66 • Impacts of Applied Genetics — Micro-Organisms, Plants, and Animals 
A comparison with the traditional source of 
animal insulin is interesting. If 0.5 milligram 
(mg) of pure insulin can be obtained from a liter 
of fermentation brew, 2,000 liters (1) (roughly 
500 gal) would yield 1 g of purified insulin— the 
amount produced by about 16 lb of animal pan- 
creas. If, on the other hand, the efficiency of 
production could be increased to that achieved 
for asparaginase (which is produced commer- 
cially by the same organism, E. coli), 2,000 1 
would yield 100 g of purified insulin— the 
amount extracted from 1,600 lb of pancreas. 
(The average diabetic uses the equivalent of 
about 2 mg of animal insulin per day.) 
The extent of the actual demand for insulin is 
a controversial issue. Eli Lilly & Co. estimates 
that there are 60 million diabetics in the world 
(35 million in underdeveloped countries, where 
few are diagnosed or treated). Of the 25 million 
in the developed countries, perhaps 15 million 
have been diagnosed; according to Lilly’s esti- 
mate, 5 million are treated with insulin. Only 
one-fourth of those diabetics treated with in- 
sulin live in the United States, but they use 40 to 
50 percent of the insulin consumed in the 
world. A number of studies indicate that while 
the emphasis on diet (alone) and oral antidia- 
betic drugs varies, approximately 40 percent of 
American patients in large diabetes clinics or 
practices take insulin injections. In the United 
States, diabetes ranks as the fifth most common 
cause of death and second most common cause 
of blindness. Roughly 2 million persons require 
daily injections of insulin. 
Today, at least, there is no real shortage of 
glands from slaughter houses for the produc- 
tion of animal (principally bovine and porcine) 
insulin. A study conducted by the National Dia- 
betes Advisory Board (NDAB) concluded that a 
maximum demand and a minimum supply 
would lead to shortages in the 1990’s. Eli Lilly’s 
projection, presented in that report, also antici- 
pates these shortages. But, Novo Industri, a ma- 
jor world supplier of insulin, told the NDAB that 
it estimates that the 1976 free-world consump- 
tion of insulin of 51 X 10® units constituted only 
23 percent of the potential supply, and the 
87X10® units projected for 1996 would only 
equal 40 percent of the supply, assuming that 
the animal population stays constant. 
Lor insulin, therefore, the limitation on bring- 
ing the fruits of genetic engineering to the 
marketplace is not technological hut institu- 
tional. The drug must first be appro\-ed by the 
Eood and Drug Administration (FD.A) and then 
marketed as a product as good as or better than 
the insulin extracted by con\entional means. 
Lilly has stated that it anticipates a 6-month 
testing period in humans. Undoubtedly, LD.A 
will examine the e\ idence presented in the in- 
vestigational new drug a[)|)lication (IND.A) w ith 
special care. Its rexiew will establish criteria 
that may influence the rex iew of suhs(‘(|uent aj)- 
plications in at least the folloxx ing re(|uirements: 
• evidence that the amino aciti .se(|uence of 
the material is identical to that of the nor- 
mal human hormone: 
• freedom from hactei'ial endoto.xins that 
may cause lex er at exti'cim'lx loxx concen- 
trations— an inhei’ent hazard as.sociated 
xvith any process using E. coli; and 
• freedom from byproducts, including sub- 
stances of xei'v similar structure that max’ 
give rise to rare a('ut(> or chronic r»*actions 
of the immune system. 
Furthermore, as dex’elopment continues, IDA 
might recjuire strict assurances that tlu* mole- 
cules j)i'oduced from hatch to hatch are not sub- 
ject to subtle xai’iations resulting Irom their 
genetic origin. 
If the insulin obtained from rD.VA techniques 
manages to pass 1D,\ i'e(|uirements, it must 
oxei'come a second obstacle— competition in the 
marketplace. I’he clinical rationale lor using 
human rather than animal insulin rests on the 
differences in structure among insulins pro- 
duced by different species Human .md porcine 
insulins for example, differ in a single amino 
acid, xvhile human and cattle insulins diller 
xvith respiH't to three. .As lar .is is known these 
variations do not impair the elleclixenes o| the 
insulin, hut no om* has i‘x (*r been in a |M)sition to 
conduct a significant lest ol the use ot hum.m 
insulin in a dialxMic |) 0 |)ulalion M.inx lonse 
(luences of thi; dise.ise, such as ri'linopatlix tret 
inal diseas(') and n(>phro|)athx Ikidnex dise.isel 
are not prm’ented by routine injection of .mim.il 
insulin. Lati(‘nts also occasionallx respond .id 
versely or produce antibodies to .inim.il insulin 
xvith suhs('(|uenl allergic or resist. ml re . k lion 
