The American military has, as indicated previously, successfully administered a WI-38 grown adenovirus vaccine to nearly 1 million recruits. Even today, other types of adenovirus vaccines prepared in WI-38 are under development by the military. Why has DBS resisted encouraging the development of vaccines produced in normal human cells of proven success overseas and in the U.S. military while steadfastly defending continued use of primary monkey kidney cells with all of its inherent risk? DBS has never officially responded to this question-a common posture that I will consider shortly.

In March of 1972, the first polio virus vaccine produced in normal human cells was licensed to Pfizer Ltd. by DBS for sale in this country, a full 10 years after the discovery of SV 40 contamination of primary monkey kidney cells and a full decade after the discovery of an alternative cell substrate. Not knowing what DBS's official view was during that decade, many observers felt that DBS has, in respect to primary monkey kidney versus WI-38, adopted the philosophy that it is better to live with the real devil you know rather than an hypothetical devil you do not know.

As indicated at the outset, this situation is one of several that speaks to the point concerning the slothful reaction by DBS to advances made in the field of vaccine development.

RUBELLA VACCINE

In 1961, the first rubella-German measles-vaccine was licensed by DBS. At least four groups of eminent scientists had developed strains of attenuated rubella viruses, each of which was a candidate strain for the first vaccine to be licensed.

In 1969, DBS awarded the first rubella vaccine license to the firm that ceased to work on its own strain and chose that developed by DBS scientists. An alternative explanation, given by the manufacturer in question, is that the "Benoit level B-the commercial strainand HPV-77 duck viruses-the DBS strain-were considered acceptable for large-scale work in children. The HPV-77 strain was chosen as the prime candidate for further vaccine pursuit by our laboratories in the best national interest of concentrating on a single virus which could be brought to general use in the shortest period of time." Under the circumstances, DBS could have hardly been expected to behave otherwise.

During the preceding years, when DBS scientists were developing their rubella strain, considerable national and international publicity for DBS's strain was generated by its public relations staff.

It now appears that the DBS rubella strain produces more undesirable side effects in recipients than do the remaining two strains, and it is very likely that in the next few years we will see a shift in use from the DBS rubella strain to one of the earlier unsuccessful candidates.

WI-38 SUBSTRATES

A reenactment of this scenario is now under way in which some of the players are changed but will act in a familiar plot.

DBS will be faced within a few years of choosing to license some human virus vaccine produced on a substrate developed under contract

to them--at a cost so far of $1 million-or a similar vaccine produced on a substrate developed by others say, WI-38. If that decision will be made by the DBS staff or by persons handpicked by them, then there is little doubt how that decision will go.

DBS IMAGE

My final point concerns a host of criticisms that have been leveled at DBS by many eminent scientists, for the most part bearing on its image as an agency that rarely acts but only reacts. Instead of assuming a leadership role in the area of biological products control, in the view of many DBS has assumed a role subservient to its constituency. This ultraconservative subservient to its

stituency. This ultraconservative position by DBS is best illustrated by the degree and kind of risk taking in which it has been involved. In general the greatest advancements made in human virus vaccine development in the past 20 years have been made by American medical scientists funded with public funds. Yet, these advancements when they have yielded new vaccine virus strains or new manufacturing processes have had their major tests for safety and efficacy in other countries. It seems to have happened by chance or otherwise that the major risks are undertaken in other countries. The live polio vaccine was licensed by DBS only after 15 million people were fed vaccines in the Soviet Union. The live measles vaccine received its first major test in Upper Volta. There are other examples.

The DBS has acted in many major areas by simply not acting at all, thus fomenting controversy and exacerbating differences that could have been aired and easily resolved. The tragedy is that the avoidance of major decisions by the DBS is unjustifiable for a regulatory agency for it inevitably works to the disadvantage of the public it is charged to protect.

RECOMMENDATIONS

On the basis of the aforementioned position, I would like to suggest the following recommendations for your consideration:

1. That all national biomedical control activities be placed under a single director and within a single agency. That is, the activities of the FDA, DBS, and the comparable control activities of the Department of Agriculture and the CDC be combined in an independent Consumer Safety Agency. Many of the activities of these agencies and others now overlap, and because they require equivalent kinds of expertise and laboratory facilities they represent a wasteful dissipation of effort. Furthermore, the distinction between those products that should be controlled by the FDA and those controlled by the DBS are becoming less discernible. The grey areas could be covered simply and more efficiently by an amalgamation of not only these two agencies but all Federal agencies responsible for the public health.

Such an amalgamation of agencies should result in a cross-fertilization, where some control activity now unique to one agency could be changed or adapted so as to improve a similar activity in another

agency.

2. The new agency should depend more on the judgment of expert panels with rotating memberships for scientific decisions and less on in-house personnel. These panels would be formed along the lines of existing study sections that advise the NIH on research grant applications and which have resulted in the highly successful and highly respected peer review system. The decisions of these proposed panels which would judge product safety, potency, purity, and efficiency would be in the form of recommendations to the director and his staff. One or more of these panels should oversee the research activities of control authority personnel.

3. No control authority should be permitted to sit in judgment of products or product components when the choice is between substances developed by that control authority and those competing with it from other laboratories. This result can be effected in either of two ways: (a) Limit research activity by control authority scientists to those areas directly related to the control and measurement of product safety, purity, potency and efficacy; or (b) disallow any control personnel from engaging in decisionmaking when a product or product component developed by them is competing with similar materials developed by others and for which licensing approval is requested. This is best accomplished by the system of expert panels drawn from the national biomedical community described in "2" above.

4. Establish within the DBS or its counterpart agency a Director or Deputy Director of Research to oversee the limited research activities appropriate to the agency's mission. However, if research at DBS is to continue to have the essentially undirected and subordinate role it now has, then the many competent scientists now there should be allowed to move on to an environment where they will enjoy a full flowering of their capabilities.

5. Replace the current DBS leadership with new individuals recruited from the biomedical community other than from the DBS itself. The scientific activity and personnel policies and responsibility of the DBS which have come under fire in recent months have so polarized its personnel and lowered morale that to choose a successor from within DBS ranks would be, in my judgment, a serious mistake. A search committee for a new Director of the DBS has in fact just been formed. This leadership change should also include reorganization by amalgamation of DBS responsibility with those of the FDA and other agencies responsible for the public health. This should include appointment of a scientific Director and establishment of an active system of expert advisory panels in all areas in which major decisions on the control and licensing of biological products depends upon the expertise of several scientists.

UNEVEN POWER STRUCTURE OF DBS

At present the structure of the DBS is uneven. Almost all of the power is centered in the Director with too little delegation of power, responsibility, and authority to others within the organization. A strong active middle echelon of administrators and scientists with authority to make decisions at a variety of levels is lacking. There is no limit to the Director's term of office, which is an unsatisfactory arrangement in any institution. His decisions are apparently unappealable and not subject to peer review or even effective peer support. This re

sults in a relationship getween DBS and the manufacturer in which the latter stands virtually in fear of the Director. Since he makes unappealable decisions that inevitably involve commercial profit, this posture on the part of the manufacturers is understandable.

The American people make a substantial investment in biomedical research, but very little attention has been paid to the widening gap between the fruits of laboratory research activity and the delivery of those accomplishments to benefit the people who pay for them. That gap should be partly filled by our control authorities whose responsibility is to narrow that gap and at the same time protect an innocent public.

Thank you.

Senator HARRIS. Thank you, Dr. Hayflick.

I think you have made a devastating case against DBS and its present policies and practices on all three criticisms which you have levelled.

I think you have made it clear that you do not feel just finding a capable scientist and administrator to head the organization will be enough, that there is going to have to be institutional changes?

REQUIREMENTS OF A NEW DIRECTOR

Senator HARRIS. I wanted to ask you, though: As you have said, HEW has already announced that a new Director of DBS is to be named. Do you have any feelings about what characteristics the research committee ought to look for in such a candidate, whether it is going to be in DBS or wherever else it is to be? Would you care to comment?

Dr. HAYFLICK. The combination of qualities that one would ideally like to have in such a Director are probably humanly impossible to obtain, so one obviously must reach a compromise.

I do not think it essential that the Director be a highly regarded basic research scientist. I do not think this is a necessary requirement. I think the individual needs to have skills in the health sciences and certainly knowledge of the field, in addition to expertise as an administrator and be an effective individual in dealing with personnel and with the community of manufacturers that the department serves. Other than those broad generalizations I am afraid I cannot give you any details.

Senator HARRIS. Are there countries you are familiar with who you feel have a more effective vaccine program than ours?

Dr. HAYFLICK. I do not know that the vaccine programs are any more effective per se because these developments largely stem from the vaccine scientists, as one might refer to them. But I do believe that some of the organization of vaccine control in other countries has meritorious components, some certainly superior to those in this country.

Senator HARRIS. Could you give us examples of countries like that and what we might learn from them.

UNITED KINGDOM

Dr. HAYFLICK. I think one of the most outstanding countries in the area of biological products control is the United Kingdom. I think

that this group is a progressive organization, that it is organized, obviously, in different ways than the Division of Biologics Standards in this country.

The Director does not wield the total power that I believe the Director of DBS does in this country. He is, in the United Kindom, answerable to a committee of specialists who command the respect of the biomedical community in the United Kingdom. This is one of the salient reasons why I make the proposal that a system of such committees might better respond to the goals of the Division of Biologics Standards as currently organized.

Senator HARRIS. Very good.

What about the question that has been raised that an agency that would be devoted primarily to regulation rather than research might not be able to attract and hold top level scientists?

Would you comment on that and, then, a related question: How is DBS doing in that regard as presently constituted?

RESEARCH ACTIVITIES

Dr. HAYFLICK. That issue is, in my judgment, largely a red herring. I think it has been raised only because historically, DBS has in fact attracted an echelon of highly qualified research scientists. And it is clear that several of these individuals-and I would probably say the Director in particular-would like to have research activities ongoing in the DBS, although they are, in my judgment, not very well organized.

I do not think that basic scientific research is an essential component of a regulatory agency. I think that what research activities might be conducted under the umbrella of the regulatory agency would best be confined to specific areas of research into tests for potency, safety, and efficacy, itself, the main charge of this particular regulatory agency. In respect to the question of attracting qualified personnel to regulatory agencies that may not be engaged in research, I think this is an issue that addresses itself to the variety of scientific species that exist among us. Many scientists find their peculiar satisfactions in the areas of basic research, others in the area of biological development that have a direct financial goal; others, in areas of quality control, or in teaching. I think the respect that their fellow scientists have for them is not colored, or at least hopefully not colored, by the kind of scientific activities, or teaching activities, that qualified scientists perform. Consequently the issue of research capability by members of a regulatory agency is in my judgment not essential.

PERFORMANCE

Senator HARRIS. You know DBS has argued that if you transfer control authority to FDA, that DBS presently has, there would be an isolation of control activities in scientific research and that would hinder the agency's performance.

Do you think that is so?

Dr. HAYFLICK. No, I do not think that is so. I think that the current activities of FDA, where research, to the best of my knowledge, is not stressed to the extent it is in DBS, has not compromised its policing