History

MassBiologics, Vaccination, and Public Health History

Cover of Publication Plea for Diphtheria Antitoxin by McCollom 1900

Cover of Publication “Plea for Diphtheria Antitoxin”. 1900.

Public health concerns regarding the prevention and treatment of communicable disease have existed in the United States since Colonial times. Many of the actions and statutes that lead to modern day public health measures such as vaccination began in Massachusetts. Advances in understanding of disease and public health set the stage for the founding and continued development of MassBiologics of the University of Massachusetts Medical School.

Early Public Health

The early public health movement in America began in 1648 with the enactment by the General Court of the Massachusetts Bay of a statute providing for maritime quarantine. This statute was passed to address the spread of disease coming from the West Indies, but was repealed the following year when the epidemic stopped. During a 1678 smallpox epidemic, Reverend Thomas Thacher of Boston published a broadsheet on the care of smallpox victim, possibly the first medical publication in the English colonies. In 1721 Massachusetts, Cotton Mather promoted small pox inoculation, which was then begun by Dr. Zabdiel Boylston. 1

Many other acts throughout the 17th and 18th centuries addressed prevention of disease and the spread of contagions. Toward the end of the eighteenth century, the appearance of several epidemics of influenza, smallpox, scarlet fever, and yellow fever brought the investigation of disease to the forefront of medical interest. Notably, on June 22, 1797, a law passed in Massachusetts provided for the formation of health organizations in towns and gave these organizations the authority to abate nuisances which they considered dangerous to the public health. 2 This law was subsequently copied and adopted by many other states. Shortly after, in 1799, a Board of Health with Paul Revere as President, known as the “Paul Revere Board of Health”, was established in Boston following a severe outbreak of yellow fever.3

Benjamin WaterhouseDuring the early part of the 19th century, Massachusetts set many precedents in vaccination and public health. In 1801 Dr. Benjamin Waterhouse, a Boston physician, introduced the use of “Cowpox Vaccine”, in Massachusetts and became the first doctor in Boston to obtain vaccine material. Soon after, in 1802, Massachusetts became the first U.S. state to encourage the use of vaccination against smallpox. Dr. Waterhouse convinced Boston’s Board of Health to sponsor a public test of vaccination. Nineteen volunteers were successfully vaccinated. Milton, Massachusetts set an even greater standard in 1809, later to be a cornerstone of Massachusetts public health, by giving all inhabitants free smallpox vaccination. Other communities soon followed this example. 4

Early Vaccine History

The terms inoculation, vaccination and immunization are often used interchangeably but, in fact, have slightly different meanings and connotations. The term immunization covers both inoculation and vaccination, generally referring to any process which exposes an individual to something in order to fortify the immune system. The main difference between inoculation and vaccination is the process of administering the organism. Inoculation is a method of purposefully infecting a person with an organism in a controlled manner so as to minimize the severity of a current infection and also to induce immunity against further infection. Vaccination is the process of administering weakened or dead pathogens to a healthy person, with the intent of conferring future immunity against the disease. 5

Inoculation had been informally used and its affect observed since ancient times, even if the scientific mechanisms were not understood. Before advancement in understanding about germ theory and immunity, inoculation was the primary and best means of disease prevention. It entered general public use and acceptance in 1721 after the work of Cotton Mather and Zabdiel Boylston and continued to be heavily used thereafter. For example, in Boston, in 1792 8,000 individuals were inoculated against smallpox.

Sophie the Cow. July 30, 1928.

Sophie the Cow. 1928.

Credit for the first modern and scientific steps toward scientific and standardized inoculation goes to Edward Jenner, an English physician. In 1796, Jenner first speculated that protection from the smallpox disease could be obtained through inoculation with a related virus, cowpox. He tested his theory by inoculating eight-year-old James Phipps with cowpox pustule liquid recovered from the hand of a milkmaid, Sarah Nelmes. Jenner then tried to infect James with smallpox but found the boy was immune. 6 Jenner’s process became known as vaccination (from the Latin vacca for cow) because it used an alternative and weakened form of the disease, cowpox from other people. The findings spread rapidly throughout the medical community and smallpox vaccination was quickly adopted, including by Dr. Waterhouse in Boston.7 The impact and importance of the smallpox vaccine is of particular note. In 1721, smallpox attacked 5,989 persons out of the 11,000 inhabitants of Boston, killing 840. In 1730, 500 died of smallpox. ­­After Jenner published his work concerning smallpox, his form of vaccination became more standardized and accepted. The last smallpox epidemic in Massachusetts occurred in 1902. In 1922 there were only two cases of smallpox in Massachusetts with no deaths.8 Today, smallpox is considered to have been eradicated, last reported case of naturally occurring smallpox in the world having been reported in 1977. 9

The next advancement in vaccines did not come until the 1870s with the discoveries of Louis Pasteur, a French chemist and microbiologist, about chicken cholera. Pasteur observed that after accidentally exposing chickens to the attenuated (weakened) form of a cholera culture, the chickens became resistant to the actual virus. This eventually led to the landmark development of a rabies vaccine. On July 6, 1885, Pasteur successfully vaccinated Joseph Meister, a 9-year-old boy who had been bitten by a rabid dog. 10

Commonhealth. Page 7. 1958

From the Commonhealth publication.

Shattuck Report and foundations for Laboratory establishment

Lemuel Shattuck

Lemuel Shattuck

With the advancements in medicine and vaccine science, the groundwork for standardized, government supported public health care systems began to be established. Lemuel Shattuck began petitioning the State in 1848, with the help of the American Statistical Association and the Massachusetts Medical Society, to make a sanitary survey of Massachusetts. The Legislature agreed, prompted in part by fears of a cholera epidemic after reports of the disease causing quarantine in New York harbor and the memories of an 1832 cholera epidemic in Boston. A commission, lead by Shattuck, was appointed in 1849, to investigate the conditions, both favorable and unfavorable, that affected the health of Massachusetts residents. Submitted to the legislature on April 25, 1850, the Report of the Massachusetts Sanitary Commission, 1850, at almost five hundred pages, was researched and prepared almost entirely by Shattuck alone. It recommended legislation that would allow for more efficient control of factors influencing the health of communities and individuals. This included the recommendation for the establishment of a central board of health that, along with local boards of health, would be charged with executing laws related to the health of Massachusetts residents. Many other recommendations were made including the need for a census, registration of births, deaths, and illness, and the investigation of all causes of disease.11

Even with the recommendations in Shattuck’s report, it was not until 1869 that the Massachusetts’ Legislature enacted a law creating the State Board of Health. The board consisted of seven members appointed by the Governor and was given general oversight of all matters related to the health of Massachusetts and its people. Henry Ingersoll Bowditch, a prominent Boston physician, was appointed first Chairman. The State Board of Health went through many changes leading up to the turn of the century. Many other departments related to health were continually created or merged, and greater powers were increasingly granted. In 1888 the State Board of Health went on record as recommending the establishment of a state vaccine institution. It was not seen as an immediate priority as there were numerous sources of vaccine lymph. However, the quality of the vaccine fluctuated greatly so that a large number of failures and undesirable reactions resulted. Because of legislation passed in Massachusetts requiring vaccination as a prerequisite to school attendance, the State Board of Health felt it was the duty of the State to provide vaccine of dependable quality for this purpose.12

Horse.

Horse. Used in vaccine production.

In the early 1890’s Emil Adolf von Behring, a German physiologist who ultimately received the first Nobel Prize in Physiology or Medicine in 1901. and Kitasato Shibasaburō, a Japanese physician and bacteriologist, discovered that injection of animals with the toxin of the diphtheria bacillus produced antitoxins in the animal’s blood serum. This serum then had beneficial powers for diphtheria when given to those exposed to the disease and even cured those already considered extremely ill. This discovery coincided with a diphtheria epidemic that swept through the United States in the 1890s, killing thousands of children. This prompted many U.S. state health departments to create laboratories to start extracting antiserum from horses’ blood. 13

While attending conferences in Paris in 1894, Dr. Henry Pickering Walcott, then chairman of the State Board of Health, heard reports from Pierre Paul Émile Roux, a French physician, bacteriologist and immunologist, about his work on the preventive and therapeutic value of antitoxin. Recognizing the importance of these developments, Walcott advocated for the establishment of a laboratory in Massachusetts, as was being done in New York City, where diphtheria antitoxin could be manufactured and freely distributed under state supervision.14 Dr. Harold C. Ernest was appointed to procure what was necessary for the production of toxin for horses and antitoxin for patients in order that that the city, as he stated, “Not to be dependent for its supply of this therapeutic agent upon what the governments of France and Germany might see fit to spare, or upon a supply furnished by private individuals, who are interested mainly in pecuniary work and secondly in the interests of the community.”15

In the autumn of 1894, the Board appointed Joseph L. Goodale, M.D. to begin preparation of antitoxin serum in a laboratory located in the State House on a tentative basis. Goodale was a recent Harvard Medical School graduate who had just returned from a year of study in Europe at some of the first laboratories to produce antitoxin. The horses necessary for the antitoxin production and some laboratory space were housed in a stable on the grounds of the Bussey Institution of Harvard University at Forest Hills. Serum began to be distributed free to physicians in Massachusetts as early as March 1895. 16

Theobald Smith and the early years

Theobald Smith, M.D. Director Antitoxin & Vaccine Laboratory 1985-1914

Theobald Smith, M.D. Director 1985-1914

It soon became apparent to the Board of Health that the nature and scope of the work required the direction of a more highly trained bacteriologist. Dr. Theobald Smith took charge of the newly established Antitoxin and Vaccine Laboratory in the summer of 1895 after outfitting a number of laboratory rooms at the Bussey Institution. Dr. Theobald Smith was a pioneer epidemiologist, bacteriologist, and pathologist. Before becoming the first Director of the Laboratory, Dr. Smith had been the Director of the Division of Pathology of the U.S. Bureau of Animal Industry. At the same time as joining the Laboratory, Dr. Smith became the first Professor of Comparative Pathology at the Harvard Medical School. As director of the Antitoxin and Vaccine Laboratory, Smith developed vaccines, antitoxins, and diagnostic tests against smallpox, meningitis, tuberculosis, and typhoid. He was one of the first to demonstrate the production of immunity by killed cultures of disease organisms and to show that a mixture of diphtheria toxin and antitoxin confers immunity.17

Bussey Building.

Bussey Building.

Even with the generosity of Harvard, Dr. Smith had limited space and resources. In an Annual report of the Presidents and Treasurer of Harvard College, the space provided is described as follows; “Facilities were provided at the Bussey Institution of Harvard College near the Forest Hills station. Three rooms of medium size were fitted up, together with a small animal house – a transformed unused greenhouse attached to the building of the institution.”18

For most of the first years of the Laboratory, the preparation of diphtheria antitoxin was carried out under the personal supervision of Dr. Smith, with little involvement by the State Board of Health and without any legislative mandate. However, the services provided through the laboratories continued to grow. A bacteriological laboratory, later known as the Diagnostic Laboratory, was established in 1895 for the purpose of experimental work and the investigation of infectious diseases, namely, the diagnosis of diphtheria and tuberculosis and examination of blood from suspected malaria patients. Blood tests of suspected typhoid cases were added to the work of the bacteriological laboratory in 1900. 19

Facilities - Equipment. Unknown Date.

Vaccine facilities.

After systematic production of diphtheria antitoxin was begun at the Antitoxin and Vaccine Laboratory, acceptance by the medical profession was rapid. Production expanded from 1,700 doses in 1895 to over 33,000 in 1899. Deaths in Massachusetts decreased from 25% to 11% during the first year. In 1901 one local physician calculated that during the preceding seven years when antitoxin had been generally available, about 10,000 lives had been saved by its use.20

A diphtheria epidemic in 1900-01 strained the already taxed resources and quarters of the laboratories at the Bussey Institution. It became evident that the State Board of Health needed to take a more official role, allowing for more stable and sustainable preparation of antitoxin. At the same time a problem regarding the preparation and distribution of vaccine lymph was facing the State Board of Health. This prophylactic substance had, to this point, largely been produced by a number of parties outside of the state with little control or oversight creating a number of problems. It was determined that the only solution was for the State itself to assume responsibility for production and distribution of the lymph. 21

Biologics Building - AV  Laboratory.

Biologics Building – AV Laboratory.

The Legislature passed a bill in 1903 authorizing the State Board of Health to produce and distribute antitoxin and vaccine lymph. The Corporation of Harvard University in conjunction with the State agreed to use a portion of the land of the Bussey Institution adjoining the Arnold Arboretum to expand and build suitable laboratory space where this newly

Construction of New Wing 1927

Construction of New Wing. 1927.

authorized preparation of diphtheria antitoxin and animal vaccine could be carried out. The new building was completed in July 1904, with the first lot of antitoxin being issued in September. Production and distribution of smallpox vaccine soon followed, beginning in 1904. However, this new building would also quickly be outgrown, and two story additions were made to both the laboratory and animal buildings in 1927.22

 

Invitation to Opening of New Laboratory Building. Tuesday, December 13, 1927.

Invitation to Opening of New Laboratory Building. Tuesday, December 13, 1927.

In 1907 the Legislature further clarified the role the State Board of Health in regards to communicable diseases. New legislation mandated that the State Board of Health was responsible for making bacteriological examinations for diagnosis, investigating the sources of infections, and the free distribution of sera, vaccines and other prophylactic agents. It also required physicians and sufferers to report certain diseases dangerous to public health within twenty-four hours. 23

Division of Biologic Laboratories in the early 20th century

On July 7, 1914, the State Department of Public Health was created, replacing the old Board of Health. The divisions first organized included: Administration, Sanitary Engineering, Water and Sewage Laboratories, Food and Drugs, Communicable Diseases, and Hygiene. Additionally, all the laboratories, including the Antitoxin and Vaccine Laboratory and Diagnostic Laboratory were organized into the Division of Biologic Laboratories.

Photo from Commonhealth Vol. 2 N.1 - 1954 p21

Pipetting serum used in Hinton test at Wassermann Lab. From Commonhealth p21. 1954

In 1915 the Wassermann Laboratory, under Dr. W. A. Hinton as Assistant Director, was established as a unit of the Division of Biologic Laboratories. The Wassermann Laboratory had originally be established through the Department of Neuro-Pathology at the Harvard Medical School for the purposes of using Wassermann tests, an antibody test for syphilis, to diagnose mental illness. The laboratory oversight and functions were transferred from Harvard to the State Department of Public Health when Dr. Allen J. McLaughlin, the first Massachusetts Commissioner of Public Health, sponsored legislation whereby free tests for syphilis were made available to all citizens of Massachusetts. The Wassermann Laboratory remained part of the Division of Biologic Laboratories until 1944.24

Dr. Smith resigned as director in 1914 to join the Rockefeller Institute and the directorship was filled by Milton J. Rosenau, M.D., Professor of Preventive Medicine at Harvard Medical School and formerly Director of the Hygienic Laboratory, U.S. Public Health Service. Rosenau carried the laboratory through six difficult years, from the outbreak of World War I, with its critical shortages of personnel and supply, into the post war period of growth.25 Rosenau served as Director of the newly formed Division of Biologic Laboratories until 1920 when Dr. Benjamin White, formally with the New York City Laboratories became the first full-time director of the Division of Biologic Laboratories.

FDA License No.64 issued to the Massachusetts Public Health Biologic Laboratories,  dated August 20, 1996. (reissue after name change of original 1917 license.)

FDA License No.64 issued to the Massachusetts Public Health Biologic Laboratories, dated August 20, 1996. (reissue after name change of original 1917 license.)

FDA License No.64 issued to the Antitoxin and Vaccine Laboratory, Department of Public Health, Commonwealth of Massachusetts dated July 27, 1923. (reissue after name change of original 1917 license.)

FDA License No.64 issued to the Antitoxin and Vaccine Laboratory, Department of Public Health, Commonwealth of Massachusetts dated July 27, 1923. (reissue after name change of original 1917 license.)

Dr. Rosenau applied to the Public Health Service in 1916 for a Federal License to ship biologic products in interstate commerce.  Federal License No. 64 was first granted in 1917 for diphtheria antitoxin, vaccine virus, and bacterial vaccine from the typhoid bacillus. There have been many subsequent amendments for additional products and reissues for name changes. Dr. Rosenau did not initially recognize licensure as being significant, but it has proved to have far-reaching consequences in the subsequent history of the Laboratories. The legal privilege of selling surplus products out-of state provided an opportunity for the Laboratory to make a small profit. The state was also then able to dispose of excess supplies of biologics to other areas in need. If less concrete, a greater significance to licensure was the relationship the Laboratory formed with the Hygienic Laboratory (later the National Institute of Health). This allowed the Antitoxin and Vaccine Laboratory to gain immeasurable advice, knowledge, assistance, and increase in standards for all aspects of biologics production. Under the direction of Dr. White, the privileges and implementation of the Federal License was formally recognized when in 1921 the Massachusetts Legislature authorized the sale of surplus products.26

Milton Rosenau, Bela Schick, Benjamin White. 1923.

Benjamin White, Milton Rosenau, Bela Schick. 1923.

Diphtheria Toxin for Schick Test Tuck - Package design and order approval by James McComb. September 20, 1957

Diphtheria Toxin for Schick Test Tuck [individual product boxes] – Package design and order approval by James McComb. September 20, 1957

Diphtheria antitoxin remained an important component of the Laboratories’ research and products. Demonstrations of the Schick test, which was used to determine prior exposure to diphtheria and the need for vaccination, began in 1915 and distribution of Schick outfits commenced in 1917. The Schick test was based on the work of Bela Schick, who developed the test to determine if a person had some immunity to diphtheria. He reasoned that the injection of a very small amount of diphtheria toxin under the skin would produce a reddening and slight swelling at the site. If such a reaction occurred, it indicated that the patient had not previously been exposed to diphtheria. A lack of reddening of the injection area indicated that the patient had previously been exposed to diphtheria and therefore had immunity to it. Having already developed immunity eliminated the need for treatment, saving precious antitoxin for those without immunity.27

In 1922-23 "Captain" produced enough Antitoxin to protect 86,000.

In 1922-23 “Captain” produced enough Antitoxin to protect 86,000.

Additional advancement occurred in the 1920s and 1930s under the direction of Dr. White. Standards within the laboratory began to conform more closely to those of the National Institute of Health (originally known as the Hygienic Laboratory, but changed to the National Institute of Health in 1930) and there were significant improvements in technical equipment. Refinements in production methods included the ‘washing’ of typhoid vaccine which reduced the number of unfavorable reactions. Other investigative activity resulted in improved methods of bleeding horses and improved methods of producing smallpox vaccine. Work on pneumonia serum was of particular note. A 1931 state wide pneumonia study was undertaken after refinement of pneumonia serum and accumulating evidence for its clinical usefulness. Significant quantities of refined type I and II serum were prepared and distributed through depots statewide. The results of the Pneumonia Control Study, lasting through 1935, showed that the case fatality rate for most of the commoner types of pneumonia could be cut in half by means of adequate serum therapy.28

Dr. Reagh (white coat) demonstrating Vaccination on Calf

Dr. Reagh demonstrating vaccination on calf to medical students.

From the early days of the Antitoxin and Vaccine Laboratory, teaching was considered an important part of its functions. Dr. Smith and Dr. Rosenau brought their students from Harvard Medical School to the Laboratory for instruction, even though there was no specific course offered in laboratory immunology. The first scheduled courses given at the Laboratory began in 1923 in conjunction with the recently founded Harvard School of Public Health. This first course, Applied Immunology, was taught by Dr. White and Dr. Elliot Robinson.

Dr. Reagh talking to Medical Students while demonstrating vaccination on a Calf

Dr. Reagh demonstrating vaccination on calf to medical students.

 Soon after, arrangements were made with other schools, such as Simmons College, for the training of students in practical public health laboratory methods. Each of the early directors also served on the faculty of Harvard Medical School, playing valuable roles in medical education, but also shedding light on to the problems of public health for other faculty and medical professionals. Collaboration with Harvard Medical School also lead to a series of new biologic products. Work with scientists from the Department of Bacteriology lead to a new serum for the treatment of meningitis in 1927 and an anti-typhus serum in 1932.29

In 1934 Dr. White resigned because of ill health and Elliot S. Robinson, M.D., Ph.D., then Assistant Director, became Director. Under Dr. Robinson’s direction noteworthy advancements were made in achieving high yields of diphtheria toxin by production using defined pepton-free media. As well, an emphasis was placed on pneumonia serum studies. Significantly, a new source of antibodies, derived from human tissues, and free from the antigenic reaction of a foreign source, was developed by Dr. Charles F. McKhann of the Harvard Medical School. He found a placental extract for the prevention and modification of measles. These antibodies, produced and distributed from 1934 to 1944, were the first products derived from human blood to be distributed by the laboratory.30

The Massachusetts Blood and Blood Derivatives Program and Post WWII

In 1942 Dr. Robinson entered the Army and Geoffrey Edsall, M.D. became Acting Director until 1947, and Director from 1947-1949. During this period and immediately post war, studies directed toward the manufacture of additional products and the addition of the Blood Laboratory became a primary focus. The Massachusetts Blood and Blood Derivatives Program and the Blood Laboratory were authorized by the Legislature in July 1945. Because of the highly technical nature of processing and distributing blood and blood products, a special addition was added to the Biologic Laboratories building on the Bussey grounds in 1946. 31

Fractionation Area B134 1950

Fractionation Area B134. 1950.

Bob Kelly in Fractionation Area B134 1950

Bob Kelly in Fractionation Area B134. 1950.

 

The Massachusetts Blood and Blood Derivatives Program was a reaction to the expanded importance of and increased technical knowledge about blood transfusion, including the war time medical experience which showed the parts, or “fractions” of plasma to be of great medical value.32 The program was designed to collect voluntary blood donations for the processing of blood and whole blood, blood plasma and plasma fractions, and for the free distribution of products for these processes throughout the state. The Massachusetts Blood Program was unique in that it was the first comprehensive statewide blood program. Other states had undertaken the provision of blood plasma, and some counties and cities developed whole blood banks. Only the Massachusetts Blood Program included these as well as the processing and distribution of whole blood, red blood cells, blood plasma and the fractions of blood plasma without charge. The second phase of this program collected blood to be used in fractionation. 33

Control testing was begun in 1946 for the Plasma Fractionation Commission. The American National Red Cross utilized the Blood Laboratory from 1948-1951 as a processing lab and pilot plant for work being done by Dr. Edwin J. Cohn at the Harvard University Laboratory of Physical Chemistry. Dr. Cohn developed new fractionation methods which were evaluated at the Biologic Laboratories and subsequently adopted by blood fractionation laboratories throughout the world.34 Additionally, a “bloodmobile” program was developed to aid in the procurement of blood. This program ran from 3 December 1945 to 31 May 1947, during which time its two bloodmobiles visited 153 communities, held 236 clinics, and registered 19,204 blood donors.35

Bloodmobile 1947

Bloodmobile. 1947.

Bloodmobile Staff 1947

Bloodmobile Staff. 1947.

 

The 1940s and post-war focus was not solely on blood products. In 1941, the Biologic Laboratories introduced a tetanus vaccine. A pertussis vaccine followed in 1949. The most notable achievement, however, was the 1950 introduction of the first combination vaccine, the “triple vaccine”, that was made available for general use in children for immunization against pertussis, diphtheria, and tetanus. 36

Reorganization

The Antitoxin and Vaccine Laboratories were administratively separated from the Diagnostic Laboratory and the Wassermann Laboratory in 1944. They were placed in the Division of Communicable Diseases. However, almost all services were still located at the facilities on the Bussey Institution grounds. Dr. Edsall resigned in 1949 to become Professor of Microbiology at Boston University School of Medicine. He was succeeded by James A. McComb, D.V.M., the former Assistant Director, who became Acting Director in 1949 and then Director in 1955. 37

Johannes Ipsen Superintendent State Laboratory Institute

Johannes Ipsen Superintendent State Laboratory Institute.

In 1951, the reorganization was solidified and formalized with the formation of the Institute of Laboratories within the Department of Public Health, with Johannes Ipsen, M.D., M.P.H., as Superintendent. Under this organization, the Division of Biologic Laboratories consisted of two parts. The first, the Antitoxin and Vaccine Laboratories, was responsible for manufacturing and distributing a variety of biologic products to Boards of Health and physicians throughout Massachusetts. The second was the Blood Laboratory, responsible for manufacturing and distributing human albumin and human serum globulin for Massachusetts under a contract with the American Red Cross. Federal License No. 64, first issued in 1917, was formally reissued to the Biologic Laboratories as “The Massachusetts Public Health Biologic Laboratories”. All functions under the Division of Biologic Laboratories, including the Antitoxin and Vaccine Laboratories, were known as the Massachusetts Public Health Biologic Laboratories or, simply, the Biologic Laboratories. 38

The Biologic Laboratories continued to maintain a goal of teaching and research. In 1951 Dr. Ipsen inaugurated a Harvard School of Public Health course, ‘Advanced Laboratory Work in Applied Immunology’. In the course the student chose a portion of the work done at the laboratory, such as antitoxin production, familiarized himself with it and explained the method to the rest of the class at group conferences. The Laboratories maintained close relationships with many other local teaching and research institutions, with cooperative investigations being carried out throughout its existence. The Laboratories also received visitors from many countries who came for training in some aspect of biologics production.

Toxin. 1961.

Toxin. 1961.

The Biologic Laboratories continued to expand research, products and amount of material produced. For example, in 1962 the Biologic Laboratory became the first state laboratory to produce and distribute tetanus immune globulin made from human blood plasma. It also produced and distributed over 2 million doses of biologic products for the control of measles, pertussis, tetanus, diphtheria, smallpox, tuberculosis, hepatitis, rubella and typhoid fever, as well as 150,000 ampoules of silver nitrate solution for prevention of gonorrheal ophthalmia.39

Filling. Unknown Date.

Filling.

Dr. McComb retired in 1967, and was succeeded by Dr. Morton Madoff, who served as Director until 1970. Dr. Madoff was followed by Dr. George Grady in 1970. Dr. Grady served as Director until 1977. During the 1960s and 1970s, the Biologic Laboratories continued to develop, improve and advance practices and products. Many were advances on the traditional products that were the foundation of the Laboratories, including combination diphtheria, tetanus and pertussis vaccines. However, Biologic Laboratories also began investigating new products. This started a new era of immune globulins. These contain high levels of antibodies to specific infectious agents and are crucial in preventing or treating infections in high-risk children.40 Immune globulins are only required for a small number of children and were not as attractive for development by commercial companies. The first was the Tetanus Immune Globulin produced in 1962, and soon after came an Rh Immune Globulin in 1970, Hepatitis B Immune Globulin in 1972, Varicella Zoster Immune Globulin (VZIG) in 1981, CytoGam in 1990, and RespiGam in 1995. 41

State Laboratory Building and Bussey Building 1972

State Laboratory Building and Bussey Building. 1972.

A replacement for the old, ever expanding and renovated Bussey Institution building was completed in 1974. The land on which the Bussey Institution stood, and other adjacent land necessary for the new facilities, was sold to the State of Massachusetts by the Harvard Corporation. The relationship between Harvard and the Biologic Institute had been becoming more distant for years.

State Laboratory Building 1970s

State Laboratory Building 1970s

While many Biologic Laboratory employees continued to teach or have other relationships with Harvard, the selling of the Bussey Institution property saw the end of the formal relationship between the two. The new building, an eight-story structure in Jamaica Plain, housed the State Institute of Laboratories, including parts of the Division of Biologic Laboratories. It was designed to provide maximum functional laboratory space. Inevitably, laboratory equipment innovations outpaced the design and were soon burdening the building’s original electrical and ventilation systems. 42 Dr. George Wright became Director upon the retirement of Dr. Grady in 1977 and was followed by Dr. George Siber in 1983. Siber served as Director from 1983 until 1996.

In 1994, the centennial of the Massachusetts Public Health Biologic Laboratories was celebrated, starting from 1894 when it was the Antitoxin and Vaccine Laboratory run by Joseph Goodale in the State House. Even after 100 years, the laboratories had continued and expanded upon its original mission  by distributing childhood vaccines free of charge throughout Massachusetts via a decentralized network involving 350 local Boards of Health.

Staff Photo. 1994

Staff Photo. 1994.

 

MassBiologics of the University of Massachusetts Medical School and a new century

Vaccine Production. 1996

Vaccine Production.

In 1997, the State Legislature transferred oversight of the Massachusetts Public Health Biologic Laboratories from the Massachusetts Department of Public Health to the University of Massachusetts Medical School (UMMS). This began scientific collaborations, technology management and partnerships for the development of products to benefit patients.  After Dr. Siber left the lab in 1996,  Dr. Jeanne Leszczynski served as Acting Director, until Dr. Donna Ambrosino became Executive Director in 1997 and oversaw this transition. She served in this role until 2012. Ambrosino also oversaw the rebranding of the Massachusetts Biologic Laboratories to MassBiologics in 2006. Other new collaborations also began to form. MassBiologics began work with the National Institutes of Health in 2003 to discover a protective Monoclonal Antibody against SARS. Work was also begun in the early 2000s on C. difficile monoclonal antibodies to combat this devastating hospital acquired infection. 43

Letter dated November 15, 2002 to Dr. Jeanne Leszczynski from Stephen V. Reeves - Brigadier General, USA, Program Officer for Chemical & Biological Defense - in recognition and thanks for work done by MBL following the events of September 11, 2001.

Letter  to Dr. Leszczynski from Stephen V. Reeves. 2002.

The Laboratories also faced challenges during this period. Dr. Jeanne Leszczynski and all at the Massachusetts Biologic Laboratory were recognized for their efforts in responding to the tragic events on September 11, 2001. According to a letter from Brigadier General Stephen V. Reeves, the Laboratory was committed to helping the nation by developing and implementing a concise strategy to manufacture Vaccinia Immune Globulin-Introvenous (VIG-IV). This and other achievements reinforced the Laboratory’s growing and invaluable contributions leading into the 21st century.

The beginning of the 21st century had seen dramatic growth in staff, research, and production needs. The staff grew by 300 people and new products were developed, including one in conjunction with the pharmaceutical company Merck. To meet the growing demand and provide significant improvements in equipment and facilities, MassBiologics opened a new facility in 2005 with state-of-the-art aseptic filling and monoclonal antibody manufacturing capability, both of which were in high demand due to limited capacity throughout the United States. This allowed MassBiologics to continue to fill its own products as well as offer this limited resource for both private and public needs. A second facility next door was opened shortly after. By summer 2013, all functions of MassBiologics were completely moved from the Jamaica Plain facilities to the new buildings. 44

Skanska Construction Ariel Photo 2004

Skanska Construction Aerial Photo. 2004.

Mark S. Klempner, MD, became the Executive Vice Chancellor for MassBiologics of the University of Massachusetts Medical School in 2012 after Donna Ambrosino left to work with Visterra. Dr. Klempner joined MassBiologics from the Boston University School of Medicine, where he served as Associate Provost for Research, Conrad Wesselhoeft Professor of Medicine, and the founding director of the National Emerging Infectious Diseases Laboratories (NEIDL).

MassBiologics is now the only publicly operated, FDA-licensed, vaccine manufacturing facility in the country still operated by a state government agency. Currently MassBiologics continues to support a mission of discovering and developing products that will significantly improve public health. This now is expanding the historical legacy products to include orphan products, which are often less researched but are important for smaller patient populations due to limited incidence of disease. Additionally, MassBiologics has been supporting outreach of information, research, and products to developing nations with limited resources and unique needs. For example in 2013 MassBiologics donated over one million doses of tetanus and diphtheria vaccine to global NGO Project HOPE which will help tens of thousands of people in the Dominican Republic, Kyrgyzstan and Tajikistan receive vaccines. 45

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The vast majority of information for this history and the timelines came from the archival records at Harvard Medical Library, Francis A. Countway Library of Medicine (Records of the Laboratories, 1930-1959 (bulk). Massachusetts. Department of Public Health. HOLLIS 000603614. Harvard Medical Library, Francis A. Countway Library of Medicine, Boston, Mass.). Other records are located in the archival material at MassBiologics.

Please also view Commonhealth and other Publications in the image gallery which were used and generally referenced in this history and the timelines.

Bibliography

The American Society for Microbiologists. The History of Microbiology in the North-East Branch of The American Society for Microbiologists. Boston.(1970).

Bloom, Barry R. and Paul-Henri Lambert, eds.  The Vaccine Book.  Boston: Academic Press, 2003.

Cohn, Edwin J. The University and the Biologic Laboratories of the State of Massachusetts: A Short History. Harvard Medical Alumni Bulletin (April 1950).

Committee for the Study of the Future of Public Health. A History of the Public Health System in The Future of Public Health, Board on Health Care Services, Institute of Medicine, (1988).

Edsall, Geoffrey. The Massachusetts Blood and Blood Derivatives Program. Proceedings of the new York State Association of Public Health Laboratories 27, no. 2 (1948): 51-57.

Edsall, Geoffrey. The Massachusetts Institute of Laboratories. Massachusetts Physician 22, no. 4 (December 1963).

Halstead, Scott B., and Bruce G. Gellin. Immunizing Children: Can One Shot Do It All? Medical and Health Annual Encyclopedia Britannica (1993).

Hsu, Jennifer L. A Brief History of Vaccines: Smallpox to the Present. South Dakota Medicine (2013): 33-37.

Moore, Loren D., Geoffrey Edsall, and Vlado A. Getting. The Massachusetts Blood and Blood Derivatives Program. The Journal of the American Medical Association 135 (November 1, 1947): 548-51.

Mumford, Emily. Massachusetts State Laboratory Institute: A Modern Blend of Public Health and Academia. Lab Matters 3 (2003).

Murphy, Robert F. Public Health Trails in Massachusetts: A History and Guide. Jamaica Plain, MA: Massachusetts Public Health Association. Massachusetts Department of Public Health, 1988.

Rosen, George. A History of Public Health. Expanded Edition. Baltimore: The Johns Hopkins University Press, 1993.

Schultz, Myron. Photo Quiz: Theobald Smith. Emerging Infectious Diseases 14, no. 12 (December 2008): 1940-42.

White, Benjamin. “Smallpox and Vaccination.” Boston Medical and Surgical Journal 188, no. 15 (April 12, 1923): 523-30.

A Brief History of the Biologic Laboratories of the Massachusetts Department of Health. Unpublished manuscript in the MassBiologics archives. (1974).

The Commonhealth: 75th Anniversary of the Massachusetts Department of Public Health. Boston: The Massachusetts Department of Public Health, 1944.

Records of the Laboratories, 1930-1959 (bulk). Massachusetts. Department of Public Health. HOLLIS 000603614. Harvard Medical Library, Francis A. Countway Library of Medicine, Boston, Mass.

Vaccines and Immunizations. Centers for Disease Control, n.d.. <http://www.cdc.gov/vaccines/>.

MassBiologics archives.

Demonstration of Optimal Incubation Temperature. Unknown Date.

Demonstration of Optimal Incubation Temperature. Unknown Date.

  1. Murphy, Robert F. Public Health Trails in Massachusetts: A History and Guide. Jamaica Plain, MA: Massachusetts Public Health Association. Massachusetts Department of Public Health, 1988.  (back)
  2. White, Benjamin. “Smallpox and Vaccination.” Boston Medical and Surgical Journal 188, no. 15 (April 12, 1923): 523-30.  (back)
  3. The Commonhealth: 75th Anniversary of the Massachusetts Department of Public Health. Boston: The Massachusetts Department of Public Health, 1944.  (back)
  4. Rosen, George. A History of Public Health. Expanded Edition. Baltimore: The Johns Hopkins University Press, 1993.  (back)
  5. Vaccines and Immunizations. Centers for Disease Control, n.d.. <http://www.cdc.gov/vaccines/>.  (back)
  6. Halstead, Scott B., and Bruce G. Gellin. “Immunizing Children: Can One Shot Do It All?” Medical and Health Annual Encyclopedia Britannica (1993).  (back)
  7. Vaccines and Immunizations. Centers for Disease Control, n.d.. <http://www.cdc.gov/vaccines/>.  (back)
  8. White, Benjamin. “Smallpox and Vaccination.” Boston Medical and Surgical Journal 188, no. 15 (April 12, 1923): 523-30.  (back)
  9. Bloom, Barry R. and Paul-Henri Lambert, eds.  The Vaccine Book.  Boston: Academic Press, 2003.  (back)
  10. Hsu, Jennifer L. “A Brief History of Vaccines: Smallpox to the Present.” South Dakota Medicine (2013): 33-37.  (back)
  11. Committee for the Study of the Future of Public Health. “A History of the Public Health System” in The Future of Public Health, Board on Health Care Services, Institute of Medicine, (1988).  (back)
  12. Records of the Laboratories, 1930-1959 (bulk). Massachusetts. Department of Public Health. HOLLIS 000603614. Harvard Medical Library, Francis A. Countway Library of Medicine, Boston, Mass.  (back)
  13. Rosen, George. A History of Public Health. Expanded Edition. Baltimore: The Johns Hopkins University Press, 1993.  (back)
  14. Cohn, Edwin J. “The University and the Biologic Laboratories of the State of Massachusetts: A Short History.” Harvard Medical Alumni Bulletin (April 1950).  (back)
  15. The American Society for Microbiologists. The History of Microbiology in the North-East Branch of The American Society for Microbiologists. Boston.(1970).  (back)
  16. Records of the Laboratories, 1930-1959 (bulk). Massachusetts. Department of Public Health. HOLLIS 000603614. Harvard Medical Library, Francis A. Countway Library of Medicine, Boston, Mass.  (back)
  17. Schultz, Myron. “Photo Quiz: Theobald Smith.” Emerging Infectious Diseases 14, no. 12 (December 2008): 1940-42.  (back)
  18. Cohn, Edwin J. “The University and the Biologic Laboratories of the State of Massachusetts: A Short History.” Harvard Medical Alumni Bulletin (April 1950).  (back)
  19. Records of the Laboratories, 1930-1959 (bulk). Massachusetts. Department of Public Health. HOLLIS 000603614. Harvard Medical Library, Francis A. Countway Library of Medicine, Boston, Mass.  (back)
  20. Records of the Laboratories, 1930-1959 (bulk). Massachusetts. Department of Public Health. HOLLIS 000603614. Harvard Medical Library, Francis A. Countway Library of Medicine, Boston, Mass.  (back)
  21. Records of the Laboratories, 1930-1959 (bulk). Massachusetts. Department of Public Health. HOLLIS 000603614. Harvard Medical Library, Francis A. Countway Library of Medicine, Boston, Mass.  (back)
  22. A Brief History of the Biologic Laboratories of the Massachusetts Department of Health. Unpublished manuscript in the MassBiologics archives. (1974).  (back)
  23. Records of the Laboratories, 1930-1959 (bulk). Massachusetts. Department of Public Health. HOLLIS 000603614. Harvard Medical Library, Francis A. Countway Library of Medicine, Boston, Mass.  (back)
  24. Records of the Laboratories, 1930-1959 (bulk). Massachusetts. Department of Public Health. HOLLIS 000603614. Harvard Medical Library, Francis A. Countway Library of Medicine, Boston, Mass.  (back)
  25. Records of the Laboratories, 1930-1959 (bulk). Massachusetts. Department of Public Health. HOLLIS 000603614. Harvard Medical Library, Francis A. Countway Library of Medicine, Boston, Mass.  (back)
  26. Records of the Laboratories, 1930-1959 (bulk). Massachusetts. Department of Public Health. HOLLIS 000603614. Harvard Medical Library, Francis A. Countway Library of Medicine, Boston, Mass.  (back)
  27. Rosen, George. A History of Public Health. Expanded Edition. Baltimore: The Johns Hopkins University Press, 1993.  (back)
  28. Records of the Laboratories, 1930-1959 (bulk). Massachusetts. Department of Public Health. HOLLIS 000603614. Harvard Medical Library, Francis A. Countway Library of Medicine, Boston, Mass.  (back)
  29. Cohn, Edwin J. “The University and the Biologic Laboratories of the State of Massachusetts: A Short History.” Harvard Medical Alumni Bulletin (April 1950).  (back)
  30. Cohn, Edwin J. “The University and the Biologic Laboratories of the State of Massachusetts: A Short History.” Harvard Medical Alumni Bulletin (April 1950).  (back)
  31. Cohn, Edwin J. “The University and the Biologic Laboratories of the State of Massachusetts: A Short History.” Harvard Medical Alumni Bulletin (April 1950).  (back)
  32. Edsall, Geoffrey. “The Massachusetts Blood and Blood Derivatives Program.” Proceedings of the new York State Association of Public Health Laboratories 27, no. 2 (1948): 51-57.  (back)
  33. Moore, Loren D., Geoffrey Edsall, and Vlado A. Getting. “The Massachusetts Blood and Blood Derivatives Program.” The Journal of the American Medical Association 135 (November 1, 1947): 548-51.  (back)
  34. A Brief History of the Biologic Laboratories of the Massachusetts Department of Health. Unpublished manuscript in the MassBiologics archives. (1974).  (back)
  35. Moore, Loren D., Geoffrey Edsall, and Vlado A. Getting. “The Massachusetts Blood and Blood Derivatives Program.” The Journal of the American Medical Association 135 (November 1, 1947): 548-51.  (back)
  36. Records of the Laboratories, 1930-1959 (bulk). Massachusetts. Department of Public Health. HOLLIS 000603614. Harvard Medical Library, Francis A. Countway Library of Medicine, Boston, Mass.  (back)
  37. Records of the Laboratories, 1930-1959 (bulk). Massachusetts. Department of Public Health. HOLLIS 000603614. Harvard Medical Library, Francis A. Countway Library of Medicine, Boston, Mass.  (back)
  38. Records of the Laboratories, 1930-1959 (bulk). Massachusetts. Department of Public Health. HOLLIS 000603614. Harvard Medical Library, Francis A. Countway Library of Medicine, Boston, Mass.  (back)
  39. Edsall, Geoffrey. “The Massachusetts Institute of Laboratories.” Massachusetts Physician 22, no. 4 (December 1963).  (back)
  40. MassBiologics archives.  (back)
  41. MassBiologics archives.  (back)
  42. Mumford, Emily. “Massachusetts State Laboratory Institute: A Modern Blend of Public Health and Academia.” Lab Matters 3 (2003).  (back)
  43. MassBiologics archives.  (back)
  44. MassBiologics archives.  (back)
  45. MassBiologics archives.  (back)

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