Who is wendell stanley

But, as you can see, many, many, many entities have been filled in here, so that if you look at the size of the structure, going from the smallest here to the largest there, there is almost a continuum with respect to structures. So that in truth there is no boundary line now between the accepted living organisms of the biologist, such as bacillus prodigiosus and the molecules of the chemists at this level. And the viruses, these infectious disease producing agents have been the structures which serve to fill in at long last this gap which has existed for years and years.

Well, now I indicated that from the time of the discovery of viruses, around the turn of the century, up until about , the basic nature of these structures in this area was unknown. It was not known whether they were still smaller ordinary living organisms like bacillus prodigiosus.

Some new kind of a chemical molecule or simply a specialised grouping attached to a chemical molecule. And it became very important to determine the exact nature of one of the viruses. And for this, the virus in the middle here, tobacco mosaic virus was selected for chemical study.

And to make a long story quite short, this virus was isolated in the form of a crystallisable nucleoprotein. And after a long series of tests designed to prove whether or not the biological activity was a part and parcel of the protein, the nucleoprotein molecule, it was concluded that beyond a reasonable doubt the virus activity was a specific property of the nucleoprotein.

Then came of course the business of finding out whether tobacco mosaic virus was a representative virus or whether it was something unusual. So studies on a variety of viruses were made. And for example another virus was obtained in the form of the beautiful dodecahedral crystals that you see here.

This is another plant virus, that of the tomato bushy stunt virus. It can be isolated in the form of the crystals that you see here. These crystals are composed of very tiny macromolecules about 30 or so millimicrons in diameter. Starting at the top upper left, we have the vaccinia, elementary bodies of vaccinia, the vaccine which is used to protect you against smallpox, you will probably all have had the little scratch on your arm.

At the upper right we have an example of a smaller virus, that of influenza virus. An extremely interesting virus, one which could serve as the subject of an entire lecture, because this virus in caused the deaths of more people than had died on the battle fields of two great world wars.

In our own country of the United States we lost over , persons within a 4 month period and activities of that virus are on the upper right hand side. And in influenza was not even recognised as a virus disease, for it was not so discovered until , first by the English workers and a similar virus in swine by Doctor Shope in our laboratory.

Here is an example of a group of viruses known as bacteria viruses, the viruses which attack bacteria. Here is a T2 bacterial virus with an unusual structure, such as you see, with the head and the sperm shape tail. On the right hand side here is an extremely interesting virus because this is a cancer producing virus. A virus which produces cancer in rabbits in the United States. It is of course of extreme interest because this provides one of the avenues that approached to the solution of the cancer problem.

This is another example of a bacteria virus or a bacterial virus. This one has the very short stubby tail, this tail organ is very important because it is believed that this provides a mechanism by means of which the infective process is carried out.

And for some time it was not recognised that this particular bacteria virus had a tail. Here is an example of the little macromolecules which go to make up the tomato bushy stunt virus, which gives the beautiful crystals that you saw just a moment ago.

Here is a familiar tobacco mosaic virus about which I shall say just a bit more in a moment. And here are some molecules, macromolecules perhaps is a better word, of a virus which affects orchids. You ladies perhaps have not realised that the flowers that you wear on your dresses in the evening, the orchids are subject also to virus infection. And when you isolate the virus which causes a disease of orchids, you obtain the material on the right.

Now, if you go from the small spherical virus through the range of sizes that you see here, you cover almost the entire range from about 20 millimicrons up to millimicrons. So that here you have a birds eye view of real structures which have been found to exist in this borderline which existed between the living and the non-living. Now, for just a little bit of chemistry, needless to say my background and my training is in chemistry.

Having isolated some of these materials such as tobacco mosaic viruses, it was only natural to subject purified preparations of this virus to the normal procedures of characterisation, analysis and so forth. And the next slide will give you an example of the building blocks which go to make up the tobacco mosaic virus.

But first this row or columns give the amounts of the various amino acids which go to make up the tobacco mosaic virus. You can see them here. These amounts are very characteristic, whether you isolate the tobacco mosaic virus in Sweden, in the United States, in Australia, whether you isolate the virus from Turkish tobacco plants, from tomato plants, from spinach plants. In other words, there is a characteristic composition which exists throughout the world and regardless of the host in which you grow this material.

Now, I indicated at the beginning of this talk that one of the characteristics of viruses is that they can mutate. Needless to say as chemists we wondered what would happen when a virus mutates and causes a slightly different kind of a disease. We therefore isolated it and purified a variety of strains of tobacco mosaic virus. And the results of these analysis are also on this slide. We have the masked strain of the virus, the JD strain of the virus, the green aucuba, the yellow aucuba, the ribgrass virus and two cucumber viruses.

These for a time have been regarded as strains of tobacco mosaic virus. Now, whenever differences in composition exist, differences in composition from the tobacco mosaic virus, the figure has been imposed in a little block.

So as I have indicated, those of you who are not chemists, you need only to determine the number of little figures enclosed in a heavy line to get some idea of the nature and extent of the changes which exist.

For example, there are only two changes in the JD strain, here and here. On the other hand, in the case of the Holmes ribgrass virus, there are many, many changes in the nature of the amino acids. And as you can see, there is an example here of the introduction of a new amino acid into the strain.

In other words, the amino acid or the building block, if you please, histidine does not exist in the tobacco mosaic virus. Yet when this strain mutated and formed the Holmes ribgrass strain, it was accompanied by the introduction of histidine, it was accompanied by the introduction of a new amino acid. This data provided therefore the first information concerning the nature of mutation in the field of viruses.

And I hope this may also serve as an indication of the nature of the changes which take place in the mutation of genes of higher organisms. And if so, this provides an experimental approach to the nature of the changes that Professor Muller has been interested in these many years.

Now, we have recently been interested in the detailed structure of tobacco mosaic virus. You can make a variety of kinds of studies on this virus and one of the useful approaches from a standpoint of technique is the newly developed spray drop technique of Professor Williams in our laboratory. In which a solution of virus is mixed in known proportions with a polystyrene latex solution.

The polystyrene latex particles are shown here and the tobacco mosaic virus particles are here. And you see a small segment at the right which has been enlarged, so that you can see the particles somewhere on the plain. By mixing the two, you get a relationship between the number of particles of polystyrene latex which you know by virtue of having prepared the solution and the number of particles of tobacco mosaic virus.

You get a micro drop and hence a representative sample of this mixture by means of a spraying technique from an atomiser. And the spray drop is showing an outline here, shows quite clearly. Hence, this micro drop gives you a representative sample and enables you to get a relationship between the number of particles of tobacco mosaic virus and the number of particles of the polystyrene latex.

And thus you can carry out much work on the relationship of biological activity to the little rods which go to make up the virus. Now, our recent work on the structure, the detailed structure of these rods, has given us some rather unusual results. This work was stimulated primarily by the results obtained in our laboratory and in other laboratories on the bacteriophage particles. And work, stemming also from the workers here in Germany on a protein component which can be obtained by degradation of tobacco mosaic virus.

The next slide shows in outline some of the electron micrographs which can be obtained from such mixtures. At the upper left in high magnification is the intact tobacco mosaic virus particle. And if you break this particle, for example by means of high sound treatment, you can simply slice it across as you would slice a piece of sausage.

If you do that, you get the two particles, or you get particles such as those that you see in the upper right hand corner. These have been found to be hexagons so it would appear that the cross section of this rod is that of a hexagon. Within the past few months it has been possible to devise a technique by means of which an individual macromolecule can be partially denatured. If you subject a solution of tobacco mosaic virus to mild temperature treatment, to mild heat, the one end will tend to ball up.

And when this is then treated with a detergent such as sodium dodecyl sulphate, the part of the protein which has balled up will disappear and leaving the fine thread that you see here. We now believe that this represents for the first time proof of the location of the nucleic acid portion of the nucleoprotein. In other words that the nucleic acid is centrally located in the virus rod.

Now, another bit of information which indicates a similar conclusion is when you take the so called X protein that can be obtained from diseased plants, or if you take a degradation product, as Dr. Klauser has shown in this country, and cause it to re-aggregate, you can retain once again the hexagonal shaped cross section material.

But as you can see, there is a hole down the centre of the tube. Well, needless to say the re- aggregation or the re-synthesis, partial re-synthesis of this unusual virus rock provides a very great challenge to the chemist. Theoretically it should be possible to bring together the protein components which go to make up this biologically active material and the nucleic acid components and hopefully be able to re-synthesise the biologically active particle.

This then gives you the beginning of the intimate detailed structure of a biologically active structure. The biological activity consisting of the ability to reproduce itself under certain specific conditions. I believe that with time the chemist should be able to synthesise the building blocks which go to make up a virus, such as for example tobacco mosaic virus with the ultimate building blocks being protein units of only 17, molecular weight.

Already synthetic approaches in connection with insulin and with some of the other hormones are well on the way. And I believe that within the next few years the biochemists should be able to synthesise these small building blocks, the structural units of a virus. And then, through a special technique, cause these to assemble around the nucleic acid component and regain their activity.

This may be a little bit on the utopian side, but I believe that it is a real possibility within the next few years. And with this of course you see because of the genetic characteristic of viruses one can then gaze just a bit further over the horizon and see that the chemist should be able eventually to determine the nature of the germ bioism of the world. And this of course would give the chemists a type of power which currently seems to rest only in the hands of the atom physicist.

Now, having gone this far with the structure of tobacco mosaic virus, I know that I dare not stop here, particularly with Professor Butenandt in the audience, or at least I believe I saw him here. Stanley turned his attention to defining the physical and chemical characteristics of tobacco mosaic and other viruses, and his subsequent work contributed immensely to our understanding of their mechanisms of action.

His technique is still in common use today. In addition, his work pushed researchers in many fields to begin looking more closely at nucleoproteins, molecules that we now understand are intimately involved in the most essential life processes, including the protection of chromosomes, the stabilization of DNA and the activation and inactivation of individual genes.

Stanley shared the Nobel Prize with Dr. Northrop and James B. Sumner of Cornell University. Stanley was born in Ridgeville, Indiana, in After earning his Ph. He remained at Rockefeller until , becoming an associate member in and a member in He later served as chairman of the departments of biochemistry and virology there.

Stanley served as an adviser to both the United States government and the World Health Organization and director at large of the American Cancer Society. Stanley died in More info here. Recent News. November 9, He won the Nobel Prize in chemistry in for his work with the tobacco mosaic virus, which shed light on viral behavior.

He was able to isolate and crystallize the nucleoprotein within the virus, single-stranded RNA, and observed that though it appeared to be an inactive chemical it still showed characteristics of life.

His work demonstrated that viruses are not living organisms because they lack components essential for metabolic function.