Drugging brains, young and old
I read two interesting articles today on brain performance-enhancing of one kind or another. Denise Grady of the New York Times contributes a long article about the quest for an Alzheimer's cure:
Answers are urgently needed. Alzheimer's was first recognized 100 years ago, and in all that time science has been completely unable to change the course of the disease. Desperate families spend more than $1 billion a year on drugs approved for Alzheimer's that generally have only small effects, if any, on symptoms. Patients' agitation and hallucinations often drive relatives and nursing homes to resort to additional, powerful drugs approved for other diseases like schizophrenia, drugs that can deepen the oblivion and cause severe side effects like diabetes, stroke and movement disorders.
It's a good article with lots of history about the disease and its social and economic toll. But I found this passage the most significant:
The potential market for prevention and treatment is enormous, and drug companies are eager to exploit it. If a drug could prevent Alzheimer's or just reduce the risk, as statins like Lipitor do for heart disease, half the population over 55 would probably need to take it, Dr. Thies said.
If new drugs do emerge, they will come from studies in patients who already have symptoms, Dr. Thies said. But he said the emphasis would quickly shift to treating people at risk, before symptoms set in. Many researchers doubt that even the best preventive drugs will be able to heal the brains of people who are already demented.
Treating preventively, Dr. Thies said, "will be more satisfying to patients and physicians, and there will be an economic incentive because you'll wind up treating more people."
The only thing that could slow the drive for early treatment, he said, would be serious side effects -- and Dr. Morris, at Washington University, said drugs powerful enough to treat Alzheimer's would probably have strong side effects.
It's interesting to me because of the recent genetic stuff I've been working on. But also in light of this other story in today's LA Times, by writers Karen Kaplan and Denise Gellene:
Drugs to build up that mental muscle
Academics, musicians, even poker champs use pills to sharpen their minds, legally. Labs race to develop even more.
People are already using various psychoactive drugs to get a leg up in whatever mental competitions they pursue. Some of this is no more sophisticated than late-night coffee drinking for the Ritalin generation. But some is more surprising:
"There isn't any question about it -- they made me a much better player," said Paul Phillips, 35, who credited the attention deficit drug Adderall and the narcolepsy pill Provigil with helping him earn more than $2.3 million as a poker player.
...
The growth of the brain drugs bears a striking resemblance to the post-World War I evolution of plastic surgery -- developed to rehabilitate badly disfigured soldiers but later embraced by healthy people who wanted larger breasts and fewer wrinkles.
The use of cognitive-enhancing drugs has been well documented among high school and college students. A 2005 survey of more than 10,000 college students found 4% to 7% of them tried ADHD drugs at least once to remain focused on exams or pull all-nighters. At some colleges, more than one-quarter of students surveyed said they had sampled the pills.
The article discusses the "blockbuster drug that labs are racing to develop," a memory pill. Which of course brings us full circle to Alzheimer's treatment.
You may be thinking there is something unnatural about this; maybe even something unfair -- like an athlete using steroids to enhance his performance. But with psychological factors, it is a little more evident that there is a continuum of uses, some of which are pretty clearly acceptable. For example, the performance artists who take a pill to calm their nerves before appearing on stage are literally enhancing their performance, but in a way that is arguably different from their skill as artists.
Likewise, there is a continuum among normal people -- how do we justify allowing Adderall for the student who has trouble taking an eight-hour exam, but denying it to the student who had trouble sleeping before the exam?
Progress on these kinds of drugs will only come with understanding the continuum of psychological and cognitive variation among living people -- along with the causes of that variation, both developmental and genetic. We might like some chemical to increase memory performance. But the brain is a complicated place with countless interactions of different structural and regulatory processes. Maybe some people already have the chemicals that enhance memory, and other people don't, or don't express them in the right places in the right amounts. If so, then Alzheimer's treatment may focus on the metabolic processes of non-Alzheimer's brains, for example.
Plus, as we've learned recently with respect to traumatic stress, it's not always good to remember things well, so there is no reason to assume that the human population has been adapting toward longer or better memory. In general, it's not obvious exactly what memory characteristics have tended to increase fitness recently or during earlier phases of human evolution. Aside from the energy and life history constraints of large brains, we don't know what evolutionary trade-offs exist with respect to memory or other aspects of cognitive function.
Athletes take performance-enhancing drugs for a relatively slight advantage. Pharmaceutical firms are pursuing brain drugs on the expectation that millions of people will take a daily pill for years on end, in order to stave off Alzheimer's. Unshackling the mind power of a large proportion of the older population will no doubt have a tremendous impact on the societies of the future.
Pretty exciting stuff, if only we could figure it out.
Coming next: virus toothpaste?
I couldn't help but wonder after reading this story:
Bacterial biofilms can form almost anywhere, even on your teeth if you don't brush for a day or two. When they accumulate in hard to reach places such as the insides of food processing machines or medical catheters, however, they become persistent sources of infection.
These bacteria excrete a variety of proteins, polysaccharides, and nucleic acids that together with other accumulating materials form an extracellular matrix, or in Lu's words, a "slimy layer," that encases the bacteria. Traditional remedies such as antibiotics are not as effective on these bacterial biofilms as they are on free-floating bacteria. In some cases, antibiotics even encourage bacterial biofilms to form.
Lu and senior author James Collins, professor of biomedical engineering at BU, aim to eradicate these biofilms using bacteriophage, tiny viruses that attack bacteria. Phage have long been used in Eastern Europe and Russia to treat infection.
The story describes research that built a sort of "phage toolkit", for those times when you don't "want to dig through sewage to find these phages."
Reviving old viruses buried in the genome
This story caught my attention:
In a controversial study, researchers have resurrected a retrovirus that infected our ancestors millions of years ago and now sits frozen in the human genome. Published online by Genome Research this week, the study may shed new light on the history of these genomic intruders, as well as their role in tumors. Although this particular virus, dubbed Phoenix, is a wimpy one, some argue that resuscitating any ancient virus is inherently risky and that the study should have undergone stricter reviews.
Basically, they took a consensus sequence of one family of human endogenous retroviruses, which have implanted their own genomes within ours over millions of years, and used the sequence to build a real virus. And it worked, creating a weakly infectious agent.
Lots of people think this is a bad idea. After all, resurrecting ancient viruses is like a box of chocolates: you never know when they'll escape from the petri dish and start eating your flesh off.
Personally, if it wasn't such a bad idea, I have to wonder why they gave the virus such an obviously military-sounding name! I mean, "Phoenix"?
DDT and the malaria wars
I'll be lecturing on hemoglobinopathies again this week, and I stumbled across this 2001 article by Malcolm Gladwell, profiling Fred Soper and the early 20th century effort to eradicate malaria.
This passage is from a longer section describing his work eliminating invasive Anopheles gambiae from Brazil in 1938:
Four thousand men were put at his disposal. He drew maps and divided up his troops. The men wore uniforms, and carried flags to mark where they were working, and they left detailed written records of their actions, to be reviewed later by supervisors. When Soper discovered twelve gambiae in a car leaving an infected area, he set up thirty de-insectization posts along the roads, spraying the interiors of cars and trucks; seven more posts on the rail lines; and defumigation posts at the ports and airports. In Soper's personal notes, now housed at the National Library of Medicine, in Bethesda, there is a cue card, on which is typed a quotation from a veteran of the Rockefeller Foundation's efforts, in the early twentieth century, to eradicate hookworm. "Experience proved that the best way to popularize a movement so foreign to the customs of the people . . . was to prosecute it as though it were the only thing in the universe left undone." It is not hard to imagine the card tacked above Soper's desk in Rio for inspiration: his goal was not merely to cripple the population of gambiae, since that would simply mean that they would return, to kill again. His goal was to eliminate gambiae from every inch of the region of Brazil that they had colonized--an area covering some eighteen thousand square miles. It was an impossible task. Soper did it in twenty-two months.
There were the great successes, and some hubris, and something of a tragic end. But it's a timely story, considering that WHO has stepped up its recommendations to use DDT to fight malaria in Africa. (via Instapundit)
And Soper was a Kansas boy.
Zimmer on E. coli and bioterror
I very much liked Carl Zimmer's Slate piece about foodborne pathogens and their lessons for defending against bioterrorism. Zimmer has a book about E. coli coming out later this spring, and he visits the topic of the 2006 outbreaks of an especially virulent strain.
This worrisome trend led a team of scientists based at Michigan State University to take a look at the DNA of the bacteria. The researchers compared bacteria from recent outbreaks with hundreds of others samples and published the results last Monday. The scientists drew an evolutionary tree based on the differences in the bacteria's genes. One branch of the tree -- the one that caused the spinach and lettuce outbreaks in 2006 -- is significantly more likely to make people sick than the others. And they found that this lineage has been exploding in recent years. In 2002, it accounted for 10 percent of the E. coli cases recorded in Michigan. In 2006, it accounted for 46 percent.
Whole-genome sequencing found large deletions and insertions of hundreds of genes in the newer virulent clade. Zimmer brings our attention to the complexity of the mechanisms that determine virulence. At present, science still can't predict how these genes will affect the pathogens. On this grounds, one may argue that the prospects are low that an enemy state or mad scientist will soon be able to create such a dangerous strain deliberately.
But this is not grounds to celebrate, since nature is busily creating dangerous strains for us. Natural selection does not design its products in a single leap of invention, but it sifts many millions of variants much more efficiently than any human laboratory.
I think that the last paragraph contains the essential lesson.
But this ignorance [of which genes must be altered to make a killer pathogen] is not cause for much comfort. Even if we don't need to worry about synthetic bacteria just yet, we do need to worry about new pathogens evolving right in our own backyard (or, rather, our own feedlots and factory farms). As things stand, we become vaguely aware of these bacteria only once they've been sickening and killing for years.
Sure, it may be difficult to engineer a more virulent pathogen for bioterror. But it is pretty easy to use the ones we already have. The evil genius is much less a threat than nature. And a saboteur looking to replicate small-scale terror on the order of the D. C. sniper may find hundreds of victims by contaminating one line of the vast American food web.
Defending against this kind of terror is the same task as defending against nature.
John Hawks Department of Anthropology
University of Wisconsin—Madison
Copyright © 2007 John Hawks