Prediction is hard, especially of medicine

Sum­mary: med­i­cal progress has been much slower than even re­cently pre­dicted.

In the Fe­bru­ary and March 1988 is­sues of Cry­on­ics, Mike Dar­win (Wikipe­dia/​LessWrong) and Steve Har­ris pub­lished a two-part ar­ti­cle “The Fu­ture of Medicine” at­tempt­ing to fore­cast the med­i­cal state of the art for 2008. Dar­win has re­pub­lished it on the New_Cry­o­net email list.

Dar­win is a pretty savvy fore­caster (who you will re­mem­ber cor­rectly pre­dict­ing in 1981 in “The High Cost of Cry­on­ics”/​part 2 ALCOR’s re­cent trou­bles with grand­father­ing), so given my stand­ing in­ter­ests in track­ing pre­dic­tions, I read it with great in­ter­est; but they still blew most of them, and not the ones we would pre­fer them to’ve.

The full es­say is ~10k words, so I will ex­cerpt roughly half of it be­low; feel free to skip to the re­ac­tions sec­tion and other links.

1 The Fu­ture of Medicine

1.1 Part 1

What we hope we are es­pe­cially good at as cry­on­i­cists is pre­dict­ing the fu­ture — par­tic­u­larly the fu­ture of medicine. After all, our lives de­pend upon it. Be­cause that’s what cry­on­ics is about — to­mor­row’s medicine to­day. In or­der for cry­on­ics to seem rea­son­able, in or­der for it to be rea­son­able, it is nec­es­sary to have some idea, at least in broad out­line, of where medicine is go­ing and of where it ul­ti­mately can go. I think that the cry­on­i­cists’ record on this point in a broad sense has been very good.

…One thing which is rarely seen in cry­on­ics pub­li­ca­tions is an at­tempt to see the shape of things to come in the near or in­ter­me­di­ate fu­ture. Oddly enough, that’s a far more difficult and dan­ger­ous un­der­tak­ing than pre­dict­ing ul­ti­mates. Nor is this a prob­lem con­fined to cry­on­ics or the fu­ture of medicine. Sadi Carnot (the founder of ther­mo­dy­nam­ics) could tell you all about the “perfect heat en­g­ine,” but would have no doubt had trou­ble giv­ing you hard num­bers on how well heat en­g­ines would be made to perform over the 20 years or so fol­low­ing pub­li­ca­tion of his work….When I look over pre­dic­tions made in the 1950’s or the 1960’s about the fu­ture of medicine and/​or tech­nol­ogy, I always chuckle about just how far afield these guys were. A good ex­am­ple is a list of pre­dic­tions made by Her­man Kahn which was sum­ma­rized in CRYONICS REPORTS in Au­gust of 1967 (vol­ume 2, #8). They are re­pro­duced as Table 1 be­low. Read ’em and weep — or laugh if you will!

Table 1. Less Likely But Im­por­tant Pos­si­bil­ities, from: The Next 33 Years: A Frame­work For Spec­u­la­tion, by Her­man Kahn and An­thony J. Weiner (1967) [pre­dic­tions for 2000 AD]

  • “True” ar­tifi­cial intelligence

  • Prac­ti­cal use of sus­tained fu­sion to pro­duce neutrons

  • Ar­tifi­cial growth of new limbs and organs

  • Room tem­per­a­ture superconductors

  • Ma­jor use of rock­ets for trans­porta­tion (ei­ther ter­res­trial or ex­trater­res­trial)

  • Effec­tive chem­i­cal or biolog­i­cal treat­ment for most men­tal illnesses

  • Al­most com­plete con­trol of marginal changes of heredity

  • Sus­pended an­i­ma­tion (for years or cen­turies)

  • Prac­ti­cal ma­te­ri­als with nearly “the­o­ret­i­cal limit” strengths

  • Con­ver­sion of mam­mals (hu­mans?) to fluid breathers

  • Direct in­put into hu­man mem­ory banks

…My per­sonal per­spec­tive is one of be­ing a hard-core cry­on­i­cist who was in­volved in clini­cal medicine for the bet­ter part of a decade. My bi­ases about pre­dict­ing the fu­ture could prob­a­bly be sum­ma­rized as fol­lows: I have a lot of sym­pa­thy for the in­cre­men­tal­ist view of progress—par­tic­u­larly in the highly reg­u­lated area of medicine. It’s reg­u­lated be­cause it di­rectly and pow­er­fully touches peo­ple’s well-be­ing and be­cause it is not a very fault-tol­er­ant area — mis­takes are costly and since peo­ple like be­ing al­ive (at least in the short run) they get edgy if an er­ror sep­a­rates them from their ac­tu­ar­ial ex­pec­ta­tions.

I thus be­lieve that any pre­dic­tions about the fu­ture of medicine have to in­clude what I call the “space pro­gram fac­tor” (SPF). By this I mean sim­ply that progress in the space pro­gram would have pro­ceeded far, far faster (and thus ap­prox­i­mated more closely what was the­o­ret­i­cally pos­si­ble) if it were not a high-visi­bil­ity pro­ject with lots of poli­ti­cal and so­cial over­tones which make it fault-in­tol­er­ant — if you could burn up as many as­tro­nauts as you do test pi­lots ev­ery month, it would cost a lot less to get where you’re go­ing. First-shot fail-safe en­g­ineer­ing is costly. Medicine suffers from the same kinds of prob­lems — wit­ness the FDA as both the solu­tion and the prob­lem.

1.1.1 Diagnostics

I fore­see a ver­i­ta­ble ex­plo­sion of di­ag­nos­tic tech­niques and pro­ce­dures. A large num­ber of ill­nesses which are poorly un­der­stood to­day will be well-char­ac­ter­ized the next decade and will be easy to di­ag­nose very early in their de­vel­op­ment or even be­fore they de­velop be­cause they will be found to have di­rect or in­di­rect ge­netic causes. Fairly pre­dic­tive tests for Alzheimer’s dis­ease, schizophre­nia, de­pres­sion, some ma­lig­nan­cies, heart dis­ease, and most of the rest of the ma­jor kil­lers and dis­ablers will prob­a­bly be in place by 2000 to 2010. Many if not most of these ail­ments will be as­sess­able in terms of a very so­phis­ti­cated ge­netic risk pro­file which it will be pos­si­ble to gen­er­ate in in­fancy or child­hood (or in utero). A wide range of ge­netic probes for ill­ness-gen­er­at­ing genes should be available by the end of the cen­tury.

A side-note: ge­netic as­so­ci­a­tions have been a very fer­tile field for John Ioan­ni­dis, and a big study just blew away a bunch of SNP-IQ cor­re­la­tions.

Real-time di­ag­no­sis will also be rev­olu­tionized by the turn of the cen­tury. The next 10 to 15 years will see in­creas­ing mi­ni­a­tur­iza­tion of sen­sors and chem­istry pack­ages. Tis­sue probes or biosen­sors which can mea­sure a wide ar­ray of biolog­i­cal and bio­chem­i­cal fac­tors will be pack­aged in very small, very sta­ble de­vices which hold cal­ibra­tion over pro­longed pe­ri­ods of time (weeks to months to years) and which can eas­ily be in­serted into the pa­tient’s body or tis­sues. For ex­am­ple, I fore­see multi-sen­sor units mounted on very small nee­dle or catheter tips which can be in­serted in­tra­venously, in­tracra­nially, in­tra-cere­brally, sub­cu­ta­neously, and so on.

Th­ese sen­sors will be able to give real-time mea­sure­ments of blood gases, pH, elec­trolytes, en­zyme lev­els, and a host of other bio­chem­i­cal pa­ram­e­ters that now in­volve costly, time-con­sum­ing, and/​or im­pos­si­ble “lab­o­ra­tory stud­ies” re­quiring with­drawal of a sam­ple and pro­cess­ing. Real-time biosen­sors will rev­olu­tionize acute care of crit­i­cally ill pa­tients.

…The first gen­er­a­tion of these de­vices should be in the mar­ket­place some­where be­tween 1990 and 1995. More so­phis­ti­cated in­stru­ments ca­pa­ble of a wider ar­ray of mea­sure­ments will quickly fol­low. Th­ese sen­sors will also have a profound im­pact in acute sta­bi­liza­tion of pa­tients in a field set­ting. It will be pos­si­ble for paramed­i­cal per­son­nel to quickly and effec­tively in­sert such in­stru­ments in an acutely ill pa­tient — a vic­tim of car­diac ar­rest or trauma, and im­me­di­ately and globally as­sess that pa­tient’s con­di­tion, re­lay­ing that in­for­ma­tion to an ex­pert (more on who that ex­pert will be later).

…Di­ag­nos­tic imag­ing should rapidly come down to a bat­tle be­tween ul­tra­sound and MRI (NMR; (nu­clear) mag­netic res­o­nance imag­ing). Be­cause ul­tra­sound units owe their size and weight al­most en­tirely to the com­puter that pro­cesses the in­for­ma­tion, the size and effec­tive­ness of these units will change on the same rapid ex­po­nen­tial curve as the size and power of com­put­ers. MRI is a tech­nol­ogy which has some other phys­i­cal limi­ta­tions, but by the year 2000, even MRI units will be far smaller, less costly, and ca­pa­ble of far, far bet­ter re­sults. Bed­side units or “on floor” units (i.e., units in the ICU or CCU) may be available for re­peated as­sess­ment of the pa­tient’s con­di­tion. MRI and its grand­chil­dren and cous­ins should in par­tic­u­lar be ex­pected to un­dergo con­sid­er­able re­fine­ment. Metabolic MRI will also be in wider use, al­low­ing for real-time eval­u­a­tion of the metabolic and work­ing state of pa­tient’s hearts, brains and other or­gans. By 2000 to 2010 the cost and size of these units may be dras­ti­cally re­duced and they may be in field use for acute metabolic and struc­tural eval­u­a­tion of pa­tients with trauma or in car­diac ar­rest.

I re­cently learned that, be­sides the usual blame for in­creas­ing med­i­cal costs, some cat­e­gories of doc­tors have been stren­u­ously urged to re­duce MRI use as ac­tively harm­ful.

By the late 1990’s there should be an an­swer to this prob­lem in the de­vel­op­ment of the Portable Doc­tor or Ex­pert Med­i­cal De­vice (EMD). The EMD will be both a di­ag­nos­ti­cian and ther­a­pist in­te­grated into one unit. In an emer­gency med­i­cal set­ting (ei­ther in an am­bu­lance or in an ICU or CCU) this pow­er­ful com­puter will be di­rectly cou­pled to a wide ar­ray of both sim­ple and com­plex med­i­cal as­sess­ment de­vices….EMDs will be a very hot item. Ini­tially (i.e., the 1990’s) they will be con­fined to am­bu­lances and the ICU, CCU, and spe­cialty ar­eas of the hos­pi­tal, such as ra­diol­ogy and car­diol­ogy labs. But there will be pow­er­ful in­cen­tives for wider ap­pli­ca­tion of these de­vices. As com­put­ing ca­pac­ity drops in cost and in­creases rad­i­cally in so­phis­ti­ca­tion (i.e., par­allel pro­ces­sors, neu­ral net­works, truly mas­sive mem­o­ries, and so on) ex­pert med­i­cal (and other) sys­tems will see in­creas­ing ap­pli­ca­tion. There will be de­vices on the mar­ket such as a “Home Doc­tor” di­ag­nos­tic pro­gram, which will ba­si­cally be an in­ter­nal medicine physi­cian in a can.

…After 2000, many peo­ple will prob­a­bly have a small sen­sor ar­ray per­ma­nently im­planted and cou­pled to teleme­try equip­ment which can be ac­ti­vated to call for help or alert the per­son that trou­ble is brew­ing. Peo­ple with a known risk of sud­den health prob­lems will be the first to use these kinds of de­vices. With the de­vel­op­ment of smaller and cheaper teleme­try equip­ment (di­rectly linked to large-an­tenna satel­lites), sep­a­rate teleme­try ar­range­ments will dis­ap­pear. Im­plantable, com­puter-con­trol­led defibrilla­tors are already a re­al­ity; analo­gous de­vices to de­liver drugs in case of car­diac or brain in­farct (stroke) will even­tu­ally be­come re­al­ity.

1.1.2 Resuscitation

Ex­pect a shift back to open-chest heart mas­sage and away from closed-chest mas­sage in med­i­cal and per­haps even paramed­i­cal set­tings. Closed-chest CPR will be re­al­ized to be in­effec­tive at main­tain­ing cere­bral vi­a­bil­ity and will be re­placed by far more effec­tive open chest meth­ods. In paramed­i­cal (i.e., field) set­tings the em­pha­sis will be on very rapid defibrilla­tion — or ac­tu­ally “leav­ing the pa­tient alone” un­til cir­cu­la­tion can be effec­tively re­stored and med­i­ca­tions given to in­hibit reper­fu­sion in­jury. Closed chest CPR and restart­ing cir­cu­la­tion by lay­men “in the field” will be re­al­ized to be do­ing more harm than good and there may well be a move away from field CPR, with lay­men be­ing in­structed to leave the pa­tient with­out cir­cu­la­tion un­til it can be restarted ad­e­quately and un­der con­trol­led con­di­tions.

By the late 1990’s, ex­tended use of CPR will be a thing of the past and ma­jor metropoli­tan ar­eas will have “death re­ver­sal units” (DRUs) in emer­gency rooms and per­haps even in larger paramed­i­cal units. The DRUs will em­ploy rapid fe­moral cut-downs and blood-pump/​oxy­gena­tor sup­ported re­sus­ci­ta­tion to re­cover peo­ple who have suffered ex­tended pe­ri­ods of is­chemia (in the 30 minute to 1 hour range). CPR will be re­al­ized very of­ten to be in­effec­tive at re­cov­er­ing pa­tients who are profoundly is­chemic and the ad­vent of phar­ma­cologic in­ter­ven­tion al­low­ing for cere­bral re­sus­ci­ta­tion will provide tremen­dous pres­sure for emer­gency rooms to de­velop the ca­pa­bil­ity to very rapidly put an is­chemic pa­tient on by­pass and com­pletely and ad­e­quately sup­port his cir­cu­la­tory and res­pi­ra­tory needs un­til his brain can re­cover and/​or his heart can be re­paired and restarted. An in­ter­me­di­ate sce­nario would be the de­vel­op­ment of small, flex­ible im­pel­ler pumps that can be col­lapsed and passed through a large bore per­cu­ta­neous catheter through the fe­moral artery and into the ab­dom­i­nal aorta. Such a pump (act­ing much like the pro­pel­ler on an out­board boat mo­tor) could then be used to sup­ple­ment CPR, per­haps pro­vid­ing 2–3 liters per minute of car­diac out­put.

…Another effect of drugs like the lazaroids and cal­cium chan­nel block­ers will be the more effec­tive treat­ment of acute in­juries to a wide range of tis­sues such as the spinal cord and brain. Much of the dam­age that oc­curs to these tis­sues is free rad­i­cal re­lated and can be in­hibited by use of these drugs…In­ter­ven­tion into sec­ondary in­flam­ma­tion will be most im­por­tant in the brain and spinal cord. De­ploy­ment of these tech­niques will re­sult in the sal­vage of many spinal cords that would be con­sid­ered ir­re­versibly in­jured by to­day’s medicine. There will be far, far fewer para­plegics. How­ever, ex­pect an in­crease in the num­ber of per­ma­nently brain-in­jured pa­tients and in the num­ber of pa­tients with “sub­tle” forms of cere­bral in­jury re­sem­bling mild stroke or the cog­ni­tive or mood di­s­or­ders seen in dis­eases like mul­ti­ple scle­ro­sis or acute head in­jury. Th­ese dis­ease states will re­sult be­cause peo­ple with brain trauma who would have died acutely from sec­ondary free rad­i­cal me­di­ated in­jury (cere­bral edema and so on) will be saved with lazaroids and other cere­bral res­cue tech­niques.

1.1.3 Antibiotics

The next twenty years should see many pow­er­ful new an­tibiotics en­g­ineered di­rectly from knowl­edge of the struc­ture of the rele­vant micro­bial en­zyme which it is de­sired to in­hibit. Not only will these an­tibiotics be more pow­er­ful, but be­cause they do not ex­ist in na­ture, strain re­sis­tance will not so eas­ily de­velop to­ward them as it has for the an­tibiotics of to­day.

In ad­di­tion, the next gen­er­a­tion of an­tibiotics will in­clude many which have been de­signed for effect against viruses, an area where medicine is presently largely pow­er­less.

The phar­ma­ceu­ti­cal in­dus­try and an­tibiotics have been a case-study in stag­na­tion, failure, and diminish­ing marginal re­turns. There is only one, highly ex­per­i­men­tal, anti-viral that I have heard of. In a fol­lowup email, Dar­win re­sponded to some­one else point­ing out DRACO:

Fi­nally, while Ge­off cites this pu­ta­tive ad­vance in an­tiviral drug ther­apy, the fact is that my pre­dic­tion about a plethora of new and highly effec­tive tar­geted molec­u­lar an­timicro­bials by 2008 was WRONG. In fact, an­tibiotic re­search is all but dead, and there are vir­tu­ally no fun­da­men­tally new an­tibiotics in the drug pipeline. This should scare the crap out of all us, be­cause we are rapidly ap­proach­ing com­plete an­tibiotic re­sis­tance with a num­ber of com­mon and highly lethal bugs, in­clud­ing staph (MRSA), strep­to­coc­cus, E. coli, pseu­domonas and can­dida. It is only a mat­ter of months to a few years, at most, be­fore com­pletely an­tibiotic re­sis­tance staph and strep­to­coc­cus emerge. Phar­ma­ceu­ti­cal com­pa­nies have a large nega­tive in­cen­tive for de­vel­op­ing new an­timicro­bials. At the cost of over a billion dol­lars a new drug (reg­u­la­tory) and the high risk of with­drawal of the drug within 5 years (2 out of 3), as well as the near cer­tainty of pun­ish­ing liti­ga­tion for ad­verse effects, an­tibiotics are not merely un­eco­nom­i­cal to de­velop, they are fis­cal suicide. Only drugs that will be chron­i­cally used by very large num­bers of pa­tients are now worth de­vel­op­ing.

(This agrees with my own gen­eral im­pres­sions, which I didn’t feel com­pe­tent to baldly state.)

1.1.4 Im­munol­ogy and cancer

…Mon­o­clonal and syn­thetic an­ti­bod­ies car­ry­ing tox­ins or reg­u­la­tory molecules will be used to turn off or de­stroy the frac­tion of im­mune cells which ini­tially re­spond and pro­lifer­ate when a trans­plant is car­ried out. More wide­spread trans­plan­ta­tion of tis­sues will be un­der­taken, in­clud­ing trans­plan­ta­tion of limbs and scalp. Xenografts will be used in­creas­ingly in the mid to late 1990’s and it will not be un­com­mon for peo­ple to have pan­cre­atic tis­sue from bov­ine or porcine sources and per­haps hearts, lungs, and livers from other an­i­mals. Ex­pect the first work­able trans­plants to be from great apes (chimps, go­rillas, orangutans), with porcine and bov­ine grafts com­ing later.

Im­munol­ogy and im­munother­apy will also be rev­olu­tionized by a far more com­plete un­der­stand­ing of the im­mune sys­tem re­sult­ing from the AIDS epi­demic and ba­sic re­search in the im­munol­ogy of dis­eases such as mul­ti­ple scle­ro­sis and ag­ing. The abil­ity to rapidly and cheaply syn­the­size bioreg­u­la­tory molecules will open up a wide ar­ray of ther­a­peu­tic pos­si­bil­ities. Ex­pect effec­tive treat­ments for most au­toim­mune dis­eases (lu­pus, mul­ti­ple scle­ro­sis, myas­the­nia gravis, and so on) by the mid to late 1990’s. The mid to late 1990’s should also see the wider ap­pli­ca­tion of im­munorestora­tives for use with the aged and ill. Cancer ther­apy will im­prove con­sid­er­ably as a re­sult of these ad­vances as well as a re­sult of se­lec­tive tar­get­ing tech­niques. By the early to mid–1990s the first gen­er­a­tions of mon­o­clonal an­ti­bod­ies linked to chemother­a­peu­tic agents or pow­er­ful nat­u­ral tox­ins will be used against a few can­cers.

1.1.5 Atherosclerosis

Atheroscle­ro­sis will un­dergo a very marked but nev­er­the­less grad­ual re­duc­tion in fre­quency and sever­ity of oc­cur­rence as physi­ci­ans slowly be­come ed­u­cated about what is already known and be­gin to use ex­ist­ing ther­a­peu­tic modal­ities more ag­gres­sively. By the mid to late 1990’s it will be more widely un­der­stood that atheroscle­ro­sis can be re­versed, and there will be wider use of drugs such as lo­vas­tatin to re­duce serum choles­terol, cou­pled with sound dietary ad­vice. How­ever, even well into the late 1990’s and per­haps be­yond, atheroscle­rotic dis­ease (heart at­tack, stroke, is­chemic limb dis­ease, and so on) will con­tinue to be a se­ri­ous source of mor­bidity and mor­tal­ity. By the late 1990’s, 2nd and 3rd gen­er­a­tion ther­a­pies will be com­ing on-line which will be able to re­verse atheroscle­rotic dis­ease and more di­rectly in­hibit it

1.2 Part 2

1.2.1 Anesthesia

Ex­pect “mod­u­lar” anes­the­sia by the 1990’s to the early 2000’s. The de­vel­op­ment of po­tent anx­ie­olyt­ics (anx­iety re­movers) which do not de­press con­scious­ness and the de­vel­op­ment of to­tal pain in­hibitors will al­low for com­pli­cated sur­gi­cal pro­ce­dures on con­scious pa­tients. Ex­pect to see ma­jor tho­racic and limb surgery on high risk pa­tients (i.e., pa­tients un­able to tol­er­ate anes­the­sia) us­ing such agents.Ma­jor ab­dom­i­nal surgery re­quiring deep mus­cle re­lax­ation will con­tinue to re­quire skele­tal mus­cle paral­y­sis and gen­eral anes­the­sia. How­ever, ex­pect new drugs in the mar­ket place in the late 1990’s which in­duce un­con­scious­ness with­out res­pi­ra­tory or car­diac de­pres­sion.

Sur­gi­cal and post sur­gi­cal mor­tal­ity will de­crease sharply due to such anes­thet­ics and the use of real-time phys­iolog­i­cal and bio­chem­i­cal mon­i­tor­ing dur­ing and af­ter surgery us­ing biosen­sors.

1.2.2 Surgery

…Ca­theters, la­paras­copes, and tho­ras­copes with sen­sors, op­er­at­ing tools, and an im­pres­sive ar­ray of ca­pa­bil­ities will be in­creas­ingly used. Ab­dom­i­nal surgery will shift more and more to­wards the use of the fiberop­tic la­paras­cope, en­do­scope, and laser as mi­ni­a­tur­iza­tion of tools oc­curs and dis­ease is di­ag­nosed ear­lier. Early di­ag­no­sis will cre­ate the need for less dras­tic pro­ce­dures.

Fine-tuned re­pair of heart valves and blood ves­sels, and ex­am­i­na­tion and biopsy of sus­pected ab­dom­i­nal and retroper­i­toneal le­sions will be early can­di­dates for ap­pli­ca­tion of this tech­nol­ogy.

…In con­trast to ther­a­peu­tic surgery, the fre­quency of cos­metic surgery will prob­a­bly in­crease dra­mat­i­cally as tech­niques are re­fined and pros­thet­ics im­prove in qual­ity and drop in cost. As peo­ple live longer, and stay pro­duc­tive longer as well, they will in­creas­ingly turn to medicine to main­tain not only their health but their ap­pear­ance. Cos­metic surgery will ex­pe­rience a boom un­til such time as the fun­da­men­tal mechanisms un­der­ly­ing the ag­ing pro­cess can be brought un­der con­trol.

1.2.3 Geriatrics

Ad­vances will be slow here, but sig­nifi­cant. Ex­pect in­creas­ing un­der­stand­ing and ap­pli­ca­tion of trophic fac­tors and bioreg­u­la­tory com­pounds. Early can­di­dates for re­ju­ve­na­tion will be the im­mune sys­tem and other stem cell sys­tems or sys­tems with higher cell turnover. By the early decades of 2000, sig­nifi­cant re­ju­ve­na­tion and gero­pro­phy­laxis of skin, bone, im­mune, and other “high turn- over” tis­sues will be pos­si­ble as the nat­u­ral reg­u­la­tory molecules which con­trol these sys­tems are un­der­stood and ap­plied.

…By the early years of the 21st cen­tury the first gen­er­a­tion of com­pounds effec­tive at “re­ju­ve­nat­ing” (i.e., restor­ing some de­gree of nor­mal main­te­nance and re­pair to ex­ist­ing brain cells) the cen­tral ner­vous sys­tem will be available. Th­ese drugs will work by turn­ing on pro­tein syn­the­sis and stim­u­lat­ing nat­u­ral re­pair mechanisms.

How­ever, patholo­gies of the brain and other non-di­vid­ing tis­sues (re­nal, car­diac, and mus­cu­loskele­tal sys­tem) will con­tinue to be ma­jor sources of mor­bidity and mor­tal­ity over the next two decades. As atheroscle­ro­sis and im­mune-re­lated di­s­or­ders are dealt with more effec­tively, ex­pect an in­creas­ing shift of mor­bidity and mor­tal­ity to cen­tral ner­vous sys­tem-re­lated causes. Beyond 2000 this may be treated to a limited ex­tent with fe­tal transplant

We all know how well this has worked out. More trou­bling is that in some re­spects, we ap­pear fur­ther from any solu­tions or treat­ments than be­fore; while resver­a­trol did well in a re­cent hu­man trial, the sir­tuin re­search that seemed so promis­ing has been bat­tered by null re­sults and failures to repli­cate. And anti-ag­ing drugs have their own method­olog­i­cal difficul­ties; from the fol­lowup email:

An­ti­ag­ing drugs are un­likely to be free of ad­verse effects. In fact, it seems very likely that they will be bur­dened with many ad­verse effects and that they will even kill a minor­ity of peo­ple who use them. The com­mon per­cep­tion is that an­ti­ag­ing drugs will make peo­ple su­per fit, healthier and more re­sis­tant to dis­ease. And yet, in calorie re­stric­tion and effec­tive an­ti­ag­ing drug stud­ies there is emerg­ing ev­i­dence that slow­ing ag­ing comes at the cost of in­terfer­ing with fun­da­men­tal pro­cesses that make or­ganisms fit­ter for both re­pro­duc­tion and for sur­viv­ing in a hos­tile en­vi­ron­ment.

Con­sider the pu­ta­tive an­tag­ing drug ra­pamycin. It seems likely that ra­pamycin in­terferes with senes­ence by af­fect­ing the PI3-ki­nase and TOR: PIKTORing cell growth path­ways. This al­most cer­tainly means that in some in­di­vi­d­u­als there will se­ri­ous and even lethal side effects—can­cer be­ing one of them. [Per­sons with a his­tory of promis­cu­ity, and thus a heavy bur­den of chronic viral in­fec­tion, and those with cer­tain “un­fa­vor­able” geno­types will likely be at very high risk.] But, be­yond can­cer, in­terfer­ing with these fun­da­men­tal and deeply evolu­tion­ar­ily con­served path­ways is likely to cause a range of ad­verse effects that nega­tively (and pos­si­bly ir­re­versibly) im­pact nor­mal body func­tions, such as en­ergy level, cog­ni­tion, sex­ual perfor­mance, and so on.. While some peo­ple are now us­ing ra­pamycin as an an­ti­ag­ing is vir­tu­ally in­con­ceiv­able that any ma­jor phar­ma­ceu­ti­cal com­pany any­where in the world would (or will) mar­ket such a drug for “nor­mal” ag­ing. This is im­por­tant to un­der­stand be­cause it gives us ba­sic in­sight into what will al­most cer­tainly be a ma­jor bar­rier to the de­vel­op­ment and mar­ket­ing of an­ti­ag­ing drugs: they will nec­es­sar­ily be used by large num­bers of peo­ple over the course of many decades (and thus mil­lions of drug/​per­son years) and they are in­cred­ibly un­likely to be free of ad­verse, and some­times even lethal side effects.

1.2.4 Psy­chi­a­try & Behavior

Di­ag­no­sis by brain scan­ning (metabolic MRI) and chem­i­cal anal­y­sis of cere­brospinal fluids will be com­mon­place in 20 years. As neu­roreg­u­la­tory com­pounds are bet­ter un­der­stood and as the bio­chem­istry un­der­ly­ing men­tal di­s­or­ders is elu­ci­dated there will be more effec­tive treat­ments. Ex­pect 2nd and 3rd gen­er­a­tion drugs and com­bi­na­tions thereof for treat­ment of de­pres­sion and psy­chosis by the late 1990’s. There will prob­a­bly be sev­eral very effec­tive ther­a­peu­tic agents for com­pul­sive di­s­or­ders in the mar­ket­place by the early to mid 1990’s.

From the pre­vi­ously quoted fol­lowup email:

Similarly, psy­chi­a­tric drugs (which are typ­i­cally chron­i­cally used) are no longer eco­nom­i­cal to de­velop and mar­ket be­cause of the liti­ga­tion costs as­so­ci­ated with them. Wide­spread chronic use of any drug means that the like­li­hood of ad­verse con­di­tions that were im­pos­si­ble to de­tect in the test­ing phase of the drug de­vel­op­ment pro­cess are al­most cer­tain to emerge. Statis­tics rule in drug de­vel­op­ment, and a Phase III study that lasts a year and en­rolls 5,000 pa­tients is sim­ply not ad­e­quately pow­ered to pre­dict what will hap­pen when 5 mil­lion pa­tients take a drug for 20 years! The only way to get that data is to do that study. And therein lies a pow­er­ful cau­tion about an­ti­ag­ing drugs. Th­ese drugs will likely need to be taken start­ing in young adult­hood, or in mid­dle age, at lat­est, and they will need to be taken for a life­time. In­deed, if they are effec­tive, for a longer life­time than any but a few su­per-cen­te­nar­i­ans has pre­vi­ously lived.

1.2.5 Im­plants & Prosthetics

Early spec­tac­u­lar ap­pli­ca­tions will be small ves­sel pros­the­ses (wide use by the early to mid 1990’s) for use in trau­ma­tized and atheroscle­rotic limbs and or­gans and ve­nous pros­the­ses (mid to late 1990’s) for use in treat­ing trau­matic in­juries and deep vein in­com­pe­tence (which re­sults in vari­cosi­ties, chronic pain, and edema-re­lated skin changes in the leg, of­ten lead­ing to non-heal­ing ul­cers or limb loss). Another ap­pli­ca­tion of non-throm­bo­genic sur­faces will be a prac­ti­cal ar­tifi­cial heart and more wide­spread use of ex­tra­cor­po­real sup­port for in­fants, trauma and car­diac ar­rest vic­tims, and oth­ers where an­ti­co­ag­u­la­tion pro­vides a ma­jor bar­rier to the use of ar­tifi­cial cir­cu­la­tion.

…Good syn­thetic bone and skin should be available by the late 1990’s to early 2000’s. Good red cell and plasma sub­sti­tutes (syn­thetic blood) should be seen in­creas­ing in clini­cal use through­out the early 1990’s and in fre­quent use by the late 1990’s to early 2000’s.

There will be steady im­prove­ment in other syn­thetic ma­te­ri­als such as hip, knee, and other joints, as well as in other less dra­matic ma­te­ri­als such as con­nec­tive tis­sue re­place­ments. Ex­pect a slow re­place­ment of pros­thetic ap­proaches to ther­apy as nat­u­ral re­pair and re­gen­er­a­tion pro­cesses are bet­ter un­der­stood and uti­lized. Ex­pect to see syn­thetic con­nec­tive tis­sue prod­ucts for ten­don re­pair which con­tain bioreg­u­la­tory molecules (BRMs) that stim­u­late ten­don re­gen­er­a­tion. Ar­tifi­cial ten­dons made of both syn­thetic and/​or nat­u­ral ma­te­ri­als will come into use in the late 1980’s to early 1990’s. In short, ex­pect stun­ning ad­vances in tis­sue re­place­ment tech­nol­ogy for all tis­sues that have pri­mar­ily struc­tural func­tion and which are not com­pli­cated chem­i­cal pro­cess­ing plants, such as the liver or kid­neys, or me­chan­i­cally ac­tive such as the heart. In ad­di­tion to con­nec­tive tis­sue and bone, a can­di­date for early (late 1980’s to early 1990’s) re­place­ment is the cornea. Ex­pect evolu­tion in bio­com­pat­i­ble ma­te­ri­als to al­low for re­place­ment of the cornea with an ap­pro­pri­ate plas­tic, much like the lens of the eye is already re­placed with polymer in­serts.

1.2.6 Hemodialysis

Ad­vances in hemodial­y­sis will also be very in­cre­men­tal. There may be a grad­ual shift to per­i­toneal dial­y­sis (PD) if good drugs to block glu­co­sy­la­tion of pro­teins and in­hibit choles­terol de­po­si­tion are available. The ma­jor prob­lem with PD to­day is that it raises blood sug­ars to as­tro­nom­i­cal lev­els, caus­ing di­a­betic-like side effects. In­hi­bi­tion of these side effects may lead to re­newed ap­pli­ca­tion of this modal­ity.

Direct changes in dial­y­sis are likely to be along the lines of bet­ter mem­brane ma­te­ri­als which al­low for trans­port of wastes not cur­rently re­mov­able by con­ven­tional dial­y­sis and non­throm­bo­genic sur­faces which will re­duce the need for an­ti­co­ag­u­la­tion. The use of BRMs such as ery­thro­po­etin to treat ane­mia and bone growth fac­tors to treat dial­y­sis bone dis­ease will help to im­prove the qual­ity and quan­tity of pa­tient’s lives on dial­y­sis.

Per­haps the biggest ad­vance in this area will be ad­vances in im­munol­ogy and in­fec­tious dis­ease treat­ment. The abil­ity to ad­minister BRMs to stim­u­late im­mune func­tion and im­prove gen­eral health should act to ex­tend dial­y­sis pa­tients’ lives con­sid­er­ably.

…Of course, the biggest im­prove­ment in the life ex­pec­tancy and health of dial­y­sis pa­tients will prob­a­bly come in the form of the in­creas­ing use of trans­plan­ta­tion and its ap­pli­ca­tion to a wider age range of pa­tients with bet­ter long term re­sults.

The most strik­ing rev­olu­tion in pros­thet­ics will prob­a­bly oc­cur in den­tistry. Ex­pect a whole fam­ily of new ma­te­ri­als to en­ter the den­tal op­er­a­tory. A work­able vac­cine against strep­to­coc­cus mu­tans should be available by the mid to late 1990’s, greatly re­duc­ing the in­ci­dence of tooth de­cay by elimi­nat­ing the ma­jor class of mouth or­ganisms that cause it. Similar ad­vances in pre­ven­tion and in treat­ment of gum dis­ease can be ex­pected as well, al­though prob­a­bly not as soon. Re­pairing den­tal defects will also be rev­olu­tionized by the in­tro­duc­tion of good, tough, and re­li­able polymers which will re­place metal­lic amalgams. By the late 1990’s to early 2000’s bio­com­pat­i­ble ce­ram­ics and coated polymers will be available that will al­low for work­able sin­gle tooth and mul­ti­tooth gum-im­planted pros­the­ses.

1.2.7 Or­gan Preservation

Ever since the work of peo­ple like Mazur, Fahy, and Pegg was pub­lished, it has be­come pretty clear what the con­straints are on long term vi­able cry­op­reser­va­tion of or­gans: don’t form any sig­nifi­cant amount of ice; it in­jures me­chan­i­cally and it in­jures chem­i­cally. The prob­lem is that wa­ter loves to turn into ice when it’s cooled be­low 0øC. To cir­cum­vent this, a lot of very dras­tic changes have to be made in the sys­tem. When­ever you at­tempt to make a dras­tic change in a com­pli­cated, in­ter­de­pen­dent liv­ing sys­tem — like re­plac­ing half the wa­ter in it with in­dus­trial chem­i­cals — you are in for trou­ble. The trou­ble will come in the form of a very tight or nar­row win­dow for suc­cess: ev­ery­thing will have to be “just right.”

This is where cur­rent vit­rifi­ca­tion tech­nol­ogy is now. The ex­is­tence of such a tight win­dow means that vit­rifi­ca­tion of large masses will be a tech­nolog­i­cal tour-de-force re­quiring very so­phis­ti­cated com­puter con­trol­led per­fu­sion equip­ment and ex­otic and very costly high pres­sure cham­bers. Qual­ity con­trol and re­li­able stor­age and re­warm­ing of or­gans will be very costly and difficult.

The fu­ture holds the pos­si­bil­ity of de­vel­op­ing bet­ter solute sys­tems which vit­rify more eas­ily and which are less toxic (have a wider win­dow for suc­cess). It is difficult to pre­dict the pace of ad­vance in this area since it will be ar­rived at by a mix­ture of em­piri­cal meth­ods and the­o­ret­i­cal in­sights. A big de­ter­min­ing fac­tor will be luck. Will the NIH and the Red Cross con­tinue to fund such efforts? And, more to the point, will tech­nolog­i­cal ad­vances in other ar­eas of or­gan preser­va­tion ob­vi­ate the need for them? If we were bet­ting men, we’d put our dol­lars on the lat­ter rather than on the former. Ma­jor ad­vances in or­gan preser­va­tion (as op­posed to cell and tis­sue preser­va­tion) over the next decade will prob­a­bly be in three ar­eas: 1) Ex­tended hy­pother­mic stor­age of or­gans in the 2 to 3 weeks range; 2) Ex­tended nor­moth­er­mic or room tem­per­a­ture stor­age of or­gans in the weeks to months range and; 3) mix­tures of the above two modal­ities which yield similar available time courses of stor­age.

…The next 5 to 10 years should also see ma­jor ad­vances in our un­der­stand­ing of the effects of deep hy­pother­mia on the tis­sues and or­gans of non-hi­ber­nat­ing mam­mals. Th­ese ad­vances should be read­ily trans­lat­able into bet­ter flush and per­fu­sion stor­age tech­niques for or­gans. A good un­der­stand­ing of lipid metabolism and mechanisms of cell swelling in deep hy­pother­mia may al­low for preser­va­tion of or­gans in the 2øC to 10øC tem­per­a­ture range for pe­ri­ods of sev­eral months — thus defini­tively end­ing the need for long term solid state preser­va­tion of trans­plantable or­gans.

1.2.8 Other Ap­proaches to Or­gan Preservation

One pos­si­bil­ity for a ma­jor ad­vance over the next two decades is room tem­per­a­ture or hy­pother­mic preser­va­tion of or­gans or or­ganisms us­ing metabolic in­hibitors. There have been tan­ta­l­iz­ing clues in the ex­am­i­na­tion of a wide va­ri­ety of es­ti­va­tors (an­i­mals which go into states of profoundly re­duced metabolism at nor­mal tem­per­a­tures, such as the Afri­can lungfish, which can shut off metabolism at tem­per­a­tures in the range of 30øC to 40øC) that anti-metabo­lite com­pounds ex­ist which may be able to in­duce states of profoundly re­duced metabolism at am­bi­ent (i.e., 70øF) tem­per­a­tures.

1.2.9 Ge­netic therapy

Ex­pect very grad­ual ap­pli­ca­tion of this tech­nol­ogy. Early can­di­dates for gene re­place­ment will be in stor­age dis­eases such as Lesch-Ny­han, Tay-Sachs, and other “sin­gle en­zyme miss­ing” di­s­or­ders. Later ap­pli­ca­tions will in­clude treat­ments for hy­per­c­holes­terolemia, some forms of hy­per­ten­sion, and other con­gen­i­tal miss­ing en­zyme syn­dromes. Very late ap­pli­ca­tions (2000 or later) may be in the treat­ment of a wide range of men­tal ill­nesses and can­cers.

1.2.10 Prevention

The prin­ci­pal les­son is the les­son of the im­pact of calorie re­stric­tion on over­all health, well-be­ing, and lifes­pan. The ba­sic mes­sage here is “you are what you eat.” In terms of treat­ing atheroscle­rotic dis­ease, the role of pre­ven­tion is already clear. By re­duc­ing fat in­take and de­creas­ing serum choles­terol to be­low 150 mg/​dl, most atheroscle­rotic dis­ease can be avoided. Similarly, ba­sic changes in nu­tri­tion such as trace el­e­ment and vi­tamin sup­ple­men­ta­tion can greatly re­duce the num­ber of late on­set ma­lig­nan­cies. Elimi­nat­ing smok­ing will also be a ma­jor fac­tor in achiev­ing this end….Calorie re­stric­tion achieved by means of ed­u­ca­tion and ther­a­peu­tic agents seems the next big area of pre­ven­tics to be ex­plored by medicine. Ex­pect the de­vel­op­ment of truly effec­tive anorec­tics for treat­ment of gross obe­sity and eat­ing di­s­or­ders by the late 1980’s and then sec­ondary use of these for treat­ment of mild obe­sity and weight con­trol in the nor­mal mid­dle aged. Prod­ucts with re­duced calories em­ploy­ing fat sub­sti­tutes such as su­crose polyester should also be en­ter­ing the mar­ket­place in the early 1990’s and these will help to re­duce the calorie load fur­ther.

1.2.11 The Downside

A lit­tle in­for­ma­tion is a dan­ger­ous thing, and some­times a lot of in­for­ma­tion can be an even more dan­ger­ous thing. The rea­son is that progress in ther­a­peu­tics, which is rel­a­tively difficult, always lags far be­hind progress in di­ag­no­sis, which is rel­a­tively easy. This im­bal­ance re­sults in a ten­sion which forces pre­ma­ture treat­ment which of­ten does more harm than good. It is well to note that each new di­ag­nos­tic modal­ity brings with it a flood of new in­for­ma­tion which will at first be grossly mi­sused be­fore any­one un­der­stands what it means (Har­ris’s Law of Di­ag­nos­tics Ad­vance).

A re­cent ex­am­ple of this sort of thing is the EKG ma­chine, which for the first time showed that many seem­ingly nor­mal peo­ple had strange car­diac rhythms, some of which were seen also around the time peo­ple died sud­denly of heart prob­lems. Be­cause of this as­so­ci­a­tion, for the last 15 years, a num­ber of very pow­er­ful drugs have been used to treat peo­ple with such rhythms. Many drug-in­duced fatal­ities re­sulted. Un­for­tu­nately, only now is it be­gin­ning to be un­der­stood that most peo­ple with good heart func­tion are less in dan­ger from such rhythms than they are from the drugs used to treat them — a find­ing of lit­tle con­so­la­tion to the peo­ple already kil­led by the drugs.

And on to the eco­nomics:

There is a sec­ond down­side to ad­vanced medicine, of course, be­sides the dan­ger, that is the cost of “mid­dlingly ad­vanced tech­nol­ogy” (such as what we’ll see in the next fifty years) in a so­ciety takes a so­cial­is­tic view of health care. Such as ours.

Non-molec­u­lar tech­nol­ogy is ex­pen­sive. It should be ob­vi­ous to the reader, with a bit of thought that in a world of non-molec­u­lar tech­nol­ogy, the po­ten­tial de­mand for med­i­cal care as tech­nol­ogy ad­vances, is (for all in­tents and pur­poses) Iin­finite. In Amer­ica, we have adopted the un­for­tu­nate policy of let­ting ev­ery­one pay for ev­ery­one else’s med­i­cal care, which has had ex­actly the same re­sult as if we had let ev­ery­one pool their money and pay for each other’s lunch: ev­ery­one or­ders lob­ster. We have paid for the lob­ster only by spread­ing the costs around to places where they are not ob­vi­ous. For in­stance, when you buy an Amer­i­can car, you pay more money for the health care costs of the peo­ple who built it than you do the steel that goes into it. This kind of thing can con­tinue very sub­tly and very in­sidiously un­til a very large frac­tion of the gross na­tional product is eaten up by health care costs. (In our coun­try, it is already 11% and ris­ing).

One day, you may find that you have had to forego your fam­ily va­ca­tion in or­der to buy Granny that new AUTODOC which mea­sures 245 differ­ent chem­i­cals in her blood ev­ery minute and trans­mits all of the re­sults to Med­i­cal Mul­ti­vac in Bethesda. Of course you may not re­al­ize this: all you will know is that the va­ca­tion went be­cause money is so tight, taxes are so high, and in­fla­tion is so bad. But your money went to Granny nev­er­the­less. The only an­swer to this prob­lem, short of nan­otech­nol­ogy, is ra­tioning.

But ra­tioning it­self be­comes the last great so­cial cost of ad­vanced med­i­cal tech­nol­ogy un­der so­cial­ism, be­cause his­tory shows that it is never done on an in­di­vi­d­ual (per­son by per­son) ba­sis. When peo­ple do not pay for their own med­i­cal care, no one (not doc­tors, fam­i­lies, or the gov­ern­ment) has ever been will­ing to make the de­ci­sion of who should benefit from a given tech­nol­ogy, and who should not. There­fore, all sys­tems of ra­tioning to con­trol med­i­cal costs ul­ti­mately have come down in the past to ra­tioning tech­nol­ogy across the board…So all of the rosy pre­dic­tions made in this ar­ti­cle must be tem­pered with the “so­cial” re­al­ities that medicine will have to deal with in the next 20 years. Many of the ad­vances we have dis­cussed may sim­ply not ma­te­ri­al­ize be­cause we are not wealthy enough to af­ford them col­lec­tively. That will be a great tragedy.

2 Reactions

On read­ing all the fore­go­ing, I com­mented: that was a de­press­ing read. As far as I can tell, they were dead on about the dis­mal eco­nomics, some­what right about the di­ag­nos­tics, and fairly wrong about ev­ery­thing else. Which is bet­ter than the old pre­dic­tions listed, only one of which struck me as ob­vi­ously right (but in a use­less way, who ac­tu­ally uses perfluoro­car­bons for liquid breath­ing?).

To which Dar­win said:

At the time I wrote it I kept say­ing to my­self, al­most none of this stuff is go­ing to hap­pen in 20 years—not here any­way. How­ever, I have to come up with some­thing.

Iron­i­cally, in the area of cere­bral re­sus­ci­ta­tion, where I am a sup­posed “ex­pert,” I tried very hard to be re­al­is­tic and to be both ac­cu­rate and pre­cise. That was ar­guably the area where I did the worst—ex­actly the way other ex­perts fare when they try to pre­dict the fu­ture of their fields…So, here I am, 24 years out from mak­ing those pre­dic­tions and I read the crap posted on Less Wrong and on Cry­o­net and I don’t whether to scream in rage and anger, or weep. How is pos­si­ble to reach and con­vince this new gen­er­a­tion of cry­on­ics “pas­sivists” that Yud­kowsky and Al­cor are breed­ing and make them un­der­stand that progress will con­tinue to be un­ac­cept­ably slow un­less the sys­tem it­self is changed?

See also Fight Aging!’s post, “Over­es­ti­mat­ing the Near Fu­ture”:

…Many of the spe­cific pre­dic­tions in the ar­ti­cle were in fact demon­strated in the lab­o­ra­tory to some de­gree, and were tech­ni­cally fea­si­ble to de­velop as com­mer­cial prod­ucts by the year 2000, and in some cases ear­lier but at much greater ex­pense. Cer­tainly there are par­tial hits for many of the pre­dic­tions by 2010, in the sense of it be­ing pos­si­ble, some­what demon­strated, or in the early stages of be­ing shown to be a prac­ti­cal goal. Yet the reg­u­la­tory en­vi­ron­ment in much of the de­vel­oped world es­sen­tially rules out any form of ad­ven­tur­ous, rapid, highly com­pet­i­tive de­vel­op­ment in clini­cal medicine—such as ex­ists in the elec­tri­cal en­g­ineer­ing, com­put­ing, and other wor­lds. We are cursed there­fore with the pas­sage of many years be­tween a new med­i­cal tech­nol­ogy be­ing demon­strated pos­si­ble and then at­tempted in the mar­ket­place … if it ever makes it to the mar­ket­place at all. This must change if we are to see sig­nifi­cant progress.

Dar­win com­ments there:

I’ve been go­ing over my origi­nal manuscript and sur­fing the web for spe­cific ap­pli­ca­tions (ap­proved or in pro­cess) which meet the crite­ria of my pre­dic­tions of 24 years ago. While many of my “lesser” pre­dic­tions are in fact be­ing re­al­ized (of­ten in ways to­tally un­fore­seen by us when we wrote the ar­ti­cle) over­all it is a profoundly de­press­ing ex­pe­rience.

Per­haps nowhere has that been more true than in the ar­eas of ag­ing and cere­bral re­sus­ci­ta­tion—two fields of en­deavor I’ve spent a life­time work­ing on, or in­ti­mately in­volved with those who are. In 1999, we an­nounced that we had achieved re­peat­able re­cov­ery of dogs fol­low­ing 16+ min­utes of whole body noro­moth­er­mic car­diac ar­rest with no neu­rolog­i­cal deficit. The en­abling molecules and tech­niques (prin­ci­pally a com­bi­na­tion of mela­tonin, alpha-phenyl-n-tert-butyl-ni­trone (PBN), and mild post-car­diac ar­rest ther­a­peu­tic hy­pother­mia) all seemed em­i­nently ap­pli­ca­ble in the (then) im­me­di­ate fu­ture. In­deed, an ana­log of PBN, 2,3-dihy­droxy–6-ni­tro–7-sul­famoyl-benzo(F)quinox­al­ine (NBQX) had passed Phase I and II clini­cal tri­als for the treat­ment of stroke with fly­ing col­ors, and seemed des­tined for ap­proval.

That was 13 years, ago, and there is still not a sin­gle drug available (ap­proved or oth­er­wise) any­where in the world to treat cere­bral is­chemia-reper­fu­sion in­jury—the real kil­ler in car­diac ar­rest and stroke! Do a liter­a­ture search on Pubmed for mela­tonin + cere­bral is­chemia and you will get ~130 hits—al­most all of them dra­mat­i­cally pos­i­tive. Me­la­tonin is a nat­u­rally oc­cur­ring bioreg­u­la­tory molecule which is in­ex­pen­sive and freely available as an over the counter “nu­tri­ent.” Even as a stand alone molecule, mela­tonin is pow­er­fully pro­tec­tive in both global and re­gional cere­bral is­chemia, and yet no hu­man ap­pli­ca­tion has been forth­com­ing. It’s been 15 years since our patent on mela­tonin and other cere­bro­pro­tec­tive molecules was is­sued, 17 years since the patent was ap­plied for, and over 20 years since I made the dis­cov­ery! In­deed, mild ther­a­peu­tic hy­pother­mia, made the sup­posed stan­dard of care for post car­diac ar­rest neu­roin­jury nearly a decade ago, is still largely ig­nored and is used well in only a hand­ful of hos­pi­tals wor­ld­wide.

What kind of black irony is it that I live in ter­ror of stroke and car­diac ar­rest (for both my­self and my loved ones) and yet the very molecules I dis­cov­ered to com­bat them are as un­available as if they had never been found? Change? Yes, change is cer­tainly needed, and soon.

3 Fur­ther reading

Pre­vi­ous Dar­win-re­lated posts:

See also Tyler Cowen’s The Great Stag­na­tion and “Peter Thiel warns of up­com­ing (and cur­rent) stag­na­tion”.