Introduction
Ever since my undergraduate days
at the University of Virginia, I have been interested and engaged in biomedical
research. However, it wasn’t until I matriculated to Meharry Medical College,
the largest historically black medical school in the country, that I developed
an appreciation for the immense scope of disparities that exist in research and
the delivery medical care as it pertains to minority populations, and
specifically, African-Americans in the United States. As I worked towards a
Healthcare MBA at Vanderbilt University and served as the Health Policy and
Legislative Affairs Committee Chair for the Student National Medical
Association, I developed an even greater understanding for the need for
top-down approaches to reducing these inequalities. At the writing of this
essay, I am a surgeon-scientist in-training completing a Master’s degree in Biomedical & Translational Sciences, specifically focused on bioethics,
biostatistics and research planning.
As an African-American physician,
basic science and clinical researcher, and aspiring academician, I am acutely aware
and concerned about the lack of ethnic diversity in specialty medicine.
Numerous studies have previously demonstrated that improving the diversity of
care providers and those that conduct clinical research will help to alleviate disparities
in health research data and clinical outcomes.1 For instance, while Latino-
and African-Americans make up 14.8% and 12.3% of the U.S. population, they
represent only 4.9% and 1.5% of academic plastic surgeons, respectively.1 And while this may seem like
a non-issue to the uninformed, several studies have demonstrated that
African-American women undergo postmastectomy breast reconstruction at
significantly lower rates when compared to Caucasian women.1 Underrepresented minorities
not only prefer healthcare providers of the same race, but are also more likely
to participate in clinical research if a minority physician is part of the
research team.1
Historically, innovative medical
research has been conducted on homogenous populations – for better or for worse.
My bioethics professor, Dr. Joel Adelson, jokes that the typical research
subject is the “white male medical student.” While this comment is made
partially in jest, it alludes to the fact that health outcomes and biomedical research
are often based on a group of similar individuals, and those findings are
extrapolated to predict the outcomes of individuals of a different race, gender,
and who may be exposed to very different environmental factors. For instance,
it was only recently discovered that African-American men are more prone to
develop more aggressive forms of prostate cancer, and therefore require
increased surveillance when compared to Caucasian men.
At an early age, I learned of the inhumane
and usually deadly research that was perpetrated on Jewish prisoners by Nazi
researchers during World War II that resulted in the Nuremberg Doctors Trial. After
visiting the United States Holocaust Memorial Museum and observing firsthand
accounts of these atrocities, I wondered how any humans in good conscience
could do such a thing to a race of people. It wasn’t until later, when I
learned of the Tuskegee syphilis experiments, that I began to develop my own skepticism
in the American healthcare system and whether the motives of academic medical
research were truly aligned with the goal of improving the lives of all
individuals, or rather to satisfy the power- and/or financial-seeking motives
of a few.
The mapping of the human genome
and the emergence of the internet and cloud-based computing marks an inflection
point in the era of biomedical research and discovery. We are now in an era of
big data, artificial intelligence and open access.2 In the past, a patient’s only
concern with regard to their personal health data was with the protection of
their tangible health records and, to a lesser degree, what would become of the
any tissue that was removed from one’s body for diagnostic purposes. Today, we
are witnessing the emergence of various forms of health data whose ultimate
fate or utilization can only be speculated. Almost everyone wears a smart phone
that tracks their every movement. Google and Apple know when you’re going for a
run, going to the gym, or pulling through the drive-through at your favorite
fast food restaurant. While this kind of data and its perpetual storage may
seem trivial now, who knows how this information can be pooled and analyzed in
the future. While some of this data is being collected in the background of our
day-to-day lives, companies, such as 23andMe are actively marketing to
individuals to relinquish their own tissue that can be used to map out one’s
genome. What are the implications of the massive personalized health data these
companies are collecting, willingly, from consumers who are simply trying to
answer questions about their ancestry or predilection towards certain chronic
illnesses?
One form of personal health data
that has created controversy over the past 60 years is that of the collection
and storage of human tissue and cells. This biobanking is a means by which
medical researchers can procure human tissue, extract the cells, and store them
for an indefinite period for further research. The cells that led to the
development of standard cell culture and biobanking principles were named HeLa
– but the origin of these cells was far less well-defined until recently. At
the completion of medical school, I moved to Baltimore, Maryland where I joined
the head & neck tumor immunology lab at the University of Maryland Medical
Center. I had the distinct privilege of working under a fellow African-American
physician. The late Dr. Duane Sewell, a surgeon and researcher, happened to know
a member of the family from which the HeLa cells were derived. It wasn’t until
recently that I read The Immortal Life of Henrietta Lacks, but it is a story that I will never forget.
Henrietta Lacks
Johns Hopkins Hospital was
originally founded as a charity hospital for the sick and poor and as such, was
built in the underserved community of East Baltimore. At the time, it was the
only hospital for miles that treated black patients. Johns Hopkins has always
been one of the leading research institutions in the U.S. and one area of
research emphasis during the late 1940s was that of gynecologic research. Dr.
Richard TeLinde was a leader in treating gynecologic cancers, but considered to
be radical in his approach. For instance, he (correctly) postulated that
carcinoma in situ, a form of cellular atypia that has not penetrated beyond the
confines of its normal environment (basement membrane), was in fact, a
premalignant lesion that progressed to invasive carcinoma. At the time,
invasive cervical cancer was treated with radical excision of the cervix and
uterus, whereas carcinoma in situ was treated as normal tissue (surveillance).
Dr. TeLinde sought to definitively characterize the link between carcinoma in
situ and invasive carcinoma, and as such, employed the services the head of
tissue culture at Johns Hopkins, Dr. George Gey. At the time, the two felt that
if they could establish an immortal cell line from cancerous cervical tissue,
they could study the differences between cancerous and healthy cervical tissue
with much more ease. They hoped to one day determine the natural course of
cervical cancer, and maybe one day find a cure.3
In the winter of 1951, an
African-American woman by the name of Henrietta Lacks presented to Johns
Hopkins complaining of a pelvic mass and hematuria (blood in her urine).
Henrietta was a young mother of five with a 7th grade education
level from Clover, Virginia who was the wife of a tobacco farmer. Together, the
family moved to Turner Station, Maryland (suburb of Baltimore) for better job
opportunities. At the time of presentation, Henrietta was brought to the
gynecology wing where she was place in stirrups and a biopsy of her cervix was
taken. Less than one month later, Mrs. Lacks was notified that her biopsy
specimen was positive for cervical cancer, and that she needed to return to the
hospital for treatment. On February 5th, 1951, Henrietta returned to
the hospital, was admitted to the gynecologic ward, and signed a consent that
read as follows:
“I
hereby give consent to the staff of The Johns Hopkins Hospital to perform any
operative procedures and under any anaesthetic either local or general that
they may deem necessary in the proper surgical care and treatment of: Henrietta
Lacks”3
It was during this admission that cervical tissue was removed and given
to Dr. Gey’s lab. Much to their surprise, the cancerous cells derived from
Henrietta’s tissue not only survived, but proliferated at an alarming rate. Dr.
Gey and his colleagues had just isolated the first immortal human cell line.3
Dr. Gey was so excited for his discovery and the potential benefits that
these cells might mean for biomedical research that he freely shared them with
whomever requested them. He would eventually ship these cells to labs around
the world that were interested in using them for research. Some of the early
and significant findings that resulted from research using HeLa cells include
the development of a method of cell cryopreservation (method for storage and
biobanking), the refinement and standardization of cell culture techniques and
the growth media in which they thrive, the biological components that enabled
the establishment of the field of virology, and the discovery/visualization of
the human chromosome and haplotyping, a technique that would eventually give
way to the mapping of the human genome.3
The most pressing issue during the
time of this explosion in biomedical research was an effort to end Polio.
President Franklin Delano Roosevelt suffered from polio, a debilitating disease
that compromises neurologic function and renders the patient crippled before
ultimately comprising the brains autonomic function of respiration. It was the
president’s mission to find a cure for this disease, and he commissioned the
National Foundation for Infant Paralysis (NFIP) to seek a cure. At the same
time, Dr. Jonas Salk at the University of Pittsburgh developed a vaccine that
he thought might permanently protect individuals from contracting this virus,
but had little means to test this hypothesis. When it was discovered that HeLa
cells were uniquely susceptible to Polio and an excellent resource for vaccine
testing, the NFIP moved swiftly to facilitate the mass production of HeLa cells
for the testing of the Salk vaccine.3
Tuskegee Institute, which at the
time was the most prestigious African-American college in an era of
segregation, was selected to develop a HeLa distribution center. Tuskegee
became the first-ever cell production factory, and at its height, employed 35
African-American scientist and technicians who produced 20,000 tubes of HeLa
cells per week. This effort proved invaluable in the validation of the Salk
vaccine which has virtually eliminated the disease from the face of the planet.
Ironically, these efforts were going on at the same time and location as the
Tuskegee Syphilis studies.3
Tuskegee Experiment and Informed Consent
In 1932, the US Public Health
Service (USPHS) began an experiment to evaluate the natural course of untreated
latent syphilis in black males. The Julius Rosenwald Fund originally
commissioned this this research to study the prevalence of syphilis and explore
the possibilities of mass treatment. At the time, Macon County, Alabama, home
of the Tuskegee Institute, had the highest population of young, black men who
were diagnosed with untreated syphilis. Dr. Taliaferro Clark, chief of USPHS Venereal
Disease Division saw this as an “unusual opportunity.”4
The Tuskegee Syphilis Study was
designed to recruit 400 syphilitic men (and 200 controls) to study the natural
course of the disease. Ironically, a similar study was conducted between 1890
and 1910 by Professor C. Boeck, Chief of the Oslo Venereal Clinic, on roughly
2,000 patients diagnosed with syphilis and left untreated. While the majority
of patients survived without significant long-lasting effects, 30% of these
individuals developed cardiovascular disease, insanity, and premature death. In
fact, the findings were so significant, that the discovery of arsenic therapy as
a treatment option was such a compelling alternative to the sequelae of
syphilis that the study was halted.4
Interestingly, Dr. J.E. Moore, one
of the nation’s leading venereologists, found that the Oslo study findings
indicated that all patients diagnosed with syphilis should be treated. In fact,
the mere fact that the morbidity associated with syphilis is communicable
through sexual contact was reason enough to treat any individual who contracted
the disease. Dr. Moore went as far to state that the Oslo study constitutes a
“never-to-be-repeated human experiment.” This concept was only further
reinforced to the scientific community after the USPHS sponsored and published
a paper that was authored by Dr. Moore and others. Ironically, Dr. Moore also
served as an expert consultant on the Tuskegee study and somehow came to the
conclusion that this research would be of “immense value” because “syphilis in
the negro is in many respects almost a different disease from syphilis in the
white.”4
Even though the scientific
community was aware of arsenic therapy as a treatment for syphilis at the time
the Tuskegee Study began, its use was not widely accepted or implemented due to
severe morbidity that often included death.5 It wasn’t until the 1950s
that the antibiotic penicillin became widely available, and was determined to
be a safe and highly effective drug for the treatment of syphilis (and is still
indicated for this use today). Despite this knowledge, the study patients did
not receive penicillin treatment, and in fact, the USPHS actively sought to
prevent the enrollees from receiving treatment or even being made aware that it
was available. In as late as the year 1969, the Centers for Disease Control and
Prevention actively permitted the continuation of this study despite continued
advances in knowledge about the disease process and treatment.4
Eventually, the free press began
reporting on the details of the Tuskegee Study which led to a public outcry
surrounding the questionable ethics, or lack thereof, employed. The Department
of Health, Education and Welfare formed an Ad Hoc Advisory Panel, and published
a Final Report in the summer of 1973. Although the issues brought to the
Panel’s attention were not aligned with the original intent of the Study, the
Panel came to the conclusion that 1) simply because the study participants
volunteered (under a false premise), this is not the same as informed consent
and, 2) once a known effective treatment became available (penicillin), it
should have been offered to the patients.4
It was less than halfway through
the Study that not only did the scientific community have an effective cure for
syphilis, but they also had the Nuremberg Code that resulted from the grossly
unethical research practices that were conducted by the Nazis in central
Europe. While the ten rules of this Code have some level of applicability to
this case, I will highlight two: “The voluntary consent of the human subject is
absolutely essential. [The] person involved… should be so situated as to be
able to exercise free power of choice, without the intervention of any element
of force, fraud, deceit…” and “During the course of the experiment the
scientist in charge must be prepared to terminate the experiment at any stage,
if he has probable cause to believe …that a continuation of the experiment is
likely to result in injury, disability or death to the experimental subject.”4
The extreme and grotesque actions
of the Nazis which included mass genocide and deadly experimentation of an
entire race of people left many physicians and scientist in the U.S. with a
complacency such that the measures outlined by the Nuremberg Code likely had no
place in a refined and advanced society.4 However, as clearly outlined
above, core principles of the Nuremberg Code strike to the core of the issues
surrounding both the recruitment phase and the continuation of the Tuskegee
experiment.
In Resolving Ethical Dilemmas: A Guide for Clinicians, a leading
textbook on the topic, the first statement on the concept of informed consent
is as follows: “Although informed consent is legally required, many physicians
are skeptical because patients can never understand medical situations as well
as doctors and because they can usually persuade patients to follow their
recommendations.”6 While I feel this
paternalistic viewpoint is slowly fading from the psyche of modern-day
clinicians and researchers, I think it is fairly easy to see how this idea,
coupled with racism (whether overt or subconscious), led researchers down a
path that compromised the lives of hundreds of young black men in Macon County,
Alabama for decades.
The four concepts communicated to
our “Ethics in Research” course include: Autonomy – the idea that an individual
should be able to act intentionally, is informed and free from interference and
control by others; Beneficence – where it is up to the physician or researcher
to ensure that they are aiming to provide a net benefit to their patients;
Nonmaleficence – the ‘do no harm’ precept that forbids physicians or
researchers to act selfishly or maliciously; and Justice – the idea that
research should be fair and people get what they deserve, e.g. a fair
allocation of resources.4 All of these tenets were
violated in the case of the Tuskegee Study.
Ethics of Tissue Collection and Future Discovery
While informed consent was central
to the complaints of the Lacks family, the most prevalent recurring concern conveyed
by her children after the discovery of the existence and mass production of the
HeLa cell line was who owned the rights, and thus the financial interest tied
to the tissue taken from Henrietta’s body. This very issue was tackled by the
California State Supreme Court in the mid-1980s. John Moore was being treated
for cancer by Dr. David Golde at UCLA over the period of a decade. During
treatment, Dr. Golde discovered that Moore’s body contained rare cells that
produced very valuable proteins that could be used for the development of
therapeutics. Dr. Golde would eventually patent Moore’s cell line and various
proteins they produced and become a millionaire in the process. Moore became
aware of this situation, sued, and lost. It was decided that once tissue leaves
a patient’s body, it is no longer the property of that patient.3
As of 2013, it was estimated that
there are greater than 300 million human tissue samples stored in biobanks in
the U.S. and this number was growing by at least 20 million samples per year.
The vast majority of samples collected today are not being used to develop
‘immortal’ cell lines, but that has not stopped a growing presence of critics
who argue that there is a need for a ‘tissue-rights movement.’7
The popularity of the book, The Immortal Life of Henrietta Lacks,
has brought to the forefront the concept of ethics in research, however, the
central tenets of this competency seem nebulous to most lay people. Two
researchers sought to quantify the impact that this book had on the discussion
of ethics in research and found that there were three concepts that were repeatedly
emphasized in the media and discussions surrounding this best-selling novel.7 Approximately 40% of the
accounts featured ‘informed consent’ as the major issue relevant to the Lacks
case, tissue research, or both. Additionally, 54% mentioned ethical
considerations related to the ‘welfare’ of the patient while 72% of the
accounts mentioned ‘compensation.’ Some second-tier considerations included ‘scientific
progress,’ ‘patient control,’ and ‘researcher accountability/oversight.’7
To this day, there doesn’t seem to
be much interest by the general public with regards to the ethics of clinical
research and data collection. Informed consent is the overwhelming issue that
the public seems to value, and I believe that strict adherence to this concept
will lay the foundation for ethical behavior as a study progresses. At the time
that Henrietta lacks was diagnosed with cervical cancer, treatment was begun
with radium therapy, which was the standard of the care at the time and relates
to the general ‘welfare’ of the patient.3 Because Ms. Lacks was
receiving free care at the time, this can be considered as ‘compensation.’
Though many individuals and institutions profited off (and continue to profit
off of) the HeLa cell line, neither Dr. Gey nor Johns Hopkins received any
financial benefit for their discoveries or dissemination of the cells.
Unfortunately, there is no legal recourse that the Lacks family can pursue to receive
financial compensation for the profits made off Henrietta’s cells. It would
certainly be reasonable, however, for Johns Hopkins, or any
individual/institution that profited off the HeLa cell line to establish a
trust that would provide free healthcare to the descendants of Henrietta as a
gesture to make up for the lack of informed consent that was clearly violated
when the cancer specimen was removed from her body.
The Tuskegee study, on the other
hand, was a violation of all three ethical issues that are important to public
perception. Had the volunteers known they were being given negligent care
(informed consent), which would eventually lead to a significant decline in
their health (welfare), these individuals should have at least been given the
option to decline participation or receive some form of payment (compensation)
as a tradeoff for the risk they incurred.
The events surrounding Henrietta Lacks appear to be a special case as
most patient-derived therapeutic discoveries today do not come from the
donation of a single patient, but rather pooled resources and data from a large
number of individuals. It is unreasonable for every individual who donates
blood or tissue for research purposes to expect their donation to lead to the
next invaluable immortal cell line, multimillion dollar vaccine, or
therapeutic. I would like to believe that the majority of individuals in
society have a component of altruism, and are not opposed to contributing to
research if it means that they might have a positive impact on society. To that
end, there must be a clear understanding that scientists are going to use their
expertise to develop technologies that are ultimately intellectual property
that has value. As long as we live in a capitalistic society, these discoveries
carry commercial value that will almost always be pursued.
The 23andMe Conundrum
Over the past five years, we have
witnessed the explosion of genomics companies such as 23andMe and AncestryDNA
who have developed simple tests that allow consumers to essentially spit in a
vial, place the sample in the mail, and have a wealth of information returned
to that individual, shedding light on their ancestral heritage and tendency
towards certain physical characteristics and chronic conditions.8 In 2013, the Food & Drug
Administration (FDA) had a very public dispute with 23andMe over the
classification of their home genetics kit. While the ancestry information is
perceived as relatively benign, the health information provided by this service
could lead a lay person to make a drastic decision regarding their health. For
instance, if someone discovered they carried a gene mutation that increased
their risk of developing breast cancer, they might decide, solely based on this
information, that they need a bilateral mastectomy without adequately weighing
all the risks and benefits. Based on this concern, the FDA decided that this
service should be classified as a medical device which necessitates a higher
level of scrutiny over the accuracy of the results delivered by this company.9
Perhaps even more concerning is
that these companies are creating massive banks of genetic information that can
be used for countless purposes. One article in Scientific American is quoted as describing these services as “…a
mechanism meant to be a front end for a massive information-gathering operation
against the unwitting public.”10 In fact, Patrick Chung, a
23andMe board member is quoted as saying, “The long game here is not to make
money selling kits, although the kits are essential to get the base level data.
Once you have the data, [the company] does actually become the Google of
personalized health care.”10 It probably shouldn’t come as
much of a surprise that at the time Anne Wojcicki cofounded 23andMe, she was
married to Sergei Brin, the cofounder of Google.10
On the one hand, 23andMe is
already conducting meaningful research that could lead to the discovery of
genetic patterns and therapeutic targets for a host of diseases such as
Alzheimer’s or hemophilia. And while there is significant potential to decrease
the morbidity of these diseases on society, it may also lead to very lucrative
patents for the company that develops them. It is ultimately up to the consumer
if this is an acceptable use of their genetic information; as it currently
stands 23andMe gives consumers the options to opt-in to their research efforts.
But what is of even greater concern is that once a company has an individual’s
genetic information, there is no turning back. Not only are we in an era of
massive data breaches and hacks, but companies are frequently changing privacy
policies, that even I admit I rarely take the time to read before clicking
‘accept.’ Once one relinquishes their genetic information, which is as personal
and specific as health information comes, one must be hypervigilant at
protecting this information, or be at risk of this information being used
against them.
Conclusion
Disparities in health outcomes and
research continue to be problems that particularly effect underrepresented
minorities in our society. As an African-American surgeon and scientist, I hope
to effect change in this area by pursuing a career in academic medicine and conducting
clinical research that will benefit underrepresented minorities, as well as
society as a whole. The HeLa cell line is arguably the most significant
development in the era of modern biomedical research, but it wasn’t until
recently that the story of its origins came into focus. Henrietta Lacks was a
wife, a mother and an individual like you, me or all of the men who enrolled in
the Tuskegee Study, and thus entitled to the central ethical tenets of
autonomy, beneficence, nonmaleficence and justice. As we move towards an age of
digitized health information and open access, consumers must be aware of the
implications of donating their tissue and what may become of it.
References
1. Butler
PD, Britt LD, Longaker MT. Ethnic diversity remains scarce in academic plastic
and reconstructive surgery. Plast Reconstr Surg 2009;123:1618-27.
2. Mauffrey C, Giannoudis P, Civil I, et
al. Pearls and pitfalls of open access: The immortal life of Henrietta Lacks.
Injury 2017;48:1-2.
3. Skloot R. The immortal life of
Henrietta Lacks. 1st pbk. ed. New York: Broadway Paperbacks; 2011.
4. Emanuel EJ. Ethical and regulatory
aspects of clinical research : readings and commentary. Baltimore: Johns
Hopkins University Press; 2003.
5. Frith J. Syphilis - Its Early History
and Treatment Until Penicilin, and the Debate of its Origins. Journal of
Military and Veterans' Health 2012;20:49-58.
6. Lo B. Resolving ethical dilemmas : a
guide for clinicians. 4th ed. Philadelphia: Wolters Kluwer Health/Lippincott
Williams & Wilkins; 2009.
7. Nisbet MC, Fahy D. Bioethics in
popular science: evaluating the media impact of The Immortal Life of Henrietta
Lacks on the biobank debate. BMC Med Ethics 2013;14:10.
8. Ramsey L. I've taken AncestryDNA,
23andMe, and National Geographic genetics tests — here's how to choose which
one to try. Business Insider 2017 April 25, 2017.
9. Dobbs D. The F.D.A. vs. Personal
Genetic Testing. The New Yorker 2013 November 27, 2013.
10. Seife
C. 23andMe Is Terrifying, but Not for the Reasons the FDA Thinks. Scientific
American 2013 November 27, 2013.
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