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A novel technique for transforming the theft of mortal human cells into praiseworthy federal policy

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Abstract

A revolution has occurred in the attitude of biologists toward their intellectual property rights. What today is patentable and highly profitable was, 20 years ago, unpatentable and given away for nothing. The history of this revolution began in the early 1960s when we made the first effort to have self-duplicating cell strains patented. The application was denied because patent law at that time did not include living matter. Because of the demand for our normal human diploid cell strain, WI-38, by NIH grantees, NIH support was provided to distribute WI-38 gratis to hundreds of recipients. These included vaccine and cell manufacturers who profited enormously from the direct sale of WI-38 or its use as a substrate for many human virus vaccines. When federal support for the distribution of WI-38 ended, but demand did not, I continued to distribute it for costs similar to those made by the American Type Culture Collection. When I took the first initiative and asked NIH to have the then unique question of title to a self-duplicating system resolved, they sent an accountant who accused me of theft of government property. I replied with a lawsuit that, after six years of litigation, we won with an out-of-court settlement. During these six years the United States Supreme Court ruled that living matter could be patented. Also, the biotechnology industry was launched by biologists who, like me, started companies using cells or microorganisms developed with federal support. This use of intellectual property rights by the nascent biotechnology industry was ultimately embraced by the entire biological community and by a directive from the President of the United States. This revolution has now evolved to the point where government biologists themselves may profit from research in federal laboratories, and the NIH itself aggressively seeks private commercial alliances. Universities have also pursued similar alliances to the extent that today the distinction between a research university and a commercial organization is only in the eyes of the Internal Revenue Service.
A NOVEL TECHNIQUE FOR TRANSFORMING THE THEFT OF
MORTAL HUMAN CELLS INTO PRAISEWORTHY
FEDERAL POLICY
LEONARD HAYFLICK
University of California, San Francisco, Department of Anatomy, P.O. Box 89, The Sea Ranch, California 95497
Abstract—A revolution has occurred in the attitude of biologists toward their intellectual
property rights. What today is patentable and highly profitable was, 20 years ago, unpatent-
able and given away for nothing. The history of this revolution began in the early 1960s when
we made the first effort to have self-duplicating cell strains patented. The application was
denied because patent law at that time did not include living matter. Because of the demand
for our normal human diploid cell strain, WI-38, by NIH grantees, NIH support was provided
to distribute WI-38 gratis to hundreds of recipients. These included vaccine and cell manu-
facturers who profited enormously from the direct sale of WI-38 or its use as a substrate for
many human virus vaccines. When federal support for the distribution of WI-38 ended, but
demand did not, I continued to distribute it for costs similar to those made by the American
Type Culture Collection. When I took the first initiative and asked NIH to have the then
unique question of title to a self-duplicating system resolved, they sent an accountant who
accused me of theft of government property. I replied with a lawsuit that, after six years of
litigation, we won with an out-of-court settlement. During these six years the United States
Supreme Court ruled that living matter could be patented. Also, the biotechnology industry
was launched by biologists who, like me, started companies using cells or microorganisms
developed with federal support. This use of intellectual property rights by the nascent
biotechnology industry was ultimately embraced by the entire biological community and by
a directive from the President of the United States. This revolution has now evolved to the
point where government biologists themselves may profit from research in federal laborato-
ries, and the NIH itself aggressively seeks private commercial alliances. Universities have
also pursued similar alliances to the extent that today the distinction between a research
university and a commercial organization is only in the eyes of the Internal Revenue Service.
©1998 Elsevier Science Inc.
Key Words: intellectual property rights, WI-38, theft, NIH, patents, profits
E-mail: len@gene.com
Modified and updated from a lecture originally presented March 6, 1989, at the Seminar on Clinical and Research
Applications of Human Cells and Tissues, American Association of Tissue Banks, Arlington, VA.
(Accepted 28 August 1997)
Experimental Gerontology, Vol. 33, Nos. 1/2, 191–207, 1998
Copyright © 1998 Elsevier Science Inc.
Printed in the USA. All rights reserved
0531-5565/98 $19.00 1.00
PII S0531-5565(97)00115-0
191
INTRODUCTION
ALEX COMFORT played a crucial role in the events to be described. He did so because, like other
colleagues, he was enraged by the enormity of an injustice that was being perpetrated by the
administration of Stanford University and the National Institutes of Health (NIH). Without his
clarion call for justice made to the editors of Science and to others who believed without
question the version of events that came from the Public Relations Offices of these institutions,
the events to be described would not have reached the happy conclusion that they did.
I dedicate this article to an uncommon man, Alex Comfort, physician, scientist, biogeron-
tologist, novelist, essayist, poet, playwright, translator, raconteur, amateur radio operator, the
Founding Editor of Experimental Gerontology, and magnificent iconoclast.
Twenty years ago a tenured medical school professor was accused of stealing government
property, handed over to the local police by their university, investigated by the district attorney,
shunned by his colleagues and illegally denied an NIH approved grant by the Department of
Health and Human Services for doing what, today, is encouraged by all universities, ignored by
the police and the district attorney, admired by their colleagues, championed by the NIH, and
stated by the President of the United States to be federal policy.
The act that I speak of is the sale, or commercial exploitation, of self-reproducing biological
systems discovered by university biologists, partially or fully funded by the NIH. As the first,
and only, American biologist ever to have experienced all of these events, I believe that I can
speak to the issues with some authority.
This episode, which began 35 years ago, should command the attention of all biologists for
at least three compelling reasons. First, the matter of title, or ownership, of novel self-
reproducing biological systems, which is the sine qua non of the biotechnology industry, has not
been settled even after my experiences and that of other colleagues. Second, the consequence of
this neglect is that all academic scientists engaged in the development of new biological systems
with potential commercial value remain potential victims of charges of theft. The third reason
why the scientific community should be interested in resolving this problem is that most of the
attitudes surrounding this issue have changed so dramatically in the last 35 years years that it
provides a monumental lesson in how fast the more than thousands of previously apathetic
scientists and their administrators can change when the interests of thousands transcend the
identical interests of a single person.
Alex Comfort, whose role in this issue will be discussed subsequently, was so distressed by
the behavior of Stanford University and NIH officials that he chose to dedicate the third edition
of his landmark book, “The Biology of Senescence” (Comfort, 1979) to me with the Latin
inscription: IN zCIVIVS zCALVMNIATORES zMINGIMVS a free translation of which is:
“We piss on those who malign.”
GENESIS
This story began 30 years ago when Paul Moorhead and I described the finite replicative
capacity of normal human fibroblasts and interpreted the phenomenon as aging at the cell level
(Hayflick and Moorhead, 1961). We showed that when human embryonic cells are grown under
the most favorable conditions, aging and death is the inevitable consequence after about 50
population doublings. We called this the Phase III phenomenon. We showed that, contrary to
dogma of 60 year’s duration, the death of cultured normal human cells was not due to some
trivial cause involving ignorance of proper medium components or culture conditions, but was
an inherent property of the cells themselves. The observation has since been confirmed in
192 L. HAYFLICK
hundreds of laboratories worldwide (Hayflick, 1979; Norwood and Smith, 1985; Norwood et
al., 1990).
At the time that our observation was made, the paramount dogma in cell culture biology since
its development in the late 1800s was that the failure of cells to proliferate indefinitely in vitro
must be attributable to errors in the “art” required to keep cells dividing forever. That dogma
was so well entrenched that our original manuscript in which we described the Phase III
Phenomenon was rejected in 1960 by The Journal of Experimental Medicine with the statement
that “The largest fact to have come out from tissue culture in the last fifty years is that cells
inherently capable of multiplying will do so indefinitely if supplied with the right milieu in
vitro.” The letter was signed by Peyton Rous, soon to be awarded the Nobel Prize in Medicine
or Physiology.
His belief, then universally accepted, was tantamount to the conviction that, given the right
milieu in vivo, human beings also will live forever. Ponce de Leon called the right milieu in vivo
“The Fountain of Youth,” and those who believe that any cultured normal cell must be immortal
if only the right medium can be found are, like Ponce de Leon, still searching for that fountain
of youth even after 35 years of failed efforts (Rubin, 1997).
In our description of the human diploid cell strains we reported that they have several
interesting properties (Hayflick and Moorhead, 1961).
First, if derived from human embryos, cell strains undergo about 50 population doublings.
The potential cell yield from 50 population doublings is about twenty million metric tons.
Second, we found that human diploid cells undergo a number of population doublings
inversely proportional to donor age. This suggested to us that the finite replicative capacity of
cultured normal cells is an expression of aging at the cell level. This notion received consid-
erable experimental support in subsequent years, and became the basis for the burgeoning field
of cell aging that we named “cytogerontology” (Hayflick, 1974).
Third, we showed that, if derived from normal tissue, cell strains have the diploid karyotype
and, unlike immortal cell lines, normal cell strains are incapable of replication in suspension
culture. Later this property was named anchorage dependence.
Fourth, we also demonstrated that human cell strains will not produce tumors when inoculated
into the hamster cheek pouch or even when directly inoculated into terminal human cancer
patients.
Fifth, we showed that human diploid cell strains can be cryogenically preserved. When, for
example, our first widely distributed normal human diploid cell strain, WI-38, which we
developed in 1962, is preserved at a particular doubling level and then reconstituted, the number
of doublings remaining is equivalent to 50 minus the number of doublings spent prior to
preservation. The cells have an extraordinary memory and “remember” at what doubling level
they were preserved even after 35 years years of continuous storage in liquid nitrogen. WI-38
has been preserved longer than any other normal human or animal cell population.
As a result of this characterization we suggested that all cultured animal and human cells be
classified into three groups: first, the primary cell culture, derived from intact tissue and
undergoing no subcultivations. Second, the cell strain that has (1) a finite capacity to replicate,
(2) does not produce tumors when inoculated into experimental animals, (3) has the karyology
of the tissue of origin, and (4) is anchorage dependent. The third class is the cell line, which is
(1) a population of immortal cells, that (2) may produce tumors when inoculated into laboratory
animals, (3) does not have the karyology of the tissue of origin, and (4) are usually anchorage
independent.
We, thus, made the distinction, for the first time, that cultured cells were either mortal or
193TRANSFORMING THEFT OF MORTAL HUMAN CELLS INTO FEDERAL POLICY
immortal, and that immortality resulted from the transformation of mortal normal cells (Hayflick
and Moorhead, 1961; Hayflick, 1965).
These distinctions, made 35 years years ago, have maintained their validity to this day when
an understanding of the mechanisms of immortalization has become a major quest.
HUMAN VIRUS VACCINES
In our first report on the human diploid cell strains we demonstrated the broad human virus
spectrum of these cells and suggested that human diploid cells could provide a superior substrate
for the production of human virus vaccines. In 1962, we prepared the first vaccine produced in
human diploid cells and showed this poliomyelitis vaccine to be safe and efficacious (Hayflick
et al., 1962). We argued that a diploid cell strain was safer than the primary cell populations then
used because of the ability to thoroughly test this class of cells before use. We introduced the
concept of a master cell bank and a working cell bank now universally used in the biotechnology
field (Hayflick and Jacobs, 1968).
These processes resulted for the first time in a reliable method for cell characterization based
on one concept—standardization.
In spite of these obvious benefits, the use of human diploid cell strains for the production of
human virus vaccines met with enormous resistance. This resistance was led chiefly by the then
Division of Biologics Standards (DBS), NIH (now called CBER and a part of the FDA) that
controlled all vaccines licensed for use in the United States. After 10 years of educational efforts
and striking successes with diploid cell strain vaccines in Europe, the DBS finally licensed a
poliomyelitis vaccine made in our human diploid cell strain WI-38 in 1972—a decade after the
original proposal was made (Hayflick, 1984).
Today, there are many licensed human virus vaccines produced in WI-38 or similar strains.
These include polio, adenovirus types 4 and 7, rubella, rubeola, varicella, and rabies. For
example, all of the rubella vaccine used in the Western Hemisphere is produced in WI-38.
Hundreds of millions of people throughout the world have been inoculated or fed vaccines
produced in WI-38 and other human diploid cell strains with no reports of untoward effects
traceable to the cell substrate itself.
TURNING THEFT INTO NATIONAL POLICY
In 1975 an incident involving WI-38 occurred that was to have a profound effect on our
concept of intellectual property rights and the emerging biotechnology industry. That incident
involved the ownership, or title, to WI-38 specifically. But generally, it involved title to all
self-reproducing systems. When we first described the human diploid cells, efforts were made
by the Wistar Institute, where I worked, to patent them. It was 1962, and the United States Patent
Office held that no patent law covered living systems like these cells.
In 1962, because of the enormous demand for WI-38 starter cultures by NIH grantees, the
NIH provided us with a contract to “Produce, Store and Distribute” it. In the spirit of the
prevailing scientific attitudes in the 1960s, original ampules of WI-38 were given gratis to
commercial cell culture manufacturers, pharmaceutical companies, and cell repositories world-
wide including those in the U.S.S.R. and in Eastern Block countries.
In the decade after WI-38 was developed I have conservatively estimated that WI-38 starter
cultures sold by cell culture manufacturers alone grossed well over twenty-five million dollars.
No value has been put on the additional hundreds of thousands of WI-38 cultures used by
vaccine manufacturers or cultures sold by third and fourth parties. No funds reverted to me, the
194 L. HAYFLICK
Wistar Institute, or to the federal government. The attitude during those years was that academic
biologists had no intellectual property rights, nor should title be vested in them or their
institutions for their development of new or unique life forms. Intellectual property was simply
given away by starry-eyed biologists because the taint of commercialism could ruin an academic
career. But, there was incredible irony and injustice in this. Commercial organizations, and even
the Eastern Block countries could, and did, freely obtain WI-26 (an earlier human diploid cell
strain that we developed) and WI-38 from me and sold or used them to produce enormous
profits. Yet, the academic institutions, the federal government, and even we, the scientists who
actually developed the cells, were forbidden from benefitting.
Our fellow academic scientists in electronics, physics, computer science, and chemistry had
long since learned that there was nothing unethical or wrong in turning their intellectual property
rights into commercial products for the benefit of the public and they and their academic
institutions benefited financially. Until 1975, the mentality of biological scientists was in the
stone-age with respect to attitudes toward profiting from their discoveries, when compared to
colleagues in other sciences. Biologists simply gave away to others what they discovered, and
the recipients of their largesse often profited immensely. Recompense to the creative biologist
often consisted of nothing more than a fine dinner. I know this to be true, because a pharma-
ceutical company freely given WI-38 for vaccine manufacture invited me to one.
From the time that our NIH contract to distribute WI-38 ended in the early 1970s until today,
WI-38 sales by commercial marketers of cell cultures have grossed well over 100 million
dollars. In addition, vaccine manufacturers in many countries have used WI-38 obtained from
me for the manufacture of millions of doses of human vaccines with a total value of well over
one billion dollars.
Because of these events I began to realize in the late 1960s the great injustice caused by the
official denial to biologists of what seemed to me to be their right to a share of some proportion
of funds that might be realized from the commercial exploitation of their intellectual property.
I felt that the exploitation of my discovery was not only commercially proper but also laudatory
on grounds of the medical benefits that had accrued and continue to accrue to the hundreds of
millions of recipients of vaccines produced in WI-38. However, the official position of the NIH
that the inventors of something having commercial value should be denied any benefits was, I
felt, not only unfair but logically absurd.
In 1975 in an effort to settle this then unique question of title to a self-duplicating system, I
took the first initiative and asked the Director of the NIH to make a definitive determination of
my title to the WI-38 cell strain. By that time my company, incorporated in 1972, and one of
the first formed in the new biotechnology era, had sold starter cultures of the cells openly for
more than five years—even to the NIH itself—in the honest belief that this was legal and fair.
The distribution contract had ended, and I had no support to store or distribute the cells. The
costs of storage, packaging, distribution, and record keeping were not trivial. I charged prices
similar to those charged by the American Type Culture Collection.
Instead of sending a lawyer, and or a scientist, who might understand the complex and then
unique circumstances of my claim, the NIH sent an accountant who, failing to understand the
law, the science, or the larger issues of my unique position, prepared a report in which he
concluded that I had stolen government property and sold that property for personal gain. Worst
of all, the NIH released his damning report after a Freedom of Information Act request was
made by a curious reporter who had heard some mischievous rumors (NIH Report, 1976).
In 1975, I decided to challenge the absurdity of the NIH’s report by filing a law suit against
the then Department of Health, Education and Welfare and the NIH, in which I claimed title to
195TRANSFORMING THEFT OF MORTAL HUMAN CELLS INTO FEDERAL POLICY
WI-38 and all proceeds from sales of WI-38 made after our contract ended. My suit also claimed
that the NIH, in releasing the accountant’s report without my rebuttal, had violated the Privacy
Act of 1974.
CRUCIAL EVENTS
During the time that this litigation was underway several crucial events occurred that
impacted on my lawsuit. First, in 1977, two years after I filed my suit, the U.S. Court of Customs
and Patent Appeals reversed itself and ruled that even though micro-organisms are alive, “we do
not see any reason to deprive it, or its creator or owner, of the protection and advantages of the
patent system.”
Four years after I filed my suit and during my litigation in 1980, the patent laws dramatically
changed with the Diamond vs. Chakrabarty decision (447 US 303, 1980). This Supreme Court
decision opened the way for the eventual patentability of micro-organisms and cell populations
that were then becoming the basis for the emerging biotechnology field. Most, if not all, were
developed with full or partial federal grant or contract support. In the late 1970s a cell or
microbial culture was simply taken from an academic institution to an emerging biotechnology
company and utilized in industrial processes.
There are dozens, if not hundreds, of examples of self-duplicating biological materials,
produced in whole or in part with government funds and exploited commercially with no benefit
to the government or, in most cases, to the inventor. One example of this generality, of many
that could be given, are the cell populations currently sold by cell culture manufacturers. A
glance at their product catalogues shows dozens of cell populations offered for sale that were
derived by scientists supported with federal funds. There are even cells being sold, like the L
cell, that was developed at the NIH itself.
Why are the companies that sell these cells not guilty of theft and sale of government property
if the NIH believed, as it did, that all of WI-38 was NIH property?
Nevertheless the NIH and the scientific community did not anticipate, until quite recently,
what we first pointed out in our suit in 1975. We argued, I believe for the first time, that not only
did my former institution and I have a legitimate claim to the cells, but a good case could be
made for title to WI-38 to be vested in the parents or estate of the embryo from which WI-38
was derived. We had anticipated by more than a decade the current controversy over title to
self-reproducing human cells by the donor patient. I refer here, for example, to the question of
title to the Mo human cell line, established at UCLA, and which was in litigation for years.
A second example of controversy over title to a cell population is the human hybridoma made
from the fusion product of the human cell line UC 729-6 and the lymphocytes of the mother of
a Japanese postdoctoral student at the University of California, San Diego. The student wanted
to use the hybridoma to treat his mother who was dying of cervical cancer. He was refused
because his preceptor was a shareholder in Hybritech, who funded part of the research, and the
student ultimately was forced to resign from the University. After some unpleasant publicity the
matter was finally settled out of court. Nevertheless the question of ownership of cells based on
familial ties has never been settled (Sun, 1983)
There is even a question of title to cells and their products when those cells are produced by
commercial organizations, patented, deposited at the American Type Culture Collection
(ATCC), and subsequently used by researchers in universities and at the NIH. The Johnson and
Johnson Company sent about 25 letters to scientists in universities, other companies, and to the
NIH warning them that their use of the hybridoma cells deposited at the ATCC may infringe on
196 L. HAYFLICK
the companies patent rights “. . . regardless of whether the thus-produced antibody is subse-
quently used or sold.” The NIH patent attorney, Mr. Thomas Ferris, said, “We don’t consider
it an infringement (for researchers to use the cells) as long as it is experimental.” But the
Johnson and Johnson subsidiary, Ortho Diagnostics, is selling the antibody for research and
diagnostic purposes; thus, use of those antibodies by NIH or others clearly compromises
potential Ortho sales to them. The NIH’s patent attorney Mr. Ferris said, “. . . ultimately (the
issue) can only be resolved in the courts” (Fox, 1984).
After six years of litigation my lawsuit was settled in 1981. During this period many scientists
profited enormously from their intellectual property rights. I applaud this.
In 1983, title to the interferon producing KG-1 cell line, partly developed with NIH funds,
was settled out of court by Hoffmann-LaRoche and UCLA. Although the settlement terms were
not made public, as mine were, Dr. David Golde, one of the cell lines developers, said that the
University received “what I consider to be a large sum.” Yet the KG-1 cell line was produced
in whole or in part with the support of NIH funding and the cells even passed through the NIH
laboratories of Dr. Robert Gallo on their way to Hoffmann-LaRoche. Never was UCLA or the
developers of the KG-1 cell line accused by the NIH of theft and sale of government property.
In fact, the NIH ignored the matter of title entirely (Budiansky, 1983).
Unlike the accusation of theft that was trumpeted by NIH in the press against me, Golde and
Koeffler were not similarly accused for their role in an identical act. This is the result of the
profound change in attitudes that has occurred in the biological community and the concomitant
revolution in the NIH’s thinking that began when they came to me in 1982 with a request for
an out-of-court settlement. Nevertheless, the acrimony of the KG-1 case caused serious harm to
the reputations of all the scientists involved, and still the matter of ownership of the cells
remains unsettled.
To do in the 1970s what is commonplace today would be to have had yourself charac-
terized by the accountant-led NIH Office of Management Survey and Review, as I was, of
having engaged in the theft of government property and its sale for personal gain (NIH
Report, 1976).
Of the many ironies that occurred during this saga none is more astounding than the fact that
after a decade of futile efforts by us to have WI-38 accepted for use in the production of human
virus vaccines by what is now the FDA, those same public servants eventually wanted WI-38
so desperately that they publicly pronounced them to be “a national resource.” Subsequently, in
my absence, they entered my laboratory in 1975 and confiscated them! A later irony appeared
in 1988 in the Guide for Grants and Contracts published by the NIH. A new NIH policy was
announced that revealed the extent to which the conversion of NIH thinking had evolved from
what they formerly characterized as theft by me in 1975, to government policy in 1988: “It is
the policy of the Public Health Service to make available to the public the results and
accomplishments of the activities that it funds. Restricted availability of unique resources upon
which further studies are dependent can impede the advancement of research and the delivery
of medical care. To facilitate the availability of biological materials and resources to the
scientific community, investigators may distribute the materials through their own laboratory or
institution....Institutions and investigators may charge the requestor for the reasonable cost of
production of unique biological materials, and for packaging and shipping. Such costs may
include personnel, supplies, and other directly related expense (NIH Guide, 1988).”
197TRANSFORMING THEFT OF MORTAL HUMAN CELLS INTO FEDERAL POLICY
WHEN IT’S PROFITABLE, LET ME KNOW
There are many other examples in science of an invention or resource that is recognized early
to be valuable by its developer but, despite the claims, it is ignored by others. An amusing
example of this phenomenon which, for lack of a more succinct term, I will call the
“I’m-not-interested-in-what-you-have-now-but-if-after-you-struggle-to-successfully prove-
that-it-is-valuable, -I-will-do-everything-possible-to-steal-it-from-you” phenomenon.
This attitude is widespread and of the many examples, other than my own that I could give,
one will suffice. The incident occurred at the University of Florida where Dr. Robert Cade, the
inventor of Gatorade, came to University officials about 25 years ago and described his
invention. He asked them to support marketing the drink because he developed it in his
university laboratory. They refused. In 1972, after Cade risked the borrowed funds from his
family and friends, Gatorade began to register millions of dollars in annual sales. Sensing that
this was now a proven winner for which now they need not take any risk, the University of
Florida sued Cade for a piece of the action claiming, as Cade had originally told them, that it
was developed in university laboratories. Ultimately, an out-of-court settlement was reached in
which the same university that originally laughed at Cade now reaps millions in annual royalties.
Cade recalls, “They said it was a crazy idea, but when it was successful, they wanted it”
(Flinchbaugh, 1987).
THE GOVERNMENT BACKS DOWN
In my case, I am pleased to say that after seven years of litigation, the Justice Department, the
NIH, and the DHEW came to me in 1981 with an offer for an out-of-court settlement. The
settlement finally agreed upon by me provided that (1) many of the original ampules of WI-38
confiscated from my laboratory would be returned to me; (2) all funds realized from the sale of
WI-38, with interest, belonged to me; (3) WI-38, which until then could be sold by anyone
except its inventor, could now be sold by its inventor; and (4) title to WI-38 was not vested
exclusively with the government, as the NIH had absolutely insisted was true, but that my claim
to title had equal merit. The Justice Department, the NIH, and the DHEW also agreed that the
Privacy Act of 1974 had been violated by the NIH and they agreed to place a copy of the
out-of-court settlement into the hands of everyone who asks for a copy of the damning report
prepared by their accountant (NIH Report, 1976).
I should add that the funds won in this settlement, plus much more, were all consumed in
payment of my costs of litigation. Many believe that one compelling reason why the NIH came
to me with the offer for an out-of-court settlement was because attitudes toward the intellectual
property rights of biologists were then changing rapidly. This occurred because of the phenom-
enal growth of the biotechnology industry at that time and the general awareness of their heavy
dependence on the exploitation of biological materials developed in universities with NIH funds
and appropriated on a massive scale by these emerging companies.
Many believe that had we not prevailed in our litigation, the current status of title to new life
forms developed in whole, or in part, with federal funds would be quite different. Title to
hybridoma populations, DNA sequences, unique cell populations, plasmids, and life forms
expressing new recombinant DNA properties is now vested in the institutions or the scientists
who developed them, regardless of federal support. Attorneys representing scientists and
nascent biotechnology companies claiming title to self-duplicating systems intended to provide
legal briefs in our support if our case had ever gone to trial. If we had lost our suit it is probable
198 L. HAYFLICK
that the assignment of patent and property rights by the government would have been quite
different than it is today.
ENTER THE PRESIDENT
My position received its greatest support from action by the President of the United States.
In 1983, President Reagan instructed federal agency heads that all businesses should be able to
retain patent rights on inventions made in the course of government-funded R&D work. He said
that the administration takes the view that giving the private sector clear title to patents on
inventions developed under federal contracts and grants will lead to more rapid commercial-
ization of new products and processes, and combat the slump in United States productivity and
competitiveness (Walsh, 1983). In 1989, Senator Pete Domenici (R—N.M.) said, “I don’t see
the problem. We’ll never make any progress in our economy unless someone can profit from a
discovery. If I had to choose between holding back development, and letting an individual profit
from publicly supported research, I’d opt for the profiting” (The Scientist, 1989).
In the next year, 1984, I received a letter from Mr. Leroy B. Randall, the Chief of the Patent
Branch of NIH (Randall, 1984). He wrote, “Please be advised that your interpretation is correct.
If the cell population is unpatentable or is not patented (as WI-38 could not), the cell population
is the property of the grantee institution or the contractor.” I should also add that his statement
came from Public Law 96-517, which specifically states that it is applicable to inventions made
with public funds prior to July 1, 1981. WI-38 was developed in 1962, partly with public funds.
This official about-face and revolutionary government policy change that fully embraces my
original position has evolved to the point where now, not only are businesses able to profit from
federally funded R&D work, but so also are government employees themselves!
This latest development could not have been dreamt of with the troglodyte mind-set that I
encountered in the 1970s. The reaction then would have been that any government employee
who profits from inventions made in government laboratories is asking for a penitentiary
sentence. Today, these employees not only avoid prison but are celebrated by the government
and entitled to a maximum of $100,000 annually in additional recompense over their regular
salary for their intellectual property rights!
The same government that accused me of stealing its property and selling it for personal gain
is now spending an enormous amount of energy and money to publicize the fact that government
employees themselves are encouraged to profit from R&D work done in their federally owned
and supported laboratories. In light of my experiences, this development is almost beyond belief.
One of the best examples of this policy occurred in 1983 when federal scientists began selling
their research on the Strategic Defense Initiative (“Star Wars”) for private gain. The White
House strongly defended them by saying that it is legal, best serves the public interest, spurs
scientific incentive, and encourages industrial productivity. The New York Times of November
4, 1985, reported that “Federal scientists are excitedly planning to capitalize on their Govern-
ment research and in some cases have already made financial gains” (Broad, 1985).
In an article on the front page of the Sunday edition of this same newspaper in 1976, I was
accused of stealing government property when, not as a government employee, I openly sold
cultures of WI-38 cells for almost six years for use in biological research, human virus detection,
and the manufacture of human virus vaccines.
I was pilloried for facilitating the development of highly successful poliomyelitis, rubeola,
rubella, adenovirus, and rabies virus vaccines almost a decade after NIH partial support ended.
Today, federal space scientists are lauded by the same government for selling the products of
199TRANSFORMING THEFT OF MORTAL HUMAN CELLS INTO FEDERAL POLICY
Star Wars. Furthermore, WI-38 cells were not developed in a federal laboratory but in a private
laboratory. Nevertheless, the same government inferred that, unlike the Star Wars’ federal
scientists, my activities in assisting biomedical research and human virus vaccine development
were illegal, did not serve the public interest, did not spur scientific incentive, nor did it benefit
industrial productivity. Nevertheless, it is common knowledge that several hundred million
people throughout the world have benefitted from vaccines produced in WI-38.
Today, many scientists and their institutions legitimately profit from the sale of self-dupli-
cating materials that they have developed with or without federal support (Nelkin, 1984). I
support this. The attitude today is exactly opposite to what I experienced in 1976. In 1998, if you
do not hold a patent on a cell population, plasmid, or microorganism, or you are not a
stockholder or scientific advisor to a company that exploits such materials, you are a failure in
biology. Indeed, as of 10 years ago more than one-third of the biomedical members of the U.S.
National Academy of Sciences have formal ties to both corporate and academic institutions
(Shulman, 1988a). In a 1990 survey, from 10 to over 30% of the biomedical facultys of this
countries leading universities had formal commercial ties (Marshall, 1990). Surely, these
percentages must be greater today. In Marcus Tullius Cicero’s orations against Cataline he put
it best when he said, “O Tempora! O Mores!” For those who have forgotten their Latin a loose
translation would be, “Oh how much our mores change with time!”
ENDURING STAINS
In spite of the profound changes that have taken place since my litigation ended, my
reputation still bears the stains of having been charged by the NIH with theft of government
property. The charges were made by a few bookkeeper-zealots from the NIH Office of
Management Survey and Review with the complicity of several other NIH and DHEW public
servants. The charges were made in a document (NIH Report, 1976), that was given to the press
by the NIH in violation of the Privacy Act of 1974, which triggered my suit against them. These
events caused the Dean of the School of Medicine at Stanford University, where I held a full
professorship, to accept the charges made by the NIH bookkeeper without question and without
the benefit of understanding the unique circumstances of my position. I am told that the Dean’s
reaction was based substantially on being advised by the bookkeeper that his cooperation was
expected because 90% of his budget came from the NIH. I resigned from Stanford University
to protest my unwillingness to be associated with an institution whose leadership behaved so
reprehensibly.
Our eventual victory in the out-of-court settlement, with one exception, was ignored by both
the popular and scientific press who had trumpeted the false charges on the front pages of many
American and foreign newspapers and science magazines six years earlier. These included The
New York Times, who published the false charges on the front page of their Sunday Edition and
Science, who published damning articles by Nicholas Wade. This publicity occurred because the
NIH and Stanford University used their Public Relations and Press Departments to trumpet their
false understanding of the situation. Individuals do not have this kind of organized and
professional relationship with the media and are left helpless to effectively communicate
protestations and to counter false charges.
The accused is often reluctant to refute his accusers because to do so will add to the list of
his faults, a persecution complex, or the belief by readers that “The dignity of truth is lost with
much protesting” (Jonson, 1611). And so the poison is almost always fatal because even if the
victim is ultimately vindicated completely, as I was, that uninteresting news will rarely be
200 L. HAYFLICK
delivered as effectively as were the original sensational charges. Thus, tens of thousands of
readers of the false charges were never informed by those publications that the lawsuit was
settled in my favor.
When we won the out-of-court settlement no press release was ever issued by the NIH or by
Stanford University. Thus, it is not popularly known that our stand, originally viewed by the
NIH as theft, actually set a precedent that is now not only vigorously encouraged by them but
also by the entire biological academic community.
In 1996, Stanford officials fell victim to poetic justice when, after being vindicated on a
government charge of fraud that was widely reported in the media, Gerhard Casper, University
President said, “. . . the reputation and integrity of individuals and institutions have been sullied
[by the] sensationalism that characterizes so much of our public life.” Donald Kennedy, the
former Stanford President on whose watch the charges were first made said, “The fact of life is
that settlements and ultimate judgments get carried on page 17 when the accusations get carried
on page one” (Friedly, 1996).
There was only one publication that was embarrassed into publishing a short note about the
resolution of these events. Science, which originally published many pages of erroneous
information and opinions, reacted to our court victory by printing a one-eighth page news item,
only because 85 of my colleagues had written a letter to Science in which they described their
displeasure about the initial publicity and the enormity of the about-face performed by the NIH
(Strehler, 1982).
ALEX COMFORT’S ROLE
It was Alex Comfort who rallied to my side when Science first published an article by
Nicholas Wade in which Wade came as close as it is possible to come to accusing me of
benefitting from the theft and sale of government property (Wade, 1976). My attempts to have
Science publish my rebuttal to the Wade article was met with outright refusal. Alex Comfort,
who was incensed with the injustice of this, wrote a scathing letter to Science demanding that
I be given equal time. The weight of his reputation and the persuasive content of his letter caused
Science to reverse itself and they reluctantly published my rebuttal (Hayflick, 1977). But, unlike
the articles written by Wade, which were published unrefereed, the editors of Science demanded
that my rebuttal be reviewed by two outside referees.
Many years later I sent to Nicholas Wade a copy of an article I wrote, which contained the
main points of the present article. He replied, “It’s certainly true that attitudes toward commer-
cialization of research have changed in the last fifteen years. With best wishes for the New Year,
Nicholas Wade.”
To add further to the irony, in 1986, I was made a Fellow of the American Association for
the Advancement of Science (publishers of Science) “for fundamental studies of the finite
lifetime of cultured normal cells....
It is not widely appreciated that, because of our out-of-court settlement many wrongly
accused scientists have not, and in the future will not, suffer from violations of the Privacy Act
of 1974 by the NIH. As a result of our litigation, every federally funded scientist in this country
is protected from defamation, because when the NIH releases investigative reports they now
cannot contain personal identifiers. This is extremely important because, again unknown to most
scientists, anyone bent on ruining a reputation can anonymously accuse a federally funded
scientist of wrongdoing and then enjoy the full cooperation of the NIH, whose policy it is to
investigate all such tips no matter how, or from whom, they are received. NIH inquisitors will
201TRANSFORMING THEFT OF MORTAL HUMAN CELLS INTO FEDERAL POLICY
then descend upon all of one’s friends and colleagues asking the most intimate questions and
arousing their darkest suspicions. When your innocence is discovered by the NIH investigators,
that fact is not reported to the persons questioned, thus leaving them with their anxieties and you
with your reputation to repair. A report always results from such an investigation, and it can be
released to the press or anyone else through a Freedom of Information Act inquiry.
Despite the favorable outcome of my experience, I cannot easily express the enormity of the
emotional stress endured by me, my family, and our friends because of a small NIH cabal who
had formed opinions about title to a self-duplicating system that, until that time, had never been
addressed by the law or by the biological community. As subsequent events proved, these public
servants were forced to do an about-face on their beliefs by edict from no less than their ultimate
boss, the President of the United States, who completely embraced our position in 1983 (Walsh,
1983).
Although my suit had a happy ending, many of the early negative feelings directed towards
me as a result of the initial tragic publicity have not changed. This can be attributed to the fact
that individual scientists do not have public relations departments capable of overcoming
negative information promulgated by similar departments at government and university facili-
ties.
THE REVOLUTION
The extent to which Universities, biologists, and the federal government have embraced the
principle that we advocated and defended, can be measured by the dramatic changes in federal
policy that have occurred over the past few years. I support all of these changes, not because I
am envious of the benefactors or bitter about my experiences, but simply to point out the extent
to which my position has been adopted by my accusers as their own philosophy.
The Federal Technology Transfer Act of 1986 (Public Law 99-502) requires federal agencies,
including the NIH, to reward their scientists with not less than 15% of royalties arising from
their work, and up to $100,000 per year. The more than 700 federally operated laboratories now
are encouraged to undertake cooperative research with private companies, universities, and state
organizations, and even to assign patent rights to them if that will accelerate technology transfer.
Science fairs are held at the NIH and other government laboratories in an effort to court
commercial interests (Byrne, 1988).
Before 1986 the attitude was that if the research was supported with public funds, then it
should be free for anyone to use. The result of this policy was that few, if any, entrepreneurs
would want to exploit an invention because what is available to everyone is commercially
worthless. The result was that what might become available to everyone became available to no
one. A former physicist at the Oak Ridge National Laboratories who started two companies put
it well when he said, “Twenty-years ago, any involvement with industry was considered
unethical. Now it is enormously encouraged” (Charles, 1988).
Ronald Cape, then President and CEO of Cetus Corporation, one of the first biotechnology
companies, also acknowledges that what was once characterized as the theft of government
property for personal gain is now acknowledged as acceptable practice. In response to being
asked about his strong support for academic research he candididly admitted that, “Biotech has
grown in a unique way. It is built on the monumental investment of the American taxpayer over
the last 40 to 45 years; an investment that has paid off handsomely. All the information deriving
from it is public and has been extensively mined by the commercial sector” (Powledge, 1987).
As for universities like Stanford objecting to the use of their facilities for private gain by their
202 L. HAYFLICK
faculty, as it did with me, the practice is so widespread that most current faculty would be
dismissed if this notion was uniformly enforced. There is one example of many that could be
given of using university facilities for personnel gain, for which most faculty are guilty and, if
enforced, would empty most universities of their staffs. Faculty members usually sign a patent
and copyright waiver as a condition of employment. The conditions normally stipulate that all
income produced when using university personnel, facilities, or equipment for writing belongs
to the university. If that rule was strictly enforced virtually every faculty member in this country
would be found guilty of theft of university funds. Furthermore, any university employee who,
in his or her capacity as a consultant, uses university equipment, personnel, typewriters, or
computers as part of their consulting duties is equally guilty of theft of university funds. That
rule is honored more in the breach than in the observance.
The Vice President of Development at one of the most successful Silicon Valley start-up
companies called MIPS, gave Stanford University 25,000 shares of stock and in doing so said,
“A lot of the technology we use was developed at Stanford’s Electrical Engineering and
Computer Science departments. We just wanted to thank Stanford for helping us get started”
(Stanford Campaign News, 1988). This is tantamount to admitting that Stanford facilities were
put to good use by this company yet, since the discovery of “misuse” of its facilities was not
made by the university when it occurred, the faculty members survived with their reputations
intact and in Kafkaesque fashion received honors from the university for their thoughtfulness in
making a contribution of stock.
With the development of the biotechnology industry a revolution occurred in the attitudes of
university administrators and their biomedical faculties. What was previously regarded as the
misuse of university facilities for personal gain has now become part of a frenzied effort by the
same administrators to lease the use of their facilities and the intellectual property rights of their
faculty members to the highest bidder. Many senior university officials have perplexed their
speech writers by having them struggle with the nuances of convoluted language to escape from
previous noble statements about the purity of their enterprises to justify their present anachro-
nistic positions.
Major universities that previously condemned their faculty for profiting from their inventions
find themselves a bit like the girl who turned to prostitution because she realized that she could
command a good price for what she used to give away for nothing.
Today, most academic biomedical scientists are consultants, board members, or shareholders
in their own or other biotechnology companies. If not, they are considered to be failures. These
new relationships are a part of what has been called the University–Industrial Complex (Kenney,
1986). In my view that term is an oxymoron because today’s large research university is only
distinguishable from an industrial enterprise because the Internal Revenue Service chooses to
tax the profits of one and not the other. In fact, the phenomenon is well recognized by University
leaders, one of whom is A. Bartlett Giametti, former President of Yale University, who
characterizes it as the “corporatization” of the American University (Fiske, 1986).
In virtually all respects, universities are indistinguishable from commercial organizations.
Today’s large research university has taken on most of the trappings of the very institutions that,
in the past, it tried so desperately not to emulate. The modern research university, like all
successful commercial enterprises has, for example, a legal department, patent offices, business
development offices, and accounting practices that differ little from most commercial enter-
prises.
University Presidents have been reduced to fund raisers, and the bottom line for a university
is indistinguishable from that of any commercial enterprise. Columbia University has developed
203TRANSFORMING THEFT OF MORTAL HUMAN CELLS INTO FEDERAL POLICY
a formula used to browbeat its research faculty that measures the amount of grant money raised
by each faculty member as a function of the square footage that they occupy. Universities, like
department stores, now calculate the amount of gross sales (grant overhead) per square foot as
a means of “motivating” their faculty and determining which department is more “productive.”
Harvard University is one of many universities that have embarked on their own marketing
ventures using a limited partnership established with a private investment consortium to profit
directly from the labor of the research of its own faculty which, in turn, is supported in full, or
in part, with taxpayers money (Shulman, 1988b).
The University of California started its own for-profit company, UC Technology Develop-
ment Co., in 1992, to exploit faculty research, and its new 1996 “STAR” project uses university
and private-company funds to support research by its faculty conducted on state property and
with some direct or indirect federal support (Anderson, 1992). The objective, in part, “...isto
build lasting linkages between California’s businesses and UC scientists. . .[and] to counteract
well-funded efforts from other states to lure away California’s biotechnology firms and UC’s
science base.”
The Johns Hopkins School of Medicine and Genetics Institute, Inc. have formed a new
company, MetaMorphix, Inc., to develop and commercialize molecules regulating cell growth
and differentiation (Genetic Engineering News, 1995). The MIT Industrial Liaison Program,
half of whose member companies are foreign (52 are Japanese), can, for 10 to 50 thousand
dollars, have easy access to the $300,000,000 a year of MIT research results, of which most is
supported by the federal government (Anderson, 1989). These university–commercial alliances
are only a few examples of many more that could be given.
The ultimate example of the profound reversal of position made after our pioneering efforts
has been adopted by the NIH itself. It is not widely known that now investigator-initiated
awards, commonly known as R01s, are available for use in commercial organizations. This
taxpayer-supported research may replace company-supported research and result in a product
beneficial to that company.
In the Federal Technology Transfer Act of 1986, federal laboratories are encouraged to enter
into Cooperative Research and Development Agreements (CRADAs) with industry to “hasten
the process of getting discoveries out of the labs and into the marketplace” (Byrne, 1988). A
CRADA allows a federal laboratory to provide personnel, services, and property toward a joint
research project and an exclusive product license with a commercial firm. The NIH scientist is
entitled to a minimum share of 15% of the royalties. This heretical concept, which virtually
mandates that NIH scientists form industrial partnerships (there were 200 commercial members
in 1989) was so unthinkable in the 1960s and 1970s that an NIH scientist who did this at that
time would have been committed to a federal penitentiary for using federal resources to benefit
a commercial enterprise (Culliton, 1989).
As stated by Niels Reimers, director of technology licensing at Stanford University and
generally regarded to be the dean of the revolution in university–commercial links, the name of
the game is “marketing, marketing, marketing” (Buderi, 1988).
SOLUTIONS
Meir Wilchek is a Professor at the Weizmann Institute of Science in Rehovoth, Israel. He is
a victim of patent law as is Cesar Milstein, the Nobel Laureate who discovered how to make
monoclonal antibodies using hybridomas. Many other scientist–victims could be named.
Wilchek discovered affinity chromatography and its application to biomedical research. At least
204 L. HAYFLICK
in respect to American patent law, appreciation of the discovery did not occur to Wilchek until
more than one year after his publication, thus preventing United States patent protection. Like
hybridoma technology, affinity chromatography has virtually revolutionized biotechnology.
Wilchek’s studies were partly conducted at the NIH, and the technology has earned tens of
millions of dollars for commercial companies. He has benefitted only trivially and takes home
$1,200 a month at the Weizmann Institute. Wilchek is satisfied with this income, but he feels
that it is unfair, if not immoral, for commercial companies to be the sole beneficiaries of
someone else’s efforts, even if they are legally entitled to do so. He has proposed that such
companies should voluntarily set aside one-half percent of their net earnings for research grants
to scientists from whom they have “borrowed” the ideas or technology that have made them
such handsome profits. This is much less than they would have to pay in royalties on a valid
patent, and it would encourage unconventional research, to say nothing of being just. In my
view, the scientific community in this country, through their professional societies, should take
the initiative in efforts to have legislation passed embodying the principles suggested by
Professor Wilchek (Meyers, 1987).
My purpose in describing these matters is to impress readers with the fact that despite the
profound turnaround in attitudes and rules by scientists and by public servants, several of the
fundamental issues of intellectual property rights have not been resolved.
Today, all federally supported university scientists are still at risk because of the apathy of the
scientific community in resolving these important issues. In a more narrow sense, the matter of
title to the progeny of a self-duplicating biological system also needs to be settled.
ENVOI
In her book, published by the American Association for the Advancement of Science
(publishers of Science) and titled “Science as Intellectual Property: Who Controls Scientific
Research?” (Nelkin, 1984), Dorothy Nelkin writes: “The rapidly changing viewpoints about
individual entrepreneurial ventures in science are illustrated by the case of microbiologist
Leonard Hayflick. In 1976 Hayflick, then at Stanford University, was embroiled in a conflict
with NIH over the ownership of a cell line that he had developed in the 1960s. It was the first
strain of normal human cells that could be established in a culture, and he formed a company
to market the cells which were found to be useful in the production of vaccines. NIH publicly
charged Hayflick with profiting from research conducted with federal support and claimed that
the cells belonged to the government.”
“. . . [Hayflick] filed suit seeking title to the cells and the proceeds from sales. After a long,
often acrimonious dispute, the case was settled out of court in 1981, with Hayflick retaining the
money from sales but with the question of ownership of the cell line still unresolved.”
“Today Hayflick’s actions would not be controversial. It is now accepted practice for
scientists and institutions to profit directly from the results of academic research through various
types of commercial ventures.”
Acknowledgments—I would like to thank the following individuals, whose judgments and decisions on diverse subjects
resulted in the circumstances portrayed herein and without whom these interesting events would not have occurred and
this article could not have been written: Dean Clayton Rich, Stanford University School of Medicine; John Schwartz,
Legal Advisor to the Dean of the Stanford University Medical School; Richard Lyman, President, Stanford University;
James W. Schriver, Director, Division of Management Survey Review, NIH, Bethesda, MD; Leon Jacobs, NIH; Hope
Hopps, Center for Drugs and Biologics, FDA; Donald Murphy, NIA, NIH; Jack Gruber, Biological Carcinogenesis
Branch, NCI, NIH; Ronald Lamont-Havers, Acting Director, NIH; Donald Fredrickson, Director, NIH; William Raub,
205TRANSFORMING THEFT OF MORTAL HUMAN CELLS INTO FEDERAL POLICY
NIH; Nicholas Wade, Science Magazine; and Joseph Califano, Assistant Secretary of Health, Department of Health,
Education and Welfare, Washington, DC. (Affiliations apply to the time the events occurred.)
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207TRANSFORMING THEFT OF MORTAL HUMAN CELLS INTO FEDERAL POLICY
... There are many amusing stories about the history of the 1961 paper and the events that occurred subsequently. They range from the confiscation of WI-38 from my Stanford University laboratory by misguided NIH zealots [25,27,37,39] to the anti-abortionists who picketed the launching pad at Cape Kennedy in an unsuccessful effort to thwart the launch of Skylab 2 which contained an elaborate experiment designed to determine whether my normal human fetal cell strain, WI-38, behaved any different at zero G from its behavior at terrestrial gravity [40]. ...
... The settlement provided that many of the confiscated ampoules of WI-38 would be returned to me and that all funds realized from the distribution of WI-38 that I had put into an escrow account until the suit was settled belonged to me with interest. The defendants also agreed that WI-38 could be sold by anyone including its inventor, and finally, that title to WI-38 was not vested exclusively with the government as they had insisted [39]. Finally, all copies of the accountants' false accusations that would be requested must be accompanied by a copy of the out-of-court settlement [45]. ...
... Although, the specific question of title to WI-38 was settled, the more general issue of title to other self duplicating biological systems has stymied lawyers and judges ever since and has remained generally unsettled to this day. A detailed discussion of this lawsuit, the issues involved and its outcome has been published [39]. ...
Chapter
Full-text available
Contrary to popular belief, very little research is done on the fundamental etiology of biological ageing. Most research is done on longevity determinants or on age associated diseases, neither of which will provide insights into the fundamental cause of ageing. Although my research did not intend to answer questions in biogerontology the accidental discoveries that we made did. The phenomenological finding we made in 1961 that normal human cells have a finite replicative capacity torpedoed a dogma held since the invention of cell culture technology in 1907. The belief since then that cultured cells were immortal, mislead researchers to believe that ageing was caused by extracellular phenomena. Our findings focused attention on intracellular events as the origin of ageing. Twenty years later the discovery of telomere attrition and the enzyme telomerase explained the molecular basis for our findings and in 2009 their discoverers were awarded a Nobel Prize in Medicine or Physiology. The most likely cause of ageing in both animate and inanimate objects is based on the 2nd Law of Thermodynamics which underlies all other theories of ageing. For decades the failure to define key words and fundamental concepts in the field of biogerontology has thwarted progress in understanding the basic cause of ageing and this failure shows little sign of change.
... There are many amusing stories about the history of the 1961 paper and the events that occurred subsequently. They range from the confiscation of WI-38 from my Stanford University laboratory by misguided NIH zealots [25,27,37,39] to the anti-abortionists who picketed the launching pad at Cape Kennedy in an unsuccessful effort to thwart the launch of Skylab 2 which contained an elaborate experiment designed to determine whether my normal human fetal cell strain, WI-38, behaved any different at zero G from its behavior at terrestrial gravity [40]. ...
... The settlement provided that many of the confiscated ampoules of WI-38 would be returned to me and that all funds realized from the distribution of WI-38 that I had put into an escrow account until the suit was settled belonged to me with interest. The defendants also agreed that WI-38 could be sold by anyone including its inventor, and finally, that title to WI-38 was not vested exclusively with the government as they had insisted [39]. Finally, all copies of the accountants' false accusations that would be requested must be accompanied by a copy of the out-of-court settlement [45]. ...
... Although, the specific question of title to WI-38 was settled, the more general issue of title to other self duplicating biological systems has stymied lawyers and judges ever since and has remained generally unsettled to this day. A detailed discussion of this lawsuit, the issues involved and its outcome has been published [39]. ...
... There are many amusing stories about the history of the 1961 paper and the events that occurred subsequently. They range from the confiscation of WI-38 from my Stanford University laboratory by misguided NIH zealots [25,27,37,39] to the anti-abortionists who picketed the launching pad at Cape Kennedy in an unsuccessful effort to thwart the launch of Skylab 2 which contained an elaborate experiment designed to determine whether my normal human fetal cell strain, WI-38, behaved any different at zero G from its behavior at terrestrial gravity [40]. ...
... The settlement provided that many of the confiscated ampoules of WI-38 would be returned to me and that all funds realized from the distribution of WI-38 that I had put into an escrow account until the suit was settled belonged to me with interest. The defendants also agreed that WI-38 could be sold by anyone including its inventor, and finally, that title to WI-38 was not vested exclusively with the government as they had insisted [39]. Finally, all copies of the accountants' false accusations that would be requested must be accompanied by a copy of the out-of-court settlement [45]. ...
... Although, the specific question of title to WI-38 was settled, the more general issue of title to other self duplicating biological systems has stymied lawyers and judges ever since and has remained generally unsettled to this day. A detailed discussion of this lawsuit, the issues involved and its outcome has been published [39]. ...
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In the invitation to write this article, I am asked to describe my “…contributions… to cell aging and the telomere story”. My research on the phenomenon of cell senescence began more than 50 years ago. From that time until today, the work done on this subject in my laboratory, and that of hundreds of other researchers, can only be described in the allotted space by a few generalizations and even fewer details. From the birth of cell culture technology in 1907, it was believed that all cultured cells, if provided with the proper conditions, would replicate indefinitely. Fifty-three years later, we overthrew this dogma by finding that, in the best conditions, normal cells have a finite capacity to replicate and that only abnormal or cancer cell populations can replicate indefinitely. We interpreted these findings to impact on our understanding of the aging process. If, as had been thought prior to our work, that normal cultured cells released from in vivo controls can replicate indefinitely, then age changes could not have an intracellular origin. Our findings demonstrated that, on the contrary, age changes do have an intracellular origin. The hundreds of changes that were subsequently found to precede the loss of replicative capacity have been interpreted to be age changes and the finitude of replication to be an expression of longevity determination. Age changes are the result of the inexorable dissipation of energy that occurs in complex biomolecules and that, unless repaired, causes their dysfunction. The positive balance of repair and synthetic processes over accumulating dysfunctional substrate molecules shifts after reproductive success to favor the increase in more dysfunctional molecules over repair capability as the repair processes succumb to the same Second Law of thermodynamics. The processes that control longevity, or how long repair and synthesis processes remain functional and retain their balance over dysfunctional molecules, are governed by the genome. Hence, the information that governs longevity determination is sexually transmitted whereas the aging process is a stochastic or random process governed by the laws of probability that are embodied in the Second Law of thermodynamics. Our search for the location of the molecular mechanism that controls the number of cell, or DNA replications, that occur in normal cells ended with our finding that the mechanism was located in the nucleus. Years later, and as the result of the confluence of studies done by others in several unrelated fields, the molecular mechanism was discovered. It was found that telomere attrition governs the limit on DNA replications in normal cells and that the expression of telomerase can circumvent this limit, thus explaining our discoveries of the phenomena of normal cell mortality and cancer cell immortality.
... There are many amusing stories about the history of the 1961 paper and the events that occurred subsequently. They range from the confiscation of WI-38 from my Stanford University laboratory by misguided NIH zealots [25,27,37,39] to the anti-abortionists who picketed the launching pad at Cape Kennedy in an unsuccessful effort to thwart the launch of Skylab 2 which contained an elaborate experiment designed to determine whether my normal human fetal cell strain, WI-38, behaved any different at zero G from its behavior at terrestrial gravity [40]. ...
... The settlement provided that many of the confiscated ampoules of WI-38 would be returned to me and that all funds realized from the distribution of WI-38 that I had put into an escrow account until the suit was settled belonged to me with interest. The defendants also agreed that WI-38 could be sold by anyone including its inventor, and finally, that title to WI-38 was not vested exclusively with the government as they had insisted [39]. Finally, all copies of the accountants' false accusations that would be requested must be accompanied by a copy of the out-of-court settlement [45]. ...
... Although, the specific question of title to WI-38 was settled, the more general issue of title to other self duplicating biological systems has stymied lawyers and judges ever since and has remained generally unsettled to this day. A detailed discussion of this lawsuit, the issues involved and its outcome has been published [39]. ...
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Full-text available
This brief historical development of the biology of the mycoplasmas begins with their discovery in 1898 to the present. Mycoplasmas are the smallest free-living microorganisms and for years were thought to be viruses because they passed through the usual bacterial filters. They lack a cell wall, are widespread in nature and many are animal, plant and human pathogens. The extensive use of cell cultures in the last fifty years and their frequent contamination with mycoplasmas, together with their possession of the smallest genome of any free-living organism, has drawn enormous attention to these organisms and has revealed considerably more about their biology.
... More importantly, the settlement of my lawsui t establis hed that biologists have intellectual property rights. Eight y-thr ee scientists published a letter in Science da mning the conduct of the government and supporting my position (Hayfl ick, 1978b(Hayfl ick, , 1998Strehler et al., 1982;Wadman, 2 013;www .webofstories.c om). ...
Article
Multiple errors appear in the book, "The Vaccine Race" causing reviewers to repeat those errors most of which are described in : www.AgingInterventionFoundation.org/BookReview2.pdf/ or https://www.researchgate.net/publication/323666095
Chapter
As we have seen, the scientific collection of tissue for research was widely viewed as unproblematic for much of the twentieth century. But this practice became contentious during the 1970s and 1980s, when excised tissues became the subject of often heated debate, with scientists, social groups, lawyers and a new breed known as ‘bioethicists’ questioning the ethics and legality of the procedures that transformed them into experimental tools. These questions played out in academic conferences and journals, in court, in bioethical reports and government legislation, in newspapers and even spilled onto the streets in protests.
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Recent books, articles and plays about the 'immortal' HeLa cell line have prompted renewed interest in the history of tissue culture methods that were first employed in 1907 and became common experimental tools during the twentieth century. Many of these sources claim tissue cultures like HeLa had a "troubled past" because medical researchers did not seek informed consent before using tissues in research, contravening a long held desire for self-determination on the part of patients and the public. In this article, I argue these claims are unfair and misleading. No professional guidelines required informed consent for tissue culture during the early and mid twentieth century, and popular sources expressed no concern at the widespread use of human tissues in research. When calls for informed consent did emerge in the 1970s and 1980s, moreover, they reflected specific political changes and often emanated from medical researchers themselves. I conclude by arguing that more balanced histories of tissue culture can make a decisive contribution to public debates today: by refuting a false dichotomy between science and its publics, and showing how ethical concepts such as informed consent arise from a historically specific engagement between professional and social groups.
Article
Debates regarding patient claims to extant tissue samples are often cited as beginning with the infamous US case of John Moore vs. the Regents of the University of California (1984–1990) – where the plaintiff unsuccessfully tried to claim title in a cell line derived from his excised spleen. Following the 1990 Supreme Court verdict, the issue of patient property in excised tissue was held by certain bioethicists as the ethical problem inhering in biomedical research from the 1980s onward: encompassing debates about a newly-avaricious biotechnology, consent, autonomy and identity. I show here that the concept of patient property was first mooted during the 1970s, some 10 years before Moore, as a response to US-based criticism of the use of foetal and human tissues in research. Rather than representing a struggle between an avaricious science and misled patients, it evolved as a result of debates between philosophers, lawyers, scientists and members of the public, amidst broader debates regarding human experimentation and abortion. Moreover, the first person to assert a patient's right to their own, or their family's tissue, in a legal arena was a scientist. This article attempts to investigate, through the evolution of ownership debates, how bioethicists and scientists themselves construct what counts as ‘public opinion’.
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Recent descriptions of the first human and chimpanzee cases of human immunodeficiency virus type 1 (HIV-1)-related retroviral infections dating from 1959 have stirred interest in the origin of AIDS. Although the theory of a chimpanzee origin of HIV-1 with cross-species transfer to man has now gained popularity, a more likely scenario is that chimps and humans were infected by an HIV-1 precursor virus derived from a contaminated poliovaccine. The reason for the rapidity and ease of cross-species transfer of this precursor virus has not been elucidated. We hypothesize that the poliovaccine was passaged in a human diploid cell strain. This simple manipulation allowed the retrovirus to adapt to human tissues and may have spawned the AIDS pandemic.
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The isolation and characterization of 25 strains of human diploid fibroblasts derived from fetuses are described. Routine tissue culture techniques were employed. Other than maintenance of the diploid karyotype, ten other criteria serve to distinguish these strains from heteroploid cell lines. These include retention of sex chromatin, histotypical differentiation, inadaptability to suspended culture, non-malignant characteristics in vivo, finite limit of cultivation, similar virus spectrum to primary tissue, similar cell morphology to primary tissue, increased acid production compared to cell lines, retention of Coxsackie A9 receptor substance, and ease with which strains can be developed. Survival of cell strains at - 70 °C with retention of all characteristics insures an almost unlimited supply of any strain regardless of the fact that they degenerate after about 50 subcultivations and one year in culture. A consideration of the cause of the eventual degeneration of these strains leads to the hypothesis that non-cumulative external factors are excluded and that the phenomenon is attributable to intrinsic factors which are expressed as senescence at the cellular level. With these characteristics and their extremely broad virus spectrum, the use of diploid human cell strains for human virus vaccine production is suggested. In view of these observations a number of terms used by cell culturists are redefined.
Article
This chapter discusses the patent issues with human diploid cell strains WI-38. When the human diploid cells were first established, efforts were made by the Wistar Institute to patent them. However, the patent laws in 1962 simply did not cover patents protecting life-forms. In 1978, all of this changed when the United States Supreme Court upheld a patent application for a microorganism. Until then, the patent laws did not allow protection for living cells. This decision opened the way for the ultimate patentability of many new organisms resulting from the then emerging rDNA and hybridoma technologies. For six years, WI-38 was freely distributed to all those who requested it. Despite the millions of dollars in gross sales earned during the period 1962–1968, not a penny reverted to the Wistar Institute or the United States Government. Today, not only is it possible to patent cell populations but universities and their scientists actually retain title to and profit from the sale of self-duplicating life-forms produced with government support.
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This report is reprinted by permission from The New York Times of 4 November 1985. © The New York Times Company. A discussion of contractors' potential conflicts may appear in a subsequent report.
Article
The author calls this book a compilation, because he has brought together the findings and thoughts of many scientists on the nature and measurement of senescence, its distribution in man, animal life and protozoa, the influence of genetic factors, the role of growth and rate of living, senescence in cells and in the endocrines. A great deal of factual information is still needed before senescence will be really understood. 733-item bibliography. (PsycINFO Database Record (c) 2012 APA, all rights reserved)