The court based its decision not directly on fears about safety, but
on the grounds that there is no legal framework for the industrial application
of gene technology in West Germany. ‘Only legislation can decide whether
or not gene technology can be used on an industrial scale,’ the judges said
in their verdict.

Even existing environmental protection laws, which include regulations
for the approval of factories where genetic engineering takes place, fail
to offer a sound enough legal basis. This, said the judges, is ‘because
of the different dimensions and the quality of the risks connected to gene
³Ù±ð³¦³ó²Ô´Ç±ô´Ç²µ²â’.

Peter Lange, of the Federal Ministry of Research and Technology in Bonn,
disagrees with the judgment. He says: ‘At the moment we are pondering the
arguments of the court, and we are checking the consequences of this verdict,
not only for gene technology but for the process of innovation throughout
West Germany.’

The judgment means that at present, no genetic engineering production
line can be approved in West Germany. Several companies are seeking approval
for such production plants: the pharmaceuticals company Grunenthal in Aachen
wants to build a plant to engineer an anti-blood- clotting substance called
saruplase; Bayer in Leverkusen seeks approval for production of blood factor
VIII, a protein essential to haemophiliacs; and Hoechst’s subsidiary Behringwerke,
in Marburg, is in the middle of an approval process for its production of
erythropoietin, a protein used as a growth factor for red blood cells.

The verdict settles, at least for now, a five-year legal battle between
Hoechst and a group of citizens living in the neighbourhood of the company’s
factory in Frankfurt.

The Hesse Supreme Court overruled a decision by the local authority
in Darmstadt in July last year, which allowed Hoechst to press on with plans
to construct a production line for making engineered human insulin for a
two-year test period.

A group of citizens called ‘Hoechster Schnuffler und Maagucker’ opposed
the ruling. But the ruling was endorsed by the administrative court in Frankfurt
this year, which confirmed support for Hoechst.

With this legal support, Hoechst had planned to begin production of
insulin next spring. Now, the programme is in tatters. Hoechst’s only recourse
is to appeal to a higher authority, the West German Constitutional Supreme
Court in Karlsruhe, which alone can overthrow last week’s verdict.

Wolf Michael Catenhusen, head of the West German parliament’s panel
on research and technology, said: ‘The court’s verdict is totally correct.
At the moment, the environmental laws only regulate the formal process of
approval. In contrast, the risk assessment is based on regulations that
are not legally compulsory.’

The new verdict redoubles pressure on the West German parliament to
pass a new law that regulates research and industrial use of gene technology.
The ‘gene law’, which is being discussed in the parliament this week, must
be ratified by next summer, the end of the current four-year parliamentary
period.

Otherwise, West Germany will have to wait for at least another two years
before a gene law is possible, because the general election for the West
German parliament takes place in autumn 1990.

A spokesman for Hoechst said last week that the company was disappointed
by the court’s decision, which he described as jeopardising the future industrial
development of genetic engineering in West Germany. The spokesman added
that the company plans to study the details of the court’s ruling before
deciding what steps it should take next, but that it would probably wait
at least two years before making a further application to construct the
plant.

The first firm indication that retroviruses might be associated with
autoimmune disease came earlier this year. Franco Bottazzo and his colleagues
at the Middlesex Hospital and the Institute of Cancer Research in London
found DNA which was similar to that of HIV in the thyroids of five patients
with Graves’ disease (¿ìè¶ÌÊÓƵ, Science, 27 May). People with this
autoimmune condition produce antibodies to thyroid cells, causing the gland
to enlarge and release too much thyroid hormone.

In Berlin, Bottazzo’s group said that they had found evidence for DNA
sequences of retroviral origin in all of eight patients suffering from Graves’
disease. A test for DNA resembling that from the gag region of HIV, which
codes for the core protein p24, was positive in all the patients. However,
in blood tests, none of the eight had antibodies to HIV-1 or HTLV-1, another
retrovirus which causes a rare type of leukaemia.

For their controls, Bottazzo and his colleagues tested thyroid tissue
removed from people having surgery for cancer of the thyroid, but who did
not have Graves’ disease. None of these four samples showed a positive result
on the test for DNA of retroviral origin. This finding suggests that the
retroviral DNA sequences are correlated with the disease.

Further evidence comes from Norman Talal and his colleagues from the
University of Texas Health Centre in San Antonio. They investigated patients
with two other autoimmune diseases, called Sjogren’s syndrome and systemic
lupus erythematosus (SLE). The symptoms of Sjogren’s syndrome are variable,
but can include inflammation, arthritis and dry eyes and mouth. In SLE,
sufferers have fever, skin rash and arthritis. Neither disease has a known
cause.

Talal’s group found antibodies against the p17 and p24 core proteins
of HIV-1 in 14 out of 20 patients with Sjogren’s syndrome, as well as in
21 out of 60 patients with SLE. This is indirect evidence that these patients
had proteins similar to those of HIV in their blood, although they were
not infected with HIV itself.

Some immunologists are sceptical about Talal’s findings, however. Friedel
Krapf, from the Institute of Clinical Immunology at the University of Erlangen-Nurnberg
in West Germany, pointed out that many people with these diseases must have
had the highly sensitive Western blot test for diagnosis of HIV infection.
He said: ‘It is astonishing that no other group found such proteins (during
these tests). On the other hand, it is known that a fraction of AIDS patients
develop autoimmune-like symptoms during the disease.’

Krapf and his collaborators provided the most direct evidence that retroviruses
are associated with an autoimmune disease. They found sequences of DNA which
closely matched retroviral genes, such as those from HIV-1 and HTLV-2 (also
the cause of a rare leukaemia). The researchers also found messenger RNA
copies of the fragments of retroviral DNA. This discovery indicates that
patients with SLE are turning retroviral genetic messages into protein products.

Krapf’s group began to investigate the possible connection with retroviruses
when they found huge amounts of fragmented DNA in the plasma of cells from
patients with SLE. Krapf said: ‘We found this phenomenon in only one other
person who did not have SLE, and this was someone who was infected with
herpes virus.’

The researchers isolated the DNA fragments from the cells of patients
with SLE and put them into an immortalised line of B cells. After several
weeks of incubation, 10 per cent of the B cells seemed to be damaged: they
developed huge vacuoles and joined up to form syncytia, or clumps of fused
cells. ¿ìè¶ÌÊÓƵs frequently observe this effect in cells infected with
HIV that have been grown in the laboratory.

The group carried out further tests to establish how closely related
the viral material was to the genome of HIV. They identified four regions
of the retroviral DNA that closely resembled fragments of the genome of
HTLV-1, as well as the tat gene and other parts of the genome of HIV-1.
(Without the protein product of the tat gene, HIV cannot reproduce itself.)
According to Krapf, other experiments suggest that as many as 40 per cent
of patients with SLE may have messenger RNA of retroviral origin.

No one knows how retroviral DNA, messenger RNA of retroviral origin
or the protein products of retroviral genes can account for the autoimmune
characteristics of these diseases. Nor does anyone know the origin of the
retroviral sequences found in some people with SLE. Krapf said: ‘We have
only a slight hint’ that this material comes from a virus that people catch,
rather than one which is passed on through the germ line. Other groups have
found that patients with SLE have antibodies that bind to the DNA fragments
in their cells. These researchers have found these antibodies in healthy
sexual partners of patients with SLE, as well as in laboratory staff who
handle material from people with SLE. Krapf said: ‘This may mean that some
sort of infectious agent is involved in SLE.’

German scientists have already protested strongly against the bill.
If it becomes law in 1991, it will be the country’s first to make a type
of research a criminal offence. The two major research agencies, the German
Research Community (DFG) and the Max Planck Society, oppose the bill.

The DFG had called for legislation that would still permit some research
on human embryos, but all the political parties were against this idea.
Now, however, the two agencies have compromised by calling for a moratorium
on research in human embryos.

The Christian Socialists in the ruling coalition say that they will
block the law, because it permits a doctor to inseminate a married woman
artificially with sperm from a man other than her husband. But the Greens
and Social Democrats say that the bill does not go far enough.

Hans Engelhard, the minister of justice, says that the main purpose
of the law is ‘to exclude even the slightest chance for programmes aimed
at so-called improvement of humans’. The issue of eugenics still provokes
strong emotions in West Germany, following the extermination of millions
of people deemed ‘inferior’ by the Nazis during the Third Reich.

The draft law prohibits researchers from inserting genes into human
germ cells (eggs or sperm). It bans not only the cloning of humans, but
any work with so-called totipotent cells – cells which can be taken from
an embryo and used to generate another, identical embryo. It also prevents
any research on human embryos that damages or destroys them, and prevents
scientists from forming any hybrids, or chimeras, between humans and any
other species.

If it is approved, the law will limit to five the number of embryos
that geneticists can produce by in vitro fertilisation for a particular
woman. This is the maximum number that doctors will be allowed to implant
into a woman after her eggs have been fertilised. Also, the bill specifies
that doctors must implant all the embryos that they produce in vitro immediately.
Embryos can live for up to 14 days in vitro.

The law would prevent researchers from producing surplus embryos. Today,
they often freeze surplus embryos from one round of fertilisation for IVF
so that, if the first pregnancy fails, they can implant the spare embryos
without the woman having to go through the whole process again. The bill
also prohibits the freezing of embryos, research on existing frozen embryos,
or the production of embryos for any purpose other than implantation.

Married couples would be the only people allowed treatment with IVF
under the proposed law. This would preclude members of lesbian couples,
for example, from becoming pregnant through IVF – a practice already permitted
in the Netherlands. It would become illegal to donate eggs or sperm and
to be a surrogate mother.

Researchers would be allowed to control the sex of a fetus only in cases
where severe genetic diseases are likely to be inherited by one sex. The
aim is to prevent parents from selecting the sex of their offspring. Anyone
who violated the law would receive a prison sentence of up to five years.

The DFG and the Max Planck Society say that the law would violate the
West German constitution, which guarantees ‘freedom of research’. They say
that research on human embryos could lead to new treatments for other diseases,
such as cancer.

The Greens, meanwhile, want to ban IVF entirely. Renate Schmidt, a Social
Democrat and a member of parliament, says that the bill does not exclude
the selection of offspring with desired characteristics – one definition
of eugenics – because a woman can choose to be inseminated by any consenting
male.

If the West German parliament passes the ‘gene law’ next autumn, it
will take effect in 1991. Like the European Community’s proposed directives
for gene technology, the German bill sets different licensing requirements
depending on: whether genetic manipulations are effected for research or
for commercial use; whether engineered organisms are confined or deliberately
released; and how dangerous they are to other species.

Klaus Toepfer, the environment minister, had wanted his own ministry
to approve each application to build biotechnological plants. The health
and research ministries, which helped to draft the bill, rejected this plan.
Instead, the Advisory Board for Biological Safety, or ZKBS, part of the
health ministry, will approve almost all proposals. The approval of other
agencies will be required only for the deliberate release of genetically
engineered organisms.

The bill says that public hearings must precede and approve releases
of genetically engineered organisms, but only when such releases ‘cannot
be limited to a certain area’. It defines neither the extent of ‘confinement’
nor the ‘area’. The Greens and other environmental groups are almost certain
to use this ambiguity as a legal device to prevent releases.

One such group, Buerger Beobachten Petunien (Citizens Observe Petunias),
opposes an outdoor test by the Max Planck Institute in Cologne of petunias
containing genetic material from maize. This, West Germany’s first major
release of engineered organisms, was approved by the ZKBS earlier this year,
but public opposition forced the experiment to be postponed until next year
(This Week, 11 March).

More conflict could arise over the distinction between ‘scientific,
small-scale’ and ‘commercial, large-scale’ work. German authorities now
define work with fermentation flasks of less than 10 litres in capacity
as ‘experimental’. Research needs only the approval of the ZKBS, whereas
commercial plants also need the approval of local authorities.

Approval also depends on the risks posed by altered organisms. Unlike
the European directive, which defines organisms as ‘dangerous’ or ‘not dangerous’,
the German bill sets four categories. The ‘safest’ organisms are ones that
cannot escape, interbreed with natural relatives, or cause disease or other
damage.

If the ZKBS does not object within 90 days of an application the project
can proceed. Commercial experimenters using organisms that fall into the
other risk categories require public hearings.

Although the requirement for public hearings is less stringent than
an existing West German law that affects chemicals companies, it is more
stringent than the European directive, and other proposed rules for genetic
technology, including those advanced this month in the US and Britain (‘Genes
at the bottom of the garden’ ¿ìè¶ÌÊÓƵ, last issue).

Last month, Toepfer led an attempt to alter the directive to permit
countries to adopt stricter rules. The European environment commissioner,
Carlo Ripa di Meana, said he would fight that change in the European Court.

Violators of the proposed gene law in Germany will be fined up to DM100
000 (Pounds sterling 33 000) and receive prison terms of up to five years.
Uniquely, the law imposes liability on the experimenter for damages caused
by genetic experiments, even if the authorities have approved the work,
and even if the risk could not be foreseen at the time of approval.