# Appendix — New York State Department of Health v. Andrulonis > Briefs, arguments, decisions, and more. URL: https://www.frixlaw.com/law-library/documents/brief%3Amicro_IA40385017_1038%3A2 ## Record - **Collection:** Supreme Court brief - **Document type:** Appendix - **Published:** January 1, 1991 - **Citation:** 502 U.S. 801 ## Text EDITOR'S NOTE: THE FOLLOWING PAGES WERE POOR HARD COPY AT THE TIME OF FILMING. IF AND WHEN A BETTER COPY CAN BE OBTAINED, A NEW FICHE WILL BE ISSUED. v oo fF oon VOU, U.S, OO-1864 | Feed | IN THE Supreme Court of the United-Seales® | October Term, 1990 NEW YORK STATE DEPARTMENT OF HEALTH, Petitioner, against JOANNA ANDRULONIS, Individually and as Conservator of the Property of JEROME ANDRULONIS; UNITED STATES OF AMERICA; GLATT AIR TECHNIQUES, INC-:; GLATT GmbH; WISCONSIN ALUMNI RESEARCH FOUNDATION, INC.; WARF INSTITUTE, INC: RALTECH SCIENTIFIC SERVICES, INC.; RALSTON PURINA COMPANY; ELI LILLY AND COMPANY; and JOHN L. THOMPSON AND SONS COMPANY, Respondents. ON PETITION FOR A WRIT OF CERTIORARI TO THE UNITED STATES COURT OF APPEALS FOR THE SECOND.-CIRCUIT Appendix to Petition for a Writ of Certiorari ROBERT ABRAMS Attorney General of the State of New York, Attorney for Petitioner The Capitol Albany, NY 12224 (518) 474-6697 O. PETER SHERWOOD Solicitor General PETER H. SCHIFF Deputy Solicitor General MICHAEL S. BusKUS Assistant Attorney General Of Counsel Dated: May 31, 1991 THE REPORTER COMPANY, INC., Walton, NY 13856—800 252-7181—1991 (1064A—LC3-622) LIT Index to Appendix. . Opinion of the United States Court of Appeals, Sec- ond Circuit, Dated January 28, 1991.......... . Opinion of the United States District Court for the Northern District of New York, Dated December TEs ass eeu tnacek saehees -6e sae re oon . Opinion of the United States District Court for the Northern District of New York, Dated October 3, Scat cada eee eked ce cian veined . Order of the United States Court of Appeals for the Second Circuit Denying Petition for Rehearing, Perr er ep ererT rrr Tre . Order of the United States Court of Appeals, Second Circuit, Dated January 28, 1991. Issued as Man- ee ick ccc cabeddawauny ne . Amended Judgment of the United States District Court for the Northern District of New York, EOORNG EPOORENOT ED, TDS 2c ccc ccc ccc csevees . Judgment of the United States District Court for the Northern District of New York, Dated October Page Al A46 A390 A399 A401 A403 Al Opinion of the United States Court of Appeals, Second Circuit, Dated January 28, 1991. ANDRULONIS v. U.S. Cite as 924 F.2d 1210 (2nd Cir. 1991) Joanna ANDRULONIS, Individually and as Conservator of the Property of Je- rome Andrulonis, Plaintiffs—Appel- lees/Cross—Appellants, v. UNIYVED STATES of America, Glatt Air Techniques, Inc.; Glatt GmbH; Wis- consin Alumni Research Foundation, Inc.; Warf Institute, Inc.; Raltech Sci- entific Services, Inc., Ralston Purina Company; Eli Lilly and Company; and John L. Thompson and Sons and Com-_ pany, Defendants, United States of America, Defendant-Appellant/Cross—Appellee. UNITED STATES of America, Third- Party Plaintiff-Appellee, v. NEW YORK STATE DEPARTMENT OF HEALTH, Third-Party Defendant~Appellant. Nos. 61, 62 and 506, Dockets 89-6274, 90-6016 and 90-6028. United States Court of Appeals, Second Circuit. Argued Sept. 11, 1990. Decided Jan. 28, 1991. A2 Bacteriologist who contracted rabies while conducting laboratory experiment with rabies viral strain brought personal injury action along with wife against New York Department of Health, federal Government, and others. The United States District Court for the Northern Dis- trict of New York, Howard G. Munson, J., 724 F.Supp. 1421, entered judgment for bacteriologist. Cross appeals were taken. The Court of Appeals, George C. Pratt, Circuit Judge, held that: (1) failure of fed- eral government scientist to warn bacteriol- ogist of danger of working with rabies viruses rendered Government liable; (2) re- mand was required for redetermination of allocation of settlement; and (3) award of $2,417,238 for bacteriologist’s future custo- dial care was not clearly erroneous. Reversed in part and remanded and affirmed. Michael S. Buskus, Albany, N.Y., Asst. Atty. Gen. of the State of N.Y. (Robert Abrams, Atty. Gen. of the State of N.Y., Peter H. Schiff, Deputy Sol. Gen., Peter J. Dooley, Asst. Atty. Gen., of counsel), Alba- ny, N.Y., for third-party defendant-appel- lant NYS Dept. of Health. Wiliam G. Cole, Washington, D.C., Ap- pellate Staff Atty., Civil Div., Dept. of Jus- tice (Stuart M. Gerson, Asst. Atty. Gen., Dept. of Justice, Robert M. Greenspan, Staff Atty., Civil Div., Frederick J. Scullin, U.S. Atty. for the N.D.N.Y., of counsel), Washington, D.C., for US. A3 James D. Featherstonhaugh, Albany, N.Y. (Roemer & Featherstonhaugh, John R. Mineaux, of counsel), Albany, N.Y., for plaintiffs-appellees/cross-appellants. Before PRATT, MAHONEY and WALKER, Circuit Judges. GEORGE C. PRATT, Circuit Judge: Jerome Andrulonis contracted the dis- ease of rabies while conducting a labo- ratory experiment with a rabies viral strain. He became tragically ill and even- tually suffered serious and permanent brain damage, leaving him with the mental capacity of a four-year-old. He also suf- fered marked personality and behavioral changes as a result of dementia secondary to rabies encephalitis. Andrulonis’s mental incapacity and emotional instability are per- manent. The experiment, which was con- ducted under the supervision of Dr. John G. Debbie, a scientist employed by the New York State Department of Health (“NYS- DOH”), and observed by Dr. George M. Baer, a federal government scientist, took place in the state-operated Griffin Labora- tories just outside Albany, New York. Joanna Andrulonis, individually, and as conservator of the property of Jerome An- drulonis, her husband, brought this action against the United States of America and a number of nongovernmental defendants to recover damages for the severe injuries they have suffered because of the rabies. A4 The claim against the United States was, of course, brought under the Federal Tort Claims Act, 28 U.S.C. §§ 1346, 2671-2680 (“FTCA” or “the act”). The United States cross-claimed against the nongovernmental defendants and filed a third-party com- plaint for contribution against the State of New York. See N.Y. Civ.Prac.L & R. §§ 1401-1404. Before trial, the district court dismissed Joanna Andrulonis’s indi- vidual claims against the United States for failure to timely file the administrative claim required by the FTCA. Andrulonis v. United States, No. 19-CV-847, slip op. at 7 (N.D.N.Y. March 8, 1984); see 28 U.S.C. § 267Ka) and § 2401(b). Before the end of trial, plaintiffs, through a series of agreements, had settled with all of the nongovernmental parties for a total of $1,300,000. The settling parties agreed that $225,000 would be paid in satis- faction of the primary claims of Jerome Andrulonis and that $1,075,000 wou!d be paid in satisfaction of the derivative claims of Joanna Andrulonis. After a nonjury trial of the remaining unresolved FTCA claims of plaintiff Je rome Andrulonis against the United States and the contribution claims of the United States against NYSDOH, Judge Munson found the government liable in negligence for Jerome Andrulonis’s injuries and also found NYSDOH liable to the government on its contribution claim. In addition, con- lilt aa AS sidering the relative culpabilities of the set- tling private defendants, he found Eli Lilly and Company and John L. Thompson & Sons and Company responsible to the ex- tent of 5 percent and exonerated the other settling defendants. The court assessed damages in the amount of $6,424,641, in- cluding $2,417,238 for the future custodial care of Jerome Andrulonis, and appor- tioned them 30 percent to the United States, 65 percent to NYSDOH, and 5 per- cent to Lilly/Thompson. Andrulonis v. United States, 724 F Supp. 1421 (N.D.N.Y. 1989). Under section 15-108 of New York’s General Obligations Law, the United States was entitled, with respect to each settle ment, to a setoff for the greater of ‘‘(a) the amount stipulated in the settlement agree- ment, (b) the consideration paid for the release, or (c) the amount of the settling defendant’s equitable share of the dam- ages.” N.Y.Gen.Oblig.Law § 15-108. As noted earlier, Jerome Andrulonis had been allocated $225,000 of the proceeds of a settlement agreement with the private de fendants. Of this amount, Lilly/Thompson paid $100,000 and the other settling private defendants paid $125,000. Since defen- dants Lilly/Thompson had settled for an amount that was less than their equitable share, the district court reduced the award by 5 percent or $321,232, representing the proportionate culpability found against Lil- ly/Thompson. Since the district court A6é found no culpable conduct attributable to the other settling defendants, it reduced Jerome Andrulonis’s award by the actual dollar amount paid to him by those defen- dants—$125,000. This left the United States primarily responsible to Jerome An- drulonis for $5,978,409, subject to recover- ing from the state 68.42 percent (“/sths) of that amount, or $4,090,427, on its third-par- ty contribution claim. N.Y¥.Civ.Prac.L. & R. § 1402. BACKGROUND Given the complexity of this case, we must delve with considerable detail into the circumstances surrounding Andrulonis'’s ill- ness and the experiment that caused it. It is unfortunate that such a long and techni- cal narrative must follow, but a full under- standing of the district court’s decision can- not be reached without careful considera- tion of the virus used, the disease it causes, and the methods of researching rabies used at the time the tragedy occurred. The following facts include those that the dis- trict court found rabies experts reasonably should have known about the disease. Since the district court’s findings are not clearly erroneous, we must accept them as true. Fed.R.Civ.P. 52(a). Jerome Andrulonis was a 34-year-old senior bacteriologist employed to conduct rabies research in NYSDOH’s Griffin Labo- ratory under the supervision of Dr. John G. A7 Debbie, a research scientist employed by NYSDOH as head of the rabies labs at Griffin. Dr. Debbie was persuaded to con- duct rabies research by Dr. George M. Baer, Chief of the Viral Zoonosis Branch and Rabies Laboratory at the Center for Disease Control (“CDC”), a division of the United States Department of Health and Human Services. The research being done by Dr. Debbie and Andrulonis was part of a joint effort by the NYSDOH and the CDC to develop a technique for mass im- munization of wildlife in the hope of eradi- cating the incidence of rabies transmitted to man. To realize this goal, Dr. Debbie was working on an ora! vaccine that could be distributed to wildlife. Because the initial virus strains tested by Dr. Debbie could not withstand the destructive stomach acids of some species, he decided, upon the advice of Dr. Baer, to try a method called “enteric coating.” Under this method, a pill, or nonpareil, would be coated first with the rabies virus, then a protective coating, and finally, a shell that could withstand stom- ach acids but would disintegrate in the animal's intestines, allowing the virus to be absorbed there. The virus would not cause development of the disease, but would cause the body to produce antibodies that would protect the animal against subse- quent exposures to the rabies virus. Dr. Debbie contacted the coating depart- ment at defendant WARF Institute, Inc. (“WARF"”), which on March 30, 1976, sent a A8 representative to demonstrate a coating technique using a Uni-Glatt machine, man- ufactured by defendant Glatt GmbH and distributed by defendant Glatt Air Tech- niques, Inc. (“the Glatt defendants”). The Uni-Glatt machine operated by suspending nonpareils in a column of upflowing air confined in a tube. The suspended nonpar- eils would then be coated with aerosolized virus. When the machine operated, the aerosol itself could be seen inside the tube, al- though any leakage into the atmosphere was not visible to the unaided eye and left no trace outside the machine. However, nonpareils would occasionally leak out of the machine into the lab environment, and the final coating process created a visible reddish dust that escaped from the machine leaving the entire laboratory coated with the reddish dust after each’run. During the initial demonstration run, it became apparent to everyone in the laboratory that the machine was not airtight. Despite this, the only precautions required of the Jab workers were the wearing of a mask and gloves, and the maintenance of a high level of rabies antibodies in their blood systems through periodic inoculations with a rabies vaccine manufactured by defendant Eli Lil- ly and Company and distributed by defen- dant John L. Thompson & Sons and Compa- ny (“Lilly/Thompson’”’). Funding for the Uni-Glatt rabies experi- ments was provided by the federal CDC. In exchange, Dr. Debbie was to provide the ea ee A9 CDC with some of the coated nonpareils prepared in the course of the Uni-Glatt experiments. Beyond providing the fund- ing, CDC officials made no attempt to di- rect the day-today operations of the project, to devise any protocol, or otherwise to control the research efforts at Griffin. Dr. Debbie used the Uni-Glatt in two more experiments in July and September of 1976, both times using a rabies viral strain prepared by Andrulonis with a titer of 6. “Titer” is the term used to indicate a stan- dardized measure of a substance’s ability to produce a defined result. With respect to the rabies virus, the titer measures the ability to kill laboratory mice after intracer- ebral injection of a solution containing that virus. The titer is expressed exponentially. During the July and September runs, heat generated by the machine killed most of the viral particles and reduced the titer of the vaccine to 1, a level that produced irregular serum antibody levels. To over- come this problem, Dr. Debbie asked Dr. Baer to prepare a viral strain with a higher titer. Dr. Baer, in keeping with CDC’s general practice of preparing and supplying viral strains to many private and state-operated labs, prepared a relatively unknown viral strain, ERA-BHK/21, with a titer of 8.1. This was derived from a commercially available ERA vaccine, but it had a much higher concentration of viral particles and was less susceptible to heat. While the basic ERA vaccine had several known fa- A10 vorable characteristics, the particular char- acteristics of ERA-BHK/21 were relatively unknown to most scientists in March of 1977, since it was several times removed from the commercial ERA vaccine. ERA- BHK/21 was created through a process calied “passaging” that had the potential for producing unpredictable changes in characteristics. The handful of studies on ERA-BHK/21 had reported mixed results about pathogenicity, and no one knew with certainty whether man was susceptible to developing the disease of rabies as a result of infection from this ERA-derived virus strain. The CDC generally recommended, as a precaution, that the virus be treated as pathogenic to man. Several other factors, in addition to un- certainty about the characteristics of ERA-BHK/21, complicated the situation. People usually contract rabies through the saliva of an infected animal during a bite. Infection through aerosol exposure, the route of infection in Andrulonis’s case, is much more rare and was not even recog- nized until the late 1950s or early 1960s. Not all exposures lead to infection; not all infections lead to the disease. Regardless of the route of infection, the chances of getting the disease after exposure are closely related to the quantity of viral par- ticles, or the dose, to which a person is exposed. When the exposure is aerosol in nature, the dose is probably the single most important factor in determining whether the virus will cause the disease. All In addition, the pathogenesis of the dis- ease is very different between the airborne and the bite routes. With a bite, the area is bathed with blood, so if the bitten person has been immunized, the antibodies in the blood have an opportunity to neutralize the virus before it can invade the central nerv- ous system. In contrast, when airborne, the virus hits olfactory nerves that are exposed to the environment and that have as their only protection the nasa] mucosa. Ordinarily, olfactory nerves do not have significant contact with antibodies in the blood stream. Thus, even if a person has been immunized, the antibodies do not have a chance to come into contact with the infected nerves, unless the vaccine is able to produce antibodies in the mucosa. In 1976-1977, when Andrulonis was ex- posed to the virus, it was not known wheth- er the Lilly vaccine he and the other lab technicians were using could protect against aerosol exposure. Lilly did not conduct studies even after becoming aware of the possibility of aerosol exposure, nor did it warn users of the potential that its vaccine might not protect against aerosol exposures. In light of the meager then-ex- isting knowledge about aerosol exposures and vaccines, the district court found that safe lab practices mandated avoidance of all aerosol exposures and that virus-laden aerosols should not even be created unless absolutely necessary for the research goal, and in those cases, the aerosols should be physically contained using one of the readi- ly-available containment systems. Al2 On the evening of March 28, 1977, Dr. Baer personally delivered the specially pre- pared ERA-BHK/21 virus strain with a titer of 8.1 to Dr. Debbie at Griffin. He informed Dr. Debbie of the titer and Dr. Debbie relayed this information to the oth- er lab workers the next morning. No dis- closure was made about how the strain was prepared or how many times it was pas- saged. No safety inspection was made of the lab premises, but this was consistent with ordinary CDC practice in similar cir- cumstances. The tragic experiment took place the pext day, March 29th. With Dr. Baer ob- serving, Dr. Debbie started the machine and began circulating the nonpareils in the glass tube. The aerosolization process us- ing the ERA-BHK/21 virus lasted over an hour, during which time both Dr. Debbie and Andrulonis worked in close proximity to the machine. The process required close attention, and usi:s!ly Andrulonis or Dr. Debbie sat near the machine and tapped the glass tube with the handle of a screw- driver to prevent nonpareils from sticking together. Commonly, Andrulonis would place his face within six to twelve inches of the tube while tapping it, and would remain that close to the machine for minutes at a time throughout the run. Dr. Baer also observed the process closely and, at times, was within a foot of the machine. Al3 Dr. Baer left on the evening of March 29th. Another coating run was done the next day, but this time using a viral strain prepared by Andrulonis that had a titer of 5.5. The district court found on adequate, al- beit disputed, evidence that Andrulonis had contracted rabies during the March 29, 1977, experiment that Dr. Baer observed. To begin with, Andrulonis’s only contact with the virus was at work. On the job, it was unlikely that he got rabies from rou- tine procedures; more likely, he contracted the disease from an “unusual” exposure. Of his four possible exposures between March of 1976 and March of 1977, compel- ling evidence points to the March 29, 1977, experiment as the cause of his illness, which first appeared in Apri of 1977. As to the other exposures, in March, July and September of 1976, a six-month incubation period is within the realm of possibility, but the average is 20-60 aays. Only 14 per- cent of the incidents of rabies have an incubation period greater than 90 days re- gardless of the method of exposure. Since this was an aerosol exposure, the incuba- tion period was more likely to be shorter than longer. Another unusual aspect of the March 29th experiment was its use of the most highly concentrated virus with a titer of 8.1. This means there were 100 times more viral particles than a 6.0 titer and 400 times more viral particles than a 5.5 titer. Al4 Further, the viral strain used in the March 29th experiment was more resistant to the heat generated by the machine. Finally, the district court accepted the opinion testi- mony of various experts ‘ho stated with a reasonable degree of medical and scientific certainty that Andrulonis contracted the disease of rabies as a result of exposuré in the March 29th experiment. The district court found the government liable under New York law on three inde- pendent theories of negligence: supplier’s duty to warn, non-negligent creation of a hazard, and negligent entrustment. The government challenges each of these hold- ings. The district court also held that the discretionary function exception of the Fed- eral Tort Claims Act was inapplicable to this case, and both the government and NYSDOH appeal from this holding. In addition, the government and NYS- DOH appeal from the district court’s ap- proval of the allocation of settlement pro- ceeds; NYSDOH appeals the district court’s apportionment of damages; and fi- nally, Jerome Andrulonis cross-appeals from the court’s determination of the cost of future custodial care. Al5 DISCUSSION We first turn to the question of whether the discretionary function exception pro- tects the government from suit in these circumstances. If the exception were to apply in this case, it would bar this action against the government, and we could dis- miss the complaint on that ground alone. However, since we determine that the ex- ception is inapplicable here, we must then discuss the question of whether New York law imposes liability on the government under the circumstances of this case. Of the three theories relied on by the district court, we determine that the failure to fur- nish an adequate warning is sufficient to hold the government liable, so we need not reach the merits of the other two theorics. We next will address the questions of whether the settlement proceeds were properly allocated between Joanna 1! Je- rome Andrulonis, and whether the district court properly apportioned the percentages of responsibility between the federal government and the state. Finally, we wili discuss the plaintiff's cross-appeal on whether the district court correctly calcu-— lated his damages for future custodial care. A. Discretionary Function Exception [1] Initially, we take up whether this action was barred by the discretionary function exception to the FTCA. The tort Al6 claims act generally authorizes suits against the United States for damages for injury or loss of property, or personal injury or death caused by the negligent or wrongful act or omission of any em- ployee of the Government while acting within the scope of his office or employ- ment, under circumstances where the United States, if a private person, would be liable to the claimant in accordance with the law of the place where the act or omission occurred. 28 U.S.C. § 1346(b). The act further pro- vides that the United States shall be liable with respect to tort claims “in the same manner and to the same extent as a private individual under like circumstances.” 28 U.S.C. § 2674. — Although the act waives the sovereign immunity of the United States, it does not do so in all respects. Congress carefully excepted several important classes of tort claims from the act’s broad waiver of im- munity. Of particular relevance here, sec- tion 2680(a) provides that the act shall not apply to [a]Jny claim based upon * * * the exer- cise or performance or the failure to ex- ercise or perform a discretionary func- tion or duty on the part of a federal agency or an employee of the Govern- ment, whether or not the discretion in- volved be abused. 28 U.S.C. § 268Qa). ‘The discretionary function exception ° * * marks the bound- Al7 ary between Congress’ willingness to im- pose tort liability upon the United States and its desire to protect certain governmen- tal activities from expocure to suit by pm- vate indivivuals.” Uniied States v. S.A. Linpresu De Viacao Acrea Rio Grandense (Varig Airlines), 467 U.S. 797, 808, 104 S.Ct. 2755, 2761-2762, 81 L.Ed.2d 660 re- hearing denied, 468 U.S. 1226, 105 S.Ct. 26, 82 L.Ed.2d 919 (1984). The Supreme Court in Dalehite v. Unit- ed States, 346 U.S. 15, 27-28, 73 S.Ct. 956, 963-964, 97 L.Ed. 1427 (1055), as:Jyzed the legislative history of the act and concluded that its waiver of sovereign immunity was inapplicable to “acts of a governmental na- ture or function.” The basis for the excep- tion was congress’s wish “to prevent judi- cial ‘second-guessing’ of legislative and ad- ministrative decisions grounded in social, economic, and political policy through the medium of an action in tort.” Varig Air- lines, 467 U.S. at 814, 104 S.Ct. at 2764- 2765. The foundation for this exception is protection of “the principles embodied in the separation of powers doctrine by keep- ing the judiciary from deciding questions consigned to the executive and legislative branches of the government.” Caban v. United States, 671 F.2d 1230, 1233 (2d Cir.1982). By barring tort liability for activities that require the alleged tortfeasor to consider and weigh competing policies in arriving at his decision, this test protects courts from “involve{ment] in making ... deci- sion{s] entrusted to other branches of the government,” and especially from ques- tions involving “not negligence but social wisdom, not due care but political practi- Al8 cability, not reasonableness but economic expediency”. Id. (citations omitted). Congress thus sought to assure that tort liability would not “seriously handicap efficient govern- ment operations.” United States v. Mun- tz, 374 U.S. 150, 163, 83 S.Ct. 1850, 1858, 10 L.Ed.2d 805 (1963). Determining whether specific conduct is protected by the discretionary function ex- ception to the FTCA is sometimes difficult. The act itself contains no definition of the types of discretionary functions within the exception. “The principal difficulty is sim- ply that all federal employees exercise a certain amount of discretion in the dis- charge of their responsibilities.” Caban, 671 F.2d at 1232. [2] To determine whether conduct falls within the exception, we must focus on “the nature of the conduct, rather than the status of the actor,” Varig Airlines, 467 U.S. at 813, 104 S.Ct. at 2764, and use a two-step process to examine the challenged conduct. See Berkovitz v. United States, 486 U.S. 531, 536, 108 S.Ct. 1954, 1958- 1959, 100 L.Ed.2d 531 (1988); In re Joint E. & So. District Asbestos Litigation, 891 F.2d 31, 36 (2d Cir.1989). First, we must consider whether the conduct was a matter of choice for the acting employee, and if so, we must then determine whether the em- ployee’s actions involved public policy con- siderations. Asbestos Litigation, 891 F.2d at 36. {3} As to the first step, the Supreme Court has determined that “conduct cannot Al9 be discretionary unless it involves an ele ment of judgment or choice.” Berkovitz, 486 U.S. at 536, 108 S.Ct. at 1958-1959. Thus, when a federal statute, regulation, or policy specifically dictates a course of ac- tion for an employee to follow, the employ- ee has no option but to adhere to the di rective. Jd. If the employee can make no choice, then there can be no discretion for the exception to protect. Jd No such directive was applicable to Dr. Baer in this case; at the critical points in these events he had the power to choose his actions. But this does not end the inquiry. As we have noted, to qualify for the exception, Dr. Baer’s critical choices had to involve policy considerations, and here they did not. The Berkovitz Court stated that ‘{t]he exception, properly construed, ° ° ° protects only governmental actions and de- cisions based on considerations of public policy.” Jd. at 537, 108 S.Ct. at 1959. If an action leaves “room for policy judgment and decision there is discretion.” Dalehite, 346 U.S. at 36, 73 S.Ct. at 968. In Indian Towing Co. v. United States, 350 U.S. 61, 76 S.Ct. 122, 100 L.Ed. 48 (1955), the Court distinguished between an initial government decision to build a light- house and subsequent actions to maintain the lighthouse. The initial decision to un- dertake and maintain a lighthouse service was a discretionary judgment; however, the failure to adequately maintain the light- house in good condition, since it did not involve any permissible exercise of policy judgment, subjected the government to suit under the FTCA. /d. at 69, 76 S.Ct at 126-127; see also Berkouvtz, 486 US. at 538 n. 3, 108 S.Ct. at 1959 n. 3. A20 Similarly, in Caban, we determined that the adoption of a regulation by the INS was discretionary but a wrongful detention by an INS employee was not discretionary. Caban, 671 F.2d at 1233. See also Cara- ballo v. United States, 820 F.2d 19, 21-22 (2d Cir.1987) (initial decision to patrol a national park was discretionary, but the manner in which decision was executed was not discretionary); Eklof Marine Corp. v. United States, 762 F.2d 200, 204-05 (2d Cir.1985) (initial decision to provide naviga- tional aid by marking obstructions was dis- cretionary, but the precise manner of mark- ing an obstruction did not implicate policy and was not a discretionary act). The government tries to distinguish this line of cases in two ways. First, it con- tends that the /nditan Towing approach is inapplicable because the government here did not decide upon a particular safety measure and then negligently implement its decision. The government would thus restrict /ndian Towing to cases involving a decision to provide safety measures. We decline to limit Jndian Towing so narrow- ly. We think that case rested not so much on the government’s decision to install a safety device, a lighthouse, but on its negli- gent maintenance of the lighthouse and the fact that decisions to maintain the light- house did not implicate policy considera- tions. In /ndian Towing, only the initial decision to install the lighthouse was dis- cretionary. A21 [4] Sometimes, even the execution of a policy decision is subject to protection by the discretionary function exception; this occurs when the steps in the execution process also require policy judgments. For example, in Varig Airlines, the Court not only found that the Federal Aviation Ad- ministration’s implementation of a program for compliance review was discretionary, but it also found that the acts of the FAA employees who executed the program were protected, because those employees ‘‘were specifically empowered to make policy judgments regarding the degree of confi dence that might reasonably be placed in a given manufacturer, the need to maximize compliance with FAA regulations, and the efficient allocation of agency resources.” Varig Airlines, 467 U.S. at 820, 104 S.Ct. at 2767-68. However, in Caban, we deter- mined that even if regulations and statutes appear to vest immigration officials with broad discretion, where the language goes only to the standard cf care by which gov- ernmental employees’ behavior is to be judged, the language does not convert the discharge of prescribed responsibilities into decisions which involve a choice between competing policy considerations. Cabdan, 671 F.2d at 1233. In short, the key inquiry is whether the decisions, be they initial decisions or implementation decisions, were necessarily susceptible to policy analysis. Asbestos Litigation, 891 F.2d at 37; Unit- ed States Fidelity 2 Guar. Co. v. United States, 837 F.2d 116, 121 (8d Cir.), cert. denied, 487 U.S. 1235, 108 S.Ct. 2902, 101 L.Ed.2d 935 (1988). A22 In this case, the government’s decisions te encourage rabies research, provide fund- ing for the research, and provide NYSDOH with the virus were all decisions that impli- cated policy considerations and therefore were protected by the discretionary func- tion exception. The same is not true, how- ever, with Dr. Baer’s alleged failure to warn of the extreme dangers presented by the particular circumstances of the March 29th experiment which Dr. Baer failed to interrupt. The situation simply did not lend itself to policy balancing, not is there any indication that Dr. Baer considered the policy implications or the pros and cons of allowing the experiment to proceed. Once he became aware of the risks, Dr. Baer was obligated to give warning. His is pre- cisely the type of negligent omission for which congress waived the government's sovereign immunity in order to provide re- dress to citizens for the torts of govern- ment actors. The government relies on Dalehite to support its contention that even mundane decisions necessary to execute a policy deci- sion are entitled to protection under the discretionary function exception. Dalehite involved a tragic explosion of fertilizer that had been manufactured and shipped at the instigation and under the supervision of the government. The Supreme Court held that even those actions that were necessary in the execution of a policy decision were enti tled to protection under the discretionary function exception. Dalehite, 346 US. at VX A23 36, 73 S.Ct. at 968. Dalehite is distinguish- able, however, because the Court could not find there any specific instance of negli- gence by an employee. The accident was “a complex result of the interacting factors of mass, heat, pressure and composition,” id. at 42, 73 S.Ct. at 971, and no single action was identified as the cause of the accident. Liability of the government thus could only have been based on the larger policy decision to manufacture and store the fertilizer. The government suggests that a similar inability to pinpoint the precise source should prevent liability in this case, be- cause this accident, too, was the result of complex processes. The district court, however, was able to penetrate the com- plex facts of this case and determine that Jerome Andrulonis’s illness resulted, at least in part, from Dr. Baer’s failure to warn of the potentially disastrous conse- quences of the March 29th experiment he was observing. This was a nondiscretion- ary negligent omission that did not impli- cate any balancing of policy factors. The district court’s findings on this point are not clearly erroneous, and the government is therefore not entitled to protection from suit under the discretionary function excep- tion. A24 B. Supplier’s Duty to Warn The district court found the government liable on three independent theories of tort liability. We need discuss only the suppli- er’s duty to warn, because it is sufficient to affirm on the liability issue. Under the FTCA, the law of the state where the tort occurred applies. 28 U.S.C. § 1346(b); Hatahley v. United States, 351 U.S. 173, 182, 76 S.Ct. 745, 752, 100 L.Ed. 1065 (1956); Montellier v. United States, 315 F.2d 180, 185 (2d Cir.1963). Because most of the acts or omissions of Dr. Baer occurred in New York, the substantive !aw of New York governs this case. [5,6] Under established New York law, a supplier of a product which the supplier knows or should know is dangerous if used in the usual and expected manner has a duty to adequately warn users of the prod- uct of the danger unless the danger is obvious or well-known. Young v. Elmira Transit Miz, Inc., 52 A.D.2d 202, 204-05, 383 N.Y.S.2d 729, 731 (4th Dept.1976) (Car- damone, J.) (citing Restatement (Second) of Torts § 388); Billiar v. Minnesota Mining and Mfg. Co., 623 F.2d 240, 243 (2d Cir. 1980). See also Schumacher v. Richards Shear Co., Inc., 59 N.Y.2d 239, 246-47, 464 N.Y.S.2d 437, 441, 451 N.E.2d 195 (1983). Breach of this duty can lead to liability in negligence. A25 The government initially argues that a supplier's duty to warn is inapplicable to this case because the doctrine should be limited to a commercial context; that pure- ly scientific activities should be exempt from the rigors of traditional tort law; that the risk-spreading rationale underlying im- position of this duty should not be applica- ble because the government is not an in- come-producing entity; and that imposing liability in this situation would tend to cur- tail scientific research, and restrict the flow of information and exchange of knowledge which are vital for producing health-related benefits. Although we are sympathetic to the government's policy arguments, they sim- ply are not supported by the applicable law. In the first place, the FTCA specifically provides for the imposition of liability on the federal! government as if it were a private person. The fact that the govern- ment does not generate income and is not considered a commercial entity is irrelevant in light of congress’s decision that govern- mental immunity is waived in certain cir- cumstances if government employees com- - mit torts. {7} Furthermore, we agree with the dis- trict court that New York does not require a commercial transaction as a prerequisite to liability for breach of a duty to warn. Restatement (Second) of Torts § 405; Pease v. Sinclair Refining Co., 104 F.2d 183, 186 (2d Cir.1939) (applying New York A26 law). In addition, and contrary to the government’s contention, there is probably no entity better able to spread the risk of scientific research than the government, which has the biggest “customer” base of all—taxpayers. Finally, in a_ situation where our entire population may benefit from eradication of rabies, it is not unrea- sonable to have the potential beneficiaries share the cost of an unfortunate incident occurring in the search for an effective method for vaccination against this lethal disease. Although the imposition of a duty to warn of potential hazardous consequences may, as the government argues, tend to chill the collegial atmosphere of the scien- tific community, we think that the benefits of imposing such a duty, at least in the highly unusual circumstances of this case, far outweigh any potentially chilling ef- fects. All scientists should assure that rea- sonable and appropriate safety precautions are taken in the lab. Laboratory staffs should not have to bear the financial bur- dens in addition to the personal risks that accompany the quest for scientific advance- ment. If identifiable negligence does oc- cur, its economic consequences need not be excused as necessary for the benefit of science, no matter how noble the goals of the supervising scientists. [8] The government also contends that even if the imposition of a supplier's duty to warn is the appropriate legal standard, A27 Dr. Baer satisfied this duty by informing Dr. Debbie of the extremely high concen- tration of the virus. The distrct court found that at the time Dr. Baer gave the warning, it was sufficient merely to advise Dr. Debbie that the viral strain was highly concentrated; given what Dr. Baer knew at that time, the warning was proportionate to the risk. However, the district court also found that when Dr. Baer actually observed the experiment, he should have realized the extreme danger created by us- ing his ERA~BHK/21 virus in a leaky aero- solizing machine and should have immedi- ately supplemented his warning. The government argues that requiring Dr. Baer to supplement the warning just because he was a rabies expert and he decided to stay at Griffin to observe the experiment is in- correct. {9,10} Under the applicable New York law, we disagree. In Cover v. Cohen, 61 N.Y.2d 261, 274-75, 473 N.Y.S.2d 378, 385, 461 N.E.2d 864 (1984), the New York Court of Appeals determined that a manufacturer or retailer may incur liability for failing to warn of newly discovered dangers in the use of a product that come to his attention after manufacture or sale. These dangers may be discovered through advancements in the state of the art, with which the manufacturer is expected to stay abreast, or through being made aware of later acci- dents involving dangers in the product, of which warning should be given to users. A28 Although a product may be reasonably safe when manufactured and sold and in- volve no then-known risks of which warn- ing need be given, risks thereafter revealed by user operation and brought to the atten- tion of the manufacturer or vendor may impose upon either or both an additional duty to warn. Id. at 275, 473 N.Y.S.2d at 385, 461 N.E.2d 864. The type of notice that will trigger a manufacturer’s post-de- livery duty to warn is a function of the degree of danger involved and the number of instances reported, id, and these are questions of fact. Jd. at 276, 473 N.Y.S.2d at 385, 461 N.E.2d 864. In this case, Judge Munson determined that Dr. Baer, while observing the expen- ment in the lab, should have known of the dangers involved and that he had sufficient notice to trigger a duty to provide addition- al warning. Dr. Baer was observing an experiment with the extremely potent ra- bies virus he had supplied being used in a leaky machine in a way that couk! poten- tially cause great harm to those present in the lab. In these circumstances, he should have realized the risks and warned against continuing the experiment without addition- al precautions. Judge Munson based his conclusion on several subordinate findings: (1) whenever aerosols were used at the CDC labs in Georgia, a laminar flow containment sys- tem was also used; (2) Dr. Baer knew that safe lab practice required containment; (3) Dr. Debbie told Dr. Baer about the red A29 dust that had escaped from the Uni-Glatt machine during the third run of the experi- ments; (4) Dr. Baer saw nonpareils escape from the machine; (5) Dr. Baer saw Dr. Debbie patch the machine with electrical tape; (6) photographs of the machine showed that it did not appear to be airtight; and (7) Dr. Baer saw that the machine had to be assembled by hand in the laboratory for each experiment. Judge Munson also found that Dr. Baer’s testimony, denying his knowledge of the Uni-Glatt’s leak, lacked credibility. When Dr. Baer saw that the Uni-Glatt was not airtight, he should have immediate- ly alerted Dr. Debbie and the lab staff, including Andrulonis, of the hazards posed by the way the ERA-BHK/21 virus was to be used; his failure to do so was, under New York law, a breach of duty to those in the lab, including Andrulonis. Finally, the government argues that even if the case is properly a duty-to-warn ac- tion, and even if Dr. Baer’s single prelimi- nary warning was inadequate, the govern- ment still cannot be liable, because the case falls within the “knowledgeable user’’ ex- ception. This argument focuses on proxi- mate cause, which is a necessary predicate to finding liability. Sheehan v. City of New Yorn, 40 N.Y.2d 496, 501, 387 N.Y. S.2d 92, 95, 354 N.E.2d 832 (1976). {11] In duty to warn cases, New York recognizes two circumstances that would preclude a finding of proximate cause: ob- viousness and the knowledgeable user. A30 Proximate cause cannot be found when the dangers are obvious or well-known. Lan- caster Silo & Block v. Northern Propane Gas, 75 A.D.2d 55, 427 N.Y.S.2d 1009, 1015 (4th Dept.1980). Nor can it be found with a knowledgeable user, one who is actually aware of the dangerous nature of the prod- uct supplied. Belling v. Haugh’s Pools Lid., 126 A.D.2d 958, 959, 511 N.Y.S.2d 732, 733 (4th Dept.), appeal denied, 70 N.Y.2d 602, 518 N.Y.S.2d 1024, 512 N.E.2d 550 (1987). Although the government re lies here solely on the knowledgeable user doctrine, loosely referred to as the “knowl- edgeable user exception”, a brief look at “obviousness” is necessary to understand why the government’s argument fails. {12,13} If a danger is obvious, there is no duty to warn against it. Kerr v. Koemm, 557 F.Supp. 283, 287 (S.D.N.Y. 1983). The Restatement (Second) of Torts § 388 and comment (k) state that a duty to inform users of a danger exists if the sup- plier of a product has no reason to expect that the user will discover its condition and realize the danger involved. See also Lan- caster Silo, 427 N.Y.S.2d at 1015; Young, 383 N.Y.S.2d at 731; Kerr, 557 F.Supp. at 287. This inquiry into the obviousness of the danger depends not upon actual knowl- edge of the user, but upon whether the danger was sufficiently obvious that it would be unreasonable to impose a duty to warn on the manufacturer. Kerr, 557 F.Supp. at 287. Thus, the focus of the A31 “obviousness” inquiry is upon the objective reasonableness of the supplier's judgment about whether users will perceive the dan- ger. Id. The danger must be so apparent or so clearly within common knowledge that a user would appreciate the danger to the same extent that a warning would pro- vide. Belling, 511 N.Y.S.2d at 733. The district court held that the danger here was not obvious because Dr. Baer actually wit- nessed the experiment and should have im- mediately recognized that neither Dr. Deb bie nor Andrulonis realized the hazards they were facing. On appeal the govern- ment does not challenge that conclusion. {14} In contrast, the “knowledgeable user exception”, on which the government does rely, involves a_ subjective test: whether the particular user was aware of the danger. McDaniel v. Williams, 23 A.D.2d 729, 257 N.Y.S.2d 702 (1st Dept. 1965); Rosebrock v. General Electric Co., 236 N.Y. 227, 140 N.E. 571 (1923); Kerv, 557 F.Supp. at 287. Its rationale is that knowledge is equivalent to prior notice. Billiar, 623 F.2d at 243. Where the plain- tiff knows of a danger, a warning cannot increase his awareness of its presence, Kerr, 557 F.Supp. at 286, and where a warning would not have prevented the harm, a failure to warn cannot be the prox- imate cause of the injury. Torrogrossa v. Towmotor Co., 44 N.Y.2d 709, 711, 405 N.Y.S.2d 448, 449, 376 N.E.2d 920 (1978); Billiar, 623 F.2d at 243. A32 [15] In this case, the district court de- termined that Dr. Debbie did not have ac- tual knowledge of the specific danger in the March 29th experiment. Of course, it determined that Dr. Baer did not have actu- al knowledge of the specific danger either. Thus, the question becomes whether the knowledgeable user exception applies where the knowledge of both supplier and user is imputed, not actual. The govern- ment suggests that the exception should apply here, because the district court found that the state was more than twice as culpable as the federal government, and that Dr. Debbie’s “failure to appreciate the hazard to which he was exposing his work- ers seems more unreasonable than Dr. Baer’s failure to recognize the same haz- ard.” Andrulonis, 724 F.Supp. at 1508. [16,17] While attractive, the govern- ment’s argument is not dispositive, because the knowledgeable user exception applies only where the user is actually aware of the precise danger involved. Belling, 511 N.Y.S.2d at 733; Kerr, 557 F.Supp. at 287. A supplier's duty to warn, on the other hand, arises if he knows or should know of the danger; actual knowledge of the pre- cise danger is not required to hold the supplier liable. Schumacher, 59 N.Y.2d at 248, 464 N.Y.S.2d at 441, 451 N.E.2d 195; Young, 383 N.Y.S.2d at 731. Here, the district court determined that the user had no actual knowledge of the precise danger, but both the supplier, Dr. Baer, and the user, Dr. Debbie, were charged with imput- A33 ed knowledge. In these circumstances, the government, through Dr. Baer’s breach of his duty to warn, is liable to Andrulonis for his injuries. Since we find that the duty-to-warn theo- ry supplies a sufficient basis to establish the government's liability and to affirm that part of the district court’s judgment, we need not address the district court’s further reliance on the other two theories of liability. C. Allocation of Settlement Proceeds (18) Before the end of trial, the Andru- lonises and the non-governmental defen- dants entered into a series of settlement agreements resulting in a total settlement of $1.3 million. The settling parties agreed to allocate $225,000 to Jerome Andrulonis and $1,075,000 to Joanna Andrulonis. Any settlement funds allocated to Joanna An- drulonis, whose claims against the govern- ment were dismissed for failure to timely file an administrative claim, could not be used to reduce the final award of damages to Jerome Andrulonis as provided under section 15-108 of New York’s General Obli- gations Law. The government and NYS- DOH now challenge this allocation and the district court’s approval of it as being con- trary to the policy underlying that section. Section 15-108 of New York’s General Obligations Law provides an incentive to settle and attempts to define the effect of a settlement on collateral rights and liabili- A34 ties in future litigation. Section 15-108(a) provides in relevant part: Effect of release of or covenant not to sue tortfeasors. When a release * ° ° is given to one of two or more persons liable or claimed to be liable in tort for the same injury, or the same wrongful death, it does not discharge any of the other tortfeasors from liability for the injury or wrongful death unless its terms expressly so provide, but it reduces the claim of the releasor against the other tortfeasors to the extent of any amount stipulated by the release or the covenant, or in the amount of the consideration paid for it, or in the amount of the re- leased tortfeasor’s equitable share of the damages under article fourteen of the civil practice law and rules, whichever is the greatest. The “right of set-off” provided by subdivi- sion (a) “is intended to avoid a result in which the non-settling tortfeasors bear more than their equitable share of the plaintiff's damages.” Lambert Houses Re- development Co. v. HRH Equity Corp., 117 A.D.2d 227, 232-33, 502 N.Y.S.2d 433, 436 (1st Dept.1986). The government and the state contend thet th: apportionment of settlement proceeds in the case at bar un- dermines this purpose. They claim that the Andrulonises intentionally allocated most of the settlement proceeds to Joanna Andrulonis in order to minimize any right A35 of setoff that might arise from trial of Jerome Andrulonis’s remaining claims. Fi- nally, they argue that the court should not have accepted the settling parties’ decision, but should have independently allocated _ the settlement funds to reflect the relative injuries suffered by Jerome and Joanna Andrulonis. In Hill v. St. Clare’s Hospital, 67 N.Y.2d 72, TT, 499 N.Y.S.2d 904, 907, 490 N.E.2d 823 (1986), the injured party and his wife, as derivative claimant, entered into a settle ment with the original tortfeasors, but con- tinued their claim against subsequent tort- feasors for aggravation of the original inju- ries. Their general release contained ro reservation of rights and no allocation of damages as between plaintiffs or as be tween the successive injuries. Jd. Al- though the court focused primarily on the problem of allocating settlement proceeds between original injuries and aggravated injuries for purposes of setoff against the subsequent tortfeasors, its analysis is help ful in determining a proper apportionment between two plaintiffs. The court stated that “[t]o the extent that the injured party and the original tort- feasor are permitted to stipulate the amount by which the liability of the succes- sive tort-feasor is to be reduced by the original tort-feasor’s payment, intent re mains a factor, but the amount stipulated must also be shown to have been arrived at in good faith.” Jd. at 84-85, 499 N.Y.S.2d A36 at 912, 490 N.E.2d 823. The court deter- mined that the finder of fact, in making a decision as to attribution of the settlement payment, should “consider the statement as to allocation, if any, * ° ° contained in the settlement documents and the gravity of the respective injuries and determine whether the amount allocated by the par- ties was arrived at in good faith.” Jd at 86, 499 N.Y.S.2d at 912, 490 N.E.2d 823 (emphasis added). In Casey v. State, 119 A.D.2d 363, 507 N.Y.S.2d 159 (2d Dept.1986), the plaintiffs sued three alleged tortfeasors for wrongful death and for conscious pain and suffering. Before trial, a settlement was reached with two of the defendants, but neither release separately allocated the proceeds to the wrongful death and the pain and suffering causes of action. Instead, the Surrogate’s Couft made the allocation decision. The court held that any settlement sum, even though allocated by the parties or by a decree of the Surrogate’s Court, must, for the purpose of a subsequent setoff, be ap- portioned at the trial; and it is the obli- gation of the finder of fact, after hearing the evidence, to make such an apportion- ment. /d. 507 N.Y.S.2d at 162, A nonset- tling party is not bound by any agreement as to allocation made without its know!l- edge or consent. /d 507 N.Y.S.2d at 162. Therefore, the self-created apportionment proffered by the claimants and approved by the Surrogate was not binding on the trial court. /d me A37 In Casey, the court was concerned that the defendant state would be responsible for the bulk of a wrongful death award because the claimants’ proposed allocation would have resulted in $175,000 cf the set- tlement being allocated to a “potentially nonexistent pain and suffering cause of action”, thereby unfairly reducing the set- off in the wrongful death action and leav- ing the state with none of the benefits of section 15-108. Jd. Thus, the court, per Justice, now District Judge, Arthur Spatt, stated: “We are dealing with two separate and distinct causes of action. The State is entitled to a true setoff based on the merits of the respective causes of action. This apportionment [of the earlier settlement] must be predicated on the evidence ad- duced at the trial with regard to the mone- tary value of each cause of action.” /d. Similarly, in Merrill v. State of New York, 110 Misc.2d 260, 442 N.Y.S.2d 352 (1981), affd, 89 A.D.2d 802, 453 N.Y.S.2d 383, 384 (4th Dept.1982), where plaintiffs had earlier settled with one of the joint, tortfeasors for a gross unallocated amount in a case involving separate claims for per- sonal injuries and loss of services, the trial court held that the proper way to apportion the settlement proceeds was in proportion to the damages found to have been sus- tained by the respective claimants. See also Hager v. Hutchins, 91 Misc.2d 402, 398 N.Y.S.2d 316 (1977) (trial court con- fronted with a settlement with several de- fendants for an unallocated sum in a case A38 involving causes of action for wrongful death and conscious pain and suffering held that a prior order of the Supreme Court which had approved the compromise of the claims against the settling defen- dants and allocated the proceeds entirely to the wrongful death cause of action was not binding on the trial court). The district court in this case assessed the reasonableness of the apportionment of the settlement monies and ultimately ap proved the allocation. It rejected the government’s suggestion that Hill and Ca- sey required that for setoff purposes, the apportionment of a settlement fund must in every instance approximate the relative in- juries of the plaintiffs. Instead, the dis- trict court conducted a good faith analysis to determine whether the amounts allocat- ed to Jerome Andrulonis and Joanna An- drulonis could be approved. First, it asked whether the amount set aside for Jerome Andrulonis was a reasonable approxima- tion of the settling defendants’ equitable share of his total damages, and second, . whether the amount set aside for Joanna Anarulonis was unreasonably excessive in light of the damages she actually suffered. The district court found that the amount allocated to Jerome Andrulonis did not grossly underestimate the settling parties’ equitable share of the damages he suf- fered. Although Judge Munson noted a significant discrepancy between Lil ly/Thompson’s settlement amount and its a eee ee A39 equitable share of Jerome Andrulonis’s damages, he considered all the settling de- fendants as a group and determined that the total amount Jerome Andrulonis re ceived did not so grossly deviate from the amount ultimately allocated to those defen- dants as to raise an inference of bad faith. Judge Munson then turned to Joanna Andrulonis’s portion of the settlement pro- ceeds. In determining whether the total amount she received was a good faith as- sessment of the value of her claims, he applied the standard used to review a jury damage award—whether the award was so excessive as to “shock the judicial con- science”. See Martell v. Boardwalk En- terprises, Inc., 748 F.2d 740, 750 (2d Cir. 1984). The district judge felt this was the appropriate standard because a settlement precluded a right to a jury trial. Sensing no shock and looking to other damage awards in loss of consortium actions, the district judge concluded that the apportion- ment of settlement monies was made in good faith. The district judge relied in part on the facts that Joanna Andrulonis was procedur- ally barred from any recovery against the government or the state, and that any amount she received from settling her claims with the private defendants repre- sented the entirety of the damages she will recover. Thus, the nongovernmental de fendants would bear the entire cost of the damages suffered by Joanna Andrulonis, A40 including that portion for which the United States and the NYSDOH would otherwise be responsible, but neither the government nor the state would be required to contrib- ute. We disagree with that analysis. Judge Munson approved the settling parties’ allo- cation of settlement proceeds after deter- mining whether it was “reasonable.” New York law, however, requires the trial court to make an independent determination of what the proper apportionment of settle ment proceeds should be, based on the monetary value of each cause of action. See Casey, 507 N.Y.S.2d at 163. Thus, the trial court should have made its allocation decision de novo, and not just reviewed the parties’ chosen apportionment for reason- ableness. {19} In addition, while the fact that Joanna Andrulonis had no claim against either the government or the state may have influenced the parties in deciding whether or not to settle, it is not conclusive under New York law of the amount that can be allocated to Joanna Andrulonis upon a subsequent setoff. If Joanna Andrulonis had timely filed an administrative claim she also could have recovered damages from the government, and it may be unfortunate that she will not be able to recover from the governmental tortfeasors; but New York does not permit the parties’ private agreements to decrease the amount of the settlement to be offset against the non-set- oot wcimilall ee eee A41 tling defendants. The district court’s point that only the settling defendants are pay- ing for Joanna Andrulonis’s injuries is in- correct, since the government and the state are, through the corresponding reduction in the setoff on Jerome Andrulonis’s claim, being required to carry a significant por- tion of her award. {20} Settling parties may not structure the apportionment to avoid a later setoff by a nonsettling defendant; to hold otherwise would permit them to circumvent the policy underlying section 15-108. The district court recognized that this is precisely what the Andrulonises had tried to do, but it felt that New York law did not prohibit such a result. We disagree. As shown above, the New York cases establish that the parties’ settlement agreement, even when con- firmed by a court order, does not bind a trial court in determining the proper alloca- tion of settlement proceeds for purposes of setoff. That allocation must follow from a comparison by the trial court of the injuries of the settling plaintiffs. We therefore remand to the district court with a direction to independently evaluate the relative inju- ries of the settling plaintiffs and to reduce the damages to be awarded to Jerome An- drulonis by the amount of the settlement thus allocated to him. A42 D. Apportionment of Culpability be- | tween the Government and NYSDOH {21} The district court, pursuant to N.Y.C.P.L.R. §§ 1401-1404 governing con- tribution claims, found the government re- sponsible for 30 percent of the damages suffered by Jerome Andrulonis and NYS- DOH responsible for 65 percent. NYS- DOH appeals this apportionment and con- tends that the court erred in finding it responsible for more of the damages than the government. Relying on the notion that culpability is correlated with duty, which in this case happened to depend on the expertise of the actor, NYSDOH ar- gues that the percentages of fault must be reassessed to reflect the federal govern- ment’s greater responsibility in causing Je- rome Andrulonis’s illness. NYSDOH ar- gues that the district court’s finding that Dr. Baer was the preeminent expert in the field of rabies mandates that the govern- ment, having greater expertise, should be charged with a greater share of the dam- ages. We disagree. NYSDOH is correct in as- serting that New York law holds experts to a higher standard of care. See Restate- ment (Second) of Torts § 289, comment m; Toth v. Community Hospital at Glen Cove, 22 N.Y.2d 255, 263, 292 N.Y.S.2d 440, 447-48, 239 N.E.2d 368 (1968) (holding spe- cialists accountable to a higher standard ge ee et drdet A43 than general practitioners); Hope v. Fall Brook Coal Co., 3 A.D. 70, 75, 38 N.Y-S. 1040, 1043 (4th Dept.1893) (duty of care is measured against knowledge and expertise of the participants). However, NYSDOH confuses application of the appropriate standard of care in defining the minimal level of duty that may be owed to another, with the entirely different process of weighing the expertise of an actor in deter- mining his portion of damages. In essence, NYSDOH urges that the percentages of damages apportioned must be directly re- lated to the relative levels of expertise of the defendants. New York law does not require such a restrictive approach. [22] The district court’s apportionment of damages, like other findings of fact, is subject to the clearly erroneous standard of review. Fed.R.Civ.P. 52(a). The district | court relied on Dr. Baer’s expertise in con- cluding that he had a duty to warn and, | thus, in holding the government liable to Jerome Andrulonis. Turning to the degree of the state’s culpability for purposes of contribution, the court had before it evi- - dence of Dr. Debbie’s expertise with the rabies virus, his prior experience with the Uni-Glatt machine, his intimate knowledge of conditions at the Griffin laboratory, and his role as supervisor of the laboratory with the attendant responsibilities. Bal- ancing all the circumstances of the case, Judge Munson found Dr. Debbie’s failure to appreciate the hazards of using the leaky machine in this series of rabies ex- A44 periments to be more culpable than Dr. Baer’s single tragic lapse. Since his find- ings are not clearly erroneous, we affirm his apportionment of damages under N.Y. C.P.L.R. § 1402. E. Damages for Future Custodial Care {23} The district court awarded Jerome Andrulonis $2,417,238 for his future custo- dial care, relying on an assumption of con- tinued care within the home. Jerome An- drulonis cross-appeals from this part of the judgment, claiming that the damage figure must be based on care in a neurological facility, since it is uncertain whether Joan- na can continue to care for Jerome in her home indefinitely into the future. He asks that the damages for future custodial care be increased to $6,841,925. This argument is without merit. The district court estimated future custodial care on the basis of 24-hour care with three shifts of nursing aides in his home for the rest of his life. Although profes- sional nurses were not considered neces- sary for Jerome’s daily care, the district court used the salary for professional nurs- es because no one else was willing to do the job at a lower cost. In addition, the district court also determined that Jerome would function best in the home environ- ment where he could live in a predictable structure provided by his family. Since the plaintiff presented no evidence as to when, if ever, institutional care would replace the A45 completely supervised home care presently being provided for Jerome, the district court was not clearly erroneous in the } amount it awarded for future custodial ; care. CONCLUSION We reverse that portion of the judgment of the district court that calculated the > setoff under New York’s General Obli- k gations Law § 15-108 from the parties’s | own allocation of settlement proceeds and remand on that issue for further proceed- ings consistent with this opinion. In all » other respects the judgment is affirmed. . ~ Se are A46 Opinion of the United States District Court for the Northern District of New York, Dated November 15, 1989. ANDRULONIS v. U.S. Cite as 724 F.Supp. 1421 (N.D.N.Y. 1989) Joanna ANDRULONIS, Individually, and as Conservator of the Property of Jerome Andrulonis, Plaintiffs, Vv. UNITED STATES of America; Glatt Air Techniques, Inc.; Glatt GmbH; Wis- consin Alumni Research Foundation, Inc.; WARF Institute, Inc.; Raltech Scientific Services, Inc.; Ralston Puri- na Company; Eli Lilly and Company; and John L. Thompson and Sons and Company, Defendants. UNITED STATES of America, Third-Party Plaintiff, v. NEW YORK STATE DEPARTMENT OF HEALTH, Third-Party Defendant. No. 79-CV-847. United States District Court, N.D. New York. Oct. 17, 1989. As Amended Dec. 15, 1989. + aes A47 Researcher who contracted rabies brought personal injury action, along with his wife, against New York State Depart- ment of Health, federal Government, and others. Following settlement with the oth- er defendants, the District Court, Munson, J., held that: (1) employee of Center for Disease Control was negligent; (2) employ- ee of New York State Department of Health who was directing the experiment was negligent; (3) negligence was proxi- mate cause of injuries suffered; (4) failure of vaccine manufacturer to warn of possi- ble ineffectiveness of vaccine against air- borne transmission of rabies rendered prod- uct defective; (5) United States was 30% at fault, NYSDOH was 60% at fault, and drug manufacturer was 5% at fault; and (6) ap- portionment of settlement between claims of researcher and claims of his wife was not unreasonable. Ordered accordingly. A48 Roemer and Featherstonhaugh, Albany, N.Y. (James D. Featherstonhaugh and John R. Mineaux, of counsel), for plaintiffs. Dept. of Justice, Civ. Div., Torts Branch, Washington, D.C. (Leon Taranto and An- thony R. Sherr, Trial Attys., of counsel), and Frederick J. Scullin, Jr., U.S. Atty., N.D.N.Y., Albany, N.Y. (William Fanciullo, Asst. U.S. Atty., of counsel), for U:S. Robert Abrams, Atty. Gen., State of N.Y., Albany, N.Y. (Kevan J. Acton and Robert Seigfried, Asst. Attys. Gen., of counsel), for defendant New York State Dept. of Health. Anderson Russel! Kill & Olick, P.C., New York City (R. Mark Keenan, of counsel), and Paul F. Donahue Associates, Albany, N.Y. (Alvin 0. Sabo, of counsel), for defen- dant Glatt GmbH. Carter, Conboy, Bardwell, Case and Blackmore, Albany, N.Y. (Philip J. Danah- er, of counsel), for defendant Wisconsin Alumni Research Foundation. McNamee, Lochner, Titus & Williams, Albany, N.Y. (Earl H. Gallup, Jr., of coun- sel), for defendants Raltech Scientific Ser- vices, Inc. and Ralston Purina Co. Maynard, O’Connor & Smith, Schenecta- dy, N.Y. (Richard Gershon, of counsel), for defendant-WARF Institute, Inc. ee peas RAE ay peaches wei BNR iihitiie weenie rnnrionrs inst * ws A49 Ainsworth, Sullivan, Tracy and Knauf, Albany, N.Y. (Thomas. F. Tracy, Frank J. Warner, Jr. and Margaret Comard Lynch, of counsel), for defendants Eli Lilly and Co. and John L. Thompson & Sons & Co. Galef & Jacobs, New York City (Christo- pher M. Houlihan, of counsel), for defen- dant Glatt Air Techniques, Inc. MEMORANDUM-DECISION AND ORDER MUNSON, District Judge. On March 29, 1977 the rabies virus invad- ed the body of plaintiff Jerome Andrulonis during an experiment conducted by his em- ployer, the New York State Department of Health (“NYSDOH” or “the State”). The experiment was a part of the State’s effort to develop a method for immunizing wild- life from the disease the virus causes. Shortly after being exposed to the virus, - Andrulonis contracted the disease of ra- bies, and his central nervous system was ravaged. He survived the disease, thus becoming one of only three individuals in human history to do so, but the neurologic damage he suffered as a result of his ill- ness left Andrulonis without the cognitive ability to appreciate this distinction. a - RELY ER aS TA ASO On December 20, 1979 this action was commenced on behalf of Jerome Andrulon- is and his wife, Joanna, against the United States of America (“United States” or “the Government”) under the Federal Tort Claims Act (“FTCA” or “the Act’), 28 U.S.C. §§ 1346, 2671-2680, and against var- ious non-governmental defendants, over whom jurisdiction was predicated on diver- sity of citizenship or the pendant party doctrine. An amended complaint adding additional non-governmental defendants was filed on October 9, 1981. Plaintiffs’ claims sounded in negligence, strict prod- ucts liability, and breach of warranty. The United States made cross-claims against the non-governmental defendants and filed a third-party complaint against NYSDOH, seeking contribution. See N.Y 4.P.LS. §§ 1401-1404 (McKinney 1976). Subse- quently, the court dismissed Joanna Andru- lonis’ derivative claims against the United States for failure to timely file an adminis: trative claim, as required by the terms of the FTCA. Andrulonis v. United States, No. 79-CV-847, slip op. at 7 (N.D.N.Y. March 8, 1984); see 28 U.S.C. § 2675(a); see also id. § 2401(b).' A trial on the re- maining claims was conducted from Febru- ary 18, 1987 until March 19, 1987. Before the end of the trial, plaintiffs entered into settlement agreements with all of the non- governmental parties,’ leaving unresolved the FTCA claims of plaintiff Jerome An- drulonis against the United States and the contribution claims made by the Govern- ment. This memorandum-decision consti- In addition, plaintiffs’ claims against one of the non-governmental defendants, Dale Wur- ster, was dismissed for lack of in personam jurisdiction pursuant to Fed.R.Civ.P. 12(b)(2), Andrulonis v. United States, slip op. at 2 (N.D. N.Y. October 1, 1982), and the third-party claims of certain of the non-governmental de- fendants against NYSDOH employees John G. Debbie and Robert H. Huffaker were dismissed on eleventh amendment grounds. Andrulonis v. United States, slip op. at 5 (N.D.N.Y. September 24, 1984). The terms of these settlement agreements are summarized infra, at note 655. Pursuant to these agreements, plaintiff Jerome Andrulonis, through his Conservator, Joanna Andrulonis. discontinued his claims against the non-govern- mental parties in exchange for payments total- ling $225,000. Plaintiff Joanna Andrulonis dis- continued her derivative claims against the non- governmental defendants for the consideration of $1,075,000. The United States has challenged the allocation of settlement monies for the pur- pose of determining its “right of set-off’ under N.Y.Gen.Oblig.Law § 15-108 (McKinney 1978). This challenge is addressed in the text infra, at 1527-1528. AS2 tutes the court’s findings of fact and con- clusions of law concerning the remaining claims.2 See Fed.R.Civ.P. 52(a). I. INTRODUCTION In some ways, the case of Jerome Andru- lonis is aberrational. Andrulonis is be- lieved to be the only person to contract the disease of rabies who prior to any exposure to live rabies virus had developed through vaccination a significant level of rabies an- tibodies in his blood stream. He is one of only two individuals in this century known to be infected after being exposed to the rabies virus in a laboratory setting. As 3. The court's factual findings are presented in narrative form. While certain important credi- bility issues are expressly discussed in this memorandum-decision, for the most part the court does not attempt to address each and every conflict in testimony present in the record. Unless the context suggests otherwise, any citation to the testimony of a witness indi- cates that the court accepts that portion of that witness’ testimony as credible and tacitly rejects contrary testimony. On a number of occasions during the trial the court reserved decision on objections to questions posed by counsel and allowed the witnesses to whom the questions were directed to answer. Most of the testimony elicited by the contested questions was not con- sidered by the court, and the evidentiary objec- tions that were made to testimony the court has disregarded will not be resolved. In making its findings in the course of this opinion, the court will address any unresolved objections to ques- tions that elicited proof that was considered by the court. A53 will be seen, he is one of only four individu- als in human history believed to have con- tracted the disease internasaily, through what is referred to as the “aerosol route” or the “airborne route” of infection.! Nonetheless, upon examination of what was known about the transmission of the virus by the researchers involved with the experiment of March 29, 1977, wnat was considered safe and reasonable laboratory practice in the relevant scientific communi- ty at that time, and the manner in which the March 29, 1977 experiment was per- formed, it can only be concluded that An- drulonis’ development of the rabies disease was the foreseeable and avoidable result of negligence on the part of the researchers involved with the project. Because a lengthy narrative is to follow, a brief summary may give some context to the matters discussed. In March 1977 Je- Trial Transcript (“Tr.”) at 1031-32 (Testimony of Dr. Michael A.W. Hattwick); Tr. at 736 (Testi- mony of Dr. James R. Tillotson); United States Department of Health, Education, and Welfare. “Rabies in a Laboratory Worker—New York.” 26 Morbidity and Mortality Weekly Report 183, 184 (1977) (admitted into evidence as Plaintiffs’ Exhibit (“Exh.”) 151 and hereinafter referred to as “Rabies in New York Laboratory Worker”): United States Department of Health, Education, and Welfare, “Follow-up on Rabies—New York,” 26 Morbidity and Mortality Weekly Re- port 249, 249 (1977) (admitted into evidence as Exh. 79 and hereinafter referred to as “Follow- up on Rabies”). Se en ee AS4 rome Andrulonis was a thirty-four year old senior bacteriologist employed by NYS- DOH who was primarily involved with re- search conducted in the rabies laboratory at the State’s Griffin Laboratory (‘Grif- fin”), located near Albany, New York. Be- cause he was constantly exposed to the rabies virus in his work, he had been im- munized against the disease of rabies through the administration of a commercial vaccine manufactured by defendant Eli Lil- ly and Company (“Lilly”) and distributed by defendant John L. Thompson and Sons and Company (“Thompson & Sons”). Peri- odically, Andrulonis received booster shots of the Lilly vaccine, which induced the cre- ation of antibodies to the rabies virus in the blood stream (‘serum antibodies”). The effectiveness of the Lilly vaccine was de- pendent on whether the rabies virus, once transmitted to an immunized individual, came into contact with serum antibodies before entering his central nervous system. In the typical case where the virus is trans- mitted to an individual by animal bite, the site of the bite wound is covered in the victim’s blood, and the antibodies that had been created in the blood stream by the vaccine would have the opportunity to kill the invading virus. In the rare case where the virus is transmitted through the air and inhaled by the victim, however, the Lilly vaccine is probably ineffective. The olfac- tory nerves within an individual's nasal cavity are exposed to the air. If live rabies A5S5 virus comes into contact with an individu- al’s olfactory nerve and infects it, the virus could travel the short distance from the olfactory nerve to the victim's brain with- out ever coming into significant contact with serum antibodies. At the time Andrulonis was exposed to the virus that ultimately caused his illness, he was attempting to coat sugar nonpar- eils > with a solution containing live rabies virus. The coating process was accom- plished through the use of a machine rec. ommended by defendant WARF Institute. Inc. (““‘WARF’’).6 The machine, known as the ‘‘Uni-Glatt,” suspended the sugar non- pareils in a stream of upflowing air vhile various solutions were sprayed onto them. The Uni-Glatt Machine was manufactured by defendant Glatt GmbH and distributed in the United States by defendant Glatt Air Techniques, Inc., and employed an air sus- pension process that had been developed by Dale Wurster. The process created “aero- 5. Throughout the trial, the nonpareils were al- ternatively referred to as “pareils.” 6. Originally, WARF was the wholly owned sub- sidiary of a Wisconsin corporation known as the Wisconsin Alumni Research Foundation (“Foundation”), a named defendant in this case. Foundation sold its stock in WARF to defendant Ralston Purina Company in late 1979, and WARF changed its name to Raltech Scientific Services, Inc., also a named defendant in this case. A56 sols,” which are suspensions of microscopic solid or liquid particles in air or gas. The Uni-Glatt machine was not airtight, and when the solution containing live rabies virus was sprayed onto the nonpareils, aer- osolized virus escaped from the Uni-Glatt and into the atmosphere of the rabies labo- ratory at Griffin. The virus was inhaled by Andrulonis, apparently infected one of his olfactory nerves, and then multiplied and travelled from his olfactory nerve to his brain, causing severe and permanent dam- age. The experiment in question was conduct- ed under the supervision of Dr. John G. Debbie, a reSearch scientist employed by NYSDOH. Also present during the experi- ment was Dr. George M. Baer, Chief of the Viral Zoonosis Branch and Rabies Labo- ratory at the Center for Disease Control (“CDC”), who conducted most of his work in the CDC's laboratories in Atlanta and Lawrenceville, Georgia. The CDC is a part of the United States Department of Health and Human Services, and in March 1977 was a subunit of the Department of Health, Education, and Welfare. The ex- periment was conducted in furtherance of a joint effort by scientists at NYSDOH and the CDC to develop a method for the mass immunization of wildlife from rabies. Dur- ing the course of this effort, Debbie re- quested Baer to prepare a solution of high- ly concentrated rabies virus for experimen- tal use in the Uni-Glatt machine. The vi- rus “strain” Baer prepared at the CDC's A5S7 laboratory in Lawrenceville in response to this request was supplied to Debbie on March 28, 1977 and used in the Uni-Glatt machine the next day. At the time of the March 29, 1977 experiment, it was not known whether the virus Baer supplied was “pathogenic,” that is, capable of caus- ing disease in man. The court wil! find that during the course of the March 29 experiment, Andrulonis was exposed to an aerosol containing the virus Baer had pre- pared and as a result of this exposure contracted the disease of rabies. Plaintiffs allege that the laboratory con- ditions under which the experiment was conducted at Griffin were unsafe, that Dr. Baer should have known this, and that Baer’s failure to stop the experiment be- fore Jerome Andrulonis was exposed to an aerosol containing rabies virus constituted negligence that was the direct and proxi- mate cause of the injuries Andrulonis suf- fered. Plaintiffs also argue that Baer act- ed carelessly in supplying a highly concen- trated virus strain to the comparatively inexperienced researchers at NYSDOH. It is asserted that Baer negligently failed to warn Dr. Debbie of the inherent dangers associated with the virus strain he provided and to which Andrulonis was exposed. Plaintiffs also maintain that the Govern- ment is liable because Dr. Baer and Dr. William G. Winkler, Chief of the Viral Zoo- noses Section of the CDC’s Viral Disease Division, negligently made representations A58 that induced WARF to recommend the use of the Uni-Glatt machine in experimental situations for which the machine was not suited. Finally, plaintiffs introduced evi- dence suggesting that the March 29, 1977 experiment was a part of a “joint venture” involving CDC and NYSDOH, and conse- quently that the United States is jointly and severally liable for any negligent acts on the part of NYSDOH employees, includ- ing Dr. Debbie. The Government denies any negligence on the part of its employ- ees, and urges that the injuries plaintiff Jerome Andrulonis suffered were the re- sult of his own negligence or the negligent acts of employees of the State or the non- governmental parties. II. BACKGROUND Unless the context indicates otherwise, this section of the opinion summarizes facts that reasonably should have been known as of March 29, 1977 by scientists who ventured beyond routine laboratory procedures involving the rabies virus and proceeded into the conception and supervi- sion of experimental research projects in- volving that virus. Specifically, Drs. Deb- bie, Baer, and Winkler, whose conduct or representations are relevant to the claims made in this lawsuit, are charged with knowledge of the principles and theories discussed in the pages that follow, as well as familiarity with the research upon which those principles and theories were based. 7. A59 In 1976 and 1977, these men were either members, or engaged in research projects that should only have been undertaken by members, of a select group referred to at trial as the “community of rabies experts,” which in the United States numbered be- tween twenty-five and fifty scientists.’ Whether Jerome Andrulonis reasonably should have been aware of the body of In 1976 and 1977, a small group of roughly twenty-five to fifty scientists were actively in- volved in serious research concerning the rabies virus in the United States. Tr. at 1251 (Testimo- ny of Dr. H Fred Clark). Baer and Winkler were members of this core group. Tr. at 1251 (Clark); Tr. at 1397-98 (Testimony of Dr. Rob- ert E. Shope). Beyond this group of rabies experts was a larger group of people who did diagnostic work or were more indirectly in- volved with the study of the rabies virus and the disease it causes. Tr. at 1251 (Clark). Some question as to Dr. Debbie's status in the rabies field in 1977 exists. Before 1970, Debbie was not involved in non-diagnostic rabies research. See Tr. at 97-98 (Testimony of Dr. John G. Debbie). Although he had a reputation as an excellent diagnostician, by 1977 Debbie's experi. ence in rabies research was still comparatively limited. Tr. at 1412 (Shope). Notwithstanding this, Debbie testified that he was familiar with most of the studies discussed in the text. See, e.g., Tr. at 255-59, 390-91, 414-15, 438 (Debbie). More importantly, much of the research he con- ducted at Griffin, including the experiments with the Uni-Glatt machine, was of the kind properly undertaken only by those who were members of the core group of rabies experts, and the court will charge him with the knowl- edge that reasonably should be possessed by members of that elite group. See, eg. Tr. at 1288-90 (Clark). a A60 scientific knowledge discussed in this mem- orandum-decision is more problematical, and this issue will be discussed separately.® For the most part, the scientific literature that is cited by the court in this section predates the March 29, 1977 Uni-Glatt ex- periment, and the testimony cited concerns knowledge available to the relevant scien- tific community of rabies experts before that date. A. The Nature of the Rabies Virus Rabies is an acute infectious disease of the central nervous system that imperils a wide range of mammal species, including man. Historically rabies has been one of man’s most dreaded diseases, no doubt be- cause of its dramatic symptoms and the severe neurologic effects associated with it. The Greeks called rabies Lyssa or Lytta which meant madness. The disease in man was described as hydrophobia in which the sick person is tormented at the same time with thirst and the fear of water. The Latin word “rabies’’ comes from an old Sanskrit word rabhas which translated means ‘‘to do violence.’ The German word tollwut originates with the Indogermanic Dhvar, to damage, and 8. See text. infra at 1504-1508 A6él wut from middle German wuct which is rage. The French word for rage is de rived from the noun robere, to be mad.° As Jerome Andrulonis noted in his Mas- ter’s Dissertation, ‘“[e]ven today, the mere mention of this affliction is sufficient to strike terror into the hearts of the general public, for facts and folklore have blended to obscure any true understanding of this deadly malady.” ' 9. J. Steele, “History of Rabies,” 1 The Natural History of Rabies at 1 (G. Baer, ed., 1975). The Vatural History of Rabies, a two volume refer- ence book. was admitted into evidence as Exh. 112 and will hereinafter be referred to as Natu- ral History. This treatise was edited by Dr. George Baer of the CDC, one of the principals in the series of events leading to Andrulonis’ con. traction of the disease of rabies. The treatise, which is cited often in this opinion, was publish- ed before the events material to this lawsuit occurred. Dr. James H. Steele's chapter in Nat- ural History will hereinafter be referred to as “History of Rabies.” 10. J. Andrulonis, “ERA Rabies Grown in PK-15 Tissue Culture” at 1 (May 1973) (admitted into evidence as Government's Exhibit (“Exh.”) G- 121 and hereinafter referred to as “Andrulonis Dissertation”) A62 The disease of rabies can develop in an animal after the introduction of the rabies virus into the body of that animal. The rabies virus is an “etiologic agent,” in oth- er words, it is an organism capable of caus- ing disease. Infection by the rabies virus in nature usually occurs through the saliva of another infected animal during a bite. Although infrequent, the virus can also be transmitted through the milk of an infected animal or, in rare cases, internasally, if an animal is exposed to an aerosol containing the rabies virus.'' Not every person or animal who comes into physical contact with an environment containing live rabies virus (“exposure” to the virus) has the live virus introduced into his or her body (“‘in- fection”), and not every person or animal infected with the rabies virus subsequently develops the disease of rabies." 11. Tr. at 968 (Hattwick). 12. See M. Hattwick & M. Gregg, “The Disease in Man,” 2 Natural History at 281-85 (hereinafter “The Disease in Man”). As used in this memo- randum-decision, “disease” will refer to the de- velopment of clinical symptoms or sickness as- sociated with the rabies virus’ invasion of the central nervous system. See td. at 282. Those symptoms are summarized in the text, infra at 1437-1438. A63 A virus is a microscopic organism con- sisting of genetic material '* surrounded by a protective protein shell. A virus can reproduce only within a living host cell.'* The rabies virus is a neurotropic virus, or a virus that proliferates primarily in nervous tissue, although it also has an affinity for certain other tissues of a host that it has infected, including the tissue comprising the salivary and adrenal glands and the epithelial (surface) tissue of the lungs, bladder and urinary tract.'> In the com- mon case where the rabies virus is trans- mitted to a previously uninfected animal through the saliva of an infected animal during a bite, the rabies virus is introduced into the cells of the bitten animal’s mus- cles, connective tissue, or nerves at the site of the bite." Once introduced, the virus may fail to multiply, or may multiply with- in an infected cell at the location of the bite but not leave that cell, or may spread to Th. > ' 13. The genetic material is ribonucleic acid (RNA). 14. Tr. at 976 (Hattwick). 1S. Exh. G-125C at 133 (Deposition of Charles V. Trimarchi). 16. G. Baer, “Pathogenesis to the Central Nerv- ous System,” | Natural History at 182 (herein- after “Pathogenesis”). A64 other cells locally but fail to invade the infected animal’s central nervous system." If any of these contingencies occur, sick- ness will not develop. On the other hand, if the virus reproduces at the site of infec- tion, leaves that site and invades the vic- tim’s central nervous system, it will pro- duce the disease of rabies in the infected animal.'® A common progression characterizes those cases where the disease of rabies develops in an animal or man after infec- tion. At the site of exposure and infection, the virus goes through an incubation period lasting from ten days to several months,’? and then invades nearby nervous tissue. The virus begins to travel along connected nerves until it reaches the central nervous system. The reproduction of the virus within the central nervous system can cause myelitis (inflammation of the spinal cord) or encephalitis (inflammation of the brain). As the animal becomes ill as a result of viral replication in the brain, the virus travels down nerve cells into the mouth and enters the diseased animal’s sa- liva. Frequently, the infected animal will 17. “Pathogenesis,” supra note 16, at 182. 18. “Pathogenesis,” supra note 16, at 182. 19. “Pathogenesis,” supra note 16, at 192; Tr. at 970 (Hattwick). A65 become aggressive or violent because of the encephalitic changes caused by the vi- rus, and this effect will often coincide with the entry of the virus into the animal’s saliva. The virus is transmitted to other animal hosts when an agitated rabid anima! bites an uninfected animal, introducing sali- va containing the deadly virus into the bit- ten animal.” When rabies virus is introduced into the muscle tissue of an animal as a result of the bite of a rabid animal, the virus has entered by the intramuscular route of in- fection. The term “route of infection’ re- fers to the manner in which the virus en- ters the body of an animal. For example, researchers can introduce the virus into a laboratory animal by the “parenteral route” if they inject the virus into the animal intramuscularly, intravenously, or subcutaneously (beneath the skin). In cases of infection by the parenteral route, researchers draw distinctions based on the proximity of the site of the parenteral inva- sion to the animal’s central nervous sys- tem. In the laboratory, rabies virus can be introduced into an animal by the “intracere- bral route,” which is accomplished by injec- tion of a solution containing virus directly into an animal’s brain. Most importantly 20. “Pathogenesis,” supra note 16, at 182-92: Tr. at 968 (Hattwick). A66 for the purposes of this lawsuit, rabies virus can infect an animal through the “‘air- borne route” (alternatively called the “aerosol route’) when the animal inhales aerosol suspensions containing rabies vi- rus. The chances that the disease of rabies will develop in an infected animal are close- ly related to the quantity of viral parti- cles?! to which the animal is exposed.** This is true regardless of the route of infection.2 With respect to the aerosol route of exposure, the “dose” or quantity of aerosolized viral particles to which an animal is exposed is the most important factor in determining whether a rabies vi- rus will likely cause disease in the animal as a result of this exposure.*4 21. A viral particle, or virion, is a single, com- plete agent comprised of genetic material and 3 protein shell. 22. Tr. at 1856-57 (Testimony of Dr. William G. Winkler); Tr. at 1403, 1412, 1451-52 (Shope); see also Tr. at 1396-97 (Shope) (discussing aero- sol exposures). 23. See Tr. at 1856-57 (Winkler) (indicating that rabies generally is a dose-related disease); Tr. at 1396-97 (Shope) (discussing aerosols). 24. See text, infra at 1447-1448. A67 As a species, man is not particularly sus- ceptible to contracting the disease of ra- bies.** Nonetheless, between 1958 and 1972 there were an average of 709 reported cases of human rabies per year worldwide (virtually all of which resulted in death), and it is believed that this total significant- ly underestimates the number of human 25. “The Disease in Man,” supra note 12, at 287- 88. The likelihood that the disease of rabies will develop in a human being following an exposure to the rabies virus varies with the route of exposure and the quantity of virus to which the person is exposed. In cases where a man is exposed to the virus by the bite of an infected animal, the risk that disease will result is dependent on the species of the animal re- sponsible for the human exposure and the loca- tion and severity of the bite. “The Disease in Man,” supra, at 284. Even with the most seri- Ous exposures, the probability of developing the disease of rabies is less than one hundred per- cent. /d. at 287-88. The chances that an other- wise untreated human being will die as a result of a severe bite by a rabid dog to the fingers or hand has been estimated to be fifteen percent: the mortality rate when a rabid dog bites a human in the trunk or legs through torn cloth- ing has been estimated to be three percent. /d. at 286; Tr. at 2149 (Testimony of Dr. George M. Baer). A68 cases worldwide.2° The rabies virus is ordi- narily transmitted to humans through the bites of wild and domestic animals. Expo- sure through rabid cats and dogs is still very prevalent throughout the world, al- though such exposure has been largely minimized in the United States in the past three decades as a result of effective ani- mal control programs and strong policies favoring the vaccination of domestic ani- mals. As a consequence of this develop- ment, the number of cases in which hu- mans contracted the disease of rabies in this country decreased from an average of more than forty a year in the 1940s to an average of less than two a year in the 1960s.27_ The most recent cases of human rabies in this country for the most part have been attributable to the bites of bats, skunks, or raccoons.” 26. “The Disease in Man,” supra note 12, at 287. A World Health Organization survey conducted for the year 1981 which accounted for under reporting estimated that 20,482 human deaths world-wide were attributable to the disease of rabies during that year, ninety-eight percent of those deaths occurring in Asia. See Tr. at 2274 (Baer). 27. “The Disease in Man,” supra note 12, at 287. 28. Tr. at 969-70 (Hattwick). A69 The disease of rabies in man can be divided into five stages.*® The first stage is the incubation period, which can last from ten days to several months, depend- ing on the intensity of exposure and the quantity of virus to which the victim has been exposed.® The average incubation period is twenty to sixty days.*! During this initial stage, the infected individual shows no signs of illness, and is usually perfectly well apart from symptoms related to the healing of any wound resulting from an animal bite.%? The incubation period ends when the vic- tim experiences the first Symptoms of sick- ness and the disease enters the prodrome Stage. This stage usually lasts between one and five days, and the infected individ- ual suffers from nonspecific flu-like symp- 29. See Tr. at 970-75 (Hattwick): Tr. at 696-97 (Tillotson) 30. Tr. at 970-71 (Hattwick). The intensity of an exposure is dependent in part on the duration of the exposure, the route ot exposure, and the proximity of the exposure to the central nervous System. See Tr. at 1064 (Hattwick): “The Dis- ¢ase in Man,” supra note 12, at 289 31. “The Disease in Man.” Supra note 12, at 289 32. “The Disease in Man.” Supra note 12, ai 290: Tr. at 970 (Hattwick). A70 toms such as malaise, headache, fever, and fatigue. In cases involving animal bites, pain or numbness at the wound area is not uncommon. The victim may also exhibit anxiety, nervousness, agitation, or irritabil- ity. Shortly after the onset of prodromal symptoms, the disease will enter the acute neurologic stage and produce the unusual symptoms that are suggestive of the dis- ease of rabies. At this point, the virus has entered the infected individual’s brain and is multiplying. Intermittent hyperactivity and violence is common at this stage, and the victim typically suffers periods of ag- jtation, thrashing, running, biting, scream- ing, or ecrying.** Hyperventilation, exces- sive salivation, and convulsions usually characterize this stage.** Between hyper- active episodes, the victim is lucid, though often anxious. Difficulties with automatic functions—breathing, swallowing, and sali- vating, for example—commonly arise. In- deed, attempts to drink water often will result in severe, painful spasms of the 33. “The Disease in Man,” supra note 12, at 290: Tr. at 971 Hattwick); Tr. at 696 (Tillotson). 34. “The Disease in Man,” supra note 12, at 290; Tr. at 971-72 (Hattwick). 35. The periods of hyperactivity are not dramatic in between five and twenty percent of reported cases of human rabies. Instead. paralytic symp- toms predominate. “The Disease in Man,” su- pra note 12, at 291. A71 pharynx and larynx, causing choking and gagging. The victim might develop hydro- phobia, a psychic reaction to the sight of liquids causing spasms often resulting in strangulation. Historically, the fact that those who contract the disease of rabies develop great thirst but fear water was one of the most dreaded side-effects of the disease. Today this effect can be avoided by the performance of tracheostomies.** If the victim does not die abruptly of suffocation or heart failure during the acute neurologic phase, paralysis gradually sets in. The victim becomes increasingly disoriented and confused, falls into a stu- por, and ultimately slips into a coma.” The acute neurologic phase persists for be- tween two and ten days, ending with the onset of coma. Historically, most victims of the disease have died at this stage, prob- ably because of a cessation of breathing, although cardiac irregularities and spasms can occur.*® If the victim survives, the coma phase can last for a few hours or for several months. At about this point in time, the virus is no longer damaging the victim, but a legion of potentially fatal com- plications can develop. Among those is an increase in intracranial pressure, cerebral 36. “The Disease in Man,” supra note 12, at 290- 91; Tr. at 971-73 (Hattwick). 37. “The Disease in Man,” supra note 12, at 291. 38. Tr. at 974-75 (Hattwick); “The Disease in Man,” supra note 12, at 29}. A72 edema (an excessive accumulation of fluid in the brain substance), and internal hydro- cephalus (an accumulation of cerebrospinal fluid in the brain).2® Post-mortem studies of victims of the disease often reveal sub- stantial damage to the brain matter caused by rabies encephalitis.” The above-described neurologic effects of the rabies virus on an infected individual are so severe that the disease of rabies is almost always fatal. In all of human histo- ry, only three individuals have survived the coma stage to enter the fifth stage of the rabies disease, the recovery stage. One of those individuals is Jerome Andrulonis. B. Modern Rabies Research and the Ef- forts to Control the Disease in Man Although man’s awareness of the disease of rabies dates to antiquity,*! most scien- tific knowledge concerning the disease and the etiologic agent that causes it has been acquired within the last century. The roots of modern scientific research concerning 39. Tr. at 97475 (Hattwick); “The Disease in Man,” supra note 12, at 291, 292-94. 40. Tr. at 867-68 (Testimony of Dr. Lawrence D. Rodichok). 41. “History of Rabies,” supra note 9, at 1. A73 rabies can be traced to the work of Louis Pasteur in the late nineteenth century.‘ In Pasteur’s tirne, dogs caused most hu- man rabies deaths in the world, and thus Pasteur’s initial work with rabies focused on the development of a vaccine for domes- tic dogs which would prevent the disease in that species by stimulating an active im- mune response to the agent that caused it.43 Early in the course of his work, Past- eur observed that dogs which recovered 42. Before Pasteur’s work in the 1880s, it had been demonstrated through crude and some. what doubtful experiments that the disease of rabies could be transmitted by the saliva of an infected animal, and some investigators suspect- ed that rabies was a disease of the nervous system. “History of Rabies,” supra note 9, at 11-12. Scientists were unaware, however, that the causal agent was a living organism, much less how that organism caused the extreme physiologica! effects associated with the disease. /d. at 11. Pasteur theorized that the disease was caused by “a microbe of infinite smallness,” L. Pasteur & M. Chamberland, “Nouvelle commu- nication sur la rage,” 98 C.R. Acad. Sci. (Paris) 457 (1884) (quoted in “History of Rabies,” supra note 9, at 20), and he was the first investigator to demonstrate that “the central nervous system . (is) particularly concerned and active in the development of the disease.” “Pathogenesis,” supra note 16, at 181 (quoting L. Pasteur, et al., 92 C.R. Acad. Sci. 1259 (Paris) (1881)). 43. See R. Sikes, “Canine and Feline Vaccines— Past and Present,” 2 Natural History at 177 (hereinafter “Canine and Feline Vaccines”). A74 from early symptoms of rabies after inocu- lation of liquid solutions (‘‘suspensions’’) containing infected central nervous system tissue into the blood stream were immune to later inoculations. He also concluded that the injection of small amounts of “in- fective material” —it was not known that a virus caused rabies at the time—would not produce immunity.- The problem was find- ing a way to inject “infective material” into an animal sufficient to yield an immune response without producing disease. Past- eur’s solution was to “attenuate” the “‘in- fective material” before injecting it into the animal to be immunized. “Attenuation” will be discussed in greater detail below. By 1885, Pasteur had reported success in developing immune responses in experl- mental dogs after injecting them with a series of inoculations of suspensions of an attenuated rabies virus strain.® That same year, Pasteur relented to the pleas of 44. “History of Rabies,” supra note 9, at 19-21. 45. “History of Rabies,” supra note 9, at 20-21. The series of shots began with a non-pathogenic suspension of material taken from the spinal cords of rabbits infected with the rabies virus. The solution in each succeeding inoculation was progressively more pathogenic. H Clark, T. Wiktor, & H. Koprowski, “Human Vaccination Against Rabies,” 2 Natural History at 341-43 (hereinafter “Human Vaccination’). A75 the mother of a young boy who had been bitten by a rabid dog numerous times and administered a series of injections of the solution he had developed for dogs to the boy. The boy never developed rabies, and as a result of this apparent success Past- eur’s work became so influential that it defined in large part the direction of mod- ern rabies research well into the second half of the twentieth century. Many of the techniques used by Pasteur in his early work persisted in modern rabies investiga- tion through 1976 and 1977, the time period in which the events most relevant to this lawsuit transpired, and discussion of these techniques will give context to terms used throughout the remainder of this opinion.‘ l. The “Passaging” of Virus In his efforts to develop a canine vaccine, Pasteur was the first rabies investigator to utilize a laboratory procedure known as “passaging”’ in order to adapt the etiologic agent that caused the disease of rabies (the rabies virus) to animal species other than the dog. After a certain number of “pas- Sages,” a virus, through a process of natu- ral selection, can become “virulent” (ex- tremely pathogenic) for the host for which 46. See “Human Vaccination,” supra note 45, at 342; “History of Rabies,” supra note 9, at 19. A76 it is adapted. However, if a solution con- taining the passaged virus is injected into an animal with a cell structure different than that of the animal species for which the virus has been adapted, it is possible that the passaged virus will lack the capaci- ty to cause disease in that animal.‘7 None- theless, in some cases a suspension of pas- saged virus in an animal for which the virus has not been adapted will act as an antigen, a substance capable of inducing the animal’s immune system to produce antibodies to the rabies virus.’ An anti- body is a protein with a structure such that it interacts only with either the antigen that induced its creation in the first place or an antigen closely related to the induc- ing antigen. If a passaged virus is capable of spurring - creation of antibodies, those antibodies once produced will be present to neutralize any rabies virus to which the immunized animal is subsequent- ly exposed in the wild.’ 47. See Tr. at 1256-57 (Clark); Tr. at 2155 (Baer); Dorland’s illustrated Medical Dictionary 138 (27th ed. 1988) (defining “attenuation”). 48. See Tr. at 1798 (Winkler). 49. Exh. G-125G at 19-22 ‘Deposition of Dr Franklin B. Peck); Dorland's Illustrated Medical Dictionary 88 (27th ed. 1988) (defining “anti- body"); see also Tr. at 976 (Hattwick). A77 Basically, a “passage” is a defined period of growth for a virus through replication and mutation within a particular cell sys- tem. An animal, an embryonated egg, or a tissue culture is infected with a solution containing a given concentration of viral particles. The virus is allowed to incubate under certain conditions for a specified pe- riod of days, during which time the virus will multiply and mutate randomly. Pre- sumably, viral particles well-adapted to the host animal or tissue culture will replicate more readily than viral particles that might be better adapted to other species or cell systems during the short-term evolution that takes place during the passage. A virus that multiplies more readily will also mutate more frequently. After a specified period of days has elapsed, live rabies virus will be “harvested” from the animal or tissue culture within which it was grown.°° Under modern laboratory practice, passag- ing often transpires in tissue culture main- tained in test tubes and bottles, and “har- vesting” constitutes the removal of liquid containing live viral particles from the cells of the tissue culture. This liquid contain- ing viral particles is called a ‘‘supernate.”’ *! Through passaging, rabies investigators seek to develop a “modified live virus ra- 50. Tr. at 1254-36 (Clark); Tr. at 2343-45 (Baer). 51. Tr. at 2343-44 (Baer). aE a ee A78 bies strain” with certain predictabie quali- ties. A “modified live virus’ is any virus strain that has been altered through some laboratory process such as passaging and possesses certain constant, identified char- acteristics.” In developing his vaccine. Pasteur isolat- ed rabies “street” virus (the virus as it occurs in the wild) from the brain of a rabid cow in 1882. The street virus was injected intracerebrally into a rabbit, and after a certain amount of time had elapsed the virus was harvested. The harvested virus was then itself injected intracerebrally into another rabbit. This process was repeated until the virus had been passaged in rabbits ninety times. The resulting virus strain §2. Tr. at 980-81 (Hattwick). Although different “strains” of rabies virus are distinguishable de pending on the animal from which the virus is initially isolated or the animal or cell system through which the virus is subsequently pas- saged, see Tr. at 523-24 (Deposition of Dr Mel. sin K. Abelseth), all strains cross-react in serum- neutralizing tests, discussed in the text, infra at 1442-1443. See H Clark & T. Wiktor, “Rabies Virus.” in Strains of Human Viruses 177, 178 (Majer & Plotkin, eds. 1972) (admitted into evi- dence as one of a packet of documents constitut. ing Exh. G-137 and hereinafter referred to as “Rabies Virus Strains’). Thus, the various ra- bies virus strains are generally considered of the same “serotype.” inducing the same specific im- mune response in an animal infected by any of the various rabies virus strains. /d $3. “Human Vaccination,” supra note 45, at 343, “History of Rabies,” supra note 9, at 20. A79 was more pathogenic to rabbits than street virus, and had a fairly constant incubation period of six to seven days when injected intracerebrally into rabbits. This virus Strain proved to be less pathogenic than Street virus for dogs, however, and it was repeatedly demonstrated in the laboratory that dogs inoculated with a series of injec- tions of suspensions containing the virus Strain not only did not develop disease but resisted disease after subsequent infection with a strain of rabies virus virulent to dogs (a so-called ‘‘challenge’’).5 The modified live virus strain Pasteur developed was a “fixed virus” with respect to rabbits but an “attenuated virus” with respect to dogs. A virus is deemed “fixed” for a particular species when it has a fairly specific incubation period—which is ordi- narily comparatively short—and is always lethal to that species.*5 The characteristics 54. Tr. at 1257 (Clark), “Canine and Feline Vac cines,” supra note 43, at 177; “Human Vaccina- tion,” supra note 45, at 343. 55. Tr. at 1796-97 (Winkler): Tr. at 882 (Deposi- tion of Dr. William G Winkler). ——————— ee A80 of a fixed virus are more predictable than those of a street virus. A virus is “‘atten- uated” for a certain species if it is less pathogenic for that species than street vi- rus when introduced into an animal by a specified route.*’ Almost invariably, when scientists attempt to attenuate a live virus for a particular species, it is done in an attempt to develop a vaccine 2gainst rabies for that species.* A rabies vaccine is a suspension of either attenuated live rabies viral particles (a “modified live rabies virus vaccine’’) or in- activated rabies viral particles (a ‘killed virus vaccine’) which is administered to an animal host in order to stimulate an im- mune response in that host without induc- 56. Tr. at 1797 (Winkler). The two most com- mon examples of fixed viruses used by modern rabies researchers are the PV virus and the Challenge Virus Standard (CVS virus). The PV virus is derived from the original virus strain developed by Pasteur. It is maintained by the Division of Biologic Standards of the National Institute of Health and is used for vaccine pro- duction. The CV® virus is derived from the original Pasteur strain by further passage in mouse brain. It is the uniform challenge virus used in rabies investigations. See Tr. at 1799 (Winkler). 57. Tr. at 1798 (Winkler); Tr. at 1253 (Clark); Tr. at 978-90 (Hattwick); Tr. at 634 (Abelseth Deposition). 58. Tr. at 1798 (Winkler); Tr. at 978-79 (Hat wick). A8l ing disease.*® Strictly speaking, the term “vaccine” is properly used to describe a specific suspension that has been licensed for use as a vaccine for a particular spe- cies. It is important to note that a virus strain, particularly an attenuated live virus Strain, that has been tested and appr: ed for use as a vaccine for one animal srecies may be pathogenic if introduced into anoth- er species.*' Moreover, a4 virus strain that has been shown to be a safe and effective vaccine when introduced into an animal by a specified route may prove to be pathogen- ic when introduced into the same animal by a different route. This is not surprising given the process by which a live virus is attenuated in order to make a vaccine: to make the virus non-pathogenic for one spe- cies, the virus is made to thrive in a cell culture different than that of the species for which the vaccine was developed. As a general rule, only by conducting labo- $9. See Tr. at 976, 980-81 (Hattwick); Tr. at 2041 (Richardson); Dorland’s [ilustrated Medical Dic- tionary 1431 (27th ed. 1988) (defining “vac- cine”). 60. Tr. at 981 (Hattwick). 61. Tr. at 979-80 (Hattwick). 62. Tr. at 979-80 (Hattwick); Tr. at 1256 (Clark). 63. Tr. at 1256 (Clark). A82 ratory tests in which a particular modified live virus strain is introduced into a particu- lar species by a specified route can it be reliably determined whether that virus strain is attenuated for the species in ques- tion when infected by the virus through the route specified.™ 2. Control of Human Rabies in the Unit- ed States: The Mass Immunization of Canines and the Lilly Vaccine The immunization method developed by Pasteur required multiple inoculations, and was never adopted for the mass immuniza- tion of dogs. It was not until the early 1920s that 2 practical one-dose vaccine for dogs was developed in Japan. The virus strain used in the vaccine had been fixed for rabbits and then inactivated,® a process by which the biological activity of the virus is destroyed either through exposure to heat, chemicals, or ultraviolet irradiation.” 64. See Tr. at 1854 (Winkler). 65. E. Tierkel, “Control of Urban Rabies,” 2 Nat- ural History at 190 (hereinafter “Urban Rabies”); “Canine and Feline Vaccines,” supra note 43, at 177-78. 66. “Canine and Feline Vaccines,” supra note 43, at 178. 67. See “Human Vaccination,” supra note 45, at 345-47 (discussing some of the methods that have been used to either partially or completely inactivate rabies virus). A83 Although this vaccine proved effective in controlling rabies in dogs in Japan and was used in other countries, use of the vaccine in the United States was sporadic. In the late 1920s, it was discovered that some lots of that vaccine contained live virus, and thereafter different methods of inactivation were tested. In the course of these tests, it was found that inactivation rendered many lots of vaccine ineffective in stimulat- ing an immune response in animals. Since there was no reliable way to determine the antigenic efficacy of a particular vaccine lot before it was used, efforts to implement an effective mass immunization programs were frustrated.® The obstacle to mass immunization posed by the inability to pre-determine vaccine efficacy was overcome in the 1940s with the development of reliable standardized tests for both the evaluation of vaccine potency and an animal’s immune response to the administration of a vaccine.” These tests, known as “titrations,” are used to yield a standardized number called a “ti- ter.” In essence, “titer” is a term that is 68. “Canine and Feline Vaccines,” supra note 43, at 178; “Urban Rabies,” supra note 65, at 190. 69. “Canine and Feline Vaccines,” supra note 43, at 179. 70. See Canine and Feline Vaccines,” supra note 43, at 179; “Urban Rabies,” supra note 65, at 190. A84 used to indicate a measure of a substance’s ability to cause some defined result. By assigning a titer to a particular solution containing a virus, for example, research- ers can compare that virus solution to oth- er solutions containing the same virus with respect to the ability to cause the result contemplated. When rabies researchers measure the “titer” of a rabies virus strain, they are measuring the ability of that virus strain to kill laboratory mice after intracerebral in- jection of a solution containing that virus strain.’! The titer of a rabies virus strain is measured in units of “50% mouse intra- cerebral lethal doses per .03 milliliters (MICLD-50/.03 ml),” a reference to the number of dilutions of the virus strain that could be injected intracerebrally into a group of mice in .03 milliliter suspensions and induce disease in fifty percent of the mice injected.*? A virus strain with a high 71. Tr. at 547 (Abelseth Deposition); Tr. at 408 (Debbie). Laboratory mice have been chosen as the standard species for titration because of their acute susceptibility to neurotropic viruses such as the rabies virus and their ready avail- ability to research laboratories. J. Thomas, “The Serum Neutralization, Indirect Fluorescent Antibody, and Rapid Fluorescent Focus Inhibi- tion Tests.” 1 Natural History at 420 (hereinafter “Serologic Tests”); “History of Rabies,” supra note 9, at 26. 72. See Tr. at 317-18 (Debbie). A85 titer has a greater capacity to kill mice than a virus strain with a low titer.”> The titer is commonly expressed exponentially, with a base number of ten raised to a certain power. For example, a virus strain could have a titer of ten raised to the power of 3.5 MICLD-50/.03 ml. The ‘‘com- mon logarithm” of the titer represented by the foregoing mathematical expression is 3.5. For the remainder of this memoran- dum-decision, the titer of a virus strain will be expressed by reference to its commen logarithm. Rabies investigators also measure an ani- mal’s immune response to a vaccine by reference to the term ‘“‘titer.” Here, “ti- ter’’ is a measurement of neutralizing anti- bodies in an immunized animal's blood stream.’”4 Blood serum isolated from a blood sample of the immunized animal is added to a solution containing the chal- lenge virus standard (“CVS”), a fixed stan- dardized rabies virus strain with constant characteristics derived from the original Pasteur virus. This mixture is incubated and then inoculated into mice. The mea- Sure of antibodies in the blood serum is determined by evaluating their ability to 73. Tr. at 547 (Abelseth Deposition). 74. Tr. at 977 (Hattwick); see “Serologic Tests,” supra note 71, at 420-23. A86 neutralize the viral particles present in the CVS strain and prevent mouse deaths. Se- rum neutralizing antibody titer is usually expressed as a ratio, such as 1:9. The higher the second number in the ratio, the greater the amount of viral particles that can be neutralized by the immunized ani- mal’s serum antibodies.” Hereafter in this opinion, references to “titer” allude to the measure of the ability of a rabies virus strain to kill laboratory mice, while the phrase “antibody titer” will be used to re- fer to the level of neutralizing antibodies in an animal’s blood stream. As a general rule, if the titer of a partic- ular virus strain is increased by some labo- ratory procedure, the pathogenicity of that virus strain is increased for species for which it has not been attenuated.’”* It ap- pears that the most important factor deter- mining the magnitude of the titer of a suspension of a modified live virus strain is the quantity and concentration of viral par- 75. “Serologic Tests,” supra note 71, at 422-23. 76. Tr. at 1126 (Deposition of Dr. George M. Baer). This is not an absolute rule; the patho- genicity of a virus strain can vary from species to species, and “titer” measures the relative pa- thogenicity of a virus strain only with respect to mice. Tr. at 408 (Debbie); Tr. at 587-88 (Abel- seth Deposition). — A87 ticles in the suspension.” The titer of a particular virus strain can be increased ei- ther by passaging or by concentration.”8 By passaging a virus strain in animals, embryonated eggs, or cell cultures, the vi- rus replicates within the vehicle chosen for passaging, thus increasing the quantity of virus obtained.”? By concentrating a virus strain through one of a variety of available laboratory techniques, live viral particles are condensed into a smaller volume of 77. See Tr. at 1856-57 (Winkler) (indicating that the titer of a virus strain is directly reiated to the “dose” or quantity of viral particles con- tained within a given volume of v [Text truncated at 120,000 characters. The full text is on the page linked above.] --- Source: Frix Law Library, https://www.frixlaw.com/law-library/documents/brief%3Amicro_IA40385017_1038%3A2. Public record. Not legal advice.