Various mRNA vaccine platforms have been developed in recent years and validated in studies of immunogenicity and efficacy 18,19,20 . Engineering of the RNA sequence has rendered synthetic mRNA more translatable than ever before. Highly efficient and non-toxic RNA carriers have been developed that in some cases 21,22 allow prolonged antigen expression in vivo (Table 1). Some vaccine formulations contain novel adjuvants, while others elicit potent responses in the absence of known adjuvants. The following section summarizes the key advances in these areas of mRNA engineering and their impact on vaccine efficacy.
Optimization of mRNA translation and stability
This topic has been extensively discussed in previous reviews 14,15 thus, we briefly summarize the key findings (Box 1). The 5′ and 3′ UTR elements flanking the coding sequence profoundly influence the stability and translation of mRNA, both of which are critical concerns for vaccines. These regulatory sequences can be derived from viral or eukaryotic genes and greatly increase the half-life and expression of therapeutic mRNAs 23,24 . A 5′ cap structure is required for efficient protein production from mRNA 25 . Various versions of 5′ caps can be added during or after the transcription reaction using a vaccinia virus capping enzyme 26 or by incorporating synthetic cap or anti-reverse cap analogues 27,28 . The poly(A) tail also plays an important regulatory role in mRNA translation and stability 25 thus, an optimal length of poly(A) 24 must be added to mRNA either directly from the encoding DNA template or by using poly(A) polymerase. The codon usage additionally has an impact on protein translation. Replacing rare codons with frequently used synonymous codons that have abundant cognate tRNA in the cytosol is a common practice to increase protein production from mRNA 29 , although the accuracy of this model has been questioned 30 . Enrichment of G:C content constitutes another form of sequence optimization that has been shown to increase steady-state mRNA levels in vitro 31 and protein expression in vivo 12 .
Although protein expression may be positively modulated by altering the codon composition or by introducing modified nucleosides (discussed below), it is also possible that these forms of sequence engineering could affect mRNA secondary structure 32 , the kinetics and accuracy of translation and simultaneous protein folding 33,34 , and the expression of cryptic T cell epitopes present in alternative reading frames 30 . All these factors could potentially influence the magnitude or specificity of the immune response.
Box 1: Strategies for optimizing mRNA pharmacology
A number of technologies are currently used to improve the pharmacological aspects of mRNA. The various mRNA modifications used and their impact are summarized below.
• Synthetic cap analogues and capping enzymes 26,27 stabilize mRNA and increase protein translation via binding to eukaryotic translation initiation factor 4E (EIF4E)
• Regulatory elements in the 5′-untranslated region (UTR) and the 3′-UTR 23 stabilize mRNA and increase protein translation
• Poly(A) tail 25 stabilizes mRNA and increases protein translation
• Modified nucleosides 9,48 decrease innate immune activation and increase translation
• Separation and/or purification techniques: RNase III treatment (N.P. and D.W., unpublished observations) and fast protein liquid chromatography (FPLC) purification 13 decrease immune activation and increase translation
• Sequence and/or codon optimization 29 increase translation
• Modulation of target cells: co-delivery of translation initiation factors and other methods alters translation and immunogenicity
Modulation of immunogenicity
Exogenous mRNA is inherently immunostimulatory, as it is recognized by a variety of cell surface, endosomal and cytosolic innate immune receptors (Fig. 1) (reviewed in Ref. 35). Depending on the therapeutic application, this feature of mRNA could be beneficial or detrimental. It is potentially advantageous for vaccination because in some cases it may provide adjuvant activity to drive dendritic cell (DC) maturation and thus elicit robust T and B cell immune responses. However, innate immune sensing of mRNA has also been associated with the inhibition of antigen expression and may negatively affect the immune response 9,13 . Although the paradoxical effects of innate immune sensing on different formats of mRNA vaccines are incompletely understood, some progress has been made in recent years in elucidating these phenomena.
Innate immune sensing of two types of mRNA vaccine by a dendritic cell (DC), with RNA sensors shown in yellow, antigen in red, DC maturation factors in green, and peptide−major histocompatibility complex (MHC) complexes in light blue and red an example lipid nanoparticle carrier is shown at the top right. A non-exhaustive list of the major known RNA sensors that contribute to the recognition of double-stranded and unmodified single-stranded RNAs is shown. Unmodified, unpurified (part a) and nucleoside-modified, fast protein liquid chromatography (FPLC)-purified (part b) mRNAs were selected for illustration of two formats of mRNA vaccines where known forms of mRNA sensing are present and absent, respectively. The dashed arrow represents reduced antigen expression. Ag, antigen PKR, interferon-induced, double-stranded RNA-activated protein kinase MDA5, interferon-induced helicase C domain-containing protein 1 (also known as IFIH1) IFN, interferon m1Ψ, 1-methylpseudouridine OAS, 2′-5′-oligoadenylate synthetase TLR, Toll-like receptor.
Studies over the past decade have shown that the immunostimulatory profile of mRNA can be shaped by the purification of IVT mRNA and the introduction of modified nucleosides as well as by complexing the mRNA with various carrier molecules 9,13,36,37 . Enzymatically synthesized mRNA preparations contain double-stranded RNA (dsRNA) contaminants as aberrant products of the IVT reaction 13 . As a mimic of viral genomes and replication intermediates, dsRNA is a potent pathogen-associated molecular pattern (PAMP) that is sensed by pattern recognition receptors in multiple cellular compartments (Fig. 1). Recognition of IVT mRNA contaminated with dsRNA results in robust type I interferon production 13 , which upregulates the expression and activation of protein kinase R (PKR also known as EIF2AK2) and 2′-5′-oligoadenylate synthetase (OAS), leading to the inhibition of translation 38 and the degradation of cellular mRNA and ribosomal RNA 39 , respectively. Karikó and colleagues 13 have demonstrated that contaminating dsRNA can be efficiently removed from IVT mRNA by chromatographic methods such as reverse-phase fast protein liquid chromatography (FPLC) or high-performance liquid chromatography (HPLC). Strikingly, purification by FPLC has been shown to increase protein production from IVT mRNA by up to 1,000-fold in primary human DCs 13 . Thus, appropriate purification of IVT mRNA seems to be critical for maximizing protein (immunogen) production in DCs and for avoiding unwanted innate immune activation.
Besides dsRNA contaminants, single-stranded mRNA molecules are themselves a PAMP when delivered to cells exogenously. Single-stranded oligoribonucleotides and their degradative products are detected by the endosomal sensors Toll-like receptor 7 (TLR7) and TLR8 (Refs 40,41), resulting in type I interferon production 42 . Crucially, it was discovered that the incorporation of naturally occurring chemically modified nucleosides, including but not limited to pseudouridine 9,43,44 and 1-methylpseudouridine 45 , prevents activation of TLR7, TLR8 and other innate immune sensors 46,47 , thus reducing type I interferon signalling 48 . Nucleoside modification also partially suppresses the recognition of dsRNA species 46,47,48 . As a result, Karikó and others have shown that nucleoside-modified mRNA is translated more efficiently than unmodified mRNA in vitro 9 , particularly in primary DCs, and in vivo in mice 45 . Notably, the highest level of protein production in DCs was observed when mRNA was both FPLC-purified and nucleoside-modified 13 . These advances in understanding the sources of innate immune sensing and how to avoid their adverse effects have substantially contributed to the current interest in mRNA-based vaccines and protein replacement therapies.
In contrast to the findings described above, a study by Thess and colleagues found that sequence-optimized, HPLC-purified, unmodified mRNA produced higher levels of protein in HeLa cells and in mice than its nucleoside-modified counterpart 12 . Additionally, Kauffman and co-workers demonstrated that unmodified, non-HPLC-purified mRNA yielded more robust protein production in HeLa cells than nucleoside-modified mRNA, and resulted in similar levels of protein production in mice 49 . Although not fully clear, the discrepancies between the findings of Karikó 9,13 and these authors 12,49 may have arisen from variations in RNA sequence optimization, the stringency of mRNA purification to remove dsRNA contaminants and the level of innate immune sensing in the targeted cell types.
The immunostimulatory properties of mRNA can conversely be increased by the inclusion of an adjuvant to increase the potency of some mRNA vaccine formats. These include traditional adjuvants as well as novel approaches that take advantage of the intrinsic immunogenicity of mRNA or its ability to encode immune-modulatory proteins. Self-replicating RNA vaccines have displayed increased immunogenicity and effectiveness after formulating the RNA in a cationic nanoemulsion based on the licensed MF59 (Novartis) adjuvant 50 . Another effective adjuvant strategy is TriMix, a combination of mRNAs encoding three immune activator proteins: CD70, CD40 ligand (CD40L) and constitutively active TLR4. TriMix mRNA augmented the immunogenicity of naked, unmodified, unpurified mRNA in multiple cancer vaccine studies and was particularly associated with increased DC maturation and cytotoxic T lymphocyte (CTL) responses (reviewed in Ref. 51). The type of mRNA carrier and the size of the mRNA–carrier complex have also been shown to modulate the cytokine profile induced by mRNA delivery. For example, the RNActive (CureVac AG) vaccine platform 52,53 depends on its carrier to provide adjuvant activity. In this case, the antigen is expressed from a naked, unmodified, sequence-optimized mRNA, while the adjuvant activity is provided by co-delivered RNA complexed with protamine (a polycationic peptide), which acts via TLR7 signalling 52,54 . This vaccine format has elicited favourable immune responses in multiple preclinical animal studies for vaccination against cancer and infectious diseases 18,36,55,56 . A recent study provided mechanistic information on the adjuvanticity of RNActive vaccines in mice in vivo and human cells in vitro 54 . Potent activation of TLR7 (mouse and human) and TLR8 (human) and production of type I interferon, pro-inflammatory cytokines and chemokines after intradermal immunization was shown 54 . A similar adjuvant activity was also demonstrated in the context of non-mRNA-based vaccines using RNAdjuvant (CureVac AG), an unmodified, single-stranded RNA stabilized by a cationic carrier peptide 57 .
Progress in mRNA vaccine delivery
Efficient in vivo mRNA delivery is critical to achieving therapeutic relevance. Exogenous mRNA must penetrate the barrier of the lipid membrane in order to reach the cytoplasm to be translated to functional protein. mRNA uptake mechanisms seem to be cell type dependent, and the physicochemical properties of the mRNA complexes can profoundly influence cellular delivery and organ distribution. There are two basic approaches for the delivery of mRNA vaccines that have been described to date. First, loading of mRNA into DCs ex vivo, followed by re-infusion of the transfected cells 58 and second, direct parenteral injection of mRNA with or without a carrier. Ex vivo DC loading allows precise control of the cellular target, transfection efficiency and other cellular conditions, but as a form of cell therapy, it is an expensive and labour-intensive approach to vaccination. Direct injection of mRNA is comparatively rapid and cost-effective, but it does not yet allow precise and efficient cell-type-specific delivery, although there has been recent progress in this regard 59 . Both of these approaches have been explored in a variety of forms (Fig. 2 Table 1).
Commonly used delivery methods and carrier molecules for mRNA vaccines along with typical diameters for particulate complexes are shown: naked mRNA (part a) naked mRNA with in vivo electroporation (part b) protamine (cationic peptide)-complexed mRNA (part c) mRNA associated with a positively charged oil-in-water cationic nanoemulsion (part d) mRNA associated with a chemically modified dendrimer and complexed with polyethylene glycol (PEG)-lipid (part e) protamine-complexed mRNA in a PEG-lipid nanoparticle (part f) mRNA associated with a cationic polymer such as polyethylenimine (PEI) (part g) mRNA associated with a cationic polymer such as PEI and a lipid component (part h) mRNA associated with a polysaccharide (for example, chitosan) particle or gel (part i) mRNA in a cationic lipid nanoparticle (for example, 1,2-dioleoyloxy-3-trimethylammoniumpropane (DOTAP) or dioleoylphosphatidylethanolamine (DOPE) lipids) (part j) mRNA complexed with cationic lipids and cholesterol (part k) and mRNA complexed with cationic lipids, cholesterol and PEG-lipid (part l).
Ex vivo loading of DCs. DCs are the most potent antigen-presenting cells of the immune system. They initiate the adaptive immune response by internalizing and proteolytically processing antigens and presenting them to CD8 + and CD4 + T cells on major histocompatibility complexes (MHCs), namely, MHC class I and MHC class II, respectively. Additionally, DCs may present intact antigen to B cells to provoke an antibody response 60 . DCs are also highly amenable to mRNA transfection. For these reasons, DCs represent an attractive target for transfection by mRNA vaccines, both in vivo and ex vivo.
Although DCs have been shown to internalize naked mRNA through a variety of endocytic pathways 61,62,63 , ex vivo transfection efficiency is commonly increased using electroporation in this case, mRNA molecules pass through membrane pores formed by a high-voltage pulse and directly enter the cytoplasm (reviewed in Ref. 64). This mRNA delivery approach has been favoured for its ability to generate high transfection efficiency without the need for a carrier molecule. DCs that are loaded with mRNA ex vivo are then re-infused into the autologous vaccine recipient to initiate the immune response. Most ex vivo-loaded DC vaccines elicit a predominantly cell-mediated immune response thus, they have been used primarily to treat cancer (reviewed in Ref. 58).
Injection of naked mRNA in vivo. Naked mRNA has been used successfully for in vivo immunizations, particularly in formats that preferentially target antigen-presenting cells, as in intradermal 61,65 and intranodal injections 66,67,68 . Notably, a recent report showed that repeated intranodal immunizations with naked, unmodified mRNA encoding tumour-associated neoantigens generated robust T cell responses and increased progression-free survival 68 (discussed further in Box 2).
Physical delivery methods in vivo. To increase the efficiency of mRNA uptake in vivo, physical methods have occasionally been used to penetrate the cell membrane. An early report showed that mRNA complexed with gold particles could be expressed in tissues using a gene gun, a microprojectile method 69 . The gene gun was shown to be an efficient RNA delivery and vaccination method in mouse models 70,71,72,73 , but no efficacy data in large animals or humans are available. In vivo electroporation has also been used to increase uptake of therapeutic RNA 74,75,76 however, in one study, electroporation increased the immunogenicity of only a self-amplifying RNA and not a non-replicating mRNA-based vaccine 74 . Physical methods can be limited by increased cell death and restricted access to target cells or tissues. Recently, the field has instead favoured the use of lipid or polymer-based nanoparticles as potent and versatile delivery vehicles.
Protamine. The cationic peptide protamine has been shown to protect mRNA from degradation by serum RNases 77 however, protamine-complexed mRNA alone demonstrated limited protein expression and efficacy in a cancer vaccine model, possibly owing to an overly tight association between protamine and mRNA 36,78 . This issue was resolved by developing the RNActive vaccine platform, in which protamine-formulated RNA serves only as an immune activator and not as an expression vector 52 .
Cationic lipid and polymer-based delivery. Highly efficient mRNA transfection reagents based on cationic lipids or polymers, such as TransIT-mRNA (Mirus Bio LLC) or Lipofectamine (Invitrogen), are commercially available and work well in many primary cells and cancer cell lines 9,13 , but they often show limited in vivo efficacy or a high level of toxicity (N.P. and D.W., unpublished observations). Great progress has been made in developing similarly designed complexing reagents for safe and effective in vivo use, and these are discussed in detail in several recent reviews 10,11,79,80 . Cationic lipids and polymers, including dendrimers, have become widely used tools for mRNA administration in the past few years. The mRNA field has clearly benefited from the substantial investment in in vivo small interfering RNA (siRNA) administration, where these delivery vehicles have been used for over a decade. Lipid nanoparticles (LNPs) have become one of the most appealing and commonly used mRNA delivery tools. LNPs often consist of four components: an ionizable cationic lipid, which promotes self-assembly into virus-sized (
100 nm) particles and allows endosomal release of mRNA to the cytoplasm lipid-linked polyethylene glycol (PEG), which increases the half-life of formulations cholesterol, a stabilizing agent and naturally occurring phospholipids, which support lipid bilayer structure. Numerous studies have demonstrated efficient in vivo siRNA delivery by LNPs (reviewed in Ref. 81), but it has only recently been shown that LNPs are potent tools for in vivo delivery of self-amplifying RNA 19 and conventional, non-replicating mRNA 21 . Systemically delivered mRNA–LNP complexes mainly target the liver owing to binding of apolipoprotein E and subsequent receptor-mediated uptake by hepatocytes 82 , and intradermal, intramuscular and subcutaneous administration have been shown to produce prolonged protein expression at the site of the injection 21,22 . The mechanisms of mRNA escape into the cytoplasm are incompletely understood, not only for artificial liposomes but also for naturally occurring exosomes 83 . Further research into this area will likely be of great benefit to the field of therapeutic RNA delivery.
The magnitude and duration of in vivo protein production from mRNA–LNP vaccines can be controlled in part by varying the route of administration. Intramuscular and intradermal delivery of mRNA–LNPs has been shown to result in more persistent protein expression than systemic delivery routes: in one experiment, the half-life of mRNA-encoded firefly luciferase was roughly threefold longer after intradermal injection than after intravenous delivery 21 . These kinetics of mRNA–LNP expression may be favourable for inducing immune responses. A recent study demonstrated that sustained antigen availability during vaccination was a driver of high antibody titres and germinal centre (GC) B cell and T follicular helper (TFH) cell responses 84 . This process was potentially a contributing factor to the potency of recently described nucleoside-modified mRNA–LNP vaccines delivered by the intramuscular and intradermal routes 20,22,85 . Indeed, TFH cells have been identified as a critical population of immune cells that vaccines must activate in order to generate potent and long-lived neutralizing antibody responses, particularly against viruses that evade humoral immunity 86 . The dynamics of the GC reaction and the differentiation of TFH cells are incompletely understood, and progress in these areas would undoubtedly be fruitful for future vaccine design (Box 3).
Box 2: Personalized neoepitope cancer vaccines
Sahin and colleagues have pioneered the use of individualized neoepitope mRNA cancer vaccines 121 . They use high-throughput sequencing to identify every unique somatic mutation of an individual patient's tumour sample, termed the mutanome. This enables the rational design of neoepitope cancer vaccines in a patient-specific manner, and has the advantage of targeting non-self antigen specificities that should not be eliminated by central tolerance mechanisms. Proof of concept has been recently provided: Kreiter and colleagues found that a substantial portion of non-synonymous cancer mutations were immunogenic when delivered by mRNA and were mainly recognized by CD4 + T cells 176 . On the basis of these data, they generated a computational method to predict major histocompatibility complex (MHC) class II-restricted neoepitopes that can be used as vaccine immunogens. mRNA vaccines encoding such neoepitopes have controlled tumour growth in B16-F10 melanoma and CT26 colon cancer mouse models. In a recent clinical trial, Sahin and colleagues developed personalized neoepitope-based mRNA vaccines for 13 patients with metastatic melanoma, a cancer known for its high frequency of somatic mutations and thus neoepitopes. They immunized against ten neoepitopes per individual by injecting naked mRNA intranodally. CD4 + T cell responses were detected against the majority of the neoepitopes, and a low frequency of metastatic disease was observed after several months of follow-up 68 . Interestingly, similar results were also obtained in a study of analogous design that used synthetic peptides as immunogens rather than mRNA 177 . Together, these recent trials suggest the potential utility of the personalized vaccine methodology.
Box 3: The germinal centre and T follicular helper cells
The vast majority of potent antimicrobial vaccines elicit long-lived, protective antibody responses against the target pathogen. High-affinity antibodies are produced in specialized microanatomical sites within the B cell follicles of secondary lymphoid organs called germinal centres (GCs). B cell proliferation, somatic hypermutation and selection for high-affinity mutants occur in the GCs, and efficient T cell help is required for these processes 178 . Characterization of the relationship between GC B and T cells has been actively studied in recent years. The follicular homing receptor CXC-chemokine receptor 5 (CXCR5) was identified on GC B and T cells in the 1990s 179,180 , but the concept of a specific lineage of T follicular helper (TFH) cells was not proposed until 2000 (Refs 181, 182). The existence of the TFH lineage was confirmed in 2009 when the transcription factor specific for TFH cells, B cell lymphoma 6 protein (BCL-6), was identified 183,184,185 . TFH cells represent a specialized subset of CD4 + T cells that produce critical signals for B cell survival, proliferation and differentiation in addition to signals for isotype switching of antibodies and for the introduction of diversifying mutations into the immunoglobulin genes. The major cytokines produced by TFH cells are interleukin-4 (IL-4) and IL-21, which play a key role in driving the GC reaction. Other important markers and functional ligands expressed by TFH cells include CD40 ligand (CD40L), Src homology domain 2 (SH2) domain-containing protein 1A (SH2D1A), programmed cell death protein 1 (PD1) and inducible T cell co-stimulator (ICOS) 186 . The characterization of rare, broadly neutralizing antibodies to HIV-1 has revealed that unusually high rates of somatic hypermutation are a hallmark of protective antibody responses against HIV-1 (Ref. 187). As TFH cells play a key role in driving this process in GC reactions, the development of new adjuvants or vaccine platforms that can potently activate this cell type is urgently needed.
Europe's Common Market founded in major step toward economic unity
On March 25, 1957, France, West Germany, Italy, the Netherlands, Belgium and Luxembourg sign a treaty in Rome establishing the European Economic Community (EEC), also known as the Common Market. The EEC, which came into operation in January 1958, was a major step in Europe’s movement toward economic and political union.
By 1950, it was apparent that centuries of Western European world supremacy was at an end. The national markets of Europe, isolated from each other by archaic trade laws, were no match for the giant market enjoyed by the United States. And looming over Europe from the east was the Soviet Union, whose communist leaders commanded vast territory and economic resources under a single system. Many European leaders also feared the resumption of conflict between traditional European antagonists such as France and Germany, which would only diminish the European economies further.
As a means of improving Europe’s economic climate and preventing war, some influential statesman and political theorists suggested economic integration. The first major step in this direction was taken in 1951, when France and West Germany formed the European Coal and Steel Community (ECSC), integrating their coal and steel industries. French leaders proposed the organization primarily as a means of monitoring German industry, and West German leaders immediately agreed, to allay fears of German militarization. To supervise the ECSC, several supranational bodies were established, including an executive authority, a council of ministers, an advisory assembly, and a court of justice to settle disputes. Italy and the three nations of the Benelux Economic Unionlgium, the Netherlands, and Luxembourg–soon joined. The groundwork for the EEC was laid.
On March 25, 1957, representatives of six European nations signed two treaties in Rome. One created the European Atomic Energy Community (Euratom) for the common and peaceful development of Europe’s nuclear resources. The other created the EEC. In the Common Market, trade barriers between member nations were gradually eliminated, and common policies regarding transportation, agriculture, and economic relations with nonmember countries were implemented. Eventually, labor and capital were permitted to move freely within the boundaries of the community. The EEC, the ECSC, and Euratom were served by a single council of ministers, representative assembly, and court of justice. In 1967, the three organizations were fully merged as the European Community (EC).
Britain and other European nations initially declined to join the Common Market and established the weaker European Free Trade Association (EFTA) in 1960 as an alternative. By the early 1960s, however, the Common Market nations showed signs of significant economic growth, and Britain changed its mind. Because of its close ties to the United States, however, French President Charles de Gaulle twice vetoed British admission, and Britain did not join the EC until January 1973, when Ireland and Denmark also became EC members. Greece joined in 1981, Portugal and Spain in 1986, and the former East Germany as part of reunified Germany in 1990.
In early 1990s, the European Community became the basis for the European Union (EU), which was established in 1993 following ratification of the Maastricht Treaty. The treaty called for a strengthened European parliament, the creation of a central European bank and common currency, and a common defense policy. In addition to a single European common market, member states would also participate in a larger common market, called the European Economic Area. Austria, Finland, and Sweden became members of the EU in 1995. In 2009, the EEC was absorbed into the EU&aposs framework. As of 2020, the EU had 27 member states.
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Edmund Hillary, in full Sir Edmund Percival Hillary, (born July 20, 1919, Auckland, New Zealand—died January 11, 2008, Auckland), New Zealand mountain climber and Antarctic explorer who, with the Tibetan mountaineer Tenzing Norgay, was the first to reach the summit of Mount Everest (29,035 feet [8,850 metres] see Researcher’s Note: Height of Mount Everest), the highest mountain in the world.
What was Edmund Hillary’s early life like?
Edmund Hillary began climbing in New Zealand’s Southern Alps while in high school, before working as a beekeeper during the summers and climbing mountains during the winters. After military service in World War II, he joined a party to the central Himalayas in 1951 and later joined a mountaineering team planning to climb Mount Everest.
What did Edmund Hillary accomplish?
Edmund Hillary and Tibetan mountaineer Tenzing Norgay were the first people to reach the summit of Mount Everest, the highest mountain in the world. The two men reached the summit by late morning on May 29, 1953. After spending about 15 minutes on the peak, they began their descent.
Why was Edmund Hillary so influential?
Edmund Hillary never anticipated the acclaim that would follow the historic ascent. Throughout his experience of celebrity, he maintained a high level of humility. His main interest came to be the welfare of Nepal’s Himalayan peoples, especially the Sherpas. He was knighted in 1953. In 2003 Hillary was made an honorary citizen of Nepal.
Hillary’s father was a beekeeper, an occupation he also pursued. He began climbing in New Zealand’s Southern Alps while in high school. After military service in World War II, he resumed climbing and became determined to scale Everest. In 1951 he joined a New Zealand party to the central Himalayas and later that year participated in a British reconnaissance expedition of the southern flank of Everest. He was subsequently invited to join the team of mountaineers planning to climb the peak.
The well-organized expedition was launched in the spring of 1953, and a high camp from which to mount attempts at the summit was established by mid-May. After a pair of climbers failed to reach the top on May 27, Hillary and Tenzing set out for it early on May 29 by late morning they were standing on the summit. The two shook hands, then Tenzing embraced his partner. Hillary took photographs, and both searched for signs that George Mallory, a British climber lost on Everest in 1924, had been on the summit. Hillary left behind a crucifix, and Tenzing, a Buddhist, made a food offering. After spending about 15 minutes on the peak, they began their descent. They were met back at camp by their colleague W.G. Lowe, to whom Hillary reputedly said, “Well, George, we knocked the bastard off.” Hillary described his exploits in High Adventure (1955). He made other expeditions to the Everest region during the early 1960s but never again tried to climb to the top.
Between 1955 and 1958 Hillary commanded the New Zealand group participating in the British Commonwealth Trans-Antarctic Expedition led by Vivian (later Sir Vivian) Fuchs. He reached the South Pole by tractor on January 4, 1958, and recorded this feat in The Crossing of Antarctica (1958 with Fuchs) and No Latitude for Error (1961). On his expedition of Antarctica in 1967, he was among those who scaled Mount Herschel (10,941 feet [3,335 metres]) for the first time. In 1977 he led the first jet boat expedition up the Ganges River and continued by climbing to its source in the Himalayas. His autobiography, Nothing Venture, Nothing Win, was published in 1975.
Hillary never anticipated the acclaim that would follow the historic ascent. He was knighted in 1953, shortly after the expedition returned to London. From 1985 to 1988 he served as New Zealand’s high commissioner to India, Nepal, and Bangladesh. Over the years numerous other honours were bestowed on him, including the Order of the Garter in 1995. Throughout it, however, he maintained a high level of humility, and his main interest came to be the welfare of the Himalayan peoples of Nepal, especially the Sherpas. Through the Himalayan Trust, which he founded in 1960, he built schools, hospitals, and airfields for them. This dedication to the Sherpas lasted into his later years and was recognized in 2003, when, as part of the observance of the 50th anniversary of his and Tenzing’s climb, he was made an honorary citizen of Nepal.
The Editors of Encyclopaedia Britannica This article was most recently revised and updated by John P. Rafferty, Editor.
Hitler becomes dictator of Germany
With the death of German President Paul von Hindenburg, Chancellor Adolf Hitler becomes absolute dictator of Germany under the title of Fuhrer, or “Leader.” The German army took an oath of allegiance to its new commander-in-chief, and the last remnants of Germany’s democratic government were dismantled to make way for Hitler’s Third Reich. The Fuhrer assured his people that the Third Reich would last for a thousand years, but Nazi Germany collapsed just 11 years later.
Adolf Hitler was born in Braunau am Inn, Austria, in 1889. As a young man he aspired to be a painter, but he received little public recognition and lived in poverty in Vienna. Of German descent, he came to detest Austria as a “patchwork nation” of various ethnic groups, and in 1913 he moved to the German city of Munich in the state of Bavaria. After a year of drifting, he found direction as a German soldier in World War I, and was decorated for his bravery on the battlefield. He was in a military hospital in 1918, recovering from a mustard gas attack that left him temporarily blind, when Germany surrendered.
He was appalled by Germany’s defeat, which he blamed on 𠇎nemies within”𠄼hiefly German communists and Jews𠄺nd was enraged by the punitive peace settlement forced on Germany by the victorious Allies. He remained in the German army after the war, and as an intelligence agent was ordered to report on subversive activities in Munich’s political parties. It was in this capacity that he joined the tiny German Workers’ Party, made up of embittered army veterans, as the group’s seventh member. Hitler was put in charge of the party’s propaganda, and in 1920 he assumed leadership of the organization, changing its name to Nationalsozialistische Deutsche Arbeiterpartei (National Socialist German Workers’ party), which was abbreviated to Nazi.
The party’s socialist orientation was little more than a ploy to attract working-class support in fact, Hitler was fiercely right-wing. But the economic views of the party were overshadowed by the Nazis’ fervent nationalism, which blamed Jews, communists, the Treaty of Versailles, and Germany’s ineffectual democratic government for the country’s devastated economy. In the early 1920s, the ranks of Hitler’s Bavarian-based Nazi party swelled with resentful Germans. A paramilitary organization, the Sturmabteilung (SA), was formed to protect the Nazis and intimidate their political opponents, and the party adopted the ancient symbol of the swastika as its emblem.
In November 1923, after the German government resumed the payment of war reparations to Britain and France, the Nazis launched the r Hall Putsch”𠅊n attempt at seizing the German government by force. Hitler hoped that his nationalist revolution in Bavaria would spread to the dissatisfied German army, which in turn would bring down the government in Berlin. However, the uprising was immediately suppressed, and Hitler was arrested and sentenced to five years in prison for treason.
Imprisoned in Landsberg fortress, he spent his time there dictating his autobiography, Mein Kampf (My Struggle), a bitter and rambling narrative in which he sharpened his anti-Semitic and anti-Marxist beliefs and laid out his plans for Nazi conquest. In the work, published in a series of volumes, he developed his concept of the Fuhrer as an absolute dictator who would bring unity to German people and lead the 𠇊ryan race” to world supremacy.
Political pressure from the Nazis forced the Bavarian government to commute Hitler’s sentence, and he was released after nine months. However, Hitler emerged to find his party disintegrated. An upturn in the economy further reduced popular support of the party, and for several years Hitler was forbidden to make speeches in Bavaria and elsewhere in Germany.
The onset of the Great Depression in 1929 brought a new opportunity for the Nazis to solidify their power. Hitler and his followers set about reorganizing the party as a fanatical mass movement, and won financial backing from business leaders, for whom the Nazis promised an end to labor agitation. In the 1930 election, the Nazis won six million votes, making the party the second largest in Germany. Two years later, Hitler challenged Paul von Hindenburg for the presidency, but the 84-year-old president defeated Hitler with the support of an anti-Nazi coalition.
Although the Nazis suffered a decline in votes during the November 1932 election, Hindenburg agreed to make Hitler chancellor in January 1933, hoping that Hitler could be brought to heel as a member of his cabinet. However, Hindenburg underestimated Hitler’s political audacity, and one of the new chancellor’s first acts was to exploit the burning of the Reichstag (parliament) building as a pretext for calling general elections. The police under Nazi Hermann Goering suppressed much of the party’s opposition before the election, and the Nazis won a bare majority. Shortly after, Hitler took on dictatorial power through the Enabling Acts.
Chancellor Hitler immediately set about arresting and executing political opponents, and even purged the Nazis’ own SA paramilitary organization in a successful effort to win support from the German army. With the death of President Hindenburg on August 2, 1934, Hitler united the chancellorship and presidency under the new title of Fuhrer. As the economy improved, popular support for Hitler’s regime became strong, and a cult of Fuhrer worship was propagated by Hitler’s capable propagandists.
German remilitarization and state-sanctioned anti-Semitism drew criticism from abroad, but the foreign powers failed to stem the rise of Nazi Germany. In 1938, Hitler implemented his plans for world domination with the annexation of Austria, and in 1939 Germany seized all of Czechoslovakia. Hitler’s invasion of Poland on September 1, 1939, finally led to war with England and France. In the opening years of World War II, Hitler’s war machine won a series of stunning victories, conquering the great part of continental Europe. However, the tide turned in 1942 during Germany’s disastrous invasion of the USSR.
By early 1945, the British and Americans were closing in on Germany from the west, the Soviets from the east, and Hitler was holed up in a bunker under the chancellery in Berlin awaiting defeat. On April 30, with the Soviets less than a mile from his headquarters, Hitler died by suicide with Eva Braun, his mistress whom he married the night before.
Hitler left Germany devastated and at the mercy of the Allies, who divided the country and made it a major battlefield of Cold War conflict. His regime exterminated some six millions Jews and an estimated 250,000 Romani in the Holocaust, and an indeterminable number of Slavs, political dissidents, disabled persons, homosexuals, and others deemed unacceptable by the Nazi regime were systematically eliminated. The war Hitler unleashed upon Europe took even more lives𠅌lose to 20 million people killed in the USSR alone. Adolf Hitler is reviled as one of history’s greatest villains.
Arms Races Continue
The Cold War ended in 1991 however, in 1987, the United States and the Soviet Union had signed the Intermediate-Range Nuclear Forces Treaty (INF) to limit the scope and reach of all types of missiles.
Other treaties such as the START 1 treaty in 1991 and the New START treaty in 2011 aimed to further reduce both nations’ ballistic weapons capabilities.
The United States withdrew from the INF treaty in 2019, however, believing that Russia was noncompliant. Though the Cold War between the United States and Russia is over, many argue the arms race is not.
Other countries have beefed up their military might and are in a modern-day arms race or poised to enter one, including India and Pakistan, North Korea and South Korea, Iran and China.
John Bell Hood: Western Theater and the Atlanta Campaign
After spending two months convalescing in Richmond, Hood rejoined Longstreet’s corps, which had been transferred to the Western Theater to assist General Braxton Bragg’s Army of Tennessee. Only days after rejoining his old unit in September 1863, Hood led a charge during the Battle of Chickamauga. While the assault succeeded, Hood was wounded in the thigh by a musket ball, sustaining his second major injury in less than three months. The severity of the wound required his right leg to be amputated, but Hood survived against extreme odds and was promoted to lieutenant general for his bravery.
Hood returned to the field in the spring of 1864 despite his injuries, which required him to wear an artificial leg and ride strapped to his horse. He assumed a corps command in General Joseph E. Johnston’s Army of Tennessee, which was then attempting to slow General William T. Sherman’s march toward Atlanta. The aggressive Hood was quick to criticize Johnston, whose strategy of strategic withdrawal had allowed Sherman to close in on the city. Furious at his commander’s cautious tactics, Hood wrote a series of letters to Richmond demanding that Johnston be relieved. His campaign succeeded, and in July 1864 Hood replaced Johnston as commander of the Army of Tennessee.
Temporarily promoted to full general, Hood promptly launched a series of bold offensives on Sherman’s forces at the Battles of Peachtree Creek, Atlanta, Ezra Church and Jonesborough, all of which failed. Hood abandoned Atlanta to Union control in September 1864, having suffered over 50 percent casualties in his once 65,000-strong force. Hood then moved the remnants of his army to the northwest, hoping to draw Sherman to Tennessee. The plan proved unsuccessful, as Sherman merely dispatched General George H. Thomas to take control of Union forces in Tennessee while he remained in Georgia to undertake his March to the Sea.