Tinnerholm v. Parke, Davis & Co., No. 315

• Court: United States Courts of Appeals. United States Court of Appeals (2nd Circuit)
• Writing for the Court: ANDERSON and FEINBERG, Circuit , and MANSFIELD
• Citation: 411 F.2d 48
• Parties: Eric R. TINNERHOLM, an infant under the age of fourteen years, by his Guardian ad Litem, Carl F. Tinnerholm, and Carl F. Tinnerholm, individually, Plaintiffs-Appellees, v. PARKE, DAVIS & CO., Defendant-Appellant.
• Decision Date: 23 May 1969
• Docket Number: Docket 32697.,No. 315

411 F.2d 48 (1969)

Eric R. TINNERHOLM, an infant under the age of fourteen years, by his Guardian ad Litem, Carl F. Tinnerholm, and Carl F. Tinnerholm, individually, Plaintiffs-Appellees,
v.
PARKE, DAVIS & CO., Defendant-Appellant.

No. 315, Docket 32697.

United States Court of Appeals Second Circuit.

Argued February 11, 1969.

Decided May 23, 1969.

411 F.2d 49

Jacob D. Fuchsberg, New York City (Richard E. Shandell, and Fuchsberg & Fuchsberg, New York City, on the brief), for plaintiffs-appellees.

William H. Hillier, Chicago, Ill. (Joseph M. Costello, and Costello, Ward, Tirabasso & Shea, New York City, R. R. McMahan, Chicago, Ill., and David C. Dethmers, Detroit, Mich., on the brief), for defendant-appellant.

Before ANDERSON and FEINBERG, Circuit Judges, and MANSFIELD, District Judge.^*

411 F.2d 50

ANDERSON, Circuit Judge:

This is an appeal by the defendant, Parke, Davis & Co., from a judgment in a personal injury action which held that Parke, Davis' biological product, Quadrigen, was defective and that the defect caused injuries to plaintiff Eric Tinnerholm, then 3 months old, which have left him permanently disabled, both physically and mentally. The District Court awarded total damages in the amount of $651,783.52. We hold there was no error.

On the basis of substantial evidence the trial court found that about noon on Saturday, November 28, 1959, the infant plaintiff, Eric Tinnerholm, then sound and healthy in body and mind, was inoculated by Dr. Gerald Feinberg with Quadrigen. On Tuesday morning, December 1, 1959, about 4:00 a. m., the child was found tangled up in his bedclothes and whimpering, but on being picked up and patted he quieted down and presumably went back to sleep. There was no indication of temperature at that time. Sometime later, between 6:30 and 7:00 a. m., the child's mother found him huddled under the covers, lethargic and bathed in perspiration. His temperature at that time was 108°, he was very white, his lips were blue, and he was limp. Dr. Feinberg was summoned, and he arrived about 7:30 a. m. He had the baby admitted to Huntington Hospital at 8:45 a. m. where the infant remained until December 18, 1959. During this time the baby developed recurrent convulsive seizures and paralysis of the right arm and leg. At the time of trial he was, and will remain, mentally retarded (with a mental age of five months) to a degree classified within the idiot-imbecile range; he is paralyzed in both right limbs and still suffers occasional seizures.

Quadrigen was developed by Parke, Davis as a quadruple antigen¹ product, combining pertussis (whooping cough) vaccine, with diphtheria and tetanus toxoids and with the Salk polio vaccine. In the early 1940's, a method of combining pertussis vaccine with diphtheria and tetanus toxoids into a triple antigent product (colloquially known as "DTP") had been devoloped. The Parke, Davis DTP was marketed under the trade name "Triogen."

Vaccines are intended to stimulate the production of antibodies in order to confer protection against disease by introducing an antigenic factor into the body of the recipient. In developing a vaccine in the cases of some infectious organisms, notably diphtheria and tetanus, it has been possible to isolate a soluble toxin or poison excreted by the bodies of these bacteria, and to inactivate this toxin with formaldehyde, thereby converting a toxin into what is called a toxoid. A toxoid preserves the ability to immunize against the disease by stimulating the production of antibodies in the recipient, although it has lost its own poisonous qualities.

In contrast, the bacterial organism which causes pertussis is so complex that it has been impossible to isolate and inactivate the toxin or poison. Since the ingredient in the pertussis bacteria which stimulates the production of protective antibodies has not been isolated, pertussis vaccine consists of whole pertussis bacteria, treated to remove their propensity to cause the disease, while preserving their ability to stimulate the production of protective antibodies.

Some fifteen or sixteen different antigens have been described in the pertussis organism, including an exotoxin, an endotoxin, a protective antigen, etc. One or more of these antigens confers protective ability; no one knows which one or what it is. In the production of the pertussis vaccine, the exotoxin is destroyed by heat, but the endotoxins inside the cell survive such treatment. Because of the complex nature of the pertussis bacteria and the inability to isolate the toxin in order to inactivate it, reactions to pertussis vaccine are not uncommon. There may be local reaction, such as soreness or

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tenderness at the site of the injection, and systemic (attacking the entire body) reaction such as fever and general discomfiture. Rarely, reactions associated with the disease itself, such as convulsions, high fever, or even brain hemorrhage and mental retardation occur

All vaccines require a preservative to keep them sterile; and one of the problems confronting Parke, Davis in the development of Quadrigen was the selection of an appropriate preservative to protect the final product from contamination. In the development of pertussis vaccines and indeed all other vaccines, up until the development of polio vaccine (licensed for distribution in 1956), the preservative universally used was merthiolate. The preservative used in Parke, Davis' Triogen had been merthiolate, but because merthiolate had a deleterious effect upon the polio virus in the Salk vaccine, a new preservative had to be chosen. The preservative ultimately selected by Parke, Davis (and according to Parke, Davis, all other manufacturers of quadruple antigen products) was benzethonium chloride (trade name Phemerol). Quadrigen was developed during 1957 and 1958 and was licensed for commercial distribution by the National Institutes of Health in the spring of 1959. The first commercial distribution took place July 10, 1959.

The findings of the court below in support of its conclusion that Parke, Davis is liable to plaintiffs-appellees may be summarized as follows:

1. "* * * by manufacturing Quadrigen in the method chosen by defendant, the chances of contracting an encephalopathy were enhanced,"² because:

2. "* * * the effect of the use of benzethonium chloride was to release the endotoxin from the bacteria cell into the fluid that was injected. One such endotoxin, the lipopolysaccharide, causes fever * * *"; and

3. "* * * the release of the endotoxin into the fluid injected into the infant plaintiff was the cause of the unusually high fever which, in turn, caused the severe and permanent brain damage."

The main thrust of appellant's appeal is directed toward a claimed lack of proof by the plaintiffs-appellees that the Tinnerholm baby's injuries were proximately caused by Quadrigen. The testimony of plaintiffs' expert witness, Dr. Joseph H. Lapin, a pediatrician, provided substantial support, however, for the chain of causation which the court found. Dr. Lapin qualified to testify as an expert on his testimony that he had been a practitioner in pediatrics for more than forty years, that he was Professor of Pediatrics at Albert Einstein Medical College and had written extensively "on various phases of whooping cough, the disease, method of treatment of the disease * * and immunization against it." It was his opinion that the benzethonium chloride caused the leaking of endotoxins from within the cell wall of the pertussis organism when maintained in a solution such as Quadrigen.³

There was also corroborating evidence to support the District Court's finding on

411 F.2d 52

this point in an article by Dr. Margaret Pittman, Pertussis Vaccine Testing for Freedom-from-Toxicity," published in Applied Microbiology, and included in appellant's evidence. Writing in 1965, Dr. Pittman said

"Recent work has shown that pertussis vaccine in DTP-P diphtheria-tetanus-pertussis-polio vaccine preserved with benzethonium chloride is unstable in potency * * *. This surface-acting preservative, no doubt, contributed to the greater toxicity of DTP-P * * by favoring the leaching of the toxin from the bacterial cell. It is well known that alkalinity favors lysis and thereby promotes toxicity * * *.

Merthiolate apparently acts as a stabilizer of potency *

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