Lecture Note: “Concepts of Malignancy in Ayurveda” (Part-1) by- Prof. Muralidhar Sharma


Concepts of Malignancy in Ayurveda

Prof. Muralidhar Sharma
Based on the lecture available at–Concepts of malignancy in Ayurveda

In my clinical experience of dealing with malignancy from an Ayurvedic point of view, the concept of malignancy has seen a huge change now.

Definition of tumor
When we were studying quite early it was something different and as it is defined now. The definition seems to be significantly different from the definition which we used to study in the beginning, as a complex statement, like a tumor is an independent growth with an atypical arrangement having no useful function and termination, but now the definition is changed. The current definition accepted by the American cancer association is-
“A large group of diseases that can start in almost any organ or tissue of the body when abnormal cells grow uncontrollably beyond their usual boundaries to invade adjoining parts of the body and/or spread to other organs”.
Nowadays it is considered a large group of diseases. The earlier tumor was considered a single disease. That’s one of the important issues. So, tumor now has become a syndrome, than really a single disease. Now, to make the diagnosis, the final diagnosis of any tumor or identification of any tumor or malignancy is based upon the microscopic findings, the pattern of the changes in the cells are the criteria to decide whether any tissue has become malignant or not.|
Now, whether Ayurveda textbooks Charaka, Sushruta, or Vagbhata would have mentioned its management is a question. I would say “impossible!” because at that time there was no question of a microscope. So, defining the cellular pathology, the division of the shapes of the cells, and then defining that kind of, the pattern would have been possible in Charaka or Sushruta.
That doesn’t mean that diseases of malignancy didn’t exist during the period, definitely as all the diseases were present. So, naturally, perception of the disease, and clinical course of the disease were identified at that period and they might not have been identified as a single disease entity or single pathological entity. At present, the pathological entity of a tumor is based upon a microscopic finding.  You can see the changes in the cells, the shape of the cells would be atypical, the shape of the nucleus would be atypical, and the number of divisions undergoing is more than normal. Then only, we will consider this as a tumor or malignancy. Now, this kind of perception would never have been possible in Sushruta’s period. So, naturally, the perception of the disease would be something different. So, we will now try to look at the resources in the text, based upon which we can identify the disease tumor. When a patient with a tumor comes to me now, of course, we would make the diagnosis based on the current parameters, but at the same time how I would perceive the same from an Ayurvedic point of view, that’s one of the very difficult questions.
Now, to come to that specific point- the theory part, the tumor pathology, of course, majority of the tumors primarily the word tumor itself meaning the mass, but at present, when you say a malignancy, it need not be that the disease should be presented as a mass there could be many types of malignancy, but the mass may not be felt as in case of the leukemia.
So, the primary definition of the tumor now would be based on the microscopic findings, not on the clinical findings. But if it comes to the question of clinical findings, the majority of the diseases are identified with palpable mass lesions and the palpable mass lesions with a similar character of the tumor pathology are described in Ayurvedic text as the arbuda.

Palpable mass lesion
Of course, now in the colloquial language, arbuda is equated or considered as a synonym for a tumor which I don’t fully agree. One group of tumors may be identified as Arbuda but not all the tumors might be identified as arbuda. If we do not consider this part, probably we will not be able to understand the disease process from Ayurvedic point of view. So, one major group of diseases where palpable mass is the presentation of the malignancy, they may be considered Arbuda.

According to Sushruta is –

गात्रप्रदेशे क्वचिदेव दोषाः सम्मूर्च्छिता मांसमभिप्रदूष्य |
वृत्तं स्थिरं मन्दरुजं महान्तमनल्पमूलं चिरवृद्ध्यपाकम् ||
कुर्वन्ति मांसोपचयं तु शोफं तमर्बुदं शास्त्रविदो वदन्ति |
Su. Ni. 11/14

But the clinical sign are-
A palpable mas which could be having its specified border
Sthiram- Firm Swelling
Mandarujam- relatively painless
Mahantam- a huge swelling
Analpamoolam- its indurated base is deeper than what you see
Chira vriddhi- which tends to take  a long time for a suppuration or progression is slow growing or maybe that time it could be fast-growing

Apakam- doesn’t suppurate.
The most important two characteristics are the- non-suppurative lesion and firm swelling, which is seen. That’s a very important characteristic of a neoplastic mass or tumor pathologies, which are malignant pathologies, which are presented as mass lesions. They are considered as Arbuda. One of the important characteristics of Arbuda is it doesn’t suppurate or Paka doesn’t occur.

The reason given by Sushruta is

न पाकमायान्ति कफाधिकत्वान्मेदोबहुत्वाच्च विशेषतस्तु |
दोषस्थिरत्वाद्ग्रथनाच्च तेषां सर्वार्बुदान्येव निसर्गतस्तु ||
Su Ni 11/21

Dosha sthiratvat and dosha grathana- these are the two forms of pathogenesis.
Now, if we go into the basis of the vyadhi.
Vyadhi is different, as dosha dushya sammurchana i.e., combination of dosha and dushya.|
In the context of arbuda, the definition goes something beyond that sammurchana. Instead, there is a sthiratva and doshagrathana. Now, the sthiratva and doshagrathana suggest about continuity of the pathological process which doesn’t have a termination. So, the definition of a tumor is where we say that there is no termination. That’s exactly what Sushruta has considered as a dosha sthiratva and grathana. So, arbuda is one section of the malignant lesions that can be taken.

So, when patient comes to me with a mass lesion which can be palpable, definitely, the diagnosis will be something around the arbuda/ moving around arbuda. Some of the variants of the arbuda, which are mentioned in the Samhita, these are very characteristic of a malignant pathology, like in case of Shonitarbuda, the characteristic feature will be the fragile tissues. Tissues are fragile and they tend to bleed as tumor which tends to bleed on touch.

कृष्णौः स्फोटैः सरक्तैश्च पिडकाभिश्च पीडितम् |
यस्य वस्तु रुजश्चोग्रा ज्ञेयं तच्छोणितार्बुदम् ||
मांसदोषेण जानीयादर्बुदं मांससम्भवम् |
Su. Ni. 14/13

(सरक्तैश्च पिडकाभिश्च) that’s the typical feature or a Mansarbuda where the surface will be fimbriated or finger-like. For a Talu arbuda, where the surface also fimbriated appearance and a soft fragile appearance like padmakara i.e. surface will have an irregular surface.

These are all the typical characteristics of neoplastic mass lesions, as we Study now and they are mentioned in Sushruta Samhita. So, palpable neoplastic conditions benign or malignant are considered without any doubt about them and they are over the surface of the body- gatra pradesha. That gatra pradesha is over the surface of the body but along with that, there are certain conditions where the mass may not be over the surface of the body but mass may be palpated within the abdomen and that abdominal masses like gulma also may be considered as some variety of the neoplastic condition. So, there is a difference between the gulma and the arbuda.  The gulma is located in the abdomen and it is tend to be movable-

Visceral mass lesion  -Gulma

हृद्बस्त्योरन्तरे ग्रन्थिः सञ्चारी यदि वाऽचलः |
चयापचयवान् वृत्तः स गुल्म इति कीर्तितः ||
Su. U. 42/4

Some variety of the gulma could be presented as the malignant lesions where the patient would have the systemic symptoms as such. Another presentation of the tumor pathologies or malignant pathologies (I would say the malignant pathologies) would be an obstruction to the passages- like oesophageal malignancies which produce obstruction to the swallowing. or maybe the pathologies of the prostate or so on where the urethra may be obstructed, common bile duct may be obstructed and so on. So, you identify a neoplastic condition based upon the evidences either the clinical or investigational evidences of obstruction to the passage of the contents, Such obstructive diseases also are mentioned in Sushruta in different contexts among them, one is Balasa.

obstructive diseases
Balasa is a situation where the annagati (the movement of the food) would be affected and you would have a circular swelling around the area.

बलास एवायतमुन्नतं च शोफं करोत्यन्नगतिं निवार्य |
तं सर्वथैवाप्रतिवारवीर्यं विवर्जनीयं वलयं वदन्ति ||
Su. U. 16/53

So, when the swallowing difficulty is presented and along with that there is a circular

swelling, a circular lesion. Valaya or like appearance so balasa and valaya- these are the two variables conditions. Balasa is where the surface would be elevated raised a fungating mass lesion in the oesophagus and an annular lesion or a circular lesion is a Valay So, variance of the esophageal obstructions were described in Sushruta.

Mudrasthila or  Mutragranthi
Similarly, the obstructive pathologies in the urinary tract like mudrasthila or the mutragranthi.
Mutrasthila is where a palpable hard mass is felt per rectal

शकृन्मार्गस्य बस्तेश्च वायुरन्तरमाश्रितः |
अष्ठीलावद्धनं ग्रन्थिं करोत्यचलमुन्नतम् |||
विण्मूत्रानिलसङ्गश्च तत्राध्मानं च जायते |
वेदना च परा बस्तौ वाताष्ठीलेति तां विदुः |
Su U 58/7,8

In between the rectal and the urinary tract the mass is felt which is stone like so that’s obviously the prostatic pathologies.

Again, it’s not the question of benign or malignant it could be a presentation of a mass lesion or similarly in case of mutragranthi which is again a palpable mass but the difference is the there would be a painful condition in mutragranthi, like aybe either the prostatics or some of the tumors of the prostate too can be painful. so that’s evidently identified.

अभ्यन्तरे बस्तिमुखे वृत्तोऽल्पः स्थिर एव च
वेदनावानति सदा मूत्रमार्गनिरोधनः ||
जायते सहसा यस्य ग्रन्थिरश्मरिलक्षणः |
स मूत्रग्रन्थिरित्येवमुच्यते वेदनादिभिः |||
Su Ut 58/18,19

Ulcerative lesions

अतिसंवृतो अतिविवृतो अतिशीतोऽत्युष्णो कृष्ण रक्त पीत शुक्लादीनां वर्णानामन्यतमः भैरवः पूतिपूयमांससिरास्नायु प्रभृतिभिः पूर्णः पूतिपूयास्रावी उत्सङ्गी अमनोज्ञदर्शनगन्धः अत्यर्थं वेदनावान् दाहपाकरागकण्डूशोफपिडकोपद्रुतः अत्यर्थं दुष्टशोणितास्रावी दीर्घकालानुबन्धी चेति दुष्ट व्रणलिङ्गानि । Su .Su22/7

There are a presentation of the human pathologies in the form of ulcers. Ulcerative lesions are another representation of the management pathologies. It could be either over the surface of the body or it could be anywhere in the area like in the stomach or so on. Sushruta has described the varieties of the Dusta Vrana, which could be suggestive of the malignant changes, malignant pathologies like

A wound which has become quite wide and the surface is wide and it continues to widen further

bhairav- itself looks unappealing and it produces some fearful feeling. Looks changed.

It could be Amanojna darshana i.e looks very wacky and suggestive of a possibility of the tumor.

utsangi i.e. surface could be raised multiple tracts or induration.

deerghakalanubandhi i.e. which tends to persist towards chronicity.

These also could be the evidences of arbuda. These also could be the evidences of the malignant changes in any ulcer that’s exactly the same. Now, whenever we have a very chronic non-healing ulcer Marzolin’s ulcer  or maybe the carcinomas basal cell carcinoma, the clinical suspicion would be based upon these features only.

Of course, the confirmation now it has to follow histopathological background. Without histopathological background it may not be possible to make the diagnosis whereas the clinical signs of both the ulcerative lesions are described by Sushruta.  or the other way, in a typical ulcer which is having an indurated surface and these edges are raised that too is considered as one of the conditions where either the ulcer surface has to be curated or excised and that’s what Sushruta has mentioned the characteristic feature of an ulcer where the surface could be hard there are the ends to disrupt repeatedly or it may have a raised fleshy surface. That is considered also as crenation which requires either a lakshana that’s a curating or excision

Though, Sushruta has not considered this as arbuda, I would consider a malignant ulcer as

one of such vranas which require either the excision (chhedana) or lekhana depending upon conditions.

That’s the point. So, when we look at from Ayurvedic point of view we have to consider the clinical presentation than the real pathology, as such. Now systemic symptoms of malignancy also are described in Sushruta in certain specific disease conditions like Raktarbuda.  In the raktarbuda characteristic clinical symptoms like raktarbuda. In raktarbuda,

दोषः प्रदुष्टो रुधिरं सिरास्तु सम्पीड्य सङ्कोच्य गतस्त्वपाकम् |||
सास्रावमुन्नह्यति मांसपिण्डं मांसाङ्कुरैराचितमाशुवृद्धिम् |
स्रवत्यजस्रं रुधिरं प्रदुष्टमसाध्यमेतद्रुधिरात्मकं स्यात् ||
रक्तक्षयोपद्रवपीडितत्वात् पाण्डुर्भवेत् सोऽर्बुदपीडितस्तु |
सू नि 11/15,16,17

Because of the lesion present over the area the patient would have Raktakshaya lakshana. i.e. anaemic features would be presented or there would also be persistent bleeding. These are the exact clinical description of a surface tumor pathology, the fragility producing the lesion as such. So, that is about the conditions which we can now identify based upon the clinical features as the malignant lesions with the evident local sites or localized malignancy conditions, but there are certain malignancy conditions which are systemic now like leukemias and Sushruta has definitely not have considered them as arbuda but this features of those leukemia like conditions can be seen in the description of the pandu, particularly among the asadhya lakshana of the pandu and in the asadhya lakshana of the pandu, the conditions which can present with the  appearance of the very chronic condition- khareebhootah which becomes chronic and becomes resistant to the other features as such and which also can present with the systemic symptoms like digdhangah, chhardi, murccha, trisharditah these are the considered as asadhya pandu so a patient of leukemia with these clinical presentation I would consider them as a one variety of the one or other variety of the pandu, either asadhya  or sadhya depending upon the same situation.

 Dhatugata Jwara
Some of the leukemic features also could be seen as dhatugata jwara, in the gambhira jwara dhatugata jwara. The features mentioned are the same.

रक्तोष्णाः पिडकास्तृष्णा सरक्तं ष्ठीवनं मुहुः|
दाहरागभ्रममदप्रलापा रक्तसंस्थिते||७७||
अन्तर्दाहः सतृण्मोहः सग्लानिः सृष्टविट्कता|
दौर्गन्ध्यं गात्रविक्षेपो ज्वरे मांसस्थिते भवेत्||७८||
स्वेदस्तीव्रा पिपासा च प्रलापो वम्यभीक्ष्णशः|
स्वगन्धस्यासहत्वं च मेदःस्थे ग्लान्यरोचकौ||७९||
विरेकवमने चोभे सास्थिभेदं प्रकूजनम्|
विक्षेपणं च गात्राणां श्वासश्चास्थिगते ज्वरे||८०||
हिक्का श्वासस्तथा कासस्तमसश्चातिदर्शनम्|
मर्मच्छेदो बहिः शैत्यं दाहोऽन्तश्चैव मज्जगे||८१||
शुक्रस्थानगतः शुक्रमोक्षं कृत्वा विनाश्य च|
Ch. Chi 3/ 77 -81

Like, the patient would have a persistent fever, sweating and loss of weight

Antardaha- the temperature (core Temperature) of the body may be raised whereas the surface body feature may not be very much raised and there could be multiple systemic symptoms including the marmaccheda i.e. consciousness also could be impaired. These are all the typical features of the dhatugata jwara. So some of the leukemic conditions based upon the clinical presentation, I would be making the diagnosis of a dhatugata jwara

Depending upon the presentation either it could be uttana dhatugata jwara and gambheera dhatugata jwara.Majority of the leukemias have the diagnosis of Gambheera dhatugata jwara

Dhatu anukramana – Neoplasm

क्रमेण उपचयं प्राप्य धातूननुगतः शनैः।
न शक्य उन्मूलयितुं वृद्धो वृक्ष इव आमयः ॥

स स्थिरत्वात् महत्वाच्च धात्वनुक्रमणेन च ।
निहन्त्यौषधवीर्याणि मन्त्रान् दुष्टग्रहो यथा ॥
Su Su 23/15,16

अत ऊर्ध्वं एतेषां अवदीर्णानां च व्रणभावमापन्नानां षष्ठः क्रियाकालः ।
Su ,Su 21/35

 Now, the pathogenesis where the disease doesn’t end up and it tends to produce a sequence of the pathologies in the same manner, their description is dhatu anutkramana, which is mentioned by Acharya Charaka. Dhatu anutkramana is a very specific word like once a pathology has occur usually in the normal course either that pathology would be having a paka it would be having a situation of further progression and then there will be paka or  maybe the suppuration and then the disease may be terminated or it may result in a stigma a vranavastu can occur, but there would be certain pathology which can result into dhatu anutkramana. Dhatu anutkramana is a disease process which has occur in one tissue.

It can produce further progression of the dhatus which are of the same nature. The next generation of the dhatu also would have the same pathology. That’s dhatu anutkramana and dhatu anutkramana is also considered one of the causes, where a disease becomes incurable  and this is exactly the malignant pathology. So, a malignant pathology  described by Ayurvedic point of view is used by the word dhatu anutkramana, where a clinical evidence of a pathological dhatu or tissue formation in the next generation is identified by clinical means. Whereas now we make the diagnosis based upon the histopathological evidence. We need a microscope. Without the microscope you may not make the diagnosis whereas Sushruta or Charaka had made the diagnosis based upon the clinical parameters. So, naturally there would be some gap some gap of identification of the lesion, some gap of the nomenclature of the lesion, some gap in predicting the prognosis and so on. But the point is the pathological process related to the malignancy were well described in the context of either dhatu anutkramana  or the dosha sthiratva or dosha grathana- these are the three variants of the pathogenesis produced in case of the tumor pathology.

Now how these are relevant, I will come to that later. When we discuss some more issues related to the malignant pathology as such or another evidence where the disease process may not have a termination, is also in mentioned by Sushruta in case of the shashtha kriyakala the bheda kriyakala where the vrana.

अत ऊर्ध्वमेतेषामवदीर्णानां व्रणभावमापन्नानां षष्ठः क्रियाकालः
Su Su 21/35

A disease may be reach a process where it become avadeerna and it tend to disrupt or spread to other areas and it will have a vrana bhava. Vrana bhava is adehadharanat- A lesion which will be remaining in the body as long as the person will live or it may end up with the patient. That’s the vrana bhava and such a situation may occur and that too is an evidence of the malignant pathology.


यज्जायतेऽन्यत् खलु पूर्वजाते ज्ञेयं तदध्यर्बुदमर्बुदज्ञैः |
यद्द्वन्द्वजातं युगपत् क्रमाद्वा द्विरर्बुदं तच्च भवेदसाध्यम् ||
Su Ni 11/20

 In addition to this the description of a secondary produced also are described in the context of arbuda. When arbuda produces another lesion of the same nature which is exactly the definition of metastasis is described as a presentation of a similar disease entity elsewhere in the body.  Sushruta has mentioned two varieties of that metastasis, one is adhyarbuda and dwirarbuda. Adhyarbuda is when a mass produce is generated over the mass and hence the surface becomes irregular, as you see over this image where a lesion- breast cancer where there is a mass and then because of the differential growth.

you will have some more lesions which look like a mass over the other area or a mass which is produced elsewhere maybe in the axilla as you see. That’s the dwirarbuda so metastatic presentations are described as one of the possible variants of the Arbuda.

So that basic pathology is identity and when it comes to the question of management too in such apaki rogas the only possible choice of the cure is a Chhedana.

Need of total excision:

अपाकेषु तु रोगेषु  कठिनेषु स्थिरेषु च ||
स्नायुकोथादिषु तथा च्छेदनं प्राप्तमुच्यते |
Su Chi  1/33,34

it’s a consideration of irreversible pathology and hence the indication for chhedana or the excision the complete surgical removal is the only possible cure and Sushruta has given you all that complete description about the importance of the surgical excision, like a disease which is presented as a firm and non-suppurative lesion, maybe that’s what we have considered as a may be a palpable tumor pathology, surgical excision has to be done. Chhedana is indicated and when you do chhedana in case of arbuda you have to ensure that the disease is completely removed. Even if a part of the lesion is left over then that could be recurrence.

सशेषदोषाणि हि योऽर्बूदानि करोति तस्याशु पुनर्भवन्ति ||
तस्मादशेषाणि समुद्धरेत्तु हन्युः सशेषाणि यथा हि वह्निः ||
Su Chi 18/42,43

A possible recurrence of the disease was also identified by Sushruta and hence when you remove, you have to be very careful.
You have to remove the lesion completely as such. If complete removal of the lesion is not possible by the surgical process, you may make use of alternative methods debulking therapy also could be possible as a surgical treatment by Sushruta and debulking may be facilitated by natural entities- the krimi- maggot formation.

अल्पावशिष्टे कृमिभक्षिते  च
लिखेत्ततोऽग्निं विदधीत पश्चात् |.
Su Chi 18/38

If it is not possible to remove the tumor completely, then it may be partially excised and whatever residual lesion is left over, it could be managed with the krimi- the natural evidence. These are the methods which are suggested by Sushruta.  So the point is almost the clinical course of the malignant disease and a basic clinical approach for malignancy is described by Sushruta, which seems to be almost the same as we follow now. The only difference now is that you have some more details as such. Unfortunately, when it comes to the question of the history of malignant lesions and neoplastic lesions, the current textbooks do not mention anything about Sushruta as such.

  • Hipocrates – Used the word cancer (450 – 370BC) – Humour  theory
  • Galen- Used the word oncos ( 2nd Century)
  • Bloodletting as a treatment
  • Percival pott- Chimney cancer (1775)
  • Rodoplh Virchow – Inflammation and cancer(1863)
  • Hilario De Govea – Inheritance of cancer(1896)
  • SM Goldberg- Radotherapy for cancer(1903)
  • Pual Ehrlich – Immune system and cancer(1909)
  • Ernst Wyden- Cigarette smoking and cancer(1960)

All that history if you read about history in the contemporary system it starts with Hippocrates and unfortunately even all our Indian doctors, Indian textbooks also start with the mentioning of the word cancer, but the Sushruta or Charaka who have written about all that pathology in detail and a basic clinical approach minus the microscopic details. So only the microscopic tests are not mentioned, but otherwise a very proficient clinical description of the pathology, and a  simple or confident clinical approach to the management, these are done or assessed 5000 years back by Sushruta and Charaka, and that part unfortunately is not included in the standard protocols of the history. But if you read the history in the contemporary situation, the history of humor starts with the Hippocrates who used the word cancer because of the shape of the crab like the lesion tends to spread but Hippocrates could not describe the pathology as such. He couldn’t make up the exact cause as such. All that he had mentioned is there is an incurable lesion, which is considered cancer. Then, of course, the milestones in the development of tumor pathology, started in 450 to 370 BC by Hippocrates, where he had mentioned a similar pathology. Galen mentioned a word oncos in the second century and bloodletting as a standard protocol of treatment, but till 1775 there was not much of a significant change in the history of the tumor or tumor management in the context of western medicine and this is a very important thing. Whereas Sushruta has a mature methodical approach to the treatment of an apparently neoplastic lesion. Whereas in western history, the pathology was not clearly defined. Only the nomenclature and certain basic details like bloodletting as treatment were practiced as such. The possibility of a theoretical approach and a study came up only in 1775 when Percival Pott identified chimney cancer where inflammation is considered to be a cause of cancer. Somewhere the theories about cancer developed in 1863. Inflammation was established as one possible cause of cancer. In 1896. Hilario described the inheritance of cancer beginning as possible. genetic pathology, a breakthrough in the approach to the management of malignancy came in 1903 when radiotherapy was introduced. for this radiotherapy was introduced as a part of the treatment. Only something around 217 years back the whole history is 217 years, but at the same time we have to appreciate the other part- the technology, which has developed so fast in those 217 years and we have a history of 5000 years but we are not able to develop the technology to that level  that’s the other part of it. Then the other more and more concepts about tumor pathologies developed later and in 1909, it was the immune system and cancer relationship was established by Paul Ehrlich and in 1960, cigarette smoking and cancer- relationship was established by Ernst Wyrden. It then the further real breakthrough came in only in the last century, 20th century 1920 and so on. The first development of the growth and the assessment, particularly the approach to the malignant lesions and understanding the malignant pathology had developed only in the last century and it was only in 1920, that experimental carcinogenesis was possible in a laboratory condition, a malignant lesion could be developed and from that day onwards or that moment onwards, new developments have started very rapidly and lots of new things have developed and the current in the last few years, the development is enormous lots of new information is added, lots of technology is added and to follow all the technological changes is quite difficult and virtually not possible. Anyway, in 64 a virus was considered to be a cause of the virus. The relationship of a viral infection and malignancy in Burkitt’s lymphomas was identified and the genes, again, this gene and specifically some genes like HER2, also was identified in 1984, gene suppressions where suppressing genes also were identified. 2014 is the situation breakthrough where a DNA analysis and cancer genome atlas was formed and this is considered to be the latest development of the course. So describe all the changes or all the developments in the past few years, it will never be possible.  I have tried to pick up certain of the major breakthroughs which have are considered game changers.


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