A mother baboon and a baby baboon die in Preeclampsia research at the Heart Research Institute, NSW

Sunderland, Thomson, Heffernan, Lim, Thompson, Ogle, Mckenzie, Kirwan, Makris, Hennessy (2011) Tumor necrosis factor α induces a model of preeclampsia in pregnant baboons (Papio hamadryas) Cytokine 56(2) 192-9

Background

In a recent 2011 publication(1) researchers at the Heart Research Institute in Newton, New South Wales have attempted to induce symptoms of preeclampsia in baboons.

Preeclampsia is a very serious disease occurring during pregnancy, characterised by maternal hypertension (high blood pressure) and proteinuria (protein in the urine).  When preeclampsia occurs in humans there is no known remedy. Once identified in a woman she is hospitalised and monitored until after delivery. Left untreated it can result in the death of mother and/or foetus.

The experiment

The study involved 9 baboons taken from the Australian Baboon breeding colony in NSW. Three pregnant and 3 non-pregnant were induced with preeclampsia through ‘administration of low-dose TNF-α (an inflammatory molecule) for 2 weeks at mid-gestation’. Three pregnant baboons (control group) were administered with saline.

In intra-arterial telemetry device was surgically implanted to allow for continuous remote blood pressure measurement. The pressure catheter was introduced via the profunda femoral artery and advanced so that the tip was positioned in the mid-abdominal aorta. The animals were carefully monitored for signs of distress, and pain relief was used 6–8 hourly post-operatively for 48 hours and further if required. Baseline data and sample collection was not performed until animals had been pain-free without chemical analgesia for at least 5 days to avoid potential effects of opioid analgesia on blood pressure.

After 7–10 days of recovery and baseline measurements the treatment (TNF-a or saline in the 3 control baboons) was administered via an intravenous catheter.  Urine was collected from an in-dwelling urinary catheter to the bladder.

An open renal biopsy was performed at the end of two weeks of treatment, and the telemeter removed. Animals were returned to the colony for delivery within their family groups. Blood pressure measurements, blood and urine sampling were undertaken fortnightly until delivery.

Pregnancy outcomes for these research animals:

All baboon babies in the pregnant saline control group were delivered normally. In the pregnant TNF-a dose group two were delivered normally, but one was stillborn due to ‘birth trauma’. Of the two mothers of the live babies, one was found to have an undiagnosed retained placenta 4 weeks after delivery and subsequently died of severe anaemia, leaving an orphaned baby baboon.

Animal welfare concerns

The study involved the induction of a very serious and potentially fatal condition. The study involved a number of invasive procedures on pregnant (and non-pregnant) baboons which would have been very stressful for both the adult and the (unborn) babies. 

It is of extreme concern that the study ultimately resulted in the death of one baby baboon and one mother baboon.

Humane Research Australia asks how was pain in the baboons assessed?  How did they demonstrate this pain?  Did the mother baboon grieve for the loss of the baby and what happened to the orphaned baby? 

Relevance to humans

It is believed that preeclampsia occurs only in humans and higher order apes.  An induced condition by administration of a molecule (TNF-a) is not the same as the condition that occurs due to a sequence of events in a pregnant woman.

Whilst TNF-a may INDUCE and mimic clinical and biochemical features of human preeclampsia that is all it can do – MIMIC.

Cost-benefit assessment

The publication by the researchers states that “these results clearly demonstrate that the cytokine TNF-α can induce the clinical and biochemical features of human preeclampisia.  We question the putting of non-consenting, highly sentient, pregnant beings through the pain and suffering of a serious disease (and death), to merely demonstrate that preeclampsia can be induced in a primate model. 

The Australian and New Zealand Council for the Care of Animals in Research and Teaching states that: “Using animals for scientific purposes is acceptable only when any harm done to the animals is very greatly outweighed by the benefits of their use”.  The study is not only highly unethical; it is unscientific. Data cannot be extrapolated from one species to another with certainty of success. 

Humane Research Australia does not believe the stress caused to the pregnant baboons by the experimental procedures, the ultimate death of a mother baboon and a baby baboon outweighs any perceived worth of this experiment.

This experiment has proved nothing and offers no help to those women who suffer this condition.

This research was approved by the Sydney South West Area Health Service Animal Welfare Committee. Humane Research Australia has emailed the committee seeking the minutes of the meeting that approved this experiment and asked if the committee was indeed informed that there would be the likelihood of death to a mother and baby baboon? 

What the experts say

According to Dr Anne Keogh(2) a senior Australian heart transplant cardiologist, the commentary (Cytokine 2011) on the tumor necrosis factor given to 3 pregnant and 3 non pregnant baboons summarises the scientific futility of the experiment.  She says that the authors note the unacceptably high mortality rate of 1 in 3 (33%) baby baboons and 1 in 3 (33%) mother baboons in their TNF model.

“Curiously inadequate chorionic villous sampling was taken to analyse and no conclusion about the pathophysiological effects on the uterus of the model could even be made due to poor study technique. Similarly the dose of TNF chosen, based on rat studies which was targeted to double blood levels of TNF did not do so in baboons. This research was a cruelty to baboons and did not contribute to human health (ie non –translational)”.

Preeclampsia (PE) in humans occurs in women who have had prior eclampsia (93%) or in those with a first degree relative with eclampsia (7%). The number of pregnancies in the baboons subjected to this high impact experiment is not stated.  PE is not in the dark ages. PE occurs more often in mothers with high blood pressure, diabetes.  The very best model of human eclampsia is the very large number of women who have it and is the scientific alternative to high impact studies in animals.

In a USA, Mexico study of 450 women with PE published in the same year (BMJ 2011;342:d2901 Felipe Vadillo-Ortega), none of 450 mothers died and only 2 of 450 (0.4%) babies died. In this human study, a simple dietary supplement of a semi essential amino acid l-arginine (Heartbar) to increase nitric oxide availability was given to half the mothers between 14 and 24 weeks of pregnancy. This simple manoeurve reduced PE by 56% and reduced premature delivery by 45%. A similar amount of l-arginine could also have very simply been derived by eating a Mediterranean diet.

What then, is the simple alternative to using baboons?

CVS (Chorionic Villus Sampling) is frequently requested by pregnant women early in their pregnancy, and tissue from the CVS can be studied for levels of cytokines/mRNA and histological changes which could then be correlated with later manifestation of PE. This would be good science.   Women with PE in past pregnancies would be lining up to participate in this research.

References

1 Sunderland, Thomson, Heffernan, Lim, Thompson, Ogle, Mckenzie, Kirwan, Makris, Hennessy (2011) Tumor necrosis factor α induces a model of preeclampsia in pregnant baboons (Papio hamadryas) Cytokine 56(2) 192-9

2. Dr  Anne Keogh AM expresses her opinion on this published, public material as a private citizen and not as a representative of any body, institution or organisation.

 

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