Sunday, April 02, 2006

Why the BU Lab is Not Important or Needed in Boston

Why the BU Lab is Not Important or Needed in Boston

By: Lynn C. Klotz, PhD, Senior Science Fellow,
Center for Arms Control and non Proliferation

The author, a former biotechnology executive,
currently consults on biotechnology and
pharmaceutical strategy to many kinds of business

Boston University's proposed laboratory complex
is to house a "Biosafety Level" BSL4 laboratory,
the numeral "4" designating the highest level of
biohazard security. (Other levels are BSL3s,
which study pathogens like anthrax for which
there are treatments, and BSL2s, which house
less-threatening infectious disease agents.)
BSL4s experiment only on the most dangerous
disease agents usually not endemic to the US like
the hemorrhagic fever viruses, Ebola and Marburg.
At present, only a very few highly exotic
pathogens qualify for BSL4.

One of Boston University's main arguments for the
BSL4 is that it is vital to Boston's economy and
bioscience communities - these composed of major
pharmaceutical companies, biotechnology
companies, and academic and other non commercial
labs. I don't believe BU's claim. Of the ten or
so major pharmaceutical company facilities, the
more than 200 biotechnology companies, and
hundreds of infectious- disease non-commercial
research labs in Massachusetts, perhaps only a
handful will ever use the BSL4 lab at Boston
University. Indeed, failure to build the BSL4
will cause at most a hiccup in the area’s
bioscience industry.

To understand why this is so, consider the major
international disease threats that won't be
studied at the BSL4: malaria, HIV/AIDS, and
tuberculosis. All three require only BSL2 level
containment since they are already present in the
population and there’s no need to protect the
public from exposure to them from escape from the
laboratory. The same is true for the vast
majority of infectious disease agents endemic to
the U.S. The deadly 1957 and 1968 influenza
strains require only BSL3 containment, even
though they are not currently present in the
population. The recently resurrected pandemic
1918 strain requires containment between BSL3 and
BSL4 (though it should require BSL4 containment.)

A closer look at the different parts of the
Massachusetts bioscience community reveals why
the Boston University BSL4 would be - at very
best - redundant, as there are already four BSL4s
elsewhere in the country.

Major pharmacetical companies

The modern pharmaceutical industry, composed of
the 40-odd companies comprising the member list
of the Pharmaceutical Research and Manufacturers
Association, cut its teeth on antibiotic
development in the 1950s and 1960s. They had
considerable expertise in developing
"countermeasures" - biodefense language for
antibiotics, antivirals, vaccines and other such
agents - against natural disease. But lately it
has been far more profitable for companies to
drift away from antibiotic development, focusing
instead on drugs for chronic conditions like high
cholesterol and depression. Sold over and over
again to patients, these drugs have sales of well
over an annual $1 billion. By contrast,
biodefense "countermeasure" sales will usually be
one-time sales to the Strategic National
Stockpile only representing a few hundred million
dollars at most.

There are other reasons why the companies are
unlikely to make use of the BU facility for
biodefense research:

Liability: Concerns over law suits from possible
use of non FDA approved drugs during emergencies.

Damage to their reputations: Concerns over
sickness or death from use of drugs, FDA-approved
or not, in false-alarm emergencies. The industry
likely would not want to see untested drugs used
at all.

Bad publicity: Working with biological weapons
agents, for whatever reason, makes for bad
publicity. The US public and our enemies, often
suspicious of the industry’s motives, could
mistake defensive research for offensive
bioweapons development. The industry stresses
that “Disease is our enemy. Working to save lives
is our job.”

Increased inspections and oversight: The industry
already feels over-inspected by the government.
Possession and work with biological weapons
agents will require considerable paper work,
security clearances, and oversight by the
government. In any mishap, an FBI investigation
could result – for a company, to be avoided at
all costs.

Confidentiality: Pharmaceutical companies are
secretive; they dislike any disclosure they deem
inappropriate or premature. So a company is
unlikely to be attracted by a facility located in
a context with a large population of students
with no financial stake in their company. The
inability to guarantee confidentiality will be a
disincentive to a company.

Here are some additional observations. The
BioShield 2004 legislation provides for the use
of non-FDA- approved countermeasures in an
emergency -- countermeasures that may never have
been tested in humans. The pharmaceutical
industry won’t support any BioShield legislation
when they’re not protected from liability for
harm caused by haphazard use of their drugs. And
while Senator Bill Frist has attached an immunity
clause to a large biodefense bill soon to pass,
it’s unlikely that the immunity provision will
survive very long. Many Congress members have
been putting up stiff resistance to letting major
corporations off the hook by granting them
immunity from lawsuits.

Ebola and the like have no natural incidence in
the US. For a market large enough to catch a
major pharmaceutical company’s interest, a
disease must be prevalent in the population or
highly expensive to maintain patients, diseases
studied in BSL2s not BSL4s. There are plenty of
BSL2s: most laboratories doing infectious disease
research have them. Moreover, for reasons of
confidentiality, major pharmaceutical companies
can easily afford and are likelier to prefer
having their own BSL2 labs.

Biotechnology companies

Biotechnology companies are different from the
forty- odd major pharmaceutical companies: they
have no products on the market and they are
struggling financially. For them, a one-time sale
worth several million dollars to the so-called
Strategic National Stockpile could be attractive.
Some biotechnology companies, drawn to antibiotic
markets, are applying their novel research skills
to infectious disease.

There are about 275 Massachusetts biotech
companies profiled by the Massachusetts
Biotechnology Council [MBC.] Seventeen of these
say they are engaging in research and development
of infectious disease therapies. Only one company
describes itself as conducting defense research
-- developing rapid means of identifying
pathogens. Only three companies identify
themselves as vaccine companies. Of these, only
one, Acambis, is actually developing a
bio-defense vaccine, which is for smallpox. Thus,
from their MBC descriptions, none of the
seventeen companies appears to need a BSL4

If the Boston University BSL4 laboratory were not
built, perhaps none, but at most only a few of
the 275 Massachusetts biotechnology companies
would be affected. Those few would have to go
elsewhere to do final experiments. Moreover, the
biotechnology industry took root around
universities in Boston and San Francisco, not
around the extant BSL4 facilities in Maryland and
Atlanta. Cambridge has no BSL4 laboratory, and a
law prohibiting rDNA research in BSL4
laboratories, yet that city has a significant
biotechnology company presence.

Academic and other non-commercial labs

There may well be over a hundred academic
laboratories carrying out infectious disease
research in the Boston area. A few quick PubMed
searches using key words such as “filovirus,”
“Ebola,” “Marburg,” “biodefense,” “bioter ror,”
“smallpox,” and the like, yield between 3 and 30
hits for each key word in the Boston-area. A
brief examination of titles and abstracts of the
Pub Med hits reveals that only a few are actual
research papers. Most are commentaries on general
areas like history, policy, and epidemiology.

So there seems to be little academic research
activity in the Boston area that would require a
BSL4 laboratory. Of course, some scientists at BU
and other surrounding universities plan research
in the BSL-4 laboratory. The BU-NIH grant
application to build the facility includes 43
resumes. Some of these came from administrators.
Some were from scientists who could "benefit"
from the lab, others were unclear about how they
would use the lab

A final comment: outbreaks of the filoviruses
which are prominent in the handful of exotic
diseases to be studied in BSL4s, have been
localized on their continent of origin, Africa.
Ebola and Marburg, two of the dreaded hemorrhagic
fever viruses, are among the filoviruses. But
while death from them is horrific, outbreaks
cause deaths in the tens to hundreds, not
millions. Thus they have not represented
international public health threats. Apparently,
they do not pose biological weapon threats to the
US, either. Government biodefense researchers at
USAMRIID have stated that most evidence suggests
they aren’t very stable by aerosol dissemination,
the only mechanism that would make them a
bioweapons threat. Since there are so few of
these agents and existing BSL4 labs are working
on them, a Boston- area laboratory would be
redundant, hardly the necessity its proponents
claim. There is no reason that work on these
agents cannot be carried out in the four existing
BSL4 facilities.

Credits: Thanks to Prof. Daniel Goodenough, Prof.
Patrica Hynes, Dr. Marc Pelletier for important
contributions. Special thanks to Ellen Cantarow
for many rounds of editing.