THE LANCET (U.K.)
Jan 23, 1999

Bovine somatotropin---who's crying over spilt milk?

A hormone used to increase milk yield in cows--recombinant bovine
somatotropin (rbST)--is
proving to be one of the most controversial drugs of the decade.

Since the 1980s there have been fears over the safety of milk from
rbST-treated cows, and last year, a leaked internal report by Health
Canada scientists identified numerous gaps in the safety data on human and
animal safety. Last week, Health Canada announced that, unlike
many other agencies, it would not approve the drug. US consumer groups
now want the drug withdrawn.

rbST was first approved by the US FDA in November, 1993. At that time,
the European regulatory authority also gave a positive opinion, but the EU
banned rbST until the end of 1999 for socioeconomic reasons.

In Canada, approval of the drug is opposed by, among others, the National
Farmers Union (NFU). The debate concerns not just animal and human health
but also the socioeconomic impact of the drug, says Richard Lloyd (NFU).
After more than 8 years of review, Health
Canada asked two external panels to review the animal and human safety
last year. Rejection of rbST was partly based on the animal-health
panel's report of adverse effects in cows, including lameness, mastitis,
and reduced lifespan. The human-safety panel found, with one exception,
"no biologically plausible reason for concern". But the findings of the
leaked Canadian Gaps Analysis and testimony by several scientists to last
year's Canadian Senate hearings on rbST indicate that the human-health
debate seems set to continue.

Critics of the hormone suggest that both rbST and its mediator,
insulin-like growth factor-1 (IGF-1), are found at higher concentrations
in milk from treated cows. IGF-1 has been linked with cellularity changes
in the human gut, and tentatively with human cancer. And,
IGF-1 is not wholly destroyed in the gut, particularly in the presence of
casein. The Gaps Analysis concluded that long-term toxicity and oral
absorption had not been fully studied. The longest toxicology study--a
90-day rat study submitted by manufacturer Monsanto--indicated that rbST
was absorbed intact from the gut at high doses and elicited "a primary
antigenic response". The external panel concluded that this possible
hypersensitivity reaction "deserves further study". The Gaps Analysis
also notes that the full significance of human exposure to rbST and IGF-1
is unknown, particularly in the neonate, "the
subpopulation at greatest risk" (http://www.nfu.ca ).

The FDA and most other agencies interpret the data differently. For
example, JECFA--the Joint Food and Agriculture Organization (FAO)/WHO
Expert Committee on Food Additives--concluded last year that rbST "does
not represent a hazard to human health". Somatotropin
and IGF-1 occur naturally in milk, and, says FDA, "milk composition of
supplemented cows appears to be well within the normal variation
observed". Further, JECFA states that "any increase of IGF-1 in milk from
rbST-treated cows is orders of magnitude lower than the
physiological amounts produced in the gastrointestinal tract as well as in
other parts of the body . . . Consequently, the potential for IGF-1 to
promote tumour growth will not increase when milk from rbST-treated cows
is consumed".

The FDA did not consider the 90-day rat study pivotal, says spokesman
Lawrence Bachorik, and further toxicology testing is not warranted. Gary
Barton of Monsanto says such tests would be toxicology studies of natural
milk components. "There is no test anywhere that can find any distinction
between milk from treated cows and untreated cows . . . What are you
testing, that milk is bad?" But, the Senate Committee heard scientists
testify for and against further study. John Verrall, member of the UK
Food Ethics Council, told the hearings that, given the uncertainty, any
approval of the hormone shows "a total disregard for the precautionary
principle".

The Canadian decision may have far-reaching consequences. The US Center
for Food Safety (CFS) and about two dozen other consumer groups have
already petitioned the FDA to reverse its 1993 decision. CFS says it will
sue the FDA if rbST is not taken off the market. Eyes are now turned to
the international food standards agency, Codex Alimentarius, which meets
this summer to consider approval of rbST. If Codex, which is advised by
JECFA, concludes that the hormone is safe, "Canada may find itself unable
under international trade
law to refuse using a drug it has proven to be unsafe", notes Jo Dufay of
the citizen's group Council of Canadians (CoC).

Scientific debate remains hampered by secrecy surrounding regulatory
reviews, which has also left several bodies open to allegations of bias.
CoC has "serious questions about the objectivity" of the external panels.
"Both panels have chairs and a number of members who have worked closely
with related industries." For example, CoC alleges that human-safety
panellist Rejeanne Gougeon has been a consultant for Monsanto on rbST
since 1993.

International agencies are also under fire. One case cited is that of
Margaret Miller, a rapporteur at the JECFA meeting who was previously
employed by Monsanto, though she was cleared of a conflict of interest for
her involvement with rbST at FDA. Senator Eugene Whelan told the Senate
hearings that he would not be impressed by any testimony quoting WHO, FAO,
or Codex because "The big companies sit behind them, and tell them what
to do". Lloyd believes that this possibility of undue influence is one of
the "dangers of moving to global homogeneous regulatory agreements.
Canada's experience shows that we need more, not less, review."

"What is most important to remember", says Verrall, is that rbST is not a
therapeutic drug to which the public has limited exposure". Yet,
regulatory agencies apply the same standards of safety and efficacy to
therapeutic and non-therapeutic agents, regardless of the potential
population exposed; other factors that might be in the public's interest
are not within their remit. rbST--one of the first biotechnology products
licensed solely for economic purposes--has challenged this thinking.

Kelly Morris