Corneal transplants are done by ophthalmologic surgeons and as a general surgeon, I have no exposure to this area. What I do remember from medical school is that the eye is an "immunologically privileged" area of the body and as such may be "immune" from rejection (pun intended). This sticks in my memory as the eye is one of the areas cited as a reservoir for the HIV virus which would help HIV to survive from a lot of "blood purification" techniques that were floated a few years back. The other reason is that the corneal, if I remember correctly, is relatively a-cellular and would not provoke an immunologic response and the few cells it does have do not directly receive blood (would cloud your vision) and are sustained from diffused oxygen and nutrients.

No. Rejection is the appropriate response by the body. With immunsuppresion, we modulate that response.

No, not quite. Their proposal is to stimulate the immune system, but to add this "complex" that says "It's ok...don't attack"

Well, if that were the case, most of the transplant pt's would be dead. Obviously you have taken this a little to far (reduce ad absurdum). First, keep in mind there are two major (humoral aka antibody mediated and c-mediated) and several minor arms to the immunesystem. The humoral system is relative untouched by immunosuppression while the cell-mediated system is what is modulated, but not turned off. And yes there is a risk of infection with immunosuppresion, but not as much as you might expect. The trick to turn off just enough of the immune system to allow the graft to survive, but not enough to endange the patient.

Well there are risks, but quality and quantity of life are better with transplant. Kindey failure itself increases the risk of infection, causes chronic refractory anemia (often requiring frequent transfusions) and increases the risk of heart disease. Hemodialysis (filtering the blood to replace kidney function) requires most people to be hooked to a machine for 3-4 hours three times a week (during business hours!). These patients often undergo numerous surgeries to create or correct the vascular access required to get HD. The HD process itself is very draining.

Liver failure really sucks. You can become encephalopathic (an altered mental state typically confusion and altered sleep cycles), you become coagulopathic (bleed easily), you can develop varices (dilated venin in the esophagus, abdominal wall, rectum, etc) which can bleed and are a bitch to stop when you are coagulopathic. Liver failure is deadly with or without treatment. Kidney failure is also deadly, but with HD you can susrvive.

I agree that stem cells and gene therapy are our ideal goals but with the state of the art being the equivalent of trying to park your car by dropping it into the city at 50,000 ft (15240 m) we still have a long way to go. In the mean time, transplants remain a sound medical treatment

For the majority, you are quite ill-informed. Most patients are quite happy with their transplants and their quality of life improved markedly. Also, kidney transplants that last 5 years are more economical than being on dialysis for that time period. This is why insurance companies actually pay for transplants.

While I am not a transplant surgeon I have worked on a surgical transplant service as part of my training. From my experience that first article has so many flaws in its description that it is not worth reading. I hope it does not reflect the original article.

For starters "killer T-cells" are usually referred to as NK-cells and they are NOT thought to be part of the normal rejection process (they do not require activation and thus would no be stopped by immunosuppresion). There are three types of rejection hyperacute (pre-formed antibodies attack the organ in minutes - the organ literally dies as soon as it is transplanted - this is avoided by the "matching" process), acute (where T-cells [not NK-cells] attack the organ since it is not "self" and therefore "bad" - this is where immunosuppresion helps) and chronic (the body slowly rejects by allowing fibrosis of the vessels leading to the organ).

Actual survival statics for all kidney allografts exceeds 95% today. 80% is quite a drop!

Grafts are not assumed to "take" after 100 days allowing us to stop immunosuppresion! Immunosuppression is currently LIFELONG. There are a few instances where people have tolerated a non-identical twin transplant without medications, but this is _very_ rare. There is active research into finding the key to allow "tolerance" whereby we can drop the medications, but this is still early.

IL-2 suppression is the _mainstay_ of current immunosuppressants both blocking its production via calcineurin ihibitors (cyclosporin and tacrolimus), inhibiting the response (sirolimus/rapamune), or by blocking the receptor with antibodies (basiliximab/daclizumab). (Please understand this is only about half of the therapies that are in use for immunosuppresion, I'm just focusing on the Il-2 aspect).

Just followed the second link and it is _much better_. Still, I strongly disagree with their assertions of 100 days, just doesn't happen in humans. Apparently this study is using IL-2 STIMULATION with a complex that attempts to increase the regulatory T-cells...To me this means that this treatment will not co-exist with the current immunopupression dogma... this means that they will have to have a "complete" replacement for immunosuppresion they won't be able to add this to the current regiment and that means this treatment protocol will be quite sometime in the pipeline. And (fortunately) the authors acknowledge that they are optimistic, but aren't rushing off to collect their Nobel yet:

Already exists. It's used in pediatrics for bradycardia (slow heart rate). http://www.drugs.com/ppa/caffeine.html

I had to.

A hand tremor as a surgeon is _not_ what your patients want to see. As an aside, to break the ice with some patients I do a variation of the Gene Wilder's deputy on "Blazing Saddles"....

Pt: So how steady are your hands?

[I hold up a steady left hand]

Pt: Good, steady as a rock!

[While bringing up a flapping right hand and with a southern draw]

Me: Yeah, but this here is ma' operatin' hand.

Usually get a good chuckle from my patients, but every once in a while I get a wild-eyed-jaw-dropping-looking-for-the-nearest-fire-exit look that totally makes the joke worth it.

Sorry, but I think you missed some of my points. Negative side-effects such as the exposed Fe+2 reducing nictric oxide in a patient are NOT acceptable. We are talking about people who are on the "knifes edge" and the "cure" can't make these people worse!

Also, please read their website. It is NOT artificial blood. It is not recombinant but rather purified bovine hemoglobin.

Directly from their website:

Manufacturing Process
Manufacture of Hemopure and Oxyglobin occurs in four major steps: First, bovine blood is processed to remove plasma and then to remove the hemoglobin protein from red blood cells.

And as such may still carry viral vectors and prions and are potentially susceptable to bacterial contamination.

And before people start knocking the FDA, please be aware that they spare the American public and to a lesser extent the world from over-eager pharaceutal companies.

While this release is a nice breakthrough, there is still *a lot* of work to replace blood. Many substances have been tried to date and they have failed.

First transfusions cause immune reactions [that are technically not rejection] but while these may be major events, they are NOT very frequent. Nurses stop transfusions at the slightest reaction. In the past six years I have seen one transfusion reaction and I work at a major urban trauma center.

Secondly, blood that is transfused is usually near the end of its shelf life and as such you are lucky if 50% of the cells are viable. Within 48 hrs, most (75-80%) of the blood is useless.

Thirdly, blood itself causes immunesuppresion. Couple this with the SIRS/sepsis response in the body and you are going to have a hard time managing this pt in the long term (this is why patients die weeks to months after surviving the initial trauma (tri-modal mortality - on-scene, early in the ED, and late).

Fourth, is the ethical issues - not everyone accepts blood - Jehovah's Witnesses classically. (We also happen to be the city's "bloodless surgery" center - but that's a whole other rant).

The problem with blood replacement is that they also fail in one of these areas. Some substances will cause immune reactions or toxic effects to the body. Hemoglobin and myoglobin (the analogue in the muslces) and their breakdown products are *toxic* to the body...fortunately we have mechanisms to eliminate them safely (most of the time). But what of this protein? Are the breakdown products safe? Does it need to be wrapped in a cell wall to protect the body from it? The article mentions the immune system attacking the molecule, but will the molecule function in physiologic conditions that allow it accept oxygen and release it appropriately? Will it cause other portions of the body to fail? Is the compound stable? How will the body eliminate it?

As for not needing a substance that transports oxygen efficiently, try again. The human body can only tolerate so much volume. If this substance is only 5% as efficient I need 20x the volume. Not very helpful - I'll stick with blood thank you. And, yes you can survive being bled out to 33 to 50% of your blood volume if you are healthy....but if you are also a trauma patient with injuries, you can tolerate much less blood loss - see above for late trauma mortality. As for the soldiers bleeding out pink koolaid...your medics need to be retrained. The current accepted protocols are not to "flood" the traumas with non-oxygen carrying fluids (crystalloids) but to try to maintain perfusion until surgical control of bleeding can be established.

And finally, one of the largest hurdles to artificial blood is the ethical concerns. Healthy volunteers may tolerate the substance, but actual "sick" people may not....In 1999 UPenn killed a young relatively healthy volunteer Jesse Gelsinger with their attempt at correcting his ornithine carbamoyltransferase deficiency with their "gene therapy". It wasn't necessarily that the treatment was bad, but due to his illness, he reacted badly to the adenovirus used as a vector. And in the early 1990's Shock Trauma in Baltimore took a huge publicity hit for proposing to use blood substitutes in acutal trauma patients...the problem was that in a trauma patient you cant' get accurate informed consent to an experimental treatment. This ended up becoming a racial issue as the young male African-American population was the largest demographic group "visiting" their facility. Major uproar.

Now, I for one would love to see a stable, safe, useful blood substitue, they are still a long way off from offering a product I can use on my patients.

What do you _want_to_do_? Do you want to work as a programmer? I'd say stay away from a PhD. Do you want to do research? Then is it theoretic (language constructs...) or practical (AI, computer vision...)? If so a strict PhD in CS is probably better. Do you want to work in management? Then experience (ok, questionable here) and an MBA are probably the way to go. Do you want to create a startup? Quit now and move back in with your parents until you create the next Facebook or Google. Think you get the drift here...you have not rigorously defined your objective.

Sounds a lot like preparing soldiers for combat....and probably just as dangerous to one's health and sanity.

Looks like a clear case of prior art:

http://www.xkcd.com/413/

I remember my trip to the NSA museum. We went in the early 1990's (c 1991). Now, please remember, this was 1) pre-Google 2) at the time when the cold war was not quite over and 3) the NSA was doing a much better job of staying out of the limelight and was rarely required to submit accounts of their actions even to Congress.

Just finding the place required a few _weeks_ of detective work. We called the NSA a few times to get directions (and did we get some interesting questions from our department chair as to why we had to call the NSA in the first place), and the stock response we received was, "We don't have a museum". Very classic for "No Such Agency."

Finally packing the group up and traveling down to Ft Mead, we must have traveled up and down the road for an hour looking for the turn off. I still remember that it was a small unmarked road (not a dirt road) that ran beside a (Shell?) gas station.

Once we got there I seem to remember having to pass though a metal detector, which was very odd for a museum at that time! We then ran into two or three guys wearing dark blue blazers and khakis who inquired as to the purpose of our visit. Too young to be "veteran volunteers" and too old to be minimum wage flunkies, these guys eerily followed us around the entire museum, always hovering within earshot, but always trading off like they were practicing "trailing". The best was having to "sign" the guest log before entering. Now mind you, after the trouble to get there, the less than hospitable welcome, a minor grilling as to the purpose of our visit, we sure as in hell we're signing our real names!

I suppose that the museum branch of the NSA has mellowed in the intervening years. At least I hope so, I fear that under President Bush, a trip there today could involve some waterboarding so that they could elicit the "true" reason for your visit....