A medical experiment designed to study the spread of germs exposed more
than 200 local preschoolers to a genetically engineered substance and
was shut down after one parent complained that it was done without consent.
The experiment was conducted at 14 day-care centers in 1996, 2000 and
2001 by a team of scientists from the Center for Pediatric Research, a
joint venture of Eastern Virginia Medical School and Children's Hospital
of The King's Daughters.
The researchers sprayed a solution containing DNA fragments of a plant
virus on toys, doorknobs and other surfaces in the day-care centers. The
solution was intended to mimic a disease-causing organism. The
researchers then monitored how and where the solution was spread by the
children.
EVMS officials say the solution was safe, parents were notified and no
children were harmed. But a parent's complaint that she was not asked to
give written consent before the study prompted the medical college to
end the experiment, launch a yearlong internal review and revamp the
school's oversight system for research studies.
It also catapulted EVMS into the international debate over genetic
engineering and triggered ethical questions about how far scientists
should go to get informed consent from their human subjects --
especially when the subjects are children.
The Virginian-Pilot contacted three medical ethicists, two in Virginia
and one nationally known. All three said the EVMS researchers didn't go
far enough.
``Informed consent is a requirement, not a courtesy,'' said Yvette
Pearson, a visiting professor of philosophy who teaches bioethics at Old
Dominion University. ``Even if it was completely undebatable, even if we
know it's perfectly safe, it's still the case that you ask people for
their consent. You ask parents for consent to do things to their children.''
EVMS now says that if such an experiment were proposed today, the school
would require advance written consent from all parents.
The stated purpose of the experiment was to devise more effective ways
of controlling the spread of infectious germs in a child-care setting.
Scientists had hoped to track the spread of contagious viruses and
bacteria, a major problem for day-care centers. Workers combat the
problem with a continuous regimen of hand washing and sanitizing of toys.
An early pilot phase of the study in 1996 was funded by Reckitt & Colman
Inc., now Reckitt Benckiser, a household cleaning products company that
makes Lysol, the popular disinfecting cleaner.
The full-scale study that started in 2000 was funded by the Research
Foundation for Health and Environmental Effects, a nonprofit group
created in the mid-1990s by the chlorine industry. Bleach, a chlorine
product, is a staple in many day-care centers' disinfection routines.
The foundation awarded grants totaling more than $200,000 to EVMS
between 1999 and 2001.
The DNA-based ``marker'' solution developed by the EVMS team was placed
in one toddler classroom in each of 14 day-care centers in Norfolk,
Virginia Beach and Portsmouth. There were 249 children, 1 to 2 years
old, in those classrooms. Hundreds more children were present in other
areas of the day-care centers and potentially were exposed to the marker
as it was spread.
EVMS declined to identify the day-care centers that participated, citing
a confidentiality provision in its agreement with the centers. After
contacting 150 day-care centers listed in the South Hampton Roads Yellow
Pages, The Virginian-Pilot was able to identify nine: Children's Harbor,
412 Bank St., Norfolk; Discovery Care Center, 811 Redgate Ave., Norfolk;
Children's World, 313 Edwin Drive, Virginia Beach; Children's World,
1893 First General Parkway, Virginia Beach; Children's World, 4300
Silverleaf Drive, Virginia Beach; KinderCare, 6025 Churchland Blvd.,
Portsmouth; KinderCare, 2205 Poplar Point Road, Virginia Beach; Mustard
Seed Child Care Center, 6900 Newport Ave., Norfolk; and Rainbow
Preschool, 3820 Virginia Beach Blvd., Virginia Beach.
The day-care centers were not paid for their participation, but the
center directors were told there would be an educational benefit: Their
employees would learn better ways to control the spread of germs.
``That's one of the reasons I think this study is very important, just
from an education standpoint for child-care providers and teachers,''
said Jean Rockwell, director of Mustard Seed Child Care Center. ``It
raises their awareness.''
EVMS officials said a two-page letter about the study was left with each
child's belongings. The letter detailed the study and encouraged parents
to ask questions, but it did not seek written consent.
Only after the experiment was under way did the researchers seek written
consent to swab some of the children's hands. They got approval to swab
the hands of 147 children.
Teresa Robinette said she first heard about the experiment on May 28,
2001, when she arrived to pick up her youngest son, Phillip Ona, then 18
months old, from Rainbow Preschool near her home in the London Bridge
area of Virginia Beach.
A member of the EVMS research team approached Robinette with a consent
form and asked if she would sign it.
``She told me that they had put a totally harmless solution around the
school and needed my permission to swab Phillip's hand to see if the
solution was present,'' Robinette said.
``I asked what the solution was and she told me it was a harmless
cauliflower solution. I asked her, `So he has already been exposed to this?'
``She said, `Yes.'
``I asked, `So you exposed him already and you only need my permission
to swab his hand?'
``Her answer was again `Yes.' ''
Robinette didn't sign the form.
She went home and began researching the topic on the Internet. What she
found alarmed her.
The marker solution used in the day-care experiment contained DNA
fragments of the cauliflower mosaic virus, a common virus that attacks
such vegetables as cauliflower, broccoli and cabbage. DNA from that
virus is used in the production of many genetically engineered crops,
which have been introduced into the U.S. food supply with relatively
little controversy but have generated heated debate elsewhere, notably
in Europe and Canada.
Robinette's Internet research tapped into that debate.
Critics of genetic engineering have expressed concerns that DNA from the
cauliflower mosaic virus could recombine with other viruses to form new,
potentially more infectious viruses.
They also have raised alarms about bacterial plasmids, small rings of
bacterial DNA that were part of the marker solution. Some DNA-based
products containing bacterial plasmids have shown the potential to
promote inflammation and disrupt the immune system.
The EVMS study had been under way at Rainbow Preschool for about five
months. During that period, Phillip had suffered a succession of
ailments, many common for children in day care. They included
bronchitis, asthma, diarrhea, ear infections and allergies.
Meanwhile, Robinette's older son, Jesse Culbertson, then 6, who attended
the same day-care center, had been troubled by headaches, fevers and
allergies.
Robinette was having health problems, too. Her medical records show that
she suffered from fatigue, back and abdominal pain, and sores on her
arms and scalp. Doctors have told her she has a degenerative disc disease.
A key finding of the EVMS pilot study in 1996 was that children exposed
to the DNA marker spread it throughout the day-care center and brought
it home with them. So, Robinette reasoned, it could be responsible for
her family's health problems.
None of her doctors has made that link.
But one scientist Robinette contacted believes there could be a connection.
Joseph E. Cummins, a professor emeritus of genetics at the University of
Western Ontario, looked into the case at Robinette's request.
In a telephone interview, Cummins said Robinette's symptoms were
consistent with the potential side effects of bacterial plasmids.
``They really needed to do follow-up, particularly with regard to
untoward side effects,'' Cummins said. ``I definitely think that Teresa
Robinette has a very reasonable concern, both for herself and her
children.''
Cummins' argument is flatly rejected by Dr. Hal B. Jenson, director of
the Center for Pediatric Research, the entity that undertook the study.
Jenson, a pediatrician and infectious disease specialist, characterized
the DNA marker as ``a totally innocuous, inert, noninfectious molecule.''
``There would be no reason to even conjecture that any illness or
disease would result from this,'' he said. ``It's just biologically
impossible.''
Such reassurances were no comfort to Robinette. She pulled her boys out
of the day-care center, quit her job and began caring for the children
at home.
``When I found out about this, I felt like I'd betrayed my children,''
she said, her eyes welling with tears. ``No one should ever have to feel
like that.''
Robinette called William J. Wasilenko, associate dean for research at
EVMS, to express her concerns.
Four days after her call, the study was suspended. Robinette was brought
in for a meeting with key researchers and top EVMS administrators. The
study was re-evaluated by two internal committees of EVMS scientists and
four external consultants.
A year later, in June 2002, EVMS told Robinette that all the evaluators
agreed: The DNA marker posed no risk to the children. Nevertheless, the
study was shut down.
``We were confident that the material was safe and still feel that
way,'' Wasilenko said. He said the study was canceled ``in an
overabundance of caution.''
As a result of Robinette's complaint, EVMS has expanded the membership
of its two institutional review boards to include three to five
non-scientists from the community. Before, there was only one such
representative. The boards must approve all research studies at the school.
The school also has placed a medical librarian on the review boards to
do the kind of research Robinette did on the Internet.
No other parent has voiced concern about the study, Wasilenko said. In
fact, he said, in the three years he has been involved with the research
review process at EVMS, this is the first time a participant's concerns
have prompted such a thorough re-evaluation of a study.
``I thank Ms. Robinette for bringing this to our attention, I really
do,'' Wasilenko said. ``I think that we need to hear the concerns of the
community and the participants in our studies. . . . In the future, with
the additional community representatives, I think we'll be able to much
better anticipate questions like this.''
Other scientists familiar with the components of the DNA marker, who
had no connection to the day-care study, said there was little if any
health risk to the children.
Earl Mitchell Jr., a professor of biochemistry and molecular biology at
Oklahoma State University who has co-written several papers on the
cauliflower mosaic virus, said the idea that DNA from the virus could
pose a health threat is ``far-fetched.''
``It's not totally impossible, but it's highly unlikely,'' Mitchell said
in a telephone interview. ``It's almost silly to be concerned about it.''
Some who agree with that risk assessment still find the day-care study
troubling.
Bacterial plasmids such as the one used in the study are a common
ingredient in experimental DNA-based vaccines now being developed to
combat AIDS, malaria and other diseases. One of the pioneers in that
research is David B. Weiner, an associate professor of pathology at the
University of Pennsylvania School of Medicine.
Weiner has an AIDS vaccine undergoing human trials. In a telephone
interview, he said the side effects of bacterial plasmids, which were
sometimes dramatic in animal tests, have proved less of a problem in humans.
``There have been probably well over 1,000 people now who have received
DNA vaccines in studies, and as far as I'm aware, there's not been a
single significant adverse event,'' he said.
Still, Weiner is bothered by the EVMS research.
``I don't understand what would justify allowing such a study, even
though I don't think there's any risk,'' he said. ``It doesn't really
have to do necessarily with risk. That's not the only thing to consider.
It's also a matter of public trust.''
That trust was broken for Robinette when EVMS failed to get written
consent from parents before exposing their children to the marker.
Wasilenko said that policy was permissible under federal regulations
governing research on human subjects. One regulation allows a waiver of
informed consent when the research involves only minimal risk and
``could not practicably be carried out'' otherwise.
Those conditions applied in this case, Wasilenko said, because ``if one
parent wished not to have their child participate, all the rest of the
children would no longer have been able to be part of the study and that
day-care center couldn't have participated.''
Ethicists consulted by The Virginian-Pilot said a higher standard should
have applied.
``This experiment went off the ethical rails,'' Arthur Caplan, chairman
of the department of medical ethics at the University of Pennsylvania
School of Medicine, said in a telephone interview. ``The standards of
informed consent and disclosure are higher where children are involved.''
``I don't know that I would draw a moral line between the swabbing and
the environmental exposure,'' Jonathan Moreno, director of the Center
for Biomedical Ethics at the University of Virginia, said in a telephone
interview. ``If you spray something in the room, even though you're not
touching them, the purpose of the spray is to expose them. Therefore it
seems to me that's a maneuver that requires permission.''
EVMS now has come around to that view as well.
``That one parent's concern was one concern too many,'' Jenson said.
``Sensitivities have been heightened here at EVMS because of it. If this
study were proposed today, we would require informed consent from all of
the parents.''
The consent issue aside, Jenson and others associated with the
experiment defend it as a worthwhile effort to deal with an important
problem.
``The premise of the study was a very good one,'' said Dr. Larry
Pickering, Jenson's predecessor as director and a principal researcher
on the day-care study. ``What you've got to realize is that infections
in day-care centers are very common and can be debilitating for the
children. Rather than wait for an outbreak of disease to occur, which
was what we had done in the past when studying infections in day-care
centers, this provided a very good way to put this inert DNA material in
there and evaluate how bacteria and viruses could be spread.''
Pickering now works for the federal Centers for Disease Control and
Prevention in Atlanta. He is one of three key researchers on the
day-care study who have left or are in the process of leaving EVMS.
Jenson said none of the departures is related to the study.
Day-care directors who participated in the study said it was beneficial
and professionally conducted.
One disappointment was that the uncompleted experiment didn't yield as
much feedback as some had hoped.
``The report that they were able to give was not as full as they would
have liked,'' said Rockwell, the Mustard Seed Child Care director. ``But
they were able to give us some information as far as how successful our
staff was in reducing the spread of the marker.''
Rockwell said parents were given the opportunity to opt out of the
experiment, but none did.
``I did have some parents before the study started who had some
questions and wanted a little more information, and the EVMS staff
member was very accommodating and answered any questions they had,'' she
said. ``They felt very comfortable with it. And I was very comfortable
with it.''
The 1996 pilot phase of the study was done at the Children's Harbor on
Bank Street in downtown Norfolk, which has since closed.
At the time, executive director Toni Cacace-Beshears said, she had no
concerns about the consent process. Now, with the benefit of hindsight,
she said, she might reconsider.
``Maybe at this point in time I would do it differently,'' she said.
``But you have to bow to people's expertise at some point. And coming
from EVMS and the children's hospital, these aren't fly-by-night folks.
. . . These are the experts who know what they're doing.''
