How Big Pharma Could Lose the War on Disease
The planned merger of pharmaceutical giant Pfizer with competitor Allergan, aimed in large part at cutting the combined company's tax bill, illustrates a troubling trend in the industry: Firms are focused more on pursuing near-term profits than on the difficult, longer-term research needed to develop truly groundbreaking new drugs. This is unfortunate, because disease may be making a comeback.
Consider the accelerating spread of multi-drug-resistant bacterial infections. There are now more than two million cases each year in the U.S. alone. Last month, scientists announced that they had found evidence, in farm animals in China, that genes for antibiotic resistance are being transferred directly among different bacteria -- a trick (known as horizontal gene transfer) that will allow the resistance to spread more quickly than ever before.
The pharmaceutical industry's reshaping doesn’t bode well for humanity's ability to respond. Almost all antibiotics in use today were discovered between 1940 and 1960. Research progress since then has been almost nil. A few synthetic drugs such as the fluoroquinolones were discovered in the 1960s, but these haven't led to many other breakthroughs. To draw a parallel from the field of electronics, it's as if progress had more or less stopped following the 1947 invention of the transistor.
Biologist Kim Lewis of Northeastern University, who has studied antibiotic development, sees the primary problem as the lack of any method for finding promising compounds. All the amazing progress a half century ago came when U.S. biochemist Selman Waksman developed a technique to systematically screen soil bacteria. This is how he discovered streptomycin, the first treatment for tuberculosis. After turning up other valuable drugs such as tetracycline, erythromycin and vancomycin, the technique eventually petered out. We still have nothing to replace it.
Another problem is that bacteria are just hard to attack. It has taken them millennia of evolution to figure out ways to exploit one another's weaknesses. Compounds we invent ourselves typically fail even to get inside bacteria, which use multiple barrier membranes to keep most chemicals out. The cell interior has sophisticated pumps to get rid of whatever does get through. Effective attacks can require doses a thousand times larger than for drugs acting against non-bacterial cells -- doses that often have toxic effects on people. When we stumble upon something that does work, bacteria quickly develop resistance.
That said, the situation isn't hopeless. A concerted scientific effort would almost certainly yield some breakthroughs, if the pharmaceutical industry played a major role.
There are new leads. Earlier this year, Lewis and his colleagues discovered an antibiotic called teixobactin that, in mice at least, killed a host of pathogens including the deadly bacterium MRSA (methicillin-resistant Staphylococcus aureus). Even better, the bacteria didn't show any signs of developing resistance. The researchers used a novel device -- an “iChip” -- to support the development of bacterial strains that do not take well to Petri dishes. The technique expands by about 50 times the number of bacterial species that biologists can grow and study in the lab. Given that most of our great ideas about antibiotics have come from bacteria, the method may promise other important discoveries.
To keep pace with deadly bacteria, we must explore these and other leads vigorously and with a genuine commitment. Last year, U.S. President Barack Obama issued an executive order establishing a strategic program to develop new antibiotics, and recognizing the challenge as a “national security priority.” Following through will require long-term vision and cooperation from government, academia and industry -- that is, movement in a direction very different than what the Pfizer-Allergan merger indicates.
The world's bacteria are sharing their best weapons, spreading new genes for antibiotic resistance, effectively cooperating against humans on a massive scale. We're not yet mounting a sufficiently symmetrical response.
This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.
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