i do not think there will be something called ' sepsis ' in 2051 because we will know much more about this entity than we do at present .
patients will still present in the same way ( clinical evidence of infection with or without organ failure ) but we will be able to determine very quickly ( using polymerase chain reaction or other techniques ) which organism the patient has been infected with , and hence the antimicrobials to use .
therefore , instead of discussing a syndrome ( which is the problem with sepsis at the present time ) , we will be able to state which organism the patient is infected with and we will know why they have ( or why they are likely to have ) organ failure .
in 2051 we will not be talking about syndromes but rather about molecular definitions of and genetic predisposition to disease , as well as about activation of specific pathways that lead to organ dysfunction . therefore , although two patients lying in beds next to each other may look alike , in fact completely different pathways may be activated in them , and we will be able to recognise this .
we will therefore move from vague diagnoses to specific descriptions of the patient 's condition .
for example , the oncologist may say that ' the patient has a b - cell lymphoma with a transposition of a certain chromosome ' , rather than simply stating that a patient has cancer ; in 2051 we will be able to make an equally specific statement , enabling us to provide specifically targeted therapy .
one of the great advances over the past few years has been to elucidate the pathway that leads from toll - like receptors to the acute inflammatory response by activating certain genes .
this , of course , eventually leads to organ system dysfunction , and the prime candidates for activating these genes are transcription factors .
one that is known to activate multiple proinflammatory genes is nuclear factor-b ; we know that patients who have greater activation of nf-b tend not to survive .
unfortunately , in 2051 we will still have to deal with endotoxin being released by escherichia coli , but by then we will be able to determine who will do poorly and who will do well . by appreciating the patient 's gene polymorphisms , including single nucleotide polymorphisms , we will know how they will react to endotoxin , because we will have deduced which of those polymorphisms leads to higher or lower expression of the molecules associated with organ dysfunction .
therefore , we will be able to identify at - risk patients early and treat them accordingly .
remember , however , that it is not enough just to turn on genes ; they must also be translated into proteins . by 2051
we will have developed techniques that will tell us within several hours , or even minutes , what pattern of proteins a patient has .
some recent data from my laboratory illustrate what happens when neutrophils are stimulated from a group of volunteers with lipopolysaccharide .
we found that there are both high and low responders , with high responders being those who consistently produced more nf-b and the low responders being those who barely reacted to the endotoxin .
therefore , the central dogma of this new field will probably be to gain an understanding of how proteins are expressed , because these are really the motors of cellular function and dysfunction in critically ill patients .
dna reflects our genomic predisposition and there will be changes in rna that we can detect with chips , but what is probably most important is how proteins are expressed .
at present we can describe a patient 's genetic make - up by looking at several thousand cells . however , the number of cells required has been dropping dramatically , and by 2051 we will need fewer than 10 cells ( which could be achieved from a buccal rub ) to determine a patient 's genomic predisposition
. this will tell us which genes are upregulated and which genes are downregulated . currently , such procedures take hours , but without a doubt in the near future , and certainly before 2051 , we will be able to do this in a similar time as routine laboratory tests require .
therefore , when a patient presents in the emergency department , we will be able to tell their genomic profile both quickly and easily .
interesting though that may be , and as i allude to above , the real issue is to be able to assess the patient 's proteomics . by 2051
we will be able to identify which proteins are being expressed , to what levels , how high or how low the protein levels are in various cell types , and how the proteins are modified after translation .
for example , if a patient upregulates the intracellular kinase akt and has increased levels of this kinase , then we will be able to give them an anti - akt therapy and thus improve their outcome .
long before 2051 we will have created a database of proteins by taking them out of the cells , running them in a two - dimensional gel , visualizing the gel using an informatics system , and deducing which spots are upregulated proteins . as and when we find a previously unidentified spot we can sequence it using mass spectroscopy and therefore identify the protein .
all this will be put into a database so that we will know what a pattern of proteins means in terms of disease severity and prognosis .
thus , by 2051 , just as a blood transfusion may be given for a low hematocrit , we will know from the spots on the gel what the patient has in terms of their molecular disease and how to treat them .
even if we do not have ' sepsis ' and even if therapies are based on molecular mechanisms and signaling pathways , there will still be a role for supportive care
. some patients will be noncompliant and will present with relatively advanced disease and organ dysfunction . for these patients
we will have to modulate activated pathophysiologic cascades that contribute to organ system dysfunction and death .
tidal volumes are currently getting smaller and smaller , and by 2051 we will have no tidal volume ventilation ; we are getting close to that now .
we will have noninvasive monitoring of organ and cellular function , and so catheters will no longer be needed .
we will have maintenance of tissue homeostasis through appropriate metabolic , nutritional , and cellular support .
we will also have more accurate outcome prediction , leading to appropriate levels of support . by being able to identify cascades and intercellular mechanisms
, we will also be able to identify those patients in whom it does not make any sense to intervene . through prophylactic care
we will be able to increase how long our patients live , as well as improving their quality of life .
if and when the patient suffers a catastrophic event we will look at the intercellular picture and make one of two choices ; either the patient is amenable to therapy or this is a terminal event . the patient will have lived a long and healthy life because of prophylactic therapies ; they will have received gene therapy , because their genetic polymorphisms will have been identified ; and they will have received appropriate vaccines -at this point there is nothing else that can be done . at this point
we will still need to talk to families  we are still physicians , we are still health care providers , and we will be better able to inform the family about the prognosis and to better tailor and choose therapies at that time .
pst received an honorarium from the international sepsis forum for helping to write this commentary .
i also thank the international sepsis forum ( isf ) for inviting me to participate in this debate during the society of critical care medicine ( sccm ) annual congress in san diego , usa , in january 2002 . for more information about the isf , see .
 great advances have been made in describing the intracellular pathways and genes that are activated by bacterial products . 
 new definitions and therapies for sepsis will be based on such cellular and genetic alterations . in particular , in 2051 sepsis will no longer be defined simply as a clinical constellation of findings , but rather will be divided into different entities dependent on the intracellular cascades or genes activated . 
 similarly , therapies will be specifically directed at such functional genetic or biochemical alterations , thereby permitting more rational therapy of specific cellular abnormalities in infected patients . 
 supportive care will also have advanced by 2051 , allowing for less iatrogenic harm to critically ill septic patients . 
 finally , a better appreciation of the cellular and genetic pathways that are activated in patients will permit an improved understanding of prognosis in critically ill infected patients , allowing more appropriate use of therapies . 
None
Lessons from nuclear factor-B
Detection
Supportive care
Competing interests
Abbreviations
Acknowledgements